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 Table of Contents

MEDICINE ..................................................................................................................................................................... 3
Cardiology. ...................................................................................................................................................................................... 4
Endocrinology. .............................................................................................................................................................................. 25
Haematology/Oncology. ................................................................................................................................................................ 47
Infectious Disease .......................................................................................................................................................................... 68
Rheumatology ............................................................................................................................................................................... 82
Neurology ..................................................................................................................................................................................... 89
Nephrology. ................................................................................................................................................................................ 114
Gastroenterology. ........................................................................................................................................................................ 133
Respiratory medicine. .................................................................................................................................................................. 154
Dermatology................................................................................................................................................................................ 174
SURGERY .................................................................................................................................................................... 190
Anatomy ...................................................................................................................................................................................... 191
Cancer ......................................................................................................................................................................................... 192
Breast surgery .............................................................................................................................................................................. 196
Plastic surgery .............................................................................................................................................................................. 198
General surgery ............................................................................................................................................................................ 202
Urology ....................................................................................................................................................................................... 209
Vascular ....................................................................................................................................................................................... 213
Orthopaedics ............................................................................................................................................................................... 216
Ophthalmology ........................................................................................................................................................................... 236
Otorhinolaryngology ................................................................................................................................................................... 240
Anaesthesia .................................................................................................................................................................................. 243
PSYCHIATRY .............................................................................................................................................................. 246
Psychiatry .................................................................................................................................................................................... 247
PAEDIATRICS, OBSTETRICS & GYNAECOLOGY ................................................................................................... 260
Gynaecology ................................................................................................................................................................................ 261
Obstetrics .................................................................................................................................................................................... 284
Paediatrics ................................................................................................................................................................................... 306
SELECTED TOPICS .................................................................................................................................................... 338
General practice ........................................................................................................................................................................... 339
EM/Critical care .......................................................................................................................................................................... 340
Interpretation of investigations..................................................................................................................................................... 344
Radiology .................................................................................................................................................................................... 345
Clinical pharmacology ................................................................................................................................................................. 347
Ethical, legal, and palliative medicine ........................................................................................................................................... 348
Miscellaneous .............................................................................................................................................................................. 354
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MEDICINE
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Cardiology.
Basic principles
CARDIAC PHYSIOLOGY

Determinants of cardiac output

Cardiac output is the product of heart rate and ventricular stroke volume .
 Stroke volume is determined by the contractility of the ventricle, and the loading conditions known as preload and afterload.
 The left ventricle does not normally eject its entire volume during systole; consequently, a common clinical measure of cardiac
performance is the left ventricular ejection fraction (LVEF) – defined as stroke volume / end-diastolic volume.
 The normal range for LVEF is 50-70%
CONTRACTILITY
Contractility is the intrinsic contractile state of the myocardium independent of preload and afterload.
 It is determined by several factors, including but not limited to:
 Number of contractile elements (i.e. alive myocardium)
 Availability of essential cofactors for excitation-contraction coupling
 Inotropic agents
PRELOAD
Preload is defined as the load (volume of blood) that passively stretches cardiac tissue
prior to the onset of contraction.
 It is defined clinically as the ventricular end-diastolic volume (although is more
easily measured as end-diastolic pressure )
 The preload is determined by venous return , which is in term determined by
venous tone, blood volume , and atrial contraction
 As ventricular end-diastolic volume increases, there is a progressive increase in the
force of ventricular contraction (and stroke volume) up to an optimal end-
diastolic volume. Further increases however lead to a fall in stroke volume,
probably due to overstretching of myocardial contractile elements – this is known
as the Frank-Starling law
 Elevation of the preload above a critical level leads to pulmonary and/or
systemic congestion
 Reduction in preload below a critical level leads to symptoms and signs of
reduced cardiac output
AFTERLOAD
Afterload is defined as the load (pressure) that the ventricle must overcome before it is able to open its semilunar valve and eject blood.
 The afterload is determined primarily by systemic vascular resistance

JVP
The jugular venous pressure (JVP) is the indirectly observed pressure of the venous system.
 Upward deflections:
 A wave – atrial contraction
 C wave – ventricular isovolumetric contraction and bulging of tricuspid into right atrium
 V wave – venous filling
 Downward deflections:
 X descent – atrial relaxation and tricuspid valve moving downwards
 Y descent – filling of ventricle after tricuspid opening
VISUALISATION
 Internal jugular vein is non-palpable, readily occludable, and fills superiorly
 Found between sternal and clavicular heads of the sternocleidomastoid muscle (lateral to carotid artery)
 It alters with changes in posture (drops if elevated)
 It drops with inspiration and rises with expiration
 If JVP  on inspiration – Kussmaul sign – constrictive pericarditis, tamponade, severe right heart failure, restrictive
cardiomyopathy
 Hepatojugular reflux aids identification of JVP
 Interpretation :
 Report as centimetres above sternal angle (regardless of elevation)
 Normal = 2-4cm
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CLINICAL CORRELATES
 Absent ‘a’ wave – atrial fibrillation
 Enlarged ‘a’ wave – tricuspid stenosis, severe pulmonary stenosis, and pulmonary hypertension
 Cannon ‘a’ wave – third-degree heart block
 Enlarged ‘v’ wave – tricuspid regurgitation
 Prominent ‘x and y’ descent – constrictive pericarditis

Adrenergic receptors
The adrenergic receptors (adrenoreceptors) are a class of G protein-coupled receptors that are targets of adrenaline and noradrenaline.
CLASSIFICATION
 α receptors (sympathetic)
 α1 – smooth muscle contraction (vasoconstriction, mydriasis, contraction of GI and urinary sphincters)
 α2 – mixed effects
 β receptors (sympathetic)
 β1 – positive chronotropy, inotropy, dromotropy, lusitropy (and  renin)
 β2 – smooth muscle relaxation (bronchodilation; relaxation of GI and urinary sphincters, minor vasodilation) (and  insulin)
 β3 – relaxation of detrusor muscle
 Muscarinic receptors (parasympathetic)
 M2 – negative chronotropy, dromotropy (nil inotropy/lusitropy as vagus nerve does not significantly innervate myocardium)
CARDIAC ANATOMY

Coronary circulation
The typical coronary arterial supply to the heart arises from the right and left coronary arteries , which originate from the root of the
aorta.
 Right coronary artery (RCA) – runs in atrioventricular groove
 Acute marginal branches
 Atrioventricular nodal artery (60% from RCA)
 Posterior descending artery (PDA)
 Left main coronary artery (LCA)
 Left anterior descending artery (LAD)
 Septal branches
 Diagonal branches
 Left circumflex artery (LC) – runs in atrioventricular groove
 Obtuse marginal branches
 Venous drainage:
 Most venous blood from heart drains into RA
through coronary sinus (although a small amount
drains through Thesbian veins into all four
chambers)
DOMINANCE OF CIRCULATION
 Right-dominant (80%) – PDA from RCA
 Left-dominant (15%) – PDA from LC
 Co-dominant (5%) – dual supply from RCA and LC
ELECTROCARDIOGRAM INTEPRETATION

Normal ECG Wave morphology

 P-wave – atrial depolarisation (repolarisation masked by QRS)
 PR interval – conduction delay through AV node
 QRS complex – ventricular depolarization
 QT interval – mechanical contraction of ventricles
 T wave – ventricular repolarisation
 ST segment – isoelectric, ventricles depolarised
SPEEDS OF CONDUCTION
 Purkinje fibers > atria > ventricles > AV node (allows for atrioventricular filing)
CONDUCTION PATHWAY
 SA node (60-100bpm pacing)  atria  AV node  common bundle  three bundle branches
(left anterior/posterior and right bundle)  Purkinje fibers  ventricles (20-40bpm pacing)
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Basic interpretation of ECG

SPEED AND VOLTAGE
 Usually the paper speed of ECG is 25mm/sec, consequently in the horizontal axis:
 1mm (small square) = 40 milliseconds
 5mm (big square) = 200 milliseconds
 Voltage is usually set at 10mm/mV, consequently in the vertical axis:
 1mm (small square) = 0.1mV
 10mm (2 large squares) = 1mV
ESTIMATING RATE
 Rate – number of complexes on rhythm strip times six (average over 10 second period)
 Remember 300-150-100-75-60-50-43 (300 / number of large squares between R-R)
CALCULATING AXIS
 Normal – positive QRS in leads 1 and aVF (0 to +90 degrees)
 Left axis deviation – positive QRS in lead 1 and negative QRS in lead aVF (0 to -90 degrees) – “leads have LEFT each other”
 Note: up to -30 degrees is considered normal; a negative QRS in lead 2 confirms pathological LAD
 Right axis deviation – negative QRS in lead 1 and positive QRS in lead aVF (+90 to 180 degrees) – “leads are RIGHT for each
other”
 Extreme axis deviation – negative QRS in lead 1 and aVF (-90 to 180 degrees)

Clinical Interpretation of ECGS

RULE OF FOURS
The ECG can be clinically interpreted using the ‘Rule of Fours’
 Four initial features
 Review history/clinical picture
 Rate
 Rhythm
 Axis
 LAD – LAFB, LBBB, LVH, inferior MI
 RAD – LPFB, RVH, lateral MI, acute (e.g. PE) or chronic (e.g. COPD) lung disease
 Four waves
 P-wave
 P-mitrale (left atrial enlargement) – M-shaped (or widened) P waves
 P-pulmonale (right atrial enlargement) – large P-wave (>2.5 small squares) in inferior leads
 QRS complex
 Left ventricular hypertrophy – large S waves in V1-V3 and large R waves in V4-V6 (with LAD)
 Right ventricular hypertrophy – large R waves in V1-V3 and large S waves in V4-V6 (with RAD)
 Pathological Q waves (current or prior myocardial infarction) – large Q waves
 R wave progression – poor in prior anteroseptal MI or LVH (absent in dextrocardia)
 T-wave
 Peaked T waves – hyperkalaemia (narrow) or STEMI (wide)
 Flattened T waves – hypokalaemia or ischaemia
 Inverted T waves – ischaemia (in contiguous leads) or BBB
 Biphasic – hypokalaemia or ischaemia
 U-wave
 May follow T wave; abnormal if prominent (digoxin or hypokalaemia) or inverted
 Four intervals/segments
 PR interval
 Shortened – pre-excitation or junctional rhythm
 Prolonged – heart block
 QRS interval
 Narrow complex – sinus, atrial, or junctional origin
 Wide complex – ventricular origin (or supraventricular with aberrant conduction)
 LBBB – dominant S wave in V1 with broad/notched R waves (and no Q waves) in lateral leads (WiLLiaM)
 RBBB – RSR’ pattern in V1 with broad S waves in lateral leads (MaRRoW)
 ST segment
 Depression – ischaemia or hypokalaemia or digoxin toxicity (‘sagging’/‘reverse tick’)
 Elevation – infarction (with reciprocal changes) or pericarditis (widespread)
 QTc interval
 Prolonged – prolonged QT syndrome or medications
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Note: RBBB does not cause axis deviation (if present suggestive of bi-
fascicular block which can progress to tri-fascicular (AV) block )
 Left anterior hemiblock – RBBB + LAD
 Left posterior hemiblock – RBBB + RAD
ECG reference ranges
FEATURE REFERENCE RANGE
PR interval 120-200 milliseconds (3-5 small squares)

QRS duration <120 milliseconds (<3 small squares)

QTc interval <440/460 milliseconds in men/women

Pacing rhythms
 Pacemakers cause LBBB (and hence LAD) (typically pace right ventricle)
Right ventricular infarcts
Up to 40% of inferior STEMIs are complicated by right ventricular infarct. These patients are very preload sensitive (due to  RV
contractility) and can become severely hypotensive in response to nitrates or diuretics (treat with IV fluids).
ECG FINDINGS
 Suggested by : ST elevation in V1
 Confirmed by : ST elevation in V4R, V5R, and V6R (right-sided mirrored precordial leads are mirrored)
Miscellaneous ECG changes
 Hypothermia – sinus bradycardia with ‘J waves’ (waves at the J point of the ST segment)
 Hyperkalaemia – peaked T waves and prolonged PR segment  widened QRS and loss of P waves  sine waves and VF/asystole

Arrhythmias
Bradyarrhythmias
 Symptoms – signs of reduced cardiac output (dyspnoea, angina, syncope) and palpitations
 Signs – bradycardia, hypotension, heart failure
Bradyarrhythmias (<60bpm) and conduction abnormalities
ARRHYTHMIA FEATURES TREATMENT
SINOATRIAL NODE DYSFUNCTION

Sinus bradycardia Sinus rhythm (<60bpm) Typically, no treatment required

 Normal response to CVS conditioning  Stop offending drugs
 Sinus node dysfunction  Atropine (if indicated)
 Drugs (β-blocker/CCB excess)  Pacemaker (if refractory)

AV CONDUCTION BLOCKS

First-degree AV block Prolonged PR interval Typically, no treatment required

 Can occur in normal individuals  Stop offending drugs
 Increased vagal tone  Atropine (if indicated)
 Drugs (β-blocker/CCB/digoxin/amiodarone)

Second-degree AV block (Mobitz 1) Progressive PR lengthening until dropped beat occurs; the PR Typically, no treatment required
 Increased vagal tone interval then resets  Stop offending drugs
 Drugs (β-blocker/CCB/digoxin/amiodarone)  Atropine (if indicated)
 Ischaemia/infarction/fibrosis  Pacemaker (if refractory)

Second-degree AV block (Mobitz 2) Unexpected dropped beat(s) without a change in PR interval  Pacemaker
 Drugs (β-blocker/CCB/digoxin/amiodarone)
 Ischaemia/infarction/fibrosis Note: cannot tell between Mobitz I/II if fixed-ratio 2:1 block

Third-degree (complete) AV block Complete failure of conduction of supraventricular impulses to  Pacemaker

 Drugs (β-blocker/CCB/digoxin/amiodarone) ventricle (no P-QRS relationship); ventricular depolarisation
 Ischaemia/infarction/fibrosis initiated by an escape pacemaker distal to block (may be
narrow QRS – junctional, or wide QRS – ventricular)

Sick sinus syndrome Intermittent supraventricular tachyarrhythmias and  Pacemaker (for bradycardia)
 Idiopathic or multi-factorial most common bradyarrhythmias  β-blockers (for tachycardia)
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Tachyarrhythmias
 Symptoms – signs of reduced cardiac output (dyspnoea, angina, syncope) and palpitations
 Signs – tachycardia, hypotension, heart failure, irregular pulse
Supraventricular tachyarrhythmias (>100bpm)
ARRHYTHMIA FEATURES TREATMENT
ORIGINATING AT THE ATRIA

Sinus tachycardia Sinus rhythm (>100bpm) Typically, no treatment required

 Normal response to fear/pain/exercise  Treat underlying cause
 Other causes: hypoxia, hyperthyroidism,  β-blockers/CCB (if indicated)
infection, anaemia, hypotension, PE

Atrial fibrillation Irregularly irregular rhythm, no P waves, and fibrillatory waves

 ACUTE AF – PIRATES (best visualised in V1, similar to atrial flutter); can be classified
 Pulmonary disease (not asthma) as slow AF (<60bpm) or fast AF (>100bpm) (or normal)
 Ischaemia
 Rheumatic heart disease
 Anaemia/Atrial myxoma
 Thyrotoxicosis Refer to notes below
 Ethanol
 Sepsis
 Chronic AF – HTN or HF

Atrial flutter Flutter waves (‘saw-tooth’ pattern) at atrial rate of ~300bpm;

 Re-entry circuit in right atrium ventricular rate determined by AV conduction ratio (‘degree of
AV block’) – 2:1 is the most common, resulting in ventricular
rate of 150bpm (i.e. 1:1 = 300bpm, 3:1 = 100bpm, 4:1 = 75bpm)

Multifocal atrial tachycardia Irregularly irregular rhythm (>100bpm); at least 3 distinctive P  Treat underlying cause
 Multiple ectopic atrial pacemakers or re- wave morphologies  CCB (if indicated)
entry pathways (seen in elderly patients with
severe COPD or heart failure)

ORIGINATING AT THE AV JUNCTION

Atrioventricular nodal re-entry tachycardia Typically, narrow-complex tachycardia (unless BBB); P waves Acute treatment pathway:
(AVNRT) buried in QRS complex or retrograde conduction  Vagal manoeuvres
 Re-entry circuit in the AV node  Valsalva manoeuvre
 Dual pathway:  Carotid massage
 Slow α-fibres (short refractory periods)  Adenosine
 Fast β-fibres (long refractory periods)  Cardioversion (rarely)

Chronic treatment pathway:

Wolff-Parkinson-White syndrome (WPW)  WPW: wide-complex with δ  β-blockers/CCB
 WPW – a pre-excitation syndrome due to an wave (upsloping PR segment)  Catheter ablation (if refractory)
accessory pathway (bundle of Kent) between  AVRT (orthodromic): similar
atria and ventricles to AVNRT (cannot see δ wave) Note: avoid AV blockers in SVT with
 Paroxysmal tachycardia (atrioventricular  AVRT (antidromic) (rare): aberrancy (antidromic AVRT) as it
reciprocating tachycardia) can occur via wide-complex tachycardia will precipitate accessory pathway
orthodromic (retrograde atrial activity from activity (treat as VT if unsure)
ventricle) or antidromic (ventricular activity
via accessory pathway)

Paroxysmal atrial tachycardia Typically, narrow-complex tachycardia (unless BBB) with

 Single ectopic atrial pacemaker consistently abnormal P waves

Ventricular tachyarrhythmias
ARRHYTHMIA FEATURES TREATMENT
Premature ventricular contraction (PVC) Premature wide QRS complex, usually followed by Typically, no treatment required
 Can occur in normal individuals compensatory pause (often occurs in repeating patterns)  Treat underlying cause
 Other causes: stress, exercise, caffeine,  β-blockers/CCB (if indicated)
alcohol, smoking, sympathomimetics

Ventricular tachycardia (VT) Wide complex tachycardia; classified as sustained (>30s) or non- Stable:
 Associated with severe cardiac pathology sustained and haemodynamically stable or unstable; may  Amiodarone
degenerate into VF if left untreated
Unstable:
 ACLS (as for VF)

Note: may appear similar to SVT with aberrant conduction, but

VT demonstrates AV dissociation – P and QRS at different rates
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Ventricular fibrillation (VF) Totally erratic wide-complex tracing Fatal unless ACLS instituted
 Associated with severe cardiac pathology (in
addition to most other severe illness)

Torsades de pointes Polymorphic ventricular tachycardia occurring in the context of  Treat underlying cause of  QT
 Long QT syndrome QT prolongation; it has a characteristic morphology in which  IV magnesium
 QT-prolonging medication the QRS complexes “twist” around the isoelectric line  Increase HR (which QT)
 Electrolyte disorders ( Mg/K/Ca)  Temporary overdrive pacing
 Isoproterenol
 Cardioversion (if unstable)

Atrial fibrillation
DIAGNOSIS
 Determine underlying cause
 Diagnosis by clinical symptoms and examination ; confirmed by ECG
 All patients should receive echocardiography (as it may influence treatment – e.g. structural abnormalities)
 Thromboembolic risk assessed by CHA 2DS 2-VASc (and conversely bleeding risk assessed by HAS-BLED)
AF scoring systems
CHA2DS2-VASC HAS-BLED
 Congestive heart failure  Hypertension
 Hypertension  Abnormal renal or liver function (1 point each)
 Age >75 years (+2 points)  Stroke
 Diabetes mellitus  Bleeding (prior history or predisposition)
 Stroke/TIA/thromboembolism (+2 points)  Labile INR
 Vascular disease  Elderly >65 years
 Age 65-74 years  Drugs (NSAIDs/antiplatelets or EtOH)
 Sex (female)

CLASSIFICATION
 Newly-detected – only one diagnosed episode
 Paroxysmal – AFib sustained for <7 days and resolves – favours rhythm control
 Persistent – recurrent AFib sustained for >7 days or AFib that terminates only with cardioversion
 Permanent – continuous AFib (>1 year) that is unresponsive to cardioversion – favours rate control
TREATMENT
 Major objectives ( RACE):
 Rate control : β-blocker  CCB (diltiazem or verapamil – and only if LVEF >40%)
 In patients with heart failure : consider digoxin as an adjunct to β-blockers
 Anticoagulation : dabigatran or rivaroxaban (if CHADS-VASC ≥1); warfarin (only if extremely poor renal function )
 Make sure to balance decision on HAS-BLED score (risk of stroke versus risk of bleeding)
 Electrical Cardioversion : considered in patients with new onset AF (poor evidence) or haemodynamic instability
 If AFib <48hr can usually cardiovert without anticoagulation
 If AFib >48hr consider anticoagulation prior to and post-cardioversion due to risk of unstable intra-atrial thrombus
 aEtiology: treat the underlying cause (PIRATES)
 Rhythm control (managed by a cardiologist) is favoured in paroxysmal or newly-detected AF, young patients (<65), poor symptom
control, or in some types of structural heart disease (amiodarone or sotalol if structural heart disease, flecainide or sotalol if no
structural heart disease; also consider pulmonary vein ablation/surgery )
 Studies suggest that there no difference in long-term survival when treating with rhythm versus rate-control strategy
COMPLICATIONS
The two major complications of AF are thromboembolism (i.e. stroke) and rate-related cardiomyopathy (that can lead to CHF)

ACLS protocol
 Shockable rhythms: pulseless ventricular tachycardia and ventricular fibrillation
 Non-shockable rhythm:
 Pulseless electrical activity – presence of a co-ordinated electrical rhythm without a detectable cardiac output (pulse)
 Causes of PEA are considered the 4H’s and 4T’s (but not hyperthermia)
 Asystole – the absence of any cardiac electrical activity
 Correction of potential reversible causes – 4H’s and 4T’s (below)
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Catheter ablation
Catheter ablation is the destruction of aberrant cardiac electrical pathways via radiofrequency ablation or cryotherapy .
INDICATIONS
 Consider catheter ablation in:
 AVNRT/AVRT (most common)
 Atrial flutter – re-entry pathway in right atrium
 Atrial fibrillation – pulmonary vein ablation
 Ventricular tachycardia (rarely – most VT is due to scarring and cannot be ablated)

Heart failure
HEART FAILURE
Heart failure is a clinical syndrom e caused by the inability of the heart to pump enough blood to maintain fluid and metabolic
homeostasis.
AETIOLOGY
 Heart failure is commonly caused by hypertension (pressure overload) and ischaemic heart disease (volume overload )
 It is also caused by arrhythmia (volume overload), valvular heart disease (pressure or volume overload), and cardiomyopathy
(volume overload apart from hypertrophic cardiomyopathy)
 Volume overload characterised by displaced apex beat and pressure overload by hyperkinetic apex beat
PATHOPHYSIOLOGY
 Myocardial insult causes pump dysfunction/impaired filling leading to myocardial remodelling
 Pressure overload (e.g. AS or HTN) leads to compensatory hypertrophy (concentric remodelling) and interstitial fibrosis
 Volume overload (e.g. AR) leads to dilation (eccentric remodelling)
 Results in decreased cardiac output and resultant activation of SNS and RAAS
 Water and sodium retention leads to increased pre- and afterload and tachycardia
 Perpetuates cycle of increasing cardiac demand and decompensation
CLASSIFICATION OF HEART FAILURE
Left-sided heart failure
There are two types of left-sided heart failure:
 Heart failure with reduced ejection fraction (HFrEF) – also called systolic failure
 Pathophysiology: a failure of contraction leading to  EF /  EDV /  EDP
 Heart failure with preserved ejection fraction (HFpEF) – also called diastolic failure
 Pathophysiology: a failure of relaxation leading to  LV filling / normal EDV /  EDP (compensatory) / normal EF
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 Increased left-sided pressures are transmitted into the pulmonary vasculature (cause for pulmonary oedema and right-sided failure)
Right-sided heart failure
 Right-sided heart failure
 Physiology: increased right-sided pressures are transmitted into the systemic vasculature (accounting for systemic oedema and
congestive effects).
High-output heart failure
A minority of patients have high cardiac output (accompanied by low systemic vascular resistance).
 This is caused by peripheral demand for increased cardiac output (e.g. excess fluids, severe anaemia, hyperthyroidism, AV fistula, L-R
shunting, renal/hepatic disease, wet beriberi) which eventually causes systolic failure
CLINICAL PRESENTATION
The clinical presentation of heart failure depends on the specific subtype, but commonly includes the following signs and symptoms:
Signs and symptoms of left versus right heart failure
LEFT FAILURE RIGHT FAILURE
Low Cardiac Output  Fatigue  Left failure symptoms ( RV output  LV underfilling)
(forward failure)  Hypotension  Tricuspid regurgitation
 Syncope  S3 heart sound
 Cool extremities
 Slow capillary refill
 Peripheral ( central) cyanosis
 Pulsus alternans (alternating strong/weak pulse)
 Mitral regurgitation
 S3 heart sound
 Displaced apex beat

Venous Congestion  Dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea  Peripheral oedema

(backward failure)  Pulmonary oedema  Elevated JVP
 Bilateral basal crepitations  Hepatomegaly
 Cough  Ascites
 Pleural effusion  Pulsatile liver

DIAGNOSIS
 Identification and assessment of precipitating factors and treatable causes is essential
 Labs: CBC, U&E (including calcium and magnesium), LFTs, HbA1c, lipids, TSH, BNP
 BNP is a hormone released in relation to myocyte (ventricular) stretch
 ECG: chamber enlargement, arrhythmia, ischaemia/infarction
 CXR (ABCDE):
 Alveolar (pulmonary) oedema
 Kerley B lines
 Cardiomegaly (most important)
 Dilated upper lobe vessels
 Pleural Effusion
 Echocardiography: systolic and diastolic function, cardiac
dimensions, wall motion abnormalities, heart pathology
TREATMENT OF ACUTE HEART FAILURE (PULMONARY OEDEMA)
Treat underlying causal factors and then PPPOND:
 P – BiPAP or CPAP
 P – position (sit patient with legs hanging down)
 P – vasoPressors (e.g. dopamine or dobutamine – in cardiogenic shock)
 O – oxygen (in hypoxaemic patients)
 N – nitrates sublingual /patch/IV (avoid hypotension)
 D – diuresis (frusemide) IV
 + VTE prophylaxis
TREATMENT OF CHRONIC HEART FAILURE
Majority of evidence applies to HFrEF (currently no proven therapy to  mortality in HFpEF – diuretics are mainstay of treatment):
 Lifestyle change (especially Na/H2O restriction )
 Pharmacologic therapy:
 β-blockers* – in all patients (unless cardiogenic shock )
 Renin-angiotensin-aldosterone blockade * – in all patients
 Mineralocorticoid (aldosterone) receptor antagonists * – in all patients
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 Diuretics – to reduce the signs and symptom s of congestion (no mortality benefit)
 Loop/thiazide diuretics oppose the hyperkalaemia that can be induced by β-blockers, ACEi/ARB, and MRAs
 Cardiac glycosides (digoxin) – in patients who have fast AF
 Antiarrhythmic drugs – in patients with existing arrhythmias
 Anticoagulants, antiplatelets , and statins – only if existing indications
 Advanced treatments*:
 Implantable cardiac defibrillator (ICD) in patients at high risk of sudden cardiac death
 Resynchronisation therapy (biventricular pacemaker) – can improve symptoms in some forms of heart failure (e.g. LBBB)
 Left ventricular assist device (LVAD) or cardiac transplantation – if unresponsive to maximal medical therapy

Note: mortality benefit*

PROGNOSIS
 The New York Heart Association (NYHA) Functional Classification of Heart Failure can be used to stratify/estimate prognosis:
 Class I: ordinary physical activity do not cause symptoms of heart failure
 Class II: comfortable at rest, ordinary physical activity results in symptoms
 Class III: marked limitation of ordinary activity, less than ordinary physical activity results in symptoms
 Class IV: inability to carry out any physical activity without symptoms or symptoms at rest
COMPLICATIONS
 Arrhythmias (most commonly atrial fibrillation)
 Sleep-disordered breathing (up to 50% of patients experience sleep apnoea or Cheyne-Stokes breathing)
 Systemic embolic phenomena (including stroke)
 Sudden cardiac death (most often via ventricular tachycardia)

Ischaemic heart disease

Ischaemic heart disease (IHD) (also known as coronary artery disease – CAD ) is a group of conditions that include stable angina,
unstable angina, myocardial infarction, and sudden cardiac death .
RISK FACTORS
 Major: diabetes mellitus, smoking, hypertension, dyslipidaemia, family history
 Minor: obesity, age, male (or post-menopausal female), heavy alcohol intake, sedentary lifestyle
Angina Pectoris
Angina pectoris (i.e. stable angina) is defined as substernal chest pain secondary to myocardial ischaemia (i.e. an imbalance between
myocardial oxygen supply and myocardial oxygen demand ) lasting less than 20 minutes.
CLINICAL PRESENTATION
 Classic triad of brief (<20m) substernal chest pain ( dull/pressure-like) precipitated by stress/exertion and is relieved b y rest/nitrates
 Pain can radiate and may be associated with shortness of breath, nausea/vomiting, sweating, or light-headedness
 Rarely, it may occur when lying down at night (called angina decubitus )
 Examination typically unremarkable
DIAGNOSIS
 Clinical diagnosis ( but must rule out other causes of chest pain – i.e. acute coronary syndrome, pericarditis, aortic dissection,
pulmonary embolism, pneumothorax, pneumonia, MSK chest pain, GORD)
 ECG is the best initial test for any type of chest pain
 Stress testing (ST-segment or wall-motion changes with exercise or pharmacologic stress are diagnostic of IHD)
 Pharmacologic stress test should be used in patients who cannot exercise, have abnormal baseline ECGs, or have a pacemaker
 CXR (suspected heart failure, valvular disease, pericardial disease, aortic dissection/aneurysm, or pulmonary disease)
 Labs: CBC, lipids, glucose
TREATMENT
 Lifestyle modification
 Sublingual GTN for immediate pain relief
 GTN: use immediately  use at 5 minutes if pain has not eased  call ambulance a further 5 minutes if pain has not eased
 β-blocker (metoprolol)  CCB (diltiazem)  and long-acting nitrate (isosorbide mononitrate) in that order for angina prophylaxis
 Initiate risk factor reduction
 Aspirin (or clopidogrel) for mortality reduction in all patients
 Statin for lipid management in all patients
 ACEI in patients with co-existing indicators (e.g. hypertension, diabetes, heart failure, previous MI)
 Revascularisation may be considered (typically provides symptomatic rather than prognostic benefit)

Note: only aspirin and β-blockers have an impact on mortality

 13

NON-CARDIAC DIFFERENTIAL DIAGNOSIS

 GORD: history described as hoarseness and worse after meals; relief of symptoms with PPI confirms diagnosis
 MSK/costochondritis : pain is described as tender to palpation and movement
 Pneumonia/pleuritis: pain is described as worsening with breathing (pleuritic)
 Anxiety: patients may have a history
Prinzmetal’s (variant) angina
Prinzmetal’s (variant) angina mimics angina pectoris but is caused by vasospasm of coronary vessels.
 Typically effects young women at rest, early morning, and is associated with ST-elevation in absence of cardiac enzyme rise
 Treated with GTN and CCBs (diltiazem)
ACUTE CORONARY SYNDROME
A spectrum of clinical syndromes caused by plaque disruption or vasospasm that leads to acute myocardial ischaemia/infarction .

Classification
Myocardial infarction
Myocardial infarction is defined by evidence of myocardial necrosis and is diagnosed by:
 Rise/fall of serum cardiac markers , plus one of
 Symptoms of ischaemia (chest/upper limb/mandibular/epigastric discomfort; dyspnoea)
 ECG changes (ST changes; new BBB; pathological Q waves)
 Imaging evidence
Unstable angina
Unstable angina is clinically defined by any of the following
 New-onset angina
 Angina at rest
 Accelerating pattern of pain ( frequency/duration or  threshold/response to treatment)
 Angina post-MI or post-procedure

Unstable angina signals the presence of a possible impending infarction based on plaque instability.
NSTEMI
NSTEMI is defined as myocardial infarction without ST-elevation or new BBB
 NSTEMI is often considered in conjunction with unstable angina as their pathological processes are similar
STEMI
STEMI is defined as myocardial infarction with ST-elevation or new BBB

Clinical presentation
 Presents with acute-onset substernal chest pain , commonly described as pressure or tightness, that can radiate to left arm, neck, or
jaw
 The pain is like angina but more severe, longer (>20m) and unrelieved by GTN
 Associated symptoms: nausea/vomiting, dyspnoea, diaphoresis, palpitations, light-headedness, syncope, anxiety
 Signs: tachycardia, hyper- or hypotension, signs of heart failure, murmur, sweating, distress
 Low-grade fever may be present
 Pericardial rub and peripheral oedema can develop later
Atypical presentation
 An atypical presentation is common (particularly in the elderly and diabetics)
 This may present as syncope, pulmonary oedema, epigastric pain, vomiting, hypotension, oliguria, confusion, stroke, hyperglycaemia
 Some patients do not report chest pain

Diagnosis
 Clinical history
 Cardiac enzymes – troponins or CK-MB
 Can take up to 6 hours to elevate; peak between 24-48 hours; and return to baseline over 5-10 days
 ECG – ST-segment change, T-wave change, new BBB, or pathological Q waves
 Sequence of ECG changes in STEMI: peaked T-waves  ST-segment elevation  pathological Q-waves  T -wave inversion
 ST-segment normalisation  T-wave normalisation
 In NSTEMI/UA: look for ST-depression, T-wave inversion, or normal
 CXR – cardiomegaly, pulmonary oedema, aortic rupture
 Additional labs
 CBC, U&E, glucose, lipids, coagulation
 Scoring criteria (e.g. TIMI – thrombolysis stratification)
 14

Note: do not delay treatment waiting for troponins/CXR

Treatment
The treatment of acute coronary syndrome varies according to the specific cardiac enzyme and ST-segment changes but follows general
principles (NICE guidelines):
General management of ACS
For all patients with suspected acute coronary syndrome :
 Complete a full clinical assessment:
 Basic first aid – Airways, Breathing, and Circulation
 Conduct preliminary history and examination
 Obtain serial ECGs (determine if STEMI or NSTEMI)
 Attach cardiac and oxygen monitoring
 Obtain IV access and blood samples (serial cardiac troponins,
CBC, coagulation, U&E and magnesium, glucose, lipids)
 Note: management does not depend on cardiac
troponins being available
 Administrate early therapy:
 300mg aspirin orally (and discontinue NSAIDs)
 Sublingual GTN (or IV GTN) for chest pain, HTN, or heart failure
 Contraindicated in haemodynamic compromise (right ventricular infarct) or PDI-5 inhibitors
 Morphine/fentanyl for pain/anxiety
 Supplemental oxygen only if O2 saturation <90%

Note: life threatening conditions should always be considered in the differential diagnosis of chest pain, especially aortic dissection ,
pulmonary embolism , and tension pneumothorax .
Unstable angina or NSTEMI
TREATMENT GUIDELINES
 All patients:
 P2Y inhibition: ticagrelor  clopidogrel (in addition to aspirin)
 Treatment with invasive therapy (determined by risk stratification and within 72 hours of first medical contact)
 IV UFH or LMWH
 Treatment with non-invasive therapy
 SC LMWH
STEMI
 All patients:
 P2Y inhibition: ticagrelor  clopidogrel (in addition to aspirin)
 Treatment with PCI (preferred if within 12 hours of symptom onset and performed within <90 minutes of first medical contact)
 IV UFH or LMWH
 Transfer to CCU for 24-48 hours post-PCI
 Treatment with fibrinolysis (performed within 12 hours of symptom onset and no active internal bleeding or history of stroke):
 Immediate transfer for angiography or PCI within 24 hours (fibrinolysis is only 50% effective on its own)
 IV LMWH loading dose followed by SC LMWH (unless >75yo where only SC given)
 Treatment without reperfusion therapy (performed if delayed treatment or contraindication to other therapy):
 IV LMWH loading dose followed by SC LMWH (unless >75yo where only SC given)
Long-term management of ACS
 Low-dose aspirin (100-150mg/day) indefinitely (clopidogrel if contraindicated)
 Dual antiplatelet therap y (clopidogrel or ticagrelor) for 12 months or more
 High-dose statin early and indefinitely (irrespective of cholesterol levels)
 β-blockers early and indefinitely (unless heart failure or cardiogenic shock)
 ACEIs should be considered in all patients (unless contraindicated)
 Perform repeat echocardiography, angiography, ECG, or stress test if indicated
 Automatic two-week stand-down from driving
PCI
PCI may involve angiography , angioplasty and stenting , suction thrombectomy if bulky thrombus, and intra-arterial antiplatelet if
thrombus burden large or slow flow after intervention

Prognosis
OUTCOMES
 5-15% mortality in hospital - resting LVEF is useful prognostic factor
 15

 The first three months post-discharge has highest mortality rate

COMPLICATIONS OF MYOCARDIAL INFARCTION
 Complications of myocardial infarction – CRASH PPAD
 Cardiac Rupture (in first week)
 LV free wall (in transmural infarction)  causes cardiac tamponade
 Papillary muscle (in inferior infarction)  causes mitral regurgitation
 Ventricular septum (in septal infarction)  causes ventricular septal defect
 Arrhythmia (in first 48hrs) – most common cause of early death (usually VT/VF)
 Shock / Heart failure (in first 48hrs)
 Pericarditis (in first week)
 Pulmonary emboli / DVT / mural thrombosis / systemic emboli (weeks to months)
 Aneurysm (weeks to months)
 Dressler syndrome (autoimmune process occurring 2-10 weeks post-MI – fever, pericarditis, pleural effusion,  WBC and
ESR)
SUDDEN CARDIAC DEATH

DEFINITION
 Unanticipated, non-traumatic, cardiac death in a stable patient which occurs within 1 hour of symptoms onset
 Most commonly due to ventricular fibrillation (or other ventricular arrhythmias)
AETIOLOGY
 Primary cardiac pathology
 Myocardial infarction
 Severe LV dysfunction
 Severe ventricular hypertrophy (HOCM or AS)
 Congenital heart disease
 Channelopathies (e.g. long QT syndrome)
CORONARY REVASCULARISATION

CLASSIFICATION
 Percutaneous coronary intervention (balloon angioplasty and intracoronary stenting)
 Can be performed more rapidly than CABG
 Coronary artery bypass graft surgery (CABG)
 Indications: severe left main disease, triple vessel disease, diffuse disease (e.g. severe diabetes mellitus)
 Graft options:
 Left internal thoracic/mammary artery – first-line (excellent patency)
 Saphenous vein grafts – used when arterial grafts not available or multiple grafts required
OUTCOME
 Similar outcome (although CABG has decreased need for repeat revascularisation procedures)

Myocardial disease
MYOCARDITIS
Myocarditis is an inflammatory process involving the myocardium.
 It is an important cause of dilated cardiomyopathy
AETIOLOGY
 Idiopathic
 Infectious (esp. Coxsackie B virus)
 Toxic (catecholamines , chemotherapy, cocaine)
 Systemic diseases (e.g. rheumatic fever, giant cell myocarditis)
CLINICAL PRESENTATION
 Typically, follows a minor pyrexical illness
 Non-specific constitutional or cardiac symptoms (e.g. acute CHF, chest pain, arrhythmia, syncope)
DIAGNOSIS
 Diagnosis of exclusion
 Labs:  troponin
 ECG: non-specific
 Echo: quantification of impaired ventricular function
 16

 Myocardial biopsy – definitive diagnosis (but rarely performed unless severe)

TREATMENT
 Supportive care (treat complications)
 Activity restriction (reduce exercise until cardiac biomarkers improved)
 Avoid exacerbating factors – NSAIDs and alcohol
 Anticoagulation
CARDIOMYOPATHY
Cardiomyopathy is intrinsic or primary myocardial disease not due to congenital, hypertensive, coronary, valvular, or pericardial disease.
CLASSIFICATION

Aetiology of cardiomyopathies
HEART FAILURE WITH REDUCED EJECTION FRACTION (HFREF) HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF)
Dilated cardiomyopathy Hypertrophic cardiomyopathy Restrictive cardiomyopathy

 Idiopathic (presumed viral– most common)  Genetic disorder affecting cardiac  Amyloidosis
 Myocarditis sarcomeres (most common cause of  Sarcoidosis (rarely dilated)
 Toxins (alcohol or cocaine) sudden cardiac death in young  Haemachromatosis (rarely dilated)
 Drugs (steroids or chemotherapy) athletes)  Scleroderma
 Collagen vascular disease
 Thiamine deficiency (wet beriberi)

Classification of cardiomyopathies
TYPE
Variable Dilated Hypertrophic Restrictive

Major abnormality Impaired contractility Impaired relaxation Impaired elasticity

LV size (end diastole)   

LV size (end systole)   

Ejection fraction   (or normal) Normal

Wall thickness   

Dilated cardiomyopathy
Dilated cardiomyopathy is unexplained dilation and impaired systolic function in one or both ventricles.
 Most common form of cardiomyopathy
CLINICAL PRESENTATION
 May be present as CHF (with reduced EF), arrhythmia, systemic or pulmonary emboli , sudden death
DIAGNOSIS
 Labs:
 High: BNP, creatinine, LFTs
 Low: bicarbonate, sodium
 CXR: global cardiomegaly (globular heart) and signs of CHF
 Echocardiography is diagnostic (as in all forms of cardiomyopathy)
TREATMENT
 Treat underlying cause
 Treat heart failure
 Anticoagulation
PROGNOSIS
 Poor prognosis – death usually to CHF or SCD

Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy is unexplained ventricular hypertrophy .
 Due to genetic defect involving cardiac sarcomere proteins
 Classified as obstructive or non-obstructive
CLINICAL PRESENTATION
 Typically, asymptomatic (or symptoms of LV outflow obstruction) – hence, screening important
 17

 Clinical signs: high volume jerky pulse ; pulsus bisferiens (biphasic pulse); heaving, non-displaced, apex with double/triple apical
impulse, ejection systolic murmur ± S4 (loudest left sternal edge;  with Valsalva manoeuvre /  with squatting)
DIAGNOSIS
 ECG: evidence of LVH
 Echocardiography is diagnostic (as in all forms of cardiomyopathy)
 Screening: resting ECG and echocardiography (genetic testing is not recommended as first-line due to varying penetrance)
TREATMENT
 Avoidance of all competitive sport (most common cause of sudden cardiac death in young athletes)
 Obstructive HCM:
 Pharmacotherapy: β-blockers or CCB
 Avoid: nitrates, diuretics, ACE (worsen LV obstruction gradient)
 Surgery (if drug-refractory): surgical myectomy or alcohol septal ablation
 ICD if high risk of sudden cardiac death (e.g. arrhythmia,  BP with exercise, syncope, family history, or severe hypertrophy)

Restrictive cardiomyopathy
Restrictive cardiomyopathy is defined as impaired ventricular filling with preserved EF in a non-dilated, non-hypertrophied, ventricle
secondary to factors that decrease myocardial compliance (i.e. fibrosis and/or infiltration).
 Presents similarly to constrictive pericarditis
 Echocardiography is diagnostic (as in all forms of cardiomyopathy)
 Treatment dependent on underlying aetiology
MYXOMA
Myxoma is the most common form of cardiac tumour (>50%).
 It is a benign tumour (80% of cardiac primary tumours are benign)
 Approximately 75% occur in the left atrium
CLINICAL PRESENTATION
 Classical triad : heart failure, embolic disease (predisposes to thromboembolism), and constitutional symptoms
 A murmur that mimics mitral stenosis (although its loudness/location varies from beat to beat with body position)
 Also associated with: atrial fibrillation , clubbing, and Raynaud syndrome
TREATMENT
 Surgical excision

Hypertension
Hypertension is a blood pressure at which an otherwise healthy person would have an increased risk of cardiovascular disease.
 HTN is a risk factor for IHD, CHF, CVD, CKD, and PVD
PATHOPHYSIOLOGY
 95% of hypertension is primary (no identifiable cause - genetic and lifestyle factors; probably due to impaired sodium handling )
 Causes of secondary hypertension – R-CHADS-P
 Renal disease (renovascular hypertension or renal parenchymal hypertension) – most common secondary cause
 Cushing’s, Hyperaldosteronism, Aortic coarctation, Drugs (e.g. OCP/steroids), renal artery Stenosis, Pheochromocytoma
CLASSIFICATION
 HTN is classified based on blood pressure:
 Stage 1 (mild): >140/90mmHg
 Stage 2 (moderate): >160/100mmHg
 Stage 3 (severe): >180/110mmHg
 Classification can also be based on isolated systolic or diastolic levels
DIAGNOSIS
 Ambulatory monitoring is gold standard for diagnosis (although a series of elevated BP readings in clinic warrant diagnosis)
 Consider white-coat hypertension (BP  in clinic) and masked hypertension (BP  in clinic)
 Tests for all patients (assessing for end-organ damage): U&E, HbA1c, lipids, 12-lead ECG, urinalysis with ACR, fundoscopy
 Tests for specific patient subgroups:
 If suspected endocrine cause: plasma aldosterone and renin
 If suspected pheochromocytoma: urine/plasma metanephrines
 If suspected LVH: echocardiography
 If suspected renal artery stenosis: renal ultrasound/arteriography
 18

TREATMENT
Treatment is indicated if stage 2 or greater hypertension or any stage with associated comorbidity (including high cardiovascular risk):
 Blood pressure goals: <140/90mmHg or <130/80mmHg if patient has comorbidity (diabetes, IHD, CVD)
 Treatment algorithm :
1. Lifestyle modification –  salt (most important),  exercise,  alcohol,  smoking,  weight; change diet; stress management
2. If <55yo: ACEI | if >55yo: CCB
3. If <55yo: CCB | if >55yo: ACE
4. Add thiazide diuretic
5. If BP remains >140/90 after full regimen above, then this is resistant hypertension
 Add MRA, α-blocker, or β-blocker
 Reassess for secondary causes of HTN and consider referral
Hypertensive emergencies
Hypertensive emergency (hypertensive crisis ) is defined as hypertension (usually >220/120mmHg) with acute end-organ damage.
CLINICAL PRESENTATION
 Typically, presents with headache, visual disturbance, or confusion (hypertensive encephalopathy)
 Visualised by fundoscopy (papilloedema and bilateral retinal haemorrhages)
 Associated with:
 Malignant hypertension (direct vascular damage due to hypertension)
 Cerebrovascular – hypertensive encephalopathy or stroke
 Cardiac – aortic dissection, myocardial infarct, or heart failure
 Renal – acute kidney injury
TREATMENT
 IV anti-hypertensives (β-blocker, CCBs, or nitrates) – aim for slow control over one-to-two hours

Pericardial disease
PERICARDITIS
Pericarditis is inflammation of the pericardial sac.
 Can compromise cardiac output via tamponade or constrictive pericarditis
AETIOLOGY
 Most commonly idiopathic (presumed to be viral)
 Several other causes including viral infection (esp. Coxsackie B virus), uraemia, drugs, neoplasm, radiation, trauma, aortic
dissection
 May also occur after MI (acutely or as Dressler syndrome) or open-heart surgery
CLINICAL PRESENTATION
 Diagnostic triad : pleuritic chest pain , pericardial rub , and characteristic ECG changes
 Pain tends to worsen in the supine position and with inspiration (‘classic patient’ sits up and bends forward)
 Also associated with dyspnoea, cough, and fever
DIAGNOSIS
 Important to exclude ACS or pneumonia
 Initial tests: CXR, ECG, and echocardiogram
 ECG changes:
 Widespread concave ST elevation and PR
depression (and reciprocal changes in aVR ± V1)
 Sinus tachycardia
 Echocardiography : pericardial effusion/thickening
TREATMENT
 Address underlying cause or symptoms
 Activity restriction (reduce exercise until cardiac biomarkers improved)
 Post-MI pericarditis – aspirin
 Avoid corticosteroids within a few days after MI as they predispose to ventricular wall rupture
 Viral pericarditis – NSAIDs
 Pericardial effusion – monitor if asymptomatic (otherwise pericardiocentesis if tamponade)
COMPLICATIONS
 Recurrent episodes of pericarditis
 Pericardial effusion
 19

 Cardiac tamponade
 Constrictive pericarditis
 Atrial arrhythmias
CONSTRICTIVE PERICARDITIS
Constrictive pericarditis is a result of fibrosed, thickened, adherent, and/or calcified pericardium due to recurrent acute pericarditis.
CLINICAL PRESENTATION
 May mimic CHF (especially right-sided HF)
 Difficult to differentiate from cardiac tamponade
 May hear a pericardial knock (similar to S3 but earlier and louder)
DIAGNOSIS
 Echo/CT/MRI: pericardial thickening
 Cardiac catheterisation is diagnostic
TREATMENT
 Medical: diuretics and Na/H2O restriction
 Surgical: pericardiectomy (if refractory)
CARDIAC TAMPONADE
Cardiac tamponade is a clinical diagnosis of a rapidly accumulating pericardial effusion.
 Classically results from pericarditis (esp. trauma, malignancy, uraemia, aortic dissection )
PATHOPHYSIOLOGY
 High intra-pericardial pressure   venous return   ventricular filling   CO  hypotension and venous congestion
CLINICAL PRESENTATION
 May mimic CHF (especially right-sided HF) and cardiogenic shock
 Beck’s triad: hypotension , increased JVP , muffled heart sounds (also tachycardia, pulsus paradoxus , and Kussmaul sign )
DIAGNOSIS
 ECG: electrical alternans (pathognomonic variation in R wave amplitude) (uncomplicated effusion – decreased ECG amplitudes)
 Echo: pericardial effusion with compression of cardiac chambers (RA/RV) in diastole
 CXR: enlarged heart shadow without pulmonary oedema
 Cardiac catheterisation
TREATMENT
 Treat underlying cause
 Echo-guided pericardiocentesis
 IV fluids may increase CO
 Avoid diuretics and vasodilators ( venous return to already under-filled RV   preload   CO)

Valvular heart disease

SUMMARY OF VALVULAR DISEASE

Aortic stenosis
AETIOLOGY
 Elderly (calcification from wear and tear)
 Aortic sclerosis is senile degeneration/thickening of valve which can progress to stenosis
 Congenital (bicuspid and unicuspid valve)
 Rheumatic heart disease
PATHOPHYSIOLOGY
 Outflow obstruction  increased EDP  concentric LVH  LV failure  myocardial ischaemia and heart failure
CLINICAL PRESENTATION
 Initially asymptomatic ; progress to symptoms of outflow obstruction – angina  syncope  heart failure (worsening prognosis)
INVESTIGATIONS
 Echocardiography: reduced valve area, pressure gradient, LVH, reduced LV function
 ECG: LAE/LVH, LBBB, AF
 CXR: LVH, LAE, CHF, calcified valve, post-stenotic aortic root dilation
PHYSICAL EXAM
 20

 Harsh systolic ejection murmur (crescendo-decrescendo pattern) +/- aortic ejection click (higher pitch than split S1)
 Radiates to carotids
 Murmur becomes longer as disease becomes more severe
 Soft S2 with paradoxical splitting
 Narrow pulse pressure
 Pulsus parvus et tardus (weak, delayed, carotid pulse)
 Brachial-radial delay
 Heaving, non-displaced, apex beat (before development of HF)
 Aortic thrill
TREATMENT
 Asymptomatic:
 Serial echocardiography
 Avoidance of exertion
 Symptomatic: aortic valve replacement (before LV dysfunction)
Aortic regurgitation
AETIOLOGY
 Acute: infective endocarditis, aortic dissection, trauma
 Chronic: congenital (bicuspid valve), rheumatic heart disease, infective endocarditis, connective tissue disorders (e.g. Marfan’s)
PATHOPHYSIOLOGY
 Regurgitation  volume overload  LV dilation  increased SV with high sBP and low dBP  increased wall tension  pressure
overload  LVH (in conjunction with low DBP causing  coronary perfusion)  myocardial ischaemia and heart failure
CLINICAL PRESENTATION
 Initially asymptomatic ; progresses to symptoms of  CO (in late disease) – angina  syncope  heart failure (worsening
prognosis)
 Acute aortic regurgitation : rapid onset of cardiogenic shock and severe left ventricular failure
INVESTIGATIONS
 Echocardiography: quantify degree of aortic regurgitation
 ECG: LAE/LVH
 CXR: LVH, LAE, CHF, aortic root dilation
PHYSICAL EXAM
 Early diastolic decrescendo murmur (“blowing”)
 Best heard sitting forwards
 Widened pulse pressure
 Water-hammer pulse
 Thrusting, displaced, apex beat
 Carotid pulsation (Corrigan’s sign )
 Head-nodding with heart beat (De Musset’s sign )
 Pulsation of uvula (Muller’s sign )
 Pulsation of the nailbed (Quincke’s sign )
 Femoral bruit (Duroziez’s sign )
 Pistol-shot femorals (Traube’s sign)
TREATMENT
 Asymptomatic :
 Serial echocardiography
 Afterload reduction (e.g. ACEIs or CCBs)
 Symptomatic :
 Avoid exertion
 Aortic valve replacement if severe

Mitral stenosis
AETIOLOGY
 Typically, rheumatic fever
PATHOPHYSIOLOGY
 Mitral stenosis  fixed cardiac output and LAE   LAP  pulmonary hypertension and CHF
 HF worse with AF (no atrial kick), tachycardia ( atrial emptying), and pregnancy ( preload)
 21

CLINICAL PRESENTATION
 Signs of left and right heart failure
 Infective endocarditis
 Atrial arrhythmias (and potential emboli)
 Malar flush with central cyanosis (‘mitral facies ’) if severe
INVESTIGATIONS
 Echocardiography: restricted opening of mitral valve
 ECG: LAE, RAE, RVH, AF
 CXR: LAE, CHF, mitral valve calcification
PHYSICAL EXAM
 Late low-pitched diastolic murmur with opening snap
 Irregularly irregular pulse (AF is common)
 Palpable diastolic thrill at apex
 Left parasternal heave
 Mitral facies if severe
TREATMENT
 Supportive:
 Serial echocardiography
 Avoid exertion
 Treat AF and CHF
 Prevention of recurrent rheumatic fever
 Increase diastolic filling time (e.g. β-blockers or digoxin)
 Surgical (if severe):
 Mitral balloon valvotomy or valve replacement for severe cases
Mitral regurgitation
AETIOLOGY
 Rheumatic heart disease and chordae tendineae rupture after myocardial infarction most common
 Also: mitral valve prolapse, myxomatous valve degeneration, infective endocarditis, annular calcification, cardiomyopathy
PATHOPHYSIOLOGY
 Mitral regurgitation  reduced CO  increased LV/LA pressure  LV and LA dilation  pulmonary hypertension and CHF
CLINICAL PRESENTATION
 Signs of left and right heart failure
 Atrial arrhythmias (and potential emboli)
 May be asymptomatic for years
INVESTIGATIONS
 Echocardiography: quantify degree of mitral regurgitation opening of mitral valve
 ECG: LVH/LAE, AF
 CXR: cardiomegaly (particularly LAE)
PHYSICAL EXAM
 Holosystolic murmur
 Radiates to axilla
 S3 (due to rapid filling of LV in early diastole)
 Displaced apex beat
 Left parasternal heave
TREATMENT
 Asymptomatic:
 Serial echocardiography
 Symptomatic :
 Diuretics to decrease preload/congestion
 ACEIs/CCBs to decrease afterload
 Anti-arrhythmics if necessary
 Surgery – valve repair or replacement if severe
Other murmurs
Uncommon murmurs
In their respective anatomical location, the following murmurs are:
 22

 Tricuspid stenosis – similar to mitral stenosis

 Tricuspid regurgitation – similar to mitral regurgitation
 Pulmonary stenosis – similar to aortic stenosis
 Pulmonary regurgitation – similar to aortic regurgitation
 Mitral valve prolapse – mid-to-late systolic murmur with click
Paediatric murmurs
 Atrial septal defect – systolic murmur with fixed split S2 (loudest at pulmonary area)
 Ventricular septal defect – holosystolic murmur (loudest at LLSB)
 Most common congenital heart defect
 Most close spontaneously
 Patent ductus arteriosus (PDA) – continuous ‘machinery-like’ systolic/diastolic
murmur (loudest at left infraclavicular area)

Extra heart sounds and clinical pearls

 S3 (ventricular gallop)
 Normal finding: young patients, trained athletes, pregnancy
 Abnormal: associated with ventricular dilation (e.g. systolic heart failure)
 S4 (atrial gallop)
 Almost always abnormal – low compliance ventricle (e.g. aortic/pulmonary stenosis, pulmonary HTN, or HOCM)
 Never heard with AF (requires atrial contraction)
 Dynamic auscultation
 Murmurs (other than HOCM) are:
 Decreased by the Valsalva manoeuvre ( preload)
 Increased by squatting ( preload)
INFECTIOUS ENDOCARDITIS
Infective endocarditis is an infection of the endocardium , commonly affecting the heart valves, especially the mitral valve.
 Typically affects already abnormal valves
 Leaflet vegetations are made of platelet-fibrin thrombi, WBCs, and bacteria
CLASSIFICATION
 Acute (sudden onset, normal valve) vs. subacute (gradual onset, abnormal valve)
 Native vs. prosthetic valve
 Right vs. left sided
PATHOPHYSIOLOGY
 Risk factors:
 Rheumatic, congenital, or valvular heart disease
 Prior endocarditis
 Prosthetic heart valves
 IV drug abuse (in 50% of IVDU-related IE the tricuspid valve is involved)
 Immunosuppression
 Opportunity for bacteraemia
 Causative agents and their common infections:
 Staphylococcus aureus: >80% of acute bacterial endocarditis cases in patients with a history of IV drug abuse
 Murmurs often negative in IV drug users
 Streptococcus viridans: left-sided sub-acute bacterial endocarditis, and following dental procedures in native valves
 Coagulase negative Staphylococcus: prosthetic heart valves
 Streptococcus bovis: occurs with coexisting GI malignancy
 Candida and Aspergillus species: accounts for most fungal endocarditis (predisposing factors include long-term IV catheters,
malignancy, AIDS, organ transplant, IV drug use)
 Rarely “HACEK” a group of fastidious gram -ve bacteria : Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella,
Kingella
CLINICAL PRESENTATION
 Commonly presents with the following signs/symptoms (mnemonic - FROM JANE):
 Fever
 Roth spots – haemorrhage in the eye with a white centre
 Osler nodes – painful, red, raised lesions on the hands and feet (due to immune complex deposition)
 Murmur
 Janeway lesions – non-tender, small, erythematous macules on the palms and soles (due to emboli)
 Anaemia – normochromic normocytic
 23

 Nail haemorrhage – due to emboli

 Emboli – may cause focal neurological deficits and other embolic phenomena
 Constitutional symptoms such as fever, weight loss and fatigue are common
 Can cause clubbing and splenomegaly

Note: the combination of a fever and new murmur should be considered endocarditis until proven otherwise.
DIAGNOSIS
 Based on risk factors , symptoms, and the Duke Criteria:
 Duke criteria – ≥2 major, 1 major and ≥3 minor, or ≥5 minor criteria merit the diagnosis of endocarditis
 Labs: CBC (anaemia,  WBC w/ left shift), U&E, ESR/CRP, rheumatic factor
 Serial blood cultures: 3 sets (of aerobic and anaerobic samples) collected from different sites >1h apart
 Persistent bacteraemia is the hallmark of endovascular infection (such as infective endocarditis)
 Echocardiogram – vegetations, regurgitation, abscess
Duke criteria
MAJOR CRITERIA MINOR CRITERIA
 Positive blood cultures for infective endocarditis  Predisposing risk factors
 At least two separate cultures for typical organisms  Fever
 Persistent bacteraemia with any organism (blood drawn >12hr apart)  Vascular phenomena: septic emboli, septic pulmonary infarcts/abscess,
 A single culture of C. burnetii mycotic aneurysms, Janeway lesions
 Evidence of endocardial involvement  Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots
 Positive echocardiogram for infective endocarditis  Microbiologic evidence that does not meet major criteria
 New valvular regurgitation (i.e. murmur)

TREATMENT
 Early empiric IV antibiotics (usually vancomycin + gentamicin )
 Switch to narrow antibiotics once pathogen identified
 Acute valve replacement is sometimes necessary (e.g. refractory CHF)
 Lifelong pre-procedure antibiotic prophylaxis (with amoxicillin or clindamycin if allergic) may be indicated if:
 Significant cardiac defects – prosthetic valves, rheumatic valvular disease, previous endocarditis, and
 Undergoing high-risk procedures – dental work involving gingival tissue, periapical region of teeth, or tonsillectomy
OUTCOME
 Mortality:
 Prosthetic valve (25-50%)
 Non-IVDU S. aureus (30-45%)
 IVDU S. aureus or streptococcal (10-15%)
RHEUMATIC FEVER
Rheumatic fever is a disease caused by pharyngeal infection with Lancefield group A β-haemolytic streptococci .
 The bacteria doesn’t enter the blood stream, but rather triggers rheumatic fever two-to-four weeks later in the susceptible population
PATHOPHYSIOLOGY
 An antibody to the carbohydrate cell wall of GAS cross-reacts with cardiac tissue (antigen mimicry), which has several effects and can
cause permanent damage
 Acute: typically, asymptomatic but causes carditis, pericarditis , valvulitis, and arrhythmia
 Chronic: valvular heart disease (mitral and/or aortic regurgitation/stenosis), infectious endocarditis, thromboembolism
CLINICAL PRESENTATION
 Most common in 5 to 15 years of age (tends to recur if not prevented; Pacific > Maori > other ethnicities)
 Acute rheumatic fever:
 Major (‘classic’) signs/symptoms – J♥NES:
 Joints – arthritis
 ♥ – Carditis
 Nodules (subcutaneous on extensor surfaces of joints and spine)
 Erythema marginatum (red raised rash with clear center on trunk, arms, and legs)
 Sydenham chorea (involuntary purposeful movements)
 Minor signs/symptoms:
 Fever
 Raised ESR/CRP
 Arthralgia
 24

 Prolonged PR interval
 Previous rheumatic fever
 Rheumatic heart disease (10-20 years after rheumatic fever):
 Valvular heart disease (esp. mitral valve)
 Infectious endocarditis
 Septic emboli
DIAGNOSIS
 Revised Jones Criteria (one major criterion for diagnosis, plus one other major criteria or two minor criteria)
 Evidence of a previous streptococcal infection – GAS pharyngitis culture, anti-streptolysin O titre, clinical history
TREATMENT
 Acute treatment:
 Admission to hospital (to ensure investigations are performed)
 Notifiable illness
 PO penicillin V until diagnosis established (typically, 10 day course), followed by IM benzathine penicillin
 Secondary prophylaxis : IM benzathine penicillin every 28 days for a minimum of 10 years (PO penicillin V if compliance issues)
 Analgesia (for arthritis) – NSAIDs
 Severe carditis – prednisone
 25

Endocrinology.
Disorders of glucose metabolism
Overview of glucose regulation
ISLET CELLS OF PANCREAS
 Alpha cells (20% of islet cells) – glucagon
 Beta cells (70% of islet cells) – insulin
 Delta cells (5% of islet cells) – somatostatin
 Gamma cells (<5% of islet cells) – pancreatic polypeptide
 Epsilon cells (<1% of islet cells) – ghrelin
DIABETES MELLITUS
Diabetes mellitus is a syndrome of disordered metabolism and
inappropriate hyperglycaemia secondary to:
 Absolute or relative deficiency in insulin , and/or a
 Reduction in insulin sensitivity
CLINICAL PRESENTATION
 Hyperglycaemic symptoms : polyuria, polydipsia, polyphagia,
fatigue, visual blurring, fungal infection
DIAGNOSIS
 Diabetes criteria:
 Fasting BGL ≥7mmol/L or random BGL ≥11.1mmol/L (needs a confirmatory test if asymptomatic)
 2-hour OGTT ≥11.1mmol/L
 HbA1 c >50mmol/L (pre-diabetes = 40-50)
 Anti-tissue antibodies may be present in T1DM (and occasionally in T2DM) (e.g. anti-islet cell, anti-GAD, anti-insulin )

Treatment of diabetes
General principles
 Glycaemic targets: aim for physiological levels (e.g. 45-55mmol/L – dependent on risk profile)
 Risk factor management:
 Diet and weight loss – aim for 5-10% weight loss over several months
 Exercise – ≥30 minutes for ≥5 days a week of moderate intensity (improves insulin sensitivity)
 Blood pressure – ACEi/ARBs (target <130/80 if possible)
 Dyslipidaemia – statins (irrespective of lipid levels)
 Screening examinations:
 Monitoring of HbA1c – long-term glucose control (typically 3-monthly)
 Unreliable in conditions that increase RBC turnover
 Annual physical examination to screen for macro- and microvascular disease:
 Diabetic foot examinations
 Diabetic eye examinations
 Urine dipstick (for microalbuminuria)
 Cardiovascular risk assessment (incl. asking about symptoms of IHD or PVD)
 Diabetes specialist clinics for T1DM or uncontrolled T2DM
T1DM-specific
 Treatment protocol:
 Insulin (consider use of continuous insulin pump )
T2DM-specific
 Treatment protocol:
 Metformin (a biguanide)
 Second (or third) agents (e.g. sulfonylureas – gliclazide; DPP-4 inhibitors – sitagliptin)
 Insulin
Insulin therapy
 There are several insulin protocols – consider starting with basal insulin and short-acting insulin
 Insulin requirements are highest in the morning (Dawn phenomenon – due to high cortisol/GH promoting insulin resistance)
 Insulin calculation:
 26

 Carbohydrate load/insulin ratio – determines number of insulin units needed for pre-meal insulin (based on carbohydrate
load)
 Correction factor – 100 divided by total daily insulin units (1 unit will bring BGL (mmol) down by the correction factor)
COMPLICATIONS

Acute and chronic complications of Diabetes Mellitus

COMPLICATION DESCRIPTION CLINICAL NOTES
ACUTE COMPLICATIONS
Diabetic ketoacidosis Often precipitated by physiological stress or non-compliance with insulin Investigations:
(occurs in T1DM or   BGL / osmolality
T2DM if severe) Pathophysiology of initial deficit:  High anion gap metabolic acidosis
 Insulin deficiency with  counter-regulatory hormones  Urine positive for glucose/ketones
 Unopposed hepatic glucose production  hyperglycaemia    Na+, N/ K+,  HCO3,  phosphate
osmotic diuresis  dehydration and electrolyte disturbance    creatinine/BUN (renal dysfunction)
 Na+ (water shift to ECF causing pseudohyponatraemia)
 Fat mobilisation   FFA  ketoacids  metabolic acidosis Treatment:
 ABCs
Pathophysiology of complications:  Monitor ketoacidosis with ABG
 Total body potassium depletion: due to  transcellular shift (ICF  ECF)  IV fluids
caused by lack of insulin (although plasma K+ may be normal/increased)  Insulin therapy (after fluids)
 Total body phosphate depletion  Potassium replacement
 Acute cerebral oedema (1% of patients): unknown pathophysiology  Bicarbonate (if pH <7)
 Mannitol (if cerebral oedema)
Clinical features:
 Polyuria, polydipsia, polyphagia with marked fatigue Up to 5% mortality
 Nausea/vomiting
 Abdominal pain
 Dehydration
 Decreased LOC (if high osmolality)
 Fruity smelling breath
 Kussmaul respiration

Hyperosmolar Often precipitated by physiological stress Investigations:

Hyperglycaemic state   BGL / osmolality
(HHS) Pathophysiology of initial deficit:  No ketosis/acidosis
(occurs in T2DM)  Relative insulin deficiency  hepatic glucose production (but the small  Urine positive for glucose
amount of insulin prevents ketosis)  hyperglycaemia    Na+, N/ K+
osmotic diuresis  dehydration and electrolyte disturbance   creatinine/BUN (renal dysfunction)

Clinical features: Treatment:

 Onset is insidious  polyuria, polydipsia, and confusion (high osmolality)  As for DKA (although less potassium
 Severe dehydration (orthostatic changes) depletion and lower insulin requirements)
 History of  fluid intake or  fluids containing glucose is common  LMWH ( risk of VTE)

Up to 50% mortality

CHRONIC COMPLICATIONS
Diabetic retinopathy  Classified as non-proliferative or proliferative (with neovascularisation); both include microaneurysms, haemorrhages,
(microvascular) hard exudates, and ‘cotton-wool’ spots
 Loss of vision from macular oedema, retinal detachment, or glaucoma
 Treatment: improved glycaemic control, retinal photocoagulation, and anti-VEGF injections

Diabetic nephropathy  See Nephrology

(microvascular)

Diabetic neuropathy  Characterised by peripheral, symmetric, sensorimotor neuropathy – leads to foot trauma, infection, and diabetic ulcers
(microvascular)  Can cause degeneration of foot arch (Charcot arthropathy) due to loss of sensation and repeated joint injury
 Late autonomic dysfunction can cause gastroparesis, diarrhoea, dysphagia, erectile dysfunction, and orthostatic
hypotension
 Treatment (no cure): preventative foot care, analgesia (neuropathic pain), metoclopramide (gastroparesis)

Macrovascular  Cardiovascular, cerebrovascular, and peripheral vascular disease

complications  CVS disease is the most common cause of death in diabetic patients

Type 1 Diabetes (T1DM)

FEATURES
 Associated with HLA-DR3/4 (but less heritable than T2DM)
 Associated with a personal or family history of autoimmune disease
 27

PATHOPHYSIOLOGY
 Autoimmune destruction of pancreatic β-cells leading to absolute insulin deficiency
 Up to 80% of β-cell mass is destroyed before features of diabetes are present
CLINICAL PRESENTATION
 Hyperglycaemic symptoms and weight loss (may present acutely as DKA – especially in children)
 Typically affects non-obese children or young adults
 If diagnosed in adulthood – LADA (latent autoimmune diabetes of adults)
Type 2 Diabetes
FEATURES
 Not associated with HLA (but more heritable than T1DM)
 Associated conditions include PCOS, dyslipidaemia , fatty liver, and gout
PATHOPHYSIOLOGY
 Complex pathophysiology – mainly due to:
 Impaired insulin secretion
 Peripheral insulin resistance
 Poor adipose tissue storage (leakage of FFA which causes insulin resistance)
 Initially compensated by increased insulin production
CLINICAL PRESENTATION
 Hyperglycaemic symptoms (insidious) and/or complications of diabetes
 Typically affects obese adults
 Hyperosmolar hyperglycaemic state may be seen in the setting of poor glycaemic control
Secondary diabetes
There are several secondary causes of diabetes (with distinct pathophysiology), for example:
 Long-term exogenous steroids
 Chronic pancreatitis
 Other endocrine disorders – especially Cushing’s syndrome , acromegaly, and pheochromocytoma
Metabolic syndrome
Metabolic syndrome is a group of risk factors that increase your risk for many health conditions (heart disease, stroke, and diabetes).
DIAGNOSIS
Several definitions exist, but commonly three out of five of the following criteria must be met:
 Abdominal obesity
  TAGs
  HDL
  BP (or requirement for anti-hypertensives)
  BGL
HYPOGLYCAEMIA
Hypoglycaemia is defined as a plasma glucose of ≤4mmol/L but the threshold for symptoms varies
AETIOLOGY
Other than starvation of glucose , hypoglycaemia can be caused by:
 Fasting hypoglycaemia (in non-diabetic adults you must EXPLAIN the mechanism):
 Exogenous drugs (chiefly insulin or anti-diabetic medication)
 Pituitary insufficiency
 Liver failure (plus rare inherited enzyme defects)
 Addison’s disease
 Islet cell tumours (insulinoma) and immune hypoglycaemia (Hodgkin’s disease )
 Non-pancreatic neoplasms
 Post-prandial hypoglycaemia – may occur after gastric/bariatric surgery
CLINICAL PRESENTATION
 Whipple’s triad:
 Low serum glucose
 Neuroglycopenic symptoms
 Rapid relief by administration of glucose
 Adrenergic symptoms (typically occur first; caused by ANS activity) – palpitations, sweating, anxiety, tremor, tachycardia
 Neuroglycopenic symptoms (caused by decreased CNS activity) – dizziness, headache, confusion, visual trouble, seizure, coma
 28

DIAGNOSIS
 Finger-prick glucose level and drug history
 Insulinoma:
 C-peptide (released when proinsulin is cleaved to insulin) – increased in insulinoma / decreased if exogenous insulin
 72-hour fast suppression test (insulin typically suppressed in the setting of hypoglycaemia – fails to suppress in insulinoma)
TREATMENT
 Treat underlying cause if fasting hypoglycaemia
 If patient can swallow – oral sugar and a long-acting starch
 If patient cannot swallow – IV glucose or IM glucagon
 Insulinoma – surgical excision

Hypoglycaemic unawareness
Hypoglycaemic unawareness is defined as the onset of neuroglycopenic symptom s before adrenergic symptoms .
 Occurs in patients with recurrent hypoglycaemia (but is reversible by good glucose control)
 More common in T1DM than T2DM
 These patients are not safe to drive

Disorders of lipid metabolism

Overview of lipid transport
Lipoproteins
LIPOPROTEIN FUNCTION
Exogenous pathway

Chylomicron  Transports dietary TG from gut to adipose tissue and muscle (metabolised by lipoprotein lipase; requires apo-CII)

Endogenous pathway

VLDL  Transports hepatic synthesised TG from liver to adipose tissue and muscle (metabolised by lipoprotein lipase; requires apo-CII)

IDL  Product of hydrolysis of TG in VLDL by lipoprotein lipase resulting in depletion of TG core (enriched with cholesterol esters)

LDL  Product of hydrolysis of TG in IDL by hepatic lipase resulting in further depletion of TG core enriched with cholesterol esters)
 Transports cholesterol from liver to peripheral tissues (gonads, adrenals)

HDL  Transports cholesterol from peripheral tissues to liver

 Acts as reservoir for apolipoproteins
 29

Disorders of lipid and cholesterol metabolism

CLASSIFICATION OF PRIMARY DISORDERS
Primary hypertriglyceridaemia
 Familial lipoprotein lipase deficiency
 Pathophysiology : autosomal recessive deficiency of lipoprotein lipase (and consequently  TG metabolism)
 Labs:  TG / chylomicrons (moderate  in VLDL)
 Familial hypertriglyceridaemia
 Pathophysiology : several genetic defects resulting in  VLDL synthesis (or  VLDL removal)
 Labs:  TG / VLDL
Primary hypercholesterolaemia
 Familial hypercholesterolaemia
 Pathophysiology : autosomal codominant defect in the LDL receptor on cell membranes (and consequently  LDL removal)
 Labs:  TC / LDL
Combined hyperlipidaemia
 Familial combined hyperlipidaemia
 Pathophysiology : autosomal dominant over-population of VLDL (and LDL) due to excess hepatic synthesis of apolipoprotein B
 Labs:  TC / TG / VLDL / LDL
 Familial dysbetalipoproteinaemia
 Pathophysiology : abnormal apolipoprotein E (and associated  IDL)
 Labs:  TC / TG / VLDL / IDL
CLINICAL PRESENTATION
 Dependent on severity of metabolic defect
 Direct signs and symptoms :
 Hypercholesterolaemia – tendinous xanthomata, xanthelasmata, corneal arcus
 Hypertriglyceridaemia – eruptive xanthomata (papules all over body)
 Dysbetalipoproteinaemia – palmar xanthomata
 Indirect signs and symptoms: macrovascular disease (pancreatitis in LPL deficiency)
TREATMENT
 Lifestyle change (diet, exercise, alcohol reduction)
 Hypertriglyceridaemia :
 Fibrates
 Niacin
 Omega-3 fatty acids
 Hypercholesterolaemia:
 Statins
 Ezetimibe
 Bile acid sequestrants
 Niacin
RISK ASSESSMENT
 LDL – major risk factor for atherosclerosis (and IHD)
 Lipoprotein(a) – major risk factor for atherosclerosis (and IHD)
 TG – minor risk factor for IHD (although treatment has not been shown to decrease morbidity or mortality)
 HDL – associated with decreased cardiovascular disease and mortality

Disorders of pituitary function

Hypothalamic-pituitary hormonal axes
 Anterior pituitary hormones
 Prolactin
 TSH
 ACTH
 GH
 FSH/LH
 Posterior pituitary hormones synthesised in supraoptic and paraventricular
nuclei of hypothalamus, transported to posterior pituitary, and released at
nerve endings:
 Anti-diuretic hormone
 Oxytocin
 30

Note: transection of the pituitary stalk leads to pituitary hypersecretion of prolactin and hyposecretion of the other hormones.
Physiology of pituitary hormones
HORMONE FUNCTION STIMULUS INHIBITION NOTES
ACTH  Stimulates growth of adrenal cortex and  CRH  Cortisol  Polypeptide
secretion of cortisol  Fever, pain, stress  Dexamethasone  Diurnal levels
 Some melanocyte stimulating activity  ADH (highest in AM)

GH  Stimulates growth of bone, muscles, and other  GHRH  IGF-1  Polypeptide

tissues via IGF-1 (indirect)  Hypoglycaemia  Glucose  Pulsatile secretion
 Stimulates protein synthesis (direct)  Somatostatin  Sustained rise
 Metabolic effects:  BGL/TG during sleep

TSH  Stimulates growth of thyroid and secretion of  TRH  Thyroid hormones  Glycoprotein
T3/T4

LH/FSH  Stimulate gonads  Pulsatile GnRH  Oestrogen  Glycoprotein

Ovary:  Progesterone  Pulsatile secretion
 LH: production of androgens (thecal cells) which  Testosterone
are converted to oestrogens (granulosa cells)  Continuous GnRH
 FSH: growth of granulosa cells
Testes:
 LH: production of testosterone (Leydig cells)
 FSH: production of spermatozoa (Sertoli cells)

Prolactin  Promotes milk production  Sleep  Dopamine  Polypeptide

 Inhibits GnRH secretion  Pregnancy / breast feeding  Episodic secretion
 TRH

ADH  Stimulates insertion of aquaporin channels in   serum osmolality   serum osmolality  Secreted by
renal collecting ducts (increasing water  Hypovolaemia posterior pituitary
reabsorption and concentrating the urine)

Oxytocin  Stimulates breast milk secretion  Suckling  Alcohol  Secreted by

 Stimulates uterine contraction  Distention of genital tract during posterior pituitary
labour via stretch receptors

Pituitary adenoma
CLASSIFICATION
 Microadenoma (<1cm) – typically, present as hormonal dysfunction
 Macroadenoma (>1cm) – typically, present with visual field defects (bitemporal hemianopia) and headache (both due to mass effect)
HISTOLOGY
 Chromophils (cells that stain) (50%)
 Acidophils (red/orange staining )
 Somatotrophs (50%) – GH
 Lactotrophs (20%) – prolactin
 Basophil (blue staining )
 Corticotrophs (20%) – ACTH
 Thyrotrophs (5%) – TSH
 Gonadotrophs (5%) – FSH/LH
 Chromophobes (cells that do not stain) (50%)
CLINICAL PRESENTATION
 Local mass effect – visual field defects (bitemporal hemianopia due to compression of optic chiasm) and headache
 Hypofunction – hypopituitarism
 Hyperfunction – prolactin (galactorrhoea), growth hormone (acromegaly/gigantism), ACTH (Cushing disease)
 Tumours secreting LH/FSH or TSH are rare
DIAGNOSIS
 MRI
 Visual field testing
 Hypothalamic-pituitary hormonal function
 31

Hypopituitarism
AETIOLOGY
 Can present suddenly (apoplexy, Sheehan syndrome) or gradually (radiation, inflammatory, invasive)
 Sheehan syndrome – pituitary infarction due to excessive post-partum blood loss
 Pituitary apoplexy – acute haemorrhage/infarction of pituitary tumour (associated with severe headache and  LOC)
DIAGNOSIS
 Triple bolus test (stimulates release of all anterior pituitary hormones in normal individuals)
 Rapid sequence IV infusion of insulin, GnRH, and TRH
 Insulin  hypoglycaemia   GH and  ACTH/cortisol
 GnRH   LH/FSH
 TRH   TSH and  PRL
ADRENOCORTICOTROPIC HORMONE
See Adrenal cortex.
GROWTH HORMONE
Growth hormone deficiency
 Cause of short stature in children
 Controversial significance in adults (often not clinically apparent, may present as fatigue)
Growth hormone excess
AETIOLOGY
 Almost exclusively due to pituitary tumour (but also carcinoid tumour)
CLINICAL PRESENTATION
 In children (before epiphyseal fusion) leads to gigantism
 In adults (after epiphyseal fusion) leads to acromegaly
 Characterised by enlargement of hands and feet, coarsening of facial features, prognathism, sweating, and acanthosis nigricans
 Additionally, can cause (ABCDEF):
 Arthritis/arthralgia
 Blood pressure increase (can lead to LVH and CHF)
 Carpal tunnel syndrome
 Diabetes mellitus
 Enlarged organs
 Field defect (visual)
DIAGNOSIS
 Initial test:  serum IGF-1
 Confirmatory test : glucose suppression test (GH is not suppressed in acromegaly)
 MRI of pituitary to assess for adenoma (unlike other pituitary tumours, typically enlarged at presentation)
TREATMENT
 Trans-sphenoidal hypophysectomy ± radiation
 Octreotide (somatostatin analogue)
 Pegvisomant (GH receptor antagonist)
COMPLICATIONS
 Diabetes mellitus
 Cardiovascular disease (most common cause of death)
 Increased risk of colon cancer
THYROID STIMULATING HORMONE
See Thyroid.
LUTEINISING HORMONE AND FOLLICLE STIMULATING HORMONE
See Gynaecology and Male Reproductive Endocrinology.
PROLACTIN
Hyperprolactinaemia
Hyperprolactinaemia is the most common hormonal disturbance of the pituitary.
 32

AETIOLOGY
 Pregnancy / breastfeeding
 Prolactinoma
 Pituitary masses with pituitary stalk compression (causes reduced dopamine inhibition of prolactin release)
 Renal/liver failure (prolactin metabolised by kidney and liver)
 Primary hypothyroidism (increased TRH)
 Medications with anti-dopaminergic properties (e.g. antipsychotics and SSRIs)
CLINICAL PRESENTATION
 Females – galactorrhoea, amenorrhoea, infertility, loss of libido, and osteoporosis (many years)
 Males – loss of libido, erectile dysfunction, infertility, gynecomastia, and galactorrhoea (rarely)
DIAGNOSIS
 Initial tests:  prolactin (with U&E and LFTs to assess clearance)
 MRI of pituitary to assess for adenoma
TREATMENT
 Prolactin-secreting tumours are very slow-growing and sometimes require no treatment
 Dopamine agonists (bromocriptine or cabergoline)
 Trans-sphenoidal hypophysectomy ± radiation (rare)
ANTI-DIURETIC HORMONE
Diabetes insipidus
CLASSIFICATION
 Central (more common) – insufficient ADH (idiopathic, familial, surgery, tumours, pituitary stalk lesion, haemorrhage, infection)
 Nephrogenic – collecting ducts in kidneys resistant to ADH (most commonly due to lithium)
CLINICAL PRESENTATION
 Passage of large volumes of dilute urine (with associated polydipsia and dehydration )
 Typically, worsens in pregnancy (secretion of anti-ADH enzymes by placenta)
 Associated with hypernatraemia (inadequate water consumption or impaired thirst mechanism)
DIAGNOSIS
 Fluid deprivation test (to exclude psychogenic polydipsia)
 Diabetes insipidus – high urine output with low urine osmolality (does not correct)
 Psychogenic polydipsia – normal urine output with high urine osmolality
 Response to DDAVP (distinguishes central from nephrogenic DI)
 Central diabetes insipidus – high urine osmolality
 Nephrogenic diabetes insipidus – low urine osmolality (does not correct)
 Labs: U&E and urinalysis (low urine osmolality)
TREATMENT
 Central – exogenous ADH (DDAVP - desmopressin )
 Nephrogenic – thiazide diuretics
Syndrome of inappropriate ADH secretion (SIADH)
AETIOLOGY
 Stress (pain, nausea, post-surgical, infection – esp. meningitis)
 Respiratory disease (pneumonia, empyema, tuberculosis)
 Malignancy (lung, pancreas, lymphoma – paraneoplastic)
 Drugs
CLINICAL PRESENTATION AND DIAGNOSIS
 Patients usually euvolaemic, normotensive, and have no oedema
 Based on clinical and laboratory findings of:
 Plasma – low serum osmolality and hyponatraemia
 Urine – less than maximally diluted (>100mOsm) and UNa >20mmol
 Absence of adrenal, renal, or thyroid insufficiency
TREATMENT
 Treat underlying cause and treat hyponatraemia
 Fluid restriction
 ADH antagonists
 33

Disorders of thyroid function

Thyroid hormone
 Synthesis of T3/T4 – involves trapping/oxidation of iodide, iodination of thyroglobulin (storage molecule), and release of T3/T4
 Free portion is hormonally active (<0.5%); remaining fraction bound to thyroxine binding globulin and albumin
 More T4 is produced , but the majority is converted to T3 (or reverse T3) in the periphery (more biologically active)
 Thyroid hormones modulate gene transcription in nearly every organ by binding to nuclear receptors
 Stimulate an increased basal metabolic rate and β-adrenergic effects
 Calcitonin , a peptide hormone, is also produced in the thyroid by parafollicular C cells (acts to decrease serum calcium)

Tests of thyroid function

 TSH – best initial test (if abnormal usually initiates laboratory reflex testing)
 Free T4/T3 – preferred screening test for thyroid hormone levels (total T4/T3 is not useful)
 Plasma thyroglobulin – used to monitor for residual thyroid tissue post-thyroidectomy (e.g. tumour marker for thyroid cancer)
 Serum calcitonin – not routinely monitored (used if suspicious for medullary thyroid cancer or MEN)
Summary of diagnostic testing in Hyperthyroidism and Hypothyroidism
TEST HYPERTHYROIDISM HYPOTHYROIDISM
TSH   in primary hyperthyroidism   in primary hypothyroidism
  in secondary hyperthyroidism   in secondary hypothyroidism
  in subclinical hypothyroidism

Free T4   in primary hyperthyroidism   in primary hypothyroidism

  in secondary hyperthyroidism   in secondary hypothyroidism
 Normal in subclinical hypothyroidism

Antibodies Graves’: thyroid stimulating antibodies Hashimoto’s: anti-thyroid peroxidase (TPO)

Radioactive Increased uptake: Decreased uptake:

iodine uptake  Graves’  Subacute thyroiditis
 Toxic multinodular goitre  Recent iodine load
 Toxic adenoma  Exogenous thyroid hormone

Radioactive  Graves’: homogenous diffuse uptake

iodine scan  Multinodular goitre: heterogenous uptake
 Toxic adenoma: single intense area of uptake with suppression elsewhere

MEDICATION THAT CAN INFLUENCE THYROID FUNCTION

 Amiodarone
 Hyperthyroidism – high iodine content
 Hypothyroidism – direct toxic effect on thyroid
 Lithium – can cause hypothyroidism
HYPERTHYROIDISM
The state of ↑ levels of T4 and/or T3 (most commonly caused by Graves’ disease ).
CLINICAL PRESENTATION

Clinical features of Hyperthyroidism

SYSTEM CLINICAL FEATURES
General Fatigue, heart intolerance, irritability, fine tremor

CVS Tachycardia, atrial fibrillation, palpitations

Graves’ disease: thyroid bruits

Respiratory Nil

GI Weight loss, thirst, increased frequency of bowel movements or diarrhoea

MSK/Neurology Proximal myopathy, increased reflexes, osteoporosis

GU Oligomenorrhoea, amenorrhoea, decreased fertility

Dermatology Fine hair, skin moist and warm, palmar erythema

Graves’ disease: clubbing, thyroid acropachy (phalangeal bone overgrowth), pretibial myxoedema (shin rash)

Eye Grave’s disease: exophthalmos, proptosis, lid lag, lid retraction, diplopia, decreased visual acuity (risk increased with smoking)
 34

TREATMENT
 Symptomatic treatment:
 Thionamides (carbimazole, methimazole, propylthiouracil ) – titrate or block and replace (with thyroxine)
 β-blockers for CVS symptom control
 Definitive treatment:
 Radioactive thyroid ablation
 Hemi, sub-total, or complete thyroidectomy
 Supportive treatment:
 Levothyroxine to prevent hypothyroidism in patients undergoing ablation or surgery
Aetiology of hyperthyroidism
DISEASE PATHOPHYSIOLOGY NOTES
Graves’ disease Autoimmune disorder caused by thyroid stimulating antibodies (TSH receptor)  50% remission with thionamides
(most common)  React with orbital antigens  leading to retro-orbital inflammation and  Definitive treatment if refractory
lymphocyte infiltration  Associated with diffuse goitre

Thyroiditis Inflammatory disorder characterised by initial hyperthyroidism (release of Two subtypes:

previously synthesised thyroid hormone); followed by hypothyroidism and  Painful – viral (preceded by URTI)
euthyroidism (in most cases)  Known as De Quervain’s thyroiditis
 10% of cases have permanent hypothyroidism (in painless thyroiditis)  Painless – auto-immune or post-partum
 May occur post-partum  Treated with β-blockers
 Consider NSAIDs/steroids if painful

Toxic adenoma / Autonomous thyroid hormone production by a functioning adenoma  May be single (toxic adenoma) or
multinodular goitre multiple (toxic multinodular goitre)
 Radioactive thyroid ablation has little
effect on function following treatment
 Associated with asymmetric goitre

Thyroid crisis/storm
An acute exacerbation of hyperthyroidism presenting in a life-threatening state secondary to uncontrolled hyperthyroidism
 Rare – but serious with a mortality rate between 10-30%
CLINICAL PRESENTATION
 Extreme hyperthyroidism – hyperthermia, tachycardia, nausea/vomiting, shock
 Mental status changes ranging from delirium to coma
DIAGNOSIS
 Labs:  T3/T4 and undetectable TSH
TREATMENT
 Thionamides
 β-blockers
 Iodide (acutely inhibits thyroid hormone release)
 Corticosteroids
HYPOTHYROIDISM
The state of ↓ levels of T4 and/or T3 (most commonly caused by Hashimoto’s thyroiditis ).
CLINICAL PRESENTATION

Clinical features of Hypothyroidism

SYSTEM CLINICAL FEATURES
General Fatigue, cold intolerance, slowing of mental and physical performance, hoarseness, macroglossia

CVS Bradycardia, hypotension, worsening heart failure or angina, hypercholesterolaemia, pericardial effusion

Respiratory Decreased exercise capacity, hypoventilation, sleep apnoea

GI Weight gain, constipation

Neurology Paraesthesia, slow reflexes, seizures

GU Menorrhagia, amenorrhoea, impotence, galactorrhoea (increased TRH in primary hypothyroidism)

Dermatology Dry skin and hair, cool and pale, puffiness of face
 35

Haematology Anaemia (10% pernicious due to presence of anti-parietal cell antibodies in Hashimoto’s thyroiditis)

TREATMENT
 Uncomplicated hypothyroidism: levothyroxine (oral T4 replacement)
Aetiology of hypothyroidism
DISEASE PATHOPHYSIOLOGY NOTES
Hashimoto’s Autoimmune disorder caused by cellular and humoral destruction of the Two subtypes:
thyroiditis thyroid tissue (associated with anti-thyroid peroxidase, anti-thyroglobulin,  Goitrous – diffuse rubbery goitre
(most common) and anti-TSH receptor antibodies)  Atrophic – nil goitre
 Increased risk of thyroid lymphoma

Thyroiditis As above (either a phase of thyroiditis or a permanent complication)

Sick euthyroid A syndrome characterised by changes to circulating thyroid hormones amongst  Associated with  rT3 and  T3
syndrome patients with serious illness, trauma, or stress ( T4 if severe)

Myxoedema coma
An acute exacerbation of hypothyroidism presenting in a life-threatening state secondary to uncontrolled hypothyroidism complicated by
stressful events (e.g. trauma, sepsis, myocardial infarction, or drugs).
 Rare – but serious with a mortality rate up to 40%
CLINICAL PRESENTATION
 Extreme hypothyroidism – hypothermia, hyponatraemia, hypoglycaemia, hypotension, hypoventilation, bradycardia, oedema
 Mental status changes ranging from delirium to coma
DIAGNOSIS
 Labs:  T3/T4 and increased TSH; also  BGL
 Check ACTH/cortisol for evidence of adrenal insufficiency
TREATMENT
 Aggressive treatment:
 ICU admission
 Corticosteroids (for concomitant adrenal insufficiency)
 IV thyroxine
 Supportive measures (fluids, rewarming, IV dextrose , IV fluids)
NON-TOXIC GOITRE
Non-toxic goitre is a generalised enlargement of the thyroid in a euthyroid patient .
AETIOLOGY
 Iodine deficiency (major cause); also, drugs (iodine/lithium), goitrogens (certain vegetables), and sporadic

Note: iodine deficiency is the greatest cause of hypothyroidism in the world setting (e.g. cretinism).
TREATMENT
 Treat underlying cause
 Surgery may be necessary for severe compressive symptoms (e.g. dysphagia, pain, hoarseness)
THYROID NODULES
Thyroid nodules are clearly defined discrete masses (separated from the thyroid parenchyma).
AETIOLOGY
 Benign tumours (95%)
 Malignant tumours (typically firm and fixed)
 Thyroid cyst
 Thyroglossal duct cyst
Types of Thyroid Carcinoma
PAPILLARY FOLLICULAR MEDULLARY ANAPLASTIC
Incidence 75% 15% 5% 5%

Spread Lymphatic Haematogenous Lymphatic and haematogenous Lymphatic and haematogenous

 36

Prognosis >95% at 10 years >90% at 10 years 50% at 10 years 10% at 10 years

Notes  Occur in follicular cells  Occur in follicular cells  Occur in C-cells  Rapid growth and metastasis
  serum thyroglobulin   serum thyroglobulin   calcitonin
 Associated with MEN2

CLINICAL PRESENTATION
 Usually, asymptomatic on initial presentation (incidental findings; suggested by firm and fixed lesions)
 Large nodules adjacent to the trachea/oesophagus present with local symptoms (dysphagia, dyspnoea, cough, choking sensation )
DIAGNOSIS
 Labs: TSH (hyperfunctioning nodules are not malignant)
 U/S imaging and guided FNA
TREATMENT
 Suspicious nodules – surgical excision
 Papillary/follicular (well differentiated): partial or total thyroidectomy
 Medullary/anaplastic (poorly differentiated): chemoradiotherapy
Thyroglossal duct cyst
EMBRYOLOGY
 The thyroid diverticulum arises from the floor of the primitive pharynx and descends into the neck
 It is connected to the tongue by the thyroglossal duct (which normally disappears but may persist)
 The foramen cecum is a remnant of the thyroglossal duct (the most common site of ectopic thyroid tissue)
CLINICAL PRESENTATION
 Presents as an anterior midline neck mass that moves with swallowing and protrusion of the tongue

Disorders of adrenal function

Adrenal cortex
LAYERS OF ADRENAL GLAND
From exterior to interior:
 Zona glomerulosa – produces mineralocorticoids (aldosterone)
 Zona fasciculata – produces glucocorticoids (cortisol)
 Zona reticularis – produces androgens (DHEA, androstenedione)
 Adrenal medulla – produces catecholamines (chromaffin cells produce adrenaline and noradrenaline)
 Noradrenaline is also produced in post-ganglionic sympathetic nerves

Adrenocortical hormones
 Aldosterone – a mineralocorticoid
 Regulates ECF volume through Na+ (and Cl-) retention and K+ (and H+) excretion
 Regulated by RAAS
 Cortisol – a glucocorticoid
 Regulates metabolism (counteracts insulin); also, pro-hypertensive, pro-osteoporotic, immunosuppressive, regulates behaviour
 Regulated by the HPA axis
 Excreted as urinary free cortisol and other metabolised steroids
 Androgens – sex steroids
 Primarily responsible for adrenarche (growth of axillary and pubic hair)
 Regulated by ACTH
 37

RAAS axis

Adrenocortical function workup

Stimulation tests (hormone deficiencies)
 Short Synacthen test (confirms adrenal insufficiency)
 Method: give Synacthen, then measure plasma cortisol levels at time 0, 30, and 60 minutes
 Physiologic response : stimulated plasma cortisol of >500nmol/L
 Inappropriate response : inability to stimulate increased plasma cortisol
 Long Synacthen test (confirms primary versus secondary adrenal insufficiency)
 Method: give IM Synacthen for three days, then perform a short Synacthen test on the fourth
 Interpretation : a normal test excludes primary adrenal insufficiency (i.e. secondary causes likely)
Stimulation tests (hormone hypersecretion)
 Dexamethasone suppression test (suppresses ACTH)
 Method: give dexamethasone at midnight, then measure plasma cortisol levels the following day at 8am
 Variants: low dose (suppress normal function); high dose (suppress pituitary adenoma but not ectopic ATCH)
 Physiologic response: suppressed plasma cortisol of <50nmol/L
 Inappropriate response : failure to suppress plasma cortisol
 Confirmatory tests:
 24hr urine free cortisol (shows overproduction of cortisol)
 Salivary cortisol (shows lack of diurnal variation; inappropriately high at night)
 Saline expansion test (suppresses RAAS  aldosterone)
 Method: IV infusion of 500ml/h of NS for 4 hours, then measure plasma
aldosterone
 Physiologic response: suppressed plasma aldosterone of <140pmol/L
 Inappropriate response: failure to suppress plasma aldosterone
GLUCOCORTICOID EXCESS SYNDROMES
Cushing syndrome results from chronic glucocorticoid excess (endogenous or exogenous
sources).
CLASSIFICATION AND AETIOLOGY
 ACTH-dependent (85%) – bilateral adrenal hyperplasia and hypersecretion due to:
 ACTH-secreting pituitary adenoma (Cushing disease) (80% of ACTH-dependent)
 Ectopic ACTH-secreting tumour (especially small cell lung cancer and carcinoid
tumours)
 ACTH-independent (15%)
 38

 Long-term use of exogenous glucocorticoids

 Primary adrenal tumours (uncommon)
CLINICAL PRESENTATION
 Symptoms: fatigue, mood disorders, muscle weakness, oligo/amenorrhoea
 Signs: central obesity, moon face, facial plethora, dorsal fat pads, abdominal striae, skin thinning, proximal muscle wasting, avascular
necrosis of the femoral head, easy bruising, poor wound healing, acanthosis nigricans, hypertension, hyperglycaemia, osteoporosis,
and baldness/facial hirsutism in females (if ACTH-dependent)
 Rarely, associated with hyperpigmentation (ACTH-dependent))
 Hyperandrogenic effects (hirsutism or acne) only occur in ACTH-dependent tumours (up-regulated androgen synthesis)
DIAGNOSIS
 Confirm with one of :
 Dexamethasone suppression test
 24hr urine free cortisol
 Salivary cortisol
 Exclude exogenous glucocorticoids
 Additional:
 MRI for pituitary adenoma
 Inferior petrosal sinus sampling to determine if pituitary or ectopic ACTH (associated with hypokalaemia)
 Adrenal vein sampling (if ACTH is undetectable and considering functional adrenal mass)
TREATMENT
 Adrenal adenoma – unilateral adrenalectomy (curative) with glucocorticoid supplementation post-operatively
 Pituitary adenoma – trans-sphenoidal hypophysectomy with glucocorticoid supplementation post-operatively
 Ectopic ACTH – treat underlying cause
 Medical treatment – ketoconazole (reduces adrenal steroid synthesis)
MINERALOCORTICOID EXCESS SYNDROMES

CLASSIFICATION AND AETIOLOGY

 Primary hyperaldosteronism – excess aldosterone production (intra-adrenal causes)
 Aldosterone-producing adrenal adenoma (Conn’s syndrome)
 Bilateral (or unilateral) adrenal hyperplasia
 Secondary hyperaldosteronism – excess RAAS stimulation (extra-adrenal causes – decreased renal perfusion)
CLINICAL PRESENTATION
 Non-specific symptoms predominant (fatigue, weakness, paraesthesia, headache)
 Characterised by hypertension, hypokalaemia, and metabolic alkalosis (may have mild hypernatraemia)
DIAGNOSIS
 Initial test :  plasma aldosterone-to-renin ratio if primary (normal if secondary)
 Confirmatory test (if primary) : saline suppression test (demonstrates inappropriate aldosterone secretion with ECF expansion)
 Imaging: CT abdomen (if negative consider MRI)
TREATMENT
 Primary: spironolactone ± surgical excision if adrenal adenoma
 Secondary: treat underlying cause
COMPLICATIONS
 Increased cardiovascular risk : LV hypertrophy, AF, stroke, MI
ADRENOCORTICAL INSUFFICIENCY
Adrenocortical insufficiency is a state of inadequate cortisol and/or aldosterone production by the adrenal glands.
CLASSIFICATION
 Primary (Addison’s disease )
 Autoimmune adrenalitis (90%) – immune reaction against 21-hydroxylase
 Other: CAH, non-functioning adrenal tumour, or infection ( esp. TB)
 Secondary – inadequate pituitary ACTH secretion (various causes; commonly withdrawal of exogenous steroids)
CLINICAL PRESENTATION AND DIAGNOSIS

Clinical presentation and diagnosis of primary and secondary adrenocortical insufficiency

PRIMARY (ADDISON’S DISEASE) SECONDARY
 39

Skin and Mucosa Hyperpigmented Pale

Potassium High Normal

Sodium Low Normal

Metabolic acidosis Present Absent

Associated disease Autoimmune disease (hypothyroid, DM, vitiligo) Pituitary deficiency or associated symptoms (visual/headaches)

Associated symptoms  Non-specific (weakness, fatigue, weight loss)  Same as primary

 Hypotension and salt craving  Salt craving uncommon
 GI: N/V, abdominal pain, diarrhoea  GI symptoms uncommon

Diagnosis  Synacthen test  Synacthen test

 High morning (8am) plasma ACTH  Low morning (8am) plasma ACTH
 Low morning (8am) plasma cortisol  High morning (8am) plasma cortisol

TREATMENT
 Primary insufficiency – glucocorticoid and mineralocorticoid (e.g. hydrocortisone and fludrocortisone)
 Secondary insufficiency – glucocorticoid (mineralocorticoid production is not ACTH-dependent)
 Additional concerns:
 If unwell, the patient must double or triple their steroid dose (to prevent adrenal insufficiency)
 If severe vomiting or diarrhoea, the patient must receive parenteral steroids (will not absorb oral steroids)
 If major stress (surgery/trauma), the patient must receive parenteral steroids (to prevent adrenal insufficiency)

Note: patients on chronic steroid therapy need tapered withdrawal to prevent secondary/tertiary adrenal insufficiency .
Adrenal (Addisonian) crisis
Adrenal crisis is a medical emergency due to severe adrenal insufficiency caused by insufficient levels of cortisol.
CLINICAL PRESENTATION
 Abdominal, lower back, or leg pain
 Electrolyte and endocrine abnormalities (hyperkalaemia, hypercalcaemia, hyponatraemia, hypoglycaemia, hypothyroid)
 Severe vomiting and diarrhoea (with dehydration and syncope)
 Severe fatigue and confusion
 Convulsions
TREATMENT
 Treat underlying cause
 Large volume of IV saline (with dextrose if hypoglycaemic)
 IV hydrocortisone
PHEOCHROMOCYTOMA

PATHOPHYSIOLOGY
 Catecholamine -secreting tumour derived from chromaffin cells of the sympathetic system in the adrenal medulla
AETIOLOGY
 Sporadic (80%)
 Genetic – MENII (50% penetrance); also, paraganglioma, NFT-1, and von Hippel-Lindau disease
 Follow 10% rule – 10% malignant, 10% extra-adrenal, 10% bilateral, 10% familial
CLINICAL PRESENTATION
 Secondary hypertension (either paroxysmal or sustained)
 Classic triad of episodic ‘pounding’ headache , palpitations/tachycardia , and diaphoresis
 Other signs : papilloedema, hyperglycaemia, dilated cardiomyopathy
DIAGNOSIS
 Definitive: plasma or urine metanephrines (metabolites of catecholamines)
 Imaging: CT abdomen (if negative consider MRI)
TREATMENT
 Surgical resection is curative (requires careful pre- and post-operative monitoring)
 Pre-operative preparation:
 α-blockers for blood pressure control
 β-blockers for heart rate control (after α-blockers for several days)
 Aggressive volume restoration (chronic SNS activity inhibits the RAAS pathway)
 40

HYPERANDROGENISM
Hyperandrogenism is characterized by excessive levels of androgens (DHEA or testosterone) in the female body.
 In males, androgens are produced by the testes and adrenal glands (although the adrenal glands produce an insignificant amount)
 In females, androgens are produced by the ovaries (50%) and adrenal glands (50%)
 DHEA is only produced by the adrenal glands (so is a marker of adrenal androgen excess)
AETIOLOGY
 Adrenal – congenital adrenal hyperplasia or adrenal tumours
 Ovarian – PCOS or ovarian (thecal cell) tumours
 Pituitary – Cushing disease (high ACTH) and acromegaly
 Medications
CLINICAL PRESENTATION
 Males – asymptomatic
 However, inhibition of GnRH may cause reduced testicular size, testicular testosterone production, and spermatogenesis
 Females
 Hirsutism (male pattern growth of androgen-dependent body hair)
 Virilisation (balding, clitoral enlargement, deepening of voice, acne, increased musculature)
 Defeminisation (loss of secondary sex characteristics – i.e. amenorrhoea, reduced breast size, infertility)
DIAGNOSIS
 Sex hormone workup (LH/FSH, androgens, 17-OH progesterone)
 Imaging: CT/MRI of adrenals and ovaries (identify tumours)
TREATMENT
 Dependent on underlying disorder
 Antiandrogens (spironolactone)
CONGENITAL ADRENAL HYPERPLASIA
Congenital adrenal hyperplasia are inherited enzyme defects that impair steroid synthesis and cause accumulation of steroid
precursors.
 Characterised by enlargement of both adrenal glands (due to  ACTH stimulation in absence of cortisol)
CLASSIFICATION

Types of Congenital Adrenal Hyperplasia

ENZYME 21-HYDROXYLASE 17-HYDROXYLASE 11-HYDROXYLASE
Mineralocorticoids   

Glucocorticoids   

Sex hormones   

Blood pressure   

Potassium   

Labs   17-hydroxyprogesterone   androstenedione   renin activity

  renin activity Note:  BP due to steroid precursor

CLINICAL PRESENTATION
 21-hydroxylase deficiency
 Classic form (severe)
 Salt-wasting
 Males – present at 1-2 weeks after birth with hypotension/shock
 Females – ambiguous genitalia
 Non-salt wasting (no signs of shock)
 Males – precocious puberty (2-4 years of age)
 Females – ambiguous genitalia
 Non-classic form (late-onset) (mild)
 Normal external genitalia at birth
 Precocious puberty
 Hyperandrogenism (hirsutism or acne) and menstrual irregularity in females
 Infertility
 Hyperpigmentation is common in all forms of congenital adrenal hyperplasia (associated with  ACTH due to low cortisol)
 41

TREATMENT
 21-hydroxylase deficiency: lifelong glucocorticoid and mineralocorticoid
 Genital reconstruction surgery (if ambiguous genitalia)
 Counselling may be required for gender identity issues

Bone and mineral disorders

Overview of calcium and phosphate regulation
ADDITIONAL NOTES
 Calcium is mainly regulated by PTH and Vit. D
 Calcium exists in three forms:
 Ionised (active) (50%)
 Bound to albumin (40%)
 Bound to anions (10%)
 However, 90% of body calcium is stored within bone
 Calcium levels need to be adjusted for albumin:
 Ionised = total calcium + 0.02(40-albumin)
 Plasma pH alters the affinity of albumin to calcium:
 Alkalosis – hypocalcaemia ( ionised Ca)
 Acidosis – hypercalcaemia ( ionised Ca)
 Only occurs in acute pH changes (too rapid for
the PTH to adjust for ionized calcium levels)
 Calcitonin (released from thyroid parafollicular cells)
opposes the action of PTH to decrease serum calcium
 Not important in normal homeostasis

Metabolic bone disease

Lab values in mineral bone disorders
CONDITION CALCIUM PHOSPHATE PTH ALP NOTES
Osteoporosis N N N N  Unremarkable

Osteomalacia/rickets       25-hydroxycholecalciferol if due to vitamin D deficiency

Paget’s disease N N N    urine hydroxyproline – indicative of bone turnover

 ALP rise is isolated (no increase in GGT)

Renal osteodystrophy      Occurs in setting of kidney disease

OSTEOPOROSIS
Osteoporosis is a metabolic bone disease characterised by decreased bone density (and a consequence increase in bone fragility)
FEATURES
 Typically, affects thin post-menopausal women (especially Caucasian and Asian)
 Risk factors (although there are many more):
 Age
 Smoking and alcohol
 Low dietary calcium (or malabsorption)
 Oestrogen-depleting conditions in women (or hypogonadism in men)
 Chronic inflammatory disease
 Endocrine disease
 Drugs (esp. long-term corticosteroid use)
CLINICAL PRESENTATION
 Typically, asymptomatic (although associated with back pain)
 Examination may reveal:
 Hip fractures
 Vertebral compression fractures (loss of height and thoracic kyphosis)
 Humerus fractures
 Distal radius fractures (Colles fracture) following minimal trauma

Note: a fragility fracture is any fall from a standing height or less, that results in a fracture.
 42

DIAGNOSIS
 Initial investigations:
 Labs: CBC, U&E (with calcium/phosphate), LFTs, TSH
 Imaging (diagnostic) :
 Dual energy X-ray absorptiometry (DEXA)
 Bone mineral density (BMD) of ≥2.5 standard deviations below the peak bone mass for young adults (T-score)
 Osteopenia : BMD with T-score between -1.0 and -2.5
 X-ray – global demineralisation (only seen after >30% of bone density is lost)
 Risk stratification (several scoring criteria – e.g. FRAX) – guides treatment and further investigation
TREATMENT
 Treatment for both men and women:
 Lifestyle – smoking cessation , alcohol reduction , and weight-bearing exercises (may maintain/restore bone density)
 Pharmacological:
 Calcium and vitamin D supplementation (first-line)
 Bisphosphonates (first-line)
 Other: RANKL inhibitors (denosumab), PTH analogues, calcitonin (second-line)
 Treatment specific for post-menopausal women:
 Hormone replacement therapy (combined oestrogen + progesterone)
 Selective oestrogen receptor modulators (raloxifene)
COMPLICATIONS
 Fracture (associated with a large increase in mortality)
OSTEOMALACIA AND RICKETS
Osteomalacia and rickets are characterised by a normal amount of bone but an increased proportion of unmineralized bone (osteoid) .
 This is the reverse of osteoporosis (where mineralisation is unchanged, but there is overall bone loss)
CLASSIFICATION
 Rickets – disorder occurring before fusion of epiphyses (during bone growth – i.e. in children)
 Osteomalacia – disorder occurring after fusion of epiphyses (after bone growth – i.e. in adults)
AETIOLOGY AND PATHOPHYSIOLOGY
 Vitamin D deficiency – leads to secondary hyperparathyroidism
 Deficient uptake/absorption (cholecalciferol) – nutritional deficiency or malabsorption
 Defective 25-hydroxylation (calcidiol) – liver disease
 Defective 1- α-25-hydroxylation (calcitriol) – kidney disease
 Mineralisation defect (abnormal matrix, enzyme deficiency, or presence of calcification inhibitors – e.g. bisphosphonates )
CLINICAL PRESENTATION
 Rickets – disturbed growth, diffuse skeletal pain, and skeletal deformities (classically bow-legged )
 Osteomalacia – diffuse skeletal pain, proximal muscle weakness, fractures, skeletal deformities, and classically a ‘waddling gait’
 Presentation is not as severe as rickets
 Signs and symptoms of hypocalcaemia
DIAGNOSIS
 Imaging: characteristic radiologic findings
 Bone biopsy: definitive (but rarely performed)
 Labs (see table)
TREATMENT
 Vitamin D supplementation ± calcium/phosphate supplementation (if indicated)
COMPLICATIONS
 Secondary hyperparathyroidism
PAGET’S DISEASE
Paget’s disease is a metabolic bone disorder characterised by excessive bone destruction and abnormal bone repair.
 Consider Paget’s disease in older adults with isolated  ALP (in absence of  GGP)
PATHOPHYSIOLOGY
 Suspected to be due to effects of a latent viral infection (paramyxovirus) in genetically susceptible individuals
 Mechanism: osteoclastic (osteolytic) phase  mixed phase  osteoblastic (osteosclerotic) phase  abnormal/fragile bone deposition
 43

CLINICAL PRESENTATION
 Usually, asymptomatic (routine X-ray finding or isolated elevated ALP)
 Associated with severe skeletal pain, skeletal deformity, and skull involvement (headaches, increased hat size, or deafness)
DIAGNOSIS
 Imaging:
 X-ray (diagnostic) – ‘mosaic’ lamellar bone pattern and thickened cortical bone
 In long bones, only affects one end of the bone (but whole bone in other bones)
 Bone scan (to establish extent of disease)
 Labs (see table)

Note: patients with Paget’s disease can develop hypercalcaemia if several bones affected and they are immobilised.
TREATMENT
 Most patients do not require treatment
 Calcium and vitamin D supplementation
 Bisphosphonates and calcitonin if severe (ALP >3x normal)
COMPLICATIONS
 Pathologic fractures
 Secondary hyperparathyroidism
 High-output cardiac failure (from AV connections)
 Nerve compression (associated with deafness if involving skull)
 Osteosarcoma (up to 1%)
PARATHYROID DISORDERS
Primary hyperparathyroidism
 Aetiology: typically, parathyroid adenoma ( also parathyroid carcinoma or ectopic PTHrP – SCLC, RCC, breast cancer)
 Treatment: surgical excision of adenoma (parathyroidectomy)
Secondary hyperparathyroidism
 Aetiology: caused by CKD ( calcitriol), vitamin D deficiency ( cholecalciferol), or hypocalcaemia (e.g. vitamin D deficiency)
Tertiary hyperparathyroidism
 Aetiology: irreversible growth and autonomous secretion of parathyroid glands due to long-term hyperparathyroidism (e.g. CKD)
Hypoparathyroidism
 Aetiology: typically, iatrogenic/post-surgica l (also autoimmune, congenital, or infiltrative disease )
Pseudohypoparathyroidism
 Aetiology: due to PTH resistance
 Associated with Albright hereditary osteodystrophy (may have shortened fourth and fifth metacarpal bones)
 Pseudopseudohypoparathyroidism – features of pseudohypoparathyroidism (without characteristic biochemistry)
Hypervitaminosis D
 Caused by excessive vitamin D (causes renal damage, nephrolithiasis, metastatic calcifications, and symptoms of high calcium)
Lab values in parathyroid disorders
CONDITION CALCIUM PHOSPHATE PTH
Primary hyperparathyroidism   

Secondary hyperparathyroidism   ( in CKD) 

Tertiary hyperparathyroidism   

Hypoparathyroidism   

Pseudohypoparathyroidism   

Hypervitaminosis D   

Disorders of multiple endocrine glands

MULTIPLE ENDOCRINE NEOPLASM

PATHOPHYSIOLOGY
 Multiple endocrine neoplasm is a group of syndromes that cause hormone-producing tumours of ectodermal origin in multiple
endocrine glands
 44

 Autosomal dominant inheritance with variable penetrance

CLASSIFICATION
 MENI (Wermer syndrome) (chromosome 11) – Pituitary, Parathyroid, Pancreas (3Ps) (± carcinoid tumours)
 Pancreas tumours – gastrinoma (Zollinger-Ellison syndrome), insulinoma, or VIPoma
 MENI is a tumour suppressor gene
 MENII (chromosome 10) – associated with RET proto-oncogene
 MENII-a (Sipple syndrome) – Medullary thyroid carcinoma (95% of cases), Pheochromocytoma, Parathyroid
 MENII-b – Medullary thyroid carcinoma (95% of cases), Pheochromocytoma, Multiple Neuromas, Marfanoid habitus

Neuroendocrine tumours
CARCINOID TUMOUR
Carcinoid tumours are slow-growing neuroendocrine tumours that can synthesise various hormones (esp. serotonin).
 Commonly located in the gastrointestinal tract (esp. small bowel) or bronchopulmonary system
 Most common malignant tumour of the appendix
CLINICAL PRESENTATION
 Typically, asymptomatic (synthesised hormones metabolised by liver)
 Carcinoid syndrome (occurs if metastatic spread to liver – bypassing first-pass metabolism)
 Characterised by diarrhoea, abdominal cramps, cutaneous flushing, and asthma-like symptoms
 Also associated with right-sided cardiac valve disease and restrictive cardiomyopathy
DIAGNOSIS
 Screening labs: 24-hour urine ( 5-HIAA) and  serum serotonin
 Definitive:
 Imaging – CT/MRI abdomen/pelvis (or somatostatin-receptor scintigraphy)
 Biopsy
TREATMENT
 First-line – surgical resection
 Second-line – octreotide (somatostatin analogue)
VIPOMA
VIPomas are neuroendocrine tumours that secrete excess VIP (vasoactive intestinal polypeptide).
 VIP causes a cholera-like secretory diarrhoea
CLINICAL PRESENTATION
 WDHA syndrome (Watery Diarrhoea, Hypokalaemia, Achlorhydria)
DIAGNOSIS
 Labs –  serum VIP (and electrolyte disturbance – mainly hypokalaemia)
 Imaging – CT/MRI abdomen/pelvis
TREATMENT
 First-line – surgical resection
 Second-line – octreotide (somatostatin analogue)

Reproductive endocrinology
FEMALE REPRODUCTIVE PHYSIOLOGY
See Gynaecology for more detail.
CLINICAL NOTES
 Androgens are produced by Theca cells (outer cells of follicle)
 Oestrogen is produced by Granulosa cells (inner cells of follicle)
 Produced from androgens via the enzyme aromatase
 Progesterone is produced by the corpus luteum (degenerated follicle)
 Inhibin is produced by Granulosa cells (and Leydig cells in males)
 Major action is negative feedback of pituitary FSH secretion
ROLES OF OVARIAN STEROIDS
 Androgens:
 Substrate for oestrogen synthesis
 Oestrogen :
 45

 Induce and maintains secondary sex characteristics

 Regulate gonadotropin secretion by negative feedback
 Development of breast ducts
 Progesterone:
 Regulate gonadotropin secretion by negative feedback
 Secretory endometrial activity
 Maintains pregnancy (inhibits uterine contraction)
 Development of breast glands
MALE REPRODUCTIVE PHYSIOLOGY

CLINICAL NOTES
 Androgens (testosterone) are produced by Leydig cells
 DHT (more active androgen) is produced by Sertoli cells
 Produced from testosterone via the enzyme 5-α-reductase
 Oestrogen is produced by Sertoli cells
 A small amount of oestrogen is required for efferent duct function
 Lack of oestrogen causes infertility in males
ROLE OF TESTICULAR STEROIDS
 Testosterone:
 Induce and maintains sex characteristics
 Regulate gonadotropin secretion by negative feedback
 Promote spermatogenesis by supporting Sertoli cell function
 Dihydrotestosterone:
 Induce and maintains somatic and secondary sex characteristics
 Oestradiol:
 Required for efferent duct function
DEFECTS IN ANDROGEN ACTION

AETIOLOGY
 Complete (or partial) androgen insensitivity
 5-α-reductase insensitivity
 Gonadal dysgenesis
 Defects in testosterone synthesis
CLINICAL PRESENTATION

Effects of testosterone deficiency

EFFECTS

Early (1st trimester) in utero  Incomplete virilisation of external genitalia (ambiguous genitalia)
 Incomplete development of Wolffian ducts to form male internal genitalia (male pseudohermaphrodism)

Late in utero  Micropenis

 Cryptorchidism (failure of normal testicular descent; risk for testicular cancer)

Pre-puberty  Incomplete pubertal maturation (high pitch voice, absence of facial hair, sparse axillary or pubic hair)
 Poor muscle development
 Eunuchoid habitus (greater growth of long bones relative to axial bones)

Post-puberty  Decrease in energy, mood, and libido

 Decrease in muscle mass and strength

GYNAECOMASTIA
Gynaecomastia is a benign proliferation of the glandular component of the male breast.
 Due to hormonal imbalance (increased oestrogen or decreased androgen activity)
 Pseudo-gynaecomastia refers to enlargement of soft adipose tissue (seen in obese individuals and does not warrant evaluation)
AETIOLOGY
 Physiologic (common):
 Pubertal – peaks in early teens and typically regresses within several years
 Neonatal – due to maternal hormone
 Elderly (involutional)
 Pathologic:
 46

 Persistent pubertal gynaecomastia

 Endocrine disturbance – primary or secondary hypogonadism
 Tumours – testicular tumours (or ectopic production of hCG – paraneoplastic)
 Chronic diseases – typically, cirrhosis (also renal failure)
 Drugs – spironolactone, chemotherapy , marijuana, alcohol, digoxin , ketoconazole
 Congenital – Klinefelter’s syndrome or androgen insensitivity
DIAGNOSIS
 Labs: endocrine workup (TSH, PRL, LH/FSH, androgens, hCG) and markers of chronic disease (U&E, LFTs)
 Imaging:
 CXR/CT chest/abdomen/pelvis (to locate neoplasm)
 MRI of pituitary if adenoma suspected
 Testicular U/S (if  hCG) – to assess for testicular tumour
TREATMENT
 Conservative treatment (observation) is appropriate for most cases
 Medical:
 Correct underlying disorder (or offending drug )
 Anti-oestrogens (tamoxifen) – first-line
 Androgens – for hypogonadism
 Surgical treatment – if refractory or for cosmetic purposes
 47

Haematology/Oncology.
Coagulation disorders
NORMAL HAEMOSTASIS

Three phases of haemostasis

 Primary haemostasis
 Goal: rapid cessation of bleeding (main effect on mucocutaneous bleeding)
 Mechanism:
 Vessel injury results in collagen/subendothelial matrix exposure and release of vasoconstrictors
 Blood flow is impeded, and platelets come into contact with damaged vessel wall, leading to:
 Adhesion: platelets adhere to subendothelium via vWF
 Activation: platelets are activated resulting in change of shape and release of ADP and thromboxane A2
 Aggregation: these factors recruit/aggregate more platelets resulting in formation of haemostatic platelet plug
 Secondary haemostasis
 Goal: reinforce platelet plug
 Mechanism:
 Reinforcement of platelet plug by fibrin clot:
 Extrinsic pathway (initiation of coagulation)
 Intrinsic pathway (amplification of coagulation)
 Fibrin stabilisation and fibrinolysis (resolution):
 Goal: conversion from soluble to insoluble clot; once healing initiated, clot dissolution
(anticoagulant pathway)

Note: all coagulation factors are made in the liver (except vWF and VIII – also made in
endothelium).

Anticoagulation
 Antithrombin – inhibits activation of factors II, VII, IX, X
 Potentiated by heparin
 Protein C/S – inactivates activated factors V and VIII (with protein S)
 Resistant to degradation in factor V Leiden mutation
 Plasminogen – activated into plasmin by tPA which leads to fibrinolysis (cleavage of fibrin clot and destruction of coagulation
factors)
 Hence, tPA is used clinically as a thrombolytic

Common tests of haemostasis

Common tests of haemostasis
TEST PURPOSE EXAMPLES
Platelet count To quantify platelet number Low in ITP, TTP, HUS, and DIC

Bleeding time To quantify platelet function Prolonged in vWD and platelet disorders

Activated partial Measures intrinsic (and common) pathways of Prolonged in haemophilia, DIC, liver disease, and heparin
thromboplastin time (aPTT) coagulation (i.e. factors VIII, IX, XI, XII) treatment

Prothrombin time (PT) Measures extrinsic (and common) pathways of Prolonged in warfarin treatment, vitamin K deficiency,
coagulation (i.e. factors VII) liver disease, and DIC

INR A standardised measure of PT between labs N/A

Mixing studies Differentiates inhibitors of clotting factors from Deficiency if test becomes normal
deficiencies of clotting factors (mix patient’s plasma with Inhibitors if test remains abnormal
normal plasma in 1:1 ratio)

Signs and symptoms of disorders of haemostasis

Signs and symptoms of disorders of haemostasis
PRIMARY (PLATELET) SECONDARY (COAGULATION)
Surface cuts Excessive/prolonged bleeding Normal/slightly prolonged bleeding

Onset after injury Immediate Delayed (or after re-injury)

 48

Site of bleeding Superficial/mucosal (e.g. nasal, gingival, uterine, GI tract) Deep (e.g. joints, muscle, GU tract) or excessive post-traumatic

Lesions Petechia / ecchymoses Haemarthroses / haematomas

Lab values in disorders of haemostasis

Lab values in disorders of haemostasis
DISORDER APTT PT (INR) PLATELET COUNT RBC COUNT
Haemophilia  N N N

vWD N/ N N N

DIC    

ITP N N  N

TTP N N  

Liver failure   N/ N

Platelet defects N N N N

HAEMOPHILIA
Haemophilia are X-linked recessive clotting factor deficiencies that result in an increased tendency to bleed .
CLASSIFICATION
 Haemophilia A – VIII (80% of cases)
 Haemophilia B – IX
 Haemophilia C – XI (rare)
 Acquired – autoantibodies that interfere with the above factors (rare)
CLINICAL PRESENTATION
 Typically, presents in young boys with spontaneous haemorrhage (into tissues, joints, and muscles)
 Leads to the Five H’s – Haemarthroses, Haematomas, Haematochezia, Haematuria, Head haemorrhage
 Mild cases may have major haemorrhage following trauma or procedures but otherwise are asymptomatic
DIAGNOSIS
 Labs:  aPTT (with normal PT/bleeding time)
 Initial test: mixing study (mix patient’s plasma with normal plasma – corrects PTT)
 Definitive test: specific factor assays
 Genetic counselling
TREATMENT
 Normal (>5% factor levels) or moderate (1-3% factor levels) – desmopressin (releases vWF and factor VIII from endothelial
cells) and tranexamic acid (antifibrinolytic)
 Severe (≤1% factor levels) – immediately transfuse factor (or cryoprecipitate if unavailable)
 Autoimmune - steroids
VON WILLEBRAND DISEASE
Von Willebrand Disease is an autosomal dominant deficiency in vWF (and decreased levels of factor VIII, which is carried by vWF).
 vWF has three roles in clotting:
 Bringing platelets into contact with exposed endothelium
 Binding platelets to each other
 Binding to factor VIII (protecting it from destruction in the circulation)
 vWD the most common inherited bleeding disorder
CLASSIFICATION
Classified by level and function of vWF:
 Type 1 (AD) – deficiency of vWF (70% of cases – mild symptoms)
 Type 2 (AD) – abnormal vWF (25% of cases – variable symptoms)
 Type 3 (AR) – absence of vWF (5% of cases – severe symptoms)
CLINICAL PRESENTATION
 Typically, presents in childhood with recurrent and prolonged mucosal bleeding (specific for platelet dysfunction)
 Examples include epistaxis, gums, teeth , menorrhagia
 Often a family history is present
 49

 Symptoms worsen with anti-platelet usage

DIAGNOSIS
 Labs:  bleeding time;  aPTT (due to low VIII); normal PT; normal platelet count
 Definitive tests:
 Ristocetin cofactor assay (decreased – measures capacity of vWF to agglutinate platelets)
 vWF antigen levels ( decreased)
TREATMENT
 Mild to moderate bleeding – desmopressin and tranexamic acid
 Severe bleeding – high-purity vWF/VIII concentrate (FFP is not useful)
 Menorrhagia – OCPs
 Avoid anti-platelets and NSAIDs
HYPERCOAGULABLE STATES
Hypercoagulable states (also called thrombophilia or prothrombotic states ) includes all conditions that increase the risk of developing
thromboembolic disease .
 The most important conditions are factor V leidin, heparin-induced thrombocytopenia, antiphospholipid syndrome
 Also, protein C/protein S/antithrombin deficiency
CLASSIFICATION

Causes of hypercoagulable states

GENETIC ACQUIRED PHYSIOLOGIC
 Factor V Leidin  Surgery  Pregnancy
 Protein C deficiency  Trauma  Age
 Protein S deficiency  Malignancy
 Antithrombin III deficiency  Immobilisation
 Prothrombin gene mutations  Smoking
 Obesity
 Antiphospholipid syndrome
 OCPs (and HRT)

CLINICAL PRESENTATION
 Present with recurrent thromboembolism (i.e. DVT, PE, MI, stroke, arterial thrombosis)
 Women may have recurrent miscarriage
DIAGNOSIS
 Genetic screening (after acquired causes have be ruled out)
 Labs: CBC, blood film, coagulation
TREATMENT
 Treat thromboembolism as standard; consider long-term prophylaxis (antiplatelet or anticoagulation )
Factor V Leiden
A polymorphism in factor V, rendering it resistant to inactivation by activated protein C .
 The most common cause of hereditary hypercoagulable state (5% of population)
 Typically, occurs in Caucasians with a family history
DIAGNOSIS
 Definitive: APC resistance test with reflexive DNA testing
Heparin-induced thrombocytopenia
An autoimmune reaction to the administration of heparin creating platelet-activating antibodies.
 Associated with <50% drop in platelets after heparin administration
DIAGNOSIS
 Definitive: PF4 antibody and serotonin release assay
TREATMENT
 Discontinue heparin ; use dabigatran
Antiphospholipid syndrome
Antiphospholipid syndrome is a multisystem vasculopathy (associated with SLE) (treated with life-long anticoagulation )
 Predisposes to arterial and venous thrombi, thrombocytopenia, and recurrent miscarriages (in women)
 50

DIAGNOSIS
 Definitive – lupus anticoagulant and anticardiolipin antibody
Protein C/S deficiency
A condition associated with skin necrosis after warfarin administration .
DISSEMINATED INTRAVASCULAR COAGULATION
Disseminated intravascular coagulation (DIC) is an acquired coagulopathy caused by deposition of fibrin in small blood vessels
(leading to thrombosis, red-cell lysis (microangiopathic haemolytic anaemia), and end-organ damage )
 Leads to consumption of clotting factors and platelets (i.e. simultaneous coagulation and fibrinolysis)
 Associated with many severe illnesses (most often seen in hospitalised patients), most often:
 Malignancy
 Sepsis
 Trauma
 Pancreatitis
 Obstetric complications
CLINICAL PRESENTATION
 Defined by the presence of both haemorrhage and clotting
 Disseminated internal and external bleeding (e.g. organs and ecchymoses/petechiae)
 Microvascular thrombosis (e.g. neurological deficits, MAHA, renal dysfunction)
DIAGNOSIS
 Clinical diagnosis
 Labs: CBC (low red cells and platelets), coagulation (consumptive coagulopathy – esp. fibrinogen with  D-Dimer)
 May be confused with liver disease, but unlike liver disease, factor VIII is depressed
TREATMENT
 Treat the underlying cause
 Replacement therapy – platelet concentrate (platelets), cryoprecipitate (fibrinogen), FFP (coagulation factors)
 Activated protein C – can reduce mortality
THROMBOTIC THROMBOCYTOPENIC PURPURA

PATHOPHYSIOLOGY
 Thrombotic thrombocytopenic purpura is a deficiency in the vWF-cleaving enzyme (ADAMTS-13) resulting in abnormally large
vWF multimers that aggregate platelets and create platelet microthrombi
 These microthrombi block small blood vessels , leading to end-organ damage
 RBCs are fragmented by contact with microthrombi, leading to haemolysis (microangiopathic haemolytic anaemia )
CLINICAL PRESENTATION
Suspect TTP if three of these five symptoms are present:
 Fever
 Thrombocytopenia (and splenomegaly)
 Microangiopathic haemolytic anaemia (and jaundice)
 Neurologic signs and symptoms
 Impaired renal function
DIAGNOSIS
 Clinical diagnosis
 Labs: CBC (low red cells and platelets), blood film (with schistocytes – fragmented RBCs), U/E (renal dysfunction), urinalysis
(haematuria/proteinuria), LFTs (unconjugated hyperbilirubinaemia); coagulation tests are normal
TREATMENT
 Plasmapheresis
 Steroids
 Platelet transfusion is contraindicated (can worsen consumptive process)
OUTCOMES
 >90% mortality if untreated
Haemolytic-uraemic syndrome
Haemolytic-uraemic syndrome (HUS ) is a condition on the same disease spectrum as TTP
 Similar presentation and lab findings to TTP (although without neurologic symptoms and with more severe creatinine levels )
 Up to >90% of cases are in children caused by O157 E. coli (produces verotoxin – damages endothelium)
 Triad of thrombocytopenia (and splenomegaly), microangiopathic haemolytic anaemia , and acute renal failure
 51

 Classically preceded by haemorrhagic diarrhoea

 May require dialysis

Note: DIC, TTP, HUS, and HELLP are the four main causes of microangiopathic haemolytic anaemia .

HELLP
HELLP syndrome is a thrombotic microangiopathy of pregnancy, characterised by haemolysis, elevated liver enzymes, and low
platelets .
 Caused by a maternal-foetal immune imbalance that induces platelet aggregation, endothelial dysfunction, and arterial hypertension
CLINICAL PRESENTATION AND DIAGNOSIS
 Occurs in late pregnancy (>30 weeks)
 Symptoms: severe abdominal pain, nausea/vomiting, and malaise
 Labs: haemolysis, elevated liver enzymes, low platelets
TREATMENT
 Urgent delivery of foetus
IMMUNE THROMBOCYTOPENIC PURPURA
Immune thrombocytopenic purpura (ITP) is a condition where IgG antibodies are formed against the patients’ platelets.
 The most common cause of isolated thrombocytopenia
PATHOPHYSIOLOGY
 IgG antibodies against platelets  platelet-antibody complex destroyed in spleen
 Hence,  bone marrow platelet production (and  marrow megakaryocytes)
CLINICAL PRESENTATION
 Typically, asymptomatic (with no splenomegaly as opposed to MAHA)
 Acute (in children): abrupt onset of haemorrhagic complications following viral illness
 Usually self-limiting in several months (up to 20% may become chronic)
 Chronic (in adults; F>M): gradual onset of fluctuating haemorrhagic complications
DIAGNOSIS
 Diagnosis of exclusion (once other causes of thrombocytopenia have been ruled out)
 Labs: CBC (thrombocytopenia), blood film (normal or  platelets), coagulation (normal), antiplatelet antibodies
 Bone marrow biopsy is definitive (but rarely done) – shows megakaryocytes
TREATMENT
 Mild – no treatment required
 Severe thrombocytopenia or bleeding issues – steroids, tranexamic acid, IVIG
 Refractory – splenectomy ± immunosuppression ± thrombopoietin receptor agonists
 Platelet transfusions are not used (except in life-threatening haemorrhage)
COMPLICATIONS
 Major concern is cerebral haemorrhage (occurs if platelets <5x109/L) but this is very rare

Red blood cell disorders

 52

ANAEMIAS

CLASSIFICATION

CLINICAL PRESENTATION
 Symptoms : fatigue, headache, malaise, weakness, decreased exercise tolerance, dyspnoea, dizziness, tinnitus, syncope
 Signs: pallor, tachycardia, heart failure

Microcytic anaemias
APPROACH TO MICROCYTIC ANAEMIA

Iron studies and blood film in common disorders

TRANSFERRIN
CONDITIONS SERUM IRON FERRITIN TS% BLOOD FILM
(TIBC)
Iron deficiency      Rarely pencil or target cells

ACD  N/    Microcytic hypochromic

Thalassaemia N/ N/ N N  Target cells +/- HbH bodies (in α)

Haemachromatosis      Normal

Iron deficiency anaemia

Anaemia in which iron loss exceeds iron intake .
 May occur due to:
 Increased demand : growth, pregnancy, EPO therapy
 Decreased iron: chronic bleeding (menorrhagia/GI), malnutrition/absorption disorders
 Toddlers, adolescent girls, and women of childbearing age most commonly affected
CLINICAL PRESENTATION
 Variable clinical presentation (asymptomatic to typical findings of anaemia)
 Pica may occur in children (consistent ingestion of non-nutritious substances – e.g. paint, faeces, soil)
 Signs of iron deficiency: glossitis, cheilitis, koilonychia (spoon nails)
DIAGNOSIS
 Labs: CBC with iron studies (± blood film)
TREATMENT
 Treat underlying cause
 Supplemental iron therapy (oral  IV if severe)

Note: ferritin is an acute phase reactant; however, if ferritin >100 in the presence of inflammation then iron deficiency is excluded.
 53

Anaemia of chronic disease

PATHOPHYSIOLOGY
 An anaemia of underproduction due to impaired iron utilisation:
 Hepatic hepcidin production is increased – trapping iron in enterocytes and macrophages (via ferroportin inhibition)
 Reduced plasma iron levels make iron relatively unavailable for haemoglobin synthesis
 Marrow unresponsive to normal or slightly elevated EPO
 Mild haemolytic component often present
 RBC survival is modestly decreased
DIAGNOSIS
 Diagnosis of exclusion
 Labs: CBC with iron studies (± blood film)
TREATMENT
 Treat underlying cause
 EPO – in chronic renal failure
Thalassaemias
Thalassaemias are autosomal recessive disorders involving decreased/absent production of normal globin chains (of haemoglobin).
CLASSIFICATION
 α-thalassaemia – caused by mutations in 1 or more of 4 genes for α-globin (chromosome 16)
 β-thalassaemia – caused by mutations in 1 or more of 2 genes for β-globin (chromosome 11)
CLINICAL PRESENTATION
 Common in Maori/Pacific/Asian population
 Variable presentation (dependent on number of genes missing)
Clinical presentation of α-thalassaemia syndromes
SUBTYPE GENES INVOLVED FEATURES
Silent carrier 3/4 α genes present  Asymptomatic

α-thalassaemia trait 2/4 α genes present  Mild anaemia

(α+ or α0)  Reproductive implications for α0
 May find HbH bodies (excess β-globin chains form tetramers seen on blood film)

Note: α+ has 1 gene on each chromosome; α0 has 0 genes on one chromosome

Haemoglobin H disease 1/4 α genes present  Severe anaemia (with haemolysis, splenomegaly, jaundice, and cholelithiasis)
 Skeletal changes often present (due to expanded erythropoiesis)
 HbH bodies present

Hydrops fetalis 0/4 α genes present  Patients die in utero/early post-natal (detection important to avoid maternal complication)

Clinical presentation of β-thalassaemia syndromes

SUBTYPE GENES INVOLVED FEATURES
β-thalassaemia minor 1/2 β genes present  Asymptomatic or mild anaemia

β-thalassaemia major and 0/2 β genes present  Severe anaemia (presenting in first year of life with FTT)
β-thalassaemia  Skeletal changes often present (due to expanded erythropoiesis)
intermedia (less severe)

DIAGNOSIS
 α-thalassaemia – diagnosed by DNA studies (HbH bodies can be found in more severe cases – excess beta chains form tetramers)
 β-thalassaemia – diagnosed by increased HbA2 level (α2δ2)
TREATMENT
 No treatment required for minor cases
 Genetic counselling for patient and family
 β-thalassaemia major and HbH disease:
 Lifelong regular transfusions (to supress endogenous erythropoiesis)
 Iron chelation
 Splenectomy (performed rarely)
 Hydrops fetalis – therapeutic abortion
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Sideroblastic anaemia
Sideroblastic anaemia is a rare cause of microcytic anaemia due to defects in haem metabolism that can be hereditary or acquired
(commonly alcohol, lead poisoning, copper deficiency , and isoniazid).
 Associated with basophilic stippling (in lead poisoning) and ringed sideroblasts on peripheral blood smear (pathognomonic)
 Lead poisoning presents with intermittent abdominal pain, peripheral neuropathy (wrist or foot drop), or acute encephalopathy
 Treated with chelation therapy (EDTA)

Non-haemolytic normocytic anaemias

Aplastic anaemia
Aplastic anaemia is a condition characterised by destruction of haemopoietic cells of the bone marrow.
 Leads to pancytopenia and hypocellular bone marrow
AETIOLOGY
 Most cases are idiopathic or triggered by drugs or irradiation
 Can be congenital (i.e. Fanconi’s anaemia – defective stem cell repair and chromosomal fragility)
CLINICAL PRESENTATION
 Presents with anaemia, thrombocytopenia , and infection
 Associated with splenomegaly and lymphadenopathy (dependent on cause)
DIAGNOSIS
 Labs: CBC (pancytopenia and decreased reticulocytes)
 Bone marrow biopsy is definitive (aplasia/hypoplasia and decreased cellularity with fat replacement)
TREATMENT
 Treat underlying cause
 Supportive care – red cell and platelet transfusions and prophylactic antibiotics
 Immunosuppression (if idiopathic – although not curative)
 Allogenic bone marrow transplant

Haemolytic normocytic anaemias

APPROACH TO HAEMOLYTIC ANAEMIAS
 Clinical features specific to haemolytic anaemia
 Jaundice ( haemolysis – haem broken down to bilirubin or obstructive jaundice from pigment stones)
 Dark urine (haemoglobinuria or obstructive jaundice from pigment stones)
 Cholelithiasis (pigment stones)
 Screening tests
 LDH – increased
 Haptoglobin – decreased (sequesters haemoglobin in blood)
 Unconjugated bilirubin – increased (although technically conjugated could occur via gallstones)
 Urobilinogen – increased (consistent with unconjugated hyperbilirubinaemia)
 Reticulocytes – increased (indicative of red cell replacement)
HEREDITARY

CLASSIFICATION
 Abnormal membrane – spherocytosis, elliptocytosis
 Abnormal enzymes – pyruvate kinase deficiency, G6PD deficiency
 Abnormal haemoglobin – thalassaemia, haemoglobinopathies (e.g. Sickle cell disease)
Hereditary spherocytosis/elliptocytosis
Hereditary spherocytosis and elliptocytosis are caused by abnormality in RBC membrane proteins (e.g. spectrin).
 The most common type of hereditary haemolytic anaemias (esp. spherocytosis)
 Both are autosomal dominant
DIAGNOSIS
 Osmotic fragility tes t (increased fragility in hypotonic solutions)
 Blood film (shows spherocytes or elliptocytes)
TREATMENT
 Splenectomy for severe haemolysis (with immunisations against encapsulated bacteria)
Pyruvate kinase deficiency
Pyruvate kinase deficiency is an autosomal recessive disorder that results in decreased ATP production causing decreased RBC survival.
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DIAGNOSIS
 Diagnosed by enzyme assay
TREATMENT
 Usually not required
G6PD deficiency
G6PD deficiency is an X-linked recessive disorder that results in decreased glutathione (GSH) which leads to  RBC sensitivity to
oxidative stress .
CLINICAL PRESENTATION
 Neonates: prolonged, neonatal jaundice
 Adults: episodic haemolysis precipitated by oxidative stress, drugs, infection, or foods (broad beans)
DIAGNOSIS
 Blood film – Heinz bodies (granules in RBCs due to oxidised Hb) and bite cells (RBCs damaged through spleen passage)
 Diagnosed by enzyme assay / neonatal screening
TREATMENT
 Avoid precipitants
 Transfusion in severe cases
Sickle cell anaemia
Sickle cell anaemia is an autosomal recessive disorder caused by mutation of adult haemoglobin (the β-chain has Glu  Val).
 Can occur as a homozygous or compound heterozygous mutation
PATHOPHYSIOLOGY
 At low oxygen saturation, deoxy-HbS polymerises leading to RBC deformation into sickle cells
 The sickle cells are fragile and haemolyse ( RBC survival) and also occlude small vessels
CLINICAL PRESENTATION
 HbAS (sickle cell trait) – asymptomatic except during extreme hypoxia or infection
 HbSS (sickle cell disease ) – chronic haemolytic anaemia (with childhood jaundice and FTT)
 Associated with splenomegaly in childhood and splenic atrophy in adulthood
 Often presents as an acute episode:
 Aplastic crises (esp. parvovirus B19 ) – transiently suppresses bone marrow
 Splenic sequestration crises – usually in children; significant pooling of blood in spleen causes acute Hb drop and shock
 Vaso-occlusive crises – causes ischaemia/infarction in many organs (e.g. stroke, mesenteric ischaemia, MI)
 Acute chest syndrome – severe respiratory symptoms and pulmonary infiltrates (affects 30% of cases)
 Infection – encapsulated organisms (sickle cell causes functional asplenism)
DIAGNOSIS
 Labs: CBC and blood film (reticulocytes and sickle cells)
 Haemoglobin electrophoresis confirms diagnosis and distinguishes different states
TREATMENT
 Genetic counselling
 HbAS: no treatment required
 HbSS:
 Chronic folic acid supplementation
 Hydroxyurea to enhance production of HbF (decreases sickling)
 Exchange transfusion (if crisis)
 Prevention of crises:
 Avoid conditions that promote sickling (hypoxia, acidosis, fever)
 Vaccination
 Prophylactic antibiotics
 Treatment of vaso-occlusive crisis:
 Oxygen
 Hydration (reduces viscosity)
 Analgesia
 Screen for complications:
 Regular blood work (CBC, iron studies, renal function, LFTs)
 Stroke (transcranial doppler), retinopathy (retinal exam), pulmonary hypertension (echocardiography) screening
COMPLICATIONS
 Splenic infarction
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 Failure to thrive
 Chronic renal failure
 Gall stones
 Retinal disease
 Iron overload
 Lung damage
ACQUIRED IMMUNE

CLASSIFICATION
 Autoimmune: warm versus cold autoimmune haemolytic anaemias (AIHA)
 Alloimmune: haemolytic disease of the foetus
Classification of Autoimmune Haemolytic Anaemia (AIHA)
WARM AGGLUTININ DISEASE COLD AGGLUTININ DISEASE

Antibody IgG (causes extravascular haemolysis) IgM (causes intra- and extra-vascular haemolysis)

Temperature >37C <30C

Aetiology Idiopathic Idiopathic

SLE Waldenstrom macroglobulinaemia
Lymphoma Lymphoma
Chronic lymphocytic leukaemia Chronic lymphocytic leukaemia
Infection (mycoplasma pneumonia or EBV)

Diagnosis DAAT / spherocytes in blood film DAAT / cold-agglutinin titre / spherocytes in blood film
Complement () Complement ()

Management Treat underlying cause Avoid cold exposure

Corticosteroids Immunosuppressive therapy with rituximab
Immunosuppression
Splenectomy

ACQUIRED NON-IMMUNE
Microangiopathic haemolytic anaemia
Caused by several disorders (predominantly DIC, HUS, TTP, HELLP ; but also, vasculitis and malignant hypertension ).
Paroxysmal nocturnal haemoglobinuria
Paroxysmal nocturnal haemoglobinuria is caused by a deficiency in GPI-anchor molecules that keep CD55/CD59 proteins ( protect
against complement-mediated haemolysis) attached to RBCs, neutrophils, and platelets – resulting in haemolysis by complement.
CLINICAL PRESENTATION
 Triad of haemolytic anaemia (iron-deficiency possible), episodic haemoglobinuria (dark urine), and venous thrombosis
 Increased risk for acute myeloblastic leukaemia
DIAGNOSIS
 Definitive: flow cytometry (for absence of CD55/CD59)
TREATMENT
 Anticoagulation
 Complement blockade

Non-megaloblastic macrocytic anaemias

Non-megaloblastic macrocytic anaemias reflect a membrane abnormality with abnormal cholesterol metabolism .
 Characterised by large, round, normal RBCs and normal neutrophils

Megaloblastic macrocytic anaemias

Megaloblastic anaemias reflects a failure of DNA synthesis resulting in asynchronous maturation of RBC nucleus and cytoplasm .
 Characterised by megaloblasts (large, oval, nucleated RBC precursors) and hyper-segmented neutrophils
Vitamin B12 (cobalamin) deficiency
AETIOLOGY
 Dietary – strict vegans
 Gastric – pernicious anaemia or post-gastrectomy
 Pernicious anaemia – anti-intrinsic factor and anti-parietal cell antibodies leading to atrophic gastritis and vitamin B12 deficiency
 Absorptive – malabsorption or resection of ileum
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 Genetic – transcobalamin II deficiency

CLINICAL PRESENTATION
 Presents with a number of neurological findings :
 Cerebral (common and reversible) – confusion, delirium, depression, dementia
 Subacute combined degeneration of the cord (irreversible)
 Dorsal column – decreased light touch, vibration, and proprioception
 Pyramidal tracts – UMN dysfunction
 Peripheral neuropathy (variable reversibility) – usually symmetrical (lower limbs > upper limbs)
 Classic triad of positive Babinski , absent knee jerk , and absent ankle jerk
 Other signs: jaundice and glossitis
DIAGNOSIS
 Labs: CBC (severe anaemia), reticulocytes (), serum B12 (), LFTs (unconjugated –  RBC breakdown)
 Blood film: oval macrocytes and hyper-segmented neutrophils
 Bone marrow: megaloblasts
 Schilling test (radiolabelled B12 and exogenous intrinsic factor) – can distinguish pernicious anaemia from other causes
TREATMENT
 Vitamin B12 IM life-long (or oral if intestinal absorption intact)
Folate deficiency
AETIOLOGY
 Dietary – alcoholics and poor intake
 Malabsorption
 Drugs – alcohol, methotrexate, anticonvulsants
 Increased demand – pregnancy, haemolysis, prematurity
CLINICAL PRESENTATION
 Unlike B12 deficiency, folate deficiency has no neurologic manifestations
 Other signs: jaundice, glossitis, angular cheilitis (similar to vitamin B12 deficiency)
TREATMENT
 Folic acid (oral) with vitamin B12 (otherwise it may mask B12 deficiency and worsen neurological degeneration)
 Prophylactic folic acid for pregnancy
PORPHYRIA
Porphyria relates to a group of inherited disorders in haem production that lead to accumulation of porphyrins .
 Include acute intermittent porphyria, erythropoietic porphyria, and porphyria cutanea tarda (most common)
CLINICAL PRESENTATION
 Characterised by a combination of photodermatitis , neuropsychiatric complaints/seizures , and abdominal pain
 Physical examination: tachycardia, skin erythema, blisters, areflexia, and non-specific abdominal examination
 Pink urine is a tell-tale sign (or brown after an acute attack)
 Acute attacks often associated with stimulants of haem synthesis (alcohol, barbiturates, OCPs )
DIAGNOSIS
 Initial test: urine and plasma porphyrin levels
 Definitive test: genetic or enzyme analysis
TREATMENT
 Remove precipitant
 Symptomatic treatment (IV fluids)
 IV haematin ( porphyrin precursors)
 High doses of glucose during attacks ( haem synthesis)

Haematological malignancies and related disorders

LEUKAEMIA
Leukaemia is a malignant proliferation of haematopoietic cells (characterised by type of cell involved and level of differentiation).
 Arise in bone marrow and spreads elsewhere (as opposed to lymphoma, which arises in lymph tissue)
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Acute leukaemias
PATHOPHYSIOLOGY
 Acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (acute lymphocytic leukaemia or ALL) are clonal disorders
of early haematopoietic cells (blasts) resulting in unregulated growth and differentiation of white blood cells in bone marrow
 As bone marrow becomes overwhelmed, anaemia ( RBC), infection ( mature WBCs), and haemorrhage ( platelets) occur
CLINICAL PRESENTATION
 AML/ALL affect both children and adults (but ALL is the most common childhood malignancy)
 Characterised by a rapid onset and progression of :
 Anaemia (e.g. pallor, fatigue)
 Thrombocytopenia (e.g. petechia, purpura, bleeding)
 Infections (due to ineffective and immature WBCs)
 DIC (seen in AML)
 Bone pain (seen in ALL – due to medullary expansion into periosteum)
 Examination: hepatosplenomegaly, lymphadenopathy, and swollen/bleeding gums (leukaemic infiltrate and decreased platelets)
 Associated with infiltration of skin (leukaemia cutis ), CNS (meningeal/cranial nerve signs ), and testicles (gonadomegaly )
DIAGNOSIS
 Initial test: CBC with blood film (demonstrates blast cells and anaemia, granulocytopenia, and thrombocytopenia)
 Definitive test: bone marrow biopsy with flow cytometry/immunohistochemistry
 AML – leukaemic cells are myeloblasts
 ALL – leukaemic cells are lymphoblasts
 Additional:
 Cytogenetics – associated with several genetic defects
 CXR – mediastinal lymphadenopathy (in ALL)

Note: although the patient may have neutrophilia , they are technically immune deficient due to dysfunctional white blood cells.
TREATMENT
 Typically, treated with chemotherapy (although some patients may receive bone marrow transplantation )
OUTCOMES
 ALL – good prognosis in children; worse in adults
 Worse prognosis – age <2 or >10, male, WBC >50, Philadelphia chromosome, CNS involvement
 AML – poor prognosis (unless acute promyelocytic leukaemia – good response to all-trans-retinoic acid therapy )
Differentiating AML from ALL
AML ALL
Cell type Myeloblast Lymphoblast

Epidemiology Adults Children

Cell size Large Small

Amount of cytoplasm Large Small

Nucleoli Many Few

Granules Many Few

Auer rods Present Absent

Myeloperoxidase Present Absent

TdT Absent Present

Chronic leukaemias
Chronic lymphocytic leukaemia
PATHOPHYSIOLOGY
 Chronic lymphocytic leukaemia (CLL) is a clonal proliferation of mature well-differentiated B lymphocytes that accumulate in
the bone marrow, peripheral blood, lymph nodes, spleen, and liver
 Known as SLL (small lymphocytic lymphoma) when predominantly in lymph tissue rather than bone marrow
FEATURES
 Most common leukaemia in adults
 Typically, affects elderly (male-to-female-ratio is 2:1)
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CLINICAL PRESENTATION
 Often asymptomatic; patients present with constitutional symptoms , anaemia, or infection
 Examination: hepatosplenomegaly and lymphadenopathy
DIAGNOSIS
 Initial test: CBC with blood film (lymphocytosis , anaemia, granulocytopenia, and thrombocytopenia)
 Characteristic smudge cells on blood film (fragile leukaemia cells crushed in handling)
 Definitive test: bone marrow biopsy with flow cytometry/immunohistochemistry
 Additional:
 Cytogenetics – associated with several genetic defects
 Immunoglobulins – associated with hypogammaglobulinaemia (due to dysfunctional B lymphocytes)
TREATMENT
 Typically, treated with chemotherapy (only when symptomatic)
OUTCOMES
 Incurable (palliative) but long disease-free intervals may be achieved
Chronic myeloid leukaemia
PATHOPHYSIOLOGY
 Chronic myeloid leukaemia (CML) is a clonal proliferation of myeloid progenitor cells that leads to granulocytosis
 The BCR-ABL translocation must be present (typically, reflected by the Philadelphia chromosome t(9,22) )
FEATURES
 Typically, affects middle aged adults (40 to 60 years of age)
CLINICAL PRESENTATION
 Often asymptomatic; patients present with constitutional symptoms or anaemia (often detected by chance)
 Examination: hepatosplenomegaly (spleen may be massive – leading to LUQ pain and early satiety)
 Three clinical phases:
 Chronic – asymptomatic
 Accelerated – constitutional symptoms, pruritis, splenomegaly (reflective of basophilia and thrombocytopenia)
 Blast crisis – resembles acute leukaemia (poor prognosis)

Note: basophilia is uncommon in other medical conditions.

DIAGNOSIS
 Initial test: CBC with blood film (extreme granulocytosis (raised basophils ), anaemia, and variable platelets)
 Definitive test: bone marrow biopsy with flow cytometry/immunohistochemistry
 Additional:
 FISH/PCR (most accurate) – assess for Philadelphia chromosome
 Radiology – assess for spleen size
TREATMENT
 Typically, treated with chemotherapy (specifically imatinib – a tyrosine kinase inhibitor)
 Young patients are also candidates for allogenic stem cell transplants (if matched donor available)
OUTCOMES
 Variable prognosis (dependent on response to treatment)
Hairy cell leukaemia
Hairy cell leukaemia is a rare malignant disorder of mature well-differentiated B lymphocytes .
 Characterised by hairy cells on blood film (mononuclear cells with many cytoplasmic projections)
 Hair cells stain with tartrate-resistant acid phosphatase (TRAP)
 Treated with cladribine
LYMPHOMAS
Lymphoma is a malignant proliferation of lymphoid cells (primarily residing in lymphoid tissue, such as lymph nodes).
 Can be classified into nodal (involving lymph nodes) or extra-nodal (involving other tissue – e.g. spleen or gut)
Non-Hodgkin lymphoma
Non-Hodgkin lymphoma (NHL) represents a diverse group of mature B and T cell neoplasms .
 Most NHLs are B-cell origin (85%)
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FEATURES
 Typically, affects older adults and elderly (occasionally presents in children as aggressive, high-stage, disease)
 Associated with autoimmune diseases , immunodeficiency , and infections
CLINICAL PRESENTATION
 Dependent on underlying condition
 Associated with painless lymphadenopathy , constitutional symptoms (‘B’ symptoms) , immunodeficiency , masses on
examination
Types of Non-Hodgkin Lymphoma
TYPE EPIDEMIOLOGY CLINICAL NOTES
B-CELL NEOPLASMS (85%)
Follicular lymphoma Adults  Indolent
 Associated with t(8;14) translocation (bcl-2 activation)

Diffuse large B-cell lymphoma Elderly  Aggressive

 Most common NHL in adults
 High cure-rate with R-CHOP therapy

Burkitt lymphoma Children  Highly aggressive

 Associated with EBV
 Characteristic jaw-lymphadenopathy
 ‘Starry-sky’ histology

Mantle cell lymphoma Elderly men  Rarest form of NHL (CD5 positive)

T-CELL NEOPLASMS
Adult T-cell lymphoma Adults  Aggressive
 Associated with human T-lymphotropic virus

Mycosis fungoides Adults  T-cell lymphoma of the skin (cutaneous eczema-like lesions and pruritis are classical)
 Can progress to Sezary syndrome (T-cell leukaemia) with characteristic Sezary cells on blood film

DIAGNOSIS
 Initial test: CBC with blood film
 Definitive test: excision lymph node biopsy with flow cytometry/immunohistochemistry
 Additional:
 Cytogenetics – associated with several genetic defects
TREATMENT
 Typically, chemotherapy or radiotherapy
 Generally, for low-grade indolent NHL – treatment is palliative
 Generally, for high-grade aggressive NHL – treatment is curative
COMPLICATIONS
 Tumour lysis syndrome (with treatment of high-grade NHL or leukaemia) – rapid cell death leads to electrolyte abnormalities
 Classically, hyperkalaemia, hypocalcaemia, hyperphosphataemia, and hyperuricaemia
 Managed with aggressive IV hydration and dialysis
Hodgkin lymphoma
Hodgkin lymphoma is a malignant proliferation of lymphoid cells with characteristic Reed-Sternberg cells (germinal centre B-cells).
 Associated with EBV
FEATURES
 Bimodal distribution – peak at age 20 (nodular sclerosing type) and age 60 (lymphocyte-depleted type)
CLINICAL PRESENTATION
 Presents as painless lymphadenopathy (classically cervical; infradiaphragmatic involvement suggests disseminated disease)
 Can present as a mediastinal mass (anterior segment) on routine imaging (rarely, presents acutely as SVC syndrome)
 Associated with constitutional symptoms , pruritis, and hepatosplenomegaly
DIAGNOSIS
 Initial test: CBC with blood film (lymphocytosis)
 Definitive test: excision lymph node biopsy with flow cytometry/immunohistochemistry
 Reed-Sternberg cells – giant abnormal B cells with bilobar nuclei (classical ‘owls-eye’
appearance)
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 Additional:
 Cytogenetics – associated with several genetic defects
 CXR – assess for mediastinal mass
TREATMENT
 Dependent on stage, involves chemotherapy or radiotherapy
 Stage I – single lymph node region
 Stage II – multiple lymph node regions on same side of diaphragm
 Stage III – multiple lymph node regions on both sides of diaphragm
 Stage IV – spread beyond lymph nodes
OUTCOMES
 Good prognosis (dependent on stage) ; improved prognosis if lymphocyte-depleted type
Differentiating Non-Hodgkin versus Hodgkin Lymphoma
NON-HODGKIN LYMPHOMA HODGKIN LYMPHOMA
Many peripheral nodes involved, extranodal, non-contiguous spread Single group of localised nodes, rarely extranodal, contiguous spread

Mainly B cells Reed-Sternberg cells

Peak incidence in elderly Bimodal

HIV and autoimmune association EBV association

Common CD markers
CELL TYPE CD MARKERS
CD2, 3, 4, 5, 6, 7 T cell antigen (CD5 is sensitive for mantle cell lymphoma)

CD19, 20, 21, 22 B cell antigen (CD15 and CD30 are sensitive for Reed-Sternberg cells)

CD13, 33 Myeloid cell antigen

CD10 Common acute lymphoblastic leukaemia antigen (CALLA)

TdT Lymphoblast antigen

PLASMA CELL DISORDERS

Multiple myeloma
PATHOPHYSIOLOGY
 Multiple myeloma is a clonal proliferation of plasma cells producing a monoclonal immunoglobulin
 The immunoglobulin is typically ineffective IgA or IgG
 Associated with excessive free light chain (kappa or lambda) production
 MGUS (monoclonal gammopathy of unknown significant ) is the presence of monoclonal immunoglobulin without evidence of
plasma cell dyscrasia or other clinical symptoms (associated with a small risk each year of developing into myeloma)
 Managed with clinical monitoring
FEATURES
 Most common plasma cell malignancy
 Typically, affects elderly (males greater than females)
CLINICAL PRESENTATION
 CRAB:
 HyperCalcaemia
 Renal disease/failure
 Anaemia
 Bone lytic lesions, pain, and fractures (myeloma cells infiltrate bone marrow and activate osteoclasts creating lytic lesions)
 Patients are prone to infection (IgA and IgG produced is monoclonal and therefore ineffective)
 Rarely, is associated with adult Fanconi syndrome (proximal RTA) due to tubular damage
DIAGNOSIS
 Initial test: serum protein electrophoresis (monoclonal spikes in the gamma-band)
 Monoclonal gammaglobulinaemia is insufficient for diagnosis on its own (other disorders can cause this)
 Definitive test: bone marrow biopsy and flow cytometry
 Additional:
 CBC with blood film – demonstrates normocytic anaemia, thrombocytopenia, leukopenia (± RBC roleaux formation)
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 Urinalysis – demonstrates Bence-Jones protein (immunoglobulin light chain/paraprotein)

 Imaging – skeletal survey indicated in all patients (note: bone scan, which detects osteoblastic activity, may be negative)
 Protein levels – elevated protein-to-albumin ratio
 U/E with calcium – assess renal function and hypercalcaemia
TREATMENT
 Young patients – autologous bone marrow transplant
 Older patients – chemotherapy
 Supportive – bisphosphonates (to decrease bone loss and hypercalcaemia)
OUTCOMES
 Poor prognosis (non-curative)
COMPLICATIONS
 Hypercalcaemia
 Spinal cord compression
 Hyperviscosity syndrome
 Acute renal injury
Waldenstrom macroglobulinaemia (lymphoplasmacytic lymphoma)
PATHOPHYSIOLOGY
 Waldenstrom macroglobulinaemia is a clonal disorder of B cells that produce a monoclonal immunoglobulin
 The immunoglobulin is typically ineffective IgM (as opposed to the IgA or IgG of myeloma)
FEATURES
 Chronic, indolent, disease of the elderly
CLINICAL PRESENTATION
 Non-specific/constitutional symptoms
 Associated with hyperviscosity syndrome (85% of all cases), coagulation abnormality , cryoglobulinaemia (Reynaud
phenomena) , cold-agglutinin disease (AIHA) , and amyloidosis
 Hyperviscosity syndrome is characterised by hypervolaemia, CNS symptoms, and bleeding
 Examination: hepatosplenomegaly, lymphadenopathy, pallor, retinal lesions
DIAGNOSIS
 Initial test: serum protein electrophoresis (monoclonal spikes in the gamma-band)
 Monoclonal gammaglobulinaemia is insufficient for diagnosis on its own (other disorders can cause this)
 Definitive test: bone marrow biopsy (with Dutcher bodies ) and flow cytometry
 Not associated with hypercalcaemia
TREATMENT
 Typically, treated with chemotherapy
 Hyperviscosity syndrome – treat with plasmapheresis (for acute reduction in serum IgM)
Amyloidosis
Amyloidosis is characterised by extracellular deposition of amyloid protein fibrils .
 Due to a variety of causes (typically, affecting the elderly)
CLASSIFICATION

Types of amyloidosis
AMYLOID FEATURES

Primary A plasma cell dyscrasia with deposition of monoclonal light chain fragments
 Associated with multiple myeloma and Waldenstrom macroglobulinaemia

Secondary Deposition of acute-phase reactant (serum amyloid-A)

 Associated with chronic inflammatory diseases, infection, and neoplasm

Dialysis related Deposition of β2 macroglobulin which accumulates in patients on long-term dialysis

Heritable Deposition of abnormal gene products

Senile-systemic Deposition of amyloid protein in elderly patients (e.g. Alzheimer disease)

CLINICAL PRESENTATION
 Various clinical presentation – amyloid protein can affect the kidneys, heart, and liver
 In some disorders, the amyloid protein is specific to one organ (e.g. brain in Alzheimer disease)
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DIAGNOSIS
 Definitive test : tissue biopsy (with Congo-Red staining showing apple-green birefringence under polarised light)
TREATMENT
 Primary – experimental chemotherapy and autologous stem cell transplant
 Secondary – treat the underlying cause
MYELOPROLIFERATIVE DISORDERS
Myeloproliferative disorders are clonal myeloid stem cell abnormalities that lead to overproduction of one or more cell lines.
CLASSIFICATION
Classified based on the cell type which is proliferating:
 Red blood cells – polycythaemia vera
 White blood cells – chronic myeloid leukaemia (CML)
 Platelets – essential thrombocythaemia
 Fibroblasts – idiopathic myelofibrosis
Features of myeloproliferative disorders
POLYCYTHAEMIA VERA CML THROMBOCYTHAEMIA IDIOPATHIC MYELOFIBROSIS

Haematocrit (RBCs)   N 

WBCs   N Variable

Platelets    Variable

Marrow fibrosis ± ± ± +++

Splenomegaly ± +++ + +++

Hepatomegaly ± + - +++

Genetic association JAK2 (>90%) brc-abl (>90%) JAK2 (50%) JAK2 (50%)

Polycythaemia vera
PATHOPHYSIOLOGY
 JAK2 mutation results in clonal proliferation of myeloid stem cell leading to polycythaemia
 Also associated with granulocytosis and thrombocythaemia (although red cells are most affected)
 Polycythaemia may be the result of secondary causes (typically, chronic hypoxia or inappropriate EPO expression)
CLINICAL PRESENTATION
 May be asymptomatic
 Symptoms secondary to high red cell mass and hyperviscosity :
 Easy bleeding/bruising
 Blurred vision
 Erythromelalgia (pathognomonic – burning sensation in hands and feet and erythema of skin)
 Thrombotic complications
 Pruritis after a warm bath
 Gout (due to increased cell turnover)
 Characteristic physical findings – plethora of face and hepatosplenomegaly
DIAGNOSIS
 Initial test: CBC ( HCT and Hb; also,  platelets/WBCs)
 Definitive test: genetic screening for JAK2 mutation
 Additional:
 EPO –  (unless secondary polycythaemia)
TREATMENT
 Mild-to-moderate – venesection and aspirin (symptom relief and prevents thrombosis)
 Severe – hydroxyurea (reduces cell counts)
OUTCOMES
 Associated with reduced lifespan (complicated by thrombosis and haemorrhage)
Essential thrombocythaemia
PATHOPHYSIOLOGY
 JAK2 mutation (in 50% of cases) results in clonal proliferation of myeloid stem cell (megakaryocyte) leading to thrombocythaemia
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CLINICAL PRESENTATION
 Typically, asymptomatic
 Associated with vasomotor symptoms (headache, dizziness, erythromelalgia), bleeding, and thrombosis (arterial and venous)
DIAGNOSIS
 Initial test: CBC ( platelets)
 Definitive test: bone marrow biopsy (± genetic screening for JAK2 mutation)
TREATMENT
 Mild-to-moderate – aspirin (symptom relief and prevents thrombosis)
 Severe – hydroxyurea (reduces cell counts)
Idiopathic myelofibrosis
PATHOPHYSIOLOGY
 Excessive bone marrow fibrosis leading to marrow failure (due to dysplastic megakaryocytes secreting growth factors)
 Associated with JAK2 mutation (in 50% of cases)
CLINICAL PRESENTATION
 Characterised by marked constitutional symptoms, massive hepatosplenomegaly, and bone pain
DIAGNOSIS
 Initial test: CBC and blood film (anaemia; variable WBCs/platelets; leukoerythroblastic blood film with teardrop RBCs)
 Definitive test: bone marrow biopsy (± genetic screening for JAK2 mutation)
TREATMENT
 Symptomatic treatment dependent on cell counts
 Young patients – allogenic stem cell transplant (potentially curative)
PANCYTOPENIA AND BONE MARROW FAILURE

CLASSIFICATION
 Pancytopenia – the reduction in all major cell lines (RBCs, WBCs, platelets), due to:
 Decreased marrow production (aplastic anaemia, marrow infiltration, myelofibrosis, paroxysmal nocturnal haemoglobinuria,
myelodysplastic syndrome, megaloblastic anaemia, and iatrogenic causes)
 Increased peripheral destruction (hypersplenism)
 Agranulocytosis – the reduction in granulocytes (neutrophils, eosinophils, basophils)
 Associated with medications
 Aplastic anaemia – rare stem cell disorder leading to pancytopenia and hypoplastic marrow
 May be hereditary (Fanconi anaemia) or secondary (autoimmune, infection, toxins, radiations, or drugs)
 Fanconi anaemia – triad of café-au-lait spots, short stature, and thumb hypoplasia
CLINICAL PRESENTATION
 Presents with features of anaemia ( RBCs), infection ( WBCs), and mucosal bleeding ( platelets)
TREATMENT
 Treat the underlying cause
 RBCs – transfusion
 Platelets – transfusion
 Neutrophils – GCSF + barrier nursing + neutropenia protocol

Transfusion medicine
TRANSFUSION
Transfusion protocols
BLOOD PRODUCT INDICATION CLINICAL NOTES

Red blood cells  Anaemia (<if 70g/L for adults)  When blood is required:
 First-line: fully cross-matched blood
 Second-line: donor blood of same ABO/Rh status
 Third-line: O- blood (O+ if Rh not a concern)

Fresh frozen plasma  Replacement of coagulation factors (INR >1.5x normal), or  Not useful in liver disease (both coagulation
(or protein concentrates)  Replacement of single plasma protein deficiency (rare) factors and coagulation inhibitors decreased)

Platelet concentrate  Medical patients (if <10x109/L)

 Surgical patients (if <80x109/L or functional platelet defect)

Cryoprecipitate  Bleeding due to low fibrinogen (<1g/L)

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 Examples: severe haemodilution or DIC

 Post-natal bleeding (if <2g/L)

Red cell screening

 ‘Group and screen’ involves:
 Determination of blood group and Rh status
 Unexpected antibody screening (e.g. Duffy)
 A compatibility test (crossmatch) occurs if red cells are required for the patient (requires a valid group and screen):
 The test is determined by the antibody results (can be done electronically if no antibody results)
 If no antibodies (most people) – rapid supply
 If antibodies present (rare) – delay (minutes to weeks – dependent on type of antibodies present)
BLOOD TRANSFUSION REACTIONS
Features of immune-related blood transfusion reactions
HAEMOLYTIC REACTION FEBRILE NON-HAEMOLYTIC ALLERGIC NON-HAEMOLYTIC TRANSFUSION-RELATED ACUTE
REACTION REACTION LUNG INJURY

Pathophysiology ABO incompatibility leading Release of cytokines from Antibodies to proteins in Unknown
to complement activation blood product cells donor plasma

Symptoms/signs Immediately after transfusion: 0-6hrs after transfusion:  Urticaria 2-4hrs after transfusion:
 Fever, chills, hypotension,  Fever, rigors, flushing,  Insidious, acute, onset of
flank pain, dyspnoea, headache, hypotension pulmonary insufficiency and
haemoglobinuria pulmonary oedema
 AKI and DIC

Treatment  Stop transfusion  Stop transfusion (if severe)  Stop transfusion (if severe)  Supportive therapy
 Notify blood bank  Paracetamol  Antihistamines
 Aggressive IV fluids
 Maintain urine output

Features of non-immune blood transfusion reactions

CIRCULATORY OVERLOAD HYPERKALAEMIA CITRATE TOXICITY

Pathophysiology Fluid overload Potassium release from stored RBCs Citrate binds to calcium and causes
symptoms of hypocalcaemia

Symptoms/signs Mimics heart failure As for hyperkalaemia As for hypocalcaemia

Treatment  Supplemental oxygen  Treat as for hyperkalaemia  IV calcium gluconate

 Diuretics

TISSUE TRANSPLANTATION

CLASSIFICATION
 Autologous – transplantation from the patient to themselves
 Allogenic – transplantation from a genetically different patient
 Syngeneic – transplantation from a genetically identical patients (identical twins or saviour sibling)
Solid organ transplant rejection
 Graft-vs-host disease (GVDH) – complication specific to allogenic bone marrow transplantation
 Donor T cells attack host tissues (esp. skin, liver, and GI tract)
 Treated with high dose corticosteroids
Types of solid organ transplant rejection
HYPERACUTE ACUTE CHRONIC

Timing after Minutes Days to months Months to years

transplant

Pathophysiology Preformed antibodies T-cell mediated immunity Chronic immune reaction causing fibrosis

Diagnosis  Histology (thrombosis and infarction)  Laboratory evidence of tissue  Gradual loss of organ function
destruction (e.g. LDH, BUN, LFTs)
 Histology

Prevention  Check ABO compatibility  N/A  N/A

Treatment  Cytotoxic agents  Corticosteroids  No treatment

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 Cytotoxic agents

Basics of oncology
BASICS OF ONCOLOGY

DEFINITIONS
 Prognostic factor – influences the risk of recurrence or survival (e.g. TMN stage)
 Predictive factor – influences response to a specific therapy (e.g. hormone receptor status)
 Adjuvant therapy – therapy following surgery to eliminate distant micrometastatic disease
STAGING
Staging refers to the spread of cancer within the body.
 Typically, reported in the TNM staging format
 Tumour – size/invasion of local tumour
 Nodes – regional lymph node involvement
 Metastases – presence of metastases
 Other parameters:
 R – resection margins after operation
 V/L/P – venous/lymphatic/perineural invasion
 Qualifiers:
 C – stage determined from evidence acquired before treatment
 P – stage determined by histopathologic examination
 Y – stage determined after adjuvant treatment
GRADING
Grading refers to the degree of abnormality in the tumour cells and tissue histopathologically.
 Typically, reported from 1 to 4 (well differentiated to undifferentiated/anaplastic )
CANCER TREATMENTS

Radiotherapy
MECHANISM OF ACTION
 Radiotherapy uses various modalities (e.g. photons) to cause DNA damage in target tissue
 Tumours generally have less efficient repair processes than normal cells so are selectively targeted
 Effect is dependent on cell kinetics:
 Acute-reacting tissues have fast cell turnover – e.g. skin, mucosa, most tumours
 Late-reacting tissues have slow cell turnover – e.g. blood vessels, muscles, fat
 The dose is typically broken up into smaller doses (fractionation) to allow for repair in normal tissues
SIDE EFFECTS OF RADIOTHERAPY
 Early (may require analgesics and are worst in acute-reacting tissues) :
 Inflammation (reaction to cell damage and death)
 Cellular depletion and ulceration
 Capillary leakage and swelling
 Malaise and fatigue
 Late:
 Atrophy of tissue – loss of cell numbers
 Reduced arteriolar lumen and blood flow
 Fibrosis – muscles and subcutaneous tissue

Oncological complications
FEBRILE NEUTROPENIA
Febrile neutropenia is the most common life-threatening complication of cancer therapy.
 Defined as fever in the presence of neutropenia
 The usual signs and symptoms of infection may be diminished (because neutrophils are required for inflammatory response)
DIAGNOSIS
 Labs: CBC, U/E, LFTs
 Cultures: blood cultures (esp. lines or ports), urinalysis (C&S/R&M), sputum (C&S), nasopharyngeal swab (for respiratory viruses)
 Imaging: CXR (if respiratory symptoms) or CT (evaluate for abscesses or other occult infection)
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TREATMENT
Dependent on hospital protocol (for example):
 Prophylaxis: G-CSF (granulocyte colony stimulating factor) and GM-CSF (granulocyte-macrophage colony stimulating factor)
 Low risk: ciprofloxacin + augmentin
 High risk: tazocin ± metronidazole (if anaerobes) ± vancomycin (if MRSA) ± amphotericin B (if fungal)
 If fever persist after 72 hours despite antibiotic therapy – routinely start antifungal therapy
SPINAL CORD COMPRESSION
Spinal cord compression is a medical emergency as it can lead to irreversible spinal cord injury .
AETIOLOGY
 Tumour (esp. NSCLC, breast cancer, prostate cancer, RCC, thyroid cancer, lymphoma, and multiple myeloma)
 Vertebral fracture
 Abscess/granuloma (e.g. tuberculosis)
 Ruptured intervertebral disc
CLINICAL PRESENTATION
 Typically, presents with severe back and radicular pain with weakness/reduced sensation below lesion
 Associated with incontinence, urinary retention , Lhermitte’s sign (intermittent shooting electrical sensation)
 Examination: hyporeflexia (when acute) followed by hyperreflexia, loss of sphincter tone, sensory deficits, weakness
DIAGNOSIS
 Initial test: X-ray spine
 Definitive test: MRI
TREATMENT
 Typically, emergency surgery
 Malignant spinal cord compression:
 Emergency radiotherapy (mainstay of treatment)
 Emergency chemotherapy (less commonly)
 Dexamethasone (may reduce oedema around lesion)
OUTCOMES
 Once complete paralysis is present for more than 24 hours, the chances of recovery are greatly diminished
 Median survival of patients with metastatic spinal cord compression is about 12 weeks

Miscellaneous
ANGIOEDEMA
Angioedema is the rapid swelling (non-itching/non-pitting) of the dermis, subcutaneous tissue, mucosa and submucosal tissues.
 Classified as histamine-mediated (e.g. NSAIDs), bradykinin-mediated (e.g. hereditary or ACE inhibitor), or unknown cause
 Typically, associated with a family history
Hereditary angioedema (C1 esterase deficiency)
An autosomal dominant disorder with recurrent episodes of angioedema evoked by minimal trauma or infection
CLINICAL PRESENTATION
 Presents with recurrent angioedema (at the same site)
 Oropharyngeal cases can be life-threatening
 Associated with abdominal pain (intestinal mucosal swelling causes colicky pain)
DIAGNOSIS
 Lab: complement assessment
TREATMENT
 Acute: IV C1 esterase inhibitor or fresh frozen plasma
 Prophylaxis: attenuated androgens (danazol)
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Infectious Disease
Basic principles
BASIC BACTERIOLOGY
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Antimicrobials
ANTIBIOTICS

Cell wall inhibitors

β-lactams
MECHANISM
 β-lactam ring inhibits cell wall synthesis by binding to penicillin binding protein preventing cross-linking of peptidoglycan
CLASSIFICATION
 Penicillins
 Narrow spectrum – penicillin (streptococcus) or flucloxacillin (streptococcus/staphylococcus)
 Broad spectrum – amoxicillin (most gram-positive, including enterococcus)
 β-lactamase inhibitors (i.e. clavulanic acid or tazobactam) – augmentin or tazocin (broad coverage)
 Cephalosporin (tend to increase in gram-negative coverage with each generation)
 First generation – cefazolin (most gram-positive/negative, not including enterococcus)
 Second generation – cefuroxime (most gram-positive/negative, not including enterococcus)
 Third generation – ceftriaxone (broad coverage, not including enterococcus)
 Carbapenems – meropenem (broad coverage)
Glycopeptides
MECHANISM
 Inhibits cell wall synthesis
CLASSIFICATION
 Vancomycin (most gram-positive, including MRSA)
CLINICAL NOTES
 Red man syndrome – erythematous whole-body rash due to too rapid infusion of vancomycin

Protein synthesis inhibitors (50S ribosomal subunit)

MECHANISM
 Binds to 50S ribosomal subunit inhibiting protein synthesis
CLASSIFICATION
 Macrolides – erythromycin , clarithromycin , or azithromycin (most gram-positive and gram-negative, including atypicals)
 Lincosamides – clindamycin or chloramphenicol (most gram-positive and anaerobes)

Protein synthesis inhibitors (30S ribosomal subunit)

MECHANISM
 Binds to 30S ribosomal subunit inhibiting protein synthesis
CLASSIFICATION
 Aminoglycosides – gentamicin or tobramycin (most gram-negative, including pseudomonas)
 Tetracyclines – doxycycline or tetracycline (variable – includes gram-positive, atypicals, malaria, rickettsial disease)

Miscellaneous
CLASSIFICATION
 Fluoroquinolones (inhibit DNA gyrase) – ciprofloxacin (most gram-negative, including pseudomonas)
 Metronidazole (toxic to microbial DNA) (anaerobes and protozoa)
 Causes disulfiram-type reaction with alcohol consumption
 Anti-metabolites (inhibit folic acid pathway) – trimethoprim-sulfamethoxazole (most gram-positive and gram-negative)
 Anti-metabolites (inhibit protein synthesis) – nitrofurantoin (UTI bacteria)
Antibiotics for selected bacteria
PSEUDOMONAS ENTEROCOCCUS ANAEROBES
 Fluoroquinolones (ciprofloxacin)  Amoxicillin  Metronidazole
 Aminoglycosides (gentamicin/tobramycin)  Clindamycin
 Anti-pseudomonal penicillin (tazocin)  Broad-spectrum β-lactams
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ANTIFUNGALS

CLASSIFICATION
 Polyenes
 Amphotericin B (severe fungal infections)
 Nystatin (candidiasis)
 Imidazoles
 Miconazole (vulvovaginal candidiasis)
 Ketoconazole (fungal skin infections)
 Triazoles
 Fluconazole (severe candidiasis or cryptococcal meningitis)
 Allylamines
 Terbinafine (fungal skin/nail infections)
ANTIVIRALS

CLASSIFICATION
 Acyclovir/valacyclovir (HSV)
 Ganciclovir (CMV)
 Interferon (Hep. B/C)
 Ribavirin (Hep. B/C and RSV)
ANTIPARASITICS

CLASSIFICATION
 Chloroquine (malaria)
 Metronidazole (protozoa)

CNS infections
MENINGITIS

CLASSIFICATION
 Bacterial – an acute emergency
 Viral – more common and less severe
 Other organisms
CLINICAL PRESENTATION
 Classic triad of fever, headache, and neck stiffness
 Associated with signs of meningism (nausea, vomiting, photophobia, and positive Kernig/Brudzinski sign)
 Associated with altered mental status and seizures
 Associated with meningococcal sepsis (presents as non-blanching petechial rash )

Note: meningism is not classically seen until two years of age (childhood meningitis presents as severe non-specific illness ).

DIAGNOSIS
 Labs – CBC, U&E (for SIADH), blood cultures (gram stain/C&S)
 Lumbar puncture (gram stain/C&S)
 Brain CT/MRI (if neurological findings – but don’t delay antibiotics)
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Note: lumbar puncture should not be performed if clinical suspicion of raised intracranial pressure (risk of herniation).
CSF profiles in meningitis/encephalitis
TYPE GLUCOSE PROTEIN WBC OPENING PRESSURE APPEARANCE
Normal Normal Normal Normal Normal Clear

Bacterial <1/2 plasma Increased Increased (mainly PMNs) Increased Cloudy/purulent

Viral (aseptic) Variable Normal Increased (mainly mononuclear) Variable Often clear

TB/Fungal >1/2 plasma Increased Increased (mainly mononuclear) Variable Fibrin strands

TREATMENT
 Empiric IV antibiotics
 Dexamethasone (associated with decreased mortality, hearing loss, and neurological complications)
 Additional:
 Acyclovir (for viral meningitis)
 Prophylactic antibiotics (for close contacts)
Treatment guide for meningitis
AGE COMMON ORGANISMS TREATMENT
Newborns  GBS, E.coli, Listeria IV cefotaxime + amoxicillin

Infants  Pneumococci, Meningococci, H. influenzae type B (if unimmunised) IV cefotaxime + vancomycin

Children/adults  Pneumococci, Meningococci IV ceftriaxone + vancomycin

Elderly/alcoholics  Listeria IV ceftriaxone + vancomycin + amoxicillin

COMPLICATIONS
 Sensorineural hearing loss
 Focal neurological deficit
 Cerebral oedema
 Hydrocephalus
 SIADH
Rapid identification
 Streptococcus pneumoniae – gram-positive diplococci
 Neisseria meningitidis – gram-negative diplococci
 Listeria monocytogenes – gram-positive rods
 The main encapsulated bacteria include all of the above (in addition to Neisseria gonorrhoeae)
ENCEPHALITIS

AETIOLOGY
 Typically, HSV (or arboviruses )
CLINICAL PRESENTATION
 Presents similar to meningitis with or without meningism
DIAGNOSIS
 Labs – CBC, U&E, blood cultures (gram stain/C&S)
 Viral PCR
 Lumbar puncture (gram stain/C&S)
 Brain CT/MRI (associated with medial temporal lobe necrosis in HSV encephalitis)
TREATMENT
 Supportive care
 HSV encephalitis – IV acyclovir

Respiratory infections
SPECIFIC PNEUMONIAS
Klebsiella pneumonia
Klebsiella pneumonia is associated with Aspiration pneumonia , Alcoholics/diabetics , Abscess (3As) (and red currant jelly sputum ).
 Treated with broad spectrum antibiotics (or guided by susceptibility )
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Pneumocystis jirovecii pneumonia

Pneumocystis jirovecii pneumonia is an AIDS-defining illness that presents with non-productive cough (treated with co-trimoxazole).
Legionellosis
AETIOLOGY
 Legionella pneumophiliae – associated with contaminated water source (including air conditioning )
 Legionella longbeacheae – associated with compost
CLASSIFICATION
 Non-pneumonic disease ( Pontiac fever) – self-limiting influenza like-illness
 Pneumonia (Legionnaires’ disease ) – pneumonia associated with hyponatraemia (and failure to respond to typical antibiotics)
DIAGNOSIS
 Sputum culture
 Serology
 Legionella urinary antigen (only detects L. pneumophilia)
TREATMENT
 Pneumonia (Legionnaires’ disease ) – macrolides

Systemic infections
SEPSIS

DEFINITIONS
 Sepsis – presence of SIRS (systemic inflammatory response syndrome) with documented infection
 Severe sepsis – presence of sepsis with end-organ dysfunction
 Septic shock – presence of sepsis with hypotension (and end-organ dysfunction )
 SIRS (≥2 of TTT-W) – Temperature (/), Tachypnoea, Tachycardia , WBC (/)
CLASSIFICATION
 Typically, classified by causative organism:
 Gram-positive – secondary to fluid loss caused by exotoxins
 Gram-negative – secondary to vasodilation caused by endotoxins
 Several others
CLINICAL PRESENTATION
 Presents with septic picture
 Associated with non-blanching petechial rash (occurs if progressed to DIC)
DIAGNOSIS
 Clinical diagnosis
 Labs – CBC, U&E, LFTs, coagulation, lactate
 Blood cultures
 Imaging (to establish site of infection)
TREATMENT
 Treat underlying cause
 Aggressive treatment:
 IV fluids
 Vasopressors (noradrenaline)
 Empiric antibiotics (tazocin)
 Corticosteroids (for relative adrenal insufficiency )
Blood culture contamination
Several organisms typically represent true bacteraemia or conversely represent culture contamination:
 Typically, bacteraemia – S. aureus, S. pneumonia, E. coli, P. aeruginosa, C. albicans
 Typically, contamination (can be ruled out by repeat culture):
 Coagulase-negative staphylococci (CONS; e.g. S. epidermidis) – unless prosthetic medical devices
 Corynebacterium spp.
 Propionibacterium acnes
 Clostridium perfringens
 Bacillus spp.
TOXIC SHOCK SYNDROME
Toxic shock syndrome has many causes but is classically associated with staphylococcal infection following retained tampon .
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 Caused by reaction to toxin (not bacterium – which is rarely found on blood culture)
 Typically, presents as septic shock with erythematous desquamating skin rash (esp. palms and soles)
 Treated similar to necrotising fasciitis (β-lactam + clindamycin )
TUBERCULOSIS

PATHOPHYSIOLOGY
 Inhalation and deposition of Mycobacterium tuberculosis in the lung can lead to one of the following outcomes:
 Immediate clearance of the pathogen
 Latent TB – asymptomatic infection contained by host immune defences (represents 95% of infected people)
 Primary TB – symptomatic/active disease (represents 5% of infected people)
 Secondary TB – symptomatic reactivation of previously dormant TB (most common cause of symptoms)
FEATURES
 Risk factors for active disease – immunosuppression (e.g. HIV/AIDS), silicosis, substance abuse, lung disease, diabetes, elderly
 Risk factors for exposure – travel to developing nations, crowded living conditions, low SES, personal or occupational contact
CLINICAL PRESENTATION
 Primary infection – usually asymptomatic (although progressive primary disease can occur in children or immunocompromised)
 Secondary infection – constitutional symptoms and site-dependent symptoms
 Site-dependent symptoms:
 Pulmonary TB – chronic productive cough ± haemoptysis
 Miliary TB – widely disseminated spread
 Extrapulmonary TB (can spread to any organ)
 Pott’s disease – osteomyelitis of vertebra
 Scrofula – cervical tuberculosis lymphadenitis
 Adrenal TB – can cause primary adrenal insufficiency
 Serosal involvement – pleural, pericardial, and peritoneal effusion
DIAGNOSIS
 Screening for latent TB:
 PPD/Mantoux test – intradermal injection of non-tuberculous protein leading to type-IV hypersensitivity reaction (induration)
 Disadvantages – false positives (BCG vaccine and non-tuberculous mycobacteria) and cannot diagnose active disease
 IFN-γ – measures response of pre-sensitised T-cells to TB antigen (more specific than PPD/Mantoux test)
 Disadvantages – cannot diagnose active disease
 Screening for active TB:
 Sputum culture – acid-fast bacilli culture
 Bronchoalveolar lavage
 CXR
 CXR findings of TB:
 Primary TB – affects middle lobe (tends to be minor)
 Secondary TB – affects upper lobe (tends to cause cavitation)
 Pleural effusion
 Hilar lymphadenopathy
 Ghon focus (represent localisation of initial infection – i.e. primary tuberculosis) – subpleural caseating granuloma
 Ghon complex – Ghon focus + ipsilateral hilar lymphadenopathy
 Ranke complex (seen in ‘healed’ primary tuberculosis) – calcified Ghon focus + ipsilateral hilar lymphadenopathy
 Miliary TB – widespread ‘miliary deposits’
TREATMENT
 Primary prevention:
 Airborne isolation (for active pulmonary disease) (note: young children have low infectivity)
 BCG vaccination (decreases meningeal/miliary TB in infants but does not prevent infection)
 Current recommendation is to vaccinate at birth if parents from a high-risk group or country
 Secondary prevention:
 Isoniazid + pyroxidine (vitamin B6 – helps prevent INH-associated neuropathy) for 9 months
 Active pulmonary disease (RIPE):
 Rifampin + Isoniazid + Pyrazinamide + Ethambutol (+ pyridoxine ) for 2 months (DOT recommended), followed by
 Rifampin + Isoniazid (+ pyridoxine) for 4 months
 Additional:
 Public health measures

Note: drug-resistant TB is classified as MDR (INH + rifampin) or XDR (INH + rifampin + any fluoroquinolone + injectable agents).
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HIV and AIDS

HIV

PATHOPHYSIOLOGY
 HIV (human immunodeficiency virus) is a retrovirus that targets and destroys CD4+ T-cells
 Leads to progressive immune system dysfunction which predisposes patients to opportunistic infection and malignancy
FEATURES
 Transmission probability per exposure (ascending order):
 Male genital tract (1 in 500)
 Female genital tract (1 in 250)
 Sharp/needlestick injury (1 in 100)
 Rectum (1 in 100)
 Placenta (1 in 20)
 Breast feeding (1 in 10)
 Contaminated blood products (>95%)
NATURAL HISTORY
 Acute infection – flu-like illness
 Asymptomatic (latent) phase – slow decrease in CD4+ T-cell count (normal is 500-1000)
 AIDS (acquired immunodeficiency syndrome) – defined as HIV-positive and CD4+ T-cell count <200 or AIDS-defining
illness
CLINICAL PRESENTATION
 CD4+ T cell count <500
 Often asymptomatic
 Constitutional symptoms
 Mucocutaneous dermatological lesions
 Recurrent bacterial infection
 Kaposi sarcoma
 Tuberculosis
 Lymphoma
 CD4+ T cell count <200
 Pneumocystis jirovecii pneumonia (treated with co-trimoxazole )
 Disseminated fungal infections
 Toxoplasmosis (cotrimoxazole prophylaxis )
 CD4+ T cell count <50
 CMV infection (retinitis or encephalitis) (treated with ganciclovir)
 Mycobacterium avium complex (weekly azithromycin prophylaxis )
 Primary central nervous system lymphoma
DIAGNOSIS
 ELISA (initial test)
 Western blot (definitive test)
 Rapid HIV test (screening test)
 Labs – routine CD4+ T-cell count (degree of immunosuppression) and HIV-RNA levels (predicts rate of disease progression)
TREATMENT
 HAART therapy (multiple medications initiated at diagnosis) (goal – keep viral load below limit of detection)
 Prevention of infection:
 Safe sexual practices
 Pregnancy – treat with HAART during 2 nd /3 rd trimester followed by treatment of infant for 6 weeks (and avoid
breastfeeding)
 Pre-exposure prophylaxis – for high-risk individuals
 Post-exposure prophylaxis – after occupational and non-occupational exposure
 Screening of blood and organ donation
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Opportunistic infections
INVASIVE CANDIDIASIS

AETIOLOGY
 Yeast with pseudohyphae
 Risk factors – immunosuppression and severe illness
CLINICAL PRESENTATION
 Invasive candidiasis – atypical mucocutaneous symptoms (e.g. oesophagitis) in addition to systemic symptoms
TREATMENT
 Oral/IV fluconazole
CRYPTOCOCCUS

AETIOLOGY
 Encapsulated yeast
 Risk factors – immunosuppression and exposure to pigeon droppings
CLINICAL PRESENTATION
 Pulmonary (immunocompetent patients) – asymptomatic or self-limited pneumonitis
 Disseminated (HIV patients) – meningitis (absent meningeal signs) and skin lesions (resembles Molluscum contagiosum)
DIAGNOSIS
 Serum cryptococcal antigen
 Lumbar puncture – India-ink stain and cryptococcal antigen test
TREATMENT
 IV amphotericin B
ASPERGILLUS

AETIOLOGY
 Fungus with branching septate hyphae (ubiquitous in the air and environment)
CLINICAL PRESENTATION
 Aspergillosis – typically, life-threatening cavitating pneumonia (also, may involve brain or skin)
 Aspergilloma – fungus ball that forms in pre-existing lung cavity (asymptomatic to massive haemoptysis )
TREATMENT
 IV amphotericin B
 Surgical resection (for aspergilloma)
HISTOPLASMOSIS

AETIOLOGY
 Fungus
 Risk factors – immunosuppression and exposure to bird/bat droppings (esp spelunking)
CLINICAL PRESENTATION
 Variable (asymptomatic to fulminant pulmonary and extrapulmonary symptoms)
DIAGNOSIS
 Urine/serum polysaccharide antigen test
 Fungal culture
TREATMENT
 IV amphotericin B
CYTOMEGALOVIRUS

FEATURES
 Most adults have been infected with CMV (typically, asymptomatic )
 Symptomatic reactivation occurs in immunocompromised patients
CLINICAL PRESENTATION
 Systemic – resembles EBV mononucleosis
 Specific manifestations:
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 CMV retinitis – associated with retinal detachment (‘pizza pie’ appearance)

 CMV cholangiopathy
 CMV pneumonitis
 CMV CNS involvement – polyradiculopathy, transverse myelitis, subacute encephalitis
DIAGNOSIS
 CMV PCR
 CMV serology
TREATMENT
 Treat underlying cause of immunosuppression
 Ganciclovir
MYCOBACTERIUM AVIUM COMPLEX

AETIOLOGY
 Acid-fast bacilli (ubiquitous in the air and environment)
CLINICAL PRESENTATION
 Lady Windermere syndrome – primary lung infection in healthy non-smokers
 Secondary pulmonary form – secondary lung infection in patients with pre-existing lung disease
 Disseminated infection – in AIDS patients (associated with weight loss and other constitutional symptoms)
DIAGNOSIS
 Biopsy – acid-fast bacilli
 Labs –  ALP/LDH
TREATMENT
 Macrolides

Parasitic infections
TOXOPLASMA GONDII

AETIOLOGY
 Toxoplasma gondii – protozoan parasite
 Risk factors – exposure to cat faeces
CLINICAL PRESENTATION
 Primary infection – asymptomatic
 Reactivation (immunosuppressed patients) – disseminated infection (associated with encephalitis )
DIAGNOSIS
 Toxoplasma PCR
 Toxoplasma serology
 CT/MRI (if CNS involvement) – multiple ring-enhancing lesions
TREATMENT
 Pyrimethamine + sulfadiazine
ROUNDWORMS

CLASSIFICATION

Common parasitic roundworm infections

PATHOGEN SOURCE CLINICAL FEATURES TREATMENT

Pinworm Faecal-oral (and oral  Nocturnal perianal itching (pruritis ani)  Hygiene (daily bath, clean environment, wash hands)
(Enterobius self-inoculation)  Abdominal pain and nausea/vomiting (if severe)  Albendazole (all family members should be treated)
vermicularis)  Sticky tape test – eggs adhere to tape applied at
Worldwide night to perianal skin

Threadworm Transmission via  Asymptomatic or pruritic dermatitis  Ivermectin

(Strongyloides unbroken skin  Transient pulmonary symptoms during
stercoralis) (walking barefoot) pulmonary migration of larvae (eosinophilic
pneumonitis – Löffler’s syndrome)
 Abdominal pain, diarrhoea, pruritis ani
Tropical/temperate
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Sexually transmitted infections

GENERAL GUIDELINES

SCREENING GUIDELINES
 Males:
 First-pass urine – chlamydia and gonorrhoea NAAT
 Urethral swab (if gonorrhoea positive) – culture and antibiotic sensitivities
 Optional tests – HIV, Hep. B/C, syphilis
 Females:
 High-vaginal swab – candida, bacterial vaginosis, trichomoniasis
 Vulvovaginal swab (or first-pass urine) – chlamydia, gonorrhoea, and trichomoniasis NAAT
 Endocervical swab (if gonorrhoea positive) – culture and antibiotic sensitivities
 Optional tests – HIV, Hep. B/C, syphilis
TREATMENT GUIDELINES
 Sexual activity – abstain from sexual activity for 7 days (including until all sexual partners are treated)
 Sexual contacts – all contacts within the last 3 months should be recommended treatment (without waiting for test results)
 Post-treatment testing – test of cure can be obtained in 6 weeks (if high risk – pregnant or anal infection)
 Latent period – testing typically positive after 2 weeks post-infection
CHLAMYDIA AND GONORRHOEAE

CLASSIFICATION
 Chlamydia trachomatis is an obligate gram-negative intracellular bacterium
 Neisseria gonorrhoeae is a free-living gram-negative diplococcus bacterium
 Co-infection with either bacterium is common
CLINICAL PRESENTATION
 Variable (see below)
 Males – urethral discharge, epididymo-orchitis, sterile pyuria
 Females – vaginal discharge, vaginal bleeding, dysuria, pelvic pain, dyspareunia
COMPLICATIONS
 Males – urethral strictures, epididymitis, infertility
 Females – pelvic inflammatory disease, ectopic pregnancy, infertility
Chlamydia versus gonorrhoeae
CHLAMYDIA TRACHOMATIS NEISSERIA GONORRHOEAE
Males
 Urethritis X X

Females
 Urethritis X X
 Vaginitis X Pre-puberty
 Cervicitis X Post-puberty

Discharge Muco-purulent Purulent

Asymptomatic
 Males <50% <5%
 Females <75% <50%

Other infection sites Eye Pharynx, rectum, disseminated (skin/eye)

Neonatal infection Ophthalmia neonatorum (self-limiting) and pneumonia Ophthalmia neonatorum (severe)

Associated arthritis Reactive Reactive or Septic (purulent)

Treatment Azithromycin (single high dose oral) – if no Sx Ceftriaxone (single high dose IM) +
Doxycycline (7 days) – if any Sx  (contraindicated in pregnancy) Azithromycin (single high dose oral)
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GENITAL HERPES

FEATURES
 Up to one-third people have genital herpes (but only 20% experience symptoms )
 It is a life-long recurring illness and individuals can be infectious even without symptoms
PATHOPHYSIOLOGY
 Caused by HSV-2 (85%) or HSV-1 (~15%)
CLINICAL PRESENTATION
 Characterised by clustered vesicles on erythematous base ( herpetiform rash )
 Onset is proceeded by prodromal pain, fever, malaise, and/or lymphadenopathy
 Associated with ulceration
 Associated with urinary symptoms
 Primary episodes are generally longer and more severe than recurrences
DIAGNOSIS
 See Dermatology.
TREATMENT
 See Dermatology.
 Patient education (refer to www.herpes.org.nz )
 Consistent condom use reduces, but does not eliminate, the risk of transmission
 Sexual contact should be avoided when lesions are present (to prevent delay in healing)
HPV INFECTION

PATHOPHYSIOLOGY
 HPV infection is typically asymptomatic, however
 Anogenital warts – caused by non-oncogenic HPV 6/11
 Anogenital/oropharyngeal cancer – caused by oncogenic HPV 16/18
DIAGNOSIS
 Testing is unavailable
PREVENTION
 Gardasil-9 (9-valent vaccine ) – funded for males and females (aged 9 to 26 years)
 Most effective before onset of sexual activity (but may still prevent acquisition of additional serotypes)
Anogenital warts
 Presentation – painless raised ‘cauliflower’ warts (condylomata acuminata)
 Treatment (cosmetic) – cryotherapy or imiquimod
VULVOVAGINAL INFECTIONS
Overgrowth of the vaginal microbiome
Overgrowth of the vaginal microbiome causes mostly low-grade infection (e.g. itching or watery discharge).
Vaginal thrush (candida albicans)
 Presentation:
 Female – vulvovaginitis and thick white ‘curd-like’ vaginal discharge
 Male – balanitis (penile pruritis and whitish rash )
 Treatment:
 Topic antifungal (miconazole or nystatin)
 Oral antifungal (fluconazole or nystatin)
Trichomonas vaginalis
 Presentation:
 Female – vulvovaginitis and offensive purulent frothy vaginal discharge
 Male – persistent urethritis
 Treatment:
 Metronidazole (single high dose oral)
Bacterial vaginosis
Bacterial vaginosis is caused by mixed anaerobic bacteria (particularly Gardnerella vaginalis).
 Presentation:
 Fishy smelling white/grey adherent vaginal discharge without vulvovaginitis
 Common in post-menopausal women with atrophic vaginitis (lack of oestrogen depletes vaginal glycogen raising pH)
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 Treatment:
 Single episode – oral metronidazole
 Recurrent – intravaginal metronidazole
 Post-menopausal – local vaginal oestrogen therapy (topical/suppository/ring )
SYPHILIS
Syphilis is caused by Treponema pallidum ss. pallidum (a non-culturable spirochaete).
CLINICAL PRESENTATION
 First stage – painless chancre at inoculation site
 Second stage (weeks after infection) – non-specific symptoms with non-pruritic maculopapular rash including soles and palms
 Associated with condylomata lata (highly infectious wart-like lesions)
 Tertiary syphilis (years after infection) – destructive gummas , cardiovascular findings (aortic aneurysms), and neurosyphilis

Note: syphilis can present as almost any disease (the ‘great imitator ’)
DIAGNOSIS
 VDRL (serology) – initial
 Causes of false positive VDRL – Viruses (CMV/HSV/HIV/Hep.), Drugs, Rheumatic fever , SLE
 Confirmatory tests – definitive
TREATMENT
 Benzathine penicillin G (single IM injection )

Traveller’s fever
INTERNATIONAL DISEASES
Fever in the returned traveller
CLINICAL PRESENTATION DIAGNOSIS TREATMENT

Malaria Caused by plasmodium falciparum  Blood smear (thick and thin)  Chloroquine
(carried by female Anopheles mosquitos)  Doxycycline (prophylaxis)
 Flu-like illness with severe nausea/vomiting

Dengue Caused by dengue virus  Serology  Symptomatic

(carried by female Aedes mosquitos)
 Flu-like illness with severe myalgia/arthralgia
 Associated with sudden onset retro-orbital pain/headache

Typhoid Caused by salmonella para-/typhi  Stool/urine/blood sample  Quinolones

 Sustained high fever with abdominal symptoms

Typhus Caused by rickettsia bacteria  Serology  Doxycycline

(carried by ticks)  Presence of tick bites
 Flu-like illness
 Scab at site of tick bite

Zoonotic disease
LEPTOSPIROSIS

FEATURES
 Zoonotic disease (mammals) caused by Leptospira (spirochaete bacteria)
 Most common occupational infectious disease in New Zealand (seen in meat-processors or farmers)
CLINICAL PRESENTATION
 Typically, self-limiting illness:
 High fever
 Severe myalgia
 Conjunctival suffusion (bilateral oedema and redness)
 Photophobia
 Severe in 10% of cases (Weil’s disease ) – characterised by multi-organ failure
DIAGNOSIS
 Clinical diagnosis
 Serology (to retrospectively confirm the diagnosis for notification purposes)
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TREATMENT
 Uncomplicated – doxycycline
 Complicated – IV benzylpenicillin (admit to ICU)
 Notifiable
BRUCELLOSIS

FEATURES
 Zoonotic disease caused by Brucella species (gram-negative coccobacilli bacteria)
 Only affects sheep (Brucella ovis) in New Zealand (seen in sheep farmers or vets)
CLINICAL PRESENTATION
 Triad of undulant fevers , sweating (characteristic foul mouldy smell), and migratory arthralgia and myalgia
DIAGNOSIS
 Serology
TREATMENT
 Uncomplicated – doxycycline
COMPLICATIONS
 Osteomyelitis
ORF

FEATURES
 Zoonotic disease caused by parapox virus
 Affects sheep and goats (seen in sheep/goat farmers )
CLINICAL PRESENTATION
 Characteristic purulent-appearing papule (self-limiting)

Miscellaneous
GAS
Group A, β-haemolytic, streptococci (GAS) ( streptococcus pyogenes), is responsible for several conditions:
 Cellulitis, erysipelas, and necrotising fasciitis
 Scarlet fever
 Streptococcal throat (pharyngitis)
 Rheumatic fever
 Post-infectious glomerulonephritis
Scarlet fever
Scarlet fever is a delayed-type hypersensitive reaction to pyrogenic exotoxin produced by GAS.
CLINICAL PRESENTATION AND DIAGNOSIS
 Acute onset of fever, sore throat, and strawberry tongue
 Several days after pharyngitis, diffuse non-pruritic, non-painful, ‘sandpaper rash’ with perioral sparing
 Rash fades after several days and may be followed by desquamation
 Evidence of a previous streptococcal infection – GAS pharyngitis culture, anti-streptolysin O titre, clinical history

Note: the differential for strawberry tongue is scarlet fever and Kawasaki disease.
TREATMENT
 PO penicillin V for 10 days (or erythromycin if allergic)
 Supportive (paracetamol and encourage fluids)
GLANDULAR FEVER
Glandular fever is a systemic viral infection caused by Epstein-Barr virus (rarely, CMV).
FEATURES
 Typically, occurs in adolescents
 Majority of children will acquire a primary EBV infection but less than 10% will have a clinical infection
 Transmission is mainly through infected saliva (‘kissing disease’ ) and sexual activity (less commonly)
CLINICAL PRESENTATION
 Classic triad – fever, generalised non-tender lymphadenopathy (especially, posterior cervical), pharyngitis/tonsillitis
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 Associated with severe fatigue, hepatosplenomegaly , jaundice, and maculopapular rash (after inappropriate β-lactam antibiotics)
 Associated with any ‘-itis’ condition (arthritis, hepatitis, nephritis, myocarditis, meningitis, encephalitis, etc.)
DIAGNOSIS
 Labs – CBC (lymphocytosis with atypical lymphocytes ± thrombocytopenia)
 Diagnostic tests:
 Initial – Monospot (heterophil antibody test)
 Definitive – EBV serology
 Additional:
 Throat culture – to rule out streptococcal pharyngitis

Note: in EBV infection, lymphocytosis is due to B-cell proliferation, but the atypical lymphocytes are T-cells.
TREATMENT
 Supportive – adequate rest, hydration, and analgesics
 Airway compromise (tonsillar or nodal enlargement) – steroids
 Avoid antibiotics
 Avoid contact sports for at least 4 weeks to avoid splenic rupture
OUTCOMES
 Acute symptoms resolve in a few weeks, although fatigue may last for months
COMPLICATIONS
 Bacterial suprainfection – many patients develop a secondary streptococcal pharyngitis
 Upper airway obstruction – common (but variable severity)
 CNS infection – rare (meningoencephalitis or Guillain-Barre syndrome)
 Splenic rupture – rare (more common in men; presents with peritonitis and haemodynamic compromise)
 Fulminant hepatic necrosis – rare (more common in men)
 Autoimmune haemolytic anaemia – rare
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Rheumatology
Basic principles
INFLAMMATORY VERSUS DEGENERATIVE ARTHRITIS
Inflammatory versus degenerative arthritis
INFLAMMATORY DEGENERATIVE

 Pain at rest / relieved by motion  Pain with motion / relieved by rest

 Significant morning stiffness (>30m)  Non-significant morning stiffness (<30m)
 Warm, swelling, erythema (inflammatory signs)  Joint instability, buckling, locking (degenerative signs)
 Malalignment/deformity  Bony enlargement, malalignment/deformity
 Night-time awakening  Crepitus on passive ROM
 Extra-articular manifestations  Evening pain
 May affect young people  Predominantly affects the elderly

Synovial fluid analysis

SYNOVIAL FLUID ANALYSIS
Synovial fluid analysis
NORMAL NON-INFLAMMATORY INFLAMMATORY SEPTIC

Colour Clear Yellow Yellow Yellow/green

Viscosity High High Low Variable

WBC Minimal Moderate High Very high

PMN (%) Low (<25%) Low (<25%) Moderate (>25%) High (>75%)

Glucose Equal to serum Equal to serum Greater than serum Less than serum

Degenerative arthritis
OSTEOARTHRITIS
Osteoarthritis is a chronic non-inflammatory arthritis of the synovial joints (articular cartilage and surrounding joint structures).
FEATURES
 Most common arthropathy (accounts for ~75% of all arthritis)
 Prevalence increases with age (80% by age 80)
CLASSIFICATION
 Primary (idiopathic)
 Secondary (e.g. family history, mechanical damage due to obesity, post-traumatic, etc.)
CLINICAL PRESENTATION
 Localised to affected joints (not a systemic disease)
 Symptoms and signs – see Inflammatory versus Degenerative Arthritis
 Joint locking is due to ‘joint mice’ (bone or cartilage fragments)
 Pattern of joint involvement:
 Typically, asymmetric weight-bearing joints
 Hands – DIP (Heberden’s nodes), PIP (Bouchard’s nodes), CMC (thumb squaring )
 Also, hip, knee, lumbar spine, and foot
DIAGNOSIS
 Labs – normal
 Joint aspirate – non-inflammatory
 Radiology – LOSS (Loss of joint space, Osteophytes, Subchondral sclerosis, Subchondral cysts )
TREATMENT
 No curative treatment
 Non-pharmacological – weight loss, physiotherapy , and occupational therapy
 Pharmacological – paracetamol ± topical capsaicin  NSAIDs ± intra-articular steroids  codeine or tramadol
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 Operative – joint replacement

Seropositive rheumatic disease

SEROPOSITIVE RHEUMATIC DISEASE
Seropositive rheumatic diseases are characterised by the presence of a serologic marker.
Common markers and their disease associations
MARKER DISEASE MARKER DISEASE MARKER DISEASE

ANA SLE (sensitive) Anti-CCP RA Anti-centromere CREST syndrome

Anti-dsDNA SLE (specific) RF RA Anti-mitochondrial PBC

Anti-histone SLE (drug induced) Anti-Scl-70 Systemic sclerosis Anti-smooth muscle Autoimmune hepatitis

Anti-TSHR Grave’s disease Anti-topoisomerase Systemic sclerosis c-ANCA Vasculitis (GPA)

Anti-Jo-1 Poly/dermatomyositis U1RNP Mixed CT disease p-ANCA Vasculitis (MPA)

Connective tissue disorders

RHEUMATOID ARTHRITIS
Rheumatoid arthritis is a systemic autoimmune disorder characterised by chronic, destructive, inflammatory arthritis.
 Results in synovial hypertrophy , pannus formation , and erosion of cartilage, bone, and tendon (associated with HLA-DR4)
FEATURES
 Typically, age of onset is 20 to 40 years old (female-to-male ratio is 3:1)
 Most common inflammatory arthritis (1% prevalence)
CLINICAL PRESENTATION
 Systemic disease – extra-articular symptoms are common, and may include:
 Rheumatoid nodules (extensor surfaces)
 Lung issues (pleural effusion; rarely, rheumatoid nodules or pulmonary fibrosis)
 Cardiovascular issues (pericarditis, myocarditis, conduction defects)
 Ophthalmic issues (keratoconjunctivitis sicca and episcleritis – not uveitis)
 Rheumatoid vasculitis (cutaneous ulcers, purpura, and ischaemia)
 Felty’s syndrome (triad of arthritis, splenomegaly, neutropenia)
 Symptoms and signs – see Inflammatory versus Degenerative Arthritis
 Pattern of joint involvement:
 Typically, symmetric polyarthritis of small joints (may also affect hips and cervical spine)
 Hands/feet – MCP, MTP, PIP (causes ulnar deviation at MTP and classical deformities)
DIAGNOSIS
 Multiple diagnostic criteria (clinical and laboratory diagnosis)
 Labs – RF and anti-CCP (specific) are classical (may be seronegative)
 Also, associated with anaemia of chronic disease, thrombocytosis,  CRP
 Imaging – X-ray (periarticular osteopenia followed by erosions and further damage)
TREATMENT
 Pharmacologic – goal of altering disease progression (measured by DAS28 score):
 DMARDs (first-line) – methotrexate, sulfasalazine, hydroxychloroquine (‘triple therapy ’)
 Biologics (second-line) – adalimumab, etanercept, infliximab
 Pharmacologic – goal of reducing inflammation and pain:
 NSAIDs ± paracetamol ± opioids ± steroids (oral or articular injection)
 Non-pharmacologic – physiotherapy and occupational therapy

Note: ‘window of opportunity ’ refers to early treatment within first 3 months of disease may allow better control/remission.
SYSTEMIC LUPUS ERYTHEMATOSUS
Systemic lupus erythematosus (SLE) is a chronic, inflammatory, multi-system disease of unknown aetiology.
 Characterised by production of autoantibodies causing multi-organ inflammation (associated with HLA-B8/DR3)
 Multifactorial aetiology (may be drug-induced – associated with anti-histone antibodies )
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FEATURES
 Typically, age of onset is reproductive years (female-to-male ratio is 10:1)
CLINICAL PRESENTATION AND DIAGNOSIS
 Relapsing-remitting illness suspected in patients who have symptoms in two or more organ systems
 Diagnostic criteria (highly likely if four or more of) – MD SOAP BRAIN:
 Malar or Discoid rash
 Serositis (pleuritis or pericarditis)
 Oral/nasal ulcers (usually painless)
 ANA (sensitive but not specific)
 Photosensitivity rash
 Blood (haematological findings – e.g. autoimmune haemolytic anaemia or pancytopenia)
 Renal (nephritic or nephrotic syndrome)
 Arthritis (symmetric polyarthritis)
 Immune (anti-dsDNA, anti-smooth muscle, or anti-phospholipid antibodies or falsely positive VDRL)
 Neurological (seizures or psychosis)
TREATMENT
 Dermatologic – sunscreen and topical steroids
 Musculoskeletal – NSAIDs + PPI
 Additional:
 Hydroxychloroquine – first-line treatment for skin and joint involvement
 Corticosteroids – acute exacerbations or refractory cases (consider steroid-sparing agents )
 Cyclophosphamide – severe cases of lupus nephritis
OUTCOMES
 Good prognosis (if treated)
SCLERODERMA (SYSTEMIC SCLEROSIS)
Scleroderma is a non-inflammatory, autoimmune, disorder characterised by widespread small vessel vasculopathy and fibrosis.
 May manifest as CREST syndrome (limited form)
 Associated with HLA-DR1
FEATURES
 Typically, age of onset is late-adulthood (male-to-female ratio is 4:1)
CLINICAL PRESENTATION
 Examination may reveal symmetric thickening of skin of face and/or distal extremities
 Limited cutaneous (associated with CREST syndrome ) – head, neck, distal upper extremities
 Diffuse cutaneous – torso, abdomen, proximal upper extremities
 Diffuse form – gastrointestinal dysmotility, pulmonary fibrosis (cor pulmonale), acute renal failure, and malignant hypertension
 CREST syndrome – Calcinosis, Raynaud’s, Esophageal dysmotility , Sclerodactyly, Telangiectasia

Note: scleroderma is the most common secondary cause of Raynaud’s phenomenon (typically, idiopathic).
DIAGNOSIS
 Clinical diagnosis (based on symptoms via diagnostic criteria)
 Labs – anti-scl-70 and anti-topoisomerase are classical (may be ANA and RF positive)
 Anti-centromere antibodies are associated with CREST syndrome
 Anti-Scl-70 antibodies are associated with diffuse form and poor prognosis
TREATMENT
 No curative treatment
 Acute flairs – corticosteroids (but increases risk of renal disease)
 Raynaud phenomenon – CCBs
 Renal disease/hypertension – ACEI/ARBs
OUTCOME
 Moderate survival (50-75% at 10 years) – typically, due to complications of pulmonary hypertension
SJOGREN’S SYNDROME
Sjogren syndrome is an autoimmune condition characterised by dry eyes (xerophthalmia) and dry mouth (xerostomia).
 Due to lymphocytic infiltration of salivary and lacrimal glands
 May evolve to systemic form with respiratory tract and skin involvement
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FEATURES
 Typically, age of onset is late-adulthood (almost exclusively female)
CLINICAL PRESENTATION
 Classical triad of dry eyes, dry mouth, and arthritis (symmetrical small joint)
DIAGNOSIS
 Diagnostic criteria:
 Labs – anti-Ro/SSA and anti-La/SSB are characteristic
 Dry eyes – on ophthalmologic assessment
 Dry mouth – on salivary gland biopsy
TREATMENT
 Symptomatic (artificial tears , hydration, and dental hygiene )
 Corticosteroids may be useful for acute symptoms
MIXED CONNECTIVE TISSUE DISEASE
Mixed connective tissue disease is a syndrome defined by features of three or more different connective tissue diseases.
 Diseases include SLE, scleroderma , and polymyositis

Vasculitides
GENERAL PRINCIPLES
Vasculitis is inflammation and necrosis of blood vessels leading to disruption (aneurysm/rupture) or stenosis .
 Any organ system can be involved (suspected in cases of unexplained multiple organ ischaemia or systemic illness )
 Typically, treated with corticosteroids and/or immunosuppressive agents
CLASSIFICATION
 Small-vessel:
 Non-ANCA-associated – e.g. Henoch-Schönlein purpura
 ANCA-associated – e.g. GPA, MPA, and eosinophilic vasculitis (predilection for respiratory tract and kidneys)
 Medium-vessel:
 Polyarteritis nodosa
 Kawasaki disease
 Large vessel:
 Giant cell arteritis
 Takayasu’s arteritis

Medium vessel
Polyarteritis nodosa
Polyarteritis nodosa is a medium-vessel vasculitis that causes multi-organ dysfunction .
 Associated with hepatitis B
 Suspect polyarteritis nodosa in non-diabetic patients with mononeuropathy multiplex
 Treated with prednisone and cyclophosphamide (± anti-viral hepatitis B therapy )

Large vessel
Giant cell arteritis
Giant cell arteritis is a large-vessel vasculitis that affects the temporal artery (and aorta).
FEATURES
 Almost exclusively occurs in those >50 years of age
CLINICAL PRESENTATION
 New-onset temporal headache ± scalp tenderness
 Prominent temporal arteries (with or without pulsation)
 Jaw claudication (pain during mastication)
DIAGNOSIS
 Diagnosis – clinical suspicion, raised ESR/CRP, and temporal artery biopsy (within 14 days of steroid therapy)
TREATMENT
 If any suspicion of GCA – immediate high dose prednisone (60mg OD)
 Taper prednisone as symptoms resolve (treatment duration of at least one year )
 Highly effective in treatment and prevention of blindness and other vascular complications
 Additional:
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 Consider vitamin D supplements and bisphosphonate for bone protection during steroid therapy
 Consider aspirin to decrease likelihood of blindness and other vascular complications
COMPLICATIONS
 Sudden, permanent, painless, loss of vision in one or both eyes (25% if left untreated)
 Increased risk of thoracic aortic aneurysm and aortic dissection
 Polymyalgia rheumatica (in up to 30% of patients)
Takayasu’s arteritis
Takayasu’s arteritis is a large-vessel vasculitis affecting the aorta (and its major branches).
 Typically, presents in young Asian females
 Diagnosed by MRI
 Classically described as ‘pulseless disease ’ – unequal peripheral pulses

Seronegative rheumatic disease

ANKYLOSING SPONDYLITIS
Ankylosing spondylitis is a chronic, inflammatory, arthritis involving the sacroiliac joints and vertebrae.
 Leads to fusion of the effective joints
 Associated with HLA-B27
CLINICAL PRESENTATION
 Typically, presents in late teens or twenties with fatigue and insidious onset intermittent hip and lower back pain
 Worsens with inactivity and in the mornings (inflammatory pattern)
 Progression involves loss of spinal movement and chest expansion
 Associated with enthesitis (pain at insertions of tendons/ligaments) – plantar fasciitis/Achilles tendonitis
 Associated with anterior uveitis and heart block
DIFFERENTIAL DIAGNOSIS
Other seronegative spondyloarthropathy must be ruled out:
 Reactive (sterile) arthritis:
 Classical triad of uveitis (can’t see), urethritis (can’t pee) and arthritis (sacroiliitis and peripheral) (can’t climb a tree )
 Typically, follows a chlamydia or gastroenteritis infection
 Psoriatic arthritis:
 Typically, asymmetric oligoarthritis with psoriatic skin lesions and sausage-shaped digit s (dactylitis)
 X-ray shows characteristic ‘pencil-in-cup’ deformity
 Enteropathic spondylitis:
 Similar to ankylosing spondylitis that is associated with IBD
DIAGNOSIS
 Clinical diagnosis
 Imaging – X-ray (characteristic syndesmophytes and bony fusion)
 Labs – ANA and RF negative (associated with raised ESR/CRP)
TREATMENT
 Non-pharmacological – physiotherapy (to prevent fusion)
 Pharmacological – NSAIDs (first-line) (biologics for refractory axial disease and DMARDs for refractory peripheral disease)
 Operative – surgical correction (e.g. hip replacement or vertebral osteotomy )
OUTCOMES
 Variable prognosis (remission and relapse is common)
 May lead to blindness (if uveitis untreated)

Crystal-induced arthropathies
Gout versus pseudogout
GOUT PSEUDOGOUT

Features Middle-aged males Elderly (male = female)

Onset Acute Acute or insidious

Crystal type Monosodium urate (needle shaped, negative birefringence – yellow) CPPD (rhomboid shaped, positive birefringence – blue)

Distribution Classically, first MTP (also midfoot, ankle, knee) Knee or wrist (mono- or poly-articular if chronic)
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GOUT

PATHOPHYSIOLOGY
 Derangement in purine metabolism resulting in hyperuricaemia
 Hyperuricaemia in a minority of patients leads to monosodium urate crystal deposition in tissues (tophi) and synovium
(microtophi)
 Acute change in uric acid concentration is more important than absolute values
 Changes in pH, temperature, or initiation of anti-hyperuricaemics/diuretics can precipitate an acute gouty attack
 Crystals in synovial fluid are ingested by neutrophils, leading to an acute inflammatory response with release of destructive enzymes
 Crystals are toxic to neutrophils leading to lysis and further inflammation
CLASSIFICATION
 Primary (idiopathic) – mostly due to idiopathic renal underexcretion
 Secondary:
 Dietary excess – beer, seafood, red meat, tomatoes
 Underexcretion – renal failure or drugs (esp. diuretics)
 Overproduction – increased turnover (malignancy or chemotherapy)
CLINICAL PRESENTATION
 Typically, presents as single episode of acute gouty arthritis that progresses to recurrent or chronic inflammatory arthritis
 Acute gouty arthritis – mimics cellulitis (severe pain, redness, swelling) but with reduced joint mobility (lasts days to weeks)
 Chronic tophaceous gout (deposits classically at first MTP, helix, olecranon, or tendon insertions) – chronic arthritis
 Kidney – predisposes to urate renal stones and nephropathy
DIAGNOSIS
 Joint aspirate – monosodium urate crystals (needle-shaped, negative birefringence)
 Labs – hyperuricaemia (although normal or low uric acid levels does not rule out gout)
 Imaging – X-ray (‘punched-out’ extra-articular bone lesions, ‘bone hooks’ overlying joint margin, reactive sclerosis)
TREATMENT
 Acute gout – NSAIDs ± steroids ± colchicine (do not start allopurinol during acute attack – may worsen symptoms)
 Chronic gout
 Non-pharmacologic – weight loss and avoid foods with high purine content
 Pharmacologic – anti-hyperuricaemics (allopurinol or others ) (± NSAID/colchicine prophylaxis )
 Target – serum urate of <0.36mmol/L (prophylaxis for 6 months after target levels achieved)
PSUEDOGOUT (CALCIUM PYROPHOSPHATE DEPOSITION)
Pseudogout is acute inflammatory arthritis due to inflammatory response to calcium pyrophosphate crystals in the joints.
 Typically, affects large joints and is polyarticular (in comparison to classical gout)
 May occur secondary to hyperparathyroidism and haemachromatosis
CLINICAL PRESENTATION
 Variable presentation (may resemble gout, osteoarthritis, or rheumatoid arthritis)
 Typically, self-limiting by one month
DIAGNOSIS
 Joint aspirate – CPPD crystals (rhomboid-shaped, positive birefringence)
 Imaging – X-ray (may show chondrocalcinosis – calcification in hyaline and/or fibrocartilage)
TREATMENT
 Pharmacological – NSAID ± steroids ± colchicine

Non-articular rheumatism
POLYMYALGIA RHEUMATICA

FEATURES
 Almost exclusively occurs in those >50 years of age
CLINICAL PRESENTATION
 Pain and stiffness of symmetrical proximal muscle s (neck, shoulder, hip, thighs)
 Stiffness worse after prolonged inactivity (i.e. morning stiffness)
 Tender muscles (but no weakness or atrophy)
 Constitutional symptoms prominent (e.g. fever, weight loss, malaise)
 GCA (in up to 15% of patients)
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DIAGNOSIS
 Labs – CBC (anaemia or thrombocytopenia), raised ESR/CRP, normal CK
 It is essential to exclude infection , malignancy, and GCA
TREATMENT
 Pharmacological – regular prednisone
 Taper prednisone as symptoms resolve (treatment duration of at least one year )
 Additional:
 Consider vitamin D supplements and bisphosphonate for bone protection during steroid therapy
FIBROMYALGIA (CHRONIC FATIGUE SYNDROME)
Fibromyalgia is a chronic non-articular rheumatism of unknown pathophysiology (on a spectrum with chronic fatigue syndrome ).
FEATURES
 Typically, affects patients aged 20 to 50 years (female-to-male ratio is 10:1)
CLINICAL PRESENTATION AND DIAGNOSIS
 Diagnosis of exclusion (there are several diagnostic criteria, but no diagnostic tests):
 Fibromyalgia – widespread, non-articular pain, with characteristic tender points (including axial skeleton)
 Chronic fatigue syndrome – unexplained persistent disabling fatigue not relieved by rest
TREATMENT
 Non-pharmacological:
 Reassurance
 Education
 Pharmacological:
 Symptomatic (e.g. antidepressants, anxiolytics , NSAIDs)
OUTCOMES
 Variable (usually chronic)

Miscellaneous disorders
BEHCET DISEASE
Behcet’s disease is a multi-system vasculitis presenting as a triad of posterior uveitis, oral-aphthous ulcers , and genital ulcers .
BEURGERS DISEASE (THROMBOANGIITIS OBLITERANS)
Beurger’s disease is a vasculitis that leads to distal claudication and gangrene (i.e. fingers/toes) and is strongly associated with smoking.
 Typically, affects young Asian males
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Neurology
Clinical neuroanatomy
CLINICAL NEUROANATOMY

Spinal tract function

Spinal tract functions
TRACT FUNCTION CLINICAL EFFECTS OF LESION
Lateral corticospinal Movement of ipsilateral Ipsilateral paresis at and
limbs and body below level of lesion

Dorsal column-medial Fine touch, vibration, Ipsilateral loss of fine touch,

lemniscus pathway conscious proprioception vibration, and proprioception
(crosses at medulla) at and below level of lesion

Spinothalamic Pain, temperature Contralateral loss of pain and

(crosses at spinal cord level) temperature at and below
level of lesion

Spinal cord lesions

Spinal cord lesion syndromes
DISEASE AREA AFFECTED CHARACTERISTICS
Tabes dorsalis Caused by tertiary syphilis (affects dorsal columns and dorsal roots)

 Symptoms: sensory ataxia and neuropathic (lancinating) pain

 Signs: impaired dorsal column function, absent lower limb reflexes, positive Romberg

Syringomyelia Caused by a syrinx (a CSF-filled cavity within spinal cord) (damages spinothalamic tract)
 70% are associated with Chiari I malformation

 Signs/symptoms: bilateral loss of pain and temperature (cape-like)

 Can expand and affect other tracts

ALS  Signs/symptoms: combined UMN and LMN deficits with no sensory/oculomotor deficits

Brown-Sequard syndrome Caused by hemi-section of spinal cord

Signs/symptoms:
 Loss of all sensation at level of lesion
 Loss of TVP (dorsal column) ipsilateral below lesion
 Loss of PT (spinothalamic) contralateral below lesion

Reflexes
Commonly tested reflexes
REFLEX NERVE ROOTS
Achilles/plantar reflex S1-S2 (plantar S1 only)

Knee reflex L3-L4

Biceps/brachioradialis reflex C5-C6

Triceps reflex C7-C8

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Cerebral blood supply and cranial nerves

DISTRIBUTION OF BLOOD SUPPLY
 Cerebral (diagram to right)
 Cerebellum and brainstem
 Cerebellum (SCA, AICA, PICA)
 Midbrain
 Medial – basilar
 Lateral – PCA
 Pons
 Medial – basilar
 Lateral – AICA
 Medulla
 Medial – anterior spinal
 Lateral – PICA/vertebral
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Vascular disorders
STROKE
Stroke is disruption of cerebral blood flow that leads to death of brain cells, resulting in acute onset of focal neurologic deficits .
CLASSIFICATION
 Ischaemic (80%):
 Arterial thrombosis
 Large vessel: stenosis or occlusion of internal carotid, vertebral, basilar, or intracranial arteries
 Small vessel/lacunar: chronic HTN, DM, or hypercholesterolaemia
 Cardioembolic
 Atrial fibrillation is most common; also, valvular heart disease and infectious endocarditis
 Systemic hypoperfusion (global cerebral ischaemia)
 Usually secondary to cardiac failure
 Primarily affects watershed areas (between the major cerebral arterial territories)
 Haemorrhagic (20%):
 Intracerebral haemorrhage
 Hypertensive (most common)
 Other: trauma, amyloid angiopathy, vascular malformation, vasculitis, drug use
 Subarachnoid haemorrhage
 Traumatic (most common)
 Spontaneous – ruptured aneurysms (75%), idiopathic, AVM

Note: TIAs are predominantly caused by thromboembolism from the carotid artery.
CLINICAL PRESENTATION

Common stroke symptoms by vessel territory

ARTERY DISTINGUISHING SYMPTOMS
MCA  Contralateral paresis and sensory loss in the face and arm (including dysphagia / dysarthria)
 Gaze preference toward the side of the lesion ± contralateral homonymous hemianopsia
 Non-dominant hemisphere – sensory neglect/agnosia
 Dominant hemisphere – aphasia and apraxia (usually on left side)

ACA  Contralateral paresis and sensory loss in the leg

 Cognitive or personality changes

PCA Homonymous hemianopsia ± macular sparing

Three D's: Dizziness (vertigo), Dysarthria, Dysphagia

Lacunar infarct Several lacunar syndromes:

(affects deep cerebral white matter,  Pure motor (posterior limb of internal capsule) – most common
basal ganglia, or pons)  Pure sensory (thalamic)
 Mixed sensorimotor (combination of thalamus and posterior internal capsule)
 Ataxic hemiparesis – second most common
Most common cause of stroke  Dysarthria-clumsy hand syndrome

TIA Any of the symptoms above (dependent on location of vascular lesion)

Definition: the sudden onset of focal neurologic deficits, due to temporary disruption (classically <24 hours) of
cerebral circulation but without infarction of cerebral tissue (± findings on MRI)

PICA (lateral medullary syndrome)  Ipsilateral facial sensory loss (pain and temperature – spinal trigeminal nucleus)
 Ipsilateral Horner’s syndrome (MEAT) (sympathetic fibres)
 Ipsilateral cerebellar ataxia (spinocerebellar pathway)
 Contralateral sensory loss (pain and temperature – spinothalamic pathway)
 Nystagmus, vertigo, nausea/vomiting (vestibular nuclei)
 Dysphagia, dysarthria (nucleus ambiguus)

(MEAT – Miosis, Enophthalmos (sunken eyeball), Anhidrosis, pTosis – sympathetic fibres)

Basilar artery Locked-in syndrome (quadriparesis, dysarthria, impaired eye movements)

Cerebellar stroke DDANISHH

Dysmetria, Dysdiadochokinesia, Ataxia, Nystagmus, Intention tremor, Slurred speech, Hypotonia, Headache
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Oxford classification of stroke

 TACS (total anterior circulation stroke) – large cortical stroke in middle / anterior cerebral artery areas – all three of:
 Contralateral hemiparesis/hemiplegia (and/or sensory deficit) of face, arm, and leg
 Contralateral homonymous hemianopia
 Higher cerebral dysfunction (e.g. dysphasia, apraxia, agnosia)
 PACS (partial anterior circulation syndrome) – cortical stroke in middle / anterior cerebral artery areas – two of:
 Contralateral hemiparesis/hemiplegia (and/or sensory deficit) of face, arm, and leg
 Contralateral homonymous hemianopia
 Higher cerebral dysfunction (e.g. dysphasia, apraxia, agnosia)
 POCS (posterior circulation stroke) – one of:
 Cerebellar or brainstem syndrome
 Loss of consciousness
 Isolated homonymous hemianopia
 LACS (lacunar syndrome) – subcortical stroke due to small vessel disease – no evidence higher cerebral dysfunction and one of:
 Pure motor signs  Ataxic hemiparesis  Dysarthria/clumsy hand  Pure sensory signs / Mixed sensorimotor signs
DIAGNOSIS
 Typically, a clinical diagnosis (history and examination)
 Emergent non-contrast head CT to RULE OUT haemorrhagic stroke (ischaemic strokes <6 hours old are usually not visible on
CT)
 MRI can often identify early ischaemic changes not detected on CT
 Lab: CBC, U&E, coagulation, troponins, BGL (purpose is to identify candidates for thrombolytic therapy)
 Determine underlying cause of stroke:
 Cardioembolic – cardiac tests/imaging (ECG, echocardiogram, Holter monitoring)
 Thrombotic – vascular imaging (carotid echo, MRA, CTA, trans-cranial doppler, angiography)
 Further neuroimaging
TREATMENT
Acute treatment:
 Haemorrhagic:
 Neurosurgery is definitive treatment
 Ischaemic:
 Intra-arterial thrombectomy (gold standard) – within 6 hours if indicated
 Patients should still receive rtPA if endovascular treatment is considered
 Window of treatment depends on stroke subtype (i.e. may extend to 24 hours in some cases)
 Thrombolysis (rtPA – alteplase) – within 4.5 hours if indicated/non-contraindicated (e.g. recent bleed)
 Dose: 0.9mg/kg over 60 minutes, with 10% of dose given as bolus over 1 minute (max 90mg)
 Anti-platelet therapy (aspirin or clopidogrel )
 At presentation of stroke/TIA if rtPA not received (delayed 24 hours if rtPA administered)
 Other management issues:
 Treat comorbidities – fever and hyperglycaemia (associated with worse prognosis)
 Hypertension – do not treat unless >220/120mmHg (otherwise IV labetalol) (maintains perfusion to ischaemic
penumbra)
 Avoid post-stroke complications:
 Dysphagia (and aspiration pneumonia) – speech-language therapist and nutritionist
 DVT – aspirin + intermittent pneumatic compression + TEDS
 UTI – catheter care
 Depression – screen and treat as necessary
 Cerebral oedema – screen and treat as necessary
Prevention (and long-term treatment) of ischaemic stroke/TIA:
 Prevention:
 Lifestyle changes – smoking cessation, physical activity, stroke rehabilitation programmes
 Lifelong anti-platelet therapy (clopidogrel  aspirin + dipyridamole ) – all patients post-ischaemic/TIA
 Management of risk factors:
 Hypertension ( biggest risk factor) – usual agents (e.g. ACEi)
 Hypercholesterolaemia – statin
 Diabetes – usual agents
 Atrial fibrillation – anticoagulant therapy in all patients if indicated (as per CHA 2DS 2-VASc)
 Carotid stenosis – carotid endarterectomy
 Other important notes:
 Mandatory one-month stand-down from driving
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Stroke recovery
 Neuroplasticity – the ability of the brain to form and reorganize synaptic connections (e.g. following injury)
 The greatest proportion of recovery occurs in the first 3 to 6 months after stroke
SCORING SYSTEMS
 NIH Stroke Scale (NIHSS) – assesses stroke severity (excellent predictor of patient outcomes)
 ABCD 2 score – predicts risk of stroke following a TIA
 Score based on Age, BP, Clinical features, Duration of symptoms, and Diabetes
 A score ≥4 indicates patient to be seen by a specialist within 24hr (all patients with suspected TIA should be seen within 7 days)

Miscellaneous definitions
 Apraxia – inability to process, plan, and sequence motor tasks (otherwise not explained by motor, sensory, or co-ordination deficits)
 Agnosia – inability to process sensory information
 Aphasia – inability to comprehend and formulate language
 Broca’s (expressive) aphasia – difficulty producing language (whilst comprehension is intact)
 Caused by damage to Broca’s area (opercular and triangular area of inferior frontal gyrus)
 Wernicke’s (receptive) aphasia: difficulty comprehending language (whilst producing language is intact)
 Caused by damage to Wernicke’s area (posterior section of superior temporal gyri)

Upper versus lower motor neuron signs

Upper versus lower motor neuron signs
SIGNS UMN LMN
Weakness + +

Pattern of weakness Distal > proximal

Equal weakness in distribution of nerve
Prominent in arm extensors and leg flexors

Atrophy - +

Fasciculation - +

Reflexes  

Tone  

Babinski reflex Positive Negative

Flaccid paralysis Negative Positive

Clasp-knife spasticity Positive Negative

CRANIAL NERVE AND BRAINSTEM DEFICITS

The combination of ipsilateral cranial nerve signs and contralateral cerebral signs is diagnostic of a brainstem lesion .

Lesions above level of pons (CNI-IV)

CN1: olfactory nerve
 Lesion: absence of sense of smell associated with a loss of taste
CNII: optic nerve
 See Neuro-ophthalmology
CNIII: oculomotor nerve
 Lesion: eye directed ‘down and out’ (unopposed SO/LR), severe ptosis, fixed dilated pupil, impaired accommodation
 Note: remember LR 6SO4 (the CNIII supplies the rest including parasympathetic pupillary constrictor fibres and levator palpebrae)
CNIV: trochlear nerve
 Lesion: diplopia of intorsion and depression (difficulty reading or going down stairs)
 Note: only cranial nerve that crosses the midline and exits posteriorly (may cause contralateral deficit)

Lesions at level of pons (CNV-VIII)

CNV: trigeminal nerve
 Lesion: ipsilateral facial numbness, weakness of muscles of mastication (jaw deviation towards side of lesion), impaired corneal reflex
CNVI: abducens nerve
 Lesion: medial strabismus at rest; defect of lateral gaze (horizontal diplopia)
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CNVII: facial nerve

 UMN lesion: contralateral facial weakness with forehead sparing (bilateral innervation)
 LMN lesion: ipsilateral facial weakness
 General deficits : taste dysfunction of anterior two-thirds of tongue, hyperacusis (stapedius innervation), impaired corneal reflex
 Note: 80-90% of lesions are due to Bell’s palsy (mostly HSV; self-limiting)
CNVIII: vestibulocochlear nerve
 Lesion: sensorineural hearing loss and vestibular issues

Lesions at level of medulla (CNIX-XII)

CNIX: glossopharyngeal nerve
 Lesion: ipsilateral loss of pharyngeal sensation, loss of gag reflex (afferent), taste dysfunction in posterior one-third of tongue
CNX: vagus nerve
 Lesion: asymmetry of soft palate and uvula (uvula deviation away from lesion); loss of gag reflex (efferent); hoarseness; dysphagia
CNXI: accessory nerve
 UMN lesion: contralateral weakness of trapezius with relative sparing of sternocleidomastoid (bilateral innervation)
 LMN lesion: ipsilateral weakness of trapezius and sternocleidomastoid (difficulty turning head to opposite side)
CNXII: hypoglossal nerve
 UMN lesion: tongue deviation away from lesion; absence of atrophy and fasciculations
 LMN lesion: tongue deviation towards side of lesion; ipsilateral atrophy and fasciculations

Further syndromes
 Internuclear ophthalmoplegia – lesion of the medial longitudinal fasciculus
 Leads to failure of adduction of the ipsilateral eye (towards the nose) – although convergence is normal
 A bulbar palsy is a lower motor neuron lesion of cranial nerves IX, X, and XII
 A pseudobulbar palsy is an upper motor neuron lesion of cranial nerves IX, X, and XII
SUBARACHNOID HAEMORRHAGE

AETIOLOGY
 Traumatic (most common)
 Spontaneous
 Ruptured saccular (berry) aneurysms (75%) (ant. communicating > pos. communicating > MCA)
 Idiopathic (20%)
 AVM (5%)
CLINICAL PRESENTATION
 Presents with abrupt-onset, intensely painful, ‘thunderclap’ headache (often followed by signs of meningeal irritation )
 May report ‘sentinel bleed’ (SAH-like symptoms) in the past few weeks
 In the absence of intervention, rapid development of obstructive hydrocephalus and seizures
DIAGNOSIS
 Non-contrast CT head – for diagnosis of SAH
 Lumbar puncture – for diagnosis of SAH if CT negative
 Findings – RBCs, xanthochromia (yellowish CSF due to RBC breakdown),  protein (from RBC), and  ICP
 MRA/CTA – to identify precise source of bleeding
TREATMENT
 Neurosurgery is definitive treatment (may perform angiographic coiling and/or stenting to stabilise aneurysm)
 Prevent rebleeding (most likely to occur in first 24 hours) by maintaining systolic BP 120-150mmHg until aneurysm treated
 Prevent vasospasm and subsequent ischaemic stroke (most likely to occur in first week) – CCB (nimodipine)
 Seizure prophylaxis – levetiracetam
 Treat hydrocephalus if indicated
COMPLICATIONS
 Rebleeding
 Vasospasm (vasoconstriction and permanent pathologic vascular changes in response to vessel irritation by blood)
 Presents as new onset ischaemic deficit
 Treated with Triple H therapy – induced Hypertension , Hypervolaemia , Haemodilution (controversial)
 Hydrocephalus (due to blood obstructing CSF flow)
 Hyponatraemia (due to cerebral salt wasting not SIADH)
OUTCOMES
 Overall 50% mortality (30% of survivors have moderate to severe disability)
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INTRACEREBRAL HAEMORRHAGE
Intracerebral haemorrhage is haemorrhage within the brain parenchyma.
 This can extend into the ventricles (IVH) or cortical surface (SAH)
 Typically, affects the basal ganglia/internal capsule (50%)
AETIOLOGY
 Intracerebral haemorrhage
 Hypertensive (most common) – affects the PTPC (Putamen, Thalamus, Pons, and Cerebellum)
 Other: trauma, amyloid angiopathy, vascular malformation, vasculitis, drug use
CLINICAL PRESENTATION
 Early symptoms/signs: focal motor or sensory deficits that worsen as the haematoma expands
 Late symptoms/signs: features of  ICP
DIAGNOSIS
 See Stroke (look for hyperdense areas, mass effect, or oedema that may predict herniation)
TREATMENT
 Neurosurgery is definitive treatment
 Blood pressure control – target of 140/90mmHg
 Seizure prophylaxis – levetiracetam
COMPLICATIONS
 Herniation (EMERGENCY)
 Hyponatraemia (due to SIADH)
SUBDURAL AND EPIDURAL HAEMORRHAGE
Subdural versus epidural haemorrhage
SUBDURAL EPIDURAL
Pathophysiology Head trauma  rupture of bridging veins  accumulation of Head trauma  lateral skull fracture  tear of middle
blood between dura and arachnoid meningeal artery  accumulation of blood between skull
and dura mater

Epidemiology  Elderly  Severe trauma

 Alcoholics

Clinical presentation Subacute or chronic (days to weeks) headache, confusion, Classically, post-traumatic  LOC  lucid interval of several
changes in mental status, or focal deficits hours  gradual  LOC / signs of  ICP / focal deficits

Diagnosis  CT: crescent-shaped haematoma (unbound by suture lines)  CT: biconvex haematoma (bound by suture lines)

Treatment  Conservative (may regress spontaneously)  Neurosurgical (can rapidly cause herniation and death)
 Neurosurgical (if severe)

CAVERNOUS SINUS THROMBOSIS

PATHOPHYSIOLOGY
 Uncontrolled infection of the central facial skin (danger area ), orbit, or nasal sinuses leads to septic thrombosis of the cavernous
sinus
 Typically, caused by S. aureus
CLINICAL PRESENTATION
 Headache is the most common symptom (changes in LOC suggest CNS spread or sepsis)
 Associated with fever, orbital pain , oedema, cranial nerve palsies ( CNIII, IV, V 1 or 2, VI)
DIAGNOSIS
 MRI (with gadolinium and MR-venography)
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 Labs: CBC and blood cultures

TREATMENT
 Aggressive empiric antibiotic therapy:
 Penicillinase-resistant penicillin (nafcillin) +
 Third-generation cephalosporin (ceftriaxone) +
 Metronidazole – to cover anaerobic infection from sinus/dental sources
 Vancomycin – can be added if MRSA concerns
 Antifungal therapy – is required for fungal cases
 IV antibiotics recommended for at least 4 weeks
 Surgical drainage may be necessary if there is no response to antibiotics within 24 hours

Headaches
HEADACHE

CLASSIFICATION
 Headaches are predominantly benign primary headaches (tension > migraine > cluster)
 However, rarely headaches can be due to secondary causes (which may be life threatening – HEAD TIE mnemonic)
 Haemorrhage
 Eclampsia
 Arterial (e.g. temporal arteritis or carotid/vertebral artery dissection)
 DVT of brain (e.g. cavernous sinus thrombosis)
 Tumour (or other SOL) – characterized by headache worse in morning and improving during day
 Infection (e.g. meningitis)
 Eye disorders (e.g. glaucoma)
DIAGNOSIS
 Primarily a clinical diagnosis
 Examination for all presentations of headache includes:
 Fundoscopy
 Visual acuity
 Blood pressure
 Examination of head and neck
 Investigations if red flags (emergent headache, systemic symptoms, neurologic signs, associated conditions) present:
 CBC – for suspected systemic or intracranial infection
 CRP/ESR – for suspected temporal arteritis
 CT/MRI – to rule out intracranial pathology
 CSF analysis – to rule out intracranial haemorrhage/infection
Common primary headaches
FEATURE TENSION MIGRAINE CLUSTER
Location Bilateral Unilateral or bilateral Unilateral (around eye)

Character Tightening (non-pulsating) Pulsating Variable

(variable duration) (hours to days) (hours – at the same time of day)

Severity Mild Moderate to severe Severe

Other symptoms Muscles of neck are often tight and Sensitivity to light/sound and/or Ipsilateral ptosis, nasal congestion,
tender nausea/vomiting watery eyes, facial sweating

Aura (1/3rd of people experience Occurs in bouts a few times a year

symptoms such as flickering lights or
sensory sensation)

Family history common

TREATMENT
 Tension headache:
 General exercise , stress reduction , and treatment of underlying musculoskeletal problems
 Acute treatment – paracetamol  NSAID (no more than two days a week – or this can cause medication overuse headache)
 Prophylaxis – TCA
 Migraine headache:
 Avoid known triggers
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 Acute treatment – paracetamol  NSAID  triptans

 Prophylaxis – TCA or β-blocker
 Cluster headache:
 Acute treatment – triptans and high-flow O2 therapy
 Prophylaxis – CCB (verapamil)

Seizure disorders
SEIZURES
Seizures are paroxysmal events with aberrant electrical activity in the brain leading to changes in neurologic perception or behaviour.
 Epilepsy is a chronic disorder characterized by two or more unprovoked seizures
 An aura is experienced by 50% of patients with epilepsy
PATHOPHYSIOLOGY
 Idiopathic epilepsy – genetics, development, etc.
 Acquired epilepsy :
 Structural brain lesion – tend to have a focal onset (suggesting focal CNS pathology)
 Non-neurologic aetiologies – such as electrolyte, glucose, or temperature abnormalities; drugs; hepatic encephalopathy; trauma
CLASSIFICATION
 Focal onset
 Aware or impaired awareness
 Motor or non-motor
 Focal to bilateral tonic-clonic
 Generalised onset
 Motor (tonic-clonic or other motor syndromes)
 Non-motor (i.e. absence)
 Unknown onset
 Motor or non-motor
 Unclassified
Focal onset seizures
 Definition – abnormal electrical activity arises from discrete region/s of the brain
 Can involve motor, sensory, autonomic, or psychic features (classically, automatisms in impaired awareness seizures)
 Post-ictal focal neurologic deficit (e.g. hemiparesis) can occur in impaired awareness seizures
 May progress to bilateral (generalised) tonic-clonic seizures
Generalised onset seizures
 Definition – abnormal electrical activity arises from both cerebral hemispheres and results in impaired level of consciousness
 Tonic-clonic: sudden loss of consciousness with tonic-clonic muscle contractions (often idiopathic)
 Marked by incontinence and tongue biting
 Patients appear cyanotic during postictal period
 Post-ictal phase is characteristic
 Absence seizures : presents with brief (often unnoticeable) episodes of impaired consciousness occurring several times per day
 Can appear to be daydreaming or staring but may include subtle motor signs
 Can be triggered by hyperventilation
 Post-ictal phase is not present
 Begin in childhood and typically subside by adulthood (often familial)
DIAGNOSIS
 Typically, a clinical diagnosis
 Labs (to rule out systemic causes): CBC, U&E (including calcium/magnesium), LFTs, BGL, toxicology (if indicated)
 Serum prolactin is often elevated in the post-ictal period
 Imaging: CT/MRI (only if new seizure with unknown cause or new neurological symptoms/signs)
 EEG:
 Focal-onset seizures – focal disturbance
 Absence seizures – 3-per-second spike-and-wave discharge
 Tonic-clonic – 10-Hz activity during tonic phase and slow waves during clonic phase
 Pseudo-seizures – EEG normal during ‘event’
TREATMENT
 Treat underlying cause
 Anti-convulsants (not indicated for single episode):
 Levetiracetam, phenytoin , carbamazepine, phenobarbital , and valproate have similar efficacy
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 Phenobarbital is first-line in children

 Absence seizures:
 First-line – ethosuximide
 Second line – valproate
 Refractory to medical treatment :
 Surgical treatment
 Mandatory twelve-month stand-down from driving

Status epilepticus
Static epilepticus is defined as unremitting or successive seizures without return to baseline state of greater than 5 minutes .
 Most commonly due to non-compliance with medical therapy
 Mortality in up to 20% of cases (usually due to underlying medical condition)
 Diagnosis and treatment should occur simultaneously
DIAGNOSIS
 Focused history and neurological examination
 Labs: CBC, U&E (including calcium/magnesium), LFTs, BGL, anti-convulsant drug levels, toxicology (if indicated)
 CT scan followed by lumbar puncture (if fever or meningism)
 Continuous EEG may be indicated
TREATMENT
 Maintain airway, breathing, circulation (ABCs) ; consider rapid sequence intubation for airway protection
 Antidotes: thiamine, glucose, and naloxone can be given to treat potential aetiologies
 Treatment protocol (differs between institutions):
 IV lorazepam
 + IV phenytoin
 + IV third-line agents
 ICU if refractory or airway compromise
 Dexamethasone if vasculitis/cerebral oedema is suspected
COMPLICATIONS
 Anoxia ( cerebral ischaemia)
 Rhabdomyolysis ( renal failure)
 Aspiration pneumonia
 Cardiac events (arrhythmia or ACS)

Dizziness and vertigo

Classification of vestibular disorders
Dizziness is a subjective phenomenon that is better characterised as:
Vertigo
A sensation of motion of either the body or of the environment (typically caused by asymmetric dysfunction of vestibular system).
Disequilibrium
A sensation of off-balance but without vertigo (typically caused by bilateral dysfunction of vestibular system; or due to issues with other
sensory organs, muscular weakness, or CNS issues).
Syncope
A sensation (or the action) of fainting (often described as light-headedness).
VERTIGO

CLASSIFICATION
There are two main types of vertigo:
 Central (15%) – caused by central stimulation (e.g. tumour, stroke, migraine, drugs, or multiple sclerosis)
 Peripheral (85%) – caused by dysfunction in vestibular apparatus or nerve
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Benign paroxysmal positional vertigo (BPPV)

PATHOPHYSIOLOGY
 Occurs when otolith in the inner ear become dislodged and enter the semi-circular canals (usually posterior)
 Usually due to head trauma (but often no cause is found)
CLINICAL PRESENTATION AND DIAGNOSIS
 Classically, brief vertigo and nystagmus caused by changes in head position
 Nausea is typical (vomiting is a red flag)
 Dix-Hallpike manoeuvre – used to test for BPPV
TREATMENT
 Reassure patient (typically resolves spontaneously)
 Epley manoeuvre (repositions otolith)
 Anti-emetics for nausea
Meniere’s disease
PATHOPHYSIOLOGY
 Caused by excess cochlear endolymph that refluxes into semi-circular canal
CLINICAL PRESENTATION
 Recurring episodes of vertigo , usually lasting several hours, associated with fluctuating hearing , tinnitus , and aural fullness
 Nausea and vomiting are typical
DIAGNOSIS
 Diagnosis based on classical symptoms and an audiogram (specific hearing loss pattern)
 An MRI is often required to exclude other pathology
TREATMENT
 Beta-histine (dual agonist/antagonist of specific histamine receptors)
 Specialist ENT treatment (e.g. intratympanic gentamicin injection or surgery)
COMPLICATIONS
 Progressive loss of hearing (particularly low frequency)
Vestibular neuritis / labyrinthitis
PATHOPHYSIOLOGY
 Vestibular neuritis – a viral or post-viral inflammation of vestibular nerve (vestibular equivalent of Bell’s palsy)
 Labyrinthitis – an acute infection (bacterial or viral) of the inner ear (risk factor for meningitis)
CLINICAL PRESENTATION
 A single, severe, episode of vertigo that lasts at least 48 hours accompanied by nausea and vomiting
 Auditory symptom s (e.g. hearing loss or tinnitus) suggest labyrinthitis (as opposed to vestibular neuritis)
TREATMENT
 Vestibular neuritis (self-limiting in weeks to months) – symptomatic treatment (e.g. for nausea) and corticosteroids
 Labyrinthitis – IV antibiotics ± drainage middle ear ± mastoidectomy
Acoustic neuroma
Acoustic neuroma (vestibular schwannoma) is a schwannoma (malignancy) of the vestibular portion of cranial nerve VIII.
 Occurs in the cerebellopontine angle
CLINICAL PRESENTATION
 Typically, presents with unilateral sensorineural hearing loss or tinnitus
 In the elderly, unilateral tinnitus or SNHL is acoustic neuroma until proven otherwise
 Associated with dizziness but true vertigo is rare as tumour grows slowly and compensation occurs
 In the elderly, unilateral tinnitus or SNHL is acoustic neuroma until proven otherwise
DIAGNOSIS
 MRI with gadolinium contrast (gold-standard)
 Audiogram (to assess sensorineural hearing loss)
TREATMENT
 Conservative management – if tumour is small or in the elderly
 Definitive management – surgical excision (or other oncologic approaches )
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SYNCOPE
Syncope is a loss of consciousness secondary to a sudden drop in cerebral perfusion (often confused with seizure)
 Pre-syncope is the sensation of imminent loss of consciousness but without fainting
CLASSIFICATION
 Cardiogenic – typically, no prodromal symptoms
 Arrhythmia
 Outflow obstruction (e.g. AS/HOCM)
 Myocardial infarction
 Noncardiogenic – typically, prodromal symptoms and rapid recovery
 Orthostatic hypotension – triggered by postural change (e.g. hypovolaemia or autonomic neuropathy such as diabetes)
 Vasovagal syncope – triggered by sudden increase in vagal tone (e.g. emotional distress, pain, prolonged standing)
 Metabolic disturbance

Note: stroke and TIA are not generally associated with syncope

Multiple sclerosis
MULTIPLE SCLEROSIS (MS)

PATHOPHYSIOLOGY
 An autoimmune disorder (thought to be T-cell mediated) that causes discrete demyelination at multiple CNS locations
 Poor white matter healing leads to relapsing and remitting symptoms
 Prolonged demyelination causes axonal loss leading to progressive symptoms
FEATURES
 The female-to-male ratio is ≥3:1, and onset is typically between 20 and 40 years of age
 More common at increasing distances from the equator during childhood (potentially related to Vit. D)
CLASSIFICATION
 Relapsing remitting (most common – best prognosis)
 Primary progressive
 Progressive relapsing
 Secondary progressive
CLINICAL PRESENTATION
 Classic descriptive triad of MS :
 Multiple neurological complaints (typically, brainstem, spinal cord, or optic nerve)
 Separate in time and space
 Not explained by a single lesion
 Classic symptom triad of MS (Carchot’s triad) : scanning speech, intranuclear ophthalmoplegia, and nystagmus (± RAPD)
 MS phenomena:
 Symptoms classically worsen with hot showers/baths
 Symptoms classically better in pregnancy
 Optic neuritis:
 Progressive monocular central vision loss with decreased acuity and colour vision on recovery
 Eye pain (esp. with movement)
 Associated with RAPD
DIAGNOSIS
 Typically, a clinical diagnosis
 Revised McDonald criteria – MRI gadolinium-enhancing lesions disseminated in space and time
 Additional tests:
 MRI – multiple, asymmetric, often periventricular white matter lesions (active lesions enhance with gadolinium)
 CSF –  IgG index or oligoclonal bands
 Evoked potentials – delayed but well-preserved wave form
TREATMENT
 Acute treatment : high-dose IV corticosteroids (plasmapheresis if refractory)
 Disease modifying treatment:
 First line – interferon- β and glatiramer acetate (injection), natalizumab (monthly IV infusion), fingolimod (oral)
 Symptomatic treatment (e.g. baclofen for spasticity)
 Education and counselling: MS Society, support groups, psychosocial issues
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OUTCOMES
 Good prognosis – female, young, relapsing-remitting, and presenting with optic neuritis
 Poor prognosis – primary-progressive

Disorders of the neuromuscular junction

MYASTHENIA GRAVIS

PATHOPHYSIOLOGY
 An autoimmune disorder caused by antibodies that bind to post-synaptic acetylcholine (ACh) receptors located at the NMJ
 Results in early saturation of the NMJ and inadequate muscle activation with increasing nerve stimulation
FEATURES
 Most often affects young adult women and elderly men
 Associated with thymoma and hyperthyroidism
CLINICAL PRESENTATION
 Presents with ocular (diplopia/ptosis), bulbar (dysarthria/dysphagia), and/or proximal limb weakness
 Symptoms worsen with activity (e.g. worse at end of day or after repetitive activity)
 Can lead to respiratory failure
DIAGNOSIS
 Initial test – acetylcholine receptor antibodies
 Single-fibre EMG – decremental response to repetitive stimulation
 Spirometry – screening for respiratory effort
 CT/MRI – screening for thymoma
TREATMENT
 Symptomatic relief – pyridostigmine (acetylcholinesterase inhibitor)
 Immunosuppression (mainstay) – steroids or other advanced medication (IVIG/plasmapheresis for crises)
 Surgical (if thymoma) – thymectomy (up to 90% of patients show improvement)
LAMBERT-EATON MYASTHENIC SYNDROME

PATHOPHYSIOLOGY
 An autoimmune disorder caused by antibodies that bind to pre-synaptic VG calcium channels leading to  ACh release at the
NMJ
 Associated with small cell carcinoma of the lung (is considered a paraneoplastic syndrome)
CLINICAL PRESENTATION
 Presents with proximal limb weakness (without ocular/bulbar paresis such as in myasthenia gravis)
 Symptoms improve with activity
 Associated with prominent anticholinergic symptoms
DIAGNOSIS
 Single-fibre EMG – incremental response to repetitive stimulation
 CT/MRI (screening for malignancy – especially small cell lung cancer)
TREATMENT
 Symptomatic relief – pyridostigmine (acetylcholinesterase inhibitor)
 Immunosuppression (mainstay) – steroids or other advanced medication (IVIG/plasmapheresis for crises)
 Oncological treatment (if SCLC)
BOTULISM
Botulism is caused by a toxin produced by the spores of Clostridium botulinum bacteria (found in soil and water).
 Infantile botulism is the most common form (usually from ingestion of honey – should not eat until 12 months old)
CLINICAL PRESENTATION
 Presents with generalised weakness and gastrointestinal upset
 Associated with prominent anticholinergic symptoms
DIAGNOSIS
 Lab – botulinum toxin blood test
TREATMENT
 Supportive (as required)
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 Definitive – botulinum anti-toxin

Neurocognitive disorders
MAJOR NEUROCOGNITIVE DISORDER (DEMENTIA)
Major neurocognitive disorder (NCD) (formerly dementia ) is defined as a chronic, progressive, global decline in multiple cognitive
areas that is associated with impairment in activities of daily living with the maintenance of intact consciousness.
AETIOLOGY
DEMENTIAS
 NeuroDegenerative disease s (esp. AD)
 Endocrine (hypothyroid)
 Metabolic (diabetes)
 Exogenous (alcohol or deficiencies – vitamin B12 / folate / thiamine)
 Neoplasm
 Trauma (diffuse axonal shear or intracranial haemorrhage)
 Infection (encephalitis, HIV, or syphilis)
 Affective (depression)
 Stroke (multi-infarct dementia)
CLINICAL PRESENTATION
Clinical presentation depends on underlying cause and involvement of different cerebral areas:
 Disease of frontal lobe – abnormalities of behaviour and judgement
 Disease of parietal lobe – impairment in visuospatial skills and integration of sensory inputs (i.e. agnosia and apraxia)
 Disease of occipital lobe – abnormalities in the visual system
 Disease of temporal lobe – leads to receptive dysphasia (Wernicke’s) and automatisms (purposeless, repetitive movements)

Alzheimer disease
Alzheimer disease is the most common cause of major neurocognitive disorder.
FEATURES
 The risk of developing increases with age (eventually everyone would develop AD if they lived long enough)
PATHOPHYSIOLOGY
 Genetics:
 Risk of developing AD is influenced by apolipoprotein E (ApoE)
 ɛ4 allele increases risk of AD and decreases age of onset
 Three genes for autosomal dominant AD identified: APP (on chromosome 21), PSEN1 (presenilin 1), PSEN2 (presenilin 1)
 Trisomy 21 – high likelihood to develop AD due to increased gene dosage of APP
 Five main subgroups of AD:
 Sporadic late-onset AD (most common)
 Familial late-onset AD (uncommon)
 Familial early-onset AD (rare)
 Associated with trisomy 21
 Associated with other neurodegenerative disease
CLINICAL PRESENTATION
 Cognitive impairment:
 Memory impaired for newly acquired information (early)
 Deficits in language, reasoning, executive function, and progressive cognitive decline
 Behavioural and psychiatric manifestations:
 Depression, agitation, and psychosis
 Signs:
 Early – typically, normal (except for mental status)
 Late – non-cognitive neurologic deficits, dyspraxia, and incontinence
DIAGNOSIS
 Diagnosis of exclusion (progressive cognitive decline without substantial motor impairment)
 Imaging – MRI/CT (diffuse cerebral atrophy particularly in parietal and medial temporal lobes)
 Autopsy – definitive diagnosis (Aβ deposits are pathognomonic; also, neurofibrillary tangles will be visualised)
TREATMENT
 Prevention of disease progression (does not affect outcome):
 Cholinesterase inhibitors (i.e. donepezil or rivastigmine )
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 NMDA-receptor antagonists (i.e. memantine ) – in severe disease

 Symptomatic management:
 Non-pharmacological – supportive education for patient and family
 Pharmacological – treat comorbid psychiatric disorders
OUTCOMES
 Progressive decline in cognition (typically, no plateaus)
 Death usually occurs within ten years of diagnosis (most frequently bronchopneumonia)

Vascular NCD
Vascular NCD is the second most common form of major neurocognitive disorder.
PATHOPHYSIOLOGY
 Due to the accumulation of neurological deficits through multiple ‘mini strokes’ and/or TIA
CLINICAL PRESENTATION
 Discrete episodes of sudden neurologic deterioration (step-wise cognitive decline)
 Associated with a history of CVS risk factors (e.g. hypertension, diabetes, dyslipidaemia, smoking, AF)
 May be associated with focal neurologic deficits
DIAGNOSIS
 Clinical diagnosis – presence of NCD and two or more of:
 Focal neurological signs
 Imaging (multiple old infarcts or extensive deep white-matter changes secondary to chronic ischaemia)
 Abrupt symptom onset or step-wise decline
TREATMENT
 Treat (and prevent) as stroke
 Monitor for depression – common in vascular dementia

Frontotemporal NCD (Pick’s disease)

FEATURES
 Common in younger patients (rarely begins after age 75 – but still less common than AD in young patients)
PATHOPHYSIOLOGY
 Unknown pathogenesis presumed genetic (characterised by atrophy of frontal and temporal lobes)
CLINICAL PRESENTATION
 Characterised by significant changes in behaviour and personality (disinhibition and apathy in particular)
 Classically, relative sparing of learning, memory, and motor function
DIAGNOSIS
 Clinical diagnosis
 Imaging – MRI/CT (frontotemporal atrophy)
 Genetic – genetic testing or family history
TREATMENT
 Symptomatic (survival is shorter, and decline is faster, compared to AD)

NCD with Lewy Bodies

NCD with Lewy Bodies is third most common cause of dementia.
CLINICAL PRESENTATION
 Classical triad:
 Fluctuating cognition with pronounced variation in attention and alertness
 Recurrent visual hallucinations that are detailed
 Spontaneous features of parkinsonism (with onset subsequent to development of cognitive decline)
DIAGNOSIS
 Clinical diagnosis
 Imaging – MRI/CT (to rule out other diagnoses)
 Autopsy – definitive diagnosis (Lewy bodies – α-synuclein proteins within neurons are pathognomonic)
TREATMENT
 Symptomatic treatment – anti-parkinsonian medication and atypical neuroleptics
 Prevention of disease progression (does not affect outcome):
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 Cholinesterase inhibitors (i.e. donepezil or rivastigmine )

 NMDA-receptor antagonists (i.e. memantine ) – in severe disease
OUTCOMES
 Death usually occurs within ten years of diagnosis
 Function is typically more impaired than other dementias (falls and depression are common)

Normal pressure hydrocephalus (NPH)

NPH is a potentially treatable form of NCD that is caused by persistent ventricular dilation in the context of normal CSF pressure.
 Thought to arise from impaired reabsorption of CSF (typically, idiopathic)
CLINICAL PRESENTATION
 Classic triad ( AID): Ataxia/Apraxia of gait (‘magnetic’), Incontinence, Dementia
 Signs of  ICP are not present (although spikes of elevated pressure may be present on continuous monitoring)
DIAGNOSIS
 Diagnosis based on – clinical features , normal CSF pressure on LP , and ventricular enlargement on CT/MRI
TREATMENT
 Continuous lumbar CSF drainage
 Surgical ventriculoperitoneal shunting (if CSF drainage is effective)

Creutzfeldt-Jakob disease (CJD)

CJD is the most common prion disease and is classified as a transmissible spongiform encephalopathy .
PATHOPHYSIOLOGY
 Caused by aggregation of abnormal conformations of PRP protein , called prions (PRPSC)
 Arise spontaneously in sporadic cases or through mutations in the PRNP gene
 New-variant CJD is slowly progressing and seen in younger people who have eaten contaminated beef
 Kuru is seen in cannibals who have eaten contaminated human brains
CLINICAL PRESENTATION
 Presents as dementia with ataxia and/or startle-induced myoclonic jerks with rapid clinical progression
DIAGNOSIS
 Suggested by clinical features – rapidly progressive dementia and myoclonus
 CSF analysis – elevation of specific CSF and tau proteins (indicating rapid destruction of neurons)
 Imaging – CT/MRI
 Autopsy – definitive diagnosis (spongiform transformation (vacuolisation), marked neuronal loss , and gliosis)
TREATMENT
 No treatment (uniformly fatal – most die within a year)

Movement disorders
Basic principles
DEFINITIONS
 Akathisia – subjective restlessness relieved by stereotypic movements
 Bradykinesia/Tachykinesia – slow/fast movement respectively
 Dyskinesia – any sudden involuntary movement
 Also used to describe stereotypical movements from long-term anti-psychotic or anti-dopaminergic use (e.g. metoclopramide )
 Tremor – rhythmic alternating muscle contraction and relaxation
TREMOR

CLASSIFICATION
 Benign essential tremor – common autosomal dominant trait that leads to progressive postural tremor of variable severity
Approach to tremor
RESTING POSTURAL INTENTION

Body part Distal upper extremities Upper extremities/head/voice Anywhere

Characteristics 4-6Hz pill rolling 6-12Hz fine tremor <5Hz coarse tremor

Worse with Rest (and better with movement) Sustained posture (outstretched arm) Cerebellar signs (e.g. finger-to-nose)

Effect of alcohol No effect Dampens essential tremor Worsens intention tremor

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Differential diagnosis Parkinson disease, parkinsonism, Physiologic, benign essential tremor, Cerebellar disorders, alcohol, multiple
Wilson’s disease drugs, hyperthyroid, hyperglycaemia sclerosis

PARKINSON DISEASE
Parkinson disease is an idiopathic disorder that is the second most common neurodegenerative disorder.
FEATURES
 Usually occurs after age 60
PATHOPHYSIOLOGY
 Loss of dopaminergic neurons in the substantia nigra pars compacta , which causes increased inhibition of cortical motor areas
 Also, associated with Lewy body formation (α-synuclein)
CLINICAL PRESENTATION
 Classically, presents with the Parkinson Tetrad (TRAP)
 Positive motor symptoms
 Resting Tremor – ‘pill-rolling’ 4-6Hz (especially in hands)
 Rigidity – lead-pipe rigidity with cogwheeling due to superimposed tremor
 Negative motor symptoms
 Akinesia/bradykinesia – slowed, small amplitude, movements; steps without arm swing
 Postural instability – stooped posture, shuffling gait, impaired reflexes, falls
 Associated with – masked facies, monotonous speech, micrographia, cognitive decline, and autonomic / psychiatric disturbances
ALTERNATE DIAGNOSES
It is important to consider an alternate diagnosis if:
 Poor response to levodopa
 Symmetric symptoms at onset (Parkinson disease is an asymmetrical disease)
 Early symptoms of – falls, cognitive impairment (NCD with Lewy bodies ), autonomic dysfunction (MSA), or gaze palsy (PSP)
TREATMENT
 Pharmacological (only indicated if affecting function):
 L-DOPA/carbidopa is mainstay of treatment (although efficacy reduces with time)
 Dopamine agonists (e.g. ropinirole/pramipexole) can be used for treatment in early disease
 Adjunct therapy:
 Selegiline (MAO-B inhibitor) – increases L-DOPA available
 Entacapone/tolcapone (COMT inhibitor) – increases L-DOPA available
 Amantadine (NMDA receptor antagonist) – improves dyskinesia
 Orphenadrine/benztropine (anticholinergic) – improves tremor
 Surgical (if refractory):
 Surgical pallidotomy or deep brain stimulation
OTHER PARKINSONIAN DISORDERS
 Drug-related parkinsonism (extra-pyramidal symptoms)
 L-DOPA can lead to dyskinesia (peak dopamine levels )
 Anti-psychotic or anti-dopaminergic use (e.g. metoclopramide ) can lead to Parkinson-like movement (dopamine
antagonism)
 However, long-time use can lead to tardive dyskinesia (irreversible dyskinesia due to D2 receptor super-sensitivity )
 NCD with Lewy bodies – parkinsonism with prominent cognitive decline and visual hallucinations
 Progressive supranuclear palsy (PSP) – parkinsonism with vertical supranuclear gaze palsy, mask-like facies, and erect posture
 Multiple system atrophy (MSA) – parkinsonism with severe autonomic features
 Vascular parkinsonism – multi-infarct presentation with lower body parkinsonism
HUNTINGTON DISEASE

PATHOPHYSIOLOGY
 Autosomal dominant CAG repeats (with anticipation) in Huntington gene on chromosome 4
 Leads to accumulation of defective huntingtin protein in neurons which leads to global cerebral atrophy (esp. affecting the
striatum)

Note: anticipation is where genetic disorders become apparent (and typically more severe) with each generation.
CLINICAL PRESENTATION
 Typical progression, of insidious onset of clumsiness/fidgetiness that progresses to frank dementia , chorea, and mood changes
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DIAGNOSIS
 Definitive – genetic testing (CAG repeats in HTT gene) (strongly indicated for genetic counselling)
 Imaging – CT/MRI (global cerebral atrophy – particularly of caudate nucleus)
TREATMENT
 Symptomatic (no disease altering treatment)
OUTCOMES
 Typically, life expectancy of twenty years from time-of-diagnosis

Motor neuron disorders

AMYOTROPHIC LATERAL SCLEROSIS (ALS)
ALS is a progressive neurodegenerative disease that causes both UMN and LMN symptoms and is ultimately fatal.
 Typically, idiopathic (although 5-10% familial)
PATHOPHYSIOLOGY
 Disorder of anterior horn cells of spinal cord, cranial nerve nuclei , and corticospinal tract
CLINICAL PRESENTATION
 Asymmetric limb motor symptoms (both UMN and LMN) with sparing of sensation, ocular muscles, and sphincters
 Bulbar findings – dysarthria, dysphagia, tongue atrophy, facial atrophy
 Suggests pathology above foramen magnum (rules out cervical myelopathy as the cause)
DIAGNOSIS
 Primarily, a clinical diagnosis (no definitive test)
 EMG/nerve conduction study – chronic denervation and spontaneous action potentials (fibrillation potentials)
 CT/MRI – to rule out cord disease/compression
TREATMENT
 Riluzole (modestly slows disease progression)
 Spasticity – baclofen and physical therapy
 Supportive therapy:
 High calorie diet and nutritional support (e.g. PEG)
 Ventilatory support (esp. BIPAP)
 Rehabilitation
 Psychosocial support
OUTCOME
 Universally fatal (within a few years) – due to respiratory failure

Peripheral neuropathies
CLASSIFICATION
 Radiculopathy – dermatomal deficit due to a single (mono-) or multiple (poly-) nerve root lesion/s
 Examples: disc herniation with root compression (monoradiculopathy) or cauda equina syndrome (polyradiculopathy)
 Neuropathy – nerve deficit due to a single (mono) or multiple (poly-) peripheral nerve lesion/s
 Mononeuropathy multiplex affects multiple discrete nerves (asymmetric) – e.g. vasculitis or collagen vascular disease
Mononeuropathy
 Carpal tunnel syndrome (most common) – compression of median nerve at wrist
 Bell’s palsy (most common cranial neuropathy)
 Entrapment mononeuropathies:
 Ulnar nerve – at elbow or Guyon’s canal
 Median nerve – at carpal tunnel (above) or pronator teres
 Radial nerve – at spiral groove of humerus or axilla
Polyneuropathy
Polyneuropathy presents as a symmetrical, distal, sensorimotor deficit (with a stocking-glove distribution )
 Classically, seen in diabetes mellitus (most common) and vitamin B12 deficiency (subacute combined degeneration of the cord)
GUILLAIN-BARRE SYNDROME
Guillain-Barre syndrome is a rapidly progressive demyelinating, inflammatory, polyradiculoneuropathy of the peripheral nerves.
 Associated with recent Campylobacter or CMV infection
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CLINICAL PRESENTATION
 Sensory – symmetric ascending loss of sensation
 Motor – symmetric ascending paralysis with areflexia (may lead to respiratory failure)
 Autonomic – blood pressure dysregulation, arrhythmia, bladder dysfunction
DIAGNOSIS
 CSF – albuminocytologic dissociation (high protein with normal WBC)
 EMG/NCS – diffuse demyelination with decreased nerve conduction velocity
TREATMENT
 Intensive monitoring ( vitals and vital capacity) – referral to ICU if impending respiratory failure
 IVIG and plasmapheresis (corticosteroids are not indicated)
 Aggressive physical rehabilitation
OUTCOMES
 Approximately 85% of patients make a complete recovery (may take up to 1 year)
 Mortality rate is <5%

Myopathies
Basic principles
CLINICAL PRESENTATION
 Myopathies are characterised by prominent symmetric proximal weakness and preserved sensation and reflexes
 Questions to assess proximal weakness:
 Upper limb – difficulty reaching above head
 Lower limb – difficulty standing from sitting or climbing stairs
DIAGNOSIS
 Diagnosis and classification is often based on serum muscle enzymes (CK) , EMG, muscle biopsy , and/or genetic testing
 EMG – decreased action potential duration and amplitude (as opposed to neuropathy where they are both increased)
CLASSIFICATION
 Hereditary
 Muscular dystrophies
 Non-progressive myopathies
 Hereditary metabolic diseases
 Periodic paralyses (‘channelopathies’)
 Acquired
 Inflammatory myopathies
 Toxic myopathies (e.g. statin, steroids , thyroxine, alcohol, or critical illness myopathy in ICU patients )
 Endocrine and metabolic myopathies (e.g. Cushing syndrome or hyperthyroidism )
INFLAMMATORY MYOPATHIES
Polymyositis/dermatomyositis
 Polymyositis is a progressive, systemic, connective tissue disease characterised by immune-mediated skeletal muscle inflammation
 Dermatomyositis presents with symptoms of polymyositis plus cutaneous involvement (although the pathogenesis is different)
CLINICAL PRESENTATION
 Polymyositis – progressive symmetric proximal myopathy and/or pain (may lead to difficulty breathing or swallowing if advanced)
 Dermatomyositis :
 Heliotrope rash – violaceous periorbital rash
 Shawl sign – rash involving shoulders and upper chest/back
 Gottron papules – papular rash with scales on hands and bony prominences
DIAGNOSIS
 Labs –  CK and anti-Jo-1 antibodies (in dermatomyositis)
 EMG
 Muscle biopsy (not typically needed)
 Screening for malignancy (as is commonly a paraneoplastic syndrome)
TREATMENT
 High-dose steroids with taper
 Azathioprine and/or methotrexate can be used as steroid-sparing agents
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Inclusion body myositis

Inclusion body myositis is the most common inflammatory myopathy in patients >50 years of age.
 Presents with asymmetrical distal myopathy
Immune-mediated necrotising myopathy
Immune-mediated necrotising myopathy presents only with proximal muscle weakness.
HEREDITARY MYOPATHIES
Duchenne muscular dystrophy
Duchenne muscular dystrophy is an X-linked recessive disorder characterised by progressive skeletal and cardiac muscle degeneration .
PATHOPHYSIOLOGY
 Missing structural protein (dystrophin)  muscle fibre fragility and breakdown  necrosis and regeneration
 Genetics – 1/3 spontaneous and 2/3 inherited mutations
Duchenne muscular dystrophy versus Becker muscular dystrophy
FEATURE DUCHENNE MUSCULAR DYSTROPHY BECKER MUSCULAR DYSTROPHY

Onset <3 years >5-15 years

Life expectancy Young adult (20-30) Middle age (30-40)

Intellectual disability Common Uncommon

Protein analysis Dystrophin /absent Dystrophin abnormal

CLINICAL PRESENTATION
 Typically, asymptomatic at birth but develops proximal myopathy in the first few years of life
 Often seen as Gower’s sign (child uses hands to ‘climb’ up legs) and unusual gait
 Pseudohypertrophy of calf muscles (muscle replaced by fat)
 Intellectual disabilities
 Cardiomyopathy
DIAGNOSIS
 Definitive – genetic studies of dystrophin gene
 Labs –  CK
 Muscle biopsy – necrotic muscle fibres with absence of dystrophin protein
TREATMENT
 Supportive (e.g. physiotherapy , wheelchairs , tendon-release , or scoliosis surgery )
 Cardiac health monitoring and early intervention
 Bone health monitoring and early intervention (vitamin D or bisphosphonates )
COMPLICATIONS
 Patients usually wheelchair-bound by early teens
 Musculoskeletal complications – flexion contractures, scoliosis, osteopenia
 Death typically due to cardiac or respiratory failure
Myotonic dystrophy
Myotonic dystrophy is an autosomal dominant disorder which is the most common adult muscular dystrophy .
CLINICAL PRESENTATION
 Distal greater than proximal myopathy (as opposed to most myopathies)
 Myotonia (delayed relaxation of muscles after exertion)
 Strongly associated with arrhythmia, hypoventilation, and ocular issues
TREATMENT
 Myotonia – phenytoin
 No curative treatment (death usually occurs around 50 years old)

Neurocutaneous disorders
NEUROFIBROMATOSIS
Neurofibromatosis consists of two neurocutaneous disorders (NF-1 and NF-2) both of
which are autosomal dominant.
CLINICAL PRESENTATION
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 Diagnostic criteria for NF-1 includes:

 Café-au-lait spots (flat, uniformly hyperpigmented macules)
 Neurofibromas (benign peripheral nerve sheath tumours)
 Freckling in axillary or inguinal area
 Optic glioma
 Lisch nodules (pigmented iris hamartomas)
 Bone abnormalities
 NF-2 is most commonly associated with bilateral vestibular schwannoma
DIAGNOSIS
 Family history (first-degree relatives)
 Physical exam – ophthalmologic, dermatologic, and auditory (screening for complications)
 MRI with gadolinium (brain, brainstem, and spine)
TREATMENT
 Symptomatic (no disease altering treatment)
TUBEROUS SCLEROSIS
Tuberous sclerosis is an autosomal dominant neurocutaneous disorder that affects many organ systems.
CLINICAL PRESENTATION
 Presents with infantile spasms , ‘ash-leaf’ hypopigmented lesions, and mental disabilities
 Other skin manifestations:
 Sebaceous adenomas (nodules on nose/cheeks)
 Shagreen patch (orange-peel like lesion in lumbosacral region)
 Other symptoms due to small benign tumours that grow in brain, heart, retina, and kidneys
DIAGNOSIS
 Clinical diagnosis
 Imaging:
 MRI brain – evaluate for benign tumours or hydrocephalus
 Echocardiography – evaluate for rhabdomyoma of the heart
 MRI abdomen – evaluate for renal disease
 EEG – evaluate for seizure activity
TREATMENT
 Symptomatic (no disease altering treatment)

Nutritional disorders
Nutritional deficiencies
FEATURE CLINICAL PRESENTATION DIAGNOSIS TREATMENT

Vitamin B12 Gradual progressive peripheral neuropathy with  Serum vitamin B12 ()  Vitamin B12 (IM or large dose oral)
symmetric paraesthesia in addition to  Serum methylmalonic acid ()
incontinence and neuropsychiatric symptoms

Folate Similar presentation to vitamin B12 without  Serum folate ()  Folate (oral)
neurological findings

Vitamin E Ophthalmic symptoms  Serum vitamin E ()  Vitamin E (IM or oral)

Thiamine Four well-described syndromes:  Clinical diagnosis  Thiamine (IV)

 Beriberi (dry or wet)  Classically, occurs in alcoholics
 Wet – heart failure and oedema
 Dry – neurological symptoms and oedema
 Infantile beriberi (dry or wet)
 Wernicke’s encephalopathy (triad of
encephalopathy, ophthalmoplegia, ataxia)
 Korsakoff syndrome (permanent progression Note: high dose glucose can
of Wernicke’s with antero-/retrograde exacerbate thiamine deficiency (so is
amnesia and confabulation) given after thiamine typically)

Pyridoxine (B6) Painful sensorimotor peripheral neuropathy  Serum vitamin B6 ()  Pyridoxine (B6)

Vitamin B3 Pellagra (4Ds):  Serum nicotinic acid ()  Nicotinamide (B6)

 Diarrhoea, Dermatitis, Dementia, Death  Urine nicotinic acid ()
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Neuro-ophthalmology
Visual loss in strokes
Lesions of the optic radiation:
 Complete – contralateral homonymous hemianopsia
 Upper (Baum’s loop) fibres – contralateral lower quandrantopia
 Lower (Meyer’s loop) fibres – contralateral upper quandrantopia
Lesion of the calcarine cortex:
 Bilateral – complete (cortical) blindness
 Unilateral partial lesion – contralateral upper or lower quadrant- or hemianopsia with or without macula sparing

Neurosurgery
BASIC PRINCIPLES

ICP
PHYSIOLOGY
 Adult skull is rigid with constant intracranial volume
 Contents (CSF, blood, brain) are incompressible (Monro-Kellie doctrine )
 An increase in one constituent (or a space-occupying lesion) leads to either:
 Increase in ICP, or
 Redistribution of CSF, blood, or brain
 Cerebral blood flow is dependent on cerebral perfusion pressure
 An ICP causing a cerebral perfusion pressure of <60mmHg causes cerebral hypoperfusion
CLINICAL PRESENTATION
 Acute elevated ICP – nausea/vomiting, visual changes (papilloedema), herniation syndromes, poor level of consciousness
 Cushing’s triad of acute raised ICP (in 1/3rd of patients) – hypertension, bradycardia, irregular respiratory pattern
 Chronic elevated ICP – headache (worse with coughing and lying down), visual changes (papilloedema), poor level of consciousness
TREATMENT
 Treat underlying cause (may require CT/MRI ± lumbar puncture)
 Conservative measures:
 Elevate head of bed
 Prevent hypotension
 Prevent hypercapnia (causes vasodilation)
 Aggressive measures:
 Hyperventilation (to prevent hypercapnia)
 Mannitol (osmotic agent)
 Corticosteroids (reduces oedema)
 Sedation
 Decompressive craniotomy

Herniation
CLASSIFICATION

Herniation syndromes
SUBTYPE DEFECT CLINICAL PRESENTATION

Subfalcine Displacement of cingulate Typically, asymptomatic (can cause ACA stroke)

gyrus under falx cerebri
(due to frontal mass)

Transcalvarial Displacement of cerebral

tissue through defect in
skull (as in traumatic head
injury)

Transtentorial Herniation of uncus of Three classical signs (caused by ipsilateral compression):

(most common) medial temporal lobe  Compression of CNIII – ipsilateral dilated fixed pupil (CNIII palsy)
through the tentorial  Compression of cerebral peduncle (corticospinal/corticobulbar fibres) – contralateral hemiparesis
notch  Haemorrhage into midbrain due to arterial stretching (Duret haemorrhage) – coma

Kernohan’s phenomenon – ipsilateral hemiparesis (due to pressure of tentorial notch on cerebral

peduncle contralaterally ) – considered a ‘false’ localising sign
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Tonsillar (coning) Herniation of cerebellar Respiratory arrest and death (disruption of cardiac and respiratory symptoms)
tonsils through foramen
magnum

HYDROCEPHALUS
Hydrocephalus is excessive CSF accumulation in the brain.
PHYSIOLOGY
 CSF is produced by choroid plexus (mainly in lateral ventricles but also in third ventricle)
 Flow: lateral ventricle  3rd ventricle  cerebral aqueduct  4th ventricle  lateral/medial foramen  subarachnoid space
 Reabsorbed by arachnoid granulations into dural venous sinuses
AETIOLOGY
 Obstruction to CSF flow
 Decreased CSF absorption
 Increased CSF production (rare)
CLASSIFICATION

Classification of hydrocephalus
SUBTYPE DEFECT AETIOLOGY IMAGING

Obstructive hydrocephalus Circulation blocked within Acquired:  Ventricular enlargement proximal to block
(non-communicating) ventricular system  Aqueduct stenosis
proximal to arachnoid  Intraventricular lesion
granulations  Mass effect

Congenital:
 Aqueduct stenosis
 Chiari malformation
 Dandy-Walker malformation

Non-obstructive hydrocephalus CSF absorption blocked at  Post-infectious (most common)  All ventricles dilated
(communicating) arachnoid granulations  Post-haemorrhagic

Normal pressure hydrocephalus See NPH See NPH See NPH

Hydrocephalus Ex Vacuo Ventricular enlargement  Normal aging  Cerebral atrophy

resulting from cerebral  Neurocognitive disorder
atrophy

CLINICAL PRESENTATION
 Acute – signs of ICP and classical ‘sunset’ eyes (iris looks like setting sun due to impaired upward gaze)
DIAGNOSIS
 CT/MRI
 ICP monitoring (lumbar puncture must be completed with care – risk of herniation)
TREATMENT
 Surgical removal of obstruction
 Ventricular drainage
 Shunts (most commonly ventriculoperitoneal)
 Lumbar puncture (for transient hydrocephalus)
IDIOPATHIC INTRACRANIAL HYPERTENSION
Idiopathic intracranial hypertension is raised intracranial pressure without any obvious cause.
 Risk factors similar to those for gallstones (“fat, female, fertile, forties” )
CLINICAL PRESENTATION
 Signs and symptoms of ICP (e.g. headaches) and visual changes but no change in consciousness
DIAGNOSIS
 CT/MRI – normal (but must exclude cavernous sinus thrombosis)
 CSF – normal
TREATMENT
 Lifestyle change (weight loss and Na/H2O restriction )
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 Pharmacological – acetazolamide ( CSF production) or diuretics (loop/thiazide)

 Surgical – serial lumbar punctures or shunt
COMPLICATIONS
 Optic atrophy and blindness (10% of cases) – treated with optic nerve sheath decompression
SPACE OCCUPYING LESIONS

Tumours
CLASSIFICATION
 Primary (rarely undergo metastasis) versus metastatic (represent 1/3rd adult brain tumours – occur at grey-white matter junction)
 Metastatic lesions – mainly from lung (most common), breast, melanoma (also, kidney and GIT)
 Benign lesions – represent 40% of all primary brain tumours
 Parenchymal versus extra-axial
 Supratentorial (mainly adult tumours) versus infratentorial (mainly paediatric tumours)
Common primary CNS neoplasms in adults
TUMOUR CLASSIFICATION CLINICAL NOTES

Astrocytoma Grading:  Pilocytic astrocytoma is most common brain tumour in children

 Pilocytic astrocytoma (I) – benign  Good prognosis if treated (surgery + chemoradiotherapy)
 Diffuse (II) – benign  Glioblastoma is most common malignant primary brain tumour
 Anaplastic (III) – malignant  Progresses rapidly and has poor prognosis
 Glioblastoma (IV) – malignant  Treated with surgery + chemoradiotherapy
 Ring-enhancing lesion with contrast

Meningioma Benign (often incidental finding)  Good prognosis if treated (surgery)

 Most common extra-axial primary tumour

Vestibular schwannoma Benign See Vertigo (note: if bilateral suggestive of NFT type II)

Common primary CNS neoplasms in children

TUMOUR PATHOLOGY PRESENTATION

Pilocytic astrocytoma  Benign  Typically, slow-growing with protracted course

 Posterior fossa/infratentorial tumour

Medulloblastoma  Malignant neuroectodermal tumour  Arises from fourth ventricle or cerebellar vermis
 Posterior fossa/infratentorial tumour  May cause obstructive hydrocephalus
 Highly malignant but radiosensitive (surgery + chemoradiotherapy)

Craniopharyngioma  Benign  May cause hypopituitarism or homonymous hemianopia

 Most common suprasellar tumour in children  Commonly calcified
 Good prognosis if treated (surgery)

CLINICAL PRESENTATION
 Dependent on tumour location and type:
 Non-localising symptoms and signs –  ICP, herniation syndrome, or seizures
 Localising symptoms and signs – e.g. focal motor or sensory deficits, visual disturbance, or behavioural changes

Pus
AETIOLOGY
 Haematogenous spread (most common) – occurs at grey-white matter junction
 Direct implantation (trauma or iatrogenic)
 Contiguous spread (from sinus, nasopharynx, or surgical site)
 Spread from peripheral nervous system (e.g. herpes zoster)
Cerebral abscess
Cerebral abscess is a focal, suppurative, infection of the brain parenchyma.
 Most commonly caused by Streptococcus, Staphylococcus, and other anaerobes
CLINICAL PRESENTATION
 Classic triad of headache, fever, and focal neurological deficit
DIAGNOSIS
 Imaging – CT/MRI (ring-enhancing lesion with contrast)
 Labs – indicative of infection (but blood culture/CSF are typically negative)
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Note: cerebral ring-enhancing lesions with contrast are typically, glioblastoma, metastatic lesions, or abscesses.
TREATMENT
 Aspiration ± excision (if location suitable)
 Aggressive IV antibiotics (vancomycin + ceftriaxone + metronidazole ) for 6-8 weeks
 Prophylactic anticonvulsants
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Nephrology.
Basic principles
RENAL PHYSIOLOGY

Renal haemodynamics
 Glomerular filtration rate (GFR) – rate of fluid transfer between glomerular capillaries and Bowman’s space
 GFR is 180L/day of which 99% is reabsorbed , giving a daily urine output of 1-1.5 litres (normal urine output is 0.5-
2ml/kg/hr)
 GFR is highest in early adulthood, and decreases with age
RENAL AUTOREGULATION
Renal autoregulation maintains constant GFR over a wide range of arterial pressures (70-180mmHg) by two mechanisms:
 Myogenic (vasoactive factors released from endothelial cells) –  perfusion pressure  afferent arteriolar constriction   GFR
 Tubuloglomerular feedback –  Na+ delivery to distal tubules sensed by macula densa  afferent arteriolar constriction   GFR

Assessment of renal function

Renal function typically declines in parallel with a  GFR.
 Inulin clearance is gold standard for measuring GFR (but is rarely used)
 Serum creatinine concentration is the typical method for GFR estimation
 Creatinine is a metabolite of creatine; it is assumed to be freely filtered at the glomerulus with no tubular reabsorption
ESTIMATION OF GFR
 Measure creatinine clearance (see equation)
 Use estimation formulas (e.g. Cockcroft-Gault) – recommended method
 These use serum creatinine and demographic factors
LIMITATIONS TO SERUM CREATININE MEASUREMENT
 Must occur in steady state – i.e. constant GFR and rate of production of
creatinine from muscles
 Sudden injury may reduce GFR substantially, but it takes time for
creatinine to accumulate and re-establish steady state
 Clinical correlation: in AKI, the rise in creatinine is often delayed
 GFR must fall substantially before noticeable changes in serum
creatinine
 Remaining nephrons can compensate with hyperfiltration and
maintain GFR despites significant structural damage
 Serum creatinine is altered by muscle mass
MEASUREMENT OF UREA
 Urea is the major end-product of protein metabolism
 Serum urea concentration reflects renal function, but it is modified by several factors:
 Dietary intake of protein and catabolic rate (sepsis, trauma, GI bleed) (also ECF depletion)
 Clinical settings in which urea level is affected independently:
 Increase – volume depletion, GI haemorrhage, high protein diet, sepsis, catabolic state, medications
 Decrease – low protein diet, liver disease

Urinalysis
A urine dipstick can be used to assess the following:
 Specific gravity (ratio of the mass of equal volumes of the urine/H2O)
 Decreased (<1.010) – dilute urine
 Increased (>1.020) – concentrated urine
 pH
 Persistently alkalotic – suggestive of RTA or UTI with P. mirabilis
 Glucose (freely filtered at glomerulus and reabsorbed in proximal tubule)
 Glucosuria – suggestive of:
 Hyperglycaemia ( >9-11mmol/L exceeds tubular reabsorption capacity)
 Increased GFR (e.g. pregnancy)
 Proximal tubule dysfunction (e.g. Fanconi’s syndrome)
 Protein (detects macroalbuminaemia)
 Leukocyte esterase (enzyme found in WBCs)
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 Positive – suggestive of infection (e.g. UTI) or inflammation (e.g. AIN)

 Nitrites (nitrates in urine are converted by some bacteria to nitrites)
 Positive – suggestive of UTI (e.g. E. coli) but poor test characteristics
 Ketones
 Positive – alcoholic/diabetic ketoacidosis, prolonged starvation, and fasting
 Haemoglobin
 Positive – haemoglobinuria (haemolysis), myoglobinuria (rhabdomyolysis), or true haematuria (RBCs seen on microscopy)

Urine microscopy
 Cells
 RBCs – >2 red cells per high power field (HPF) indicative of haematuria
 WBCs – >5 white cells per HPF indicative of pyuria
 Epithelial cells – presence of small number of squamous cells is normal; renal tubular epithelial cells are pathologic
 Casts
 Hyaline casts – physiologic (concentrated urine, fever, exercise)
 RBC casts – glomerular bleeding (GN, vasculitis)
 WBC casts – infection (pyelonephritis) or inflammation (interstitial nephritis)
 Pigmented granular casts – ATN or acute GN
 Fatty casts – heavy proteinuria
 Crystals
 Uric acid – acid urine or hyperuricosuria
 Calcium phosphate – alkaline urine
 Calcium oxalate – hyperoxaluria
 Sulphur – sulpha-containing antibiotics
RENAL ANATOMY

Glomerular structure
 The glomerulus is a vascular structure formed of an anastomosing network of capillaries that arise from the afferent arteriole and
drain into the efferent arteriole
 The tuft of capillaries lies within the lumen of the Bowman capsule
 The visceral epithelium (composed of podocytes ) line the outside of the capillary wall
 The parietal epithelium line Bowman (urinary) space which is the cavity in which plasma ultrafiltrate (urine) collects
GLOMERULAR CAPILLARY WALL
The glomerular capillary wall consist of:
 A thin layer of fenestrated endothelial cells
 A glomerular basement membrane
(GBM)
 Podocytes (with foot processes adherent to
the outside of the GBM)
 Mesangial cells that support the glomerulus
(lie between the capillaries in the mesangial
matrix)

This acts as a filtration barrier with ‘selective

permeability’ that depends on the size and
charge of filtering molecules (podocytes are
main barrier to albumin filtration)
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BASIC TUBULAR REABSORPTION

Diuretics
Diuretics are medications that promote diuresis (increased production of urine).
CLASSIFICATION

Types of diuretics
DRUG SITE OF ACTION MECHANISM ADVERSE EFFECTS NOTES

Thiazide DCT  Secreted in proximal tubule  Hypovolaemia  Ineffective at low GFR

diuretics  Inhibits Na/Cl co-transporter (eNCC-1)  Electrolyte depletion  Little effect on GFR (effect
  in Na/H2O excretion  Hyponatraemia occurs distal to macula densa)
  in K/H excretion (high Na load at DT)  Hypokalaemia  May  briefly (effect on
 Also, promotes calcium reabsorption  Metabolic alkalosis carbonic anhydrase)
 Hypercalcaemia ( reabsorption)
 Uric acid retention
 Impaired glucose tolerance  Example:
 Impotence (reversible) bendroflumethiazide

Loop TAL  Secreted into proximal tubule  Hypovolaemia  Effective at low GFR
diuretics  Inhibits Na/K/Cl co-transporter (NKCC2)  Electrolyte depletion  Highly protein bound – must 
  in Na/K/Cl excretion (direct)  Hyponatraemia dose in nephrotic syndrome
  in Na/Ca/Mg excretion (indirect)  Hypokalaemia  Little effect on GFR (blocks the
  in K/H excretion (high Na load at DT)  Hypocalcaemia TGF feedback mechanism)
 Also, vasodilatory effect  Hypomagnesaemia
 Metabolic alkalosis
 Ototoxicity Example: frusemide

MRAs CD (acts non-  Inhibits mineralocorticoid receptor  Hyperkalaemia  Potassium-sparing

tubular)   ENaC expression ( Na excretion)  Anti-androgenic effects
 ATPase expression ( K excretion) Example: spironolactone
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Osmotic Filtered  Osmotic diuresis as is poorly reabsorbed  Hypovolaemia

diuretics Example: mannitol

NOTES
 Diuretics only act if sodium reaches their site of action (the magnitude of effect relates to the amount of sodium)
 As GFR drops, less sodium is excreted so thiazides (weak diuretics) have little effect; consequently, loop diuretics (or
combination treatments) can be used in low GFR to provide additional diuretic effect
 All diuretics, except spironolactone, act from the luminal side of the tubular cellular membrane

Electrolyte disorders
SODIUM DISORDERS
 Sodium disorders are disorders of water balance:
 Sodium deficiency leads to ECF volume contraction (symptoms due to cerebral oedema )
 Sodium excess leads to ECF volume expansion (symptoms due to cerebral shrinkage)
Clinical assessment of ECF volume (total body sodium)
FLUID COMPARTMENT HYPOVOLAEMIC HYPERVOLAEMIC

Intravascular
JVP  
Blood pressure Orthostatic drop  Persistently low (severity dependent) N/
Capillary refill  (peripheral  central) N
Auscultation of heart Tachycardia S3
Auscultation of lungs Normal Inspiratory crackles

Interstitial
Skin turgor Decreased N/
Oedema (dependent) Absent Present

Other
Urine output (best but slow)  ( in some renal abnormalities – osmotic diuresis) Variable
Body weight  
Haematocrit/serum protein  

Hyponatraemia
CLASSIFICATION
 Hypo-osmolar (dilutional) – most common cause
 Hypovolaemic
 High urinary sodium (renal losses) (UNA >20)
 Diuretics (esp. thiazides)
 Salt-wasting nephropathy
 Low urinary sodium (extra-renal losses) (UNA <10)
 Diarrhoea/vomiting
 Excessive sweating
 Third-spacing (e.g. peritonitis, pancreatitis, burns)
 Euvolaemic
 High urinary osmolality
 SIADH (FENA/UNA high)
 Adrenal insufficiency
 Hypothyroidism
 Low urinary osmolality (true dilutional)
 Psychogenic polydipsia
 Low solute intake – ‘tea and toast’
 Hypervolaemic
 High urinary sodium (renal losses)
 Heart failure
 Cirrhosis
 Nephrotic syndrome
 Pregnancy
 Low urinary sodium
 AKI or CKD
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 Iso-osmolar – typically due to mannitol

 Hyper-osmolar – extra osmoles in ECF draw water out of cells diluting the sodium in ECF (typically glucose)
 Consequently, must correct sodium levels for hyperglycaemia
CLINICAL PRESENTATION
 Presentation depends on degree and acuity of hyponatraemia
 Chronic hyponatraemia less likely to be symptomatic due to adaptation of brain volume
 Neurologic symptoms predominate (secondary to cerebral oedema) – e.g. weakness, confusion,  reflexes,  LOC
 Complications include seizures, respiratory arrest, coma, permanent brain damage (inc . herniation), and death
DIAGNOSIS
 Classified on the basis of ECF volume assessment
 Labs: serum (and urine) electrolytes and osmolality
TREATMENT
 Treat underlying cause
 Hypovolaemic – replace volume with normal (or hypertonic) saline
 Euvolaemic – treat underlying cause
 Hypervolaemic – water restriction ± loop diuretics

 Ensure that correction does not occur too rapidly if chronic (over 48-72 hours is ideal) ; can correct rapidly if acute change
 Monitor urine output – high output of dilute urine is a danger sign
 Rapid correction can cause rapid brain cell shrinkage which causes osmotic demyelination (central pontine myelinolysis)
 Characterised by severe neurological deficit (e.g. paralysis) or coma

Hypernatraemia
CLASSIFICATION
 Reduced free-water intake
 Elderly (dementia, swallowing difficulty, stroke, bed-bound)
 Infants
 Iatrogenic
 Increased free-water losses
 Extra-renal losses
 Gastrointestinal losses (diarrhoea, fistula, etc.)
 Insensible losses (exercise, seizures, etc.)
 Renal losses
 Diabetes insipidus (central and nephrogenic)
 Osmotic diuresis (hyperglycaemia, mannitol, etc.)
CLINICAL PRESENTATION
 Presents with thirst (due to hypertonicity) and neurological symptoms (due to cerebral shrinkage) similar to hyponatraemia
TREATMENT
 Treat underlying cause
 Replace free water deficit with free water (oral  IV) or hypotonic IV solution
 Ensure that correction does not occur too rapidly (over 48-72 hours is ideal)
 Rapid correction can cause rapid brain swelling
POTASSIUM DISORDERS

Hypokalaemia
CLASSIFICATION
 Transcellular shifts (K+ shift intracellularly): drugs (insulin or β2-agonists ), alkalosis
 Gastrointestinal losses: diarrhoea, chronic laxative abuse, vomiting, NGT
 Renal losses: diuretics (loop or thiazide), hypomagnesaemia, hyperaldosteronism, DKA, RTA, drugs
CLINICAL PRESENTATION
 Non-specific (constipation, fatigue, muscle weakness, decreased reflexes, and arrhythmia predominate)
 Severe hypokalaemia associated with rhabdomyolysis and paralysis
DIAGNOSIS
 Labs: serum electrolytes (including magnesium)
 Can differentiate between renal and gastrointestinal losses by urine potassium:creatinine ratio
 A potassium of <2.5mmol/L is a medical emergency (can also exacerbate digoxin toxicity)
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 ECG: may show T-wave flattening , U-waves (additional wave after T wave), prolonged QT, or depressed ST segment
TREATMENT
 Treat underlying cause
 Potassium repletion (oral  IV)
 MRAs can prevent renal potassium loss
 Magnesium repletion (this deficiency makes potassium repletion more difficult)

Hyperkalaemia
CLASSIFICATION
 Factitious:
 Haemolysis (most common cause)
 Prolonged use of tourniquet
 Sample taken from vein where IV potassium is running
 Delayed analysis (K+ leaks out of RBCs)
 Increased intake: diet or iatrogenic
 Transcellular shift (K+ shift into plasma):
 Tissue injury (rhabdomyolysis, tumour lysis syndrome, cell lysis)
 Insulin deficiency
 Acidosis
 Drugs (β-blockers, digoxin )
 Decreased excretion:
 Renal failure
 Hypoaldosteronism
 Drugs (MRAs, NSAIDs)
CLINICAL PRESENTATION
 Cardiac arrhythmia and other non-specific symptoms (fatigue, muscle weakness, decreased reflexes)
 Associated with hyperventilation, paralysis, and cardiotoxicity
DIAGNOSIS
 Labs: serum electrolytes (confirm with repeat blood draw to rule out factitious hyperkalaemia)
 Urgent ECG
 Can progress to sine waves, ventricular fibrillation, and asystole
TREATMENT
 Treat with C BBIG K DROP
 Calcium gluconate – for cardiac membrane stabilisation
 BIG – β-agonist, Bicarbonate, Insulin, Glucose (shifts K+ into cells)
 K DROP (enhance K+ removal)
 Via urine (preferred ) – loop diuretics or mineralocorticoid agonists
 Via gastrointestinal tract – enema therapy (sodium polystyrene sulfonate )
 Dialysis if renal failure or unresponsive to therapy
CALCIUM DISORDERS
Calcium in serum is bound to proteins, principally albumin; as a result, calcium must be corrected for albumin levels.

Hypocalcaemia
PATHOPHYSIOLOGY
 Most common cause is hypoparathyroidism (post-surgical, idiopathic)
 Other causes: CKD, hypomagnesaemia , pancreatitis , alkalosis (due to pH) and pseudohypoparathyroidism
CLINICAL PRESENTATION
 Presents with abdominal muscle cramps , tetany, paraesthesia , long QT, and convulsions (i.e. hypocalcaemia = hyper-reflexia)
 Signs in severe hypocalcaemia:
 Chvostek sign – facial spasm elicited from tapping of facial nerve
 Trousseau sign – carpal spasm after arterial occlusion by BP cuff
DIAGNOSIS
 Labs: calcium and phosphate, magnesium, albumin, PTH
 Additional workup:
 Review surgical notes – to see if parathyroid damage in thyroidectomy
 Vitamin D – can assist in appreciating clinical situation
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 ECG – may show prolonged QT interval

TREATMENT
 Treat underlying cause
 Calcium repletion (oral  IV)
 Magnesium repletion

Hypercalcaemia
PATHOPHYSIOLOGY
 Most common causes are hyperparathyroidism and malignancy (e.g. SCLC, renal cell carcinoma, or multiple myeloma)
 Other causes: diuretics (thiazides), granulomatous disease , increased bone turnover
CLINICAL PRESENTATION
 Usually asymptomatic, but can present with:
 Bones – bone pain (osteolysis and fractures)
 Stones – kidney stones and polyuria/polydipsia (via NDI)
 Groans (abdominal) – anorexia, nausea/vomiting, constipation, PUD, or pancreatitis
 Psychiatric overtones – weakness, fatigue, altered mental status
DIAGNOSIS
 Labs: calcium and phosphate, albumin, PTH
 Additional workup:
 Parathyroid hormone-related peptide (PTHrP) – if malignancy suspected
 Serum protein electrophoresis – for multiple myeloma
 Vitamin D – if granulomatous disease (macrophages convert vitamin D into active form through 1α-hydroxylase)
 ECG – may show short QT interval
TREATMENT
 IV hydration
 Calcitonin and bisphosphonates (and dialysis) if severe
 Corticosteroids may be useful in malignancy ( GI absorption)
 Avoid diuretics
MAGNESIUM DISORDERS

Hypomagnesaemia
The most important causes of hypomagnesaemia are alcoholism and DKA.
 Treated with magnesium repletion (oral  IV)
 Hypokalaemia and hypocalcaemia will not correct without magnesium correction

Acid-base disorders
Metabolic acidosis
CLASSIFICATION
 Normal anion gap (hyperchloraemic acidosis)
 Diarrhoea (or ostomy losses)
 Renal tubular acidosis
 Addison’s disease
 Increased anion gap ( TALK)
 Toxins (esp. methanol, ethylene glycol , aspirin)
 Advanced renal failure
 Lactic acidosis (typically, hypoperfusion)
 Ketoacidosis (diabetic, starvation, alcoholic)
TREATMENT
 Treat underlying cause
 Correct co-existing disorders of K+
 Consider treatment with sodium bicarbonate (may cause hypokalaemia)

Metabolic alkalosis
CLASSIFICATION
 Chloride sensitive (saline responsive) – urine Cl <20
 GI losses – vomiting or NGT
 Diuretics
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 Post-hypercapnia – renal compensation

 Chloride resistant (saline resistant) – urine Cl >20
 Hyperaldosteronism (or Cushing’s syndrome ) – if high blood pressure
 Hypokalaemia / Hypomagnesaemia / Bartter syndrome / Gittelman syndrome / Liquorice – if normal blood pressure
TREATMENT
 Treat underlying cause
 Correct co-existing disorders of K+/Mg+
 Saline responsive – volume repletion ± carbonic anhydrase inhibitor (facilitates loss of HCO3 in urine)
 Saline resistant – remove source of aldosterone or glucocorticoid ± spironolactone

Renal tubular acidosis

RENAL TUBULAR ACIDOSIS
Renal tubular acidosis (RTA) is a condition that involves an accumulation of acid (acidosis) due to a failure of the kidneys to
appropriately acidify the urine.
 The term RTA is reserved for individuals with poor urinary acidification with well-functioning kidneys (as opposed to AKI/CKD)
 There are two main mechanisms:
 Failure to resorb sufficient bicarbonate in the proximal tubule
 Failure to secrete sufficient hydrogen in the distal tubule
CLASSIFICATION

Classification of RTA
TYPE TYPE 1 (DISTAL) TYPE 2 (PROXIMAL) TYPE 4

Location Collecting ducts Proximal tubules Adrenal

Acidaemia Yes (severe) Yes Mild (if present)

Potassium Hypokalaemia Hypokalaemia Hyperkalaemia

Pathophysiology Failure of α-intercalated cells to secrete Failure of proximal tubular cells to Deficiency of aldosterone or a resistance
H+ and reclaim K+ reabsorb HCO3 to its effects (e.g. ACEIs/ARBs)

Most commonly due to autoimmune Most commonly due to Multiple

disorders or hereditary myeloma or Fanconi syndrome

Treatment Bicarbonate Thiazides Loop diuretics

Bicarbonate

Complications Nephrolithiasis Rickets or osteomalacia (due to

phosphate wasting)

Fanconi syndrome
Fanconi syndrome is a typically congenital syndrome (X-linked) which leads to inadequate reabsorption in the proximal renal tubule .
 This leads to loss of several molecules into urine (glucose, phosphate, bicarbonate)
 Variable clinical presentation that includes proximal RTA , rickets/osteomalacia , glucosuria (polyuria/polydipsia), and growth
delay

Acute kidney injury

Acute kidney injury is an abrupt↓in renal function that leads to (and is defined as) either:
 Retention of creatinine/BUN (≥26.5umol/L within 48hrs, or ≥1.5 times baseline within 7 days), and/or
 Oliguria (<0.5ml/kg/h for >6 hours)
CLASSIFICATION
 Pre-renal (90% of cases) – due to decreased renal perfusion
 Hypovolaemia – haemorrhage, shock, sepsis, renal artery stenosis
 Hypotension (with normal volume) – typically, heart or liver failure
 Disordered autoregulation – typically, drugs (diuretics, NSAIDs, ACEI/ARBs)
 Acute tubular necrosis – ischaemic tubular damage (intra-renal) due to pre-renal aetiology
 Intra-renal
 Glomerulonephritis
 Interstitial nephritis – typically, drugs (esp. β-lactams, NSAIDs, PPIs, sulpha drugs)
 Other rarer causes (vasculitis, hypertension, etc.)
 Post-renal – can only occur if affects both kidneys (or a single kidney)
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 Functional or anatomical (ureter, bladder, urethra, or extra-urinary) obstruction

CLINICAL PRESENTATION
 The clinical presentation is often dominated by the underlying disease
 However, can present as azotaemia ( BUN/Cr) and abnormal urine volume (oliguria)
 Signs: fatigue, nausea/vomiting
 Symptoms : metabolic acidosis, pericarditis, asterixis, encephalopathy, uraemic frost
 Hypocalcaemia, hyperphosphatasaemia , hyperkalaemia, and metabolic acidosis common
DIAGNOSTIC APPROACH
 Assess volume status (pre-renal aetiologies)
 May involve fluid challenge
 Urinalysis (R&M) (intra-renal aetiologies)
 IN – white cell casts (sterile pyuria), polyuria/nocturia, normal blood pressure
 GN – red cell casts, oliguria, high blood pressure
 Consider ultra-sound (post-renal aetiologies)
 Post-void residual of >50ml or obvious obstruction
 Additional:
 Labs – CBC, U&E, electrolytes (with Ca/PO4)
 Renal biopsy only indicated if unclear cause of intra-renal AKI
Differentiating pre-renal and renal AKI
INDICES PRE-RENAL INTRINSIC

Urine sediment Hyaline casts (normal but increased suggests Abnormal (red cells, white cells, granular casts)
volume depletion)

Urine osmolarity >500 <350

Urinary sodium (mmol/L) <20 >40

Fractional excretion of sodium <1% >1%

Plasma BUN/Cr ratio >20 (urea is hyper-responsive to volume depletion) <10-15

TREATMENT
 Basic approach ( treat the underlying cause):
 Correct volume status (pre-renal aetiologies)
 Stop offending medications and adjust renally excreted medications (intra-renal aetiologies)
 Correct obstruction (post-renal aetiologies)
 Wait (renal function will take time to correct itself)
 Additional considerations:
 Fluid overload/HTN – loop diuretics and Na/H2O restriction
 Correct electrolyte imbalances
 Consider dialysis
INDICATIONS FOR DIALYSIS
Dialyze if indicated using haemodialysis (use the AEIOU mnemonic):
 Peritoneal dialysis is only considered for long-term dialysis or patients who are haemodynamically unstable
 AEIOU:
 Acidosis
 Electrolyte abnormalities (e.g. hyperkalaemia)
 Ingestion of dialyzable substances
 Overload (fluid)
 Uraemia (encephalopathy, pericarditis, or very high serum urea)
OUTCOMES
 High mortality (~20%)
 Markedly increased risk of CKD/ESRD

Chronic kidney disease

CHRONIC KIDNEY DISEASE (CKD)
Chronic kidney disease is a progressive and irreversible loss of kidney function, which is defined as:
 Markers of kidney damage for ≥3 months (e.g. structural, imaging, laboratory), or
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 GFR <60mL for ≥3months

FEATURES
 Aetiology: diabetes mellitus > hypertension > glomerulonephritis > other
 Genetic cause: PCKD
CLASSIFICATION
 Classified by GFR and degree of proteinuria
CLINICAL PRESENTATION
 Asymptomatic until GFR <30mL
 Therefore, screening of at-risk individuals is essential
 CKD is associated with several pathological features:
 Fluid retention (and hypertension)
 Electrolyte and acid-base disorders
 Hypocalcaemia and hyperphosphatasaemia (leads to
metabolic bone disease)
 Hyperkalaemia and metabolic acidosis
 Azotaemia ( BUN/Cr)
 Anaemia of chronic disease (  EPO production,  hepcidin
(iron sequestration), low-grade haemolysis,  RBC survival,
uraemic bone marrow suppression)
 Abnormal haemostasis ( impaired platelet aggregation)
 Sex hormone dysfunction
 Dyslipidaemia
TREATMENT
 Control of hypertension, diabetes mellitus, and cardiovascular risk factors
 Treat reversible causes (e.g. obstruction, drugs)
 Lifestyle changes:
 Dietary advice
 Na/H2O restriction (to prevent volume overload )
 Potassium, phosphate, magnesium restriction (to prevent electrolyte imbalance )
 Protein restriction with adequate caloric intake to limit endogenous protein catabolism (to prevent uraemia)
 Medical therapy:
 Adjust dosages of renally excreted medications
 Avoid nephrotoxins
 Volume overload and hypertension – ACEi or loop diuretics if GFR <30mL
 Electrolyte and acid-base disorders
 Calcium and phosphate disorders – see Renal osteodystrophy
 Hyperkalaemia – see Electrolyte disorders
 Metabolic acidosis – sodium bicarbonate
 Uraemia – dialysis
 Dyslipidaemia – statins
 Anaemia of chronic disease – EPO or iron supplementation
 Abnormal haemostasis – desmopressin (acts to reverse platelet dysfunction)
 Renal replacement therapy
 Dialysis (haemodialysis or peritoneal dialysis) – see AEIOU for indications
 Renal transplantation
COMPLICATIONS
 Acquired renal cystic disease in patients undergoing long-term dialysis
 Cardiovascular complications (MI or sudden cardiac death) are the most common cause of death
Renal osteodystrophy
Renal osteodystrophy is the alteration in bone morphology in patients with chronic kidney disease .
 Represents a mixture of four types of bone disease (seen radiologically) – osteomalacia, adynamic bone disease (suppression of
parathyroid), osteitis fibrosis cystica (secondary hyperparathyroidism) mixed uraemic osteodystrophy
CLINICAL PRESENTATION
 Osteodystrophy (generalised bone pain and fractures) and pruritis
 Also associated with neuromuscular irritability and tetany
 Calciphylaxis – vascular calcification, thrombosis, and skin necrosis can occur if [Ca] x [PO4] is >4.5 (high mortality)
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PATHOPHYSIOLOGY
 See figure (right)
TREATMENT
 Dietary phosphate restriction and oral phosphate binders
(sevelamer) to reduce hyperphosphataemia
 Calcium supplements and calcitriol to improve hypocalcaemia
 Calcimimetics (sensitises parathyroid to Ca2+   PTH) for
hyperparathyroidism

Parenchymal kidney disease

GLOMERULAR DISEASE
Glomerular disease can present anywhere on a spectrum from:
 Asymptomatic urinary abnormalities
(proteinuria/haematuria)
 Nephritic syndrome (acute GN, RPGN)
 Nephrotic syndrome
 ESRD
DIAGNOSTIC APPROACH TO GLOMERULAR DISEASE
 Labs: CBC, U&E, albumin, lipids
 Urinalysis (R&M/C&S)
 Imaging – CXR and renal U/S
 Renal biopsy
 Indicated in: nephrotic syndrome (not diabetic), AKI or CKD (unknown cause), and renal transplant dysfunction
 Aetiological investigations:
 Anti-GBM
 Complement levels
 ANCA
 Anti-streptolysin titres
 Serum immunoelectropheresis
 Urine immunoelectropheresis (for Bence-Jones protein)
EFFECTS OF GLOMERULAR DISEASE
 Damage to glomerulus  restriction of blood flow  compensatory increase in blood pressure
 Damage to filtration mechanism  protein and/or blood enter urine
 Loss of filtration capacity  kidney injury
Proteinuria
 Hallmark of nephrotic syndromes
 Typical investigations:
 24-hr urine protein – gold standard
 Urine dipstick – most common
 Urine ACR (or PCR) – recommended
 Corrects for the degree of urinary concentration/dilution
AETIOLOGY
 Physiologic (exercise, fever, CHF, orthostatic)
 Pathologic
 Tubulointerstitial (impaired reabsorption) – e.g. Fanconi syndrome ( proximal tubule reabsorption) (not due to albumin)
 Glomerular (i.e. nephrotic syndrome – due to albumin)
 Overflow ( production of low molecular weight proteins) – e.g. multiple myeloma, amyloidosis, MGUS (not due to albumin)
Haematuria
 Hallmark of nephritic syndromes
ASSESSMENT AND CLASSIFICATION
 Pseudohaematuria (-ve dipstick, no RBCs) – food, dyes, medication
 Haemoglobin (+ve dipstick, -ve RBCs) – haemolysis
 True haematuria (+ve dipstick, +ve RBCs) – renal or urologic
 Microscopic – glomerular (GN or IgA nephropathy) or non-glomerular (nephrolithiasis, UTI, or BPH)
 Macroscopic – painful (nephrolithiasis, UTI, or BPH) or non-painful (bladder or kidney cancer)
 Myoglobin (+ve dipstick, -ve RBCs) – rhabdomyolysis
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Nephritic syndrome
Typically characterised as:
 Haematuria (with red cell casts)
 Hypertension / fluid overload
 Oliguria
 Proteinuria (<3.5g/24hr)
 Azotaemia
 Often reduced renal function
Glomerulonephritis presenting with nephritic syndrome
CLASSIFICATION

PATHOPHYSIOLOGY
Nephritic syndrome is typically seen in inflammatory glomerular diseases (highest incidence seen in 5-15 year olds).
Causes of Nephritic Syndrome
DISORDER PATHOPHYSIOLOGY CLINICAL PRESENTATION INVESTIGATIONS/PATHOLOGY TREATMENT

ANTI-GLOMERULAR BASEMENT MEMBRANE MEDIATED (CAUSE TYPE I RPGN)

Anti-GBM disease Antibodies against type IV Presents with RPGN (AKI and  LM:  Plasmapheresis
collagen present in GBM (renal- nephritic syndrome)  Collapsed glomerulus  Immunosuppressives
limited)  Crescents of proliferated parietal epithelial cells  Steroids
and fibrin (become sclerosed over time)
 Diffuse WBC infiltration
 EM: focally disrupted GBM Progression to CKD if untreated, but
 IF: linear IgG (collapsed glomerulus) possible recovery with treatment

Goodpasture Antibodies against type IV Presents with RPGN (AKI and  Identical to anti-GBM disease  Plasmapheresis
syndrome collagen present in GBM and nephritic syndrome) and  Additionally:  Immunosuppressives
lungs haemoptysis  Iron-deficiency anaemia  Steroids
 Haemosiderin-filled macrophages in sputum
 Consolidation on CXR As above

Alport syndrome Inherited defect in type IV Asymptomatic haematuria and  LM: non-specific Supportive
collagen proteinuria with sensorineural  EM: GBM thickening/splitting/lamination
deafness and eye disorders  IF: non-specific Progression to CKD in 100% of cases

IMMUNE COMPLEX MEDIATED (CAUSE TYPE II RPGN)

Post-infectious GN Typically, follows GAS infection Nephritic syndrome following  LM: marked diffuse proliferation; WBC infiltration Supportive
(usually 2-6 weeks prior); caused flu-like illness  EM: sub-epithelial immune complexes
by streptococcal pyrogenic  IF: granular IgG, IgM, C3
Most common in exotoxin B   serum C3 levels
children   anti-streptolysin antibodies Typically, self-limiting

IgA nephropathy Typically, follows URT/GI Episodic gross haematuria (or  LM: mesangial proliferation Supportive
infection (usually a few days persistent microscopic haematuria)  EM: mesangial immune complexes
Most common in prior); caused by IgA deposition  IF: mesangial IgA
adults in mesangium   serum IgA / normal C3 Progression to CKD in 25% of cases

IgA vasculitis Small vessel vasculitis (systemic Presents in children with a typical  Identical to IgA nephropathy Supportive
Henoch-Schönlein form of IgA nephropathy) triad of purpura (esp. buttocks/legs),
purpura arthralgia, and abdominal pain Typically, self-limiting (long-period)

 SLE (can present as any of the glomerular syndromes – nephrotic most common)
Other (with  C3)  Cryoglobulinaemia (IgM and IgG precipitate at reduced temperatures and cause immune complex deposition; associated with  C3 and Hep. C)
 Infective endocarditis

PAUCI-IMMUNE/ANCA-ASSOCIATED VASCULITIS (NO FINDINGS ON IMMUNOFLUORESCENCE) (TYPE III RPGN)

Granulomatosis Small vessel vasculitis with  Kidney  RPGN  ANCA-c positive (proteinase 3 – PR3)  Plasmapheresis
with polyangiitis granulomas affecting:  Lungs  haemoptysis / cavitation  Immunosuppressives
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(GPA)  Kidney  Nasopharynx  ulcers / bleeding  Steroids

Wegener’s  Lung
granulomatosis  Nasopharynx/sinuses Severe with high relapse rates

Microscopic Small vessel vasculitis Identical to GPA but no  ANCA-p positive (myeloperoxidase – MPO)  Plasmapheresis
polyangiitis nasopharyngeal involvement  Immunosuppressives
 Steroids

Mild with low relapse rates

Eosinophilic Small vessel vasculitis with Associated with asthma/rhinitis  ANCA-p positive (myeloperoxidase – MPO)  Plasmapheresis
vasculitis granulomas  Immunosuppressives
Churg-Strauss  Steroids

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

Rapidly progressive (crescentic) glomerulonephritis (RPGN) is a subset
of nephritic syndrome in which the clinical course proceeds over weeks to
months (AKI and nephritic syndrome):
 Most forms of GN can cause RPGN (not MCD)
 Classified by immunofluorescence staining:
 Type 1: anti-GBM mediated (15% of cases)
 Type 2: immune-complex mediated (25% of cases)
 Type 3: pauci-immune (non-immune mediated) (60% of cases)
 Type 4: double antibody positive

Strongly associated with end-stage renal disease (ESRD) if left untreated

(due to large loss of nephron units).

Nephrotic syndrome
Typically characterised as:
 Proteinuria (>3.5g/24hr)
 Hypoalbuminaemia
 Oedema
 Hyperlipidaemia/hyperlipiduria (side-effect of  albumin production)
 Often normal renal function

Note: also associated with infection (encapsulated bacteria) and thromboembolism .

PATHOPHYSIOLOGY
Nephrotic syndrome is typically seen in non-inflammatory glomerular diseases.
 Characterized by increased permeability of glomerular capillary wall to plasma proteins (due to alterations in structural
components of glomerular filtration barrier - mainly podocytes - the main barrier against albumin filtration)
 Typically, occurs in paediatric patients (<5 years old) with an idiopathic aetiology
Causes of Nephrotic Syndrome
CLINICAL INVESTIGATIONS TREATMENT
DISORDER DESCRIPTION
PRESENTATION

PRIMARY (IDIOPATHIC)
Focal segmental Idiopathic Nephrotic  LM: focal, segmental, sclerosis (non-proliferative) Various (e.g. steroids,
glomerulosclerosis syndrome  EM: foot process effacement immunosuppressives, and
 IF: focal segmental IgG and C3 ACEi/ARBs)
Most common in adults
Slow progression to CKD

Membranous nephropathy 75% of cases are due to HLA-related Nephrotic  LM: GBM thickening with ‘spike’ formation (silver stain) Various (e.g. steroids,
autoimmune disease against syndrome (non-proliferative) immunosuppressives, and
Membranoproliferative phospholipase A2 receptor (PLA2R)  EM: sub-epithelial immune complex deposits and foot ACEi/ARBs)
disease presents similarly but on podocytes process effacement
with cellular proliferation  IF: granular IgG and C3 Variable (1/3rd remission, 1/3rd ESRD,
(associated with low C3) 1/3rd persistent proteinuria)

Minimal change disease Idiopathic Nephrotic  LM: minimal change Steroids and ACEi/ARBs
syndrome  EM: foot process effacement
Most common in children  IF: minimal change Responds well to treatment

SECONDARY (SYSTEMIC DISEASES AFFECTING KIDNEY)

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Diabetes mellitus Diabetic nephropathy – presence of microalbuminuria or overt nephropathy (e.g. macroalbuminuria) in
patients with diabetes mellitus who lack indicators of other renal disease (most common cause of ESRD)

Pathophysiology:
 Glomerular lesions
 Glomerular basement membrane thickening
 Progressive glomerulosclerosis (diffuse > nodular)
 Nodular type (Kimmelstiel-Wilson lesions) – specific to diabetes
 Accelerated atherosclerosis
 Hyaline arteriolosclerosis of renal arterioles
 Autonomic neuropathy (affects bladder leading to functional obstruction / obstructive nephropathy)
 Papillary necrosis (may present as renal colic or obstruction ± hydronephrosis)

Note: diabetic nephropathy is strongly associated with diabetic retinopathy

Amyloidosis Nodular deposits of amyloid in mesangium (can be primary or associated with multiple myeloma or chronic inflammatory disease – e.g. RA)

SLE Can present as any of the glomerular syndromes – nephrotic most common (associated with low C3)

Others Medication (NSAIDS; treated with corticosteroids); infection (Hep. B/C, HIV); malignancy

General management principles

 Conservative:
 Treat underlying cause
 Na/H2O restriction
 Vaccination against encapsulated organisms in nephrotic syndrome (S. pneumoniae, H. influenzae, N. meningitidis)
 VTE prophylaxis in nephrotic syndrome
 Medical:
 RAAS blockade (diminish progression of proteinuria and renal disease)
 Diuretics
 Statins
 Anti-hypertensives
 Corticosteroids/immunosuppression (e.g. ciclosporin)
 Renal replacement therapy (i.e. dialysis or transplant)
COMPLICATIONS OF NEPHROTIC SYNDROME
 Susceptibility to infections –  serum IgG / complement activity / T cell function
 Thromboembolism – hypercoagulable state due to  clotting factors and platelet abnormalities
 Hyperlipidaemia –  cholesterol and triglycerides due to hepatic lipoprotein synthesis in response to low oncotic pressure
TUBULOINTERSTITIAL DISEASE
Tubulointerstitial nephritis is defined as cellular infiltrates affecting primarily the renal interstitial and tubular cells.
 Can be defined as acute or chronic (or acute tubular necrosis – ‘super-acute’)
 Acute tubulointerstitial nephritis represents a significant proportion of acute kidney injury
CLINICAL PRESENTATION
 Non-specific (can cause, for example, distal RTA, proximal RTA, and salt-wasting nephropathy)

Vascular diseases of the kidney

CLASSIFICATION
Vascular disease of the kidney can be related to large vessel or small vessel disease .
 Large vessel – renal infarction, renal artery stenosis, renal vein thrombosis
 Small vessel – hypertensive nephrosclerosis and others
LARGE VESSEL KIDNEY DISEASE
Renal infarction
An important (potentially reversible) cause of renal failure.
 Caused by any acute artery occlusion (trauma, surgery, embolism, vasculitis)
CLINICAL PRESENTATION
 Symptoms: flank pain, fever, nausea and vomiting
 Signs: acute onset of new or worsening HTN
DIAGNOSIS
 Imaging: renal arteriography (gold-standard) or contrast-enhanced CT/MR-angiography
TREATMENT
 Prompt localisation of occlusion and restoration of blood flow (e.g. anticoagulation , thrombolysis , thrombectomy , or angioplasty)
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Renal artery stenosis

Renal artery stenosis is the most common cause of secondary hypertension (caused by  RAAS activation due to  renal perfusion).
 Associated with large vessel disease elsewhere (the combination of PVD and HTN is renal artery stenosis until proven otherwise)
 Typically, caused by atherosclerotic plaque (90%); occasionally, caused by fibromuscular dysplasia (10%) – esp. in young women
DIAGNOSIS
 Screening: doppler U/S
 Definitive: renal arteriography (gold-standard) or contrast-enhanced CT/MR-angiography
TREATMENT
 Medical: anti-hypertensives (ACEi if unilateral; contraindicated if bilateral)
 Surgical: percutaneous angioplasty ± stent (nephrectomy if refractory)
Renal vein thrombosis
Renal vein thrombosis occurs in hypercoagulable states (e.g. cancer, infection, nephrotic syndrome, coagulopathy).
 Classically presents as pulmonary embolism with flank pain
DIAGNOSIS
 Screening: doppler U/S
 Definitive: renal arteriography (gold-standard) or contrast-enhanced CT/MR-angiography
TREATMENT
 Thrombolytic therapy ± percutaneous thrombectomy
 Anticoagulation
RENAL HYPERTENSION
Primary hypertension can cause kidney disease (hypertensive nephrosclerosis ); and conversely, kidney disease can cause secondary
hypertension (renal parenchymal hypertension ).
Chronic hypertensive nephrosclerosis
CLINICAL PRESENTATION
 Hypertension (typically with underlying CKD)
 Mild proteinuria (haematuria is seen in malignant nephrosclerosis )
TREATMENT
 ACEi/ARB are first line treatment
OUTCOME
 Can progress to renal failure despite patient adherence.

Cystic disease of the kidney

CYSTIC KIDNEY DISEASE
Adult polycystic kidney disease
Adult polycystic kidney disease (AD-PCKD) is an autosomal dominant condition that causes epithelium-lined cavities filled with fluid
or semi-solid debris in the kidney and other organs.
 At least two genes: PKD1 (more common) and PKD2
 PKD1 encodes a protein responsible for cell-cell and cell-matrix interaction and sensing fluid flow by associating with cilia
 PKD2 encodes a protein that is a calcium channel associated with cilia
 Defect leads to abnormal proliferation and apoptosis of tubular epithelial cells leading to cyst growth
 Likely, a two-hit phenomenon (heterozygous mutation with accumulated ‘somatic mutations’ that precipitate the condition)
FEATURES
 Polycystic changes are always bilateral and can present at any age (may enlarge up to 10x normal size)
CLINICAL PRESENTATION
 Often asymptomatic (discovered on imaging or by family screening)
 Clinical manifestations are rare if <30 years old
 Symptoms: abdominal pain, haematuria, nocturia, UTI
 Signs: hypertension (due to intrarenal arterial compression by cysts) and palpable kidneys
 Common extra-renal manifestations: hepatic cysts, mitral valve prolapse, cerebral aneurysm, diverticulosis
DIAGNOSIS
 Radiographic diagnosis : best accomplished by renal U/S (abdominal CT with contrast for equivocal cases)
 Labs: CBC, U&E, urinalysis (R&M/C&S)
 Genetic linkage analysis (family screening for PKD1 and PKD2)
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 Neuroimaging (if family history of aneurysmal haemorrhages)

TREATMENT
 Goal of treatment is to preserve renal function and treat complications
 Education:
 Educate patient and family about disease, manifestation and inheritance
 Advise to avoid contact sports due to risk of kidney injury
 Treatment:
 Overhydration – may inhibit cyst development
 Antihypertensives (ACEi/ARB) – for hypertension
 Antibiotics (cotrimoxazole) – for UTI or cyst infection
 Renal replacement therapy – for ESRD
 Diseases does not recur in transplanted kidneys

OUTCOMES
 Variable progression in renal functional impairment (ESRD in up to 50% by age 60)
Autosomal recessive polycystic kidney disease
Autosomal recessive polycystic kidney disease (AR-PCKD) is an autosomal recessive condition similar to AD-PCKD.
 Less common than AD-PCKD
 Clinical manifestations occur perinatally
CLINICAL PRESENTATION AND DIAGNOSIS
 Prenatal ultrasound diagnosis – enlarged kidneys
 Typically, perinatal death – respiratory failure
 Patients who survive perinatal period develop CHF, HTN, CKD, and liver failure (death in first few years of life if untreated)
TREATMENT
 Kidney and/or liver transplant
Medullary sponge kidney
Medullary sponge kidney is an autosomal dominant disorder which causes multiple cystic dilations in the collecting ducts of the kidney.
 Associated with renal stones , haematuria , and recurrent UTIs but not with renal failure
 Characteristic appearance on IV pyelogram (‘bouquet of flowers’)

End-stage renal disease

END-STAGE RENAL DISEASE
End-stage renal disease represents a decline in kidney function requiring renal replacement therapy (dialysis or renal transplantation )
which can occur over days to weeks (AKI) or months to years (CKD) (or a combination of the two).
RENAL REPLACEMENT THERAPY

Dialysis
Peritoneal versus Haemodialysis
PERITONEAL DIALYSIS HAEMODIALYSIS

Mechanism Blood is filtered through the peritoneum via osmotic pressure Line from AV fistula to artificial kidney which uses hydrostatic
due to dextrose dialysate introduced via an indwelling pressure to filter blood via a semi-permeable artificial
catheter in the peritoneal cavity (which is drained) membrane

Rate Slow Fast

Location Home Hospital (usually); although can be delivered at home

Indication Young, high functioning, residual renal function Bed-bound, comorbidities, no renal function

Complications Infection, peritonitis, poor clearance if large body mass Infection, vascular access, bleeding

Renal transplantation
Renal transplantation (deceased or living donor) provides the maximum replacement of GFR.
 Preferred modality in CKD (but not in AKI)
 Only therapy shown to improve survival in CKD patients with ESRD
 Effective at reversing uraemic syndrome
 Native kidneys typically left in-situ
 Transplant kidney typically placed in iliac fossa, and transplant renal artery anastomosed to external iliac artery of recipient
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COMPLICATIONS
 Transplant rejection
 Infection (due to immunosuppression)
 Cardiovascular disease (top cause of mortality in transplanted patients)
Key medications used in Renal Transplant Medicine
CYCLOPHOSPHAMIDE
 MoA: irreversible cross-linking of DNA (at guanine nucleobases) which leads to cell apoptosis (particularly in T-cells)
CYCLOSPORIN A
 MoA: binds to calcineurin-calmodulin complex and inhibits phosphorylation of transcription factors required for interleukin and
other cell signalling molecule production (highly T cell and lymphocyte specific)
 Adverse effects: nephrotoxic, neurotoxic, gingival hypertrophy, hirsutism
MYCOPHENOLATE
 MoA: non-competitive inhibitor of an enzyme in the purine synthesis pathway (lymphocytes are highly dependent on this pathway)
 Adverse effects: GI irritation and ulceration, leukopenia (dose dependent)
TACROLIMUS
 MoA: similar to cyclosporin (but more efficient)
 Adverse effects: as for cyclosporin, but also diabetes

Nephrolithiasis
RENAL STONES (NEPHROLITHIASIS)

CLASSIFICATION

Classification of renal stones

TYPE FREQUENCY AETIOLOGY AND CHARACTERISTICS URINARY PH
Calcium ~80% Most common causes are:  pH (calcium phosphate)
oxalate/calcium  Idiopathic hypercalciuria  pH (calcium oxalate)
phosphate  Primary hyperparathyroidism

Characteristics:
 Radiopaque
 Oxalate  spiky
 Phosphate  smooth

Struvite ~10% Associated with urease-producing organisms (e.g. proteus mirabilis)  pH

Characteristics:
 Forms staghorn calculi (perpetuates UTI because stone harbours bacteria)
 Radiopaque

Uric acid <10% Associated with gout, xanthine oxidase deficiency, and high purine turnover  pH
states (e.g. chemotherapy)

Characteristics:
 Radiolucent (but detectable by CT)
 Smooth and brown

Cystine Rare Due to defect in renal transport of certain amino acids (COLA – cystine,  pH
ornithine, lysine, arginine)

Characteristics:
 Hexagonal yellow crystals
 Positive urinary cyanide nitroprusside test
 Radiopaque

PATHOPHYSIOLOGY
 Stone formation is a result of supersaturation of stone constituents (crystal formation around a stone nidus)
 Contributory factors: low urine flow or volume, urine stasis, or low urinary citrate (prevents supersaturation)
FEATURES
 Risk factors:
 Lifestyle: low fluid intake, specific diets (e.g. high protein or salt)
 Medications: loop diuretics, chemotherapy
 Medical conditions: UTI, gout, obesity, hyperparathyroidism
 Hereditary: RTA, other enzyme deficiencies
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 Most commonly occurs in older men (M:F = 3:1); there is a high recurrence rate
 The three narrowest passage points for upper tract stones are:
 Pelviureteric junction
 Pelvic brim (where ureter crosses common iliac artery bifurcation)
 Vesicoureteric junction
CLINICAL PRESENTATION
 Urinary obstruction causes upstream distension
 Non-colicky flank pain from renal capsular distension
 Colicky flank pain that may radiate to testes/penis or vulva from ureter distension
 Associated with nausea and vomiting
 Patients classically unable to get comfortable (as opposed to peritonitis)
 If fever, must rule out pyelonephritis
DIAGNOSIS
 Labs: CBC, U&E and uric acid, urinalysis (R&M/C&S)
 Urine analysis may show gross/microscopic haematuria (85%) and an altered urine PH
 Imaging:
 First-episode: KUB non-contrast CT scan
 Follow-up: KUB X-ray
 Paediatric/obstetric: abdominal U/S (to avoid radiation)
 Bladder stones: cystoscopy
 Additional labs (if recurrent calcium stone formers or paediatric cases): PTH and electrolytes (including oxalate, citrate, cystine)
TREATMENT
 Admit if necessary
 Acute treatment:
 Medical treatment:
 Supportive – IV fluids (does not help with stone passage), analgesia (diclofenac 75mg IM), anti-emetics , antipyretics
 Medical expulsion therapy (MET) – α-blockers or calcium channel blockers can be used to facilitate stone passage
 Note: stones <5mm can typically pass through urethra
 Antibiotics if infection present
 Interventional treatment (if obstruction dangerous – e.g. sepsis, renal failure, or hydronephrosis)
 First line – ureteric stent (via cystoscopy)
 Second line – image-guided percutaneous nephrostomy
 Elective treatment:
 Conservative if no complications
 Treatment specific to stone type:
 Calcium – hydration,  dietary Na/protein, alkalinize urine with sodium bicarbonate (if oxalate), thiazide diuretics
 (note: do not decrease calcium intake as it can lead to hyperoxaluria and osteoporosis)
 Struvite – hydration, antibiotics , surgical removal of staghorn stones
 Uric acid – hydration, alkalinize urine with sodium bicarbonate, allopurinol
 Cystine – hydration,  dietary Na/protein, alkalinize urine with sodium bicarbonate, penicillamine
 Interventional:
 Kidney stones:
 Extracorporeal shockwave lithotripsy (ESWL) if stone <2cm
 Percutaneous nephrolithotomy (PNL) if stone >2cm
 Ureteral stones:
 ESWL
 Ureteroscopic lithotripsy (URS)
 Bladder:
 Transurethral stone removal (or removal of outflow obstruction – e.g. TURP)

Urinary tract infection

URINARY TRACT INFECTION

FEATURES
 Overwhelmingly more common in females (location of urethral orifice)
CLASSIFICATION
 Sterile pyuria – typically contamination (also STI, TB, tumours, interstitial nephritis)
 Asymptomatic bacteriuria – relatively common (esp. if catheterised)
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 Only important in two main scenarios:

 Pregnancy – increased risk of pre-term delivery and upper UTI
 Urological procedures
 Uncomplicated lower or upper UTI – occurs only in young, sexually active, females
 Aetiology: E. coli (70%) and S. saprophyticus (rest)
 Complicated lower or upper UTI – occurs in the rest of cases
 Aetiology: E. coli (70%) and other atypical bacteria (Proteus, Pseudomonas, Enterobacter, Enterococcus)
CLINICAL PRESENTATION
 Lower UTI – dysuria, frequency, urgency, haematuria, suprapubic pain
 Upper UTI – as per lower UTI but with more severe symptoms (fevers/chills, nausea/vomiting, flank pain)

Note: may present as confusion/delirium in elderly.

DIAGNOSIS
 Uncomplicated lower UTI – no investigation required
 Complicated lower UTI – urine culture required
 Upper UTI
 Labs: CBC, U/E, urinalysis (R&M/C&S) ± blood cultures
 Imaging: U/S (if refractory – looking for abscess)
TREATMENT
 Uncomplicated lower UTI
 Empirical therapy: trimethoprim (3/7) or nitrofurantoin (7/7)
 Uncomplicated upper UTI
 Supportive: fluids, analgesia, antiemetic , antipyretic ; consider admission
 Empirical therapy: single dose IV gentamicin + oral co-trimoxazole (10/7)
 Complicated UTI – as per uncomplicated, but treat for longer (e.g. 14/7) and guide treatment by cultures
Recurrent uncomplicated UTI
 Suggestive of colonic colonisation ; urine culture indicated
 Treatment: long-course prophylactic antibiotics (12 weeks) (most likely work by altering gut flora)
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Gastroenterology.
General principles
GASTROINTESTINAL BLEEDING
Gastrointestinal bleeding presents as haematemesis, haematochezia (fresh blood in stool), or malaena (black, tarry stools).
 Upper GI bleeding occurs proximal to ligament of Treitz (i.e. duodenum and higher)
Features of upper and lower GI bleeding
VARIABLE UPPER GI BLEEDING LOWER GI BLEEDING

Clinical  Haematesis (‘coffee-grounds’)  Haematochezia > malaena (but can be either)

presentation  Malaena > haematochezia (very severe)
 Hypovolaemia (e.g. tachycardia, hypotension, light-
headedness)

Severity classified by Rockall or Blatchford scores

Aetiology  Above GE junction: epistaxis, oesophageal varices, Mallory- Diverticulosis (60%), angiodysplasia, IBD, haemorrhoids, fissures,
Weiss tear, oesophagitis, oesophageal cancer neoplasm, AVM, infection, upper GI bleed (if brisk)
 Stomach: PUD, gastritis, gastric cancer, GAVE, Dieulafoy lesion
 Duodenum: PUD
 Other: coagulopathy, AVM

Initial  Stabilise (1-2 large bore IVs, NBM, IV fluids/blood, monitor)  Stabilise (1-2 large bore IVs, NBM, IV fluids/blood, monitor)
management  Labs: CBC, cross match, coagulations, U&E, LFTs  Labs: CBC, cross match, coagulations, U&E, LFTs
 NGT can determine upper vs lower bleeds in some cases Haemodynamically unstable:
 Endoscopy (OGD): establish bleeding site + treat lesion  Colonoscopy and OGD (potentially upper GI)
 Treatment: haemospray, ligation, adrenaline, haemostasis Haemodynamically stable:
 PUD: IV PPI (decreases risk of rebleed)  Colonoscopy or flexible sigmoidoscopy
 Variceal bleeds: IV octreotide (decreases portal HTN)  Further scans:
 IV erythromycin (accelerates gastric emptying to remove  SLOW bleeding – Tc-99m RBC scan
clots)  RAPID bleeding – angiography ± embolisation

Long-term Follow-up endoscopy; dependent on underlying cause Depends on underlying cause

management

PROCEDURES
Explanation of gastrointestinal endoscopy procedures
UPPER ENDOSCOPY (GASTROSCOPY) COLONOSCOPY ERCP CAPSULE ENDOSCOPY
Reason  Diagnose and treat conditions of the oesophagus,  Diagnose and treat conditions of the colon  Diagnose and treat conditions of the bile ducts  Diagnose conditions of the small bowel
stomach, and duodenum and pancreas

Pre-procedure  Outpatient procedure  Outpatient procedure  Admitted before procedure  No food for 10 hours before procedure
 Do not take any medications (except inhalers)  Do not take any medications (except inhalers)  Do not take any medications (except inhalers)  No fluid for 4 hours before procedure
 Tell doctor about blood-thinners  Tell doctor about blood-thinners  Tell doctor about blood-thinners
 Cannot eat/drink before procedure (>4 hours)  Bowel preparation  Cannot eat/drink before procedure (>8 hours)

Procedure  Two choices:  Two choices:  One choice: Process:

 Sedation (IV cannula) (+ throat anaesthesia)  Sedation (IV cannula)  Sedation (IV cannula) (+ throat anaesthesia)  A capsule is swallowed with a camera
 Throat anaesthesia  No sedation  Lie on stomach (disposable and passes within 1 to 2 days)
 Camera: mouth  oesophagus  stomach   Camera: anus  large bowel  small bowel  Camera: mouth  oesophagus  stomach   A radio recorder is worn around your waist
duodenum  Procedures: duodenum  papilla (you should not remove this)
 Procedures:  Biopsies  Procedures:  No sedation is required
 Biopsies  Polypectomy  Inject X-ray dye (and X-rays taken)  Eating:
 Dilation  Papillotomy  No eating/drinking in first 2 hours
 Haemostasis 20m-1hr in most cases  Stone removal  Fluid after 2 hours
 Stent placement  Food after 4 hours
20m-1hr in most cases
20m-1hr in most cases 8 hours (plus 1 hour to attach/remove system)

Post-procedure  Cannot drive for 24 hours if sedation  Cannot drive for 24 hours if sedation  Cannot drive for 24 hours if sedation  Results sent to GP
 Accompanied for the evening if sedation  Accompanied for the evening if sedation  Discharged to ward (most leave afternoon)  May require further treatment
 Results sent to GP  Results sent to GP  Accompanied for the evening if sedation
 Dietary restriction may be in place
 Results sent to GP

Risks Common: Common: Common: Uncommon:

 Throat/abdominal discomfort  Abdominal discomfort  Throat/abdominal discomfort  1% have difficulty passing the capsule
 Feeling unwell with sedation  Small amount of bleeding/discharge  Feeling unwell with sedation Other: failed procedure (or missed lesions)
Uncommon:  Feeling unwell with sedation  Pancreatitis (5%) – can be severe
 Aspiration  Dehydration/electrolyte issues (bowel prep) Uncommon:
 Bleeding (1/1000) Uncommon:  Aspiration
 Perforation (1/5000)  Bleeding (1/100)  Bleeding (1/200)
Other: failed procedure (or missed lesions)  Perforation (1/1000)  Perforation (1/200)
Other: failed procedure (or missed lesions) Other: failed procedure (or missed lesions)
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Mouth and oesophagus

DYSPHAGIA AND ODYNOPHAGIA
Difficulty swallowing (dysphagia) or pain with swallowing (odynophagia) to abnormalities of the oropharynx or oesophagus.

Dysphagia
CLASSIFICATION
 Oropharyngeal (difficult initiating swallowing  choking, coughing, nasal regurgitation)
 Neurological (e.g. stroke, Parkinson disease) (common)
 Muscular (e.g. myasthenia gravis)
 Structural (e.g. thyromegaly, Zenker’s diverticulum)
 Oesophageal (inability to move food down oesophagus)
 Solid food only  mechanical obstruction
 Progressive ( common)
 Carcinoma (esp. with constitutional symptoms)
 Peptic stricture (esp. with dyspepsia)
 Intermittent
 Lower oesophageal webs or ring
 Solid foods and liquids  neuromuscular disorders
 Progressive (common)
 Achalasia
 Scleroderma (esp. with reflux symptoms)
 Intermittent
 Diffuse oesophageal spasm (DES)
DIAGNOSIS
 Oropharyngeal dysphagia – barium swallow
 Oesophageal dysphagia – OGD (oesophagogastroduodenoscopy) followed by secondary tests (barium swallow, manometry, etc.)

Odynophagia
DIFFERENTIAL DIAGNOSIS
 Infectious oesophagitis
 Erosive oesophagitis (GORD)
 Caustic oesophagitis
 Radiation oesophagitis
 Eosinophilic oesophagitis (associated with allergies in young men)
 Oesophageal cancer (although tends to progress to constant pain)
DIAGNOSIS
 Odynophagia – EGD
INFECTIOUS OESOPHAGITIS
Infectious oesophagitis is severe mucosal inflammation and ulceration as a result of a viral or fungal infection .
PATHOPHYSIOLOGY
 Occurs in immunocompromised patients – candida (most common), HSV, or CMV
CLINICAL PRESENTATION AND DIAGNOSIS
 Odynophagia (rather than dysphagia)
 Diagnosis via endoscopic visualisation and biopsy
TREATMENT
 Candida: antifungal (e.g. fluconazole)
 HSV: antiviral (e.g. acyclovir)
 CMV: antiviral (e.g. ganciclovir)
OESOPHAGEAL MOTOR DISORDERS

AETIOLOGY
 Idiopathic
 Achalasia
 Scleroderma
 Diabetes mellitus
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 DES
Oesophageal motor disorders
DISORDER ACHALASIA SCLERODERMA DIFFUSE OESOPHAGEAL SPASM

Definition Motility disorder of oesophagus Systemic disease characterised by Normal peristalsis interspersed with
characterised by impaired relaxation of vasculopathy and tissue fibrosis (esp. frequent, high pressure, non-
LES and loss of peristalsis skin thickening) – see Rheumatology peristaltic waves

Aetiology Idiopathic Variable (dysphagia caused by reflux, Idiopathic

dysmotility, or both)

Pathophysiology Inflammatory degeneration of myenteric Blood vessel damage  intramural Not elucidated
plexus   LES pressure, incomplete neuronal dysfunction  oesophageal
relaxation of LES,  peristalsis muscle weakening   peristalsis,  LES
tone  reflux  stricture  dysphagia

Diagnosis  CXR: no air in stomach, dilated  Clinical: features of scleroderma  Clinical

oesophagus with fluid level  Manometry (motility study)  Barium: ‘corkscrew’ pattern
 Barium: oesophagus terminates in  Endoscopy: normal
narrowing at LES (‘bird beak’ pattern)  Manometry (motility study): definitive
 Endoscopy: normal
 Manometry (motility study): definitive

Treatment  Balloon dilation of LES +/- GERD  Medical: aggressive GERD therapy  Reassurance
prophylaxis  Surgery: anti-reflux surgery  Various treatments (low evidence)
 Botulinum toxin into LES
 Surgery (myotomy)

OESOPHAGEAL DIVERTICULA
Oesophageal diverticula can be present in any location.
 Zenker diverticulum is defined as cervical outpouching superior to cricopharyngeus muscle (it is a posterior, false, diverticulum)
CLINICAL PRESENTATION
 Chest pain, dysphagia, halitosis, and regurgitation of undigested food
 Commonly associated with motility disorders
DIAGNOSIS
 Barium swallow – will demonstrate outpouchings
TREATMENT
 Surgical excision of the diverticulum (if symptomatic)
 Myotomy of cricopharyngeus (if Zenker diverticulum)
GORD
Gastroesophageal reflux disease (GORD) is a condition where stomach contents (acid) move from the stomach to the oesophagus.
 GORD is not the result of H. pylori
PATHOPHYSIOLOGY
 Inappropriate transient relaxation of LES (most common cause) or low basal LES tone (esp. in scleroderma)
 Contributing factors: gastroparesis, obesity, pregnancy, Zollinger-Ellison syndrome, hiatus hernia
CLINICAL PRESENTATION
 Oesophageal signs and symptoms
 Typical – heart burn, acid regurgitation, sensation of lump in throat, belching
 Atypical – chest pain (can mimic CAD), dysphagia (late), odynophagia (rare)
 Non-oesophageal signs and symptoms
 Respiratory – cough, wheeze, aspiration pneumonia
 Non-respiratory – sore throat, hoarseness, dental erosions
DIAGNOSIS
 Usually, a clinical diagnosis is sufficient (history or relief following pharmacotherapy)
 Endoscopy if red flags (VBAD – vomiting, bleeding, abdominal mass, dysphagia), failure of medical therapy, or long-standing
 24-hour pH monitoring – definitive but rarely performed (most useful if PPIs do not improve symptoms)
TREATMENT
 Lifestyle change (other than weight loss and head-of-bed elevation ) does not help disease (but improves symptoms)
 Non-erosive reflux disease (symptom relief) – PPI or antacids
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 Oesophagitis (aim to heal inflammation) – indefinite PPI or surgical fundoplication

COMPLICATIONS
 Erosive oesophagitis and peptic stricture
 Aspiration pneumonia
 Upper GI bleeding
 Barrett oesophagus (and consequently adenocarcinoma)
PEPTIC STRICTURE
Peptic strictures develop from oesophagitis as a result of long-term GORD.
CLINICAL PRESENTATION
 Progressive dysphagia with a long history of GORD (although reflux symptoms may disappear as stricture develops)
DIAGNOSIS
 Endoscopy or barium swallow
TREATMENT
 Endoscopic dilation
 Indefinite PPI
 Surgical fundoplication
WEBS AND RINGS
Webs (partial occlusions of upper oesophagus) and rings (circumferential narrowing of lower oesophagus) are normal tissue obstructions.
 Schatzki ring – a mucosal ring at squamous-columnar junction above a hiatus hernia (treated by endoscopic dilation )
 Webs – associated with Plummer-Vinson syndrome (triad of iron deficiency anaemia, oesophageal webs, and atrophic glossitis)
 Approximately 10% of patients with Plummer-Vinson will develop oesophageal carcinoma
CLINICAL PRESENTATION
 Typically, asymptomatic (provided peristalsis is normal)
 Intermittent dysphagia with large food boluses
MALLORY-WEISS TEAR
Mallory-Weiss tears are longitudinal lacerations in the distal oesophagus and proximal stomach near the gastroesophageal junction ,
 Typically, caused by excessive vomiting or retching
 Can lead to upper GI bleeding (potentially fatal)
 Boerhaave syndrome is complete effort rupture of the oesophagus (usually normal oesophagus)
CLINICAL SIGNS OF THE MOUTH

CLINICAL SIGNS OF THE MOUTH

 Leucoplakia – oral mucosal white patch that will not rub off and is not attributable to known disease
 Leucoplakia is considered a pre-malignant condition (and should be referred to an oral medicine specialist)
 Aphthous ulcers – painful shallow ulcers on the tongue and oral mucosa that heal without scarring
 Causes: IBD (CD), coeliac disease, Behcet syndrome, HIV
 Cheilitis (angular stomatitis) – fissuring of the corners of the mouth
 Causes: denture issues, candidiasis, iron or vitamin B2 (riboflavin) deficiency
 Glossitis – smooth, red, sore, tongue
 Causes: iron, folate, or B12 deficiency
 Macroglossia – large tongue
 Causes: severe hypothyroidism, acromegaly, amyloid
 Teeth – can be discoloured with childhood tetracycline (yellow), lead (blue), or excessive fluoride (white) exposure

Stomach and duodenal

GASTRITIS
Gastritis is inflammation of the gastric mucosa (determined histologically).
CLASSIFICATION
 Acute gastritis: rapidly developing superficial lesions, often due to NSAID use, alcohol, H. pylori , infection, and severe
illness/stress
 Chronic gastritis:
 Type A (10%): occurs in the fundus and is due to autoantibodies to parietal cells
 Causes pernicious anaemia and is associated with autoimmune disorders and increased risk of malignancy
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 Type B (90%): occurs in the antrum and may be caused by NSAIDs or H. pylori
 Often asymptomatic, but associated with increased risk of peptic ulcers and malignancy
CLINICAL PRESENTATION
 Often asymptomatic; can present with epigastric pain, nausea/vomiting, or bleeding
TREATMENT
 Determined by aetiology (e.g. H. pylori, NSAID)
 Avoid mucosal irritants
 Consider antacids, PPIs, misoprostol
PUD
Peptic ulcer disease is characterised by focal defects in the gastric or duodenal mucosa that result in erosion and/or scarring.
 By definition, penetrate the muscularis mucosa resulting in scarring
 Duodenal ulcers are four-times more common than gastric ulcers
PATHOPHYSIOLOGY
 Caused by an imbalance of defensive and offensive factors:
 Defensive – mucous, bicarbonate, blood flow (affected by smoking), cell-turnover
 Offensive (more important clinically) – H. pylori  drugs (esp. NSAIDs and steroids)  acid  physiological stress (e.g.
ICU)
 Alcohol damages gastric mucosa but rarely causes ulcers
 Up to 15% of cases are idiopathic
 PUD also associated with cirrhosis, COPD, and CKD
CLINICAL PRESENTATION
 Dyspepsia is the most common presenting symptom (only 5% have ulcers – most have functional disease)
 Can interrupt sleep
 Duodenal ulcers: pain Decreases after meal
 Gastric ulcers: pain is Greater after meal
 May present with complications:
 Bleeding (severe if from gastroduodenal artery)
 Perforation (typically anterior – causes peritonitis)
 Gastric outlet obstruction
 Penetration (typically posterior – causes pancreatitis)
 Examination: usually normal, but may reveal epigastric tenderness (or acute abdomen if perforated)
 Red flags (ALARM): Anaemia, Loss of weight, Anorexia, Recent onset/progressive, Melaena/hematemesis, Swallowing difficulty
DIAGNOSIS
 Endoscopy with biopsy (definitive)
 Gastric ulcers must always be biopsied to rule out malignancy (10% of cases); duodenal ulcers are rarely malignant
 H. pylori testing (test and treat strategy, without endoscopy, is acceptable if no alarm features)
 Upright CXR – evaluate free abdominal air (if perforation considered)
 Fasting serum gastrin (if Zollinger-Ellison syndrome suspected)
TREATMENT
 Acute management – see Gastrointestinal bleeding
 Long-term management:
 Specific management dependent on aetiology (e.g. H. pylori or NSAIDs)
 Discontinue exacerbating factors (e.g. NSAIDs, steroids, alcohol, tobacco)
 Medical therapy – PPI
Helicobacter pylori induced ulceration
Helicobacter pylori is a gram-negative flagellated rod that resides in (but does not invade) the gastric mucosa.
 Associated with peptic ulceration, but specific mechanism not elucidated
OUTCOME
 Asymptomatic (non-erosive) gastritis in 100% of patients
 Peptic ulcer in 15% of patients
 Gastric malignancy (gastric carcinoma and MALT) in 0.5% of patients
DIAGNOSIS
 Non-invasive testing
 Serology – useful in a high-risk population
 Antibody titre will remain elevated after eradication (not useful as a test of cure)
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 Stool antigen – useful in a low-risk population (and to document eradication)

 Urea breath test (CLOtest)
 Invasive testing (histology or rapid urease test on biopsy )
TREATMENT
 Triple therapy – two-weeks omeprazole, clarithromycin , amoxicillin (or metronidazole if allergic to amoxicillin)
COMPLICATIONS
 MALT lymphoma is a rare gastric tumour that can present with chronic H. pylori infection (treated with eradication therapy)
NSAID induced ulceration
NSAID usage is strongly associated with peptic ulceration.
PATHOPHYSIOLOGY
 Direct effect: erosions/petechia due to local effect of drug on gastric mucosa
 Indirect effect: systemic reduction in protective prostaglandin synthesis
OUTCOME
 Gastric mucosal petechia e in 100% of patients
 Erosions in >50% of patients
 Peptic ulcers in 25% of patients
TREATMENT
 Reduce (or cease) NSAIDs (or replace with paracetamol )
 Medical therapy – PPI (or combine NSAID with misoprostol if it is indicated – e.g. arthritis)
ZOLLINGER-ELLISON SYNDROME
Zollinger-Ellison syndrome is a rare condition characterised by gastrin-secreting tumours in the duodenum and/or pancreas.
 This leads to  gastric acid production and recurrent, severe, peptic ulcers
CLINICAL PRESENTATION
 Refractory PUD (persistent despite medical therapy)
 Secretory diarrhoea (mucosal damage and malabsorption)
 Hypercalcaemia (association with MEN type 1)
DIAGNOSIS
 Labs:  fasting serum gastrin levels and  gastrin with administration of secretin is diagnostic
 Abdominal CT for staging
TREATMENT
 Symptomatic: high-dose PPI
 Curative: surgical resection

Small and large bowel

GASTROINTESTINAL FLUID LOSSES
Electrolyte abnormalities in gastrointestinal fluid loss
FLUID LOSS ABNORMALITIES
Gastric fluid (vomiting or NGT)  Hypochloraemic metabolic alkalosis (when H+ is excreted, a HCO3 ion is gained into the extracellular space)
 Hypokalaemia (increased RAAS activation due to volume depletion)
 Hyponatraemia (increased ADH activation due to volume depletion)

Diarrhoea  Hyponatraemia (increased ADH activation due to volume depletion)

 Metabolic acidosis (loss of bicarbonate and organic acid anions)
 Hypokalaemia (loss of potassium)
 Hypernatraemia (rarely)
 Metabolic alkalosis (rarely)

Ileostomy or enteroenterofistulae Normal volume loss is less than 1 litre

(fluid loss similar to Addison’s)  Hyponatraemia (can lose >1500mL of fluid/day)
 Hyperkalaemia
 Hypomagnesaemia

DIARRHOEA

CLASSIFICATION
 Acute diarrhoea – passage of more frequent, or loose, stools than normal for <2 weeks
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 Most commonly due to infection (i.e. infectious gastroenteritis)

 Chronic diarrhoea – passage of more frequent, or loose, stools than normal for >2 weeks
 Most commonly non-infectious
 Classification:
 Secretory (e.g. cholera, Zollinger-Ellison syndrome, carcinoid tumours, VIPoma)
 Osmotic (malabsorption – e.g. coeliac disease, Whipple disease, pancreatic insufficiency ) – high stool osmotic gap
 Inflammatory (e.g. IBD)
 Motility (e.g. IBS)

Gastroenteritis (Infectious/traveller’s Diarrhoea)

Bacteria in gastroenteritis
PATHOGEN SOURCE CLINICAL FEATURES DURATION TREATMENT NOTES

Campylobacter Uncooked meat  Diarrhoea (+/- blood) <2 weeks Symptomatic (unless severe Notifiable
(esp. poultry)  Abdominal pain or food handlers, childcare
 N/V workers, pregnant, or
 Fever immunocompromised)

Erythromycin

Salmonella Various (esp. raw  Diarrhoea (profuse +/- blood) <2 weeks Symptomatic (unless severe Notifiable
eggs or dairy)  Abdominal pain or immunocompromised)
 N/V
 Fever Ciprofloxacin

Shigella Various  Diarrhoea (+/- blood) <2 weeks Symptomatic (unless severe Notifiable
 Abdominal pain or immunocompromised)
 N/V
 Fever Guided antibiotics

E. coli O157 Food/water  Diarrhoea (blood) <2 weeks Symptomatic Notifiable

 Abdominal pain
 N/V
 No fever
 HUS (rare – esp. in children)

Clostridium Normally present  Diarrhoea Variable Symptomatic and Primary risk factor is
difficile in colon  Pseudomembranous colitis metronidazole exposure to
 Toxic megacolon (rare) (or vancomycin if severe) antibiotics

Vibrio cholerae Water  Diarrhoea (watery – ‘rice-water’ stool) <2 weeks Ciprofloxacin Notifiable
 No abdominal pain
 N/V High mortality if
 No fever severe and untreated

Protozoa in gastroenteritis
PATHOGEN SOURCE CLINICAL FEATURES DURATION TREATMENT NOTES

Giardia Various  Diarrhoea (greasy, malodorous, floats) Variable Symptomatic and Notifiable
 Indicative of malabsorption (persist) metronidazole (for
 Abdominal pain confirmed giardiasis)
 N/V
 No fever

Cryptosporidium Various  Diarrhoea Variable Symptomatic Notifiable

 No abdominal pain (persist)
 N/V
 No fever

Viruses in gastroenteritis
PATHOGEN SOURCE CLINICAL FEATURES DURATION TREATMENT NOTES

Norovirus Faecal-oral  Diarrhoea <1 day Symptomatic Notifiable

 Abdominal pain
 N/V Primary risk factor is
 No fever cruise ships /
institutions

Rotavirus Faecal-oral  Diarrhoea <1 week Symptomatic Notifiable

 No abdominal pain (rotavirus vaccination)
 N/V Primary risk factor is
 Fever childcare facilities
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DIAGNOSIS
 Laboratory investigation is not routinely indicated for patients with acute diarrhoea
 Faecal culture and microscopy (one sample) is indicated in at-risk patients (young, old, rural, food handlers, child-care
workers)
 Giardia and Cryptosporidium faecal antigen tests are indicated if: persistent, travel, rural, immunocompromised, following
attendance at childcare centre, drinking from untreated water
 Clostridium difficile faecal toxin tests are indicated if this is suspected
 Sigmoidoscopy (rarely done, but useful if bloody diarrhoea and no obvious clinical suspicion) – abnormal mucosa if inflammatory
TREATMENT
 Rehydration (mainstay of therapy)
 Increased fluids (at least 2 litres a day plus 200mL for every loose stool – avoid sugar/caffeine), or
 Oral rehydration therapy (6 tsp sugar, 0.5 tsp salt, in 1 litre water or commercial), or
 IV rehydration if oral intake insufficient to replace fluid loss
 Symptom management:
 Paracetamol (not NSAIDs – as they can cause kidney injury in dehydrated patients)
 Antidiarrheal agents (loperamide) are typically not recommended (often delay excretion of causative pathogens)
 Contraindications: diarrhoea with fever, bloody stool, or diarrhoea caused by C. difficile
 Antiemetics are typically not recommended (a single dose if required)
 Public health measures:
 High risk individuals (food handlers; staff of healthcare or childcare facilities) or others (if persistent/severe)
 Acute gastroenteritis: excluded from work until free of symptoms for 48 hours
 Salmonella/Shigella/VTEC: excluded from work until two consecutive negative faecal specimens (at least 24 hours apart)
CONSTIPATION
Constipation is defined by symptoms: <3 stools per week, stool form that is hard or lumpy, and difficult stool passage
(strain/incomplete).
 Sometimes classified by colon transit time (abdominal X-ray series with radio-opaque markers)
AETIOLOGY
 Most common cause is idiopathic
 DOPED
 Drugs (esp. opiates and antidepressants)
 Obstruction (esp. malignancy)
 Painful anal conditions (e.g. fissures)
 Electrolyte or endocrine dysfunction (hypothyroidism, hypercalcaemia, hypokalaemia, uraemia)
 Depression
TREATMENT
In order of increasing potency :
 Bulk-forming laxatives (e.g. psyllium) – need adequate fluid intake or will exacerbate constipation
 Faecal softeners (e.g. docusate sodium )
 Osmotic laxatives (e.g. lactulose, polyethylene glycol, glycerin )
 Stimulant laxatives (e.g. senna, bisacodyl) – tolerance may occur / risk of laxative abuse
 Enemas and suppositories (e.g. sodium bisphosphate enema , glycerin suppository )
 Prokinetic agents (e.g. prucalopride)
MALDIGESTION AND MALABSORPTION

DEFINITIONS
 Maldigestion – inability to break down large molecules in the lumen of the intestine into their component small molecules
 Malabsorption – inability to transport molecules across the intestinal mucosa into circulation
 Malassimilation – encompasses both maldigestion and malabsorption
AETIOLOGY

Causes of maldigestion and malabsorption

MALABSORPTION MALDIGESTION
 Inadequate absorptive surface  Inadequate mixing of food with enzymes (e.g. post-gastrectomy)
 Infection (e.g. Whipple’s disease, Giardia)  Pancreatic exocrine deficiency
 Inflammatory (e.g. coeliac, IBD)  Bile salt deficiency
 Infiltration (e.g. malignancy, amyloidosis)  Cholestasis
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 Fibrosis (e.g. systemic sclerosis, radiation enteritis)  Terminal ileal disease (impaired bile salt recycling)
 Bowel resection (length, site, and location – all important factors)  Bacterial overgrowth (deconjugation of bile salts)
 Drug-induced (e.g. cholestyramine)  Specific enzyme deficiencies
 Endocrine (e.g. diabetes)

CLINICAL PRESENTATION
 Symptoms vague unless disease is severe (e.g. weight loss, diarrhoea, steatorrhea, weakness, fatigue, and failure-to-thrive in children)
Basics of absorption and digestion
DEFICIENCY ABSORPTION/DIGESTION CLINICAL PRESENTATION INVESTIGATIONS
Iron  Duodenum and upper jejunum Hypochromic microcytic anaemia;   Hb,  serum Fe,  serum ferritin
glossitis; koilonychia (spoon nails)

Calcium  Duodenum and upper jejunum Metabolic bone disease; or effects of   serum Ca / Mg
hypocalcaemia (see Electrolyte disorders)   ALP
Calcium binds to calcium binding protein  DEXA ( bone mineralisation)
in cells; levels increased by vitamin D.
Calcium malabsorption typically causes 
bone density (rather than hypocalcaemia)
as serum calcium levels protected by
leaching calcium from bone.

Folic acid  Jejunum Megaloblastic anaemia; glossitis   serum folic acid

Vitamin B12  Ileum (also only place to bind bile acids) Subacute combined degeneration of the   serum B12
spinal cord; megaloblastic anaemia;  Anti-IF antibodies, anti-parietal cell
B12 binds to intrinsic factor (IF) secreted dementia; glossitis antibodies, and atrophic gastritis in
by stomach and binds to transcobalamin pernicious anaemia
in the ileum.

Carbohydrate  Monosaccharides absorbed in Generalised malnutrition and weight loss;  Hydrogen breath test (detects poor
duodenum and jejunum diarrhoea absorption or bacterial overgrowth)
 Complex polysaccharides hydrolysed to  D-xylose test (detects poor absorption or
oligosaccharides and disaccharides by bacterial overgrowth)
salivary and pancreatic enzymes  Trial of carbohydrate-restricted diet
 Small bowel biopsy

Protein  Absorption primarily in the jejunum Generalised malnutrition and weight loss   serum albumin
 Digestion at stomach, brush border, and
inside cell

Fat  Fatty acids diffuse into cell cytoplasm Generalised malnutrition and weight loss;   faecal elastase (chronic pancreatitis)
 Lipase, co-lipase, phospholipase A diarrhoea +/- steatorrhea   lipase (acute pancreatitis)
(pancreatic enzymes) and bile salts  Quantitative stool fat test
needed for digestion  Small bowel biopsy
 Products of lipolysis form micelles which  MRCP/ERCP
solubilise fat and aid in absorption

Fat-soluble  Vitamins: ADEK  Vitamins: ADEK Occurs in the presence of issues with fat
vitamins  A: dietary sources  A: night blindness, dry skin and eyes digestion or absorption
 D: skin (via UV light) or dietary sources  D: osteomalacia (in adults) or rickets
 E: dietary sources (in children)
 K: synthesised by intestinal flora  E: retinopathy, neurological issues
 K: prolonged INR and bleeding

Bile acid diarrhoea

Bile acid diarrhoea is a commonly unrecognised condition that results from ileal disease (resection or inflammation – e.g. Crohn
disease).
 Due to loss of enterohepatic circulation , and consequent stimulation of water secretion and motility in the colon by bile salts
 Treated with bile acid sequestrants (cholestyramine)
Lactase deficiency
Lactose intolerance results from a deficiency of lactase (a brush-border enzyme that hydrolyses lactose into glucose and galactose).
CLINICAL PRESENTATION
 Non-specific gastrointestinal symptoms (bloating, flatulence, cramping, and diarrhoea) following milk ingestion
 Often follows gastroenteritis
DIAGNOSIS
 Treatment-as-diagnosis – lactose-free diet
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 Hydrogen breath test ( hydrogen following ingestion of lactose)

TREATMENT
 Lactose-free diet
 Oral lactase enzyme replacement

Coeliac disease
Coeliac disease is a chronic autoimmune condition against dietary gluten that causes gastrointestinal inflammation and tissue damage .
 Gluten is found in barley, rye, and wheat (oats are controversial)
PATHOPHYSIOLOGY
 Inappropriate T-cell and IgA mediated response against gluten (specifically gliadin ) in genetically predisposed persons
 Associated with HLA-DQ2/DQ8
 Leads to villous atrophy (in the duodenum and jejunum) and hyperplastic glands with dense lymphocytic inflammation

Note: villous atrophy is also seen in small bowel bacterial overgrowth, IBD, lymphoma, giardia, Whipple disease, HIV.
CLINICAL PRESENTATION
 Variable clinical presentation , that can include:
 Malabsorption (and complications of malabsorption)
 Iron or folate deficiency
 B12 deficiency uncommon (small effect on ileum)
 Chronic fatigue
 Weight loss
 Unexplained diarrhoea (± steatorrhea)
 Bloating and flatulence
 Failure to thrive
 Delayed puberty in children
 Dermatitis herpetiformis (a chronic, itchy, herpetiform skin condition)
 Symptoms improve with gluten-free diet and deteriorate when gluten is reintroduced
 Common in those with a family or personal history of coeliac disease or other autoimmune conditions
DIAGNOSIS
 Initial test: anti-tTG antibodies (anti-tissue transglutaminase) + total IgA level
 Anti-tTG not reliable if IgA is low (which is common in people with coeliac disease)
 Definitive test (positive serology or high clinical suspicion): duodenal biopsy
TREATMENT
 Test for, and treat, nutritional deficiency – CBC/iron, calcium/vitamin D, folate/B12, LFTs
 Permanent removal of gluten from the diet
COMPLICATIONS
 Associated with increased risk of intestinal lymphoma , carcinoma (e.g. bowel or oesophagus), and autoimmune disease
Whipple’s disease
Whipple’s disease is an extremely rare systemic disease caused by infection with Tropheryma whippelii.
 Associated with defects in cell-mediated immunity
CLINICAL PRESENTATION
 Primarily affects white men aged 30 to 60 years of age
 The four cardinal symptoms of Whipple disease are: arthralgia, chronic diarrhoea , abdominal pain, and weight loss
 Diarrhoea, due to villous atrophy of the small bowel (in almost all cases), is caused by malabsorption (diagnosed by endoscopy)
TREATMENT
 Ceftriaxone followed by long-term co-trimoxazole (>1 year)
INFLAMMATORY BOWEL DISEASE
Inflammatory bowel disease is a term that encompasses Crohn disease and ulcerative colitis (pathophysiology poorly understood).
Crohn disease versus Ulcerative colitis
FEATURE CROHN DISEASE ULCERATIVE COLITIS

Site Skip lesions in any portion of GI tract (rectal sparing) Rectum always involved, extends in continuous fashion
(most commonly involves ileum + ascending colon) (however, is isolated to large bowel)
(upper GI involvement is more common in children)
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Depth Transmural (thickened bowel wall with mesenteric fat creeping) Limited to mucosa/submucosa

Pathology Gross: Gross:

 Skip lesions with serpiginous ulcers / cobblestone mucosa  Continuous diffuse disease with pseudopolyps
Microscopic: Microscopic:
 Non-caseating granulomas and lymphoid aggregates  Gland disruption
 Ulceration/fissuring  Reduced goblet cells
 Glands intact  Crypt abscesses

Complications  Strictures (and obstruction)  Bleeding (very common)

 Perforation  Toxic megacolon
 Fistulas (to skin, bladder, vagina, or bowel loops)
 Perianal disease

Extra-intestinal  Skin: erythema nodosum, pyoderma gangrenosum, and perianal  Similar to Crohn disease
manifestations skin tags/oral mucosal lesions (CD)
(non-exhaustive list)  Rheum: arthritis, ankylosing spondylitis
 Ocular: uveitis/iritis
 Hepatobiliary: PSC (UC), gallstones (CD)
 Skin: erythema nodosum, pyoderma gangrenosum

Incidence of cancer  Mildly increased  Markedly increased

Smoking  Risk factor  Protective factor

Radiological features  Frequent strictures and fistulae  Lack of haustra

 Bowel wall thickening  Strictures rare

DIAGNOSIS
 Colonoscopy with biopsy is sufficient for diagnosis (CT colonography if severe disease; or sigmoidoscopy sufficient if UC)
 CT/MR-enterography may be necessary to visualise small bowel in CD
 Abdominal X-ray may assist in identifying structural changes
 Labs: CBC, CRP, faecal calprotectin, anti-tTG, stool cultures

Crohn disease
CLINICAL PRESENTATION
 Most often presents as recurrent abdominal cramps, fever, watery diarrhoea, and weight loss
 Signs: abdominal tenderness, fever, palpable mass, perianal fissures or tags, or other extra-intestinal manifestations
TREATMENT
 Induction of remission / supportive therapy
 Nutritional support (e.g. parenteral feeding ) (esp. in children)
 Symptomatic therapy (e.g. loperamide , paracetamol )
 Antibiotics (ciprofloxacin /metronidazole) – for complications (e.g. abscess)
 Induction therapy (oral/IV corticosteroids )
 Maintenance of remission
 Immunosuppression (e.g. azathioprine, infliximab , methotrexate )
 Surgical intervention (up to 50% will require in first 5 years of disease)

Note: 5-ASA agents (sulfasalazine) have little evidence for use in CD.
Ulcerative colitis
CLINICAL PRESENTATION
 Most often presents as recurrent rectal bleeding , tenesmus, urgency, and incontinence ± abdominal cramps
 Signs: blood on rectal examination, or other extra-intestinal manifestations
TREATMENT
 Medical management:
 5-ASA agents (e.g. sulfasalazine) – are mainstay of treatment
 Oral/IV corticosteroids – if severe
 Immunosuppression (e.g. infliximab ) – if refractory
 Surgical management (curative):
 Total colectomy
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IRRITABLE BOWEL SYNDROME

Irritable bowel syndrome (IBS) is a complex biopsychosocial illness that is influenced by the following: altered GI motility , altered
sensation within the GI tract , and psychosocial factors .
 Post-infectious IBS occurs in a small number of patients following gastroenteritis (unknown pathophysiology)
CLINICAL PRESENTATION
 Presents with chronic, intermittent, abdominal pain that is relieved by bowel movements; diarrhoea and/or constipation;
abdominal distention; and mucous stools (symptoms often worsen with stress)
 Non-associated symptoms : awakens patients with sleep, vomiting, weight loss, or constitutional symptoms
 Examination: normal (patients often have co-morbid psychiatric disorders )
DIAGNOSIS
 A diagnosis of exclusion (CBC, CRP, TSH, coeliac serology , and faecal calprotectin may be useful in this regard)
 ROME III criteria: at least 3 days per month in the last 3 months of episodic abdominal discomfort that is (1) relieved by
defecation and (2) associated with change in stool frequency or consistency
TREATMENT
 Psychosocial – reassurance and stress reduction
 Dietary – fibre supplements and low FODMAP diet (dietician referral indicated)
 Pharmacological (symptomatic):
 Global symptom relief – TCAs or SSRIs
 Diarrhoea – loperamide
 Constipation – laxatives
 Pain – anti-spasmodics (hyoscine) (however, long-term therapy not indicated)
OUTCOMES
 Typically, improves over time (and no impact on life expectancy)
PEUTZ-JEGHERS SYNDROME
Peutz-Jeghers syndrome is an autosomal dominant disorder characterised by intestinal harmatomatous polyps (pre-malignant but low-
risk) and a distinct pattern of skin and mucosal (circumoral) melanin deposition .
 Associated with an increase risk of various cancers
 Managed by surveillance imaging

Liver
ABNORMAL LFTS
Tests of liver function can be broadly classified as tests to assess hepatic injury, hepatic function , or to assess for cholestasis:
Tests of hepatic function
 Serum bilirubin (total and conjugated)
 Urine bile salts and urobilinogen
 Total protein, serum albumin, and albumin/globulin ratio
 Prothrombin time
Tests of liver protein synthesis
TEST CORRELATION TO LIVER FUNCTION INTERPRETATION

Prothrombin time  Hepatic protein synthesis  Increased in hepatocellular dysfunction or vitamin K

(PT or INR)  All clotting factors (except VIII and vWF) are produced deficiency (which is amenable to vitamin K therapy)
exclusively by the liver
 Best general prognostic factor in liver disease

Serum albumin  Hepatic protein synthesis  Decreased in hepatocellular dysfunction, renal losses,
malnutrition, inflammation, and malignancy

Serum globulin  Hepatic protein synthesis (the α and β-globulins are mainly  Increased in hypoalbuminaemia (as a compensatory
synthesised by the liver) measure)  i.e. a  albumin/globulin ratio

Tests to detect hepatic injury

Serum aminotransferase levels are typically elevated in all forms of liver injury :
 Alanine aminotransferase (ALT)
 Specific to liver
 Aspartate aminotransferase (AST)
 Non-specific to liver
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INTERPRETATION OF AMINOTRANSFERASES
  AST or ALT – indicates hepatocellular damage
 ALT>AST – most causes of hepatitis
 AST>ALT – alcoholic liver disease or other causes of hepatitis that have progressed to advanced cirrhosis
Tests to detect cholestasis
 Alkaline phosphatase (ALP)
 Originates from liver and bone
 Rises in third-trimester of pregnancy (due to placental cells)
 Gamma-glutamyl transferase (GGT)
 Specific to liver; however, increased by alcohol and medications (esp. anti-epileptics)
INTERPRETATION OF CHOLESTATIC ENZYMES
 ALP/GGT>ALT/AST – indicates cholestasis (obstruction, infiltration of liver, destruction of ducts, bile acid transport defects)
 Isolated ALP – indicates bone disease (osteoblast activity) or cancer; also, found in placenta (third trimester pregnancy)
 Isolated GGT – indicates alcohol, medications , or low-grade liver insult (e.g. fatty liver)
HEPATITIS
Hepatitis is inflammation of the liver leading to cell injury and necrosis.
CLASSIFICATION
 Acute: most common causes are the hepatitis viruses (Hep. A to E) and drugs (alcohol, paracetamol )
 Fulminant (acute liver failure) – severe with INR >1.5 and hepatic encephalopathy (without underlying chronic liver disease)
 Chronic:
 Chronic viral infection (Hep. C or B)
 Alcoholic liver disease
 Non-alcoholic steatohepatitis
 Autoimmune hepatitis
 Biliary disease (primary biliary cirrhosis, primary sclerosing cholangitis)
 Metabolic syndromes (Wilson’s disease, Haemachromatosis, α1AT deficiency)
CLINICAL PRESENTATION
 Clinical presentation is dependent on underlying aetiology:
 Most hepatitis is subclinical
 Acute hepatitis:
 Symptoms – non-specific viral prodrome (malaise, myalgia, fever, N/V, URTI symptoms, change in bowel habit, anorexia)
 Signs – jaundice and tender hepatomegaly (± splenomegaly and cervical lymphadenopathy)
 Chronic hepatitis:
 Symptoms – often asymptomatic, but may cause fatigue and/or joint and muscle pains
 Signs – jaundice and complications of cirrhosis

Note: paracetamol toxicity can cause a life-threatening hepatitis

DIAGNOSIS
 Acute hepatitis:
 ALT/AST:  (±  ALP/bilirubin)
 Chronic hepatitis:
 ALT/AST: /N (±  ALP/bilirubin)
 Viral hepatitis:
 Diagnosed by hepatic serology
 Other causes:
 Investigations dependent on specific cause (i.e. ceruloplasmin, iron studies, α1AT testing)
 May require liver biopsy if cause is uncertain
Types of viral hepatitis
TYPE TRANSMISSION PRESENTATION COMPLICATIONS NOTES

Hep. A Faecal-oral Self-limiting hepatitis  Acute liver failure (<5%) Never becomes chronic

Hep. B Bodily fluids Variable presentation (asymptomatic or  Acute liver failure The only DNA virus (other
presenting as typical hepatitis)  Chronic infection in infants (90%) hepatitis viruses are RNA)
 Chronic infection in adults (<10%)
 Cirrhosis  HCC Extremely high transmission rate
 HCC (independent of cirrhosis)
 Glomerulonephritis
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 Cryoglobulinaemia

Hep. C Bodily fluids Variable presentation (asymptomatic or  Chronic infection (80%) Less likely to be sexually
presenting as typical hepatitis)  Cirrhosis  HCC transmitted than HBV
 Cryoglobulinaemia
 Non-Hodgkin lymphoma

Hep. D Bodily fluids Co-infection with HBV or superinfection in  Vasculitis Requires HBV surface antigen
patient with prior HBV (more severe)

Hep. E Faecal-oral Self-limiting hepatitis  Acute liver failure in pregnant women, High mortality rate in pregnant
third trimester (10-20%) women (third trimester)

TREATMENT
 Acute hepatitis:
 Supportive care (may require treatment with antivirals if severe)
 HAV: vaccine available (for high risk groups – transplant patients, chronic liver disease, close contacts)
 HBV: vaccine available (on immunisation schedule)
 Chronic hepatitis:
 Antivirals (depending on serotype/disease stage):
 HBV: interferon , tenofovir , entecavir
 HCV (dependent on genotype) : typically, two direct-acting antivirals (DAAs) or one DAA + ribavirin
 HDV: interferon
 Vaccination for HAV/HBV to prevent further liver damage
 Avoidance of alcohol
 Adjustment of liver-metabolised medication
 Blood-borne precautions (esp. in HCV)
 Liver transplant is definitive treatment
 Paracetamol overdose:
 Gastric lavage/emesis (if <2hr after ingestion)
 Oral activated charcoal
 N-acetylcysteine PO/IV (indicated based on paracetamol blood level) (excellent prognosis if given before worsening LFTs)
COMPLICATIONS
 Cirrhosis
 Liver failure
 Hepatocellular carcinoma (risk increases per year of cirrhosis)
Hepatitis serology
Key Hepatitis Serologic Markers
VIRAL HEPATITIS TEST CORRELATION

Hep. A IgM HAV antibody Acute HAV

Hep. B HBsAg (antigen found on surface of HBV) Carrier of HBV

HBsAb (antibody to HBsAg) Immunity to HBV

HBcAg (antigen found in core of HBV) Not measured in clinical practice

HBcAb (antibody to HBcAg) IgM: positive in window period (acute infection)

IgG: past or current HBV infection

HBeAg (antigen found in core of HBV) Indicates high transmissibility (can also use HBV-DNA to determine viral load)

HBeAb (antibody to HBeAg) Indicates low transmissibility

Hep. C IgG/IgM HCV antibody or HCV-RNA in serum Serum HCV-RNA inversely corresponds to response to treatment

Hep. D HBsAg and IgG/IgM HDV antibody

Hep. E IgG/IgM HEV antibody

Autoimmune chronic hepatitis

Autoimmune hepatitis presents as a chronic hepatitis without serological evidence of viral infection (diagnosis of exclusion).
 Associated with other autoimmune conditions (Raynaud’s, thyroiditis, Sjogren’s)
DIAGNOSIS
 Labs – hypergammaglobulinaemia (anti-smooth muscle antibody is definitive)
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 Biopsy – piecemeal (interface) hepatic necrosis

TREATMENT
 Corticosteroids ± azathioprine (without this, most will relapse as corticosteroids withdrawn)
Differential diagnosis of hepatomegaly
 Congestive – right heart failure, constrictive pericarditis, hepatic vein thrombosis
 Infiltrative – malignant or benign (fatty liver, cysts, haemochromatosis, amyloidosis)
 Proliferative – infectious (viral hepatitis, tuberculosis) or inflammatory (granulomatous)
CIRRHOSIS
Cirrhosis is bridging fibrosis and nodular regeneration resulting from chronic hepatic injury.
CLASSIFICATION
 Intrahepatic: all causes of chronic hepatitis (commonly alcohol, HCV, HBV, HDV, auto-immune, non-alcoholic steatohepatitis)
 Extrahepatic:
 Biliary tract disease (primary biliary cirrhosis, primary sclerosing cholangitis)
 Post-hepatic causes (right sided heart failure, constrictive pericarditis, hepatic vein thrombosis)
 Other: Wilson’s disease, haemachromatosis, α1-antitrypsin deficiency
CLASSIFICATION
 Stage 1 – compensated and asymptomatic (can last for 10-20 years with almost normal life expectancy)
 Stage 2 – onset of decompensation (ascites, variceal bleeding, encephalopathy, or hepatocellular carcinoma)
CLINICAL PRESENTATION
 The clinical presentation of cirrhosis can be divided into:
 The effects of portal hypertension:
 Varices (oesophageal, caput medusae and anorectal varices)
 Splenomegaly
 Ascites
 Portal hypertensive gastropathy
 The effects of liver cell failure:
 Hepatic encephalopathy
 Jaundice
 Fetor hepaticus (musty smelling breath)
 Increased oestrogen (spider nevi, gynaecomastia, testicular atrophy, loss of sexual hair)
 Anaemia
 Peripheral oedema
 Bleeding/bruising tendency ( clotting factors /  INR)
 Specific signs: asterixis, palmar erythema, Dupuytren contracture, leukonychia, clubbing, xanthelasmata
 May also present with enlarged, palpable, or firm liver (hepatomegaly)

Complications of cirrhosis
COMPLICATION NOTES TREATMENT

Ascites  Pathophysiology: multifactorial (due to portal HTN and fluid retention)  Sodium restriction
 Clinical presentation: abdominal distension, shifting dullness  Diuretics (frusemide or spironolactone)
 Large-volume paracentesis
Paracentesis: cell count, chemistry, gram stain, cytology  TIPS (transjugular intra-hepatic porto-
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systemic shunt)

Associated with 50% 2-year mortality

Spontaneous  Pathophysiology: infection of peritoneum (diagnostic paracentesis  IV antibiotics (3rd gen. cephalosporins)
bacterial peritonitis reveals >250 PMNs/mL) (typically E. coli or other gram-negatives)  IV albumin
 Clinical presentation: abdominal pain, fever, nausea/vomiting  Prophylactic antibiotics (fluoroquinolones)

Associated with poor 1-year prognosis

Oesophageal varices  Pathophysiology: portal hypertension with  blood flow through the  Endoscopic surveillance
portosystemic anastomoses  β-blocker (prophylaxis for bleed)
 Clinical presentation: haematemesis (or malaena)  IV octreotide ( portal HTN)
 Endoscopic band ligation or sclerotherapy
 TIPS

Coagulopathy  Pathophysiology: impaired synthesis of all clotting factors (except VIII)  FFP (for acute bleeding)
 Clinical presentation: bleeding/bruising tendency
Vitamin K will not correct coagulopathy

Hepatic  Pathophysiology:  ammonia clearance (often precipitated by infection,  Lactulose (oral or enema)
encephalopathy dehydration, electrolyte abnormality, drugs, or GI bleeding) leads to  Rifaximin
osmotic imbalance resultant cerebral oedema
 Clinical presentation: confusion, drowsiness, asterixis, coma
 Can be graded by the West Haven Criteria

Hepatorenal  Pathophysiology: pre-renal AKI due to splanchnic vasodilation and renal  Trial volume load (does not improve)
syndrome vasoconstriction  Octreotide ( splanchnic vasodilation)
 Clinical presentation: pre-renal AKI (UNA <10)  Midodrine ( blood pressure)
 Albumin
 Dialysis if indicated

Hepatopulmonary  Pathophysiology: complex Liver transplant only definitive treatment

syndrome  Clinical presentation: syndrome of liver disease,  A-a gradient, and
evidence for intrapulmonary vascular abnormalities

DIAGNOSIS
 Definitive diagnosis is histological (liver biopsy)
 Other tests may be suggestive:
 The ‘W’ of cirrhosis :  platelets   INR   albumin   bilirubin
 Liver elastography (ultrasound measurement of liver fibrosis)
 Imaging:
 U/S – primary modality (only finds advanced cirrhosis)
 Abdominal CT
 Gastroscopy (varices)
 Aetiology – hepatic serologies, autoimmune markers, serum ferritin, ceruloplasmin, α1AT, ECRP
TREATMENT
 The goal is to treat and prevent progression of cirrhosis and minimize factors that can lead to complications (e.g. alcohol
cessation, avoidance of hepatotoxic drugs, and immunisation for HAV/HBV if non-immune)
 Liver transplant is the only definitive treatment (only for patients with no alcohol intake for <6 months )
OUTCOME
 Prognosis determined by Child-Pugh Score (life-expectancy) and MELD Score (used to stratify patients on transplant list)
 Usual causes of death: renal failure (hepatorenal syndrome), sepsis, GI bleed, or HCC
Portosystemic anastomoses
There are three main portosystemic anastomoses which can be identified in portal hypertension:
 Oesophageal varices – left-gastric vein with oesophageal veins
 Caput medusae – paraumbilical vein with epigastric veins
 Rectal varices – superior rectal vein with middle and inferior rectal veins
Aetiologies of ascites by SAAG
The aetiology of ascites can be determined by the serum-ascites albumin gradient (SAAG = serum albumin – ascites albumin)
 SAAG >1.1 (related to causes of portal hypertension):
 Pre-sinusoidal – splenic or portal vein thrombosis
 Sinusoidal – cirrhosis, schistosomiasis (commonest worldwide)
 Post-sinusoidal – right heart failure, constrictive pericarditis, hepatic vein thrombosis (Budd-Chiari syndrome)
 SAAG <1.1 (not related to portal hypertension):
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 Nephrotic syndrome
 Tuberculosis
 Malignancy with peritoneal carcinomatosis (e.g. ovarian cancer)

Note: portal hypertension is defined as a pressure gradient of >5mmHg (between hepatic vein and wedged hepatic vein pressure).
ALCOHOLIC LIVER DISEASE

CLASSIFICATION
 Fatty liver (all alcoholics) – always reversible if alcohol stopped
 Alcoholic hepatitis (one-third of alcoholics) – usually reversible if alcohol stopped
 Variable severity with potentially high mortality (correlated with increased white blood cell count )
 Cirrhosis (10% of alcoholics) – potentially irreversible
DIAGNOSIS
 Blood test are non-specific, but in general:
 LFTs: AST:ALT >2:1,  ALP/GGT (GGT increases with alcohol regardless), impaired liver function
 CBC: macrocytic anaemia and neutrophilia
 Imaging: U/S / CT (diffuse fatty infiltration)
 Biopsy (to exclude other causes)
TREATMENT
 Alcohol cessation
 Multivitamin supplements (especially thiamine)
 Caution with liver-metabolised medications
NON-ALCOHOLIC FATTY LIVER DISEASE
Non-alcoholic fatty liver disease is a spectrum of disorders characterised by macrovesicular hepatic steatosis .
 Insulin resistance is the key factor implicated in the pathophysiology (likely a component of metabolic syndrome )
 Histologically indistinguishable from those of alcoholic hepatitis (despite negligible intake)
TREATMENT
 Weight loss (and modification of metabolic syndrome risk factors)
OUTCOMES
 Less than one-quarter progress to cirrhosis (most patients die from cardiovascular disease)
 Risk of progression increases if inflammation or scarring occurs alongside fat infiltration (non-alcoholic steatohepatitis – NASH)
HAEMOCHROMATOSIS
Haemochromatosis is a state of iron overload in which haemosiderin accumulates in the liver, pancreas (islet cells), heart, adrenals, testes,
and pituitary (does not affect the lung, kidney, or eye).
CLASSIFICATION
 Primary: an autosomal recessive disorder characterised by mutations in the HFE gene ( absorption of dietary iron)
 HFE gene (chromosome 6) is common (5%) – esp. among Caucasian
 Secondary: occurs in patients receiving chronic transfusion therapy (e.g. sickle cell or α-thalassaemia)
CLINICAL PRESENTATION
 ABCD’s of Haemochromatosis
 Arthritis (esp. MCP joints – due to CPP deposition)
 Bronze skin (due to melanin)
 Cardiomyopathy (restricted > dilated) / Cirrhosis
 Diabetes (pancreatic damage)
 Hypogonadism (anterior pituitary damage) / Hepatomegaly
DIAGNOSIS
 Labs: iron studies ( serum iron,  serum ferritin,  transferrin,  transferrin saturation %,  total iron binding capacity)
 Liver biopsy (to determine hepatic iron index and presence of cirrhosis)
 HFE gene mutation screen
TREATMENT
 Weekly phlebotomy to normalize serum iron levels (followed by maintenance every 2 to 4 months)
 Iron chelating agents (e.g. deferoxamine ) if phlebotomy contraindicated
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OUTCOMES
 Normal life expectancy if treated before development of cirrhosis or diabetes mellitus
COMPLICATIONS
 Liver: cirrhosis (30%) or hepatocellular carcinoma (x200 risk) (one-third of mortality)
 Pancreas: diabetes mellitus
 Heart: restrictive/dilated cardiomyopathy or arrhythmia
 Testes: impotence
 Pituitary: hypopituitarism
WILSON DISEASE (HEPATOLENTICULAR DEGENERATION)
Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder that results in defective copper transport .
 Leads to accumulation and deposition of copper in the liver and brain
CLINICAL PRESENTATION
 Usually occurs in patients <30 years of age (50% symptomatic by age 15)
 Triad: hepatitis/cirrhosis (asterixis/encephalopathy), neurologic dysfunction (Parkinson-like symptoms), and psychiatric
abnormalities
 Kayser-Fleischer rings (green-to-brown deposits of copper encircling the iris) are pathognomonic
DIAGNOSIS
 Labs:  serum ceruloplasmin,  urinary copper excretion
 Liver biopsy (to determine hepatic copper infiltration)
TREATMENT
 Penicillamine or trientine (copper chelators)
 Dietary copper restriction
 Zinc ( faecal copper excretion)

Biliary
JAUNDICE
Jaundice (yellow skin, mucous membranes, and sclera) is a clinical sign that occurs when there is increased plasma bilirubin levels
(hyperbilirubinaemia ).
CLASSIFICATION
 Unconjugated hyperbilirubinaemia
 Overproduction – haemolytic anaemia (e.g. hereditary spherocytosis)
 Defective conjugation – Gilbert’s syndrome (or rarely Crigler-Najjar syndrome)
 Impaired hepatic uptake – drugs, right-sided heart failure
 Conjugated hyperbilirubinaemia
 Intrahepatic obstruction – hepatitis, cirrhosis, drugs, Wilson’s disease
 Extrahepatic obstruction – stones, strictures, cancer
 Defective excretion – Dubin-Johnson syndrome, Rotor’s syndrome
 Mixed hyperbilirubinaemia
 Hepatocellular damage
CLINICAL NOTES ON JAUNDICE

Urinary signs of jaundice

URINE DIPSTICK NORMAL UNCONJUGATED CONJUGATED

Urinary bilirubin (only conjugated bilirubin Negative Negative Positive (causes dark urine)
can be excreted in urine)

Urobilinogen (recirculated from intestine) Positive Positive Negative (causes pale faeces)

Clinical correlations of jaundice

SIGN OR SYMPTOM CLINICAL CORRELATION

Abdominal pain Suggests biliary tract obstruction from stone or pancreatic tumour (obstructive jaundice)

Painless jaundice (in elderly) Suggests pancreatic tumour (although most patients with pancreatic cancer have pain)

Kernicterus Unconjugated bilirubin-induced brain dysfunction in children; rarely seen in adults to maturation of BBB
 Management: monitor neonatal bilirubin and treat with phototherapy (or exchange transfusion)
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Investigations for jaundice

INVESTIGATION INDICATION

Abdominal U/S or CT For evidence of bile duct obstruction (e.g. bile duct dilation)

MRCP Non-invasive direct bile duct visualisation

Endoscopic U/S Sensitive for stones and pancreatic tumour

ERCP Invasive direct bile duct visualisation (most accurate; allows for therapeutic intervention)

PTC Indicated if ERCP fails (endoscopic access not possible)

GILBERT SYNDROME
Gilbert’s syndrome is defined as a decrease in glucuronyltransferase activity leading to defective conjugation of bilirubin .
 Autosomal dominant condition which has no clinical relevance (Crigler-Najjar syndrome is a rare form with complete deficiency)
CLINICAL PRESENTATION
 Usually presents in teens-20s as intermittent jaundice (esp. with fasting or illness)
DIAGNOSIS
 Labs:  unconjugated bilirubin
TREATMENT
 No treatment indicated (entirely benign)
PRIMARY SCLEROSING CHOLANGITIS
Primary sclerosing cholangitis is an idiopathic disorder characterised by progressive inflammation and fibrosis accompanied by
strictures of the extra- and intra -hepatic bile ducts .
 Usually presents in young men with ulcerative colitis (strong association with UC)
 Patients are at an  risk for cholangiocarcinoma
CLINICAL PRESENTATION
 Often insidious, may present with jaundice, fatigue, pruritis
 May present with cholangitis secondary to biliary obstruction
DIAGNOSIS
 Labs:  ALP ± bilirubin; pANCA present in 80% of cases
 Investigations:
 MRCP/ERCP – multiple bile duct strictures and dilatations (‘beading’)
 Liver biopsy – ‘onion skin’ fibrosis of bile ducts (periductal sclerosis)
 Colonoscopy – all newly diagnosed patients should undergo to evaluate for IBD
TREATMENT
 ERCP with dilation and stenting of strictures
 Liver transplantation is the definitive treatment (one of the most common indications for liver transplant)
OUTCOMES
 Mean survival after diagnosis is less than 10 years
PRIMARY BILIARY CIRRHOSIS
Primary biliary cirrhosis is an autoimmune granulomatous disorder characterised by destruction of intrahepatic bile ducts .
 Usually presents in middle-aged woman with other autoimmune conditions
 Can be fatal (although not all patients show progression)
CLINICAL PRESENTATION
 Often insidious, may present with jaundice, fatigue, pruritis
 Associated with fat-soluble vitamin deficiencies (A, D, E, K)
 Strong association with osteoporosis and hypercholesterolaemia
DIAGNOSIS
 Labs:  ALP ± bilirubin,  serum cholesterol; anti-mitochondrial antibodies are pathognomonic
 Investigations:
 MRCP/ERCP – normal extra-hepatic bile ducts
 Liver biopsy – confirms diagnosis and stages severity (associated with intrahepatic duct destruction and granulomas)
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TREATMENT
 Ursodiol – slows progression of disease
 Cholestyramine – for pruritis and hypercholesterolaemia
 Calcium and vitamin D – for low bone density
 Liver transplantation is the definitive treatment
PSC vs PBC
PRIMARY SCLEROSING CHOLANGITIS PRIMARY BILIARY CIRRHOSIS

Predominant gender Male Female

Associated comorbidities IBD, especially UC Other autoimmune disorders (Sjogren’s, CREST, RA)

Affected ducts Both intra- and extra-hepatic Intra-hepatic only

Investigations ERCP/MRCP (narrowing and dilations of ducts), Anti-mitochondrial antibodies, increased serum
colonoscopy, liver biopsy, pANCA cholesterol, liver biopsy, normal ERCP/MRCP

Pancreas
PANCREATITIS
Acute versus chronic pancreatitis
VARIABLE ACUTE PANCREATITIS CHRONIC PANCREATITIS
Pathophysiology Leakage of activated pancreatic enzymes into pancreatic and Irreversible parenchymal destruction, inflammation, and
peripancreatic tissues fibrosis leading to pancreatic dysfunction and insufficiency

Time course Abrupt (severe pain) Persistent and recurrent (episodes of severe pain)

Risk factors I GET SMASHED  Alcohol abuse (>90%)

 Idiopathic  Other: CF, hereditary, idiopathic
 Gallstones (common)
 Ethanol (common)
 Trauma (most common in children)
 Steroids
 Malignancy/mumps
 Autoimmune (assoc. with  IgG4, responds to prednisone)
 Scorpion/spider (not relevant)
 Hyper-calcaemia, Hyperlipidaemia ( TAGS), Hypothermia
 ERCP/emboli (or ischaemia)
 Drugs (steroids, NSAIDs, thiazide and loop diuretics)

Gallstone pancreatitis (a general surgical condition) –

obstruction of pancreatic duct by gallstones and biliary sludge
– stone often passes spontaneously

Presentation  Severe non-colicky, tender, epigastric pain (can radiate to Early stages: recurrent episodes of persistent epigastric pain
back; can improve when leaning forward)
Later stages: steatorrhea, weight loss, diabetes
 Nausea, vomiting, ileus, jaundice, fever, shock

 Associated with respiratory compromise (ARDs)

 Flank bruising (Grey Turner sign) and peri-umbilical

discolouration (Cullen sign) may be present

Diagnosis  Labs:  lipase/amylase;  calcium (if severe),  WBC,  BGL  Labs:  faecal elastase, (N) lipase/amylase,  BGL,  ALP
  ALT/AST strongly suggestive of gallstone/biliary aetiology
 Lipase is more sensitive and specific than amylase  Imaging:
  calcium due to fat necrosis binding  AXR/US/CT – pancreatic calcification and alternating
stenosis and dilation of pancreatic ducts (‘chain of lakes’)
 Imaging:
 AXR – sentinel loop and colon cut-off sign
 US/CT – enlarged pancreas, fat-stranding
 ERCP/MRCP – if cause uncertain or biliary aetiology

Treatment Supportive therapy: Supportive therapy:

 IV fluids/electrolyte replacement  Analgesia (incl. coeliac ganglion blocks)
 Analgesia  Pancreatic enzyme replacement
 Oxygen  Avoidance of alcohol
 NBM +/- NG suction (bowel rest)
 Nutritional support Endoscopic:
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 Sphincterotomy and stone removal

Other:
 Antibiotics only if documented infection Surgery (last-line):
 Surgery if necrotic pancreas (rare)  Pancreaticojejunostomy (if duct dilated -  drainage)
 Pancreaticoduodenectomy (if proximal disease)
 Distal pancreatectomy (if distal disease)
 Total pancreatic resection (last line)

Prognosis  90% self-limiting Chronic pain and pancreatic dysfunction

 10% severe requiring ICU (up to 50% mortality)
 Mortality predicted by modified GLASGLOW criteria

Complications  Pseudocysts – drained if symptomatic Chronic pain, diabetes mellitus, pancreatic cancer, opiate
 Infected necrosis/abscesses – as above addiction, malnutrition/weight loss
 Fistula formation
 Other: hypocalcaemia, renal failure, pleural effusion, chronic
pancreatitis, sepsis, ARDs
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Respiratory medicine.
Basic principles
BASIC RESPIRATORY PHYSIOLOGY

Definitions
 V/Q mismatch – occurs whereby ventilation (V) and perfusion (Q) are not evenly matched in the lung
 There is a degree of V/Q mismatch in the normal lung
 Relatively high ventilation and low perfusion in apex of lung (wasted ventilation)
 Relative low ventilation and high perfusion in base of lung (wasted perfusion)
 Dead-space – ventilation without perfusion (i.e. an extreme of V/Q mismatch  V/Q = ∞)
 Anatomical – portion of airways which conduct gas but in which gas exchange is not possible
 Pathological – portion of alveoli in which no gas exchange occurs
 Shunt – perfusion without ventilation (i.e. an extreme of V/Q mismatch  V/Q = 0)

Alveolar-arterial gradient
The Alveolar-arterial gradient (A-a gradient ) is the difference between the alveolar (A) and arterial (a) concentration of oxygen.
 It is an indirect measure of gas exchange and is useful for diagnosing the cause of hypoxaemia
CALCULATION
 A-a gradient = P AO2 – P aO2

Alveolar CO2
The partial pressure of carbon dioxide in the alveolus is proportional to the production of carbon dioxide and inversely proportional
to the alveolar ventilation.
CALCULATION
 PACO2 = VCO2 / VA

Spirometry
INTERPRETATION
 Obstructive disorders
 N/ FVC
 N/ TLC
  FEV1
  FEV1/FVC (<0.7)
  PEFR
 Restrictive disorders
  FVC
  TLC
  FEV1
 N/ FEV1/FVC
 N/ PEFR
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ANATOMY

Airway anatomy
 Each lung has a primary bronchus entering at the hilum
 Each lobe of the lung has a secondary (lobar) bronchus
 Lobes are divided into bronchopulmonary segments which have a tertiary
(segmental) bronchus
 Bronchopulmonary segments are divided into pulmonary lobules which have a
terminal bronchiole

Gross lung anatomy

 Left lung (8 bronchopulmonary segments)
 Upper lobe (containing the lingula)
 Lower lobe
 Right lung (10 bronchopulmonary segments)
 Upper lobe
 Middle lobe
 Lower lobe
 Fissures
 Oblique – T5, to 5 th rib mid-axillary line, to 6th rib costal cartilage
 Horizontal – 5 th rib in mid-axillary line to 4 th rib costal cartilage
EXAMINATION OF THE RESPIRATORY SYSTEM
Evaluation of patient with respiratory signs
CHEST WALL MEDIASTINAL PERCUSSION BREATH SOUNDS ADDED SOUNDS FREMITUS/RESONANCE
DISEASE
MOVEMENT DISPLACEMENT

Consolidation  affected area None Dull Bronchial () Crackles  affected side

Collapse  affected area Towards Dull /absent affected area Nil  affected side

Pleural effusion  affected area Away (if massive) Stony dull  affected area Pleural rub  affected side

Pneumothorax  affected area Away (if tension) Hyper resonant /absent affected area Absent  affected side

Asthma  both sides None Hyper resonant Normal/ Wheeze  affected side

COPD  both sides None Hyper resonant Normal/ Wheeze/crackles  affected side

Fibrosis (general)  both sides None Normal  both sides Crackles  both sides

 Fremitus/resonance is greater over areas of increased tissue density (consolidation or fibrosis)

 Fine (late) inspiratory crackles are suggestive of fibrosis
 Crackles only occurring during inspiration
 Wheeze only occurs during expiration (monophonic wheeze is a red flag – single airway obstruction)
COMMON CAUSES OF CLUBBING
 Pulmonary: lung cancer, bronchiectasis, pulmonary fibrosis, cystic fibrosis, abscess/empyema
(NOT COPD)
 Cardiac: cyanotic heart disease, endocarditis, myxoma
 GI: IBD, coeliac disease, cirrhosis
 Endocrine: Graves’ disease

Diseases of airway obstruction

ASTHMA
Asthma is a reversible airway obstruction secondary to bronchial hyperreactivity , airway inflammation (mast cell, TH2 cell, eosinophils
 inflammatory mediators), mucous plugging and smooth muscle hypertrophy .
CLINICAL PRESENTATION
 Presents with recurrent episodic symptoms of wheeze, dry cough, dyspnoea, and chest tightness
 Cough is worse in cold, at night and in early morning ; is triggered by a variety of stimuli
 Clinical signs:
 Basic: tachypnoea, audible polyphonic wheeze, hyperinflated chest, hyper-resonant percussion, decreased breath sounds
 Respiratory distress: tachycardia, accessory muscle use, intercostal indrawing, ‘see-sawing’, pulsus paradoxus
 Life-threatening: coma, confusion, exhaustion, tripod position, silent chest, bradycardia, hypotension,  O2 sats
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 Near-fatal:  PaCO2 or requiring mechanical ventilation

DIAGNOSIS
 Diagnosed clinically (supported by allergy, family history, and improvement in function with treatment)
 Tests: O2 sats, PEFR (esp. before and after trigger), ABG (if acute); spirometry (± methacholine challenge) (when stable)
 ABG:
  pH/ PaO2/ PaCO2 during attack (respiratory alkalosis)
 Normal or increased PaCO2 is an ominous sign (patient unable to hyperventilate – fatigue or worsened obstruction)
 Spirometry for diagnosis of asthma (looking for reversible airway obstruction)
  FEV1/FVC below lower limit of normal (<0.8), AND
  FEV1 of ≥12% after bronchodilator (6 puffs salbutamol)
DIFFERENTIAL DIAGNOSIS
 Respiratory – COPD, PE, pneumothorax, bronchiectasis
 Cardiology – pulmonary oedema (“cardiac asthma”), SVC obstruction, bronchiectasis
TREATMENT
 Avoid triggers (e.g. allergic, occupational, etc)
 Treatment regimen for chronic asthma (step-wise) (use an asthma action plan ):
1. SABA (salbutamol)
2. + ICS (fluticasone or budesonide) and titrate to required levels
3. + LABA (salmeterol) or symbicort SMART therapy
4.  to high dose ICS and/or add oral medication – montelukast (leukotriene antagonist) or theophylline (multiple effects)
5. Frequent/continuous use of oral steroids (prednisolone) or anti-IgE treatment
 Spacers should always be used for inhalers
 The Asthma Control Test (ACT) can be used to determine whether treatment intensification is required
 Poor control: symptoms >2 days/week; SABA use >2 days/week; night-time symptoms; interference with activity
 SMART therapy involves using symbicort (budesonide/formoterol – ICS/LABA) as both a maintenance and reliever inhaler
 This is more effective than combined ICS/LABA + SABA therapy at reducing exacerbations (due to compliance)
 Treatment for acute severe asthma :
 SABA + oral/IV corticosteroids + O2 (if sats <92%) – 90% of bronchodilator response within first 15 minutes
 If severe: add SAMA (ipratropium)
 If life-threatening: add single dose IV magnesium sulphate
 Consider antibiotics if infection (amoxicillin or augmentin)
 Consider ICU for ventilatory support and intensification of medical therapy (IV aminophylline or salbutamol)
COPD
COPD is a group of chronic, progressive, obstructive lung diseases characterized by airflow limitation, air trapping, and variable
destruction of lung tissue.
AETIOLOGY
 Risk factors: smoking (>95% of cases); almost exclusively a disease of the elderly
 Environmental – air pollution, occupation
 Traits – α1AT deficiency, bronchial hyperactivity
 Demographic – age, family history, male, low SES

Classification
Definition of Bronchitis and Emphysema
CHRONIC BRONCHITIS EMPHYSEMA

Defined clinically – productive cough on most days for at least 3 Defined pathologically – dilation and destruction of air spaces distal to
consecutive months in 2 consecutive years. terminal bronchiole and without obvious fibrosis.

Obstruction is due to narrowing of the airway lumen by mucosal Decreased elastic recoil of lung parenchyma causes  expiratory driving
thickening and excess mucous pressures, airway collapse, and air trapping

In patients whom chronic bronchitis predominates,  alveolar ventilation, In patients whom emphysema predominates,  alveolar ventilation and
 PaO2, and  PaCO2 leading to cor pulmonale and early type 2 respiratory normal PaO2/PaCO2 can be expected (until later in the disease course)
failure can be expected
Two types:
 Centriacinar – respiratory bronchioles predominantly effected
 Typically seen in smokers and affects upper lung zones
 Panacinar – respiratory bronchioles, alveolar ducts, and alveolar sacs
affected
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 Accounts for 1% of emphysema cases (usually α1AT deficiency)

 Typically affects lower lung zones

Clinical presentation and diagnosis

Note: a mixed presentation of chronic bronchitis and emphysema is the norm, so features of either appear in the same patient.
Clinical presentation and diagnosis of Bronchitis and Emphysema
SYMPTOMS SIGNS DIAGNOSIS

Bronchitis  Chronic productive cough  Cyanosis (secondary to Spirometry:

(Blue bloaters)  Purulent sputum hypoxaemia and   FEV1
 Haemoptysis hypercapnia)   FEV1/FVC (<0.7 even after bronchodilator)
 Mild dyspnoea initially  Signs of RVF (cor pulmonale)  Normal TLC
 Crackles/wheeze CXR:
 Prolonged expiration  Normal AP diameter
 Frequently obese   bronchovascular marking
 Enlarged heart with cor pulmonale

Emphysema  Dyspnoea (+/- exertion)  Pink skin Spirometry:

(Pink puffers)  Minimal cough  Pursed-lip breathing   FEV1
 Tachypnoea  Accessory muscle use   FEV1/FVC (<0.7 even after bronchodilator)
 Decreased exercise  Cachectic appearance   TLC (hyperinflation)
tolerance  Hyperinflated chest (hyper-   RV (gas trapping)
resonant percussion) CXR:
 Decreased breath sounds   AP diameter / flat hemidiaphragm
  heart shadow
  retrosternal space
  bronchovascular marking
 Bullae/blebs

 Additional tests
 ABG – to determine tissue oxygenation and acid-base levels
 Sputum culture – in the setting of fever/productive cough (rule out infection)
 Scoring tests of severity:
 COPD assessment test (CAT)
 Modified Medical Research Council (mMRC) questionnaire for dyspnoea

Treatment
TREATMENT OF CHRONIC COPD
 Lifestyle change (e.g. smoking cessation)
 Vaccination (e.g. influenza , pneumococcal)
 Pulmonary rehabilitation (through physiotherapy/respiratory therapy)
 Treatment Regimen per GOLD guidelines:
 Group A ( less symptoms; low exacerbations)
 SAMA or SABA or SAMA/SABA or LAMA or LABA
 Group B (more symptoms; low exacerbations)
 LAMA or LABA  LAMA/LABA
 Group C (less symptoms; high exacerbations)
 LAMA  LAMA/LABA
 Group D (more symptoms; more exacerbations)
 LAMA/LABA  ICS/LAMA/LABA  add a macrolide
(azithromycin) in former smokers or roflumilast if chronic bronchitis
 Advanced COPD:
 Morphine – relieves dyspnoea anxiety
 BZD – reduces dyspnoea anxiety
 Oxygen – in the consistently hypoxic patient, polycythaemia, or pulmonary hypertension (improves QOL and mortality)
 Surgical intervention (i.e. lung transplant or lung volume reduction surgery )

Note: do not prescribe SAMA and LAMA concurrently

Inhaler examples
DRUG CLASS GENERIC

SAMA (short-acting muscarinic antagonist)  Ipratropium

SABA (short-acting beta-2 agonist)  Salbutamol

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LAMA (long-acting muscarinic antagonist)  Tiotropium

LABA (long-acting beta-2 agonist)  Salmeterol

 Formeterol

ICS (inhaled corticosteroid)  Beclomethasone diproprionate

 Budesonide
 Fluticasone proprionate

TREATMENT OF COPD EXACERBATIONS

 Acute exacerbations of COPD are defined as >24-48 hours of worsened symptoms/increased medication usage – the more frequent
these occur the worse the prognosis
 Aetiology: viral URTI (majority), bacteria, pollution; heart failure, pulmonary embolism, and MI must also be considered
 Treatment:
 SABA (± SAMA)
 PO/IV corticosteroids for five days if moderate to severe exacerbation
 Antibiotics if evidence of infection (amoxicillin or augmentin)
 BiPAP if respiratory acidosis ( minute ventilation)
 Supplementary oxygen (aim for O2 sats. of 88-92% as per explanation below)
 If no response – consider aminophylline , doxapram (respiratory stimulant), or ICU and ventilatory support

Note: excessive oxygen administration can lead to type II respiratory failure in some COPD (or severe asthma) patients
 Traditional theory of loss of hypoxic drive (and CO2 insensitivity) is incorrect
 COPD patients typically have supra-normal respiratory drive
 Correct explanation:
  V/Q mismatch (most important): excess oxygen overcomes hypoxic vasoconstriction leading to  blood flow to poorly
ventilated alveoli (increasing V/Q mismatch)
 Haldane effect: deoxygenated haemoglobin binds CO2 with greater affinity than oxygenated haemoglobin; hence, oxygen
induces a rightward shift of the CO2 dissociation curve
COMPLICATIONS
 Chronic hypoxaemia and/or hypercapnia (i.e. respiratory failure)
 Polycythaemia secondary to hypoxaemia
 Pulmonary hypertension
 Cor pulmonale
 Pneumothorax due to rupture of emphysematous bullae
OUTCOMES
 BODE index can be used to stratify risk of mortality – BMI, airway Obstruction, Dyspnoea (best predictor), Exercise
α1-antitrypsin deficiency
PATHOPHYSIOLOGY
 Autosomal co-dominant mutation in SERPINA1 that results in reduced α1-antitrypsin
 The protein α1-antitrypsin typically inhibits neutrophil elastase (an enzyme that disrupts connective tissue)
 Consequently, individuals with the condition develop liver fibrosis/cirrhosis and emphysema
TREATMENT
 Treat underlying cirrhosis and/or COPD
 Conservative – smoking cessation
 Medical – IV α1-antitrypsin
 Surgical – lung (or liver) transplant
PNEUMONIA
Pneumonia is an acute lower respiratory tract illness due to an infection.
CLINICAL PRESENTATION
 Typical presentation: cough (± sputum or haemoptysis), fever, dyspnoea, tachypnoea, tachycardia, night sweats, pleuritic chest pain
 Atypical symptoms: gradual onset, dry, non-productive cough; headaches, malaise, and sore throat (‘walking pneumonia’ )
 Signs: cough, fever, tachypnoea, tachycardia, crackles,  or bronchial breath sounds, dullness on percussion,  fremitus

Note: confusion may be only sign in elderly.

DIAGNOSIS
 Diagnosis requires at least 2 of the above symptoms/signs plus chest abnormalities on a CXR or CT
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 Imaging is not routinely recommended in a community setting unless severe/refractory or risk of malignancy
 Labs: FBC, U&E, LFTs, CRP (also consider troponins and urinalysis)
 Sputum gram stain/culture , nasopharyngeal/pleural aspirate , blood culture , and ABG are obtained in minority of cases
 Consider bronchoscopy or bronchoalveolar lavage if patient is immunocompromised or intubated to culture the organism
Classification and common causes of pneumonia
CLASSIFICATION COMMON ORGANISMS

Community acquired Typical (+ve gram stain/culture): S. pneumoniae > H. influenzae > Moraxella catarrhalis
(typical/atypical presentation not useful Atypical (-ve gram stain/culture): Mycoplasma pneumoniae > Chlamydia pneumoniae > Legionella
for determining empiric treatment) Viral: Influenza, Adenovirus, others

Hospital acquired Enteric GNB (e.g. E. coli); Pseudomonas aeruginosa (intubated patients); S. aureus (including MRSA)
(in hospital for 48 hours before infection)

Aspiration Oral anaerobes (e.g. Bacteroides); Enteric GNB (e.g. E. coli); S. aureus; Gastric contents

Immunocompromised Pneumocystis jirovecii (HIV); Fungi; Viruses; Tb; Mycobacteria; Staphylococcus

PNEUMONIA DISTRIBUTION
 Lobar pneumonia – only involves a single lobe/section of lung (often due to S. pneumoniae)
 Multi-lobar pneumonia – affecting multiple lobes/sections of the lung (associated with worse prognosis)
 Bronchopneumonia – affects the lungs in patches around the bronchi/bronchioles (often bilateral)
 Interstitial pneumonia – involves areas between the alveoli (most likely due to viruses or atypical organisms)
SEVERITY
Severity of pneumonia (30-day mortality) is classified by the “CURB-65” criteria (1 point for each of the below):
 Confusion (abbreviated mental test ≤8)
 Urea >7mmol/L
 Respiratory rate ≥30/min
 BP <90 systolic or <60 diastolic
 Age ≥65
Treatment strategy via CURB-65 score
SCORE TREATMENT GUIDELINE

0 to 1 Discharge (to community) with prescription

2 Hospital admission for medical therapy

≥3 Indicates severe pneumonia (high mortality, may require intubation)

Note: the CURB-65 score is not useful if several co-morbidities, pleural effusions, or bilateral/multi-lobar pneumonia.
TREATMENT
Community acquired pneumonia:
 CURB-65 score 0-1: amoxicillin  doxycycline
 CURB-65 score 2 : amoxicillin + macrolide (roxithromycin or clarithromycin)
 CURB-65 score 3-4: augmentin IV + macrolide IV
 CURB-65 score 5: tazocin IV + macrolide IV
Aspiration pneumonia:
 Mild to moderate: amoxicillin IV
 Severe: ceftriaxone IV + metronidazole PO
Hospital acquired pneumonia:
 Low risk: augmentin IV
 High risk: tazocin IV (meropenem if allergic)
Specific infections:
 Streptococcus: benzylpenicillin IV (if susceptible) or flucloxacillin IV for staph. aureus
 MRSA: vancomycin
 Mycoplasma: macrolide
 Legionella: doxycycline or macrolide
Supportive care:
 Supplemental oxygen , IV fluids, SABA
COMPLICATIONS
 Parapneumonic effusion (simple, complicated, or empyema)
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 Lung abscess (treat with antibiotics rather than drainage)

 Necrotising pneumonia
 Respiratory failure
 Cardiovascular disease
 Sepsis
PREVENTION
 Vaccination:
 Pneumococcal – funded in NZ under the immunisation schedule and for those at high risk (e.g. HIV, renal disease,
immunocompromised, splenectomy) – prevents S. pneumoniae
 Influenza – funded at any stage of pregnancy, in >65 years of age and for other certain co-morbidities
BRONCHIECTASIS
Bronchiectasis is irreversible dilation of the airways due to inflammatory destruction of the airways due to persistently infected
mucous.
 Usually affects the medium-sized airways
 Typical pathogens : Pseudomonas (most common); also, S. aureus, H. influenzae, Strep. pneumoniae, and Mycobacteria
AETIOLOGY
 Post-infectious (e.g. measles, pertussis, influenza; aspergillosis; mycobacteria (TB and MAC); severe pneumonia)
 Immunodeficiency (e.g. immune globulin deficiency or ciliary dysfunction)
 Genetic (e.g. cystic fibrosis)
 Bronchial obstruction (e.g. foreign body, tumour)
CLINICAL PRESENTATION
 Difficult to differentiate from chronic bronchitis
 Symptoms: chronic cough, purulent sputum, haemoptysis (can be massive), recurrent pneumonia
 Signs: crackles, wheeze, clubbing
DIAGNOSIS
 Spirometry – obstructive pattern or normal
 CXR –  bronchovascular markings and tram lines (parallel lines outlining dilated bronchi)
 CT (gold standard) – dilated airways with thickened walls (diameter bronchus greater than diameter of accompanying artery)
 Sputum cultures
 Serum Ig levels
 Sweat electrolytes if cystic fibrosis suspected
TREATMENT
 Vaccination: influenza and pneumococcal
 Antibiotics :
 Oral/IV/inhaled antibiotics for exacerbations (guided by sputum sensitivity)
 Macrolides may be used chronically for anti-inflammatory effect
 Inhaled antibiotics may be used chronically for pseudomonas suppression
 Corticosteroids:
 Inhaled corticosteroids may be used chronically for anti-inflammatory effect
 Oral corticosteroids for major exacerbations
 Physiotherapy: cough control, breathing exercises, postural drainage
 Surgical intervention: in select cases with focal bronchiectasis
CYSTIC FIBROSIS
Cystic fibrosis is a common genetic disorder, with 1 in 25 individuals being a carrier of the disease gene.
PATHOPHYSIOLOGY
 Autosomal recessive disorder: CFTR gene on chromosome 7 – results in dysfunctional chloride channels on apical membranes of
cells
 This causes thick secretions from exocrine glands (lung, pancreas, skin, reproductive organs) and blockage of secretory ducts
 Relative dehydration of airway secretion  impaired mucociliary transport and airway obstruction  recurrent infection
CLINICAL PRESENTATION
 Can present at any age – typically affects Caucasians
 Presenting signs – CF PANCREAS :
 Chronic cough and wheezing
 Failure to thrive
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 Pancreatic insufficiency (malabsorption)

 Alkalosis and hypotonic dehydration
 Neonatal intestinal obstruction (meconium ileus)/Nasal polyps (almost all cases of meconium ileus are due to cystic fibrosis)
 Clubbing/Chest X-ray signs
 Rectal prolapse
 Electrolyte elevation in sweat (salty skin)
 Absence or congenital atresia of vas deferens (infertility in males)
 Sputum with S. aureus (early stage) or Pseudomonas (most common) – i.e. recurrent pneumonia
DIAGNOSIS
 Diagnosis by sweat chloride test ( NaCl and K+)
 Heterozygotes have normal sweat tests (and no symptoms)
 Confirmed by genetic testing
 Additional:
 Spirometry : obstructive pattern
 ABGs: hypoxaemia and hypercapnia in late disease
 CXR: hyperinflation and increased pulmonary markings
TREATMENT
 Nutritional counselling :
 High calorie diet
 Pancreatic enzyme replacement
 Fat soluble vitamin supplements
 Management of chest disease :
 Mechanical: physiotherapy , postural drainage , exercise
 Airways: bronchodilators, aerosolized DNase , inhaled hypertonic saline
 Infection: antibiotics (with Pseudomonas cover)
 Advanced: lung (or pancreas) transplantation
 Genetic counselling
COMPLICATIONS
 Respiratory: respiratory failure, pneumothorax, cor pulmonale
 Gastrointestinal: pancreatic fibrosis, gallstones, cirrhosis, diabetes mellitus
 Genitourinary: infertility in males and reduced fertility in females

Diseases of airway restriction

INTERSTITIAL LUNG DISEASE
Interstitial lung disease is a group of disorders which cause fibrosis of lung tissue which impairs lung function and gas exchange .
 There are >100 known disorders; the majority are due to unknown agents or cause
PATHOPHYSIOLOGY
 Several characteristic features:
 Lung restriction ( TLC/VC)
 Decreased lung compliance (N/ FEV1/FVC)
 Poor diffusion ( DLCO)
 Hypoxaemia due to V/Q mismatch
 Pulmonary HTN (or cor pulmonale) secondary to hypoxaemia and blood vessel destruction
CLASSIFICATION
 Exposure-related (pneumoconioses, hypersensitivity pneumonitis, and drug/radiation related lung injury)
 Associated with systemic disease (e.g. sarcoidosis, amyloidosis, vasculitis, collagen vascular disease)
 Idiopathic (e.g. IPF)
CLINICAL PRESENTATION
 Clinical presentation dependent on underlying disease
 Associated with:
 Symptoms – dyspnoea (especially on exertion), non-productive cough, and features of cor pulmonale
 Signs – fine end-inspiratory crackles and clubbing (esp. in IPF and asbestosis)
DIAGNOSIS
 Depends on underlying disorder
 Imaging (CXR/CT):
 Decreased lung volume (due to fibrosis)
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 Reticular, nodular, or reticulonodular pattern

 Honey-combing in advanced disease
 Hilar/mediastinal adenopathy (esp. in sarcoidosis)
 Spirometry:
 Restrictive pattern:  lung volume and compliance
 ABG:
 Hypoxaemia and respiratory alkalosis with progression of disease
Causes of fibrotic shadowing on CXR
UPPER ZONE LOWER ZONE

SCART CIA
 Silicosis / Sarcoidosis  Collagen vascular disease
 Coal workers lung / Chronic allergic alveolitis (hypersensitivity pneumonitis)  IPF
 Ankylosing spondylitis  Asbestosis
 Radiation
 Tuberculosis

Unknown aetiologic agents

Idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis is a condition characterized by progressive, irreversible, fibrosis of lung parenchyma with no known
cause.
 Commonly presents over age 50
CLINICAL PRESENTATION
 Symptoms : dyspnoea on exertion, non-productive cough, constitutional symptoms
 Signs: crackles and clubbing
DIAGNOSIS
 Labs: non-specific
 CXR/CT: reticular or reticulonodular pattern esp. in lower lung zones; may show honeycomb lung in advanced disease
 Lung biopsy may be required for diagnosis – histology shows changes of usual interstitial pneumonia (UIP)
TREATMENT
 Oxygen
 Antifibrotics (pirfenidone and nintedanib)
 N-acetylcysteine (anti-oxidant) – benefits unclear
 Lung transplantation
OUTCOME
 Mean survival 3-5 years after diagnosis
Sarcoidosis
Sarcoidosis is an idiopathic non-infectious granulomatous multisystem disease with lung involvement in 90% of cases.
 Characterized pathologically by non-caseating granulomas (as opposed to Tuberculosis)
CLINICAL PRESENTATION
 Typical presentation: asymptomatic CXR finding (in young or middle-aged patients)
 Symptoms – non-specific respiratory and/or constitutional symptoms
 Chest exam – often normal
 Common extrapulmonary manifestations:
 Cardiac – arrhythmia, restrictive (or dilated) cardiomyopathy, sudden death
 Eye – uveitis, conjunctivitis, glaucoma
 Skin – erythema nodosum, violaceous skin plaques
 Joints - arthralgia
 Organs – hepatomegaly +/- splenomegaly
 Infection – peripheral lymphadenopathy
 Löfgren syndrome – the triad of arthritis, erythema nodosum, and bilateral hilar adenopathy
DIAGNOSIS
 CXR (initial test) : nodular opacities esp. in upper lung zones +/- bilateral hilar lymphadenopathy
 Lung/lymph node biopsy (definitive test): assessing for non-caseating granulomas
 Labs:
 CBC (cytopenia), U&E, LFTs
 Calcium (hypercalcaemia/hypercalciuria due to vitamin D activation by granulomas )
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 Serum ACE levels ( – not specific or sensitive)

 Spirometry : variable
 ECG: to rule out arrhythmia
 Slit-lamp eye exam: to rule out uveitis
TREATMENT
 Low stage sarcoidosis typically resolves spontaneously
 Symptomatic: corticosteroids for symptoms, declining lung function, or extrapulmonary manifestations
 Methotrexate or immunosuppressives used occasionally

Note: if unilateral hilar lymphadenopathy think neoplasia or tuberculosis; however, if bilateral consider sarcoid or lymphoma.
Known aetiologic agents
Hypersensitivity pneumonitis
Hypersensitivity pneumonitis (chronic allergic alveolitis) is a non-IgE mediated inflammation of lung parenchyma due to
sensitisation to inhaled agents (usually organic dusts ).
 Exposure usually related to occupation or hobby, for example:
 Farmer’s or mushroom worker’s lung (Thermophilic actinomycetes)
 Bird Fancier’s lung (immune response to bird IgA)
 Humidifier (or sauna) lung (Aureobasidium spp.)
 Characterised pathologically by air-way centred poorly formed granulomas (chronically) and lymphocytic infiltration
CLINICAL PRESENTATION
 Acute presentation (4-6 hours after exposure ): dyspnoea, cough, fever/chills, malaise (lasts <24 hours)
 Chronic presentation: insidious onset of dyspnoea, cough, malaise, weight loss
DIAGNOSIS
 Gather an occupational and travel history
 Associated with progressively restrictive pattern spirometry and reticulonodular pattern esp. in upper lobe zones in CXR
 Blood tests may show positive serum precipitins (neither sensitive or specific)
TREATMENT
 Avoidance of exposure (as chronic changes are irreversible)
 Corticosteroids can relieve symptoms and speed resolution
Pneumoconioses
Pneumoconioses are a group of inflammatory restrictive lung conditions caused by exposure to inhaled inorganic dusts .
CLASSIFICATION

Types of Pneumoconioses
DIAGNOSIS AETIOLOGY CLINICAL PRESENTATION DIAGNOSIS COMPLICATIONS

Asbestosis Exposure: asbestosis (e.g. Insidious onset of CXR:   risk of bronchogenic

insulation, plumbers, dyspnoea, cough,  Reticulonodular pattern (esp. lower carcinoma and
pipe-fitters) crackles, and clubbing lung zones) malignant
 May develop IPF-like honeycombing mesothelioma
Usually >10-20 years of (Clubbing much more  Pleural plaques, pleural effusion, and  Risk of lung cancer
exposure and >20-30 likely in asbestosis than atelectasis dramatically increased if
years between exposure silicosis or CWP) patient is a smoker
and clinical disease Microscopy:
 Ferruginous bodies (yellow-brown rod-
Causes slowly shaped structures represent asbestosis
progressive diffuse fibres coating in macrophages)
interstitial fibrosis
(induced by asbestosis
fibres)

Silicosis Exposure: silica dust (e.g. Dyspnoea, cough, and CXR:   risk of
mines, quarries, potters, wheezing  Early: nodular/'egg shell' pattern mycobacteria/TB
glass workers) (upper > lower zones) infection (require annual
 Late: progressive massive fibrosis TB skin test)
Usually >20 years of  Potential hilar enlargement  Progressive massive
exposure fibrosis

Coal Worker’s Exposure: coal dust Pathologic hallmark is CXR:  Progressive massive
pneumoconiosis coal macules in lung  Simple: nodular fibrosis – progression of
(CWP) (upper > lower zones) CWP – CXR shows upper
Varies from asymptomatic  Complicated: progressive massive zone fibrotic masses (1-
to progressive massive fibrosis 10cm)
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fibrosis

Berylliosis Exposure: beryllium (e.g. Similar to above CXR: Requires chronic

high-technology field  Diffuse infiltrates corticosteroid treatment
manufacturing)  Hilar adenopathy

TREATMENT
 No effective treatment – exposure prevention through use of protective equipment
 Additional considerations : supportive therapy, smoking cessation, vaccination, rehabilitation, lung transplant for end-stage disease
Iatrogenic interstitial lung disease
CLASSIFICATION
 Drug induced – for example: methotrexate , nitrofurantoin, amiodarone, and chemotherapeutic agents
 Radiation induced (conforms to shape of radiation field)
EOSINOPHILIC PULMONARY SYNDROMES
Eosinophilic pulmonary syndromes are a diverse group of disorders characterised by:
 Eosinophilic pulmonary infiltrates (seen on CXR)
 Peripheral eosinophilia (seen on CBC)
AETIOLOGY
 Allergic bronchopulmonary aspergillosis
 Acute eosinophilic pneumonia
 Löffler syndrome
 Drug-induced
TREATMENT
 Dependent on underlying cause
 Corticosteroids (typically exceptionally sensitive to steroids)

Pulmonary vascular disease

PULMONARY HYPERTENSION AND COR PULMONALE
Pulmonary hypertension is defined as:
 Mean pulmonary arterial pressure >25mmHg at rest (and >30mmHg with exercise), or
 Systolic pulmonary arterial pressure >40mmHg at rest

Cor pulmonale is right-sided heart failure caused by pulmonary hypertension.

CLASSIFICATION
 Pulmonary arterial hypertension (e.g. idiopathic, collagen-vascular disease, vasculitis)
 Pulmonary HTN from left-sided heart disease (e.g. VHD or HF)
 Pulmonary HTN secondary to chronic lung disease (e.g. COPD, cystic fibrosis, interstitial disease, or chronic hypoxia)
 Pulmonary HTN secondary to chronic thromboembolic disease (e.g. pulmonary embolism)
 Pulmonary HTN with unclear mechanisms
PATHOPHYSIOLOGY
 Hypoxic vasoconstriction
 Decreased area of pulmonary vascular hypoxia
 Volume and pressure overload
CLINICAL PRESENTATION
 Symptoms : dyspnoea, fatigue, syncope, retrosternal chest pain (± symptoms of underlying disease)
 Signs: loud P2, right-sided S4, left parasternal heave (± signs of RHF if cor pulmonale)
DIAGNOSIS
 CXR – enlargement of central pulmonary arteries
 CT – to assess lung parenchyma
 ECG – RVH/right-sided strain, P pulmonale
 Echocardiogram (initial test) and right heart catheterisation (definitive test) – right ventricular overload
TREATMENT
 In all patients:
 Treat underlying cause
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 Supplemental oxygen
 Exercise
 Consider anticoagulation
 Treat RHF if present
 Additional treatments (pulmonary arterial hypertension):
 CCBs – very effective in some patients
 Advanced therapy – prostaglandin inhibitors , sildenafil (PDE5 inhibitor), or lung transplantation
OUTCOMES
 Mortality: 2-3 year survival from diagnosis (<1 year if cor pulmonale)

Respiratory failure
RESPIRATORY FAILURE
Respiratory failure can be classified as type 1 or type 2.
Type 1 versus Type 2 respiratory failure
TYPE DEFINITION PATHOPHYSIOLOGY

Type 1 PaO2  (<60) and PaCO2 normal/ Normal A-a gradient (<15mmHg – i.e. normal gas exchange)
 Improves with oxygen
 Hypoventilation (always associated with  PaCO2; but not necessarily type 2 failure)
 Central (e.g. drugs, coma)
 Chest wall disorder (e.g. obesity, chest-wall deformity, neuromuscular conditions)
 Respiratory fatigue
 Low-inspired FiO2 (e.g. high altitude)

High A-a gradient (>15mmHg – i.e. poor gas exchange)

 Improves with oxygen
 V/Q mismatch (95% of cases)
 Airway disorders (e.g. asthma, COPD)
 Vascular disorders (e.g. pulmonary embolism)
 Alveolar disorders (e.g. consolidation)
 Thickened diffusion barrier
 Interstitial lung disease
 Alveolar disease
 Pulmonary vascular disease

 Does not improve with oxygen

 Right-to-left shunt
 Alveolar shunt (alveolar blocked from ventilation – severe consolidation or atelectasis)
 Vascular shunt (pulmonary artery bypasses alveoli to pulmonary vein – AV malformation)
 Cardiac shunt (blood bypasses lungs – tetralogy of Fallot)

Type 2 PaO2  (<60) and PaCO2  (>50)  High inspired CO2 (e.g. rebreathing)
 Low total ventilation (e.g. central causes, chest wall disorders, or fatigue)
 High dead space ventilation (e.g. status asthmaticus, advanced COPD)
 High CO2 production (e.g. fever, sepsis, acidosis)

Remember – high CO2 is alleviated by  ventilation

CLINICAL PRESENTATION
 Signs of underlying disease
 Hypoxia: dyspnoea, restlessness, agitation, central cyanosis, confusion, coma
 Long-standing hypoxia can lead to polycythaemia and/or cor pulmonale
 Hypercapnia: headache, peripheral vasodilation, tachycardia, asterixis, confusion, coma
DIAGNOSIS
 Serial ABGs
 CXR and/or CT (+/- bronchoscopy ) to characterize underlying cause if unclear
TREATMENT
 Type 1:
 Treat underlying pathology
 Oxygen therapy – maintain oxygenation (not effective in shunt)
 Positive pressure support (BiPAP/CPAP) – can recruit alveoli and redistribute lung fluids
 Haemodynamic support (fluids, vasopressors, inotropes ) – can reduce O2 requirements
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 Intubation and ventilation – if severe

 Type 2:
 Treat underlying pathology
 Oxygen therapy (aim to 88-92% due to CO2 retention)
 Non-invasive ventilation (BiPAP) – essential to reduce hypercapnia ( ventilation)
 Intubation and ventilation – if severe (persisting acidosis or hypercapnia)
 Correct exacerbating factors:
 Bronchodilators: reduction of airway resistance
 Antibiotics : treatment of infection
 NTT/ETT suction : clearance of secretions
 Diet: high carbohydrates can  PaCO2 and high lipids can  PaCO2 in those with mechanical/limited ventilation
ACUTE RESPIRATORY DISTRESS SYNDROME
Acute respiratory distress syndrome is a syndrome characterised by pulmonary oedema , hypoxaemia , and severe respiratory distress .
AETIOLOGY
 Direct (mainly aspiration, pneumonia, and inhalation injury)
 Indirect (mainly sepsis, shock, and trauma) lung injury
PATHOPHYSIOLOGY
 Disruption of alveolar capillary membranes  leaky capillaries  interstitial and alveolar oedema
 This leads to  lung compliance, V/Q mismatch , hypoxaemia , and pulmonary hypertension
CLINICAL PRESENTATION
 Exudative phase (first week)
 Dyspnoea, tachypnoea, and  work of breathing  respiratory fatigue  respiratory failure
 Due to loss of tight alveolar barrier due to damaged alveolar capillary and type I pneumocyte cells
 Fibroproliferative phase (after first week)
 Typically, clinical improvement
 Some patients may develop fibrotic lung changes that require long-term supplemental oxygen or ventilation
DIAGNOSIS
 Berlin criteria
 Acute onset (within 7 days and typically within 72 hours) of respiratory distress after a defined event (e.g. sepsis, pneumonia)
 CT/CXR bilateral opacities consistent with pulmonary oedema
 Not fully explained by cardiac failure or fluid overload (echocardiogram, should be performed even if no clear risk factors)
TREATMENT
 Treat underlying disorder
 Mechanical ventilation using low tidal volumes to prevent barotrauma
 Titrate PEEP to recruit collapsed alveoli and allow the use of lower FiO2 to achieve adequate oxygenation
 Consider prone ventilation , inhaled nitric oxide , or ECMO (extracorporeal membrane oxygenation) if refractory
 Slowly wean patients from ventilation (follow with extubation trials)
 Fluids/inotropes if poor cardiac output
OUTCOMES
 Mortality: 30-40%, usually due to non-pulmonary complications
 Most survivors gain near-normal lung function, often with mildly reduced diffusion capacity
 Associated with cognitive impairment and psychologic difficulties (slowly improve)

Disease of the mediastinum and pleura

PLEURAL EFFUSION
Pleural effusion is an abnormal accumulation of fluid in the pleural space (normally >25ml).
CLASSIFICATION
 Transudate: secondary to  pulmonary blood pressure (e.g. HF) or  oncotic pressure (e.g. cirrhosis, nephrotic syndrome)
 Typically, are bilateral
 Exudate: secondary to  pleural vascular permeability
 Examples: pneumonia, tuberculosis, malignancy, pancreatitis, trauma, collagen vascular disease (RA/SLE)
 Can be either bilateral or unilateral
 A pleural effusion is an exudate if >35g/L protein or 25-35g/L and meets any of Light’s criteria :
 Protein – pleural/serum (>0.5)
 LDH – pleural/serum (>0.6)
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 Pleural LDH (>2/3 upper limit of N serum LDH)

CLINICAL PRESENTATION
 Symptoms : dyspnoea, pleuritic chest pain, and/or cough
 Signs: as detailed above; additionally, a pleural friction rub may be present
DIAGNOSIS
 CXR (initial test) – look for costophrenic angle blunting (a lateral decubitus view is more sensitive and can assess loculation)
 Thoracentesis – indicated if pleural effusion is new finding
 Light’s criteria (LDH and protein)
 Other tests: CBC, cytology, glucose, pH, etc.
 Pleural biopsy – indicated if suspected tuberculosis or malignancy
TREATMENT
 Treat the underlying cause
 Complicated parapneumonic effusions (pH <7.2, LDH >0.5 serum, glucose <3.3mmol, and/or organisms on gram-stain/culture):
 Fibrin layer leads to loculation of pleural fluid
 Treatment: antibiotics and chest drain (treat as empyema)
 Empyema (pus in pleural space, often loculated):
 Associated with fever
 Diagnose with a pleural aspirate (as above and/or macroscopic pus)
 Treatment: antibiotics for at least 4 to 6 weeks (rarely effective on its own) and chest drain
 If difficult to drain – surgical drainage or surgical removal of fibrin coating to allow lung re-expansion (decortication )
 Recurrent effusions:
 Treatment: indwelling pleural catheter or pleurodesis (obliterate pleural space via chemicals)
PNEUMOTHORAX
Pneumothorax is the presence of air in the pleural space .
PATHOPHYSIOLOGY
 Entry of air into pleural space raises intrapleural pressure causing partial lung deflation
AETIOLOGY
 Traumatic
 Iatrogenic (e.g. central venous catheter, thoracentesis, mechanical ventilation)
 Spontaneous:
 Primary (no underlying lung disease) – predominantly tall, healthy, young males who smoke
 Due to rupture of apical subpleural bleb of lung into pleural space
 Secondary (underlying lung disease) – e.g. COPD, severe asthma, or infection
CLINICAL PRESENTATION
 Can be asymptomatic; or presents as acute-onset pleuritic chest pain , dyspnoea, tachypnoea, tachycardia
 Signs:  breath sounds,  chest expansion,  fremitus, hyperresonance
DIAGNOSIS
 CXR – separation of visceral and parietal pleura and/or decreased lung volume on side of pneumothorax
TREATMENT
 Treat underlying cause
 Small pneumothorax – resolve spontaneously; supplemental oxygen is helpful
 Large pneumothorax – chest tube 5 th ICS AAL

Tension pneumothorax
PATHOPHYSIOLOGY
 A pulmonary or chest wall defect acts as a one-way valve causing air
trapping in the pleural space
 Build-up of air pushes the mediastinum to the opposite side of the chest,
which can obstruct venous return to the heart, leading to cardiac arrest and
haemodynamic instability
 Shock and death unless immediately treated
CLINICAL PRESENTATION
 Tension pneumothorax: severe respiratory distress, contralateral tracheal
deviation,  JVP, pulsus paradoxus, hypotension/haemodynamic instability
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DIAGNOSIS
 Tension pneumothorax should be a CLINICAL DIAGNOSIS
 Signs of tension on CXR:
 Reduced lung volume (arrow heads)
 Contralateral tracheal deviation (arrow)
 Contralateral mediastinal (heart) shift (red line)
 Hemidiaphragmatic depression (yellow line)
TREATMENT
 Do NOT perform CXR if clinical diagnosis (life-threatening)
 Needle thoracostomy (large bore needle) 2 nd ICS MCL (or 5 th ICS AAL)  chest tube 5 th ICS AAL

Open pneumothorax
Open pneumothorax occurs in trauma whereby there is a chest wall defect that allows environmental air to enter into the pleural space.
TREATMENT
 Immediate: 3-sided valve (occlusive dressing, taped on 3 sides, that allows air to leave the pleural space but not to enter)
 Curative: surgical wound repair and chest tube 5 th ICS AAL
ATELECTASIS
Atelectasis is the collapse of alveoli within the lung.
PATHOPHYSIOLOGY
 Obstructive ( most common): air distal to obstruction is reabsorbed causing alveolar collapse
 Post-surgical (most common), foreign body, inflammation or infection, or mucous plug (e.g. CF)
 Compressive
 Tumour, lymph node, tuberculosis
 Adhesive: lack of surfactant
 Hyaline membrane disease or prematurity
 Passive (relaxation): a result of air or fluid in the pleural space
 Pleural effusion, pneumothorax
TREATMENT
 Post-surgical: pre-operative smoking cessation ; chest physiotherapy and incentive spirometry ; good analgesic control
ASBESTOS-RELATED PLEURAL DISEASE AND MESOTHELIOMA

PATHOPHYSIOLOGY
 Benign manifestations of asbestos exposure:
 Benign asbestos pleural effusion
 Exudative effusion, typically ~10 years after exposure, self-limiting
 Pleural plaques (usually calcified)
 Marker of exposure, usually asymptomatic
 Mesothelioma (occurs decades after asbestos exposure)
 Primary malignancy of the pleura
 Smoking is not a risk factor (but asbestos and smoking act synergistically to increase the risk)
CLINICAL PRESENTATION AND DIAGNOSIS
 Typically presents as persistent chest pain and progressive dyspnoea
 Open or pleuroscopic biopsy (needle biopsy may seed needle tract with tumour) is diagnostic
 CT staging
TREATMENT
 Supportive (no curative treatment)
CHEST DRAINS
Chest drains are inserted to allow draining of the pleural space of air, blood, or fluid.
MECHANISM
 A simple chest drain utilises an underwater seal (employs positive expiratory pressure and gravity to drain pleural space)
 Acts as a one-way valve to expel air from pleural space and prevent re-entry during inspiration
 Should never be raised above the level of the patient (can allow air/fluid to enter the pleural cavity)
 In certain situations, drainage can also be applied under suction
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MONITORING
 Swinging – fluid in the tube should swing with respiration (rise on inspiration / fall on expiration – due to intra-pleural pressure)
 Bubbling
 Air (pneumothorax) – bubbling is normal
 Bubbling usually occurs during expiration or coughing
 If ceased – suggested of either a blockage or a re-expanded (resolved) lung
 If continuous – suggestive of air leak (e.g. a bronchopleural fistula )
 Fluid (effusion or haemothorax) – bubbling may be due to an air leak (e.g. a bronchopleural fistula )
 Clamping
 Air (pneumothorax) – should never be clamped (may lead to pneumothorax )
 Fluid (effusion or haemothorax) – clamped if excessive fluid drainage (>1L/hr) (can cause re-expansion pulmonary oedema )
MEDIASTINITIS
Mediastinitis is a common post-operative complication of cardiovascular or thoracic surgical procedures .
 Can be acute (secondary to organ perforation) or chronic (secondary to long-standing inflammation and fibrosis)
 Clinical presentation is similar to pneumonia (esp. substernal pain and fever)
 Acute mediastinitis is treated with antibiotics ± drainage ± surgical closure of perforation
MEDIASTINAL MASSES

CLASSIFICATION
 Anterior (4Ts) – Thymoma, Thyroid (goitre), Teratoma, Tumour (esp. lymphoma)
 Middle – typically foregut duplication cysts or lymphadenopathy
 Posterior ( most common ) – neurogenic tumours

Lung neoplasm
LUNG CANCER

FEATURES
 Leading cause of cancer death in New Zealand (20% of all cancer deaths)
 90% smoking related (and consequently 70% preventable)
 Main risk factors include tobacco smoke (except for bronchoalveolar carcinoma) and radon/asbestos exposure .
CLASSIFICATION
 Bronchogenic carcinoma (epithelial lung tumours) are the most common type of primary lung tumour
 Small cell lung cancer (SCLC): 10-15% of cases
 Non-small-cell lung cancer (NSCLC) : 85-90% of cases
 Benign epithelial lung tumours can be classified as papillomas or adenomas
Characteristics of Bronchogenic Cancer
CELL TYPE SMOKING LOCATION HISTOLOGY METASTASIS SURVIVAL (5YR)
Small cell lung Strong Central Neuroendocrine Disseminated at 1% (poorest prognosis)
cancer (strongest (associated with presentation (LABS – Liver,
(10-15%) relation to paraneoplastic Adrenals, Brain, Bone)
smoking) syndromes)
NSCLC are less likely to
metastasise

Adenocarcinoma Weak (most Peripheral Glandular Early, distant 10% (60% for bronchoalveolar carcinoma – a
(most common) common in (mucin subtype with a resectable solitary lesion and
non-smokers) producing) prolific sputum production; may occur at
sites of previous lung scarring)

Squamous cell Strong Central Proximal Local invasion and distant 25%
carcinoma (almost respiratory spread; may cavitate
(30%) exclusively epithelium
seen in (keratin,
smokers) intercellular
bridges)

Large cell / Strong Peripheral Anaplastic, Early, distant 15%

neuroendocrine undifferentiated
carcinomas
(10-15%)
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CLINICAL PRESENTATION
 Primary lesions – present with chronic cough, dyspnoea, chest pain, haemoptysis, constitutional symptoms , and/or clubbing
 Metastases or advanced cancers:
 Pancoast’s tumour (tumour at apex of lung)
 Horner’s syndrome (MEAT – Miosis, Enophthalmos, Anhidrosis, pTosis)
 Brachial plexus palsy (typically C8 and T1 nerve roots)
 Erosion of first rib
 SVC syndrome (with obstruction of the SVC)
 Supraclavicular venous engorgement and facial swelling
 Pemberton’s sign (facial congestion, cyanosis, and respiratory distress on raising both arms above head)
 Hoarseness (with recurrent laryngeal nerve involvement)
 Cardiac tamponade (with pericardial involvement)
 Paraneoplastic syndromes – for example:
 Non-small cell – clubbing, hypertrophic pulmonary osteoarthropathy
 Small cell – ectopic ACTH, SIADH, Lambert-Eaton Myasthenic syndrome
 Squamous cell – hypercalcaemia (osteolysis or PTHrP)
DIAGNOSIS
 Imaging: CXR or chest CT (PET/bone scan for metastases)
 Cytology: sputum
 Biopsy: fine-needle aspiration (CT guided) for peripheral lesions; bronchoscopy (biopsy or brushing) for central lesions
 Labs: CBC, U&E, LFTs, calcium, ALP; genetic screen if adenocarcinoma
TREATMENT
 SCLC – typically unresectable
 Radiation +/- chemotherapy
 Usually recurs and has a low survival rate (1-2 year median survival; 12 weeks without treatment)
 NSCLC – typically resectable
 Surgical resection (if early) +/- adjuvant chemotherapy (or radiotherapy if non-surgical)
SOLITARY LUNG NODULE

CLASSIFICATION
 Benign (70%)
 Infectious granuloma (e.g. TB)
 Other infections (e.g. aspergilloma)
 Benign neoplasms (e.g. lipoma)
 Inflammatory (e.g. GPA, rheumatoid, sarcoidosis)
 Other
 Malignant (30%)
 Bronchogenic carcinoma
 Metastatic lesions
 Pulmonary carcinoid
CXR characteristics of benign versus malignant solitary nodule
PARAMETERS BENIGN MALIGNANT
Size <3cm, round, regular >3cm, irregular, spiculated

Margins Smooth Ill-defined

Features Usually calcified without cavitation Usually not calcified; may have cavity, pleural effusions, and/or
lymphadenopathy

Doubling time Doubles in <1 month or >2 years Doubles in >1 month or <2 years
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TREATMENT

Sleep disordered breathing

Sleep apnoea
Sleep apnoea occurs secondary to disturbances in airflow during sleep that lead to excessive daytime sleepiness and sleep disruption.
 Quantitively measured by the Apnoea/Hypopnoea Index (HPI) – the number of apnoeic and hypopnoeic events per hour of sleep
 Sleep apnoea generally accepted if AHI >15
 Apnoea – absence of breathing for ≥10 seconds
 Hypopnoea –  rate or depth of breathing (>50% reduction in ventilation)
CLASSIFICATION
 Obstructive (OSA) – caused by transient, episodic, obstruction of the upper airway despite persistent respiratory effort
 Risk factors: male gender, obesity, upper airway abnormality, large tongue or uvula, sedative use
 Adenoidal hypertrophy is the most common cause of OSA in children
 Central (CSA) – caused by transient, episodic, decrease in CNS drive to breath (no airflow because no respiratory effort)
 Risk factors: LV failure, brainstem lesions
 Cheyne-Stokes respiration – a form of CSA where apnoea alternates with hyperpnoea (crescendo-decrescendo pattern of TV)
 Mixed (MSA)
CLINICAL PRESENTATION
 Obtain history from spouse or partner
 Typical presentation for OSA is a middle-aged obese male who snores (OSA is strongly associated with snoring)
 Secondary to sleep disturbance: daytime sleepiness, personality changes
 Secondary to hypoxaemia/hypercapnia: morning headache, polycythaemia, pulmonary/systemic hypertension, cor pulmonale/CHF
DIAGNOSIS
 Sleep study (polysomnography) – evaluates sleep stages, airflow, ribcage movement, ECG, EOG, SaO2, and limb movements
 Indicated if: excessive daytime sleepiness, unexplained pulmonary HTN/polycythaemia, daytime hypercapnia
 Important to distinguish CSA from OSA
TREATMENT
 Treat modifiable factors – e.g. weight loss,  sedatives, treatment of underlying medical conditions
 OSA – nasal CPAP, postural therapy (e.g. no supine sleeping), dental appliance , surgery (e.g. tonsillectomy or uvula reduction)
 CSA (or hypoventilation syndromes) – nasal BiPAP/CPAP or respiratory stimulants
COMPLICATIONS
 Associated with sudden death in infants and elderly
 Associated with depression , weight gain , decreased QOL , cardiac complications (e.g. HTN) , and reduced social functioning
NARCOLEPSY
Narcolepsy is a disorder characterised by excessive daytime sleepiness and abnormal REM sleep (enter directly into REM sleep).
 Presumed orexin/hypocretin deficiency due to autoimmune attack (occasionally secondary – head injury, MS, tumour)
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 Associated with cataplexy – intermittent loss of skeletal muscle tone (particularly with strong emotions); sleep paralysis – inability to
move upon wakening; and hypnagogic hallucination – vivid dreams at sleep onset
DIAGNOSIS
 Clinical history
 Polysomnography (with short sleep latency and rapid REM sleep)
TREATMENT
 No cure; but can improve symptoms significantly
 Sleep hygiene
 Restricted driving
 Alerting agents: methylphenidate

Airway management
OXYGEN THERAPY

PHYSIOLOGY
 Adequate oxygenation is required for normal physiologic processes
 Hypoxaemia occurs where PaO2 <60mmHg (approximately SaO2 of 90%)
 Below this point, rapid decreases in oxygen saturation (due to HbO2 saturation curve)
 For example, a PaO2 of 50mmHg is approximately SaO2 of 80%
 The FiO2 of room air is 21%, but by applying supplemental oxygen this can increase up to 100%
INDICATIONS FOR OXYGEN THERAPY
 Hypoxaemia
 CPR
 Patients with chronic hypoxaemia or increased cardiopulmonary workload
 Carbon monoxide or cyanide poisoning
OXYGEN TOXICITY
 Excessive oxygen has several negative effects (e.g. atelectasis, direct pulmonary damage, hypercapnia)
Oxygen-delivery systems
DEVICE OXYGEN DELIVERY ADVANTAGES DISADVANTAGES
Nasal prongs  Flow: 1 to 6 L  Comfort +++  Variable FiO2
 FiO2: 24-44% (4% per L)  Drying (non-humidified air)

Hudson mask  Flow: 8 to 12 L  Comfort  Variable FiO2

 FiO2: 35-60%  Drying (non-humidified air)

Venturi mask  Flow: variable  Comfort  Limited oxygenation

 FiO2: variable  Controlled FiO2

Non-rebreather  Flow: 10 to 15L  Highest FiO2 (of passive devices)  Claustrophobic

mask  FiO2: >60%

Bag and mask  Flow: 0 to 15L  Highest FiO2  Claustrophobic +++

 FiO2: 80-100%  Can assist ventilation  Requires constant attention

NON-INVASIVE VENTILATION

CPAP
Continuous Positive Airway Pressure (CPAP) allows determination of PEEP (peek expiratory end pressure) and FiO2
 Oxygenation levels are related to both PEEP and FiO2
 PEEP allows for recruitment of alveoli and increased oxygenation
 Indicated in: OSA, cardiogenic pulmonary oedema, and atelectasis
EFFECTS
  oxygenation
  work of breathing
  intrathoracic pressure   preload   cardiac workload

BiPAP
Bilevel Positive Airway Pressure (BiPAP) allows determination of two levels of positive pressure , FiO2, and ventilation rate :
 IPAP (inspiratory positive airway pressure)
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 EPAP (expiratory positive airway pressure) – a lower pressure that occurs during exhalation
EFFECTS
 Useful if type 2 respiratory failure or respiratory fatigue ( ventilation and  CO2 levels) (e.g. COPD/asthma exacerbation )
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Dermatology
Basic principles
DEFINITIONS

Lesions versus rashes

 A lesion is a single area of altered skin (and may be single or multiple)
 A rash is a widespread eruption of lesions

Primary lesions
Primary lesions are changes that occur as a direct consequence of a disease process:
 Macule – <1.5cm non-palpable
 Patch – >1.5 cm non-palpable
 Papule – <0.5cm palpable
 Plaque – >0.5cm palpable or raised/plateau like (a confluence of papules)
 Nodule – >0.5cm palpable and nodular
 Cyst – papule or nodule that contains fluid
 Vesicle – <0.5cm fluid filled blister
 Bulla – >0.5cm fluid filled blister
 Wheal – oedematous papule or plaque (caused by swelling in the dermis)
 Pustule – pus filled vesicle

Secondary changes
Secondary changes are changes in the skin that evolve from the primary lesion, or may be caused by trauma/healing:
 Excoriation – marks/abrasions on the skin due to scratching
 Crusting – the result of drying of plasma/exudate which has oozed onto skin
 Fissuring – cracking of epidermis due to excessive dryness
 Lichenification – palpable thickening of epidermis with exaggeration of normal skin lines – usually due to repeat rubbing
 Ulceration – full thickness loss of epidermis (as compared with erosion which is shallow loss of part of epidermis
 Scar – permanent fibrotic changes in skin following damage to the dermis

Distribution
 Annular – ring-like
 Clustered
 Discoid – disc-shaped
 Reticular – lace-like
 Follicular – arise from hair follicles
 Target lesions
 Serpiginous – snake like
 Dermatomal
 Flexural – affecting skin folds

Other dermatological terms

 Confluent – joining together
 Desquamation – peeling skin
 Erythematous – red appearing
 Herpetiform – a rash that looks like a herpes infection with grouped vesicles
 Koebner phenomenon – skin condition affects injured areas of skin
 Morbilliform – a rash that looks like measles (multiple red macules, often confluent)
 Petechiae – <2mm small haemorrhages, non-blanching
 Purpura – >2mm small haemorrhages, non-blanching
 Ecchymoses – large bruises, non-blanching
 Telangiectasia – visible broken capillaries
 Pedunculated – on a stalk
 Scale – flakes of compacted dead skin cells
 Sessile – appears to be stuck to skin surface
 Pigmented – coloured
 Maculopapular – a combination of macules and papules (seen in viral illness)
 Umbilicated – lesion with a central dimple
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Layers of the skin

Allergic and immune-mediated disorders

ECZEMA (ATOPIC DERMATITIS)
Eczema (atopic dermatitis ) is an itchy inflammatory skin condition that is often chronic or relapsing.
 Thought to be due to immune mediated response to environmental factors with skin barrier defects playing a role
CLINICAL PRESENTATION
 Presents as an itchy rash with lichenification (± excoriation) in addition to a history of allergy and dry skin
 Distribution:
 Infants – face, trunk, and limb involvement (diaper area often spared)
 Children and adults – flexures, face, and hands
DIFFERENTIAL DIAGNOSIS
 Pityriasis alba – presents like eczema but with hypopigmentation; it is self-limiting over months to years
 Perioral dermatitis – presents like perioral eczema, but worsens with steroids (treat with metronidazole)
DIAGNOSIS
 Clinical diagnosis
 Formal definition – itchy skin condition in last 12 months, plus three or more of:
 Involvement of skin creases
 History of atopy (asthma, eczema, and allergic rhinitis – the ‘allergic triad’ )
 History of dry skin
 Visible flexural eczema (cheeks, forehead and outer aspects of limbs)
 Onset under two years old
TREATMENT
 Minimise irritants (infections, sweating, stress, soaps and detergents, smoking, food allergies)
 Treatment depends on severity of eczema:
 Clear (normal skin) – emollients (aqueous cream or fatty cream).
 Mild (dry skin and infrequent itching) – emollients and low potency topical corticosteroids (hydrocortisone 1% )
 Moderate (dry skin, itching, redness ) – emollients and moderate topical corticosteroids (Aristocort)
 Severe (widespread dry skin, itching, redness, bleeding) – emollients + potent topical corticosteroids (Beta/Locoid cream )
 May require wet wraps (hydrate and prevent scratching) and referral to dermatology
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 Supportive:
 Anti-histamines to control itchiness
 Anti-biotics for secondary infection
 Anti-septics for cleanliness
COMPLICATIONS
 Eczema herpeticum – secondary HSV infection
 Characterised by rapidly worsening, painful, vesicles or erosions
 Requires urgent referral to dermatology
CONTACT DERMATITIS
Contact dermatitis is a type-IV hypersensitivity reaction that results from allergen contact.
 Common allergens include nickel or perfume (latex allergy is NOT a contact dermatitis – it is a type 1 hypersensitivity reaction)
CLINICAL PRESENTATION
 Presents as rash distributed in the area of allergen contact (often described as linear or angular)
DIAGNOSIS
 Clinical diagnosis
 Patch testing
TREATMENT
 Allergen avoidance
 Corticosteroids (topical  systemic)
HYPERSENSITIVITY REACTIONS

CLASSIFICATION

Types of hypersensitivity
TYPE MECHANISM NOTES EXAMPLES

Type I Antigen cross-links IgE on pre-sensitised mast Fast (occurs in minutes as Anaphylaxis
(anaphylactic/atopic) cells and basophils  triggers release of antibodies are preformed) Asthma
cytokines such as histamine Urticaria

Type II IgM and IgG bind to antigen on host cells, Antibody + complement  MAC Autoimmune haemolytic anaemia
(cytotoxic) leading to lysis by complement or phagocytosis Rheumatic fever
Goodpasture syndrome

Type III IgG and complement binds to soluble antigen, Polyarteritis nodosa
(immune complex) forming a circulating immune complex SLE
Rheumatoid arthritis
This can activate PMNs or deposit in tissues,
fixing complement, which cause inflammation

Type IV Sensitized T-lymphocytes encounter antigen Slow/delayed Tuberculosis skin tests

(delayed/cell-mediated) then release lymphokines (leading to Transplant rejection
macrophage activation) Contact dermatitis

SEBORRHEIC DERMATITIS
Seborrheic dermatitis is a common chronic inflammatory skin disease caused by a hypersensitivity reaction to yeast (Malassezia furfur)
found in sebum and hair follicles.
 Occurs in areas rich in sebaceous glands
CLINICAL PRESENTATION
 Infants:
 Severe, red, diaper rash with scale, erosions, and blisters
 Scalp scaling and crusting (‘cradle cap’)
 Children/adults:
 Red, scaly, patches around the face, scalp, and mid-chest
DIAGNOSIS
 Clinical diagnosis
TREATMENT
 Adults: selenium sulphide shampoo , topical antifungals (ketoconazole), and topical corticosteroids
 Infants: routine bathing and emollients
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PSORIASIS
Psoriasis is a T-cell mediated inflammatory skin condition of unclear aetiology.
CLINICAL PRESENTATION
 Characterised by erythematous plaques with silvery scales
 Typically, affects extensor surfaces (as opposed to eczema)
 Affected by Koebner phenomenon
DIAGNOSIS
 Clinical diagnosis
 Auspitz sign – pinpoint bleeding when scale is scraped
 Biopsy (if uncertain)
TREATMENT
 Local disease: emollients , topical corticosteroids , topical vitamin D analogues , or topical retinoids (vitamin A analogues)
 Severe disease (or psoriatic arthritis): immunosuppressants (except oral steroids), biologics, or phototherapy
COMPLICATIONS
 Psoriatic arthritis (up to 30% of cases) – arthritis of small joints of hands and feet
URTICARIA (HIVES)
Urticaria is a type-I hypersensitivity response characterised by superficial, intense, erythema and oedema in a local area.
 Typically, due to an unidentified trigger (food, drug, virus, etc.)
CLINICAL PRESENTATION
 Urticaria lesions (wheals) – reddish/white transient papules/plaques representing dermal oedema
 If severe – can manifest as angioedema, asthma, joint swelling , and fever
DIAGNOSIS
 Clinical diagnosis (often difficult to determine cause)
TREATMENT
 Systemic antihistamines
 Treat anaphylaxis as indicated
ERYTHEMA MULTIFORME
Erythema multiforme is a cutaneous reaction pattern with many triggers (often infection).
 Associated with HSV or mycoplasma pneumoniae infections
CLINICAL PRESENTATION
 Characterised by targetoid lesions (often on the palms and soles)
 May involve mucous membranes (major form)
DIAGNOSIS
 Clinical diagnosis
 Nikolsky sign – negative (as opposed to SJS/TEN)

Note: the Nikolsky sign is exfoliation of skin on slight rubbing.

TREATMENT
 Symptomatic
 Major form – treated as a burn
STEVENS-JOHNSON SYNDROME (SJS) & TOXIC EPIDERMAL NECROLYSIS (TEN)

FEATURES
 Often caused by first-time exposure to certain drugs
CLASSIFICATION
 SJS/TEN represent two disorders on the spectrum of life-threatening exfoliative mucocutaneous disease
 SJS – involves less than 10% of total body-surface area (BSA)
 TEN – involves greater than 30% of total BSA
CLINICAL PRESENTATION
 Presents as severe mucosal erosions with widespread erythematous macules
 Skin sloughing secondary to full-thickness epidermal necrosis
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DIAGNOSIS
 Clinical diagnosis
 Nikolsky sign – positive
 Biopsy:
 SJS – degeneration of the basal layer of the epidermis
 TEN – full thickness eosinophilic epidermal necrosis
TREATMENT
 LIFE-THREATENING EMERGENCY (admit to ICU/burn unit )
 Stop the offending agent
 Supportive care (as for burns)
COMPLICATIONS
 Similar to burns (see Plastic surgery)
ERYTHEMA NODOSUM
Erythema nodosum is a panniculitis (inflammation of subcutaneous adipose tissue) due to various causes.
AETIOLOGY
 Idiopathic (>50% cases)
 Infection (GAS, tuberculosis, chronic infection)
 Drugs (oral contraceptives , sulpha-containing drugs )
 Chronic inflammation (esp. sarcoidosis, IBD)
CLINICAL PRESENTATION
 Presents as painful erythematous nodules on the anterior shins
 Lesions may turn brown or grey in colour
 Associated with falsely-positive VDRL
DIAGNOSIS
 Clinical diagnosis (must determine underlying cause)
TREATMENT
 Treat underlying cause
 Symptomatic
VESICULOBULLOUS DISEASE
Acquired, Autoimmune, Blistering Dermatoses
FEATURE BULLOUS PEMPHIGOID PEMPHIGUS VULGARIS

Location of blisters Basement membrane zone Intra-epidermal

Autoantibodies IgG produced against hemi-desmosomal proteins IgG anti-desmoglein (desmoglein – keratinocyte adhesion)

Blister appearance Firm, stable, blisters (may be preceded by urticaria) Erosions are more common than intact blisters

Clinical signs Nikolsky negative Nikolsky positive

Asboe-Hansen positive (bullae extend laterally with pressure)

Mucosal involvement Rare Common

Patient age Usually >60 years of age Usually 40-60 years of age

Associated triggers Generally idiopathic ACEs, penicillamine, phenobarbital, penicillin

Mortality Rare Possible

Diagnosis Clinical or skin biopsy Same as bullous pemphigoid

Treatment Steroids (prednisone) High-dose steroids (prednisone) and immunomodulatory

therapy (e.g. azathioprine and IV immunoglobulin)
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Skin manifestations of viral infection

HERPES SIMPLEX (HSV)
Herpes simplex is a recurrent, painful, vesicular eruption due to infection with herpes simplex virus.
 HSV-1 and HSV-2 typically cause oral-labial and genital lesions respectively
PATHOPHYSIOLOGY
 Initial infection is by direct contact, after which the virus remains dormant in local nerve ganglia
 HSV infects epidermal cells, fusing them into multinucleated giant cells
 Local inflammation causes erythema, pain, and swelling
 Recurrences are limited to cutaneous areas innervated by the involved nerve
CLINICAL PRESENTATION
 Characterised by clustered vesicles on erythematous base ( herpetiform rash )
 Onset is proceeded by prodromal pain, fever, malaise, and/or lymphadenopathy
 Primary episodes are generally longer and more severe than recurrences
DIAGNOSIS
 Clinical diagnosis
 Herpes PCR via vesicle swab (can confirm diagnosis)
TREATMENT
 Treatment may be episodic or suppressive (unlike genital herpes, supportive treatment is recommended for all but first episode)
 Episodic treatment: valaciclovir (or acyclovir) for three days
 Provide this as a back-pocket prescription to allow for quick treatment
 Suppressive treatment: regular valaciclovir (or acyclovir) for up to 12 months
 Supportive treatment:
 Salt washes
 Topical anaesthetics
 Oral analgesics
 Oral fluids
VARICELLA-ZOSTER VIRUS (VZV)

CLASSIFICATION
 VZV causes two main diseases:
 Varicella (chicken pox)
 Present as an evolution of red macules to pruritic vesicles that eventually crust over
 Associated with prodromal symptoms (malaise, fever, headache)
 Herpes zoster ( shingles)
 Presents as clustered vesicles on an erythematous base in a dermatomal distribution
 Represents recurrence of VZV in previously infected nerve
 Preceded by intense local pain
 Associated with post-herpetic neuralgia
FEATURES
 Transmission – airborne or direct contact
 Infective period – before lesions till lesions have crusted over
DIAGNOSIS
 Clinical diagnosis
TREATMENT
 Varicella
 Children – self-limiting (and vaccine preventable )
 Adults – systemic antivirals (acyclovir) (to treat symptoms and prevent complications)
 Post-herpetic neuralgia – neuropathic agents
COMPLICATIONS
 Teratogenic – post-exposure prophylaxis (VZV-IG) required for pregnant women
 Bacterial suprainfection (rarely, necrotising fasciitis)
 Progressive varicella (in immunocompromised) – meningoencephalitis, pneumonia, and hepatitis (life threatening)
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MOLLUSCUM CONTAGIOSUM
Molluscum contagiosum is caused a pox-virus infection
FEATURES
 Most common in young children and in AIDS patients
 Transmission – direct contact or sharing infected clothing or towels (highly infectious)
CLINICAL PRESENTATION
 Presents as flesh-coloured dome-shaped papules with central umbilication
(asymptomatic)
DIAGNOSIS
 Clinical diagnosis
TREATMENT
 Reassurance (resolve over months to years)
 Local destruction for cosmetic reasons
VERRUCAE (WARTS)
See Anogenital warts (albeit these occur anywhere on the body).
MEASLES
Measles is a viral exanthem caused by measles virus (a paramyxovirus).
FEATURES
 Transmission – airborne
 Infective period – just before onset until 5 days after rash appears
CLINICAL PRESENTATION
 Presents as non-pruritic erythematous maculopapular rash (morbilliform)
 Appears from head to toe (starts at headline and spreads downwards; palm/sole sparing)
 Palm/sole sparing
 Associated with Koplik spots (irregular red spots with white central areas) on buccal surface
 Preceded by the 3C’s of Measles – Cough, Coryza, Conjunctivitis in addition to low-grade fever
DIAGNOSIS
 Clinical diagnosis
 PCR via swab or measles serology (can confirm diagnosis)
TREATMENT
 Symptomatic (but notifiable)
 Airborne precautions
 Prevention (and post-exposure prophylaxis) – MMR vaccine
COMPLICATIONS
 Secondary bacterial infections ( otitis media, sinusitis, pneumonia) and subacute pansclerosing encephalitis (specific to measles)
RUBELLA (GERMAN MEASLES)
Rubella is a viral exanthem caused by rubivirus.
FEATURES
 Transmission – airborne
 Infective period – 1 week before onset until 1 week after rash appears
CLINICAL PRESENTATION
 Presents as morbilliform rash (but differentiated from measles as children do not appear as ill)
 Associated with STAR complex (Sore Throat, Arthritis, Rash)
 Preceded by low-grade fever and tender generalised lymphadenopathy (esp. posterior nodes)
DIAGNOSIS
 Clinical diagnosis
 Rubella serology (can confirm diagnosis)
TREATMENT
 Symptomatic (but notifiable)
 Airborne precautions
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 Prevention (and post-exposure prophylaxis) – MMR vaccine

COMPLICATIONS
 Acquired disease – excellent prognosis (rarely, encephalitis)
 Congenital disease – congenital rubella syndrome
Congenital rubella syndrome
 Classical triad – sensorineural deafness , eye abnormalities (cataracts) , and congenital heart disease (PDA)
 Additionally, associated with mental retardation and classical purpuric rash (‘blueberry muffin’ lesion)
 It is recommended that all expectant women are tested for immunity status
ERYTHEMA INFECTIOSUM (SLAP CHEEK OR FIFTH DISEASE)
Erythema infectiosum is a viral exanthem caused by parvovirus B19 (targets red cells in the bone marrow).
FEATURES
 Transmission – airborne
 Infective period – low-risk of transmission once symptomatic
CLINICAL PRESENTATION
 Presents as an evolution of rashes (can be present intermittently for up to 6 weeks):
 First rash – hot, firm, red cheeks with perioral sparing (slap cheek )
 Second rash (few days later) – pruritic, erythematous, maculopapular rash with a reticular pattern on limbs and trunk
 Preceded by non-specific prodrome
 Classically, worsens with fever and sun exposure
DIAGNOSIS
 Clinical diagnosis
TREATMENT
 Supportive (e.g. cold flannel to cheeks)
COMPLICATIONS
 Polyarthropathy
 Congenital infection
 Aplastic anaemia
HAND, FOOT, AND MOUTH DISEASE
Hand, Foot, and Mouth Disease is a viral exanthem caused by Coxsackie A16 virus.
FEATURES
 Transmission – direct contact or faecal-oral
 Infective period – infectious for days to months
CLINICAL PRESENTATION
 Presents as classic triad of:
 Lesions of hands and feet – macules that occasionally blister
 Lesions in mouth – painful vesicles/ulcers
 Other lesions – macules on buttocks and arms
 Preceded by fever, anorexia, and oral pain
DIAGNOSIS
 Clinical diagnosis
TREATMENT
 Supportive care (esp. fluids – as dehydration occurs due to painful swallowing)
ROSEOLA (SIXTH DISEASE)
Roseola is a viral exanthem caused by Human Herpes Virus 6 and 7.
FEATURES
 Transmission – saliva
CLINICAL PRESENTATION
 Classic sequence of high fever for several days followed by maculopapular rash as fever subsides
DIAGNOSIS
 Clinical diagnosis
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TREATMENT
 Supportive (e.g. antipyretics )
COMPLICATIONS
 Febrile seizures (in up to 25% of cases)
 Aseptic meningitis
 Thrombocytopenia

Skin manifestations of bacterial infection

IMPETIGO
Impetigo is a local infection of the epidermis that primarily occurs in children.
 Typically, caused by GAS and staphylococci
CLINICAL PRESENTATION
 Presents as pustules and honey-coloured crusts on erythematous base around the face (school
sores)
 Rarely, can cause bullae (almost always due to staphylococci and can be complicated by SSSS)
DIAGNOSIS
 Clinical diagnosis
TREATMENT
 Topical (localised area of infection): hydrogen peroxide 1%
 Oral (extensive/multiple lesions): flucloxacillin
 Complicated/MRSA: co-trimoxazole or erythromycin
Staphylococcal scalded skin syndrome (SSSS)
Staphylococcal scalded skin syndrome is a life-threatening dermatological condition affection children.
 Caused by an exotoxin from coagulase-positive S. aureus
 Characterised by diffuse warm, tender, erythematous skin and flaccid bullae
CELLULITIS
Cellulitis is a skin infection involving the dermis and subcutaneous tissue.
 Typically, caused by GAS (more common) and staphylococci
CLINICAL PRESENTATION
 Presents with red, hot, swollen, tender skin ; often associated with fever and chills
DIAGNOSIS
 Clinical diagnosis
 Culture swabs (may aid in diagnosis and determine antibiotic sensitivities)
TREATMENT
 First choice: flucloxacillin
 Complicated/MRSA: co-trimoxazole or erythromycin
 Diabetic foot infection: augmentin
 Periorbital or facial cellulitis – admit to hospital for IV antibiotics
Erysipelas
Erysipelas is a type of cellulitis confined to the dermis – causes a raised, indurated, well-demarcated, erythematous area of skin .
NECROTISING FASCIITIS
Necrotising fasciitis is a deep bacterial infection along a fascial plane.
 Termed Fournier’s gangrene if involving perineum
PATHOPHYSIOLOGY
 There are three main types of necrotising fasciitis:
 Type 1 (polymicrobial) – mixed anaerobic and aerobic – e.g. S. aureus and E. coli
 Typically, associated with diabetes or other conditions
 Type 2 (GAS) – due to GAS
 Type 3 (gas gangrene) – due to Clostridium perfringens
CLINICAL PRESENTATION
 Presents as acute onset of severe pain and swelling that progresses to anaesthesia
 Associated with an area of erythema , that can progress to a dusky/purplish colour , ultimately leading to necrosis
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 Examination: yellow-green necrotic fascia easily separated by finger, crepitus (gas production), bullae, putrid discharge
DIAGNOSIS
 Urgent surgical exploration (clinical diagnosis is insufficient)
 Tissue culture (determines organisms and antibiotic sensitivities)
TREATMENT
 EMERGENCY surgical exploration and debridement
 Broad-spectrum IV antibiotics: tazocin + clindamycin
OUTCOMES
 Skin-grafting/amputation (if significant tissue loss)
 Up to 25% mortality
COMPLICATIONS
 Sepsis
 Multi-organ failure
INFECTION OF HAIR FOLLICLES

CLASSIFICATION
 Folliculitis – pustule at opening of hair follicle (with hair penetrating)
 Furuncle – abscess at hair follicle
 Carbuncle – multiple confluent furuncle
DIAGNOSIS
 Clinical diagnosis
 Culture swabs (may aid in diagnosis and determine antibiotic sensitivities)
TREATMENT
 First choice: flucloxacillin
 Complicated/MRSA: co-trimoxazole or erythromycin
 Hygiene (most infections are contagious):
 Frequent hand-washing and antiseptics
 Hot wash clothes/bedding/towels and avoid sharing
 Furuncle/carbuncle – may require I&D
ACNE VULGARIS
Acne vulgaris is a skin disease common among adolescents.
 Typically, occurs at puberty and persists for several years
PATHOGENESIS
 Infection of hormonally activated sebaceous gland by Propionibacterium acnes leading to comedo (plugged pilosebaceous follicles)
CLINICAL PRESENTATION
 Acne presents in three different ways:
 Comedonal – open (blackheads) or closed (whiteheads) comedones
 Inflammatory – ruptured comedones creating papules, pustules, nodules, and cysts
 Scarring – may develop as inflammation heals (picking at lesions exacerbates scarring)
 Males are at greater risk for severe cystic acne
 Females are at a risk for cyclical flares with menstruation
DIAGNOSIS
 Clinical diagnosis
TREATMENT
 General hygiene
 Mild acne – topical benzoyl peroxide , topical retinoids , or topical macrolides
 Moderate acne – six-months doxycycline or COC in females (preferred over antibiotics)
 Severe acne – isotretinoin
 Isotretinoin is a major teratogen – contraception and pregnancy test is essential
 Side effects – dry skin/mucous membranes, nose bleeds, skin photosensitivity, depression, elevated lipids/LFTs
 Monitoring – LFTs, lipids, depression screen

Note: progesterone-only contraceptives may can worsen acne.

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PILONIDAL CYSTS
Pilonidal cysts are abscesses in the sacrococcygeal region .
FEATURES
 Most common in 20 to 40 year old men
 Risk factors include deep and hairy natal clefts, obesity, and a sedentary lifestyle
PATHOPHYSIOLOGY
 A folliculitis that becomes an abscess complicated by perineal microbes (esp. Bacteroides) because of repetitive trauma
CLINICAL PRESENTATION
 Presents as an abscess at the natal cleft that can be tender, fluctuant, and warm
 Associated with purulent drainage , cellulitis, and perianal fistulas
 Systemic symptoms are uncommon
DIAGNOSIS
 Clinical diagnosis
TREATMENT
 I&D and sterile packing of wound
 Local hygiene and shaving of sacrococcygeal skin can help prevent recurrence

Skin manifestations of fungal infection

PITYRIASIS (TINEA) VERSICOLOR
Pityriasis versicolor is a fungal infection caused by Malassezia furfur (a yeast that is part of normal skin flora).
 Humid conditions or poor hygiene can create a pathogenic environment for the yeast
CLINICAL PRESENTATION
 Presents with small scaly patches of varying pigmentation on the chest or back
DIAGNOSIS
 Clinical diagnosis
 KOH test – reveals spaghetti and meatball pattern of hyphae and spores
TREATMENT
 Topical antifungals (ketoconazole)
CANDIDIASIS
Candidiasis can be caused by any Candida species.
 C. albicans is the most common causative species
CLINICAL PRESENTATION
 Typically, presents in patients with a history of broad-spectrum antibiotics , long-term steroids , diabetes , or immunocompromise
 Oral candidiasis – presents as painless white plaques that can be easily scraped off
 Oral thrush is common in infancy, but in adults it is often a sign of a weakened immune system
 Skin candidiasis – presents as markedly erythematous patches with occasional erosions and satellite lesions
 In infancy, often seen in diaper area (must differentiate from nappy rash – a form of contact dermatitis)
DIAGNOSIS
 Clinical diagnosis
 KOH test – candida spores and pseudohyphae
 Fungal culture (definitive if diagnosis uncertain)
TREATMENT
 Superficial (skin) candidiasis: topical antifungals (ketoconazole)
 Oral candidiasis: topical nystatin or oral fluconazole tablets
 Diaper rash: topical nystatin
DERMATOPHYTE INFECTION
Dermatophytes are fungi that live in tissues with keratin (skin, nails, and hair) and are a common cause of infection.
FEATURES
 Trichophyton fungi are the most common causative organism
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CLASSIFICATION
 Tinea corporis (ring worm) – pruritic scaly skin infection with sharp irregular border and central clearing
 Tinea pedis – chronic interdigital scaling with erosions (athlete’s foot) or thickened scaly skin on soles (moccasin distribution )
 Tinea cruris (jock itch) – a scrotum-sparing fungal infection of the groin
 Tinea capitis – pruritic scaly scalp infection causing hair loss
 Onychomycosis – fungal nail infection
DIAGNOSIS
 Clinical diagnosis
 KOH test – hyphae
 Fungal culture (definitive if diagnosis uncertain)
TREATMENT
 Non-complicated: topical antifungals (ketoconazole)
 Complicated, onychomycosis, or tinea capitis: oral antifungals (terbinafine)

Parasitic skin infections

LICE

PATHOPHYSIOLOGY
 Lice live off blood and infect specific parts of the body dependent on species (head, body, or pubic lice)
 Sprea d through body contact or sharing of bedding/garments
 They secrete local toxins causing pruritis
CLINICAL PRESENTATION
 Typically, presents as severe pruritis of affected area
 Secondary bacterial infection of excoriation is common
 Classroom epidemics of head lice are common
 Pubic lice contain anti-coagulant in their saliva so bites often turn blue
DIAGNOSIS
 Clinical diagnosis (lice and their eggs, nits, can be seen on hairs or in clothes with the naked eye)
TREATMENT
 General hygiene (wash body, clothes, and bedding thoroughly)
 Head/pubic lice – topical solutions (dimethicone) and mechanical removal
SCABIES

PATHOPHYSIOLOGY
 Scabies is caused by Sarcoptes scabiei (an arthropod) that burrows into the epidermis
 Leads to pruritis that increases in intensity due to an allergy to the mite or its products
 Spread through body contact or sharing of bedding/garments
CLINICAL PRESENTATION
 Typically, presents as severe pruritis (especially at night and after hot showers)
 Secondary bacterial infection of excoriation is common
 Examination – erythematous papules with linear tracks (representing the burrows of the mite)
 Most commonly affects skin folds of the hand , wrist, axillae, and genitals
DIAGNOSIS
 Clinical diagnosis
 Scrapings – mite may be identifiable by scraping an intact tunnel and looking under the microscope
TREATMENT
 Topical permethrin from the neck down (head-to-toe for infants ) for patients and all contacts
 Pruritis can persist up to 2-weeks after treatment
 Clothes and bedding should be thoroughly washed as for lice

Ischaemic disorders of the skin

DECUBITUS ULCERS
Decubitus ulcers result from ischaemic necrosis following continuous pressure on an area of skin that restricts the microcirculation .
 Commonly seen in bedridden populations or patients with limited cutaneous sensation (diabetes)
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CLINICAL PRESENTATION
 Typically, occur on bony prominences (i.e. sacrum or heels)
 May be worsened by incontinence in the classical population
DIAGNOSIS
 Clinical diagnosis
TREATMENT
 Prevention: routinely move bedridden patients and utilise pressure distribution beds
 Low-grade lesions – routine wound care
 High-grade lesions – surgical debridement
GANGRENE
Gangrene is necrosis of body tissue.
CLASSIFICATION
 Dry gangrene – due to insufficient blood flow to tissue (typically, atherosclerosis)
 Wet gangrene – involves bacterial infection (typically, skin flora)
 Gas gangrene – due to Clostridium perfringens infection
DIAGNOSIS
 Clinical diagnosis
 Imaging – X-ray (air in soft tissue is suggestive of gas gangrene)
TREATMENT
 Surgical debridement ± amputation is the mainstay of treatment (antibiotics are an adjuvant therapy)
 Hyperbaric oxygen (toxic to anaerobic C. perfringens) can be used after debridement

Miscellaneous disorders of the skin

ACANTHOSIS NIGRICANS
Acanthosis nigricans is a condition in which the skin in the intertriginous areas (where two skin areas may touch) is hyperkeratotic and
hyperpigmented with a velvety appearance.
 Represents a cutaneous marker of insulin resistance
AETIOLOGY
 Obesity
 Endocrine disease (acromegaly, Cushing syndrome, diabetes)
 PCOS
 Paraneoplastic syndrome (esp. adenocarcinoma of the stomach)
TREATMENT
 Encourage weight loss
LICHEN PLANUS
Lichen planus is a self-limiting, recurrent, or chronic inflammatory disease affecting the skin, oral mucosa, and genitalia.
 Typically, drug-induced (rarely associated with Hep. C infection )
CLINICAL PRESENTATION
 Six P’s (Planar, Purple, Polygonal, Pruritic, Papules, and Plaques)
 Otherwise described as violaceous, flat-topped, polygonal papules
 Associated with Wickham striae (lacy white lines)
 Affected by Koebner phenomena
TREATMENT
 Mild: topical or intralesional corticosteroid
 Severe: systemic corticosteroids ± phototherapy
ROSACEA
Rosacea is a chronic skin disorder of pilosebaceous units with unclear aetiology.
 Occurs in middle-aged patients with fair skin (female predominance)
 Patients with rosacea often have an abnormal flushing response to spicy foods, alcohol, and sun exposure
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CLINICAL PRESENTATION
 Central facial erythema with telangiectasia
 Associated with rhinophyma (severe overgrowth of nasal connective tissue)
 Can predispose patients to blepharitis, hordeolum, and chalazion
TREATMENT
 Mild – topical metronidazole
 Severe or ocular involvement – oral doxycycline
PITYRIASIS ROSEA
Pityriasis rosea is an acute dermatitis probably due to viral infection with HHV-7.
 Typically, self-limiting (heals in 6 to 8 weeks without treatment)
CLINICAL PRESENTATION
 Initial herald patch – erythematous lesion with a peripheral scale
 Secondary eruption – ‘Christmas tree’ pattern of papules and plaques with fine scale (palm/sole sparing)
DIAGNOSIS
 Clinical diagnosis (often confused with tinea corporis)
 Consider VRDL (presents similarly to secondary syphilis)
TREATMENT
 Symptomatic
VITILIGO
Vitiligo is an acquired loss of function or absence of melanocytes leading to distinct areas of depigmentation.
 Unknown aetiology (probably secondary to autoimmune disease)
CLINICAL PRESENTATION
 Present as sharply demarcated, depigmented, macules or patches on otherwise normal skin
 Presents at any age and varies from small to large areas, with or without progression
DIAGNOSIS
 Clinical diagnosis
 Labs (may have serologic markers of autoimmune disease)
TREATMENT
 Topical calcineurin inhibitors ( tacrolimus), topical corticosteroids , or phototherapy
 Supportive:
 Sunscreen (to prevent burns)
 Make-up (or advanced ‘bleaching’ procedures) for cosmetic concerns
KAPOSI SARCOMA
Kaposi sarcoma is a vascular proliferative disease attributed to HHV-8.
 Thought of as an AIDS-defining illness (i.e. typically occurs in patients with HIV)
CLINICAL PRESENTATION
 Presents as multiple violaceous lesions that can progress to plaques (and may involve GIT or lungs)
DIAGNOSIS
 Skin biopsy
TREATMENT
 HAART therapy in HIV positive patients
 Small local lesions – radiation or cryotherapy
 Widespread disease – systemic chemotherapy
CHERRY ANGIOMA (HAEMANGIOMA)
Cherry angioma are small, vascular, red papules that appear anywhere on the body.
 They are the most common benign vascular tumour
TREATMENT
 No treatment necessary
 Small local lesions – excision for cosmetic concerns
 Widespread disease – β-blockers
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DERMATITIS HERPETIFORMIS
Dermatitis herpetiformis is a skin condition that is associated with coeliac disease (due to transglutaminase IgA deposits in the skin).
 Characterised by painful, pruritic, herpetic rash on extensor surfaces
 Diagnosed by biopsy (IgA deposits in the skin)
 Treated with gluten-free diet and dapsone
PORPHYRIA CUTANEA TARDA
Porphyria cutanea tarda is a skin porphyria disorder characterised by formation of tense vesicles/bullae on photo-exposed skin .
 Associated with diabetes , alcohol, hepatitis , haemachromatosis, and several drugs (esp. oestrogen or NSAIDs)
ALOPECIA
Alopecia is a condition in which hair is lost from some or all areas of the body.
CLASSIFICATION
 Androgenetic alopecia (action of testosterone on hair follicles)
 Treatment:
 Minoxidil shampoo (reduce rate of loss/partial restoration)
 Spironolactone or cyproterone acetate (antiandrogens) in women
 Finasteride (5α-reductase inhibitor) in men
 Hair transplant (or other cosmetic procedures)
 Alopecia areata (autoimmune disorder – loss of patches or all hair)
 No satisfactory treatment
EYELID LESIONS
Xanthelasmata
Xanthelasmata are soft yellow plaques seen on the medial aspects of the eyelids.
 Associated with hyperlipidaemia and primary biliary cholangitis
TREATMENT
 Cosmetic
 Lipid-lowering therapy is not typically effective
Blepharitis
Blepharitis is inflammation of the eyelids.
 Associated with crusting of eyelashes, excessive tearing, and a painful burning sensation
 Occurs more frequently in patients with rosacea and seborrheic dermatitis
 Dry eye disease is a frequent complication of blepharitis
TREATMENT
 Warm compresses
 Topical antibiotics (chloramphenicol) if severe
Hordeolum (stye)
Hordeolum is a painful, acute, infection of the tear glands (internal) or eyelid hair follicle (external)
 Typically, due to S. aureus
 May progress to chalazion if untreated
TREATMENT
 Warm compresses
Chalazion
Chalazion is a painless, chronic, inflammatory, cyst of the tear glands.
TREATMENT
 Warm compresses
 Surgical removal (if persistent)
NAEVI (MOLES)
Naevi (moles) are benign tumours made of naevus cells (derived from melanocytes)
CLASSIFICATION
 Junctional nevi (dermoepidermal junction) – flat macule
 Compound nevi (partially in dermis) – slightly elevated papule
 Intradermal nevi (completely in dermis) – dome-shaped papule
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SURGERY
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Anatomy
GASTROINTESTINAL

Layers of abdominal wall

There are six layers to the anterolateral abdominal wall:
 Skin
 Superficial fascia
 Camper’s fascia – fatty superficial layer
 Scarpa’s fascia – deep fibrous layer
 Muscle
 External oblique
 Internal oblique
 Transverse abdominal
 Transversalis fascia
 Extraperitoneal fat
 Peritoneum

Relation of abdominal wall to scrotum

 Skin  forms scrotum
 Superficial fascia  forms dartos muscle and fascia
 External oblique (aponeurosis)  forms external spermatic fascia
 Internal oblique (muscle and fascia)  forms cremaster muscle and cremaster fascia
 Transversalis fascia  forms internal spermatic fascia
 Peritoneum  forms processus vaginalis (obliterated) and tunica vaginalis

Important anatomical structures

 Inguinal canal walls (2-MALT):
 2 Muscles – roof (internal oblique, transversus abdominis)
 2 Aponeuroses – anterior wall (external oblique, internal oblique)
 2 Ligaments – floor (inguinal, lacunar)
 2 T’s – posterior wall (Transversalis fascia, conjoint Tendon)
 Superficial inguinal ring – opening in external oblique aponeurosis; palpable superior and lateral to pubic tubercle
 Deep inguinal ring – opening in transversalis fascia; palpable superior to mid-inguinal ligament
 Structures passing through inguinal canal
 In Males – the spermatic cord and ilioinguinal nerve
 Contents of spermatic cord
 3 Arteries – artery to vas deferens, testicular artery, cremasteric artery
 3 Nerves – genital branch of genitofemoral nerve, SNS and visceral afferent fibres, ilioinguinal nerve (passes outside
spermatic cord, travelling next to it into the scrotum; it passes through the superficial inguinal ring but does not run
through the canal formally)
 3 Fascial layers – external spermatic, cremasteric, and internal spermatic fascia
 3 Other structures – pampiniform plexus, vas deferens, testicular lymphatics
 In Females – the round ligament of uterus and ilioinguinal nerve
 Femoral triangle :
 Superior border – inguinal ligament
 Lateral border – sartorius muscle
 Medial border – medial border of adductor longus
 Roof – fascia lata
 Floor – pectineus, iliopsoas, and adductor longus
 Contents (NAVEL – lateral to medial)
 Femoral sheath
 Femoral Nerve
 Femoral Artery
 Femoral Vein
 Empty space (i.e. the femoral canal)
 Site of femoral hernias through the opening of the femoral canal called the femoral ring
 Lymphatics
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Cancer
Gastrointestinal cancer
OESOPHAGEAL CANCER

PATHOPHYSIOLOGY
 Adenocarcinoma – occurs in Western countries due to Barret oesophagus (intestinal metaplasia)
 Squamous cell carcinoma – occurs in Asian countries due to smoking and alcohol
 Oesophageal cancer metastases early (due to lack of serosa)
CLINICAL PRESENTATION
 Typically, presents late with progressive dysphagia (solids  liquids) and odynophagia then constant pain
 Associated with constitutional symptoms, reflux/regurgitation, and gastrointestinal bleeding
DIAGNOSIS
 Full metastatic workup (CBC, U&E, LFTs, CXR, CT chest/abdomen/pelvis, bone scan)
 Barium study (initial test) – narrowing of oesophagus and irregular border protruding into lumen
 EGD with biopsy (definitive test)
 Endoscopic U/S (useful for staging)
TREATMENT
 Chemoradiotherapy ± surgical resection with large margins (poor prognosis )
Barrett’s oesophagus
PATHOPHYSIOLOGY
 Long-standing GORD causes pre-malignant intestinal metaplasia of stratified squamous epithelium lining the oesophagus
 Strongly associated with adenocarcinoma
TREATMENT
 Indefinite acid suppressive therapy (medical or surgical)
 Surveillance endoscopy ± mucosal ablation or resection
STOMACH CANCER (ADENOCARCINOMA)

FEATURES
 Typically, occurs in Asian countries
 Risk factors – H. pylori, smoking, alcohol, diet high in nitrites, pernicious anaemia, blood type A
CLINICAL PRESENTATION
 Typically, presents late with refractory gastric ulcers and constitutional symptoms
 May present with epigastric mass or gastrointestinal bleeding
 Associated with acanthosis nigricans
 Classical signs:
 Virchow’s node – left supraclavicular lymphadenopathy
 Krukenberg tumour – metastases to ovary
 Sister Mary Joseph node – metastases to umbilicus
DIAGNOSIS
 Full metastatic workup (CBC, U&E, LFTs, CXR, CT chest/abdomen/pelvis, bone scan)
 EGD with biopsy (definitive test)
 Endoscopic U/S (useful for staging)
TREATMENT
 Surgical resection ± chemoradiotherapy
HEPATOCELLULAR CARCINOMA

FEATURES
 Risk factors – cirrhosis, chronic hepatitis B or C, OCP, smoking, alcohol
CLINICAL PRESENTATION
 Symptoms – typically, RUQ pain with signs of chronic liver disease and constitutional symptoms
 Signs – tender hepatomegaly
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DIAGNOSIS
 Full metastatic workup (CBC, U&E, LFTs, CXR, CT chest/abdomen/pelvis, bone scan)
 Labs – classical triad of elevated ALP, bilirubin, AFP (serum marker )
 Imaging – abdominal U/S, CT, or MRI
 Liver biopsy (definitive)
TREATMENT
 Non-surgical – transarterial chemoembolization (TACE) and/or radiofrequency ablation
 Surgical – partial hepatectomy (liver transplantation if indicated – Milan criteria)
OUTCOMES
 Mortality – 5% at 5-years (higher if complete resection)

Note: metastatic lesions are the most common malignant tumours in the liver (most often from gastrointestinal tract )
PANCREAS CANCER

FEATURES
 Typically, adenocarcinoma of head of pancreas
 Risk factors – smoking, chronic pancreatitis, family history
CLINICAL PRESENTATION
 Typically, vague abdominal pain with obstructive jaundice and constitutional symptoms
 Although, painless jaundice is pancreatic cancer until proven otherwise
 May present with Courvoisier sign (palpable, non-tender, gallbladder)
DIAGNOSIS
 Full metastatic workup (CBC, U&E, LFTs, CXR, CT chest/abdomen/pelvis, bone scan)
 Labs – CA-19-9 (serum marker) (otherwise non-specific cholestatic picture)
 Imaging – abdominal U/S or ERCP/MRCP/PTC or CT/MRI
TREATMENT
 Resectable (10%) – pancreaticoduodenectomy ± adjuvant chemotherapy (poor prognosis)
 Non-resectable – palliative chemotherapy ± decompression (ERCP with stenting )
OUTCOMES
 Mortality – 1% at 5-years (higher if complete resection)
BOWEL CANCER

FEATURES
 Risk factors (typically, patients have no specific risk factors):
 Age (>50 years old) (dominant factor)
 Smoking
 Diet (low-fibre)
 Colonic conditions – adenomatous polyp, IBD (esp. UC), personal history
 Genetic conditions – FAP, HNPCC, family history
CLINICAL PRESENTATION
 Approximately one-quarter of patients have metastatic disease at time of presentation (typically, liver, lung, bone, and brain)
 Elderly patients who present with iron-deficiency anaemia should be investigated for colon cancer
Clinical presentation of CRC
RIGHT COLON LEFT COLON RECTUM

Morphology Exophytic lesions with occult bleeding Annular, invasive, lesions Ulcerating lesions

Clinical  Constitutional symptoms  CIBH (constipation ± overflow)  CIBH (constipation ± overflow)

presentation  Iron-deficiency anaemia  Decreased stool calibre  Tenesmus
 Obstruction is rare  Abdominal pain  Rectal bleeding
 Rectal bleeding

Signs  Iron deficiency anaemia  BRBPR  BRBPR

 RLQ mass (10%)  LBO  Palpable mass on DRE
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INVESTIGATIONS
 Full metastatic workup (CBC, U&E, LFTs, CXR, CT chest/abdomen/pelvis, bone scan)
 Labs – CEA (serum marker)
 Imaging:
 Colonoscopy with biopsy (gold standard)
 CT colonography
 Endorectal U/S
TREATMENT
 Colon cancer – wide surgical resection and lymphadenectomy ± adjuvant chemotherapy
 Rectal cancer – LA resection (if adequate distal margins) or AP resection (if inadequate distal margins)
 Palliation – proximal diversion (for obstruction) and radiation (for bleeding or pain)
OUTCOMES
 Mortality – 50% at 5-years (anastomotic leakage associated with poor prognosis)

Genitourinary cancer
RENAL CELL CARCINOMA

FEATURES
 Risk factors – smoking, hypertension, obesity
 Typically, a clear cell histology
CLINICAL PRESENTATION
 Typically, presents late with gross haematuria, palpable mass , and flank pain
 Constitutional symptoms are a poor prognostic factor
 Associated with early metastases and several paraneoplastic syndromes
DIAGNOSIS
 Full metastatic workup (CBC, U&E, LFTs, CXR, CT chest/abdomen/pelvis, bone scan)
 Labs – urinalysis (including cytology )
 Renal U/S
 Renal biopsy (to confirm diagnosis)
TREATMENT
 Partial or radical nephrectomy and lymphadenectomy ± chemoradiotherapy
OUTCOMES
 Mortality – variable (metastases associated with poor prognosis)
BLADDER (UROTHLELIAL) CANCER

FEATURES
 Typically, occurs in elderly males
 Risk factors – smoking (first-world) and schistosomiasis (third-world)
CLINICAL PRESENTATION
 Typically, presents with painless haematuria (± other urinary symptoms)
DIAGNOSIS
 Full metastatic workup (CBC, U&E, LFTs, CXR, CT chest/abdomen/pelvis, bone scan)
 Labs – urinalysis (including cytology )
 Cystoscopy with biopsy (gold standard)
TREATMENT
 Superficial (non-muscle invasive) – TURBT ± intravesical chemo/immunotherapy (e.g. BCG or mitomycin )
 Invasive (muscle) – radical cystectomy or TURBT + chemoradiotherapy
PROSTATE MASS

CLASSIFICATION
 Benign prostatic hypertrophy (BPH) – a normal process affecting the transition (peri-urethral) zone of prostate
 Prostate cancer – an adenocarcinoma affecting the peripheral zone of the prostate (most common cancer in men)
 Risk factors – age and family history
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FEATURES
 Both BPH/prostate cancer increase in prevalence with age (almost all elderly men will be affected)
 Both BPH/prostate cancer can co-exist (but are not associated with each other)
 However, there is only a minor risk of death from prostate cancer
CLINICAL PRESENTATION

Benign prostatic hypertrophy versus prostate cancer

BENIGN PROSTATIC HYPERTROPHY PROSTATE CANCER

Clinical  Presents with obstructive and irritative urinary symptoms  Typically, asymptomatic
presentation  Obstructive – hesitancy, weak/intermittent stream, retention  May present with obstructive urinary symptoms
 Irritative – frequency, urgency, nocturia  May present with back pain, lymphoedema, and constitutional
symptoms due to bony metastases (sclerotic)

DRE  Smooth, uniformly enlarged, rubbery prostate  Hard, irregular, nodular prostate

Diagnosis  Clinical diagnosis  Transrectal ultrasound guided needle biopsy

 As for prostate cancer (if diagnosis uncertain)  Metastatic imaging (CT/bone scan)

Treatment  Medical:  Watchful waiting (if elderly/low-grade)

 α-blockers (doxazosin)  Chemoradiotherapy
 5α-reductase inhibitors (finasteride)  Hormonal therapy (androgen ablation)
 Surgical (gold standard) – TURP  Radical prostatectomy (risk of impotence/incontinence)

Prostate-specific antigen (PSA)

 Prostate cancer screening with PSA is controversial
 Many causes of increased PSA – BPH, prostate cancer, prostatitis, instrumentation, ejaculation
 Not useful as a diagnostic test (more useful for monitoring levels over time )
TESTICULAR CANCER

FEATURES
 Typically, affects young males
 Risk factors – cryptorchidism, infertility (e.g. Klinefelter’s syndrome), past/family history
CLASSIFICATION
 Germ cell (malignant)
 Seminoma (most common) (placental ALP)
 Embryonal cell carcinoma
 Teratoma ( AFP/β-hCG)
 Choriocarcinoma (β-hCG)
 Yolk sac (AFP)
 Non-germ cell (usually benign)
 Leydig (testosterone/oestrogen )
 Sertoli

Note: serum tumour markers are highlighted .

CLINICAL PRESENTATION
 Typically, presents with painless testicular enlargement
DIAGNOSIS
 Full metastatic workup (CBC, U&E, LFTs, CXR, CT chest/abdomen/pelvis, bone scan)
 Testicular U/S (initial test)
 Radical inguinal orchidectomy (definitive test and component of treatment)
 Tumour markers (as above)
TREATMENT
 Radical inguinal orchidectomy ± adjuvant chemoradiotherapy
OUTCOMES
 Very good prognosis
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Breast surgery
Basic principles
BREAST LESIONS

DIFFERENTIAL DIAGNOSIS
 Breast mass:
 Fibrocystic disease
 Fibroadenoma
 Mastitis/abscess
 Fat necrosis
 Breast cancer
 Nipple discharge:
 Intraductal papilloma (unilateral bloody)
 Mammary duct ectasia (unilateral green)
 Mastitis/abscess (unilateral purulent)
Differential diagnosis of breast mass
CONDITION CLINICAL PRESENTATION TREATMENT

Fibrocystic disease  Fibrous/cystic changes in the breast which vary with menstrual cycle  Reassurance
 Cyclical bilateral breast pain (most prominent before menstruation)  Analgesia
 Associated with nipple discharge (straw-like or green)  OCP

Fibroadenoma  Painless, firm, rubbery, mobile mass (benign tumour)  Observation

 Similar presentation to Phyllodes tumour (requires biopsy to differentiate)  Surgical excision (if large)

Mastitis/abscess  Inflammatory signs ± nipple discharge (usually S. aureus)  Antibiotics (flucloxacillin)

 I&D (if abscess)

Fat necrosis  Ill-defined mass resulting from breast trauma  Reassurance

Breast cancer See Breast cancer. See Breast cancer.

Differential diagnosis of nipple discharge

CONDITION CLINICAL PRESENTATION TREATMENT

Intraductal papilloma  Benign tumour leading to spontaneous, unilateral, bloody nipple discharge  Surgical excision

Mammary duct ectasia  Blockage of ducts leading to spontaneous, unilateral, green nipple discharge  Reassurance

Assessment of breast lesions

DIAGNOSIS
Triple Assessment (a clinical approach to breast lesions):
 Clinical examination
 Radiology
 Ultrasound (if premenopausal)
 Mammography (if postmenopausal)
 Histology/cytology
 FNA or core biopsy (rarely, excision biopsy)
BREAST SCREENING
 Breast Screening Aotearoa – mammograms for asymptomatic women between 45 to 69 every two years
BREAST CANCER

FEATURES
 Female gender (greatest risk factor)
 Age (second greatest risk factor)
 Excess oestrogen (early menarche, late menopause, nulliparity; also, obesity, DM, PCOS, unbalanced HRT)
 Alcohol
 Personal history (or prior breast biopsy)
 Family history (or genetic factors, such as BRCA1/2)
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Note: breastfeeding is a protective factor and smoking is not a risk factor for breast cancer.
CLINICAL PRESENTATION
 Early – painless, immobile, mass with ill-defined margins
 Late – lymphadenopathy, fixation, skin changes, nipple inversion
 Peau d’orange – redness, thickening, and dimpling of the skin
 Metastasis – typically, metastasis to bone, lung, liver and brain

Note: majority of breast cancer occurs in the upper outer quadrant.

DIAGNOSIS
 Triple Assessment
 Receptor status – ER/PR/HER2
 Additional:
 Imaging – CXR, CT chest/abdomen/pelvis, MRI brain, or bone scan (screening for metastatic lesions)
 Labs – LFTS, ALP, CRP, calcium (screening for metastatic lesions)
 Genetic screening – BRCA1/BRCA2 (consider if male, bilateral, young, family history, or breast and ovarian cancer)
TREATMENT
 Early:
 Breast-conserving surgery (lumpectomy) + radiotherapy or mastectomy
 Sentinel node biopsy ± axillary dissection (if node positive)
 Late:
 Mastectomy + axillary dissection + radiotherapy + neoadjuvant chemotherapy
 Receptor-specific treatment:
 ER/PR
 Tamoxifen (SERM – selective oestrogen receptor modulator)
 Aromatase inhibitor if postmenopausal (inhibits aromatase – converts peripheral androgens to oestrogen)
 HER2
 Transtuzumab
OUTCOMES
 Prognosis most reliably staged by TNM staging
 ER/PR positive – good prognosis
 HER2 positive – poor prognosis
 Overall mortality is 50% at 5-years
TNM staging
T N M
I – tumour size <2cm I – movable ipsilateral axillary node I – distant metastases
II – tumour size 2-5cm II – fixed ipsilateral axillary node
III – tumour size >5cm III – ipsilateral infra/supraclavicular node; or
IV – extension (chest wall/skin) clinically detected lymph node with axillary
node

BRCA1/2 (tumour suppressor genes)

Autosomal dominant:
 BRCA1 mutation – major risk factor for breast and ovarian cancer
 BRCA2 mutation – major risk factor for breast and ovarian cancer (also prostate cancer in men)

Clinically relevant breast anatomy

 Lymphatic drainage
 Axillary lymph nodes – 75% of lymph drainage
 Parasternal lymph nodes – 25% of lymph drainage
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Plastic surgery
NON-MALIGNANT LESIONS
Seborrheic keratosis
Seborrheic keratosis is a benign skin lesion of unknown aetiology that appears in almost all people after age 40.
CLINICAL PRESENTATION
 Exophytic waxy brown papules/plaques with superficial keratin cysts
 Lesions can become irritated either spontaneously or by external trauma
DIAGNOSIS
 Clinical diagnosis
 Biopsy lesions in which diagnosis is uncertain
TREATMENT
 Surgical – cryotherapy , curettage, or excision
Actinic keratosis
Actinic keratosis is a pre-malignant skin lesion (transforms to SCC) that occurs on sun-exposed areas in older patients.
CLINICAL PRESENTATION
 Ill-defined erythematous lesions on sun-exposed areas with a light scale/crust
DIAGNOSIS
 Clinical diagnosis
 Biopsy lesions in which diagnosis is uncertain or if refractory to treatment
TREATMENT
 Surgical – cryotherapy , curettage, or excision
 Medical – topical fluorouracil (5-FU) or imiquimod
MALIGNANT LESIONS
Basal cell carcinoma
Basal cell carcinoma is the most common malignant skin cancer (and most common malignancy in humans).
FEATURES
 Slow growing and locally destructive, but virtually no metastatic potential
 Risk factor – cumulative sun exposure (occurs on sun-exposed areas)
CLINICAL PRESENTATION
 Presents as slowly enlarging lesion (in elderly) that does not heal and that bleeds when
traumatized (may have rolled outer edges and a central depression)
 Varying degrees of pigmentation, ulceration, and depth of growth
DIAGNOSIS
 Clinical diagnosis but requires biopsy (e.g. by excision)
TREATMENT
 Surgical – cryotherapy , curettage, or excision
 Medical – imiquimod
 Mohs surgery (gold standard)
OUTCOMES
 Extremely good prognosis (but can rarely be advanced and require chemoradiotherapy )
Squamous cell carcinoma
Squamous cell carcinoma is the second most common malignant skin cancer .
FEATURES
 Locally destructive, with potential for metastasis and death
 Risk factors – cumulative sun exposure (occurs on sun-exposed areas)
 Also, smoking (esp. lower lip lesion), radiation, burns/chronic trauma, and immunosuppression
CLINICAL PRESENTATION
 Variable clinical presentation – e.g. erythematous, ulcerated, papule or nodule (typically, more rapid enlargement than BCC)
 Typically occurs in older adults with sun-damaged skin and arises from actinic keratoses
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DIAGNOSIS
 Clinical diagnosis but requires biopsy (e.g. by excision)
TREATMENT
 Surgical – excision
 Mohs surgery (gold standard)
OUTCOMES
 Good prognosis (but requires life-long follow-up)
Bowen’s disease (SCC in situ)
Bowen’s disease is an in situ precursor to squamous cell carcinoma.
MELANOMA
Melanoma is the most common life-threatening dermatologic disease.
PATHOPHYSIOLOGY
 Malignant melanoma begins in the epidermal basal layer (where melanocytes are found)
 Melanomas metastasise anywhere in the body (5% patients with metastatic disease have no known primary lesion)
FEATURES
 Risk factors – fair skin , red hair, intense bursts of sun exposure , multiple nevi , personal/family history , and
immunosuppression
CLINICAL PRESENTATION AND DIAGNOSIS
 ABCDE of melanoma:
 Asymmetry
 Irregular Border
 Variations in Colour
 Diameter (>6mm)
 Evolution (changing or new skin lesions)

Note: pruritis in a changing skin lesion is suspicious feature for malignant change.
TREATMENT
 Treatment algorithm:
 Excision biopsy with margins (2mm of normal skin and a cuff of subcutaneous fat deep to lesion), followed by
 Excision of full depth of dermis and additional margin after histologic diagnosis
 1cm margin – if <1mm Breslow thickness
 2cm margin – everything else
 Requires lifelong clinical follow-up
 Advanced disease:
 Chemotherapy , biologic, or radiation therapy may be used for recurrent/metastatic melanoma (palliative)
OUTCOMES
 Malignant melanomas are staged by Breslow thickness (depth of invasion in millimetres) and TMN staging
 The greatest prognostic factor is Breslow thickness
 Mortality ranges from 90% at five-years for low stage/thickness to 10% at five-years for high stage malignant melanomas
 Sentinel lymph node biopsy is useful for staging but does not increase survival
BURNS

AETIOLOGY
 Burns can be due to thermal (most common), chemical, radiation, or electrical sources
PATHOPHYSIOLOGY
 Functions of the skin (and consequences of burn injuries):
 Thermoregulation – must keep patient covered and warm to prevent loss of body heat
 Fluid regulation – fluid resuscitation is imperative due to large loss of water and protein from skin and other body tissues
 Immunological barrier – antimicrobial dressings or antibiotic cover necessary due to high risk of infection
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Burn depth
NOMENCLATURE DEPTH CLINICAL FEATURES
First degree Epidermis Painful, sensation intact, erythema, blanchable
(superficial epidermal)

Second degree Epidermis and varying (partial) thicknesses of the dermis Painful, sensation intact, erythema, blisters, blanchable
(superficial, mid, or (difficult to distinguish from full thickness if deep dermal)
deep dermal thickness)

Third degree The epidermis, the full thickness of the dermis, and Painless, insensate, white/grey/black leathery skin
(full thickness) potentially deeper tissues are involved

Acute care of burn patients

First aid
 STOP – the burning process
 COOL – the burn (run under cool water for 20 minutes)
 Reduces inflammatory mediators
 Maintains viability of the zone of stasis
Four stages of management
 SURVEY – primary and secondary survey (look for myoglobinuria – can cause discolouration of urine in burns)
 ASSESSMENT – determine depth
 MANAGEMENT – treatment specific to depth of burn and associated injuries
 First degree – topical creams/oral NSAIDs
 Second degree – daily dressing changes with topical antimicrobials (e.g. silver sulfadiazine)
 Third degree – surgical (e.g. debridement, grafting), dressing, prevention of wound contracture (e.g. splints, physiotherapy)
 Management may include escharotomy or tracheostomy
 REHABILITATION
Other considerations
 Parkland formula (fluid repletion in severe burns):
 Fluids for the first 24 hours (mLs) = 4 x patients’ weight (kg) x TBSA (%)
 Delivered 50% over 8 hours followed by 50% over 16 hours
 Analgesia – IV opiates
 Nutritional supplementation
TRANSFER TO BURN CENTRE CRITERIA
 Burns greater than 10% (5% if full thickness) TBSA in adults
 Burns greater than 5% TBSA in children
 Burns over critical areas (face, hands, feet, genitals, perineum, major joints)
 Circumferential burns
 Chemical, electrical, or lightning injury
 Inhalation injury
 Burns at extremes of age, with pre-existing medical disorders, or associated with trauma
OUTCOMES
 Prognosis best determined by: burn size (TBSA) , age of patient , and presence/absence of inhalational injury
 TBSA is clinically determined by the rule of 9s (for second- and third-degree burns):
 Head and each arm – 9%
 Back and chest each – 18%
 Each leg – 18%
 Perineum – 1%
 Inhalational injury – worsens mortality significantly (three major causes)
 Airway injury above larynx – burn to airway from hot gases causing neck and airway oedema
 Airway injury below larynx – due to inhalation of products of combustion
 Systemic intoxication – carbon monoxide (treat with 100% O2) or cyanide (fatal)
COMPLICATIONS
 Shock, compartment syndrome (due to stricture), and superinfection (most likely due to pseudomonas)
CARPAL TUNNEL SYNDROME
Carpal tunnel syndrome is caused by median nerve compression at the level of the flexor retinaculum .
 As opposed to pronator teres syndrome , which is median nerve compression at the level of the elbow
 Most common entrapment neuropathy
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AETIOLOGY
 Typically, idiopathic (esp. if job/hobby related repetitive usage)
 Secondary causes:
 Space occupying lesions
 Physiologic (pregnancy, hypothyroidism, acromegaly, rheumatoid arthritis)
 Infection
 Neuropathy
 Familial disorders
CLINICAL PRESENTATION
 Numb/painful hand (esp. at night) that is typically relieved by shaking/dangling/rubbing
 Sensory loss in median nerve distribution
 Advanced cases: thenar wasting/weakness (due to involvement of motor branch of nerve)
 Carpel tunnel compression test (more useful than Tinel/Phalen signs):
 Examiner presses thumbs over carpal tunnel and holds pressure for 30 seconds
 Onset of pain or paraesthesia within 30 seconds is a positive result of the test
DIAGNOSIS
 Clinical diagnosis
 EMG (confirms, but does not exclude, diagnosis)
TREATMENT
 Basic advice – avoid repetitive wrist and hand motion
 Conservative – wrist splints at night and when repetitive wrist motion is required (reduces pressure on median nerve)
 Medical – NSAIDs +/- local corticosteroid injections
 Surgical – transverse carpal ligament incision to decompress median nerve (if unresponsive to conservative measures)
 Complications : injury to median motor nerve branch, scar formation, pain, and damage to transverse vascular arch
TENDON CONDITIONS

CLASSIFICATION
 De Quervain’s tenosynovitis – inflammation in first extensor compartment (APL and EPB)
 Clinical presentation – radial wrist pain and positive Finkelstein test (thumb in fist and ulnar deviation of hand causes pain)
 Treatment – NSAIDS ± steroid injection ± surgical release of APL and EPB tendon sheaths
 Ganglion cyst – fluid-filled cyst originating from tendon sheath (most common soft tissue tumour of hand and wrist)
 Treatment – conservative ± aspiration (highly recurrent) ± surgical excision
 Stenosing tenosynovitis (trigger finger) – inflammation of synovium causing locking of finger in flexion/extension
 Treatment – NSAIDS ± steroid injection
PAEDIATRIC PLASTIC SURGERY

Orofacial clefts (cleft lip and palate)

CLASSIFICATION
 Cleft lip – failure of fusion of maxillary and medial nasal processes
 Male-to-female ratio is 2:1 (more common on the left side)
 Cleft palate – failure of fusion of lateral/median palatine processes and nasal septum
TREATMENT
 Multi-disciplinary approach (special feeding, speech language therapy , orthodontics ,
surgery)
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General surgery
Surgical complications
POST-OPERATIVE FEVER
Post-operative fever does not necessarily imply infection.
DIFFERENTIAL DIAGNOSIS
5W’s of post-operative fever :
 Wind (first few days) – pneumonia (also, atelectasis – controversial)
 Water (first week) – infection (esp. UTI)
 Wound (first week) – wound infection or abscess (consider C. difficile or GAS if early)
 Walk (after first week) – DVT/PE
 Wonder about drugs (anytime) – drug fever or reaction to blood products

Stomach
HIATUS HERNIA

CLASSIFICATION

Types of hiatus hernia

TYPE DESCRIPTION TREATMENT
Sliding (95%) Herniation of both stomach and gastroesophageal junction into the thorax  Medical therapy (as for GORD)
 Nissen fundoplication
Paraesophageal (5%) Herniation of stomach fundus into thorax

CLINICAL PRESENTATION
 Majority are asymptomatic (larger hernias may cause GORD)

Intestine
ABDOMINAL HERNIA
Abdominal hernia is a defect in the abdominal wall causing abnormal protrusion of intra-abdominal contents .
FEATURES
 Male-to-female ratio is 10:1 (lifetime risk for males is 25%)
 Frequency – indirect > direct > incisional > femoral > umbilical > other
CLINICAL PRESENTATION
 Mass of variable size
 May be tender (relieved by supine position or with reduction)
 Associated with vomiting or constipation
 Examination – transmits palpable impulse with coughing or straining
DIAGNOSIS
 Clinical diagnosis
 Imaging – U/S ± CT (if suspected)
TREATMENT
 Asymptomatic – observation
 Symptomatic – tension-free hernioplasty (mesh closure)
 Complicated – herniorrhaphy (surgical closure under tension)
COMPLICATIONS
 Bowel obstruction (within hernial sac)
 Incarceration (irreducible hernia)
 Strangulation (ischaemic hernia) – surgical emergency
 Presents as intense pain
 Small hernias are more dangerous as a tight defect is more likely to strangulate (esp. femoral hernias)
 Reduction en-masse (manual reduction with persistently incarcerated/strangulated hernia)
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CLASSIFICATION

Types of groin hernia

TYPE LOCATION AETIOLOGY PREVALENCE
Indirect (inguinal)  Herniation through both external/internal inguinal rings  Results from congenital patent Most common hernia in
 Lateral to the inferior epigastric vessels processus vaginalis (20% of adults) men and women
 Often descends into scrotal sac, or labia majora

Direct (inguinal)  Herniation through floor of Hesselbach triangle (area  Mechanical breakdown in
bound by inguinal ligament, inferior epigastric vessels, and transversalis fascia (‘wear and tear’)
rectus abdominis)  Increased intra-abdominal pressure
 Medial to inferior epigastric vessels
 Usually does not descend into scrotal sac

Pantaloon  Hernia sac exists as both a direct and indirect hernia N/A Rare
straddling the inferior epigastric arteries

Femoral  Herniation below inguinal ligament through femoral canal  Increased intra-abdominal pressure Mostly affects females
 Below and lateral to pubic tubercle  Weakened pelvic floor

SMALL BOWEL OBSTRUCTION (SBO)

CLASSIFICATION
 Partial – passage of flatus but not stool
 Complete – no passage of flatus or stool (obstipation)
 Closed loop – intestine obstructed proximally and distally (e.g. volvulus)
AETIOLOGY
 Causes of SBO – SHAVING (Stricture , Hernia, Adhesions, Volvulus, Intussusception /IBD, Neoplasms, Gallstones)
 Frequency – adhesions (from prior surgery) (75% of SBO) > hernias > neoplasms

Note: patients presenting with SBO in a ‘virgin’ abdomen are indicated for surgical exploration.
DIAGNOSIS
 Imaging:
 AXR – triad of dilated small bowel , air-fluid levels , paucity of air in colon
 CT – 3-6-9 rule (distension classified as small bowel ≥3cm; colon ≥6cm; caecum ≥9cm)
 Labs – non-specific
TREATMENT
 Surgical Support Squad – NPO ± NGT ± IV fluids ± catheter ± analgesics ± anti-emetics
 Partial obstruction – supportive care
 Complete obstruction – urgent surgery
COMPLICATIONS
 Strangulation (if closed-loop)
 Bowel rupture (presents with peritonism and sepsis)
Paralytic Ileus (functional SBO)
Ileus is a temporary loss of peristalsis without structural obstruction.
 Typically, due to abdominal operations, infection, immobility, and electrolyte abnormalities
LARGE BOWEL OBSTRUCTION

CLASSIFICATION
 Open loop (20% of cases) – incompetent ileocaecal valve allows colonic pressure relief (presents similar to SBO)
 Closed loop (80% of case) – competent ileocaecal valve (causes dangerous colonic pressure and distension)

Note: LBO is much less frequent than SBO (represents 25% of bowel obstruction).
AETIOLOGY
 Causes of LBO – cancer > diverticulitis > volvulus > other causes (e.g. constipation, stricture, foreign body)
TREATMENT
 Surgical Support Squad – NPO ± NGT ± IV fluids ± catheter ± analgesics ± anti-emetics
 LBO – surgical correction (usually resection + temporary diverting colostomy )
 Rarely, may be able to treat with conservative treatment (enema, colonoscopy, or rectal tube )
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Colonic pseudo-obstruction (Ogilvie’s syndrome)

Colonic pseudo-obstruction is distension of the colon without mechanical obstruction.
 Typically, occurs in bedridden patients with serious illness or trauma
Classification of bowel obstruction
FEATURE SBO LBO PARALYTIC ILEUS
Nausea/vomiting  Early and copious (± bilious)  Late (± feculent)  Present

Abdominal pain  Colicky  Colicky  Minimal

Distention  Minor  Severe  Variable

Bowel sounds  High-pitched (borborygmic)  High-pitched (borborygmic)  Absent

AXR  Air-fluid levels (‘step-ladder’ pattern)  Air-fluid levels  Air throughout small bowel and colon
 Paucity of colonic gas  ‘Picture-frame’ appearance

INTESTINAL ISCHAEMIA

AETIOLOGY
 Occlusive – thrombotic, embolic, extrinsic compression (e.g. hernia or bowel obstruction)
 Non-occlusive – systemic hypoperfusion

Note: atherosclerosis is the classic cause of chronic intestinal ischaemia.

CLINICAL PRESENTATION
 Severe abdominal pain out of proportion to physical findings (i.e. minimal peritonism)
 Associated with nausea, vomiting, bloody diarrhoea, hypotension, shock, and sepsis
 May present as post-prandial pain (‘mesenteric angina ’)
DIAGNOSIS
 Labs – lactic acidosis (acute abdomen + metabolic acidosis is intestinal ischaemia until proven otherwise)
 Imaging –
 AXR/CT – free air, thickened bowel wall, or pneumatosis intestinalis
 CT-angiography (definitive)
TREATMENT
 Surgical Support Squad – NPO ± NGT ± IV fluids ± catheter ± analgesics ± anti-emetics
 Medical – broad-spectrum IV antibiotics (cef-met-gent – cefuroxime + metronidazole ± gentamicin (if severe))
 Surgical – resection of necrotic intestine ± vascular intervention
APPENDICITIS

FEATURES
 Prevalence – 5% of population (80% between 5 and 30 years of age)
 Appendix anatomy – retrocaecal (two-thirds) > pelvic (one-third) > other positions (rest)
PATHOPHYSIOLOGY
 Luminal obstruction  bacterial overgrowth  inflammation  pressure  ischaemia  perforation  abscess or peritonitis
 Cause of obstruction – lymphoid hyperplasia > faecalith > carcinoid
CLINICAL PRESENTATION
 Classical sequence – anorexia  central abdominal pain  nausea/vomiting  localized RLQ pain
 Fever (dependent on severity/perforation)
 Peritonism (if perforated)
 Clinical signs:
 McBurney’s sign (tenderness 1/3rd from ASIS to umbilicus)
 Rovsing’s sign (palpation of LLQ causes RLQ pain)
 Psoas sign (passive hyperextension of hip causes RLQ pain)
 Obturator sign (rotation of right hip causes RLQ pain)
DIAGNOSIS
 Clinical diagnosis – may be supported by clinical scoring systems (i.e. Alvarado score)
 Labs –  WBC/CRP (also, β-HCG to rule out ectopic pregnancy and urinalysis to rule out urinary causes)
 Imaging (if clinical diagnosis is equivocal) – U/S (screening) or CT (definitive)
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TREATMENT
 Surgical Support Squad – NPO ± NGT ± IV fluids ± catheter ± analgesics ± anti-emetics
 Medical – broad-spectrum IV antibiotics (cef-met-gent – cefuroxime + metronidazole ± gentamicin (if severe))
 Surgery – appendectomy
OUTCOMES
 Mortality – 0.1% (non-perforated), 0.5% (perforated)
DIVERTICULAR DISEASE

DEFINITIONS
 Diverticulum – abnormal sac-like protrusion from the wall of hollow organ
 True (congenital) – contain all layers of colonic wall (often right-sided)
 False (acquired) – contain mucosa and submucosa (often left-sided)
 Diverticulosis – presence of multiple diverticulum
 Diverticulitis – pericolitis due to micro- or macroperforation of diverticula secondary to faecalith impaction
FEATURES
 Risk factors – low-fibre diet, inactivity, obesity, connective tissue disorders
 Prevalence – age-dependent (two-thirds by age 80)
 Site – 95% involve sigmoid colon (left-sided) in Western countries (may be right-sided in Asian countries)
Diverticulosis
CLINICAL PRESENTATION
 Asymptomatic (or vague) until sudden, intermittent, painless bleeding (most common cause of acute lower GI bleeding)
Diverticulitis
CLINICAL PRESENTATION
 Typically, LLQ pain for several days before admission
 Associated with nausea/vomiting , fever, change in bowel habit, and urinary symptoms (with adjacent inflammation)
 Complications (present in 25% of cases):
 Abscess (presents as palpable tender abdominal mass)
 Fistula (to bladder, bowel, vagina, or skin)
 Colonic obstruction (from stricture)
 Perforation (feculent or purulent)
DIAGNOSIS
 Imaging:
 AXR – ileus, thickened bowel wall, obstruction, free air
 CT with rectal contrast (definitive) – bowel wall thickening with pericolic soft tissue density due to inflammation
 Elective evaluation:
 Colonoscopy (or flexible sigmoidoscopy ) – useful but not in acute phase (may cause perforation)
TREATMENT
 Surgical Support Squad – NPO ± NGT ± IV fluids ± catheter ± analgesics ± anti-emetics
 Medical – broad-spectrum IV antibiotics (cef-met-gent – cefuroxime + metronidazole ± gentamicin (if severe))
 Uncomplicated (outpatient) – conservative management (clear fluids until improvement and broad-spectrum IV antibiotics as
above)
 Complicated (inpatient) – Surgical Support Squad and broad-spectrum IV antibiotics as above and surgical treatment as below)
 Indications for surgery:
 Hinchey stage 2, 3, or 4
 Unstable patient with peritonism or sepsis
 Failure to improve with conservative management
Classification (Hinchey staging)
HINCHEY STAGE DESCRIPTION ACUTE TREATMENT
1 Phlegmon/small pericolic abscess Medical

2 Large abscess/fistula Abscess drainage ± resection with primary anastomosis

3 Purulent peritonitis Hartmann procedure

4 Feculent peritonitis Hartmann procedure

Note: Hartmann procedure is a colon resection with colostomy and rectal stump with potential colostomy reversal in 3 to 6 months.
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OUTCOMES
 Mortality – 5% for purulent peritonitis and 35% for faecal peritonitis
 Recurrence – 15% after first attack and 30% after second attack
TOXIC MEGACOLON

AETIOLOGY
 IBD (esp. UC)
 Infectious colitis
CLINICAL PRESENTATION AND DIAGNOSIS
 Diagnostic criteria:
 Local symptoms – sequence of infectious colitis followed by colonic dilatation
 Systemic symptoms – fever, peritonism, sepsis, shock, fluid/electrolyte disturbances
 Laboratory evidence – septic picture
 Radiological evidence – CT/AXR (severely dilated colon)
TREATMENT
 Treat underlying cause (e.g. IBD or infection)
 Surgical Support Squad – NPO ± NGT ± IV fluids ± catheter ± analgesics ± anti-emetics
 Medical – broad-spectrum IV antibiotics (cef-met-gent – cefuroxime + metronidazole ± gentamicin (if severe))
 Surgical – colectomy
OUTCOMES
 Mortality up to 25%
VOLVULUS
Volvulus is rotation of a segment of bowel about its mesenteric axis.
 Typically, sigmoid (two-thirds) or caecum (one-third)
 Represents 10% of large-bowel obstruction (but occurs more frequently in pregnancy)
CLINICAL PRESENTATION
 LBO or intestinal ischaemia
DIAGNOSIS
 AXR (classic findings)
 Sigmoid – coffee-bean (central-cleft points to LLQ)
 Caecal – coffee bean (central cleft points to RLQ)
TREATMENT
 Surgical Support Squad – NPO ± NGT ± IV fluids ± catheter ± analgesics ± anti-emetics
 Non-surgical – colonoscopic decompression
 Surgical – colectomy

Anorectum
HAEMORRHOIDS

CLASSIFICATION
 Internal (above dentate line) – PAINLESS rectal bleeding
 Treated conservatively or with rubber band ligation, sclerotherapy, haemorrhoidectomy if severe
 External (below dentate line) – PAINFUL bowel motions
 Treated conservatively (tendency to recur)
ANAL FISSURES

CLINICAL PRESENTATION
 Very painful bright red bleeding (especially after bowel movement)
 Sphincter spasm on rectal examination
TREATMENT
 Conservative (stool softeners and sitz baths) (topical GTN if chronic)
ANAL FISTULA

IDENTIFICATION
 Goodsall’s rule – anterior fistulas are straight and exit anteriorly and posterior fistulas are curved and begin in midline
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Biliary
CHOLELITHIASIS
Cholelithiasis is the presence of gallstones in the gallbladder.
PATHOPHYSIOLOGY
 Cholesterol stones (80% of gallstones) – risk factors are the 4F’s (Fat, Female, Fertile, Forties)
 Pigment (calcium bilirubinate) stones (20% of gallstones) – risk factors are cirrhosis, haemolysis, biliary stasis
CLINICAL PRESENTATION
 Typically, asymptomatic (although strongly associated with other biliary syndromes)
DIAGNOSIS
 Labs – WBC, LFTs, lipase (all normal)
 Imaging – U/S (first-line), ERCP/MRCP, PTC
ACUTE BILIARY PAIN (BILIARY COLIC)
Acute biliary pain is transient impaction of a gallstone in the cystic duct (non-infectious pathophysiology).
CLINICAL PRESENTATION
 Constant, severe, dull pain in epigastrium/RUQ for several hours
 Typically, occurs post-prandially (esp. after a fatty meal)
 Can radiate to right shoulder or scapula
 Associated with nausea/vomiting
 Examination – normal or epigastrium/RUQ tenderness (but no peritonism or systemic symptoms)
DIAGNOSIS
 Labs – WBC, LFTs, lipase (all normal)
 Imaging – U/S (first-line), ERCP/MRCP, PTC
TREATMENT
 Acute – analgesia
 Surgical (if recurrent) – elective cholecystectomy
CHOLECYSTITIS
Cholecystitis is inflammation of the gallbladder due to sustained impaction of a gallstone in cystic duct or Hartmann’s pouch.
CLINICAL PRESENTATION
 Constant, severe, dull pain in epigastrium/RUQ for several hours or days
 Often patients have a history of acute biliary pain
 Can radiate to right shoulder or scapula
 Associated with nausea/vomiting, anorexia, fever
 Examination – focal peritonism (Murphy’s sign – cessation of inspiration on palpation of RUQ)
DIAGNOSIS
 Labs – WBC (elevated), LFTs (mildly elevated), lipase (normal)
 Imaging – U/S (first-line), ERCP/MRCP, PTC (demonstrates gallstones with thickened gallbladder wall)
TREATMENT
 Surgical Support Squad – NPO ± NGT ± IV fluids ± catheter ± analgesics ± anti-emetics
 Medical – broad-spectrum IV antibiotics (cef-met-gent – cefuroxime + metronidazole ± gentamicin (if severe))
 Surgical – acute cholecystectomy (within one week)
COMPLICATIONS
 Gallbladder perforation
 Cholecystoenteric fistula (can lead to gallstone ileus)
 Mirizzi syndrome (extra-luminal compression of CBD/CHD due to large stone in cystic duct)
Acalculous cholecystitis
Acalculous cholecystitis is cholecystitis without the presence of gallstones (represents 10% of cases)
 Typically, due to gallbladder stasis and ischaemia (occurs in critically-ill patients)
CHOLEDOCHOLITHIASIS
Cholelithiasis is the presence of gallstones in the common bile duct .
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CLINICAL PRESENTATION
 Typically, asymptomatic (however, may cause dull pain in epigastrium/RUQ)
 Often patients have a history of acute biliary pain
 Associated with obstructive jaundice (jaundice, dark urine, acholic stool)
 Examination – normal or epigastrium/RUQ tenderness (but no peritonism or systemic symptoms)
DIAGNOSIS
 Labs – WBC (normal), LFTs (elevated), lipase (elevated if gallstone pancreatitis)
 Imaging – U/S (first-line), ERCP/MRCP, PTC (demonstrates CBD gallstones with intra/extra-hepatic duct dilatation)
TREATMENT
 If no evidence of cholangitis – ERCP with CBD gallstone extraction ± elective cholecystectomy
COMPLICATIONS
 Cholangitis
 Gallstone pancreatitis
CHOLANGITIS
Cholangitis is obstruction of the CBD causing biliary stasis, biliary infection, and sepsis.
 Typically, caused by choledocholithiasis (also, stricture, neoplasm, or biliary stent)
CLINICAL PRESENTATION
 Charcot’s triad – fever, RUQ pain, jaundice
 Reynolds’ pentad – as above in addition to shock and confusion
DIAGNOSIS
 Labs – WBC (elevated), LFTs (elevated), lipase (elevated if gallstone pancreatitis)
 Imaging – U/S (first-line), ERCP/MRCP, PTC (demonstrates obstruction with intra/extra-hepatic duct dilatation)
TREATMENT
 Surgical Support Squad – NPO ± NGT ± IV fluids ± catheter ± analgesics ± anti-emetics
 Medical – broad-spectrum IV antibiotics (cef-met-gent – cefuroxime + metronidazole ± gentamicin (if severe))
 Biliary decompression:
 ERCP + sphincterotomy
 PTC (percutaneous transhepatic cholangiography) with catheter drainage
 Laparotomy with CBD exploration and T-tube placement
OUTCOMES
 Mortality – up to 50%
GALLSTONE ILEUS
Gallstone ileus is obstruction of the ileocaecal valve by a gallstone due to cholecystoenteric fistula .
 Hence, ‘gallstone ileus’ is a misnomer (as it represents a true bowel obstruction)
CLINICAL PRESENTATION AND DIAGNOSIS
 Rigler’s triad – SBO, evidence of gallstone, pneumobilia (air in biliary tree)
TREATMENT
 Surgical Support Squad – NPO ± NGT ± IV fluids ± catheter ± analgesics ± anti-emetics
 Surgical – enterolithotomy ± fistula repair ± cholecystectomy
BILIARY MALIGNANCY
Biliary malignancy may represent intrinsic (gallbladder or cholangiocarcinoma) or extrinsic (pancreatic) cancers.
CLINICAL PRESENTATION
 Courvoisier’s sign – a palpable, non-tender, gallbladder is associated with pancreatic or gallbladder cancer or cholangiocarcinoma
 Associated with gradual obstructive painless jaundice (biliary malignancy, particularly pancreatic, until proven otherwise)
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Urology
Lower urinary tract dysfunction
URINARY INCONTINENCE
Urinary incontinence is defined as involuntary leakage of urine.
FEATURES
 Most common in females (esp. multiparous) and the elderly
CLASSIFICATION
 Causes of reversible urinary incontinence (without specific urogenital pathology) – DIAPERS:
 Delirium
 Infection
 Atrophic urethritis/vaginitis
 Psychiatric or Pharmaceutical
 Excessive urine output (hyperglycaemia, hypercalcaemia, CHF)
 Restricted mobility or Retention
 Stool impaction
 Other types:
 Total incontinence – uncontrolled urine leakage at all times (usually due to urinary tract to skin fistula or loss of sphincter tone)
Urinary incontinence: types and treatments
URGENCY STRESS OVERFLOW
Definition Involuntary leakage of urine Involuntary leakage of urine with sudden increases in intra- Involuntary leakage of urine that
preceded by a strong, sudden, abdominal pressure results as a complication of
urge to void urinary retention

Aetiology  Bladder (detrusor overactivity)  Urethral/sphincter weakness  Urinary retention

 Post-partum anatomic weakness
 Post-surgical anatomic weakness

Diagnosis  History (and MSU)  History (and MSU)  History (and MSU)
 Urodynamics  Urodynamics  Physical examination
 Stress test (patient bear down/cough)  Bladder scan (U/S)

Treatment Conservative treatment: Conservative treatment: Treat underlying urinary retention

 Behavioural training  High-fibre diet and weight reduction
Medical treatment:  Pelvic exercises (‘Kegels’)
 Anticholinergics  Local vaginal oestrogen therapy (topical/suppository/ring)
 TCAs  Vaginal pessary (intravaginal suspension disc)
 β3 agonists Surgical treatment:
 e.g. slings or tension free-vaginal tape

URINARY RETENTION

AETIOLOGY
 Outflow obstruction – bladder, prostate, or urethral
 Bladder innervation – neurogenic
 Pharmacological – anticholinergics
 Infection – UTI
CLINICAL PRESENTATION
 Suprapubic pain with palpable and/or percussible bladder
 Other symptoms and signs dependent on cause (e.g. neurological findings or prostate pathology)
TREATMENT
 Treat underlying cause
 Decompression – catheterisation ± suprapubic aspiration
Post-obstructive diuresis
Post-obstructive diuresis is polyuria (>200ml/hour) resulting from relief of severe chronic obstruction.
 Typically, is a self-limiting excretion of retained solutes
 Treated by monitoring and management of fluid and electrolyte balance
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Infectious and inflammatory disease

EPIDIDYMO-ORCHITIS

AETIOLOGY
 Child – mumps
 Young/sexually active – N. gonorrhoeae or C. trachomatis
 Elderly/non-sexually active – ascending infection (esp. E. coli)
CLINICAL PRESENTATION
 Sudden onset scrotal pain and swelling (may radiate to flank)
 Examination:
 Scrotal tenderness, swelling, and erythema ± discharge
 Present cremasteric reflex (as opposed to torsion)
 Prehn’s sign positive – pain may be relieved with elevation of testicles (as opposed to torsion)
DIAGNOSIS
 Labs – CBC, U/E, urinalysis (C&S/R&M)
TREATMENT
 Rule out testicular torsion
 Conservative – bed rest, analgesia, scrotal support
 Medical – antibiotics (ceftriaxone and doxycycline if sexual infection or ciprofloxacin if considering non-sexual infection)
COMPLICATIONS
 Testicular atrophy
 Persistent fertility issues
PROSTATITIS
Prostatitis is inflammation of the prostate leading to pain and tenderness (common urologic diagnosis in men younger than 50 years
old).
CLASSIFICATION
 Acute bacterial – ascending urethral infection (typically, E. coli)
 Chronic bacterial – recurrent infection as above
TREATMENT
 Conservative – bed rest, analgesia
 Medical – antibiotics (as for UTI)

Penile complaints
CLASSIFICATION

Penile complaints
PEYRONIE’S DISEASE PRIAPISM PARAPHIMOSIS PHIMOSIS
Definition Benign curvature of penile Prolonged erection (>4hr) in Foreskin caught behind glans Inability to retract foreskin
shaft due to fibrous thickening the absence of desire leading to oedema and over glans penis
inability to reduce foreskin

Clinical  Penile curvature  Pain with erection  Typically, follows trauma,  Limitation and pain when
presentation  Pain with erection  Signs of ischaemia instrumentation, or balanitis attempting to retract foreskin
 Poor erection

Treatment  Watchful waiting  Treat underlying cause  Manual reduction  Proper hygiene
 Topical verapamil  Needle aspiration  Circumcision  Topical corticosteroids
 Surgical treatment  Surgical shunting  Circumcision

Erectile dysfunction
Erectile dysfunction is consistent inability to obtain/maintain an adequate erection for satisfactory sexual performance.
CLASSIFICATION
 Psychogenic (10%) – psychological factors
 Typically, sudden onset and affects young patients
 Organic (90%) – iatrogenic, neurogenic, mechanical, pharmacological, endocrine factors
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 Typically, gradual onset and affects older patients

TREATMENT
 Non-invasive:
 Treat underlying cause
 Lifestyle change (alcohol/smoking)
 Psychological therapy
 Medical:
 Sildenafil (PDE-5 inhibitor)
 Intracavernous vasodilator injection
 Surgical – penile artery reconstruction or implant

Scrotal mass
TESTICULAR TORSION
Testicular torsion is twisting of the spermatic cord causing ischaemia of the testicle.
FEATURES
 Typically, occurs in young adolescents (but can occur in any age)
 Risk factors – trauma, cryptorchidism, ‘bell clapper deformity’
CLINICAL PRESENTATION
 Sudden onset scrotal pain and swelling (may radiate to flank)
 Associated with nausea/vomiting
 Examination:
 Scrotal tenderness and swelling
 Absent cremasteric reflex (as opposed to epididymo-orchitis)
 Retracted and transverse testicle
 Prehn’s sign negative – pain not relieved with elevation of testicles (as opposed to epididymo-orchitis)

Note: up to 50% of cases occur during sleep (hypothesised due to scrotal relaxation).
DIAGNOSIS
 Clinical diagnosis
 Doppler U/S
TREATMENT
 EMERGENCY surgical bilateral orchiopexy
 Manual treatment (not recommended) – rotate testicles outwards
OUTCOMES
 Treatment must be achieved within 6 hours (90% chance of saving testicle)
 Otherwise, testicular infarction (treated with orchiectomy )
Torsion of the testicular appendix
Torsion of the testicular appendix is twisting of the testicular appendix (most common cause of acute scrotum in children).
 Presents similar to testicular torsion but with small-firm nodule (‘blue-dot’ sign) and present cremasteric reflex
 Typically, self-limiting within one-week (treated with analgesics) (have a high suspicion for testicular torsion)
BENIGN SCROTAL MASS

CLASSIFICATION
 Varicocoele – tortuous dilated pampiniform plexus due to incompetent valves in the testicular veins
 Clinical presentation – painless ‘bag of worms’ that pulsates with Valsalva (occur in up to 15% of men and 90% left-sided)
 Treatment – conservative or surgical repair
 Complications – reduced sperm count and quality
 Spermatocoele – a benign, sperm-filled, epididymal retention cyst
 Clinical presentation – non-tender, transilluminating, cystic epididymal mass
 Hydrocoele – a serous-fluid collection in the tunica vaginalis (can be due to a communicating patent processus vaginalis in
newborns)
 Clinical presentation – non-tender, transilluminating, cystic intrascrotal mass
 Haematocoele – a blood collection in the tunica vaginalis
 Clinical presentation – diffusely tender, non-transilluminating, intrascrotal mass
 Inguinal hernia – particularly indirect hernia
 Clinical presentation – classically a scrotal mass that cannot ‘get above’ on examination)
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 Testicular torsion
 Epididymo-orchitis

Paediatric urology
CRYPTORCHIDISM
Cryptorchidism is failure of one or both of the testes to fully descend into the scrotum.
PATHOPHYSIOLOGY
 Typically, testes descend through the inguinal canal in the seventh month in utero
 The testes can be located:
 Along the normal path of descent (inguinal canal or abdominal)
 Outside the normal path (ectopic testis )
FEATURES
 Associated with prematurity and low birth weight
DIAGNOSIS
 Clinical diagnosis (testes absent or cannot be manipulated into the scrotal sac with gentle pressure)
TREATMENT
 Observation (a referral is required if undescended after three months)
 Surgical:
 Orchiopexy if pre-pubertal (translocation of testes into scrotum)
 Orchiectomy if post-pubertal (to reduce risk of testicular cancer)
OUTCOME
 Reduction in fertility (100% infertile if untreated bilateral cryptorchidism)
 Increased risk of testicular cancer (reduced, but not eliminated, by surgery)
 Increased risk of testicular torsion (reduced, but not eliminated, by surgery)
HYPOSPADIAS
Hypospadias is a common condition where the urethral meatus opens on the ventral penis (proximal to the normal location).
 Classified by location (e.g. glandular, shaft, scrotal, perineal)
 Treated with early surgical correction (circumcision should be deferred as the foreskin may be utilised in the correction)
POSTERIOR URETHRAL VALVES
Posterior urethral valves are abnormal mucosal folds at the prostatic urethra causing obstruction.
 Represent the most common congenital obstructive urethral lesion in male infants
CLINICAL PRESENTATION AND DIAGNOSIS
 Pre-natal (detected by U/S) – distended bladder, hydronephrosis, oligohydramnios
 Post-natal (detected by voiding cystourethrogram) – palpable abdominal mass, recurrent UTI, voiding dysfunction
 May present with urosepsis if not recognised
TREATMENT
 Acute – immediate catherisation (to relieve obstruction)
 Surgical – cystoscopic resection (when stable)
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Vascular
Peripheral vascular disease
PERIPHERAL ARTERIAL DISEASE
Peripheral arterial disease is chronic ischaemia due to inability of the arterial supply to meet metabolic demands.
PATHOPHYSIOLOGY
 Typically, due to atherosclerosis
 Risk factors – as for cardiovascular disease (esp. smoking/diabetes)
CLINICAL PRESENTATION
 Claudication – a triad of:
 Pain with exertion (typically, in calves)
 Pain that is relieved with short rest
 Pain that is reproducible/consistent
 Critical limb ischaemia (CLI) – defined as rest pain , night pain, or tissue loss (ulceration or gangrene)
 Classical history – midfoot pain, waking patient at night, and relieved by hanging foot of bed
 May present with other manifestations of atherosclerosis (e.g. CVS, CAD, impotence)
 Examination – see OSCE handbook.
DIAGNOSIS
 Labs – routine cardiovascular assessment
 Ankle-Brachial Index (>1.2 suggestive of vessel calcification; <0.9 is abnormal; <0.4 is critical limb ischaemia)
 Duplex U/S
 Imaging – CTA /MRA or invasive arteriography
TREATMENT
 Lifestyle modification ( exercise, smoking cessation , diet)
 Risk factor modification ( hypertension , hyperlipidaemia )
 Foot care (proper footwear, podiatrist, wound care)
 Medical – anti-platelet agents
 Surgical – endovascular angioplasty/stenting ± bypass grafting ± amputation
OUTCOMES
 Claudication – good prognosis (if treated adequately)
 CLI – high risk of amputation (and subsequent mortality)

Aortic disease
AORTIC ANEURYSM

DEFINITION
 Aneurysm – localised dilation of an artery (at least 1.5x normal diameter)
 True aneurysm – involving all vessel wall layers
 False (pseudo) aneurysm – containment of blood outside vessel without surrounding fibrous capsule
CLASSIFICATION
 Thoracic
 Thoracoabdominal
 Abdominal – most common (>90% are infrarenal)
PATHOPHYSIOLOGY
 Typically, due to atherosclerosis
 Also, trauma, infection, vasculitis, or connective tissue disorders
CLINICAL PRESENTATION
 Typically, asymptomatic
 Associated with other vascular disease (CVS, CVD, CKD, HTN)
 Acute presentation (expansion/rupture) – hypotension, palpable pulsatile mass , pain (may radiate to back)
DIAGNOSIS
 Labs – CBC, coagulation, cross match
 Imaging – U/S or CT with contrast
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TREATMENT
 Conservative – watchful waiting
 Surgical (when risk of rupture ≥ risk of surgery – classically at >5.5cm for AAA):
 Open surgery with graft replacement
 Endovascular aneurysm repair (EVAR)
AORTIC DISSECTION
Aortic dissection is a tear in the aortic tunica intima allowing blood to create a false-lumen (dissection) in the tunica media.
 Typically, occurs due to hypertension (male-to-female ratio is 3:1)
CLASSIFICATION
 Stanford – type A (involves ascending aorta) versus type B (does not involve ascending aorta)
CLINICAL PRESENTATION
 Sudden onset of tearing chest pain that radiates to back with:
 Hypertension
 Asymmetric limb blood pressures and pulses
 Ischaemic syndromes (myocardial infarct, stroke, or other ischaemia)
 Rupture into pleura (haemoptysis), peritoneum (shock), or pericardium (cardiac tamponade)
DIAGNOSIS
 Labs – CBC, coagulation, cross match (also, consider lipase and troponin to rule out pancreatitis/myocardial infarction)
 Imaging – CT angiography (gold-standard)
TREATMENT
 Medical – β-blockers (or other vasodilators ) to lower blood pressure and heart rate
 Surgical:
 Type A – emergency surgery with cardiopulmonary bypass
 Type B – may be managed medically (or may require surgery)

Peripheral venous disease

VARICOSE VEINS
Varicose veins are distended, tortuous, superficial veins resulting from incompetent venous valves.
AETIOLOGY
 Primary – venous valve incompetence or obstruction (due to age, prolonged standing, pregnancy, obesity)
 Secondary – deep vein thrombosis or malignancy
CLINICAL PRESENTATION
 Visible varicose veins
 Associated with aching (particularly after prolonged standing and at night)
 Associated with venous ulceration, hyperpigmentation (haemosiderin deposits) , and thrombophlebitis
TREATMENT
 Conservative – compression stockings , elevation of leg , and avoidance of prolonged standing
 Interventional – laser ablation, foam sclerotherapy , or surgical ligation and stripping
LYMPHOEDEMA
Lymphoedema is obstruction of lymphatic drainage resulting in oedema.
 May be primary (congenital/idiopathic) or secondary (infection, iatrogenic lymph node removal, malignant infiltration)
 Typically, causes non-pitting oedema
VENOUS THROMBOEMBOLISM (VTE)
Venous thromboembolism is a disease that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE)
PATHOPHYSIOLOGY

Virchow’s triad
VENOUS STASIS ENDOTHELIAL INJURY HYPERCOAGULABILITY

Immobility (e.g. air travel, limb traction) Trauma (including surgery) Pregnancy
Heart failure Previous DVT OCP
Obesity Vasculitis Malignancy
Severe burns/sepsis
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DIAGNOSIS
 Clinical diagnosis (based on Wells score)
 High likelihood – compression U/S (for DVT) or CTPA or V/Q scan (for PE)
 Low likelihood – D-dimer (order imaging if elevated)
TREATMENT
 LMWH for 5 days + warfarin (concurrently) or NOAC (after) (consider IVC filter in patients who cannot be anticoagulated)
 Anticoagulation – 3 months if provoked (lifelong if unprovoked)
 VTE prophylaxis triad – TEDS, low-dose LMWH, mobilisation
Deep vein thrombosis
CLINICAL PRESENTATION
 Typically, presents with unilateral, lower extremity, pain and swelling
 Associated with local inflammatory signs, mild fever, and a palpable thrombosed vein

Note: absence of physical findings (or symptoms) does not rule out disease.
Pulmonary embolism
PATHOPHYSIOLOGY
 Lung effects – V/Q mismatch (infarction is rare)
 CVS effects – hypotension, pulmonary hypertension, right heart failure
CLINICAL PRESENTATION
 Diverse clinical presentation – typically, occurs one to two weeks post-surgery
 Symptoms and signs:
 Sudden-onset dyspnoea, tachypnoea, and hypoxia/cyanosis
 Pleuritic chest pain, pleural rub, pleural effusion, and haemoptysis
 Haemodynamic instability (including tachycardia and hypotension)

Note: fewer than 30% of patients have clinical evidence of DVT (e.g. leg swelling, pain, or tenderness).
DIAGNOSIS
 Definitive – CTPA (or V/Q scan)
 Additional:
 ABG – respiratory alkalosis (tachypnoea)
 BNP – elevated (right heart strain)
 CXR – typically, normal (may show pleural effusion or wedge-shaped infarct)
 ECG – typically, sinus tachycardia (S1Q3T3 is rare: deep S wave in lead I, a Q wave in lead III, and inverted T wave in lead III)
 ECHO – right heart strain
 Troponin – elevated
TREATMENT
 Treatment as for VTE (in addition to supplemental oxygen and analgesia)
 Massive pulmonary embolism – catheter-directed IV thrombolytic therapy (rapid recovery but no reduction in mortality)
OUTCOMES
 Often leads to pulmonary infarction , right heart failure , respiratory failure , and death
 Use the PESI (pulmonary embolism severity index ) to estimate risk of 30-day mortality in acute pulmonary embolism

Note: a patent foramen ovale can result in a TIA or stroke (rather than a PE) from a DVT – a ‘paradoxical embolus ’.
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Orthopaedics
General principles of orthopaedics
DERMATOMES AND MYOTOMES

Dermatomes
Dermatomes are areas of skin supplied by a single spinal nerve , which
are as follows:
 8 cervical nerves (although C1 has no dermatome)
 12 thoracic nerves
 5 lumbar nerves
 5 sacral nerves
CLINICALLY RELEVANT DERMATOMES
 C5 – shoulders
 C6 – lateral arm and thumb
 C7 – middle finger
 C8 – medial arm and pinkie finger
 T4 – nipple
 T10 – umbilicus
 L5 – lateral calf and medial foot
 S1 – lateral foot and sole of foot
 S5 – perianal

Myotomes
Myotomes are group of muscles supplied by a single spinal nerve.
LIST OF MYOTOMES

Myotomes
UPPER LIMB LOWER LIMB

C5 Shoulder abduction L2/L3 Hip flexion

C6/C7/C8 Shoulder adduction L3/L4 Knee extension

C5/C6 Elbow flexion L4/L5 Dorsiflexion (and inversion)

C7/C8 Elbow extension L5 Great toe extension

C6/C7 Wrist flexion/extension L4/L5 Hip extension

C7/C8 Finger flexion/extension L5/S1 Knee flexion (and eversion)

T1 Finger abduction/adduction (small muscles of hand) S1/S2 Plantarflexion

S1/S2 Great toe flexion

PLEXUSES

CLASSIFICATION
 Cervical plexus (C1-C4) – innervates the diaphragm, shoulders, and neck
 Brachial plexus (C5-T1) – innervates the upper limbs
 Lumbosacral plexus (L2-S1) – innervates the lower limbs
Brachial plexus
ANATOMY
 Structure (Real Teens Drink Cold Beer )
 Roots, Trunks, Divisions, Cords, Branches
 Nerves (MAMRU):
 Musculocutaneous
 Axillary
 Median
 Radial
 Ulnar
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Palsies of the brachial plexus

LOCATION MECHANISM PRESENTATION

Erb’s Upper brachial plexus (C5-C6) Shoulder dystocia ‘Waiter’s tip deformity’
 Internally rotated, extended arm, with wrist flexion

Klumpke’s Lower brachial plexus (C7-T1) Traction on abducted arm ‘Claw hand’ – paralysis of small muscle of hands
(esp. during difficult delivery)

Thoracic Lower brachial plexus (C8-T1) Pancoast tumour Atrophy of intrinsic muscles of hand
outlet and subclavian vessels
syndrome

Winged Long thoracic nerve (C5-C7) Axillary node dissection after Loss of motor function to serratus anterior (inability to anchor scapula
scapula mastectomy to thoracic cage and cannot abduct arm above horizontal positional)

FRACTURES

Describing a fracture
 Name of injured bone
 Integrity of skin/soft tissue
 Closed – skin/soft tissue over and near fracture is intact
 Open – skin/soft tissue over and near fracture is lacerate or fracture exposed to outside environment (requires IV antibiotics )
 Location
 Epiphyseal – end of bone (forming part of adjacent joint)
 Metaphyseal – flared portion of bone at the ends of the shaft
 Diaphyseal – shaft of a long bone
 Physis – growth plate
 Orientation/fracture pattern (see image)
 Alignment of fracture fragments
 Non-displaced – fracture fragments in anatomic alignment
 Displaced – fracture fragments are not in anatomic alignment
 Distracted – fracture fragments are separated by a gap (opposite of impacted)
 Impacted – fracture fragments are compressed (resulting in shortened bone)
 Angulated – direction of fracture apex
 Translated – percentage of overlapping bone at fracture site
 Rotated – fracture fragment rotated about long axis of bone

Management of fractures
MANAGEMENT
 Thorough history and physical examination (including imaging)
 Initial splinting of extremity (reduces pain, further damage to tissue, and worsening of
fracture)
 Adequate analgesia
 Orthopaedic management:
 Obtain reduction
 Open (NO CAST) – surgical
 Closed – traction in the long axis of limb and reverse mechanism of injury
 Maintain reduction
 External stabilisation – splints, casts, traction, external fixator
 Internal stabilisation – percutaneous pinning, extramedullary fixation (screws, plates, wires), intramedullary fixation (rods)
 Rehabilitate
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Fracture healing
STAGES OF FRACTURE HEALING
 Inflammation – formation of a haematoma with inflammatory cells
 Soft callous – cartilage production
 Hard callous – ossification of cartilage
 Remodelling – weight-bearing causes remodelling of bone framework for maximum strength
TIMING OF HEALING
 Fractures ‘classically’ take 6 weeks to heal , unless:
 Paediatric – take 3 weeks to heal
 Complicating factors – double the time to heal (diaphyseal, open, or lower limb fractures)
COMPLICATIONS OF FRACTURES
 Early – local (neurovascular injury, infection, compartment syndrome) or systemic (sepsis, DVT, PE, fat embolus, haemorrhage)
 Late – mal/non-union, avascular necrosis, osteomyelitis, joint dysfunction
ARTICULAR CARTILAGE

BASIC PRINCIPLES
 Articular cartilage provides a near-frictionless surface for articulating bones
 Composed of collagen (90% type II – tensile strength), proteoglycans (compressive strength), chondrocytes, and water
 Articular cartilage is avascular (nutrition from synovial fluid), aneural, and alymphatic
 Damage leads to symptoms similar to osteoarthritis or symptoms of locking (related to torn/displaced cartilage)

Orthopaedic emergencies
FAT EMBOLISM
A fat embolism (which via major trauma may progress to fat embolism syndrom e) is typically caused by long bone or pelvic fractures.
CLINICAL PRESENTATION
 Symptoms usually occur 1–3 days after a traumatic injury and consist of:
 Respiratory distress syndrome
 Neurological (decreased level of consciousness)
 Haematological symptoms (anaemia and thrombocytopenia)
COMPARTMENT SYNDROME

PATHOPHYSIOLOGY
 Increased pressure within an anatomical compartment which compromises nerve, muscle, and soft-tissue perfusion leading to necrosis
CLINICAL PRESENTATION
 6Ps of compartment syndrome :
 Pain (out of proportion to injury) – most sensitive symptom
 Pain (with passive stretch of compartment muscles) – most sensitive sign
 Paraesthesia
 Pallor
 Pulselessness
 Paralysis
DIAGNOSIS
 Clinical diagnosis (compartment pressure monitoring with catheter AFTER clinical diagnosis)
TREATMENT
 Operative – urgent fasciotomy ± necrotic tissue debridement
COMPLICATIONS
 Volkmann’s ischaemic contracture (ischaemic necrosis of muscle followed by secondary fibrosis and calcification)
 Rhabdomyolysis (renal failure secondary to myoglobinuria due to muscle necrosis)
OSTEOMYELITIS

PATHOPHYSIOLOGY
 Most commonly due to S. aureus (haematogenous versus inoculation versus contiguous spread)
 Pseudomonas is common in IV drug users/central lines; Salmonella is common in Sickle Cell Disease
 Typically, occurs in long bones in children and vertebra in adults
 Risk factors : recent trauma, immunocompromise, diabetes, IV drug use, neurovascular dysfunction
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CLINICAL PRESENTATION
 Symptoms – pain and fever
 Signs – erythema, tenderness, oedema ± abscess/draining sinus tract
DIAGNOSIS
 Imaging – MRI (gold standard) or X-ray (demonstrates periosteal elevation)
 Definitive test – aspirate culture/bone biopsy
 Labs – CBC, WBC, CRP, blood culture
TREATMENT
 Aggressive IV antibiotics (flucloxacillin  vancomycin) ± surgery (I&D) ± hardware removal (if present)
SEPTIC ARTHRITIS

PATHOPHYSIOLOGY
 Most commonly due to haematogenous spread of:
 S. aureus (in adults)
 CONS (if hardware present)
 N. gonorrhoea (if sexually active or newborn)
CLINICAL PRESENTATION
 Localised joint pain, erythema, warmth, swelling, and inability to weight bear (may be associated with systemic symptoms)
DIAGNOSIS
 Labs – CBC, WBC, CRP, blood cultures
 Imaging – X-ray (to rule out fracture, tumour, or metabolic disease)
 Joint aspirate (REQUIRED if suspected) – cloudy yellow fluid,  WBC (neutrophils),  protein,  glucose, positive gram stain
TREATMENT
 Empiric IV antibiotics ( flucloxacillin  vancomycin) (followed by adjustment for joint aspirate culture )
 Non-operative – therapeutic joint aspiration
 Operative – arthroscopic or open irrigation and drainage
OUTCOMES
 Rapid joint destruction
 10-15% risk of mortality

Shoulder
SHOULDER DISLOCATION
Shoulder dislocation (most common dislocation)
ANTERIOR DISLOCATION OF SHOULDER POSTERIOR DISLOCATION OF SHOULDER

Mechanism >90% – forced external rotation or blow to posterior shoulder Rare – associated with seizures and electrocution (or FOOSH)

Presentation  Pain  Pain

 ‘Squared off’ shoulder on examination  Arm held in adduction and internal rotation
 Arm slightly abducted and externally rotated  Inability to externally rotate
 Inability to internally rotate

Treatment NOP:
 Closed reduction (with sedation and muscle relaxants)
 Sling
 Anterior – avoiding abduction and external rotation
 Posterior – avoiding adduction and internal rotation
 Shoulder rehabilitation

Complications  Highly recurrent (esp. if first-episode at young age)

 Risk of axillary nerve palsy (in anterior dislocation)

ROTATOR CUFF DISEASE

Rotator cuff muscles stabilise the humeral head within the glenoid fossa.
Subacromial impingement
MECHANISM
 Compression of rotator cuff tendons (esp. supraspinatus) and subacromial bursa
between head of humerus and underside of acromion
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 Causes spectrum of bursitis, tendonitis , and tearing of rotator cuff

CLINICAL PRESENTATION
 Insidious onset of pain and weakness worse with active motion (especially overhead between 60-120o – the ‘painful arc’)
TREATMENT
 Non-operative – physiotherapy ± NSAIDs ± steroid injection
 Operative – arthroscopy or open surgical repair (i.e. acromioplasty or rotator cuff repair)
Rotator cuff muscles
MUSCLE MUSCLE ATTACHMENTS NERVE SUPPLY MUSCLE FUNCTION

Supraspinatus Scapula Greater tuberosity of humerus Suprascapular n. Abduction

Infraspinatus Scapula Greater tuberosity of humerus Suprascapular n. External rotation

Teres minor Scapula Greater tuberosity of humerus Axillary n. External rotation

Subscapularis Scapula Lesser tuberosity of humerus Subscapular n. Internal rotation/adduction

ACROMIOCLAVICULAR JOINT PATHOLOGY

MECHANISM
 Fall onto shoulder with adducted arm causes subluxation or dislocation of AC joint
 May cause damage to the two supporting ligaments – acromioclavicular and coracoclavicular ligaments
CLINICAL PRESENTATION
 Pain with adduction of shoulder and/or palpation over AC joint
 Palpable ‘step deformity ’ between distal clavicle and acromion
TREATMENT
 Non-operative – sling, analgesia, and rehabilitation
 Operative – surgical (ligament reconstruction or internal fixation )
CLAVICLE FRACTURE

MECHANISM
 Fall on shoulder (most common) (also, direct trauma or FOOSH)
 Common in children (unites rapidly without complications)
CLINICAL PRESENTATION
 Pain and tenting of skin
 Arm is clasped to chest to splint shoulder
TREATMENT
 Non-operative – figure-of-eight sling and rehabilitation
 Operative – ORIF (open reduction and internal fixation )
FROZEN SHOULDER (ADHESIVE CAPSULITIS)

MECHANISM
 Primary adhesive capsulitis – idiopathic (typically, self-limiting within two-years)
 Secondary adhesive capsulitis – due to prolonged immobilisation or modest injury (poor outcomes)
CLINICAL PRESENTATION
 Gradual onset (weeks to months) of diffuse shoulder pain with:
 Decreased active AND passive ROM
 Pain worse at night (and often preventing sleeping)
 Increased stiffness as pain subsides
 May be separated into painful phase, stiff phase, and thawing phase (with gradual return of motion)
 Investigations are typically equivocal
TREATMENT
 Non-operative – physiotherapy ± NSAIDs ± steroid injection
 Operative – manipulation under anaesthesia (to break adhesions) ± arthroscopy for debridement/decompression
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Humerus
Fractures of the humerus
PROXIMAL HUMERUS FRACTURE HUMERAL SHAFT FRACTURE DISTAL HUMERUS FRACTURE

Mechanism  Young – high energy trauma

 Elderly – FOOSH (esp. osteoporotic patients)

Presentation Arm pain, swelling, deformity ± shortening in humeral shaft fractures

Treatment  NOP – closed reduction + sling  NOP – hanging cast ± closed reduction  NOP – cast
 OP – ORIF ± hemiarthroplasty  OP – ORIF  OP – ORIF

Complications  Axillary nerve palsy  Radial nerve palsy  Brachial artery injury
 AVN of humeral head  Volkmann’s ischaemic contracture
 Varus deformity of elbow
 Median, ulnar, or radial nerve palsy

Supracondylar fracture
Supracondylar fracture is a subclass of distal humerus fracture that is almost exclusive to the paediatric population.
 Described as an extra-articular fracture above the condyles (transverse)
 Almost always due to FOOSH (e.g. fall off monkey bars) and is commonly complicated by joint stiffness

Elbow
Fractures of the elbow
RADIAL HEAD FRACTURE OLECRANON FRACTURE

Mechanism  FOOSH (common in young adults)  FOOSH or direct trauma onto point of elbow

Presentation  Localised tenderness  Localised tenderness (palpable defect)

 Decreased ROM at elbow ± supination/pronation  ± loss of active extension (avulsion of triceps tendon)

Treatment  NOP – sling  NOP – cast

 OP – ORIF or radial head excision ± prosthesis  OP – ORIF (tension band wire)

Complications  Myositis ossificans (calcification of muscle)  Symptomatic hardware requiring removal

 Recurrent instability (esp. if radial head excised)

ELBOW DISLOCATION
Elbow dislocation (second most common dislocation)
ELBOW DISLOCATION

Mechanism  Posterior (common) – elbow hyperextension via FOOSH

 Anterior (rare and devastating)

Presentation  Elbow pain, swelling, deformity

 Fixed flexion of arm
 ± absent radial or ulnar pulses (due to brachial artery injury)

Treatment  NOP – closed reduction (with sedation and muscle relaxants) (requires post-reduction X-rays)
 OP – ORIF

Complications  Neurovascular injury (ulnar nerve, brachial artery)

EPICONDYLITIS

MECHANISM
 Repeated or sustained contraction of the forearm muscles/chronic overuse
CLASSIFICATION
 LaTeral epicondylitis (Tennis elbow) – inflammation of common ex Tensor tendon as it inserts into the lateral epicondyle
 Medial epicondylitis (Golfer’s elbow) – inflammation of the common flexor tendon as it inserts into the medial epicondyle
CLINICAL PRESENTATION
 Localised tenderness over affected epicondyle
 Pain associated with wrist extension (lateral epicondylitis) and wrist flexion (medial epicondylitis)
 Generally, self-limiting (may take up to two-years to resolve)
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TREATMENT
 Non-operative – physiotherapy ± NSAIDs ± steroid injection
 Operative – percutaneous or open release of common tendon from epicondyle

Forearm
RADIUS AND ULNA SHAFT FRACTURE
Fractures of the radius and ulna shaft
RADIAL SHAFT / ULNA SHAFT FRACTURE

Mechanism  High energy trauma (usually accompanied by displacement due to high energy)

Presentation  Arm pain, swelling, deformity

 Loss of function in arm and forearm

Treatment  OP – ORIF (anatomic reduction is essential as imperfect alignment limits pronation/supination)

Complications  Soft tissue contract resulting in limited forearm rotation

EPONYMOUS FRACTURES
Eponymous fractures of the forearm
MONTEGGIA FRACTURE NIGHTSTICK FRACTURE GALEAZZI FRACTURE
Definition Fracture of proximal ulna with Isolated fracture of ulna without Fracture of distal radius with
radial head dislocation radial head dislocation dislocation of the DRUJ

Mechanism  FOOSH (esp. if hyperextended/pronated)  Direct trauma to posterior forearm  FOOSH

 Direct trauma to posterior forearm (e.g. defence injury)  Direct trauma to wrist

Presentation  Pain, swelling, deformity  Pain, swelling, deformity  Pain, swelling, deformity
 Radial head dislocated anteriorly

Treatment  NOP – closed reduction + cast (in kids)  NOP – below elbow cast  OP – ORIF (all cases are operative)
 OP – ORIF (in adults)  OP – ORIF

Wrist
EPONYMOUS FRACTURES
Factures of the wrist
COLLE’S FRACTURE SMITH’S FRACTURE
Definition Extra-articular transverse distal radius Reverse Colle’s fracture
fracture ± ulnar styloid fracture (i.e. ventral displacement of distal radius)

Mechanism  FOOSH  Falling onto flexed hand

Presentation  ‘Dinner fork’ deformity  Pain, swelling, deformity

(dorsal displacement of distal radius)
 Most common fracture of those >40y old
(esp. women and osteoporotic bone)

Treatment  NOP – closed reduction + below elbow  OP – ORIF

cast
 OP – ORIF

Complications  Most common complications are poor grip strength, stiffness, and radial shortening

SCAPHOID FRACTURE

MECHANISM
 FOOSH (common in young men)
 Most common carpal bone injured
 May occur in conjunction with other carpal or wrist injuries (i.e. Colle’s)
CLINICAL PRESENTATION
 Tenderness in the ‘anatomical snuff box’
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TREATMENT
 Non-operative – thumb-spica cast
 Operative – ORIF

Note: radiological evidence may not be present until two weeks post fracture.
COMPLICATIONS
 Avascular necrosis (if proximal)

Hand
HAND FRACTURES AND DISLOCATION

CLINICAL NOTES
 Almost all hand fractures are stable in flexion (and are splinted like this to prevent extension)
 Stiffness secondary to immobilisation is the most important complication (prevented by early
motion)
CLASSIFICATION
 Phalanx (treated via buddy tape)
 Distal phalanx – most common fractured bone in hand
 Metacarpal
 Boxer’s fracture – extra-articular fracture of neck of 5th metacarpal (treated with ulnar gutter splint )
 Dislocations and subluxation (treated with closed or open reduction and buddy tape)
DUPUYTREN’S DISEASE

PATHOPHYSIOLOGY
 A fibrotic contraction of longitudinal palmar fascia (not the flexor tendons) forming painless nodules and cords
 Eventually leads to flexion contractures at the MCP and interphalangeal joint (affects all fingers – ring most common)
 Genetic disorder (but associated with alcohol and diabetes)
TREATMENT
 Operative – surgical fasciectomy (only indicated if lack of extension)

Spine
THORACOLUMBAR SPINE

GENERAL PRINCIPLES
 Spinal cord terminates at conus medullaris (L1)
 Individual nerve roots exit below pedicle of vertebra (i.e. L4 nerve root exits below L4) (as opposed to cervical spine)
SPECIAL TESTS
 Straight leg test – passive lifting of leg reproduces radicular symptoms of pain
 Femoral nerve stretch test – in prone position extend hip, flex knee, and plantar-flex (pain in thigh if L4 radiculopathy)
Clinical presentation of lumbar radiculopathy
L4 L5 S1
Motor Tibialis anterior Extensor hallucis longus Gastrocnemius/soleus
weakness (ankle dorsiflexion + inversion) (great toe extension) (plantar flexion + eversion)

Sensory Medial aspect of lower leg Lateral aspect of lower leg and Lateral dorsal foot and sole of foot
deficit medial dorsal foot

Reflexes Knee (patellar) N/A Ankle (achilles)

DIFFERENTIAL DIAGNOSIS OF BACK PAIN

 Mechanical or nerve compression (>90%):
 Degenerative
 Peripheral nerve compression
 Spinal stenosis
 Cauda equina syndrome (EMERGENCY)
 Others (<10%):
 Neoplastic (primary, metastatic, multiple myeloma)
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 Infectious (osteomyelitis or TB)

 Traumatic or metabolic (osteoporosis)
 Spondyloarthropathies (ankylosing spondylitis)
 Referred (AAA or pancreatitis)
CLASSIFICATION OF BACK PAIN
 Acute – <6 weeks
 Chronic – >12 weeks
DIAGNOSIS
 Clinical examination (musculoskeletal and neurological) – must exclude RED FLAGS
 Imaging – not indicated as part of initial investigation (CT/MRI if red flags or X-ray if trauma)
 Labs – CBC, CRP, ALP, calcium/phosphate, PSA, myeloma screen (if infection/cancer suspected)
TREATMENT
 Red flags present – referral for evaluation and treatment
 Acute/subacute:
 Patient education:
 90% of back pain resolves within six weeks
 Physical activity and early return to work is important
 Self-care strategies include local heat therapy and massage
 Analgesics – paracetamol  NSAIDs  short-course muscle relaxants  short-acting opioids (only for severe pain)
 Chronic:
 Referral is essential
 Prescribe physical exercise
 Analgesics – paracetamol  NSAIDs  low-dose tricyclic antidepressants
SPONDYLOLYSIS AND SPONDYLOLISTHESIS

DEFINITION
 Spondylolysis – defect in pars interarticularis (bone that form facet joints)
 Spondylolisthesis – defect in pars interarticularis leading to anterior displacement of vertebra (usually L5-S1)
SPINAL STENOSIS
Spinal stenosis is narrowing of the spinal canal leading to compression of nerve roots and spinal cord.
 Can be idiopathic or acquired (degenerative joint disease, ankylosing spondylosis, Paget’s disease, trauma)
CLINICAL PRESENTATION
 Neurogenic claudication ± bilateral back/leg pain/paraesthesia ± motor weakness
 Improves with flexion of the hips
 Positive straight leg raise
DIAGNOSIS
 Imaging – CT/MRI (but CT myelogram is gold standard)
TREATMENT
 Non-operative – NSAIDS and physiotherapy ± lumbar epidural steroids
 Operative – decompressive surgery
LUMBAR DISC HERNIATION

PATHOPHYSIOLOGY
 Tear in annulus fibrosis allows protrusion of nucleus pulposis leading to posterolateral disc herniation
 Typically, occurs in L5/S1 > L4/L5 > L3/L4
CLINICAL PRESENTATION
 Back or leg pain (exacerbated by increased abdominal pressure)
 Sciatica (most common symptom) – leg dominant, constant, burning pain that may involve foot
 Cauda equina syndrome (in up to 10% of cases)
 Examination:
 As above (for radiculopathy)
DIAGNOSIS
 Imaging – CT/MRI
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TREATMENT
 Non-operative – NSAIDS and extension protocol (90% of patients improve in 3-months with non-operative treatment)
 Operative – surgical discectomy
CAUDA EQUINA SYNDROME

PATHOPHYSIOLOGY
 Compression/irritation of lumbosacral nerve roots (cauda equina) below conus medullaris (below L2 level)
 Typically, due to herniated disc , spinal stenosis , vertebral fracture, or tumour
CLINICAL PRESENTATION
 Acute presentation of:
 Motor LMN signs – lower limb weakness and reduced reflexes
 Sensory signs – sciatica, lower limb sensory loss, saddle anaesthesia
 Autonomic dysfunction – urinary or faecal incontinence (impotence is a late finding)
 Persistent cauda equina syndrome leads to permanent paraplegia, sensory loss, and autonomic dysfunction
DIAGNOSIS
 Imaging – urgent MRI
TREATMENT
 Operative – emergency surgical decompression
OUTCOMES
 Recovery correlates with function at initial presentation :
 If patient ambulatory – likely to be ambulatory post-surgery
 If unable to walk – unlikely to walk post-surgery

Pelvis
PELVIC FRACTURE

MECHANISM
 Young – high energy trauma (e.g. MVA)
 Elderly – low energy trauma
 Due to lateral compression (most common), anteroposterior compression, or vertical shearing
CLASSIFICATION
 Classified as rotationally stable or unstable and vertically stable or unstable
 An ‘open book’ fracture refers to disruption of the pelvic ring (due to both an anterior and posterior defect)
CLINICAL PRESENTATION
 Pain, swelling, deformity
 May present as haemorrhagic shock (an orthopaedic emergency )
DIAGNOSIS
 Imaging – pelvic X-ray and CT
 Assess genitourinary injury – rectal, vaginal, and urethral exam (if involved, the fracture is considered an open fracture)
TREATMENT
 DRS ABCs
 Non-operative (stable fracture) – protected weight bearing
 Operative (unstable fracture) – ORIF
 Emergency management
 IV fluids/blood
 Pelvic binder /sheeting
 External fixation or emergent endovascular embolisation
 Laparotomy (indicated if FAST positive)
COMPLICATIONS
 Exsanguination
 Injury to rectum or urogenital structures (leading to sexual, voiding, or obstetric difficulties)
 High risk of DVT/PE
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Hip
HIP DISLOCATION
Hip dislocation
ANTERIOR HIP DISLOCATION (RARE) POSTERIOR HIP DISLOCATION (>90%)

Mechanism  Posteriorly force to lower limb with hip widely abducted  Severe force to knee with hip flexed/adducted
(e.g. knee into dashboard during MVA)

Presentation  Shortened, abducted, externally rotated lower limb  Shortened, adducted, internally rotated lower limb

Treatment  NOP – closed reduction (with sedation and muscle relaxants) (requires post-reduction CT)
 Posterior may require traction if reduction is unstable

Complications  Post-traumatic osteoarthritis

 AVN of femoral head
 Nerve palsy (sciatic in posterior; obturator in anterior)
 Comorbid fracture (up to 50% of patients with hip dislocation suffer fractures elsewhere at the time of injury)

HIP FRACTURE
Hip fracture
FEMORAL NECK (SUBCAPITAL) INTERTROCHANTERIC SUBTROCHANTERIC

Definition Intracapsular fracture Extracapsular fracture, affecting the Extracapsular fracture, involving the
(Garden classification system) greater or lesser trochanters proximal femoral shaft

Mechanism  Young – high energy trauma (e.g. MVA)

 Elderly – low energy trauma (esp. fall with osteoporosis)

Presentation  Pain, inability to weight bear, and reduced ROM

 Shortened and externally rotated leg
 Bruising of the posterior upper thigh (if inter/subtrochanteric)

Treatment  OP – ORIF (if young)  OP – closed reduction under fluoroscopy + dynamic hip screw or IM nail
 OP – hemi-/total hip arthroplasty (if elderly)

Complications  High risk of DVT/PE

 AVN of femoral head (if subcapital)

Avascular necrosis of femoral head

 Occurs distal to proximal blood supply to femoral neck and head (medial and lateral femoral circumflex arteries )
 Occurs in femoral neck fracture , chronic steroid use , SCFE, Legg-Calve-Perthes , SLE, and RA
Hip dislocation post-total hip arthroplasty
MECHANISM
 May occur when hip is flexed, adducted, and internally rotated (‘avoid crossing legs ’ for at least six weeks post-surgery)
 Occurs in up to 5% of primary surgeries and 15% of revision surgeries
TREATMENT
 Non-operative – closed reduction + external abduction splint (to prevent hip adduction)
 Operative – revision THA or conversion to larger femoral head or resection arthroplasty
COMPLICATIONS
 As for posterior hip dislocation (sciatic nerve palsy in particular)

Femur
Femur fractures
SHAFT FRACTURE DISTAL FRACTURE

Mechanism  High energy trauma (enormous force required)  High energy trauma
 Lower force spiral fractures in children (suspicious of child abuse)

Presentation  Pain, swelling, deformity, inability to weight bear  Pain, swelling, deformity, inability to weight bear
 Shortened, externally rotated, leg (if fracture displaced)  Shortened, externally rotated, leg (if fracture displaced)
 Knee effusion (haemarthrosis)

Treatment  NOP – consider femoral nerve block for analgesia  NOP – consider femoral nerve block for analgesia
 OP – ORIF + IM nail  OP – ORIF
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Complications  Neurovascular injury  Neurovascular injury (esp. femoral/popliteal artery)

 Fat embolism leading to ARDS  Extensive soft tissue damage
 Extensive soft tissue damage

Knee
CRUCIATE LIGAMENT TEARS
Cruciate ligament tears
ANTERIOR CRUCIATE LIGAMENT (MORE COMMON) POSTERIOR CRUCIATE LIGAMENT

Anatomy Resists anterior displacement and internal rotation of tibia Resists posterior displacement of tibia in relation to femur

Mechanism  Sudden deceleration  Sudden posterior displacement of tibia on a flexed or

 ‘Plant & turn’ (hyperextension/internal rotation of tibia on femur) hyperextended knee (e.g. dashboard MVA injury)

Presentation  Pain (tenderness on posterolateral joint line)  Pain (tenderness on anteromedial joint line)
 Audible ‘pop’  Audible ‘pop’
 Immediate swelling/effusion (haemarthrosis)  Immediate swelling/effusion (haemarthrosis)
 Inability to continue activity (knee ‘gives way’)  Inability to continue activity (pain with push off)
 Positive anterior drawer  Positive posterior draw
 Associated with MCL/meniscal injuries (unhappy triad)

Treatment  NOP – immobilisation for several weeks followed by physiotherapy

 OP (if high-demand lifestyle) – ligament reconstruction (hamstring or patellar tendon graft)

Note: ligamentous injury is best characterised by MRI imaging .

COLLATERAL LIGAMENT TEARS
Collateral ligament tears
MEDIAL COLLATERAL LIGAMENT (MORE COMMON) LATERAL COLLATERAL LIGAMENT

Mechanism  Valgus force to knee  Varus force to knee

Presentation  Pain (above and below medial joint line)  Pain (above and below lateral joint line)
 Swelling/effusion  Swelling/effusion
 Joint laxity  Joint laxity
 Associated with ACL/meniscal injuries (unhappy triad)

Treatment  NOP – immobilisation for several weeks followed by physiotherapy

 OP (if multiple ligamentous injuries) – ligament reconstruction

MENINSCAL TEARS

MECHANISM
 Acute twisting injury
 Requires moderate force in young person
 Requires mild force in elderly due to degeneration
 Medial tear more common than lateral (unhappy triad)
CLINICAL PRESENTATION
 Classically, presents with immediate pain, difficulty weight-bearing , instability , and clicking
 Leads to insidious swelling/effusion (haemarthrosis) several days after injury (as opposed to cruciate ligament tears)
 Associated with locking of knee (if portion of meniscus is causing a mechanical obstruction)
 Examination:
 Joint line tenderness medially or laterally
 Positive McMurray test
 Asking patients to squat and/or duck-walk will frequently reproduce symptom
DIAGNOSIS
 Imaging – MRI (as for other ligamentous injuries)
 Arthroscopy can be considered
TREATMENT
 Non-operative – physiotherapy
 Operative (indicated if locking) – arthroscopic repair or partial meniscectomy
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QUADRICEPS/PATELLAR TENDON RUPTURE

MECHANISM
 Sudden forceful contraction of quadriceps during an attempt to stop (especially in obese patients)
CLINICAL PRESENTATION
 Inability to extend knee (straight leg raise)
 Patella in a lower or higher position with palpable gap above or below patella respectively
 May have an effusion
TREATMENT
 Non-operative – immobilisation in brace
 Operative (indicated if complete tear) – ligament reconstruction
DISLOCATED KNEE

MECHANISM
 High energy trauma (by definition is caused by tears of multiple ligaments)
CLINICAL PRESENTATION
 Classically, causes pain, effusion, knee instability , and ischaemic limb
DIAGNOSIS
 Ankle brachial index (abnormal if <0.9)
 CT angiogram if abnormal vascular exam
TREATMENT
 Non-operative – urgent closed reduction
 Operative (indicated if vascular injury) – operative repair
 Additional – 6 weeks of knee immobilisation
COMPLICATIONS
 High incidence of associated injuries (popliteal artery , with compartment syndrome, or common peroneal nerve )
 Chronic instability, stiffness, or post-traumatic arthritis

Patella
PATELLAR FRACTURE

MECHANISM
 Direct blow to patella (e.g. dashboard MVA injury)
CLINICAL PRESENTATION
 Classically, causes pain, inability to extend knee , deformity , and effusion/haemarthrosis
TREATMENT
 Non-operative – straight leg immobilisation
 Operative (indicated if displaced) – ORIF (tension band wire )
PATELLAR DISLOCATION

MECHANISM
 Usually, a non-contact twisting injury or direct blow to knee causing lateral dislocation
CLINICAL PRESENTATION
 Severe pain (tenderness anteromedially from rupture of capsule)
 Knee catches or gives way with walking
 Obvious dislocation (may be recurrent and self-reducing)
 Examination:
 Positive patellar apprehension test (passive lateral translation results in guarding and patient apprehension)
TREATMENT
 Non-operative (first-line) – immobilisation followed by progressive weight bearing /isometric quadriceps strengthening
 Operative – surgical tightening of medial capsule
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PATELLOFEMORAL SYNDROME (CHONDROMALACIA PATELLAE)

Patellofemoral syndrome is a syndrome of anterior knee pain associated with idiopathic articular changes of the patella.
MECHANISM
 Softening, erosion, and fragmentation of patella articular cartilage (commonly in active young females)
CLINICAL PRESENTATION
 Classically, insidious onset of deep, aching, anterior knee pain (esp. after prolonged sitting) and sensation of instability
 Examination:
 Palpable crepitus
 Pain with compression of patella
TREATMENT
 Non-operative – vastus medialis strengthening
 Operative – arthroscopic lateral retinaculum release or arthroscopic debridement of patella

Tibia
Tibia fractures
TIBIAL PLATEAU TIBIAL SHAFT

Mechanism  Varus/valgus load ± axial loading (esp. in osteoporosis)  Low energy torsional injury or high energy trauma
 Most common long bone and open fracture

Presentation  Pain, swelling, deformity, inability to weight bear  Pain, swelling, deformity, inability to weight bear
 Associated with compartment syndrome  Commonly open fracture
 Associated with ligamentous injuries

Treatment  NOP – immobilisation followed by progressive weight bearing  NOP – long leg cast
 OP – ORIF  OP – ORIF ± IM nail

Complications  As above  Neurovascular injury (esp. popliteal artery)

 AVN  Compartment syndrome (common)
 Poor soft tissue coverage (critical to outcome)

Ankle
BASIC PRINCIPLES

Ottawa Ankle Rules

The Ottawa Ankle Rules are used as a guide to determine the indications for X-ray use in suspected ankle or foot sprain or fracture.
GUIDELINES
 A patient with traumatic ankle pain (in malleolar zone) with any of the following:
 Point tenderness at posterior edge (of distal 6cm) of tip of lateral or medial malleolus
 Inability to weight bear (four steps) immediately and in emergency department
 A patient with traumatic foot pain (in midfoot zone) with any of the following:
 Point tenderness at base of fifth metatarsal or navicular
 Inability to weight bear (four steps) immediately and in emergency department
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ANKLE FRACTURE

CLINICAL NOTES
 Pattern of fracture depends on position of ankle at time of trauma (classified based on level of fibula fracture )
 Typically, involves:
 Ipsilateral ligamentous tears or transverse bony avulsion
 Contralateral shear fractures (oblique or spiral)
 Treated non-operatively with below knee cast + non-weight bearing or operatively with ORIF
 Ankle fracture has the highest incidence of post-traumatic arthritis
Ankle dislocation
Ankle dislocation is a complication of ankle fracture and is an orthopaedic emergency .
 Associated with gross deformity of ankle , severe stretching of skin (with skin necrosis ), and neurovascular injury
 Treated with emergency closed reduction (with analgesia)
LIGAMENTOUS INJURY OF ANKLE

CLASSIFICATION
 Medial ligament complex (rare) – eversion injury
 Lateral ligament complex (>90%) – inversion injury
 Strongly associated with bruising
TREATMENT
 Mild-to-moderate – RICE (Rest, Ice, Compression, Elevation)
 Severe – physiotherapy ± below-knee walking cast

Foot
Foot fractures
TALAR CALCANEAL

Mechanism  Axial loading (e.g. fall from height) or violent dorsiflexion  Axial loading (e.g. fall from height)

Treatment  NOP – NWB below knee cast  NOP – NWB below knee cast
 OP – ORIF  OP – ORIF

Complications  AVN (tenuous blood supply)  May be associated with compression fractures of spine

ACHILLES TENDONITIS

MECHANISM
 Chronic inflammation from activity or poor-fitting footwear (may be associated with familial hypercholesterolaemia)
CLINICAL PRESENTATION
 Thickened tendon (palpable lump)
 Pain, stiffness, and crepitus of tendon
 Normal Thompson test
TREATMENT
 Non-operative – rest, NSAIDs, and shoe-wear modification
 Steroid injections are NOT indicated (risk of tendon rupture)
ACHILLES TENDON RUPTURE

MECHANISM
 Loading activity (may occur secondary to chronic tendonitis, steroid injection, or ciprofloxacin)
CLINICAL PRESENTATION
 Classically, presents as audible pop and sudden pain with push-off movement
 Examination:
 Abnormal Thompson test (no plantar flexion when calf is squeezed)
 Weak plantar flexion strength
 Palpable gap
TREATMENT
 Non-operative ( low demand) – equinus cast (cast foot in plantar flexion to relax tendon)
 Operative ( high demand) – surgical repair followed by cast as above
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PLANTAR FASCIITIS
Plantar fasciitis is inflammation of the plantar aponeurosis at the calcaneal insertion.
MECHANISM
 Repetitive strain injury causing microtears and inflammation of plantar fascia
CLINICAL PRESENTATION
 Insidious onset of burning pain in the heel and sole of foot
 Typically, intense when walking from rest but subsides as patient continues to walk
 Examination:
 Local tenderness at plantar fascia (esp. at calcaneus)
 Pain with toe dorsiflexion (stretches the fascia)
TREATMENT
 Non-operative – rest and stretching ± physiotherapy ± orthotics ± NSAIDs ± steroid injection
 Operative – surgical release of fascia
BUNIONS (HALLUX VALGUS)

MECHANISM
 Bony deformity characterised by medial displacement of first metatarsal and lateral deviation of hallux
 Reactive exostosis forms with thickening of the skin creating a bunion
 Most often associated with poor-fitting footwear
 Typically, occur in women with a family history
CLINICAL PRESENTATION
 Painful skin thickening (‘ bunion’) at medial eminence of first metatarsal head
TREATMENT
 Non-operative – properly fitted shoes ± toe spacers
 Operative – osteotomy with realignment

Paediatric orthopaedics
BASIC PRINCIPLES

CLINICAL NOTES
 Types of fracture:
 Thicker, more active, periosteum results in – greenstick (one cortex), torus (impacted cortex) , and plastic (bowing)
fractures
 Distal radius fracture is most common
 Typically, treated with closed reduction and casting (anatomic reduction may cause limb length discrepancy in children)
 Epiphyseal growth plate:
 Weak part of bone which is susceptible to fractures
 Often mistaken for fractures on imaging (compare with opposite limb)
 Intra-articular fractures have worse consequences in children because they usually involve the growth plate
 Healing rate – faster in children
EPIPHYSEAL INJURY
Epiphyseal injury in children is classified using the Salter-Harris Classification .
 Salter-Harris types III, IV, and V are managed with open reduction
CLASSIFICATION
Note: types III and IV are most likely to cause growth arrest and progressive deformity.
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NURSEMAID’S ELBOW
Nursemaid’s elbow (radial head subluxation ) occurs in pre-school children secondary to being pulled/lifted by the hand.
 Presents as pain, pronation, and refusal to bend at the elbow
 Treated with manual reduction (supination of arm and slowly bringing it to flexion ) (does not require immobilisation)
OSGOOD-SCHLATTER DISEASE
Osgood-Schlatter disease is inflammation of the patellar ligament at the insertion point on the tibial tuberosity .
FEATURES
 Age of onset is ten to fifteen years (more common in boys)
MECHANISM
 Repetitive tensile stress on insertion of patellar tendon causes minor avulsion and inflammation at tibial tuberosity
CLINICAL PRESENTATION
 Anterior knee pain (exacerbated by jumping or kneeling)
 Examination:
 Tender lump over tibial tuberosity
 Pain on resisted leg extension
TREATMENT
 Benign, self-limited, condition (does not resolve until growth halts)
 Symptomatic relief
DEVELOPMENTAL DYSPLASIA OF THE HIP
Developmental dysplasia of the hip is abnormal development of the hip resulting in dysplasia and subluxation/dislocation of the hip .
 Most common orthopaedic disorder in newborns
PATHOPHYSIOLOGY
 Due to ligamentous laxity , muscular underdevelopment , and abnormal shallow slope of acetabular roof
 Risk factors – female, family history, breech presentation, firstborn
CLINICAL PRESENTATION AND DIAGNOSIS
 Clinical diagnosis by physical examination:
 Limited abduction of the flexed hip
 Asymmetry of skin folds and gluteal muscles
 Specific clinical signs:
 Barlow manoeuvre (checks if hips are dislocatable) – posterior pressure is placed on inner aspect of abducted thigh, and hip is
then adducted, leading to an audible ‘clunk’ as the femoral head dislocates posteriorly
 Ortilani manoeuvre (checks if hips are dislocated) – thighs are gently abducted from the midline with anterior pressure on the
greater trochanter leading to a ‘soft click’ on reduction of femoral head into acetabulum if femur is dislocated
 Allis (Galaezzi) sign – knees at unequal heights when hips and knees are flexed (the dislocated side is lower)
 Definitive diagnosis via ultrasound (if <6 months old) or pelvic X-ray (if >6 months old)
TREATMENT
 0-6 months – Pavlik harness (maintains hip flexed and abducted)
 6-18 months – spica cast (similar to Pavlik harness but non-removable)
 >18 months – surgical reduction followed by spica cast
COMPLICATIONS
 Joint contractures and avascular necrosis of the femoral head
 Without treatment, a significant defect is likely in young children
LEGG-CALVE-PERTHES DISEASE (COXA PLANA)
Legg-Calve-Perthes disease is idiopathic AVN and osteonecrosis of the femoral head.
 Typically, is unilateral
FEATURES
 Most common in boys (4 to 10 years of age)
 Usually self-limiting, with symptoms lasting <18 months
CLINICAL PRESENTATION
 Typically, child with antalgic or Trendelenburg gait ± pain
 If pain is present, it can be in the groin, anterior thigh, or referred to the knee
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 Examination – limited abduction and internal rotation of affected limb

DIAGNOSIS
 Imaging:
 X-ray (may be normal if early; eventually, characteristic collapse/flattening of femoral head)
 Consider bone scan or MRI if equivocal
TREATMENT
 Non-operative – physiotherapy or bracing (in flexion and abduction)
 Operative (if severe or >8 years old) – femoral or pelvic osteotomy
SLIPPED CAPITAL FEMORAL EPIPHYSIS

PATHOPHYSIOLOGY
 Slipped capital femoral epiphysis is a type I Salter-Harris epiphyseal injury at the proximal hip (bilateral in 50% of cases)
 The femur head remains in the acetabulum, whilst the metaphysis displaces anteriorly and superiorly
FEATURES
 Most common adolescent hip disorder
 Peak incidence at pubertal growth spurt
 Risk factors : obesity (main), male, hypothyroidism (risk for bilateral)
CLINICAL PRESENTATION
 Insidious onset of dull hip pain or referred knee pain with painful limp
 Restricted ROM (internal rotation and abduction)
 Patients hold hip in passive external rotation
 Tenderness of joint capsule
 Inability to weight bear or ambulate (classified as unstable SCFE)
DIAGNOSIS
 X-ray (frog-leg lateral and AP views) – demonstrates posterior and inferior displacement of femoral head
 Labs – TSH (rule out hypothyroid)
TREATMENT
 Immediate surgical screw fixation (reduces risk of AVN)
 No weight bearing should be allowed until defect is surgically stabilised
COMPLICATIONS
 AVN
 Chondrolysis (loss of articular cartilage, resulting in narrowing of joint space)
 Premature hip osteoarthritis
CLUB FOOT (TALIPES EQUINOVARUS)
Club foot is a congenital foot deformity due to muscle contractures of the ankle and foot.
 Can be described anatomically as a CAVE deformity (midfoot Cavus, forefoot Adductus, hindfoot Varus, hindfoot Equinus)
 Associated with DDH and spinal dysraphism (unfused vertebral bodies)
TREATMENT
 Typically, non-operative via Ponseti technique (serial manipulation and casting)
 Surgical release if refractory
OUTCOMES
 Mild recurrence common
 Affected foot is permanently stiffer/smaller than normal foot with calf muscle atrophy
SCOLIOSIS
Scoliosis is a lateral curvature of the spine greater than 10 degrees.
 Typically, idiopathic (90% of cases)
 More common and severe in females
 Treatment is based on Cobb angle (measurement of scoliotic curve) – observation versus bracing versus surgical correction
 An important complication is restrictive lung disease
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Orthopaedic oncology
GENERAL PRINCIPLES

CLINICAL NOTES
 Primary bone tumours are common in children and adolescents (but not adults)
 Metastatic bone tumours are common in adults and elderly (but rarely children – other than neuroblastoma)
 Most common source of metastatic bone lesions are – BLT with a Kosher Pickle (Breast, Lung, Thyroid, Kidney, Prostate)
 Breast and prostate are most common (over two-thirds); also, they are the common sclerotic/osteoblastic bony metastases
 Typically, affect regions of high growth such as the distal femur, proximal tibia, or proximal humerus
 The most common benign bone tumour is osteochondroma
Distinguishing benign from malignant bone lesions on X-ray
BENIGN MALIGNANT

 No periosteal reaction  Acute periosteal reaction

 Thick endosteal reaction  Codman’s triangle
 Well-developed bone formation  ‘Onion skin’
 Intraosseous and even calcification  ‘Sunburst’ – tumour extension into periosteum
 Broad board between lesion and normal bone
 Varied bone formation
 Extraosseous and irregular calcification

DIFFERENTIAL DIAGNOSIS
 Osteochondroma (benign) – cartilage capped bony tumour at metaphysis

Common peripheral nerve lesions

Upper extremity nerves lesions
NERVE MECHANISM PRESENTATION

Axillary (C5-C6)  Fractured surgical neck of humerus  Motor (deltoid) – loss of arm abduction
 Anterior dislocation of humerus  Sensory – loss of sensation over deltoid

Median (C5-T1)  Proximal (above elbow)  Motor (‘hand of benediction’ when trying to make a fist if proximal lesion)
 Distal (carpal tunnel/wrist laceration)  Loss of wrist flexion
 Loss of flexion of lateral fingers
 Loss of thumb opposition
 Weakness in lumbricals of 2nd/3rd digits
 Wasting of thenar eminence
Note: distal lesion only affects highlighted.  Sensory – as usual in hand

Radial (C5-T1)  Fracture of humeral shaft  Motor

 Compression of axilla (‘Saturday night’ palsy)  Loss of wrist extension (with wrist drop)
 Sensory – as usual in hand (in addition to posterior arm/forearm)

Ulnar (C8-T1)  Proximal (cubital tunnel of elbow)  Motor (‘ulnar claw’ at rest if distal lesion)
 Distal (Guyon’s canal of hand)  Loss of wrist flexion (flexor carpi ulnaris)
 Loss of flexion of medial fingers (medial flexor digitorum profundus)
 Loss of finger adduction/abduction (interosseus muscles)
 Weakness in lumbricals of 4th/5th digits
 Wasting of hypothenar eminence
 Sensory – as usual in hand

Note: can remember nerve root origin via brachial plexus diagram (all intuitive other than axillary – which is C5/C6).

Hand muscles
 Thenar (median nerve) – Opponens pollicis, Abductor pollicis brevis, Flexor pollicis brevis
 Hypothenar (ulnar nerve) – Opponens digitis minimi, Abductor digiti minimi, Flexor digiti minimi brevis
 Both groups perform the same function (OAF – Oppose, Abduct, and Flex)
 Dorsal interossei muscle – ABduct the fingers (DAB)
 Palmar interossei – ADduct the fingers (PAD)
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Lower extremity nerves lesions

NERVE MECHANISM PRESENTATION

Obturator (L2-L4)  Pelvic surgery  Motor – loss of hip adduction

 Anterior hip dislocation  Sensory – loss of medial thigh sensation

Femoral (L2-L4)  Pelvic fracture  Motor – loss of hip flexion and leg extension

Common  Trauma to fibula  Motor – foot drop (Peroneal Everts and Dorsiflexes – PED)
peroneal (L4-S2)  Knee dislocation

Tibial (L4-S3)  Knee trauma  Motor – loss of tiptoe (Tibial Inverts and Plantarflexes – TIP)
 Bakers cyst  Sensory – loss of sole of foot sensation

Superior  Iatrogenic during IM injection to upper  Motor – Trendelenburg gait (loss hip abduction)
gluteal (L4-S1) medial gluteal region

Inferior  Posterior hip dislocation  Motor – loss of hip extension

gluteal (L5-S2)

Lower limb clinical notes

 Sciatic nerve (L4-S3) innervates posterior thigh and splits into common peroneal and tibial nerves
 Superior gluteal nerve innervates gluteus medius and minimus (hip abductors and internal rotators)
 Inferior gluteal nerve innervates gluteus maximus (hip extender)

Anatomical correlations
 Branches of median nerve:
 Anterior interosseus nerve (at forearm) – relevant forearm muscles
 Motor branch in the hand (at palm) – relevant hand muscles
 Palmar cutaneous branch (at palm) – relevant sensory distribution
 Branches of ulnar nerve:
 Deep branch of ulnar nerve – relevant hand muscles
 Muscular branch (at forearm) – relevant forearm muscles
 Palmar cutaneous branch (at forearm) – relevant sensory distribution
 Dorsal cutaneous branch (at forearm) – relevant sensory distribution
 Nerve supply to leg:
 Sciatic nerve
 Tibial nerve – posterior compartment of leg (plantar flexors and inverters) (also sensory to sole of foot)
 Common peroneal nerve
 Superficial fibular nerve – lateral compartment of leg (plantar flexors and everters) (also sensory to L5 distribution)
 Deep fibular nerve – anterior compartment of leg (dorsiflexion) (also sensory to great toe web space)

Note: the tibial and common peroneal nerve combine to form the sural nerve (sensory supply to posterolateral leg and lateral foot).
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Ophthalmology
Conjunctiva
CONJUNCTIVITIS

CLASSIFICATION

Conjunctivitis
AETIOLOGY CLINICAL PRESENTATION TREATMENT

Bacterial  Purulent discharge  Antibiotic drops/ointment

Chlamydia trachomatis  Mild bilateral purulent conjunctivitis and marked eyelid oedema  Caesarean section (prevent colonisation)
 Occurs in neonates (ophthalmia neonatorum) within two weeks  Erythromycin

Neisseria gonorrhoea  Severe bilateral purulent conjunctivitis and marked eyelid oedema EMERGENCY (causes corneal ulceration)
 Occurs in neonates (ophthalmia neonatorum) within one week  Caesarean section (prevent colonisation)
 Ceftriaxone

Viral (adenovirus)  Copious watery discharge (associated with preauricular nodes)  Self-limiting (very contagious)

HSV  Vesicular eruption associated with corneal ulcer EMERGENCY (causes corneal ulceration)
 Occurs in neonates (neonatal herpetic conjunctivitis)  Caesarean section (prevent colonisation)
 Acyclovir

DIAGNOSIS
 Clinical diagnosis (± swab for culture or viral PCR)

Uvea
UVEITIS

CLASSIFICATION
 Anterior uveitis (iritis) – painful photophobia and eye redness
 Associated with connective tissue disease and inflammatory bowel disease
 Intermediate uveitis (inflammation of vitreous) – painless blurred vision and vitreous floaters (snowbank appearance)
 Associated with sarcoidosis
 Posterior uveitis (inflammation of choroid and/or retina) – painless blurred vision and vitreous floaters
 Associated with infection and Behcet disease

Lens
CATARACTS
Cataracts are opacifications of the lens resulting in obstructed passage of light (most common cause of reversible blindness).
AETIOLOGY
 Age-related (>90% of cataracts)
 Associated with systemic disease (esp. diabetes)
 Radiation
CLINICAL PRESENTATION
 Gradual, painless, progressive loss of visual acuity (particularly, loss of night vision)
TREATMENT
 Surgical – phacoemulsification and prosthetic lens (excellent prognosis)

Retina
RETINAL DETACHMENT

CLINICAL PRESENTATION
 Triad of sudden onset flashes of light , floaters, and blurred vision
 Occurs secondary to ocular trauma, diabetic retinopathy, retinopathy of prematurity, or central retinal vein occlusion
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RETINAL VASCULAR OCCLUSION

CLASSIFICATION

Central retinal artery versus central retinal vein occlusion

CENTRAL RETINAL ARTERY OCCLUSION CENTRAL RETINAL VEIN OCCLUSION

Clinical presentation  Sudden, painless, unilateral blindness  Rapid, painless, visual loss of variable severity
 Associated with RAPD  Associated with retinal haemorrhage
 Associated with cherry-red spot on fovea  Associated with hypertension

Treatment  Ocular massage  Laser photocoagulation

 Intra-arterial thrombolysis

Amaurosis fugax
Amaurosis fugax is a sudden, painless, loss of vision that lasts for seconds to minutes and is followed by spontaneous recovery .
 Typically, caused by transient occlusion of the central retinal artery by microemboli from carotid artery stenosis
AGE-RELATED MACULAR DEGENERATION

CLASSIFICATION

Age-related macular degeneration

ATROPHIC (DRY) EXUDATIVE (WET)

Clinical presentation  Gradual painless loss of central vision  Rapid painless loss of central vision

Fundoscopy  Drusen (accumulation of white/yellow cellular material)  Haemorrhage

 Pigmentary changes  Subretinal fluid

Treatment  No treatment  VEGF inhibitors

 Phototherapy

Glaucoma
CLASSIFICATION

Closed-angle versus open-angle glaucoma

FEATURE CLOSED-ANGLE OPEN-ANGLE

Pathophysiology Disrupted flow of aqueous humour into the anterior chamber Diseased trabecular meshwork results in decreased drainage
results in increased pressure in the posterior chamber leading and increase in IOP
to angle closure that decreases drainage and increase in IOP

Important risk factors Asian ethnicity and prolonged pupillary dilation Diabetes and myopia

Clinical presentation  Extreme, sudden-onset, eye pain and blurred vision  Gradual loss of peripheral vision
 Associated with headache, nausea, and vomiting

Diagnosis  Clinical diagnosis (history and fixed pupil and hard, red, eye)  Visual field test (loss of peripheral vision)
 Tonometry (measurement of IOP)
 Fundoscopy (cupping of optic disk)

Treatment EMERGENCY  Topical β-blocker ( aqueous humour production)

 Topical β-blocker ( aqueous humour production)  Topical pilocarpine ( aqueous humour outflow)
 Topical pilocarpine ( aqueous humour outflow)  Oral acetazolamide (carbonic anhydrase inhibitor)
 IV acetazolamide (carbonic anhydrase inhibitor)  Trabeculotomy (definitive)
 Laser peripheral iridotomy (definitive)
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Gaze defects
GAZE DEFECTS
Gaze defects
GAZE DEFECT CLINICAL PRESENTATION

CNIII Ipsilateral eye directed ‘down and out’ at rest; severe diplopia and ptosis; fixed dilated pupil; impaired accommodation

CNIV Ipsilateral diplopia when eye is adducted and looking downwards (difficulty reading/walking down stairs)

CNVI Ipsilateral weakness of abduction (lateral movement) of the eye and medial strabismus at rest

Internuclear Failure of adduction of the ipsilateral eye towards the nose

ophthalmoplegia

Relative afferent Eye dilates in swinging light test (partial damage to ipsilateral afferent pathway where consensual relaxation response dominates)
pupillary defect

Paediatric ophthalmology
STRABISMUS
Strabismus is ocular misalignment in one or both eyes.
CLASSIFICATION
 Heterotropia (manifest deviation or ‘squint’) – deviation apparent when patient is using both eyes
 Termed esotropia if ‘cross-eyed’ and exotropia if ‘wall-eyed’
 Heterophoria (latent deviation) – deviation established by cover test (i.e. deviated when using one eye)
 Concomitant strabismus – a deviation that is the same magnitude regardless of gaze position
 Incomitant strabismus – a deviation that that varies as the patient shifts his or her gaze up, down, or to the sides
 Accommodative esotropia – the eyes turn inward due to the effort of focusing far-sighted eyes
 Pseudostrabismus – the ‘appearance’ (but not the presence) of esotropia due to prominent epicanthal folds (esp. in Asians)
DIAGNOSIS
 Thorough ophthalmic assessment
 Hirschberg test (corneal light reflex) – assessing for asymmetry
 Cover test – assessing for deviation
TREATMENT
 All children with strabismus require prompt referral to ophthalmologist , treatment may include:
 Glasses (for accommodative esotropia)
 Ophthalmic surgery
 239

AMBLYOPIA
Amblyopia is a neurodevelopmental visual disorder with unilateral (or less commonly, bilateral) reduction of visual acuity.
 It cannot be attributed directly to structural abnormality of the eye (and cannot be treated by glasses alone)
 It is most commonly caused by strabismus (mainly esotropia)
DIAGNOSIS
 Holler test (young children) – child upset if good eye covered
 Quantitative visual testing (older children)
TREATMENT
 Occlusion therapy – patching the good eye forces the brain to use non-dominant eye and redevelop its vision
 Glasses (for refractive error or accommodative esotropia)
OUTCOMES
 Up to 90% of patients have good vision if treated before 4 years old (much less successful after 8 years old)
 However, treatment should be trialled no matter the age
 Risk of permanent visual loss

Clinical correlates
Important ophthalmic conditions
CONDITION CLINICAL PRESENTATION CLINICAL NOTES

Corneal abrasion  Traumatic eye abrasion (stains with fluorescein)

Corneal ulcer  Local necrosis due to infection forming corneal opacity (stains with fluorescein)

HSV keratitis  Dendritic (linear branching) corneal ulcer (stains with fluorescein) Treatment – antivirals

VZV keratitis  Shingles in V1 distribution can cause corneal ulcer Treatment – antivirals

Retinitis pigmentosa  Tunnel vision (loss of peripheral vision) and night blindness
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Otorhinolaryngology
Audiometry
INTERPRETATION

CLASSIFICATION
 Conductive hearing loss – disease of middle or external ear
 Sensorineural hearing loss – disease of inner ear, acoustic nerve, or CNS (can be caused by aminoglycosides or loop diuretics )
INTERPRETATION OF PURE TONE AUDIOMETRY
 Conductive hearing loss – bone conduction normal and air conduction reduced (bone-air gap)
 Sensorineural hearing loss – both bone conduction and air conduction reduced
INTERPRETATION OF TYMPANOGRAPHY
 Type A – normal
 Type A S – otoSclerosis
 Type A D – ossicular chain Discontinuity
 Type B – middle ear effusion / perforation
 Type C – eustachian tube dysfunction

Disease of external ear

EXOSTOSIS
Exostosis is bony protuberance in the external auditory canal (typically, due to swimming in cold water ).
OTITIS EXTERNA

FEATURES
 Typically, bacterial (esp. pseudomonas )
 Associated with swimming and auditory canal trauma
CLINICAL PRESENTATION
 Acute – purulent otorrhoea and ear pain worsened by movement of auricle
 Chronic – pruritis and excoriation of auditory canal
TREATMENT
 Antipseudomonal ear drops

Disease of middle ear

OTITIS MEDIA

PATHOPHYSIOLOGY
 Dysfunction of Eustachian tube  air absorbed in middle ear  negative pressure (an irritant to middle ear mucosa)  oedema of
mucosa with effusion  infection of effusion from nasopharyngeal secretions (typically, viral complicated by bacterial infection)
 Viral causes: RSV, influenza, parainfluenza, adenovirus
 Bacterial causes: S. pneumoniae, H. influenzae, M. catarrhalis, GAS, S. aureus
CLINICAL PRESENTATION
 Triad of rapid onset otalgia, fever, and conductive hearing loss
 Associated with URTI, ear tugging (in young children), otorrhoea (if perforated), irritability, poor feeding, difficulty settling
 Up to 80% of children have spontaneous resolution within two weeks
DIAGNOSIS
 Diagnosis based on clinical history and otoscopic examination
 Otoscopic findings – bulging (due to effusion), erythema, loss of landmarks (e.g. handle of malleolus)
 Reduced mobili ty (flat tympanogram) may be visible on tympanometry
TREATMENT
 Antibiotics are usually unnecessary
 Treat symptomatically (e.g. paracetamol )
 Arrange a ‘back-pocket prescription’ to be dispensed if not improved in 48 hours (or if <2 years, high risk child , or perforation ):
 Amoxicillin for 5 days, or
 Co-trimoxazole for 5 days (if allergic to penicillin)
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COMPLICATIONS
 Main concerns: conductive hearing loss leading to developmental delay
 Extracranial: perforation, extension of infection to adjacent structures (e.g. mastoiditis), cholesteatoma
 Intracranial: meningitis, abscesses, thrombosis
Otitis media with effusion
Otitis media with effusion is the presence of fluid in the middle ear without signs or symptoms of ear infection.
 Associated with recurrent acute otitis media
 Most common cause of paediatric hearing loss
CLINICAL PRESENTATION
 Presents with conductive hearing loss ± tinnitus ± pain or fullness of the ear
 Otoscopic findings – discolouration (grey), meniscus fluid level, air bubbles, retraction pockets
 Reduced mobility (flat tympanogram) is classical on tympanometry
TREATMENT
 Conservative approach (90% resolve by 3 months): audiogram and monitoring
 Surgical approach: myringotomy ± ventilation tubes ± adenoidectomy (if enlarged or if ventilation tubes fail)
CHOLESTEATOMA
Cholesteatoma is a keratinised epithelial cyst in the middle ear , mastoid, and temporal bone.
CLASSIFICATION
 Acquired (common) – presents as retraction pockets in tympanic membrane with chronic foul discharge and progressive hearing loss
 Associated chronic inflammatory process causes progressive destruction of surrounding bony structures
 Associated with a history of otitis media
 Congenital – presents as ‘small white pearl’ behind an intact tympanic membrane or as conductive hearing loss
DIAGNOSIS AND TREATMENT
 Clinical diagnosis
 Audiometry
 Imaging – CT head
 Surgical treatment – mastoidectomy ± tympanoplasty ± ossicular reconstruction
COMPLICATIONS
 Local – ossicular (conductive hearing loss) or inner ear (SNHL) erosion and mastoiditis
 Intracranial – meningitis, intracranial abscess, or sinus thrombosis
MASTOIDITIS
Mastoiditis is infection of mastoid air cells (typically, after inadequately treated suppurative otitis media).
 Presents as classical triad of otorrhoea, tenderness over mastoid , and retroauricular swelling with protruding ear
 Treated with IV antibiotics ± mastoidectomy

Peripheral facial paralysis

PERIPHERAL FACIAL PARALYSIS
Differential diagnosis of peripheral facial paralysis
BELL’S PALSY RAMSAY-HUNT SYNDROME

Aetiology HSV infection of CNVII VZV infection of CNVII/CNVIII

Clinical presentation  LMN CNVII palsy (unilateral paralysis of all facial muscles)  LMN CNVII palsy (unilateral paralysis of all facial muscles)
 Hyperacusis  LMN CNVIII palsy (SNHL)
 Vesicular rash (shingles)

Diagnosis  Clinical  Clinical (with audiology)

Treatment  Protect eye with patching  Systemic steroids/acyclovir (poor prognosis)

 Consider steroids/acyclovir (typically, self-limiting)

Epistaxis
EPISTAXIS

TREATMENT
 ABCs ± topical vasoconstrictors ± cauterisation with silver nitrate ± packing ± ligation or embolisation
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Miscellaneous
PERITONSILLAR ABSCESS

CLINICAL PRESENTATION
 Typically, presents in late adolescence/early adulthood with a triad of trismus, uvular deviation , and dysphonia (‘hot potato
voice’)
 Most commonly caused by GAS (50% of cases)
TREATMENT
 Secure airway
 Surgical drainage
 IV penicillin (if GAS positive)
COMPLICATIONS
 Airway obstruction
 Aspiration pneumonia (due to rupture of abscess)
 Sepsis
INFECTIOUS PHARYNGITIS/TONSILLITIS
Infectious pharyngitis/tonsillitis
BACTERIAL INFECTION EPSTEIN BARR VIRUS OTHER VIRAL INFECTION

Aetiology GAS Epstein Barr Virus Adenoviruses, rhinovirus, enterovirus,

(also, N. gonorrhoea or M. pneumonia) (also, CMV) influenza, coxsackie virus

Epidemiology Older children (20% of all cases) Affects all ages (80% of all cases)

Site of pain Pharynx/tonsils Pharynx/tonsils Often trachea

Severity Often cannot eat Often cannot eat Can usually eat

Radiation Sometimes to ear Sometimes to ear Usually no radiation

Time course Abrupt onset Varies Varies

(starts in throat and stay in throat)

Temperature Not useful Not useful Not useful

Appearance of Large, red, pockets of pus in crypts Like GAS infection, or very enlarged Normal
tonsils (can cause peritonsillar absence) (can obstruct airways)

Lymph nodes Tender anterior triangle Large, rubbery, non-tender posterior Non-tender nodes
triangle nodes (± systemic nodes)

Liver and spleen Normal Hepatosplenomegaly Sometimes liver tenderness

Lab Bacterial swab and culture CBC / Monospot / EBV serology Often normal
investigations

TREATMENT
 Streptococcal infection – amoxicillin
 EBV/viral illness – paracetamol/NSAIDs and supportive therapy

Note: (do NOT give amoxicillin in EBV as it can cause a widespread rash.
STREP. THROAT GUIDELINES
 You must assess for risk of rheumatic fever :
 Maori or pacific people
 Age 3 to 45 years old
 Lives in low SES areas
 Past history of acute rheumatic fever
 Use the Centor criteria (see picture) to guide treatment:
 Low risk – symptomatic treatment
 Medium risk – throat swab and treat if positive
 High risk – throat swab and treat empirically
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Anaesthesia
Basic principles
PRE-OPERATIVE CARE

ASA classification
ASA classification is a classification of physical status at the time of surgery (represents a gross predictor of overall outcome):
 I – normal healthy individual
 II – mild systemic disease
 III – severe systemic disease
 IV – severe systemic disease that is a constant threat to life
 V – not expected to survive

Airway assessment
 Mallampati score
 Cervical mobility
 Thyromental distance
 Oral/dental assessment

Fasting guidelines
 Solids – 6 hours
 Clear fluids – 2 hours
INTRA-OPERATIVE CARE

Anaesthetic agents
 Intravenous anaesthetics (e.g. propofol) – produce unconsciousness
 Muscle relaxants (e.g. rocuronium) – produce profound muscle relaxation
 Inhalation anaesthetics (e.g. sevoflurane) – produce or maintain unconsciousness
 Analgesia (e.g. opioids) – prevents intra- and post-operative pain
 Local anaesthesia – including regional, spinal, epidural, infiltration, and topical anaesthesia
 Epidural – continuous infusion of local anaesthetic and opioid agents into epidural space (can cause hypotension)
 Spinal – single infusion of local anaesthetic and opioid agents into subarachnoid space (can cause post-dural puncture headache)

Types of anaesthesia
 Routine induction:
 Pre-oxygenation Common doses:
 Induction  Propofol – 1.5 to 2.5mg/kg (20–40 mg every 10 seconds until response)
 Muscle relaxants  Lidocaine – maximum 3mg/kg (6mg/kg with adrenaline)
 Pre-ventilation
 Intubation
 Rapid sequence induction (if risk of aspiration):
 Pre-oxygenation
 Induction (fast-acting)
 Muscle relaxants (fast-acting – typically, suxamethonium )
 Cricoid pressure
 Intubation (without pre-ventilation)

Fluid management
FLUID MANAGEMENT
Intravenous fluid is typically given for one of three reasons:
 To replace normal obligatory daily losses of water and electrolytes (maintenance )
 To replace abnormal losses of water and electrolytes (replacement)
 To act as a carrier to administer IV drugs
FLUID COMPARTMENTS
 Total body water:
 Male – 60% bodyweight
 Female – 55% bodyweight
 Child/infant – 70% bodyweight
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 Water distribution:
 ICF – 2/3rds
 ECF – 1/3rd
 Plasma – 4/5ths
 Interstitial fluid – 1/5th
 Blood volume – estimate approximately 70ml/kg
Key ion concentrations
CONTENT ICF ECF
Sodium 140 15

Potassium 4 150

Chloride 100 9

Fluid products
Balanced salt solutions
CONTENT 0.9% SALINE HARTMANN’S (LACTATED RINGERS)
Sodium (mmol) 150 130

Potassium (mmol) 0 5

Chloride (mmol) 150 108

Bicarbonate (mmol) 0 30

Dextrose 0 0

pH 5 6.5

Osmolality (mOsm/L) 300 280

COMMENT  Causes hyperchloraemic acidosis  Causes hypochloraemic alkalosis

 Causes coagulation of blood products (due to calcium)

Maintenance solutions
CONTENT 5% DEXTROSE 4% DEXTROSE/0.18% NACL (DEX/SALINE)
Sodium (mmol) 0 30

Potassium (mmol) 0 0

Chloride (mmol) 0 30

Bicarbonate (mmol) 0 0

Dextrose 50g 40g

pH 4 4.5

Osmolality (mOsm/L) 278 300

Fluid losses
PRINCIPLES
 Average adult loses 700ml of insensible losses each day (skin, lungs, and faeces)
 Average adult requires 500ml of urine output to excrete obligatory solute load
Average daily requirements
CONTENT REQUIREMENTS

Water 4-2-1 rule:

4ml/kg/hr for first 10kg, added to;
2ml/kg/hr for second 10kg, added to;
1ml/kg/hr for each subsequent 1kg

Sodium 2mmol/kg/day

Potassium 1mmol/kg/day

Glucose 50-100g/day (irrespective of patient weight)

Note: most patients do not get enough potassium in IV fluids (but due to large body reserve it is buffered).
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Types of fluid loss

LOSSES THAT APPROXIMATE ECF LOSSES THAT ARE PRINCIPALLY WATER
Blood loss (transfusion of red cells is a separate issue) Fever
Vomiting Increased respiratory rate
Diarrhoea Prolonged water deprivation (e.g. in hospital)
Gut fistulas Diabetes insipidus
Third-spacing (e.g. sepsis, burns, or pancreatitis)
Glycosuria (as in DKA or HHS)

 Principles of losses:
 Losses of ECF-equivalent fluid (isotonic dehydration) leads to changes in ECF
 Losses of primarily-water fluid (hypertonic dehydration) leads to changes in both ECF and ICF

Fluid replacement
TREATMENT ALGORITHM
 Replacement – in patients with abnormalities in volume status and/or serum electrolytes
 Choice of fluid – replacement solution
 Administration of fluid:
 Moderate – calculate dose via estimated fluid loss
 Severe – bolus intravenous fluids (500ml bags as needed)
 Maintenance – in patients with normal kidney function who are unable to eat or drink for a prolonged period
 Choice of fluid – maintenance solution (consider adding 20mmol potassium/litre)
 Administration of fluid – calculate dose via 4-2-1 rule

Note: chronic losses are best replaced slowly and orally if possible.
Fluid challenge
In patients with suspected hypovolaemia, a fluid challenge of 500ml replacement solution can have four possible outcomes:
 Vital signs improve and remain stable – likely hypovolaemic (now stable)
 Vital signs improve but then deteriorate – likely hypovolaemic (with ongoing loss)
 Vital signs are unchanged – likely hypovolaemic (requires further fluids)
 Vital signs deteriorate – likely heart failure (requires diuretics)
IV cannula selection
 Orange (lava) – 14g (largest)
 Grey (soil) – 16g
 Green (grass) – 18g
 Pink (flowers) – 20g
 Blue (sky) – 22g
 Yellow (sun) – 24g
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PSYCHIATRY
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Psychiatry
Mood (affective) disorders
MAJOR DEPRESSIVE DISORDER
Major depressive disorder is characterised by one or more major depressive episodes .
FEATURES
 M:F – 1:2
 Classical onset in twenties (in elderly, prevalence increases with age)
PATHOPHYSIOLOGY
 Multifactorial (genetic and psychosocial)
 Neurotransmitter deficiency theory – doesn’t account for diversity of anti-depressant agents
 Neurotrophic theory – suggests  BDNF levels, possible in relation to stress/cortisol, alters brain connectivity and hence mood
 Anti-depressants increase BDNF
DIAGNOSTIC CRITERIA
 Depressed mood or anhedonia and ≥5 signs/symptoms (C GASP DIE) for ≥2 weeks
 Can be further classified as having psychotic or melancholic (severe) features
 May occur after pregnancy (postpartum depression ) or seasonally (seasonal depression )
TREATMENT
 Lifestyle changes ( exercise, sleep hygiene, etc.)
 Psychotherapy – CBT
 Pharmacotherapy – SSRI/SNRI  TCA  MAOI
 May give adjunct agents – buproprion or lithium
 May take 2 to 6 weeks to have effect (and may initially increase suicidality if present)
 Treatment for 6 months after symptoms have resolved (maintenance therapy) (i.e. typically, 9 to 12 months total)
 Refractory depression – electroconvulsive therapy (typically, 2 to 3 treatments a week for 6 to 12 treatments)
 Associated with retrograde or anterograde amnesia , mild cognitive impairment , headaches, and myalgia
 Additional indications include acute schizophrenia, mania, high suicidality, catatonia, and OCD (safe in pregnancy)
 Management notes:
 Combined therapy (CBT and medication) is more effective than monotherapy
OUTCOMES
 Good prognosis with first-episode within 6 months (but there is a tendency for recurrent depression)
 Depression is a major risk factor for suicidality
BIPOLAR DISORDERS

CLASSIFICATION
 Bipolar I – at least one manic or mixed (depressive/manic) episode
 Usually requires hospitalisation
 Bipolar II – at least one major depressive episode and hypomanic episode (but no manic episodes)
 While hypomania is less severe than mania – bipolar II is not a ‘milder’ form of bipolar I
 May be classified as ‘rapid cycling ’ where there is four or more mood episodes in one year
FEATURES
 M:F – 1:1
 Prevalence (life-time) – 1% for type I and 3% for type II
 Classical onset in teens to twenties (frequency of episodes increases with age)
PATHOPHYSIOLOGY
 Strong genetic component (family history of major mood disorder is common)
 Psychosocial factors have a strong contribution
DIAGNOSTIC CRITERIA
 Manic episode (persistently elevated, expansive, or irritable mood) and ≥3 signs/symptoms (DIGFAST) for ≥1 week
 Can be further classified as having psychotic features (very common)
 Hypomanic episode – as for manic episode but for ≥4 days and not involving marked impairment, psychosis, or hospitalisation

Note: if irritable mood requires ≥4 signs/symptoms.

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TREATMENT
 Lifestyle changes (exercise, sleep hygiene, and emergency plan for manic episodes )
 Psychotherapy – CBT
 Bipolar mania (a psychiatric emergency – risk of harm to self and others):
 Acute therapy – antipsychotics or mood stabilisers (lithium or valproate) (and lamotrigine for bipolar II)
 Maintenance therapy – mood stabilisers
 Refractory agitation – BZDs
 Bipolar depression:
 Maintenance therapy – mood stabilisers ± antidepressants
 Must start mood stabilisers first (antidepressant monotherapy may trigger manic episodes)
 Refractory depression – electroconvulsive therapy
OUTCOMES
 Bipolar disorder is a major risk factor for suicidality (10% of patients die from suicide)
 Bipolar is classically a recurrent disorder

Anxiety disorders
BASIC PRINCIPLES

DEFINITION
 Anxiety is a normal human trait, but becomes pathological when:
 Fear is greatly out of proportion to risk/severity of threat
 Response continues beyond existence of risk/threat
FEATURES
 Classical onset in adolescence/twenties with slight female preponderance (except for OCD which is equal)
GENERALISED ANXIETY DISORDER

DIAGNOSTIC CRITERIA
 Excessive anxiety about multiple activities on most days and ≥3 somatic symptoms for ≥6 months
 Somatic symptoms include restlessness, fatigue, irritability, muscle tension, and poor concentration
TREATMENT
 Acute therapy – reassurance, de-arousal therapy , short-term BZDs
 Maintenance therapy:
 Lifestyle change (exercise, sleep hygiene, etc.)
 Psychotherapy – CBT or mindfulness
 Pharmacotherapy – SSRIs/SNRIs  buspirone
OUTCOMES
 Typically, decreases over time but difficult to treat
PANIC DISORDER

DIAGNOSTIC CRITERIA
 Recurrent panic attacks and anxiety about panic attacks for ≥1 month
 Panic attacks – discrete periods of intense fear/discomfort with ≥4 somatic symptoms that peak within minutes
 Somatic symptoms include chest pain, palpitation, diaphoresis, fear of dying
 Associated with agoraphobia
TREATMENT
 As for GAD
OUTCOMES
 Typically, chronic but episodic with psychosocial stressors
AGORAPHOBIA

DIAGNOSTIC CRITERIA
 Marked fear or anxiety about agoraphobic situations and associated avoidance and distress for ≥6 months
 Agoraphobic situations – using public transport, being in open spaces, being in closed spaces, standing in line or being in a
crowd, and being outside of the home alone
 The fear or anxiety is due to thoughts that escape may be difficult or help may not be available
 The agoraphobic situation almost always provokes fear or anxiety
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TREATMENT
 As for GAD
PHOBIAS

CLASSIFICATION
 Social – anxiety of social/performance situations (typically, occur in adolescence)
 Specific – anxiety of specific object/situation (typically, occur in childhood)
DIAGNOSTIC CRITERIA
 Marked fear or anxiety about phobia situations and associated avoidance and distress for ≥6 months
 The fear or anxiety is recognised (by the patient) as unreasonable/excessive
 The phobia almost always provokes fear or anxiety
TREATMENT
 Psychotherapy – CBT (involving desensitisation through incremental exposure)
 Pharmacotherapy – SSRIs/SNRIs (may use short-term BZDs or beta-blockers in acute situations)
OBSESSIVE-COMPULSIVE DISORDER

DIAGNOSTIC CRITERIA
 Obsessions, compulsions, or both for ≥1 hour per day (‘time consuming’)
 Obsessions – persistent, unwanted, intrusive thoughts that lead to anxiety
 Compulsions – repeated mental acts or behaviours to reduce anxiety from obsessions

Note: patients recognise behaviour as excessive/irrational (as opposed to OCD personality disorder).
TREATMENT
 Psychotherapy – CBT (involving desensitisation through incremental exposure)
 Pharmacotherapy – SSRIs/SNRIs
OUTCOMES
 Tends to be refractory and chronic

Trauma disorders
POST-TRAUMATIC STRESS DISORDER

DIAGNOSTIC CRITERIA
 Exposure (direct or indirect) to a traumatic event and ≥1 symptom in each of four symptom clusters for ≥1 month
 Four symptom clusters:
 Intrusive thoughts
 Avoidance behaviour
 Alterations in mood or cognition
 Changes in reactivity or arousal (i.e. hypervigilance, sleep disturbance, irritability, or poor concentration)

Note: acute stress disorder presents similarly but duration of symptoms for 3 days to 1 month.
TREATMENT
 Acute therapy:
 Anxiety – short-term BZDs
 Disturbing dreams and nightmares – α2 agonists (clonidine)
 Maintenance therapy:
 Lifestyle change (exercise, sleep hygiene, etc.)
 Psychotherapy – trauma therapy and support groups
 Pharmacotherapy – SSRI/SNRI  TCA  MAOI
ADJUSTMENT DISORDER

DIAGNOSTIC CRITERIA
 Clinically significant distress following profound life change which is not severe enough to meet criteria for other mental disorder
 Occurs within 3 months after onset of the stressor and usually resolves within 6 months
TREATMENT
 Supportive counselling
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Psychotic disorders
BASIC PRINCIPLES

DEFINITION
 Psychotic disorders are characterised by a significant impairment in reality testing , and include:
 Delusions – fixed, false, beliefs
 Hallucination – perception without external stimulus
 Illusion – misperception of actual external stimulus
DIFFERENTIAL DIAGNOSIS OF PSYCHOSIS
Differential diagnosis of psychosis
DISORDER CHARACTERISTICS DURATION

Brief psychotic disorder Presents like schizophrenia <1 month

Schizophreniform disorder Presents like schizophrenia 1 to 6 months

Schizophrenia See Schizophrenia >6 months

Schizoaffective disorder Schizophrenia + major mood disorder (depression or bipolar) within the same episode of illness N/A

Delusional disorder Persistent non-bizarre delusions without disorganised thought, hallucinations, or negative symptoms >1 month
 Day-to-day functioning mostly unaffected

Personality disorders Schizotypal – ‘magical thinking’ Lifelong

Schizoid – ‘loners’

Substances Psychotic features secondary to drug intoxication or withdrawal N/A

SCHIZOPHRENIA

FEATURES
 Prevalence – 1% (in all genders)
 Onset – earlier in men (18-25) than women (25-35)
PATHOPHYSIOLOGY
 Thought to be due to dopamine (or glutamate) dysregulation
 Prominent genetic and environmental component
DIAGNOSTIC CRITERIA
 ≥2 ‘Criterion A’ symptoms for ≥1 month within ≥6 months of overall dysfunction
 ‘Criterion A’ symptoms:
 Delusions
 Hallucinations (auditory are most common)
 Disorganised speech (incoherence)
 Disorganised behaviour (may involve catatonia)
 Negative symptoms (5As – Alogia, Avolition, Apathy, Anhedonia, Affective blunting

Note: catatonia is a marked disturbance in motor function due to disturbed mental state.
TREATMENT
 Lifestyle changes ( exercise, sleep hygiene, etc.)
 Psychotherapy – CBT, patient and family education , supported housing , rehabilitation
 Pharmacotherapy – antipsychotics
 May give adjunct therapy – mood stabilisers (aggression/impulsivity) ± anxiolytics (anxiety) ± ECT (depression)
 Management notes:
 Must be treated for at least 1 to 2 years after first episode (≥5 years after multiple episodes) as relapse causes severe
deterioration
 Typically, negative symptoms increase and positive symptoms decrease with treatment
OUTCOME
 Majority of individuals display a prodromal phase
 Typically, chronic and relapsing course with prolonged disability
 Reduces life-expectancy by ~15 years (both suicide and comorbidity)
 Up to 50% of patients attempt suicide and 10% are successful (depressive features are greatest risk factor)
 Poor outcome – male, insidious onset, long-episode, younger age at onset, family history, comorbidities, substance use
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 Good outcome – acute onset, identifiable trigger, affective component, minority status

Delirium
DELIRIUM
Delirium is an acute disturbance of consciousness with altered cognition that develops over a short period of time (usually hours to
days).
PATHOPHYSIOLOGY
 Children , elderly, and hospitalised patients are most susceptible (lower threshold explanation )
 Various causes – often reversible (commonly infection, particularly UTI, and medications)
CLINICAL PRESENTATION
 Acute onset of fluctuating consciousness/cognition , with lucid intervals, and perceptual disturbance
(hallucination/delusion/illusion)
 Perceptual disturbances are typically unpleasant
 Patients may be hyperactive or hypoactive, combative, anxious, paranoid, or stuporous
 Classically, associated with:
 Decreased attention
 Decreased short-term memory
 Reversed sleep-wake cycle and increased symptoms at night (sundowning)
DIAGNOSIS
 Labs (to find underlying cause) – CBC, U&E, LFTs, TSH, vitamin B12/folate, urinalysis (C&S/R&M)
 Imaging – as indicated
TREATMENT
 Intrinsic:
 Treat underlying cause
 Cessation of non-essential medications
 Maintain nutrition, hydration, and electrolyte balance
 Monitor vitals and cognitive status
 Extrinsic:
 Optimise sensory environment – quiet, well-lit, room (with supervision)
 Frequent re-orientation – calendar, clock, reminders
 Family members – present for reassurance and re-orientation
 Provide necessary visual and hearing aids
 Physical restraints – if patient becomes violent
 Pharmacotherapy:
 Low-dose antipsychotics (haloperidol)
 Avoid BZDs and anticholinergics
OUTCOMES
 Up to 50% one-year mortality rate after an episode of delirium
Delirium versus Dementia
FEATURE DELIRIUM DEMENTIA

Level of consciousness Impaired Intact

Onset Acute Gradual

Course Fluctuating (with sundowning) Progressive deterioration

Alertness Decreased Normal

Hallucination Present (often visual or tactile) Occurs in approximately 30% of cases with advanced disease

Prognosis Reversible Largely irreversible but up to 15% of cases are treatable

Personality disorders
PERSONALITY DISORDERS

Basic principles
 Personality can be defined as an individual’s set of emotional and behavioural traits, which are generally stable and predictable
 Personality disorder occurs when an individual personality becomes chronically rigid and maladaptive (MEDIC)
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 Maladaptive, Enduring, Deviates from cultural norms, Inflexible, Causes impairment in social or occupational functioning
 Typically, onset occurs by early adulthood
Classification of personality disorders
DISORDER CHARACTERISTICS CLINICAL PRESENTATION
CLUSTER A: ‘WEIRD’
Paranoid  Distrustful, suspicious, interprets other’s motives A 59-year-old man who lives alone and constantly feels as if his
as malevolent (but not delusional) neighbours are spying on him; he feels he cannot trust the police
because they will take the side of the neighbours.

Schizoid  Isolated, detached, ‘loners’ A 66-year-old man who moves to Thailand alone after retirement, he
 Restricted emotional expression does not remain in good contact with his family or interact with the
locals. When he does interact with others he seems very distant.

Schizotypal  Odd behaviour, perceptions, and appearance A 36-year-old man with very strange ideas regarding the importance of
 Magical thinking and ideas of reference crystals and their effect on health; he collects crystals feeling like they
(but not psychotic) will one day prevent him from acquiring cancer.
 Social anxiety

CLUSTER B: ‘WILD’
Borderline  Unstable mood, relationships, and self-image A 28-year-old woman presents to clinic after having praised her new
 Feelings of emptiness clinician as better than all the others; she reveals that she fired her last
 Impulsiveness therapist; you notice she has fresh cuts in a row on her forearm.
 History of suicidal ideation or self-harm

Use splitting as defence mechanism

Histrionic  Excessively emotional, theatrical, and attention A 35-year-old woman presents to clinic wearing a very low-cut skirt,
seeking adjusting her position to draw attention to herself; when she does not
 Sexually provocative get attention, she breaks into tears, saying that no-one notices her,
not even her friends.

Narcissistic  Grandiose A 46-year-old man sits impatiently tapping his foot in the waiting
 Sense of entitlement room; he approaches the receptionist, demands to know where the
 Need for admiration doctor is, and tells her that he will have her fired if the doctor is not
 Lack empathy seen shortly – you are all wasting his time.

Antisocial  Violates rights of others, social norms, and laws A 22-year-old man who was in juvenile detention after assault says he
 Impulsive doesn’t need to be seen by a ‘shrink’ because his victim offended him
 Lacks remorse and deserved the assault.

Note: must have a prior diagnosis of conduct

disorder

CLUSTER C: ‘WEAK AND WIMPY’

Obsessive-Compulsive  Preoccupied with perfectionism and control at the A 36-year-old woman presents at the request of her boss, who feels
expense of efficiency she is too focused on the minute details of team projects and doesn’t
 Inflexible morals and values allow others to participate in fear of unwanted errors. She doesn’t see
anything wrong with this style of work and believes her co-workers
cannot be trusted to pay attention to detail.

Avoidant  Socially inhibited A 33-year old man stays at home to avoid a Christmas party, as he
 Rejection sensitive fears having to make small talk. He wants to go but is afraid he will be
 Fear of being disliked or ridiculed inadequate or rejected by others.
 Desires to have friends and social interactions

Dependent  Submissive and clingy A 30-year-old woman presents in crisis, saying that her parents have
 Need to be taken care of just kicked her out of their house and she is struggling to survive. She
 Have difficulty making decisions says she is too weak to even make choices at the grocery, as her
 Feel helpless mother would always care for her. She has been sitting outside of their
house daily, hoping they will let her live there again

DIAGNOSIS
 Clinical diagnosis
 Patients have chronic problems dealing with responsibilities, roles, and stressors
 They may also deny their behaviour , have difficulty changing behaviour , or frequently refuse psychiatric care
TREATMENT
 Psychotherapy (pharmacotherapy reserved for cases with comorbid symptoms)
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Eating disorders
EATING DISORDERS

CLASSIFICATION

Anorexia nervosa versus Bulimia nervosa

FEATURE ANOREXIA NERVOSA BULIMIA NERVOSA

Diagnostic criteria  Restriction or binge/purge leading to low bodyweight  Recurrent binge eating
 Intense fear of weight gain  Recurrent compensatory behaviour (e.g. purge or fasting)
 Distorted body image (perceive themselves as fat)  Occurs at least once a week for ≥3 months
 Self-evaluation unduly influenced by body image

Risk factors  Female (overwhelmingly)

 Other psychiatric disorders (esp. mood disorders, anxiety, and OCD)
 Vocations where patient is expected to be thin (modelling, gymnastics, ballet, running) – esp. in anorexia
 Sexual abuse – esp. in bulimia

Weight Underweight Normal/overweight

Attitude Not distressed by illness (resistant to treatment) Distressed by illness (treatable)

Treatment  Psychotherapy – family (gold standard) and individual  Psychotherapy (CBT) ± SSRI/SNRIs
 Inpatient/outpatient rehabilitation programmes  Hospitalise if required for severe nutritional deficiency
 Hospitalise if required for severe nutritional deficiency
 Medications not useful

DIAGNOSIS
 Thorough physical examination (anthropometry, vital signs, hydration, and muscle power)
 Labs – CBC, U&E, endocrine levels (screening for complications)
 ECG (screening for complications)
 Psychiatric evaluation (screening for comorbidity)
 Medical indicators for hospitalisation:
 Rapid weight loss (>4kg in 1 month)
 BMI <13
 Inability to eat/retain food
 Hypothermia or extreme cold sensitivity
 Marked lab abnormalities (particularly electrolytes, WBC, and renal function)
 Severe physical complications (particularly CNS or CVS)
COMPLICATIONS
 Constitutional – cachexia, hypothermia, fatigue, osteoporosis, seizures, electrolyte abnormalities
 Cardiac – arrythmia, bradycardia, hypotension, prolonged QT interval
 Gastrointestinal – dental enamel erosions and decay, enlarged parotid glands, abdominal pain
 Genitourinary – amenorrhoea, nephrolithiasis
 Other:
 Lanugo (fine white hairs over body) – in anorexia
 Scars on dorsal hand surface – if repeated vomiting
OUTCOMES
 Early intervention is much more effective (adolescent onset has better prognosis than adult onset)
 Anorexia – life-long disease (with high mortality due to suicide and comorbidities )
 Bulimia – relapsing-remitting disease (with good treatment outcomes )
Refeeding syndrome
Refeeding syndrome is a life-threatening metabolic response to refeeding in severely malnourished patients.
 Due to excessive insulin release leading to cellular uptake (and low serum levels) of phosphate, magnesium, and potassium
 Prevention – slow refeeding, gradual increase in nutrition , supplemental electrolytes /phosphate/vitamins
 Complications – heart failure, arrhythmia, delirium, and death
BODY DYSMORPHIC DISORDER
Body dysmorphic disorder is characterised by preoccupation with imagined (or slight) defects in physical appearance .
 Defects are usually imperceptible to others
 Treated with SSRI/SNRIs
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Substance use disorders

BASIC PRINCIPLES
 A drug is defined as a chemical entity self-administered non-medically for its psychoactive effect
 Lifetime prevalence of recreational drug use is ~50% of adults
DEFINITIONS
 Tolerance – reduction in response to a drug after repeated administration
 Dependence – compulsive drug-taking behaviour
 Withdrawal – rebound physiological effects upon cessation or reduction of drug intake

Substance use disorders

Substance use disorder is a maladaptive pattern of substance use that leads to clinically significant impairment .
DIAGNOSTIC CRITERIA
 ≥2 criteria (ISRP) for ≥1 year
 Impaired control :
 Greater amounts than intended
 Failure to reduce or abstain use
 Increased time spend acquiring, using, or recovering
 Craving
 Social impairment:
 Failure to fulfil responsibilities (e.g. at work, school, home)
 Continued use despite recurrent social/interpersonal problems secondary to use
 Isolation from life activities
 Risky use:
 Use of substances in physically hazardous situations (e.g. driving while intoxicated)
 Continued use despite recurrent physical/psychological problems secondary to use
 Pharmacologic:
 Tolerance (less effect or more used to gain effect)
 Withdrawal symptoms
CLASSIFICATION

Drug intoxication and withdrawal

DRUG INTOXICATION WITHDRAWAL

Marijuana Hallucination, dry mouth,  appetite, conjunctival injection No withdrawal (hyperemesis syndrome in chronic users)
 Also presents with amotivational syndrome or paranoia

Opioids Pupillary constriction, constipation, respiratory depression, seizures Unpleasant flu-like symptoms (not life threatening)

BZDs Amnesia, ataxia, drowsiness, stupor Rebound anxiety, insomnia, and seizures (life-threatening)

Amphetamines Pupillary dilation, psychomotor agitation, sympathetic activation Post-use ‘crash’ – anxiety, insomnia, nightmares

Cocaine Pupillary dilation, psychomotor agitation, sympathetic activation Severe craving, depression, and suicidality
 Also presents with chest pain with ECG changes (severe vasospasm)

Ecstasy Hyperthermia, hyponatraemia Mood offset for several weeks

LSD Hallucination, heightened senses, anxiety, depression, panic No withdrawal (flashbacks can occur years later)

Drug treatment
DRUG TREATMENT FOR INTOXICATION TREATMENT FOR WITHDRAWAL

Marijuana Symptomatic management N/A (anti-emetics for hyperemesis syndrome)

Opioids Naloxone (opioid receptor antagonist) Methadone (long-acting opioid)

BZDs Flumazenil (competitive GABA-A antagonist) Long-acting BZD taper

Amphetamines Antipsychotics, BZDs, and symptomatic management Supportive management

Cocaine Antipsychotics, BZDs, and symptomatic management Supportive management

Ecstasy Symptomatic management Symptomatic management

LSD Antipsychotics, BZDs, and symptomatic management N/A

Note: drug classed as ‘depressant’, ‘stimulant’, or ‘hallucinogen’

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Alcohol use disorder

FEATURES
 The male-to-female ratio is 4:1
 Typically, occurs in those in twenties and thirties
 Associated with a family history
PATHOPHYSIOLOGY
 Type 1 alcoholism (75% of cases)
 Weak genetic link (male = female cases)
 Typically, drink in response to circumstance, helps them manage strong emotions
 Type 2 alcoholism (25% of cases)
 Strong genetic link (male > female cases)
 Typically, drink regardless of circumstance; poly-substance abuse is common as part of an antisocial lifestyle
CLINICAL PRESENTATION
 Intoxication:
 Variable (e.g. disinhibition, slurred speech, ataxia, aggression, impaired judgment, impaired memory, stupor, coma)
 Withdrawal:
 Minor withdrawal – tremor, tachycardia, irritability, anxiety, headache, insomnia
 Delirium tremens (a severe alcohol withdrawal – life-threatening – up to 20% mortality)
 Altered mental state (confusions, hallucination, severe agitation)
 Autonomic instability (tremor, tachycardia, hypertension, seizures, delirium, death)
DIAGNOSIS
 Screen with CAGE questionnaire (≥2 in men and ≥1 in women is positive):
 C – have you ever felt the need to Cut down on drinking?
 A – have you ever felt Annoyed at criticism of your drinking?
 G – have you ever felt Guilty about your drinking?
 E – have you ever needed to have a drink first thing in the morning (Eye opener)?
 The AUDIT-C questionnaire can also be used
 Additional:
 Labs – characteristic increase in LFTs, LDH, and MCV (macrocytosis)
TREATMENT
 Intoxication – supportive management (DRS ABCs); consider thiamine, glucose, magnesium , and multivitamins
 Withdrawal – BZDs ± haloperidol (if psychotic symptoms); give supplements as for intoxication
 Addiction – disulfiram , naltrexone, and individual or group psychotherapy
 Advice for alcohol intake:
 Men – ≤3 stds/day, ≤15 stds/week, and at least 2 alcohol-free days
 Women – ≤2 stds/day, ≤10 stds/week, and at least 2 alcohol-free days
COMPLICATIONS
 Gastrointestinal bleeding (gastritis, ulcers, varices, or Mallory-Wiess tears)
 Pancreatitis
 Alcohol hepatitis and cirrhosis
 Wernicke encephalopathy and Korsakoff psychosis
 Foetal alcohol syndrome
 Cardiomyopathy
Smoking (nicotine) cessation
BASIC PRINCIPLES
 Smokers, on average, die 10 years earlier than non-smokers (single most preventable cause of premature death and illness )
 The earlier smoking cessation is achieved, the better the chance for reversal of long-term effects
 In recent quitters the highest relapse rate is within 3 months of quitting
 Most patients will require multiple attempts to achieve long-term cessation
TREATMENT
 ABC (in all patients) – Ask about smoking status , give Brief advice, offer Cessation support
 Quitline – offer telephone counselling and online support (other services do face-to-face coaching)
 Pharmacotherapy:
 First-line – nicotine replacement therapy (patches, gum, or lozenges)
 Mechanism – decreases urge to smoke
 Benefits – low dependence potential
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 Disadvantages – dry mouth, palpitations, gastrointestinal upset, and mild skin reactions with patch
 Second-line – buproprion or nortriptyline
 Mechanism – antidepressants (decreases urge to smoke and elevates mood)
 Benefits – doesn’t contain nicotine
 Disadvantages – dry mouth, gastrointestinal upset, and insomnia (buproprion lowers seizure threshold)
 Third-line – varenicline
 Mechanism – partial nicotinic agonist (reduces nicotine reward)
 Benefits – very effective
 Disadvantages – requires special authority and may cause neuropsychiatric symptoms or increased suicidality

Psychotherapy
BRIEF INTERVENTION

STEPS OF A BRIEF CLINICAL INTERVENTION

 Express concern about unhealthy behaviour/activity
 Feedback unhealthy behaviour/activity to health problems
 Education about healthy behaviour/activity
 Offer explicit advice to reduce unhealthy behaviour/activity
 Follow-up in several weeks to assess patient response (and refer to
further services if indicated)
STAGES OF CHANGE MODEL
The ‘stages of change’ model refers to the ‘steps’ that a patient will go
through when undertaking behavioural change.
COGNITIVE BEHAVIOURAL THERAPY
Cognitive behavioural therapy teaches patients to identify, evaluate,
and challenge thoughts and feelings that maintain a psychological state
that has a negative influence on behaviour .
 Structured format
 Collaborative agenda
 Mood check
 Check on homework from last week
 Assign homework for coming week
 Duration – typically, 6 to 18 1-hour sessions

Suicide
FEATURES
 Account for 1% of deaths worldwide
 The male-to-female ratio is 3.5:1 (but females attempt more suicide)
 Prevalence:
 10 per 100,000 in adults (20 per 100,000 if Maori)
 20 per 100,000 in youth (50 per 100,000 if Maori)
RISK FACTORS
54321 SPACE:
 Sex (male), SES (), Sexual orientation (LGBT), Substance abuse, Social support (lacking)
 Personality (hopelessness), Physical disability, Psychiatric co-morbidity, Previous attempt
 Adverse life events, Availability (of means), Age (teenager or elderly)
 Custody, Change in circumstance
 Exposure to suicide
TREATMENT
 Comprehensive documentation (of attempts, risk, and danger to self/others)
 Aggressive treatment of mental illness (but do not prescribe lethal doses of medication)
 Low risk (managed in community):
 Safety plan (ensuring help is available)
 Enlist help of relatives
 Removal of means where practical
 Promote protective factors and supports in their life
 Instil hope
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 High risk (admitted to unit – compulsorily if necessary):

 Direct observed monitoring in a safe environment
 Intense supportive intervention

Mental Health Act

The Mental Health (Compulsory Assessment and Treatment) Act 1992 is legislation that governs the management of patients that
have been determined to be ‘mentally disordered’.
 It allows for compulsory detainment , for the purposes of assessment or treatment (allowed under the act)
 It is actioned by a duly authorised officer , who is qualified to facilitate the process of the act

Sections of the Mental Health Act

Sections relating to ‘definitions’ of the act
 Sec. (2) – a statutory definition of a ‘mental disorder ’
 A ‘mental disorder ’, in relation to any person, means an abnormal state of mind (whether continuous or intermittent in
nature), characterised by delusions, or by disorders of mood , or perception , or volition , or cognition , of such a degree that it
–
 (a) Poses a serious danger to the health or safety of that person or of others; or
 (b) Seriously diminishes the capacity to take care of themselves
 Sec. (4) – rules relating to liability to assessment or treatment
 The procedures in parts I and II of the MHA shall not be invoked in respect of any person by reason only of:
 (a) That person’s political, religious, or cultural beliefs; or
 (b) That person’s sexual preferences; or
 (c) That person’s criminal or delinquent behaviour; or
 (d) Substance abuse; or
 (e) Intellectual handicap
Sections relating to ‘administration’ of the act
 Sec. (8a & 8b) – an application for assessment under the act and a medical certificate supporting the application respectively
 8a – undertaken by anyone (if they are >18 years old and have seen that person in the last 72 hours)
 8b – undertaken by a ‘medical practitioner’ (e.g. a GP)
 Sec. (9) – a notice to patient to attend an assessment examination
 Given to a patient after a section 8 has been filed; the patient is required to attend but may bring a support person
 Sec. (10) – a certificate of preliminary assessment
 Where a qualified person (usually a psychiatrist) determines whether a patient is ‘mentally disordered’
 Must be undertaken within 6 hours of section 9 being issued
 Sec. (11) – a notice requiring patient to undergo a 5-day further period of assessment and treatment (if indicated)
 Can occur as an outpatient or an inpatient
 Sec. (12) – a certificate of further assessment
 A report by a qualified person that refers to section 11
 Sec. (13) – a notice requiring patient to undergo a 14-day further period of assessment and treatment (if indicated)
 Can occur as an outpatient or an inpatient
 Sec. (14) – a certificate of final assessment
 With this certificate, the responsible clinician determines whether:
 The person can be released from compulsory status , or
 An application be made in court for a CTO (compulsory treatment order) under part II of the act

Miscellaneous disorders
MISCELLANEOUS DISORDERS
Miscellaneous psychiatric disorders
DISORDER CHARACTERISTICS TREATMENT

Primary insomnia  History of non-restorative sleep or difficulty initiating or  Sleep hygiene

maintaining sleep ≥3 times per week for ≥1 month  Short-term zopiclone (non-BZD hypnotic)

Conversion disorder  Somatic symptoms incompatible with physical examination  Psychotherapy

and highly related to stress or emotion

Factitious disorder  Fabrication of symptoms or self-injury to assume the sick role  Minimal diagnostics and treatment
 Munchausen by proxy – caregiver makes someone else sick  Psychotherapy

Malingering  Fabrication of symptoms or self-injury for secondary gain  Minimal diagnostics and treatment
(e.g. financial benefits, housing, unemployment benefit)  Psychotherapy
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Pharmacology of psychiatry
ANTIDEPRESSANTS
Classification of antidepressants
FEATURE SSRI SNRI TCA MAOI
Examples Fluoxetine Venlafaxine Amitriptyline Moclobemide
Sertraline Nortriptyline
Citalopram

Mechanism Block serotonin reuptake Block serotonin and Nonselective inhibitor of Reversible and selective
norepinephrine reuptake monoamine (5-HT/NA) uptake inhibitor of monoamine
(anti-cholinergic, -adrenergic, oxidase A (preventing
and -histamine effects also) breakdown of 5HT/NA/DA)

Side Effects  Gastrointestinal upset  Gastrointestinal upset  Anti-cholinergic  Gastrointestinal upset

 Anxiety  Anxiety (dry mouth, urinary
 Sympathetic activity  Sympathetic activity retention, constipation) Older, non-selective, MAOIs
(including tremor/insomnia) (including tremor/insomnia)  Anti-adrenergic cause hypertensive crisis when
 Sexual dysfunction  Sexual dysfunction (sympathetic activity) eating foods with tyramine
 Anti-histaminergic (such as EtOH and cheeses)
Rarely, serotonin syndrome Rarely, serotonin syndrome (weight gain, sedation)
 QRS prolongation

Rarely, serotonin syndrome Rarely, serotonin syndrome

Overdose Relatively safe Less safe than SSRIs (may Fatal (3Cs): Relatively safe
cause seizures and arrhythmia)  Cardiotoxicity
 Convulsions
 Coma

Treatment:
 NaHCO3 for arrhythmia
 Diazepam for convulsions
 Supportive treatment

Serotonin syndrome
Serotonin syndrome is due to over-stimulation of the serotonergic system.
 Results from combinations use of antidepressants (with synergistic anti-serotonergic effects)
 Classically, presents as SMARTS – Sweating , Myoclonus, ANS instability , hyperReflexia,  Temperature, Seizures
 Treatment – cyproheptadine (a 5-HT2 antagonist) and supportive care
Anti-depressant discontinuation syndrome
Discontinuation syndrome results from abrupt cessation of antidepressant (particularly SSRI/SNRIs).
 Classically, presents as FINISH – Flu-like symptoms , Insomnia, Nausea, Imbalance,  Sensory disturbance , Hyperarousal
(anxiety)
 Treatment – restart antidepressant and cease with slow taper
ANTIPSYCHOTICS

CLASSIFICATION
 Antipsychotics can be divided into typical (i.e. haloperidol ) and atypical (e.g. risperidone ) antipsychotics
 All antipsychotics are equally effective (except clozapine which is considered to be the most effective)
 Antipsychotics have an immediate calming effect, although disorganisation may take several weeks to respond
 Atypical antipsychotics are thought to have better side-effect profiles (metabolic rather than movement side effects)
PATHOPHYSIOLOGY
 Mechanism of action – not a homogenous class but antagonise, to varying degrees, dopamine (D2) activity in target brain pathways
 Mesolimbic pathway (emotion, reward) – HIGH dopamine causes positive symptoms
 Mesocortical pathway (cognition, executive function) – LOW dopamine causes negative symptoms
 Nigrostriatal pathway (movement) – LOW dopamine causes EPS
 Tuberoinfundibular (prolactin hormone release) – LOW dopamine causes hyperprolactinaemia

Note: need 65% D2 antagonism for efficacy (>80% leads to EPSE).

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SIDE EFFECTS
 Side effects vary by antipsychotic, but can be classed as:
 Sedation
 Anti-cholinergic effects
 Weight gain and metabolic effects
 Drug-induced parkinsonism (particularly, typical antipsychotics)
 Hyperprolactinaemia (particularly, typical antipsychotics)
 Clozapine – causes fatal agranulocytosis , constipation , cardiomyopathy , and seizures
 Indication – failure of two antipsychotics
 Monitoring – haematological (for agranulocytosis) (also, monitor bowel movements)
 Interactions – nicotine
Extrapyramidal side effects (EPSE)
Extrapyramidal side effects occur due to the dopaminergic effects of antipsychotics.
 Some of these effects may result from antiparkinsonian medication (which has an opposite effect)
Extra-pyramidal side effects (and their treatment)
SUBTYPE DESCRIPTION TIME OF ONSET TREATMENT
Acute dystonia Prolonged, painful, tonic muscle contraction Hours  IM benztropine (anti-cholinergic)
(due to excess dopamine receptor activity)  Amantadine (NMDA receptor antagonist)
 Discontinue drug
Dyskinesia Pseudo-parkinsonism Days
(due to excess dopamine receptor activity)

Akathisia Subjective restlessness Weeks  Propranolol

 Discontinue drug

Tardive dyskinesia Irreversible dyskinesia (due to prolonged Months  Change to clozapine

dopaminergic blockade leading to supersensitivity)  Discontinue drug
 Often involve orofacial muscles

Neuroleptic FARM: Anytime  Dantrolene

malignant syndrome Fever, Autonomic instability, Rigidity, and Mental  Bromocriptine
status changes (due to dopaminergic blockade)  Supportive care in ICU (cooling/hydration)
 Discontinue drug
Similar to serotonin syndrome but global rigidity
and no gastrointestinal symptoms

Labs –  WBC/CK

MOOD STABILISERS
Mood stabilisers include lithium and anticonvulsants (valproate and lamotrigine ).
 All have equivalent efficacy, but vary in ability to ‘treat’ versus ‘stabilise’ manic or depressive symptoms
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PAEDIATRICS,
OBSTETRICS &
GYNAECOLOGY
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Gynaecology
Basic principles
STAGES OF PUBERTY
 See Paediatrics for full description
 Female stages of puberty (Boobs, Pubes, Grow, Flow):
 Adrenarche – increase in secretion of adrenal androgens (usually precedes gonadarche by 2 years)
 Gonadarche – increase in secretion of gonadal sex steroids (usually at age 8)
 Thelarche (Boobs) – breast development
 Pubarche (Pubes) – pubic and axillary hair development
 Menarche (Flow) – onset of menstruation (usually following peak height velocity – Grow)
NORMAL MENSTRUATION
The progression of a normal menstrual cycle is as follows:
FOLLICULAR PHASE (DAYS 1-13)
 Starts at menstruation and ends at LH surge/ovulation
 Physiology :  GnRH pulse   FSH  growth of 3-30
follicles   oestrogen production
 Oestrogen results in development of straight glands and
thin secretions of uterine lining (proliferative phase )
 By late follicular phase, a dominant follicle is selected
(others undergo atresia); also, the uterine endometrium
begins to thicken, and cervical mucous becomes stringy
(allows passage of sperm)
OVULATION (DAY 14)
 Physiology: oestrogen reaches a peak  switch from
negative to positive feedback on pituitary gland  LH surge
(smaller FSH rise)  rupture of ovarian follicle and release
of mature ovum  travels to oviduct/uterus
 Ruptured follicular cells differentiate into corpus
luteum (which produces progesterone)
 Women are born with 2 million oocytes which degenerate
by apoptosis/atresia (300,000 at puberty)
 Menopause occurs when there are no more follicles
responding to FSH to produce eggs
LUTEAL PHASE (DAYS 15-28)
 Represents the length of time (10-14 days) that the corpus
luteum can survive without further LH or hCG stimulation
 Physiology: change from oestrogen to progesterone predominance (due to corpus luteum )
 Stabilises the endometrium resulting in development of thick tortuous endometrial glands with thick secretion (secretory
phase)
 Outcomes:
 Absence of fertilisation and implantation  degeneration of corpus luteum   progesterone  menstruation (and loss of
negative feedback to FSH which restarts the follicular phase)
 Fertilisation and implantation  ovum produces hCG which prevents degeneration of corpus luteum  continued production
of progesterone (prevention of menstruation)  placenta eventually takes role of corpus luteum (from 8 weeks)
Characteristics of normal menstrual cycle
 Menarche – occurs between 10-15 years of age
 Cycle – 28 days ± 7 days with bleeding for 2-7 days
 Menstrual blood does not clot (‘clots’ are endometrial fragments)

Note: a regular period is the best indicator of ovulation occurrence.

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ANATOMY
External genitalia
 Blood supply – internal pudendal artery (from internal iliac artery)
 Nerve supply – pudendal nerve (from sacral nerves)
 Lymphatic drainage – inguinal nodes
Vagina
 Blood supply – vaginal branch of internal pudendal artery
 Anastomotic contribution from uterine, inferior vesical, and middle rectal arteries
Uterus
 Thick walled, muscular organ, between bladder and rectum, consisting of two major parts:
 Uterine corpus (blood supply – uterine artery (from internal iliac artery))
 Cervix (blood supply – cervical branch of uterine artery)
 Supported by the pelvic diaphragm (levator ani and coccygeus), pelvic organs , and four sets of paired ligaments :
 Round ligaments – from anterior uterus, through inguinal canal, to labia majora (function – anteversion)
 Uterosacral ligaments – from posterior uterus to sacral fascia (function – mechanical support and contains autonomic nerves)
 Cardinal ligaments – from cervix to lateral pelvic wall (function – mechanical support and contains uterine arteries)
 Broad ligaments – from lateral uterus to lateral pelvic wall (specifically the mesometrium )
 Contains fallopian tube, round ligament, ovarian ligament, nerves, vessels, and lymphatics
 Position of uterus:
 Anteverted anteflexed (palpable on bimanual; cervix faces posteriorly)
 Retroverted (non-palpable on bimanual; cervix mid-position)
 Retroverted retroflexed (non-palpable on bimanual; cervix faces anteriorly)

Note: the ureters run posterior to the uterine arteries (‘water under the bridge’ ).
Fallopian tubes
 Muscular tubes that extend laterally from uterus to ovary
 Mesosalpinx – peritoneal fold that attaches fallopian tube to broad ligament
 Separated into isthmic, ampullary, and infundibular segment s (terminating at
fimbriae)
 Blood supply – uterine and ovarian arteries
Ovaries
 Consist of cortex with ova and medulla with blood supply
 Mesovarium – peritoneal fold that attaches ovary to broad ligament
 Ovarian ligament – from ovary to lateral uterus
 Supported by infundibulopelvic ligament (suspensory ligament of ovary ) – contains arteries, veins, nerves, and lymphatics
 Blood supply – ovarian arteries (from aorta), left ovarian vein ( left renal vein), right ovarian vein ( IVC)
 Lymphatic drainage – para-aortic nodes
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Disorders of menstruation
PRIMARY AMENORRHOEA

DEFINITION
Either:
 Absence of menses by age 16 (with secondary sexual characteristics present), or
 Absence of menses by age 14 (with absence of secondary sexual characteristics )
AETIOLOGY AND CLASSIFICATION
 Presence of secondary sexual characteristics:
 Anatomic abnormalities (outflow tract obstruction)
 Imperforate hymen
 Transverse vaginal septum
 Mullerian agenesis
 Receptor or enzyme abnormalities
 Androgen insensitivity syndrome
 Congenital adrenal hyperplasia
 PCOS
 Absence of secondary sexual characteristics:
 Hypothalamic and pituitary disease (hypogonadotropic hypogonadism)
 Kallmann syndrome (isolated GnRH deficiency; associated with anosmia)
 Constitutional delay of puberty (most common physiological reason)
 Other: hypo-/hyperthyroidism, hyperprolactinaemia, chemoradiotherapy
 Gonadal dysgenesis/primary ovarian insufficiency (hypergonadotropic hypogonadism)
 Turner syndrome (XO) (most common pathological reason)
 Primary ovarian insufficiency (XX)
DIAGNOSTIC APPROACH
 Labs: hCG and hormonal workup (TSH, prolactin, FSH/LH, androgens, oestrogen)
 Imaging: U/S (to confirm normal anatomy or identify PCOS)
 Presence of sexual characteristics
 Yes
 Karyotype analysis
 XX  anatomic abnormalities, PCOS, or CAH
 XY  androgen insensitivity syndrome
 No
 Measure FSH/LH
 High  hypergonadotropic hypogonadism  karyotype analysis
 XO – Turner syndrome
 XX – primary ovarian insufficiency
 Low  hypogonadotropic hypogonadism
Mullerian agenesis (vaginal agenesis)
Mullerian agenesis is a congenital malformation characterised by failure of the Mullerian duct to develop, resulting in a missing uterus
and absence of upper two-thirds of the vagina .
 The patient will have normal secondary sexual characteristics
 Treated with surgery
Androgen insensitivity syndrome
Androgen insensitivity syndrome is characterised by the inability of cells in an affected genetic male to respond to androgenic
hormones.
 Classified be degree of genital masculinisation (normal female, normal male, or partially male); expect male-range serum testosterone
 Associated with normal breast development (aromatisation of testosterone to oestrogen) but amenorrhoea and lack of pubic hair
Congenital adrenal hyperplasia
See Endocrinology.
SECONDARY AMENORRHOEA

DEFINITION
 Absence of menses for >6 months (or 3 cycles) after documented menarche
AETIOLOGY AND CLASSIFICATION
 Pregnancy (must be excluded in every patient)
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 Hypothalamic dysfunction
 Functional hypothalamic amenorrhoea (FHA) (caused by malnutrition, exercise, stress) (most common)
 Systemic illness (T1DM, coeliac disease)
 Pituitary dysfunction
 Hyperprolactinaemia
 Sheehan syndrome
 Other causes
 Thyroid dysfunction
 Hyper/hypothyroidism
 Ovarian abnormality
 Primary ovarian insufficiency
 PCOS
 Uterine abnormality
 Asherman syndrome
 Rare causes (with hyperandrogenism): adrenal or ovarian tumour; late-onset or mild congenital adrenal hyperplasia
DIAGNOSTIC APPROACH
 Labs: hCG and hormonal workup (TSH, prolactin, FSH/LH, androgens, oestrogen)
 Imaging: U/S (to confirm normal anatomy or identify PCOS)
 Progestogen challenge (assess if adequate oestrogen to thicken endometrium)
 Withdrawal bleed (i.e. anovulation)
 FSH/LH
 High  primary ovarian insufficiency or PCOS (with hyperandrogenism)
 Normal/low  hypothalamic or pituitary dysfunction (esp. FHA)
 No withdrawal bleed
 Uterine defect
 Asherman syndrome
Sheehan syndrome
Sheehan syndrome is characterised by infarction (and consequent dysfunction) of the pituitary gland following post-partum
haemorrhage .
 Typically, occurs after unusually heavy haemorrhage (causing hypotension or transfusion)
 Treatment is the same as for other causes of hypopituitarism
Asherman syndrome
Asherman syndrome is characterised by acquired intrauterine adhesion.
 Typically, occurs after post-partum haemorrhage or endometrial infection (following uterine instrumentation)
 Adhesions prevent normal build-up/shedding of endometrial cells leading to very light or absent menses
ABNORMAL UTERINE BLEEDING
Abnormal uterine bleeding refers to changes in frequency, duration , or amount of menstrual flow .
CLASSIFICATION
The causes of abnormal uterine bleeding are classified by the acronym PALM-COEIN:
 PALM refers to structural causes: Polyps, Adenomyosis, Leiomyoma (fibroids), and Malignancy/hyperplasia
 COEIN refers to non-structural causes: Coagulopathy , Ovulatory dysfunction , Endometrial , Iatrogenic, and Not classified

Note: DUB (dysfunctional uterine bleeding) can be diagnosed if anatomical lesions and systemic disease are excluded.
CLINICAL PRESENTATION
 Regular (predictable) bleeding
 Heavy – adenomyosis, leiomyoma, endometrial, coagulopathy
 Intermenstrual – polyps
 Irregular (unpredictable) bleeding
 Ovulatory dysfunction or malignancy/hyperplasia
DIAGNOSIS
 Labs: CBC, coagulation, endocrine (thyroid/prolactin), STI screen, and hCG
 Investigations:
 Transvaginal U/S
 Endometrial biopsy – performed if:
 Endometrium ≥4mm in post-menopausal women
 Risk factors for endometrial hyperplasia (e.g. obesity or diabetes)
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Note : pregnancy is the most common cause of abnormal uterine bleeding and amenorrhoea.
TREATMENT
 Treat underlying cause
 General principles
 Ovulatory bleeding:
 NSAIDS (mefenamic acid) (decrease blood loss – given during menses)
 Tranexamic acid (anti-fibrinolytic – given during menses)
 Contraceptives – COC or IUS  progestogen contraceptives
 Acute heavy bleeding:
 Resuscitation
 IV oestrogen (stabilises endometrium) (transition to COC when stabilised)
 Severe/refractory cases:
 Endometrial ablation
 Hysterectomy
Ovulatory dysfunction
Ovulatory dysfunction presents as irregular (unpredictable) bleeding of varying intensity (amenorrhoea or menorrhagia).
 Common with ‘endocrinopathies’ (PCOS, hypothyroidism, hyperprolactinaemia, stress, obesity, extreme exercise, or weight loss)
 In woman with anovulatory uterine bleeding , typically no pathology is found
 Classically, occurs with extremes of reproductive age (adolescence and perimenopause)
CLASSIFICATION
 Poor proliferation and unstable endometrium – due to insufficient oestrogen (oestrogen is treatment)
 Typically, occurs with extremes of reproductive life (associated with symptoms of menopause )
 Good proliferation (or hyperplasia) but unstable endometrium – due to insufficient progesterone (progesterone is treatment)
 Goals is to convert proliferative endometrium to secretory endometrium (to  risk of malignancy/hyperplasia)
 Start with initial therapy for ten days followed by cyclical therapy (days 5 to 25 of cycle) for maintenance (consider IUS)
 Also called unopposed oestrogen effect – typically, occurs with extremes of reproductive life or PCOS
Intermenstrual, postcoital, and postmenopausal bleeding
Intermenstrual, postcoital , and postmenopausal bleeding is always abnormal.
AETIOLOGY
 Intermenstrual
 Physiologic (spotting)
 Uterine – polyps, adenomyosis, fibroids, cancer
 Vagina – vaginitis, cancer
 Cervical – polyps, ectropion (esp. COC), cancer
 Obstetric – pregnancy, ectopic pregnancy, gestational trophoblastic disease
 Postcoital – ectropion, cervicitis, cervical and endometrial polyps, vaginal or cervical cancer, infection, trauma
 Postmenopausal – atrophic vaginitis (90%), cervical and endometrial polyps, vaginal/cervical/endometrial/ovarian cancer

Note : post-menopausal bleeding is cancer until proven otherwise (present in 95% of cases).
DYSMENORRHOEA (MENSTRUAL PAIN)
Dysmenorrhoea is menstrual pain.
CLASSIFICATION
 Primary – associated with ovulatory cycles and in the absence of pathological findings
 Pathophysiology: excess prostaglandin  uterine vasoconstriction and contraction  ischaemic pain
 Secondary – associated with an organic cause
 Differential diagnosis:
 Endometriosis or adenomyosis
 Fibroids
 IUD (copper)
 PID
 Cysts or tumours
 Cervical stenosis
CLINICAL PRESENTATION
 Primary dysmenorrhoea:
 Presents with low, midline, spasmodic pelvic pain that radiates to lower back or inner thighs
 Associated with nausea/vomiting , diarrhoea , headache, and flushing (prostaglandin-related)
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 Begins hours before onset of bleeding and persists for 1-3 days
 Examination – no findings
 Secondary dysmenorrhoea:
 Presents with persistent or refractory dysmenorrhoea ; associated with dyspareunia, abnormal bleeding, infertility , or
discharge
 Examination – uterine/adnexal/cervical tenderness, pelvic mass, uterine abnormality (findings are rare in young women)
DIAGNOSIS
 Primary dysmenorrhoea – a diagnosis of exclusion (rule out secondary dysmenorrhoea)
 Secondary dysmenorrhoea – warrants a thorough examination:
 Pelvic examination
 Ultrasonography, laparoscopy, or hysteroscopy should be considered
 Lab: β-HCG (to exclude pregnancy), CBC (to exclude infection/neoplasm), UA (to exclude UTI), and STI swabs
TREATMENT
 Primary dysmenorrhoea:
 Analgesia – paracetamol/NSAIDS ± topical heat therapy (initiate before onset of menstruation)
 Contraceptives (most effective at reducing pain) – COC  progestogen contraceptives
 Secondary dysmenorrhoea:
 Treat underlying cause

Endometriosis and adenomyosis

ENDOMETRIOSIS
Endometriosis is the presence of endometrial tissue (glands and stroma) outside of the uterine cavity .
 Endometrioma is an endometriotic cyst on the surface of the ovary
FEATURES
 Incidence: up to 1 in 7 pre-menopausal women (regresses after menopause); typically presents in late-twenties
 Risk factors:
 Family history (10x risk if first-degree relative)
 Nulliparity
 Outflow tract obstruction (earlier onset – resolves with treatment)
PATHOPHYSIOLOGY
 Several proposed mechanisms (combination likely involved):
 Retrograde menstruation – seeding of endometrial cells by trans-tubal regurgitation during menstruation
 Immunologic theory – altered immunity (?NK cells) may limit clearance of transplanted endometrial cells from pelvic cavity
 Metaplasia of coelomic epithelium – chemical factors may induce undifferentiated peritoneal cells to develop into
endometrium
 Free blood then irritates, provoking fibrosis, adhesions and infertility
SITES OF INVOLVEMENT
 Occurs anywhere in the abdominopelvic cavity (esp. the ovaries, involves in >50% of cases)
 Rarely, may occur in sites outside of abdomen/pelvis
CLINICAL PRESENTATION
 Asymptomatic , or presenting as one of three classical presentations:
 Pain – the ‘4Ds of endometriosis’:
 Dysmenorrhoea
 ‘Deep’ Dyspareunia (with cul-de-sac involvement)
 Dysuria (with bladder involvement, associated with cyclical haematuria)
 Dyschaezia (with bowel involvement, associated with cyclical diarrhoea/constipation)
 Infertility – in one-third of patients (most common cause among menstruating women older than thirty)
 Mass – endometrioma
 Signs (uncommon in adolescents):
 Tender nodularity on rectovaginal exam
 Fixed retroversion of uterus
 Firm, fixed, adnexal mass (endometrioma)
DIAGNOSIS
 Initial test – transvaginal U/S
 Definitive diagnosis – requires direct visualisation (via laparoscopy) and biopsy (endometrial glands and stroma required)
 Classic lesions have blue-black (‘raspberry’) or dark-brown (‘powder-burned’) appearance
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 Endometrioma – appears as chocolate cysts on the ovaries

TREATMENT
 Medical therapy:
 Analgesia – NSAIDs

 Ovulation inhibition (to prevent endometrial proliferation from oestrogen action):

 Contraceptives – high-dose continual oral progestogen contraceptives
 GnRH analogues (suppress FSH/LH as not pulsatile) – leuprorelin
 Anti-oestrogens – danazol
 Surgery:
 Conservative: laparoscopic excision/cauterisation/ablation of lesions ± lysis of adhesions
 Best time for pregnancy is immediately following conservative surgery (however, only 20% fertility following)
 Definitive: TAH ± BSO ± lysis of adhesions
 BSO – bilateral salpingo-oopherectomy
 TAH – total abdominal hysterectomy
OUTCOMES
 Recurrence:
 Medical therapy – up to 50%
 Surgery – up to 25%
ADENOMYOSIS
Adenomyosis is the presence of endometrial tissue within the myometrium of the uterus .
 May rarely progress to uterine carcinoma
FEATURES
 Incidence: up to 15% of older women (regresses after menopause); typically presents in middle age (older than endometriosis)
CLINICAL PRESENTATION
 Asymptomatic , or classical triad of 2 o dysmenorrhoea , AUB (cyclical menorrhagia) , and enlarged, boggy, symmetric uterus
DIAGNOSIS
 Clinical diagnosis (± CBC to assess for anaemia)
 Definitive diagnosis – pathological (but can be predictably identified by U/S or MRI)
 Endometrial biopsy – to rule out uterine cancer (esp. if post-menopausal)
TREATMENT
 Medical therapy for AUB ( only if symptomatic):
 Analgesia – NSAIDs
 Iron supplementation (as indicated)
 Ovulation inhibition:
 Contraceptives – COC  progestogen contraceptives
 GnRH analogues (suppress FSH/LH as not pulsatile) – leuprorelin
 Anti-oestrogens – danazol
 Definitive therapy (treatment of choice):
 Surgery – total hysterectomy
LEIOMYOMA (FIBROIDS)
Leiomyoma (fibroids) are benign smooth muscle tumours of the uterus.
 They are the most common gynaecological tumour
 They may rarely progress to leiomyosarcoma (50% originate from fibroids)
FEATURES
 Incidence: up to 50% of older women (regresses after menopause)
 Hormone (oestrogen) sensitive: size  in pregnancy/COC and  after menopause

Note: if a uterine mass continues to grow after menopause, suspect malignancy.

CLASSIFICATION
 Subserosal (± pedunculated)
 Intramural
 Submucosal (± pedunculated) – most symptomatic
 Cervical
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PATHOGENESIS
 Oestrogen stimulates monoclonal smooth muscle proliferation (and progesterone prevents apoptosis)
 Degenerative changes can occur, including calcification , sarcomatous change, or parasitic blood supply
CLINICAL PRESENTATION
 Majority asymptomatic , often discovered as incidental finding
 Symptoms:
 AUB (cyclical menorrhagia)
 Pressure symptoms – pelvic ‘heaviness’, constipation, urinary frequency or retention, oedematous legs
 Typically, painLESS (unless red degeneration or fibroid torsion)
 Signs: classically described as non-tender, irregular, and mobile uterus
DIAGNOSIS
 Clinical diagnosis (± CBC to assess for anaemia)
 Imaging: U/S (to confirm diagnosis) or MRI (for pre-operative planning)
 Endometrial biopsy – to rule out uterine cancer (esp. if post-menopausal)
TREATMENT
 Medical therapy for AUB ( only if symptomatic):
 Analgesia – NSAIDs
 Iron supplementation (as indicated)
 Ovulation inhibition:
 Contraceptives – COC  progestogen contraceptives
 GnRH analogues (suppress FSH/LH as not pulsatile) – leuprorelin
 Anti-oestrogens – danazol
 Definitive therapy (treatment of choice):
 Women of childbearing years – abdominal or hysteroscopic myomectomy or Myosure (preserves fertility)
 Women who have completed childbearing – total hysterectomy
 Interventional radiology : uterine artery embolisation (not in childbearing women)
COMPLICATIONS
 Infertility, recurrent pregnancy loss , and complications of pregnancy (potential enlargement, implantation impairment,
obstructed labour, difficult caesarean-section)
 Fibroid torsion (occurs in pedunculated fibroids and is a surgical emergency)
 ‘Red degeneration’ causing pain following thrombosis of the fibroid blood supply, occurs in pregnancy (requires only analgesia)

Contraception
Classification of Contraceptive Methods
TYPE EFFECTIVENESS (PERFECT / TYPICAL)
Withdrawal
Rhythm method Ineffective (other than abstinence)
Lactational amenorrhoea

Condom 98% 85%

COC / POP >99% 90%

LARCS (IUD, IUS, Depo-Provera, sub-dermal implant) >99%

Surgical (tubal ligation/vasectomy) >99%

Emergency – Postinor-1 >99% (if within 72 hours)

Emergency – IUD >99% (if within 5 days)

Daily contraceptive methods

Condoms
MECHANISM OF ACTION ADVANTAGES DISADVANTAGES
 Physical barrier  Readily available (on prescription)  Occasional breaks
 Ideally, used in conjunction with lubricant  Protection against STIs  Reduces glans sensation
 Latex allergy (non-latex condoms available)
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Combined oral contraceptive pill

 Combined oral contraceptive pill – oestrogen (ethinyloestradiol ) and progestogen (varies depending on type )
 NuvaRing and Transdermal patch (not available in New Zealand)
 Worn continuously for three weeks (then removed for one week to enable withdrawal bleed)
 Similar mechanism, advantages, and disadvantages to COC
 Guide to COC usage:
 Starting: start straight away with 7-day rule (7-days alternative contraception) (unless within 5 days of LMP)
 Methods:
 Withdrawal bleed – 21 hormone tablets : 7 sugar pills
 No withdrawal bleed – continuous hormone tablets (safe, but may notice breakthrough bleeding after several months)
 Missed pill:
 One pill – take next pill when it would be taken
 Two or more pills within 7-days (or severe vomiting/diarrhoea) – 7-day rule
 Missed pill if week before withdrawal bleed – skip sugar pills and 7-day rule (if more than two)

MECHANISM OF ACTION ADVANTAGES DISADVANTAGES

 Suppression of ovulation (inhibits LH/FSH)  Reversible (immediate)  Daily compliance
 Thinning of endometrium  Cycle regulation  Breakthrough bleeding (typically settles)
 Thickening of cervical mucous resulting in    AUB  Headaches with withdrawal bleed
sperm penetration   dysmenorrhoea
  acne/hirsutism
Note: oestrogen may cause an unwanted   risk of ovarian and endometrial cancer
mucous discharge (treat by  oestrogen dose)   risk of benign breast disease/ovarian cysts

Side effects and contraindications of oestrogen and progesterone

SIDE EFFECTS ABSOLUTE CONTRAINDICATIONS RELATIVE CONTRAINDICATIONS
Oestrogen-related:  CVS: DVT/PE, CVD, IHD, HTN (uncontrolled)  CVS: HTN (controlled)
 Major risks:  Cancer: breast, cervical, liver  Smoker (age <35)
 CVS:  DVT/PE, CVD, IHD, HTN  Known/suspected pregnancy  Migraines without aura
 Cancer:  breast, cervical, liver  Smoker (age >35)  Liver enzyme inducers
 Minor risks:  Migraines with aura  Obesity (30-34BMI)
 Nausea/vomiting  Obesity (≥35BMI)  Gallbladder disease
 Fluid retention  SLE
 Breast tenderness Contraindications are primarily due to oestrogen
 Breakthrough bleeding (low oestrogen) (progestogen-only medication is very safe) Refer to the UKMEC guidelines for detail
 Progestogen-related
 Menstrual irregularity
 Acne/oily skin
 Low-mood
 Headache
 Breast tenderness
 Loss of libido

Progestogen-only pill
 Various progesterone pills (and various strengths)
 Guide to POP usage:
 Starting: start straight away with 7-day rule (7-days alternative contraception) (unless within 5 days of LMP)
 Methods:
 Continuous – must take within 3-hour (low-dose) or 12-hour (high dose) window each day
 Missed pill (or severe vomiting/diarrhoea):
 One pill (low-dose – e.g. noriday) – 2-day rule
 One pill (high-dose – e.g. cerazette) – 7-day rule (for effective ovulation suppression)

MECHANISM OF ACTION ADVANTAGES DISADVANTAGES

 Inconsistent ovulation suppression Indications:  Daily compliance (3-hour window)
 Thinning of endometrium  Post-partum women  Menstrual irregularity
 Thickening of cervical mucous resulting in   Contraindications to COC  Progestogenic side effects
sperm penetration  Intolerable oestrogenic side effects  Risk of ovarian cysts
 Decreased tubal motility

Long-acting reversible contraceptives (LARCs)

Intra-uterine systems (IUS)
 Mirena and Jaydess – intra-uterine systems that secrete progestogen-only (levonorgestrel )
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 Effective for up to 5 years (Mirena) or 3 years (Jaydess) (not subsidised)

 Similar mechanism, advantages, and disadvantages to POP – but must note:
 Inconsistent ovulation suppression
 Typically, leads to amenorrhoea (after a period of menstrual irregularity)
 Risk of insertion (e.g. infection/salpingitis, perforation, expulsion (1 in 20), vasovagal reaction)
 Contraindications to insertion – pregnancy, PID, active STI, undiagnosed vaginal bleeding, genital malignancy, anatomic issues
Intra-uterine device (IUD)
 Copper IUD – no hormonal action
 Effective for up to 10 years (dependent on model)
 Effective as a post-coital emergency contraceptive

MECHANISM OF ACTION ADVANTAGES DISADVANTAGES

 Copper causes reaction which inhibits sperm  Non-hormonal  Risks of insertion (similar to IUS)
motility and fertilisation  Very effective  Typically, heavier/painful periods
 Can also affect implantation  Can be used up to 5-days after intercourse (or
predicted ovulation) as an emergency
contraceptive

Depo-Provera
 Depo-Provera – three-monthly intramuscular injection (buttock) of progestogen-only (medroxyprogesterone-acetate )
 Similar mechanism, advantages, and disadvantages to POP – but must note:
 Consistent ovulation suppression
 Typically, leads to amenorrhoea (after a period of menstrual irregularity)
 Risk of injection (e.g. infection) and weight gain (only contraceptive with proven link)
 Concerns about decreased bone density (if young or old) and small increased risk of breast cancer
Sub-dermal implants
 Jadelle implant – two rods, sub-dermally, in non-dominant arm that secrete progestogen-only (levonorgestrel )
 Effective for up to 5 years (and fully subsidised)
 Implanon/Nexplanon (no longer available in NZ)
 Similar mechanism, advantages, and disadvantages to POP – but must note:
 Consistent ovulation suppression
 Typically, leads to amenorrhoea (after a period of menstrual irregularity)
 Risk of insertion (e.g. infection)

Surgical contraception
All procedures carry typical surgical risks (e.g. infection, haemorrhage, pain).
Sterilisation for women
 Tubal ligation (laparoscopic or laparotomy) – many methods (typically, Filshie Clip in NZ – >80% reversible)
 Increased risk of ectopic pregnancy if pregnancy does occur (rare)
 Micro-insert to fallopian tubes (no longer available) – causes scarring and tubal blockage
 Hysterectomy
Sterilisation for men
 Vasectomy – many methods
 There is no change to sexual function post-vasectomy (but post-reversal fertility may be affected due to anti-sperm antibodies)
 Sperm granulomas may form (which can rarely restore sperm passage)
 Up to 50% reversible (greater if less than ten-years post-operation)

Emergency contraception
Postinor-1
 Postinor-1 – single progestogen tablet (levonorgestrel 1.5mg )
 Most effective at preventing pregnancy within 72 hours (may be effective up to 5 days)
 Less effective if BMI >25 or mid-cycle
 A follow-up pregnancy test in 3 weeks is always recommended
 Mechanism: delays ovulation and creates inhospitable uterine environment; may alter corpus luteum and tubal function
 Side effects : nausea/vomiting (may need to re-dose if vomit within 3 hours of taking medication)
IUD
See above.
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Termination of pregnancy
LEGALITY
 Governed by the Crimes Act 1961
 Before 20 weeks: two certifying consultants agree that continuing the pregnancy would result in serious danger to a woman’s
mental or physical health (or there is a substantial risk that the child if born would be seriously handicapped)
 After 20 weeks: to save the life of the woman or to prevent serious permanent injury to her physical or mental health
 Foetal anomaly is not in itself a ground for termination of pregnancy
THE TWO METHODS OF ABORTION
The same legal requirements and the same pre-abortion tests (antenatal screen and others) are required for both methods:
 Early medical abortion (EMA) (>90% effective – dependent on gestation)
 Indicated up to nine weeks gestation
 Two medications – mifepristone (anti-progesterone) and misoprostol (synthetic prostaglandin)
 Mifepristone – degeneration of uterine lining and softening of cervix
 Misoprostol – causes uterine contraction
 Typically, taken two days after mifepristone (but if less than seven weeks, can take both medications on same day)
 Method:
 Patient takes medications at clinic (legal requirement) and gets a baseline β-hCG
 Miscarriage occurs at home; associated with strong cramping and heavy bleeding (typically, a few hours after misoprostol )
 Miscarriage occurs over several hours or days
 The patient should have a support person, phone, and transport available during the miscarriage
 The patient requires a repeat β-hCG one-week post-miscarriage to confirm abortion
 Surgical abortion (>99% effective)
 9 to 14 weeks gestation – vacuum aspiration (suction D&C)
 14 to 19 weeks gestation – forceps dilatation and evacuation
 >20 weeks gestation – may be able to travel to Australia (strict criteria)
 May also use mifepristone or misoprostol
 Method:
 Patient gets a baseline β-hCG
 Procedure takes several minutes (but the women will spend several hours in clinic)
 Associated with cramping or heavy bleeding for a few weeks
 Typically, performed under general anaesthetic
 The patient requires a repeat β-hCG one-week post-miscarriage to confirm abortion
COMPLICATIONS
 Uterine perforation (surgical abortion)
 Retained products of conception (typically, medical abortion)
 Acute endometritis (10% of cases)
 Withdrawal bleeding secondary to a degenerating corpus luteum (presents several days after as hCG levels fall)

Note: the baseline fertility remains similar after abortion (unless late abortion or several early abortions).

Reproductive endocrinology
INFERTILITY

DEFINITION
 Infertility – inability to conceive or carry to term a pregnancy after one year of regular, unprotected, intercourse
 Primary – infertility in the context of no prior pregnancies
 Secondary – infertility in the context of a prior conception
 Subfertility – fertility is still possible but delayed
 Sterility – fertility is not possible
 Normal fertility (expected):
 75% of couples achieve pregnancy within 6 months
 85% of couples achieve pregnancy within 1 year
 90% of couples achieve pregnancy within 2 years
 Fecundity – the capacity to conceive (measured as the monthly probability of conception)
 Female fecundity decreases with increasing age (dropped markedly by 40 years)
 After 40 years of age, there is a rapidly rising rate of miscarriage and chromosomal abnormalities
AETIOLOGY
 Female causes – 60% of cases
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 Male causes – 25% of cases

 Unexplained – 15% of cases

Female factors (60%)

PATHOPHYSIOLOGY

 Ovulatory dysfunction (15%)

 Hypothalamic (functional hypothalamic amenorrhoea)
 Pituitary (prolactinoma, hypopituitarism)
 Ovarian (PCOS or premature ovarian failure)
 Outflow tract abnormality ( 15%)
 Tubal factors (PID, adhesions, occlusion)
 Uterine factors (congenital factors, fibroids, polyps, Asherman syndrome)
 Cervical factors (anti-sperm antibodies, hostile cervical mucous, structural defects)
 Endometriosis (30%)
 Multiple factors (30%)
 Unknown factors (10%)

Note: PCOS (most common) and endometriosis are common causes of infertility in women.
DIAGNOSIS
 Thorough clinical history (reproductive, sexual, medical, and surgical)
 Initial investigations:
 Antenatal screen (esp. Rubella status)
 Baseline hormonal screen (days 2-5) – FSH/LH, androgens, oestrogen, TSH, prolactin
 Luteal phase progesterone (conducted at day 21 (or 7 days before expected menses) to confirm ovulation – >30nmol/L)
 Can also consider LH urine kit (expensive) or cervical mucous changes (free but unreliable)
 Anti-Mullerian hormone (estimates ovarian reserve)
 Anatomical factors and patency (hysterosalpingogram or laparoscopy)
TREATMENT
 Lifestyle change (healthy diet, increased exercise, weight loss or gain, smoking cessation, alcohol reduction)
 Sexual change (increased sexual activity and timing of intercourse)
 Pregnancy probability maximised days 12 to 14 of menstrual cycle
 Folic acid supplementation
 Dependent on underlying cause:
 PCOS – clomiphene (on days 2 to 6 of menstrual cycle) (anti-oestrogen –  endogenous FSH via negative feedback to
pituitary)
 Can also consider pulsatile GnRH therapy if clomiphene-resistance
 Assisted reproduction

Male factors
 Azoospermia – no sperm in ejaculate
 Oligozoospermia – reduced number of sperm in ejaculate
PATHOPHYSIOLOGY
 Semen abnormality (85%) – e.g. medication, smoking, alcohol, testicular cancer, varicocele, or idiopathic
 Reduced sperm (5%)
 Pre-testicular – medication, hypogonadism, Kalmann’s syndrome, pituitary adenoma
 Non-obstructive – cryptorchidism, orchitis, 47XXY, chemoradiotherapy
 Obstructive – CBAVD, vasectomy, STI
 Immunological (5%) – e.g. anti-sperm antibodies
 Coital dysfunction (5%) – e.g. retrograde ejaculation or failure in ejaculation

Note: varicocele is the most common cause of infertility in males.

DIAGNOSIS
 Thorough clinical history (reproductive, sexual, medical, and surgical)
 Initial investigations:
 Semen analysis (if abnormal, arrange a repeat sample with 3 days abstinence)
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 Karyotype (exclude 47XXY)

 Baseline hormonal screen (days 2-5) – FSH/LH, androgens, oestrogen, TSH, prolactin (FSH elevated in testicular failure)
 Cystic fibrosis screen (assess for CBAVD – congenital bilateral absence of vas deferens)
TREATMENT
 Lifestyle change (healthy diet, increased exercise, weight loss or gain, smoking cessation, alcohol reduction)
 Dependent on underlying cause:
 Review medications
 Antispermatogenic – e.g. alcohol or anabolic steroids
 Antiandrogenic – e.g. spironolactone
 Erectile dysfunction – e.g. anti-depressants or thiazide diuretics
 Assisted reproduction

Assisted reproduction
Approximately 25% of couples wanting children experience infertility in their reproductive lifetime.
 With assisted reproduction , 40% will achieve pregnancy
CLASSIFICATION
 Donor insemination (DI) or Intrauterine insemination (IUI)
 In Vitro Fertilisation (IVF) (most common)
 IVF using Pre-implantation Genetic Diagnosis (PGD)
 IVF using Intracytoplasmic Sperm Injection (ICSI)
 IVF using donor oocytes and/or donor sperm (regulated if both donor oocyte and donor sperm)
 IVF using surrogate (regulated)
 Embryo donation (regulated)
Steps of IVF
 Pituitary control – non-pulsatile GNRH agonist or antagonist
 Stimulate ovary – FSH agonist and LH agonist/hCG (once follicles developed – triggers final stage of egg maturation)
 Oocyte pickup
 Fertilisation and embryo development (direct or via ICSI)
 Embryo transfer
 Luteal support – progesterone (to retain pregnancy)
COMPLICATIONS
 Ovarian hyperstimulation syndrome (high levels of progesterone due to excessive corpus luteums – ideal target in IVF is 6-10 follicles)
 Can be life-threatening – associated with ascites, abdominal pain, pleural effusion, and respiratory distress
 Multiple pregnancy
 Well-being of IVF children (lack of data)
Anti-Mullerian hormone
Anti-Müllerian hormone is a protein that inhibits the development of the Müllerian ducts (paramesonephric ducts) in the male embryo.
 AMH expression occurs in ovarian granulosa cells of females – acts as a biomarker for relative size of the ovarian reserve
 Can be used to predict response to IVF and fertility prognosis
Pre-implantation Genetic Diagnosis
Pre-implantation Genetic Diagnosis involves biopsy of one cell of a developing embryo to genetically test before IVF.
 Useful for single gene disorders (e.g. CF or HD), chromosome abnormalities (e.g. recurrent miscarriage), and X-linked disorders
POLYCYSTIC OVARY SYNDROME (PCOS)

FEATURES
 Affects 10% of women of reproductive age; is the most common cause of infertility
PATHOPHYSIOLOGY
 The exact pathophysiology of PCOS is unknown, but women have a genetic predisposition to excess ovarian androgen secretion
 Reduced insulin sensitivity (and hyperinsulinaemia ) is present in PCOS (as in metabolic syndrome)
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CLINICAL PRESENTATION
 Common presentation : obesity, abnormal (irregular) uterine bleeding, infertility, acne, androgenic alopecia, and hirsutism
 Associated with:
 T2DM – acanthosis nigricans
 Metabolic syndrome – insulin resistance, atherogenic dyslipidaemia, and hypertension
DIAGNOSIS
 Rotterdam criteria (two of three):
 Polycystic ovaries (via U/S – enlarged ovary volume with at least 12 or more antral follicles in one ovary)
 Oligo- and/or anovulation (i.e. irregular periods )
 Clinical and/or biochemical evidence of hyperandrogenism
 Biochemical test:  free testosterone
 DHEA – exclude adrenal tumour
 U/S – exclude androgen-secreting ovarian tumour
 17-OH progesterone – exclude non-classical CAH
 Consider screening for Cushing syndrome or acromegaly (other causes of hirsutism)
 Additional tests:
 Labs: lipids, HbA1c, LH:FSH ratio (>2:1 in PCOS)
 Transvaginal ultrasound – ‘pearl necklace’ sign
TREATMENT
 Lifestyle change – weight loss/diet/etc. (reduces peripheral oestrogen formation) (does not increase ovulation)
 Women who are not attempting to conceive – COC (with anti-androgenic cyproterone acetate as the progestogen) ± metformin
 Women who are attempting to conceive – clomiphene (selective oestrogen receptor modulator) ± metformin
 There is a risk of multi-pregnancy from clomiphene
 Symptom-specific treatment:
 Hirsutism – COC, antiandrogens (spironolactone, finasteride ), or metformin (or mechanical removal of hair )
 Infertility – laparoscopic ovarian drilling (only proven non-drug treatment)
 Metabolic syndrome – as normal
COMPLICATIONS
 Increased risk of T2DM/metabolic syndrome , breast/endometrial/ovarian cancer , hypertension , and miscarriage
MENOPAUSE

DEFINITION
 Menopause – occurrence of last spontaneous menstrual period (lack of menses for one year)
 Perimenopause – period around menopause (characterised by fluctuating hormones, irregular menstruation, and symptoms)
 Also, known as climacteric
CLASSIFICATION
 Physiological menopause – average age of onset is 51 years (due to follicular depletion)
 Primary ovarian insufficiency (premature ovarian failure) – menopause before age 40
PATHOPHYSIOLOGY
 Mechanism: degenerating thecal cells fail to react to endogenous gonadotropins (FSH/LH)   oestrogen/progesterone  
negative feedback on HPA axis   FSH/LH  stromal cells continue to produce androgens as result of  LH stimulation
 Although oestrogen/progesterone decreases, there may be excessive hormones due to fluctuations in perimenopause
CLINICAL PRESENTATION
 Symptoms are associated with oestrogen deficiency:
 Vasomotor instability – hot flushes, night sweats, sleep disturbance
 Urogenital atrophy – vaginal dryness, pruritis, dyspareunia; also, urinary urgency, frequency, and incontinence
 Skeletal – osteoporosis
 Skin and soft tissue – decreased breast size, skin thinning
 Psychological – mood disturbance, poor concentration, loss of libido, irritability
DIAGNOSIS
 Clinical diagnosis
 Labs (optional):  FSH/LH (FSH>LH),  oestrogen (later)
TREATMENT
 Symptomatic (for example):
 Vasomotor instability – HRT (first-line)  SSRI/SNRIs, clonidine, gabapentin
 Vaginal atrophy – local vaginal oestrogen therapy (topical/suppository/ring) or lubricants
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 Osteoporosis – as normal
 CVS disease – as normal (risk management)
OUTCOMES
 Osteoporosis is the single most important hazard associated with menopause
 Cardiovascular disease is the leading cause of death post-menopause (oestrogen is a protective factor )
Hormone replacement therapy
 Used in the treatment of menopausal symptoms (particularly vasomotor instability)
TREATMENT
 Components (in various regimens) (preferably for <5 years):
 Continuous oral/transdermal oestrogen
 Continuous oral progesterone (if intact uterus) – prevents development of endometrial hyperplasia/cancer

Note: can be given as cyclical combined therapy in peri-menopausal women (<1 year) (produces predictable withdrawal bleeding).
SIDE EFFECTS
 Amenorrhoea (after a period of menstrual irregularity)
 Breast tenderness
 Fluid retention/bloating
 Mood changes (progesterone)
CONTRAINDICATIONS
ABCD:
 Acute liver disease
 Undiagnosed vaginal Bleeding
 Cancer (breast/uterine) or Cardiovascular disease
 DVT (thromboembolic disease)
CLINICAL NOTES
 Increases risk of – breast cancer, ovarian cancer, CAD, CVD, and VTE
 Decreases risk of – osteoporosis and bowel cancer
 Pre-treatment screening : cardiovascular assessment , liver assessment, and screening mammogram

Urogynaecology
PELVIC RELAXATION/PROLAPSE
Pelvic relaxation/prolapse is protrusion of pelvic organs into or out of the vagina.
PATHOPHYSIOLOGY
 Relaxation, weakness, or defect in the reproductive muscles, ligaments, and other
anatomical structures of the pelvic floor
 Risk factors:
 Aging (post-menopause)
 Multiparity (esp. vaginal births)
 Prior pelvic surgery
 Increased intra-abdominal pressure (e.g. obesity, chronic constipation, ascites)
 Collagen disorders
CLASSIFICATION
 Graded by degree of descent of pelvic organs relative to the hymen whilst performing the
Valsalva manoeuvre (lithotomy position )
CLINICAL PRESENTATION
 Symptoms: urinary or faecal incontinence, urinary symptoms, pain, sensations of heaviness/pressure, and dyspareunia
 Signs: prolapse is apparent on examination
Types of pelvic prolapse
TYPE CLINICAL FEATURES
Cystocoele  Urinary symptoms: frequency, urgency, nocturia, recurrent UTIs
Protrusion of bladder into anterior vaginal wall  Stress incontinence

Rectocoele  Difficulty defecating (not strictly constipation)

Protrusion of rectum into posterior vaginal wall  Straining/digitation to evacuate stool
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Uterine prolapse  Groin/back pain (stretching of uterosacral ligaments)

Protrusion of cervix and uterine into vagina  Feeling of heaviness/pressure in the pelvis (worse with standing/at end of day)
 Ulceration/bleeding (esp. if hypoestrogenic)
 Urinary incontinence

Enterocoele
Protrusion of small bowel into posterior vaginal wall (associated with constipation)

Vault prolapse
Protrusion of apex of vaginal vault into vagina post-hysterectomy

TREATMENT
 Conservative treatment (for pelvic relaxation/prolapse and urinary incontinence):
 High-fibre diet and weight reduction
 Pelvic exercises (‘Kegels’)
 Local vaginal oestrogen therapy (topical/suppository/ring) – if post-menopausal
 Vaginal pessary (intravaginal suspension disc) – in geriatric population
 Surgical treatment:
 Cystocoele – anterior colporrhaphy (anterior repair )
 Rectocoele – posterior colporrhaphy (posterior repair )
 Uterine prolapse – vaginal hysterectomy ± vaginal vault suspension
 Enterocoele – surgical reduction and repair of peritoneal defect (pouch of Douglas) (posterior repair )
 Vault prolapse – vaginal vault suspension
URINARY INCONTINENCE
See Urology.

Benign vulvar and vaginal disorders

PRURITIS VULVAE
Atrophic vaginitis
Atrophic vaginitis is a result of post-menopausal tissue atrophy.
CLINICAL PRESENTATION AND DIAGNOSIS
 Clinical diagnosis : thinning of tissue, pale tissue, and vaginal dryness on examination
 Symptoms : pruritis, dyspareunia, post-coital spotting
TREATMENT
 Local vaginal oestrogen therapy (topical/suppository/ring) or lubricants
 Consider HRT if indicated
Candidiasis
See Dermatology.
Lichen sclerosus
Lichen sclerosus is a chronic skin disorder of unknown aetiology that affects the genital and perianal areas.
 Lichen sclerosus is 10 times more common in women than men
CLINICAL PRESENTATION AND DIAGNOSIS
 Presents as white crinkled or thickened patches of skin that have a tendency to scar
 May become confluent extending around the vulvar and perianal skin in a ‘figure of eight’ configuration
 Associated with increased risk of vulvar, penile, or anal cancer (biopsy may be indicated)
TREATMENT
 Extra-potent topical steroids (clobetasol)
Lichen simplex
Lichen simplex is a localised dermatitis due to repeated rubbing or scratching.
 Treated by preventing rubbing/scratching ± extra-potent topical steroids (clobetasol)
VULVAR HAEMATOMA
Vulvar haematoma can result from trauma to the vulva (particularly ‘fall astride’ injuries ).
 Small haematomas – managed conservatively with analgesia and reassurance
 Large haematomas – urgent surgical exploration (large potential bleed space that can lead to haemodynamic instability)
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BARTHOLIN GLAND CYST

Bartholin gland cysts are due to blockage of the Bartholin gland duct , and subsequent infection (typically, anaerobic polymicrobial ).
 Associated with gonococcal infection (microbiology sample indicated if abscess has formed)
CLINICAL PRESENTATION
 Unilateral swelling and pain in inferior lateral opening of vagina
 Sitting and walking may become difficult and/or painful
TREATMENT
 Supportive – Sitz bath and warm compresses
 Medical – antibiotics (if cellulitis or systemic symptoms)
 Surgical:
 I&D using local anaesthesia with placement of a Word catheter for 2 weeks , or
 Marsupialisation (under general anaesthesia)
IMPERFORATE HYMEN
Imperforate hymen is a congenital malformation characterised by the hymen completely obstructing the vagina .
 Presents as haematocolpos (blood in vagina) with a bulging hymen
 Treated with surgery
VULVODYNIA
Vulvodynia is a chronic pain syndrome affecting the vulvar area associated with severe tenderness to light touch.

Oncogynaecology
Gynaecological cancers include uterine, endometrial, ovarian, cervical, and vulvar neoplasms (ovarian has the highest mortality).
 Frequency: endometrial > ovarian > cervical
UTERINE (ENDOMETRIAL) CANCER

FEATURES
 Risk factors (type 1):
 Excess oestrogen (early menarche, late menopause, nulliparity; also, obesity, DM, PCOS, unbalanced HRT, tamoxifen )
 Hormonal contraceptives are protective against endometrial cancer
 Tamoxifen is a risk factor for endometrial cancer (despite decreasing the risk of breast cancer)
 Typically, a disease of post-menopausal women (mean age of 60)
 Typically, detected at an early stage with a good prognosis (type 2 cancers have poor prognosis)
CLASSIFICATION
 Type 1 (well-differentiated endometrial adenocarcinoma) – 80% of cases
 Typically, presents as:
 Post-menopausal – bleeding
 Pre-menopausal – AUB (menorrhagia, intermenstrual bleeding)
 Type 2 (serous, clear cell carcinoma, carcinosarcoma, or undifferentiated) – 15% of cases (typically, due to P53 mutations)
 Typically, presents with advanced stage disease (e.g. bloating, bowel or bladder dysfunction, pelvic pressure)
DIAGNOSIS
 Imaging:
 Transvaginal U/S (not acceptable as an alternative to endometrial sampling)
 Endometrial sampling (pipelle sampling, unless cervical stenosis, or D&C ± hysteroscopy) after U/S and indicated if:
 Post-menopausal – any bleeding
 Pre-menopausal – sustained intermenstrual bleeding, menorrhagia, or amenorrhoea with unopposed oestrogen (e.g. obesity/DM)

Note: an endometrial thickness of 5mm or more is considered abnormal in a post-menopausal women with vaginal bleeding.
TREATMENT
 Typical ( good prognosis) – TAH/BSO ± radiation ± pelvic washings ± pelvic and para-aortic node dissection ± omentectomy
 Advanced stage / recurrent disease – as above ± adjuvant chemotherapy ± hormonal therapy (high dose progestogens)
COMPLICATIONS
 Metastasis:
 Direct extension (most common)
 Lymphatic spread – pelvic and para-aortic nodes
 Haematogenous spread – usually, lungs and/or liver
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OVARIAN CANCER
Most ovarian tumours are benign (>90%), but malignant tumours are the leading cause of death from reproductive tract cancer.
 There are several different kinds of benign and malignant tumours (serous carcinoma is the most common ovarian cancer)
FEATURES
 Risk factors:
 Excess oestrogen (early menarche, late menopause, nulliparity; also, obesity, DM, PCOS, unbalanced HRT)
 Hormonal contraceptives are protective against ovarian cancer (50% reduction if taken for more than 5 years)
 Breastfeeding is protective against ovarian cancer
 Genetic (family history, BRCA1 (50% lifetime risk), BRCA2 (25% lifetime risk), HNPCC)
CLINICAL PRESENTATION
 Both benign and malignant typically asymptomatic; may present with non-specific abdominopelvic symptoms (e.g. pressure or
pain)
 Typically, presents as advanced stage disease (pain, bleeding, palpable mass, ascites, urinary/bowel symptoms due to mass effect)
 Examination: early disease not detected
Benign versus malignant pelvic masses
BENIGN MALIGNANT
EXAMINATION
Mobility Mobile Fixed

Consistency Cystic Solid/firm

Location Unilateral Often bilateral

Cul-de-sac Smooth Often nodular

TRANSVAGINAL ULTRASONOGRAPHY
Size <8cm >8cm

Consistency Cystic Solid or cystic

Septation Unilocular Multilocular

Location Unilateral Often bilateral

Other Calcifications Ascites

DIAGNOSIS
 Transvaginal U/S (first-line investigation)
 Surgical biopsy and staging (definitive)
 Tumour markers:
 Ca-125 – associated with epithelial cell cancers (90% of ovarian cancers)

Note: any ovarian or adnexal mass in a premenarchal or post-menopausal patient is suggestive of an ovarian neoplasm.
TREATMENT
 Treatment of ovarian masses:
 Premenarchal – observation ± surgical removal
 Premenopausal:
 Likely benign – observation (most resolve spontaneously)
 Likely malignant – surgical evaluation
 Postmenopausal – surgical evaluation (unless significantly suggestive of benign mass)
 Treatment of ovarian cancers:
 Surgery – TAH/BSO ± pelvic washings ± pelvic and para-aortic node dissection ± omentectomy
 Adjuvant chemotherapy – routine (except for early-stage or low-grade)
 Radiation therapy – effective for dysgerminomas
 Consideration of genetic screening:
 BRCA1 – treatment may include surveillance only, chemoprevention , prophylactic BSO and/or prophylactic mastectomy
COMPLICATIONS
 Infarction or haemorrhage (mimics ovarian torsion)
 Torsion of the tumour
 Rupture (can present as peritonism)
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 Meigs syndrome is the triad of ascites, pleural effusion , and benign ovarian tumour (typically, fibroma)
 Resolves after resection of the tumour

Benign ovarian tumours

TYPE DESCRIPTION CLINICAL PRESENTATION TREATMENT

Follicular cyst Follicle fails to rupture during Symptoms: typically, asymptomatic  Observation
ovulation  May rupture causing pain/peritonitis  COC (prophylaxis)
U/S: >4-8cm mass (is abnormal)  Laparoscopic cystectomy

Lutein cyst Corpus luteum fails to regress Symptoms: rupture causing pain/peritonitis  Same as for follicular cyst
(lined with epithelial tissue – i.e.  May delay onset of next period
skin, hair, teeth) U/S: >10cm mass

Dermoid Most common ovarian germ cell Symptoms: torsion (most likely of all cysts)  Laparoscopic cystectomy
(cystic teratoma) neoplasm

Note: a Krukenberg tumour is a metastatic ovarian tumour originating from the GI tract or breast (characteristic ‘signet-ring’ cells).

CERVICAL CANCER

BASIC PRINCIPLES
 At birth, the vagina is lined with squamous epithelium ; columnar epithelium lines only the
endocervix and the central area of the ectocervix (original squamocolumnar junction )
 During puberty, oestrogen stimulates eversion of a single columnar layer (ectopy), exposing it
to the acidic pH of the vagina, leading to metaplasia (and a new squamocolumnar
junction)
 The transformation zone is the area located between the original and new SCJ
 The majority of dysplasia occurs here (requires active metaplasia and an inducing agent)
 Human papilloma virus (HPV) acts as an inducing agent (stimulating abnormal
proliferation) in >99% of cervical cancers (esp. HPV 16/18)
 HPV 16 is most prevalent type in cervical SCC (95%)
 HPV 18 is most prevalent type in cervical adenocarcinoma (5% but increasing)
 Ectropion represents temporarily increased endocervical epithelium visible in the ectocervix
 Due to the effects of oestrogen (puberty, menstrual period, COC, pregnancy)
 Most common cause of post-coital bleeding
BENIGN CERVICAL LESIONS
 Nabothian cysts (mucous inclusion cysts) – no treatment required
 Endocervical polyps – treatment is polypectomy
 Cervicitis – caused by STIs (predominantly chlamydia, gonorrhoea, and HSV); may mask neoplasia
FEATURES
 Risk factors: HPV is the main risk factor
 High risk – types 16/18 (>99% of cervical cancers contain one of the high-risk types)
 Low risk – types 6/11 (although high risk for genital wart)
 Risk factors for HPV infection – multiple partners, other STIs, early age first coitus
 Smoking is another risk factor
CLINICAL PRESENTATION
 Ideally, pre-cancerous lesions are detected in the Cervical Screening Programme
 Otherwise, typically presents as irregular vaginal bleeding
 May present with discharge, pelvic or back pain, and/or bowel/urinary symptoms (if invasion has occurred)
 Examination: may be able to directly visualise cellular change (e.g. raised, reddened, ulcerated cervix; fungating tumour if advanced)
DIAGNOSIS
 Cervical Screening Programme – three-yearly cervical smear test from age 20 to age 69 (for all women)
 Cervical smear:
 Normal – repeat smear in 3 years
 Unsatisfactory – repeat smear in 3 months
 ASC-US/LSIL
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 No abnormal smear in last 5 years – repeat smear in 1 year

 If >30 years old – HPV test (and refer to colposcopy if positive)
 Abnormal smear in last 5 years – refer to colposcopy
 HSIL – refer to colposcopy
 Colposcopy:
 ASC-US/LSIL
 Normal – refer back to smear-taker (with yearly repeat smears for 2 years)
 Abnormal – biopsy
 CIN1 – as for normal
 CIN2/3 – treatment
 HSIL
 Abnormal – biopsy
 CIN1 – management based on MDT
 CIN2/3 – treatment
 New guidelines incorporate HPV testing into the screening process
 Full metastatic workup (CBC, U&E, LFTs, CXR, CT chest/abdomen/pelvis, bone scan)
TREATMENT
 CIN2/3 (or as indicated by MDT opinion):
 Loop electro-excisional procedure (LEEP)
 Large loop excision of transformation zone (LLETZ)
 Cone biopsy
 Pregnant women – delay treatment until after deliver (unless invasive cancer)
 Invasive cancer – radical hysterectomy ± lymphadenectomy ± chemoradiotherapy
OUTCOMES
 Survival rates inversely proportionate to stage of cancer (5-year median survival of 70%)
COMPLICATIONS
 Ureteral obstruction (can lead to fatal uraemia due to post-renal kidney injury)

VULVAL CANCER

FEATURES
 Risk factors: HPV (types 16/18/31), lichen sclerosis, and prior history of genital malignancy
 Typically, occurs in the elderly (average age is between 70 to 90 )
CLASSIFICATION
 Vulvar intra-epithelial neoplasia (VIN) – pre-cancerous lesion (similar to LSIL/HSIL) (more common in pre-menopausal women)
 Squamous cell carcinoma (more common in post-menopausal women)
CLINICAL PRESENTATION
 Presents with pruritis , pain, or ulceration of the mass
 Associated with white lesions of lichen sclerosis
DIAGNOSIS
 Punch biopsy for any suspicious lesions (or persistent vulvar pruritis – esp. in post-menopausal women)
TREATMENT
 VIN – wide local excision , laser ablation, or topical chemotherapy
 Invasive – radical vulvectomy and regional lymphadenectomy ± pre-operative chemoradiotherapy
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VAGINAL CANCER

CLASSIFICATION AND CLINICAL PRESENTATION

Types of malignant vaginal lesions

TYPE CLINICAL PRESENTATION
Vaginal intra-epithelial neoplasia (VAIN) Pre-cancerous lesion (similar to LSIL/HSIL) that is more commonly found in pre-menopausal women

Squamous cell carcinoma (majority) Most common in upper one-third of vagina

 Asymptomatic, or presenting with abnormal vaginal bleeding, discharge, or post-coital bleeding

Adenocarcinoma Typically, metastatic (cervix, endometrium, ovary, or colon)

DIAGNOSIS
 Cytology
 Colposcopy
 Biopsy
 Schiller test (normal squamous epithelium takes up Lugol’s iodine)
TREATMENT
 Low stage – local excision
 High stage – partial or complete vaginectomy ± radiotherapy
GESTATIONAL TROPHOBLASTIC DISEASE
Gestational trophoblastic disease (GTD) refers to a range of proliferative trophoblastic abnormalities that can be benign or malignant.
 A mole refers to proliferative chorionic villi which have swollen and degenerated
CLASSIFICATION
 Benign GTD – includes complete and incomplete molar pregnancies
 Malignant GTD (may progress from molar pregnancy) – 20% of cases
 Invasive moles (more common)
 Choriocarcinoma
Complete versus incomplete molar pregnancies
INCOMPLETE COMPLETE
Mechanism Normal ovum fertilised by two sperm Sperm fertilisation of empty ovum

Karyotype 69, XXY (triploid) 46, XX

Foetal tissue Contains foetal tissue Does not contain foetal tissue

CLINICAL PRESENTATION
 Incomplete mole – typically, presents similar to threatened/spontaneous/missed miscarriage
 Complete mole – first-trimester uterine bleeding , hyperemesis gravidarum , excessive uterine size for LMP , and pre-eclampsia
 May present with abdominal pain due to theca-lutein cyst rupture or torsion (cysts present in 50% of cases)
 May present with hyperthyroidism (as β-hCG resembles TSH)
 Invasive mole – as above (metastases rare)
 Choriocarcinoma – typically, presents with symptoms of metastases (lung, vagina, pelvis, liver, and brain)
 Tumour is highly vascular, and has a tendency to bleed (esp. if biopsied)
DIAGNOSIS
 Imaging:
 Pelvic U/S:
 Incomplete – molar degeneration of placenta ± foetal abnormalities
 Complete – ‘snow-storm’ appearance (with no gestational sac or foetus present) in a uterus that is large for LMP
 CXR – pulmonary metastases (most common metastatic site)
 Labs: β-hCG is abnormally high for gestational age (typically, >100,000)
 Examination:
 No foetal heartbeat detected
 Grapelike molar clusters (may protrude into vagina)
 Enlarged ovaries (bilateral theca-lutein cysts)
 D&C – grapelike molar tissue
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TREATMENT
 D&C followed by:
 Contraception required to avoid pregnancy during entire follow-up period
 Serial β-hCG (as tumour marker) for at least one-year (weekly for one-month, then monthly)
 Anti-D antibody (if Rh negative)
 Chemotherapy or radiotherapy – if persistent or metastatic
 Hysterectomy can be considered if residual uterine disease (or fertility not desired)
OUTCOMES
 Good prognosis (if not metastatic)
 Fertility is usually retained
 Increased risk of future molar pregnancies (that increases based on the previous number)

Miscellaneous disorders
PELVIC INFLAMMATORY DISEASE
Pelvic inflammatory disease is defined as inflammation of the upper genital tract (above the cervix).
 Includes any combination of endometritis , salpingitis , parametritis , tubo-ovarian abscess, oophoritis and pelvic peritonitis
AETIOLOGY
 Typically, C. trachomatis or N. gonorrhoeae
 Risk factors – same as for STI in addition to IUD (within first 10 days of insertion)
CLINICAL PRESENTATION
 Typically, asymptomatic/mild symptoms
 Lower abdominal pain with cervical motion tenderness
 Associated with fever, deep dyspareunia, abnormal discharge or bleeding
DIAGNOSIS
 Clinical diagnosis , supported by:
 Labs – CBC, urinalysis (R&M), β-hCG
 STI testing
 Ultrasound
 Laparoscopy
TREATMENT
 Antibiotics – IM ceftriaxone stat + 2/52 PO doxycycline + 2/52 PO metronidazole
 Removal of IUD
COMPLICATIONS
 Chronic pelvic pain
 Tubal factor infertility (and ectopic pregnancy )
 Fitz-Hugh-Curtis syndrome (peri-hepatic adhesions)

Note: PID is associated with a 10% infertility rate after adequately treated first episode (>30% after second episode).
PREMENSTRUAL SYNDROME

DEFINITION
 Premenstrual syndrome is a multifactorial condition that leads to physiological and emotional disturbances before menstruation.
DIAGNOSIS
 Symptom diary (usually for two months) – a symptom free week after menstruation is required
TREATMENT
 Lifestyle change:
 Exercise
 Relaxation
 Supplements:
 Calcium carbonate (first-line for lowered mood, fluid retention and pain)
 Pyridoxine (vitamin B6)
 Medication:
 Low mood – SSRIs or COC
 Discomfort and pain – NSAIDs or COC
 Fluid retention – spironolactone
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Obstetrics
Basic principles
ANATOMY
The placenta is the site of foetal nutritive, respiratory, and excretory function .
 Composed of foetal (chorion frondosum) and maternal (decidua basalis) tissues
 Divided into lobules (cotyledons) on the uterine side
 Produces hormones such as progesterone, placental lactogen , oestrogen, relaxin, β-hCG, and IGFs

PHYSIOLOGY OF A NORMAL PREGNANCY

Basics
DEFINITIONS
 Gravidity – number of times a women has been pregnant (regardless of outcome)
 Parity – the number of pregnancies that either:
 Led to a birth beyond 20 weeks gestational age , or
 Comprised of a foetus weighing greater than 400 grams
 More detailed information in the TPAL format:
 Term infants (>37 weeks)
 Premature infants (20 to 36 weeks)
 Abortions and miscarriages (induced or spontaneous)
 Living children (number)
 Gestational age – determined in several different ways:
 LMP – the number of weeks and days (measured from the first day of the last menstrual period – called LMP)
 Naegele's rule (estimates EDD) – LMP + 1 year – 3 months + 7 days (280 days)
 Fundal height – using a nomogram
 Roughly corresponds to gestational age in weeks between 16 and 36 weeks for a vertex foetus
 Ultrasonography (advised if irregular periods or needing more accurate measure):
 Measures foetal crown-rump length (CRL) from 6 to 12 weeks gestation (most reliable in first trimester)
 Measures biparietal diameter, femur length, and head and abdominal circumference from 13 weeks gestation
 Trimesters
 First trimester – 0 to 13 weeks gestation
 Second trimester – 14 to 26 weeks gestation
 Third trimester – 27 to 40 weeks gestation
 Normal pregnancy term – 37 to 42 weeks gestation

Diagnosis of pregnancy
 β-hCG
 Produced by placenta
 Approximately doubles every 48 hours until reaching a peak level at 10 weeks gestation
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 Declines in the second trimester, and levels off in the third trimester (although still above normal range)
 Ultrasonography
 Used to confirm an intrauterine pregnancy
 The gestational sac is visible (on transvaginal U/S) by five weeks gestation
 The foetal heart activity is visible (on transvaginal U/S) by eight weeks gestation
 An intrauterine pregnancy is visible (on transabdominal U/S) by eight weeks gestation
 Clinical signs
 Chadwick’s sign – bluish discolouration of cervix and vagina (by 6 weeks)
 Uterine enlargement
 Breast engorgement, areolae darkening, and prominent vascular patterns

Physiological changes of pregnancy

Body system changes in pregnancy
BODY SYSTEM PHYSIOLOGIC CHANGES
Haematological  Hypercoagulable state (due to venous stasis)
 Anaemia/ HCT (due to dilution)

Cardiovascular  Increased cardiac output (HR and stroke volume)

 Conditions causing pulmonary oedema/HTN, e.g. MS, or stress on the heart, e.g. aneurysm in Marfan’s, are dangerous)
 Decreased blood pressure in the first 24 weeks (gradually returns to normal)/HTN
 Increased plasma volume by 50%

Pulmonary  Increased ventilation (due to progesterone)

 Results in chronic respiratory alkalosis with renal compensation to allow for foetal CO2 off-load

Gastrointestinal  Reduced gut motility (leading to constipation and haemorrhoids)

 Increased risk of GORD (due to decreased oesophageal sphincter tone)
 Increased risk of gallstones

Renal  Increased renal plasma flow

 Increased GFR (and consequent decreased serum urea and creatinine)
 Decreased tubular reabsorption of glucose
 Increased urinary frequency
 Increased incidence of UTIs (due to urinary stasis)

Endocrine  Progesterone – synthesised by corpus luteum and then placenta (increases body temperature)
 Oestrogen – increases breast and nipple growth, water retention, and protein synthesis
 Prolactin – increases steadily during pregnancy

Prenatal care
ANTENATAL CARE
Recommendations for pregnant women
RECOMMENDATIONS
Weight gain Guidelines for weight gain (for normal BMI women) in pregnancy:
 Inadequate gain – <1.0kg/month
 Excessive gain – >1.5kg/month

A weight gain of 12kg throughout pregnancy, at a rate of 1kg per fortnight from 20 weeks is appropriate in most women

Nutrition  An additional 100-300kcal/day (500 kcal/day if breast feeding) (do not ‘feed for two’)
 Avoid foods that may be contaminated with listeria or salmonella (unpasteurised cheese, cold salads, and deli foods)
 Folic acid (1mth prior to 12w GA) ( neural tube defects) (high dose 5mg if FMHx or drugs – insulin, valproate, carbamazepine)
 Iron
 Calcium
 Vitamin D/B12 (if vegetarian)

Exercise  Thirty to sixty minutes of moderate exercise daily

Prenatal testing schedule

RECOMMENDATIONS
Prenatal visits  Weeks 0 to 28 – every 4 weeks
 Weeks 28 to 36 – every 2 weeks
 Weeks 36 to birth – every week
At each visit: blood pressure, weight, height, urine dipstick, abdominal pregnancy examination, inspection for oedema

Initial visit  Haematological: CBC, group and screen, Rh type and antibodies
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(10 weeks or earlier)  Infectious: rubella, HBsAg, HIV, VRDL ± HCV IgG/IgM, endocervical gonorrhoea and chlamydia swab, smear
 Additional (if indicated): HbA1c, genetic screening; additionally, viability U/S can be ordered from 6 weeks

18 to 20 weeks  U/S for full anatomical screen

24 to 28 weeks  One-hour glucose challenge test for gestational diabetes screen

 Haematological: CBC, group and screen, Rh type and antibodies

36 weeks  Infectious: GBS swab

 Haematological: CBC, group and screen, Rh type and antibodies

36 weeks to birth  Infectious: endocervical gonorrhoea and chlamydia swab, HIV, VRDL (if high risk)

Foetal abnormality screening

Ultrasound
 First trimester nuchal translucency (11 to 13 weeks)
 Calculates maternal age-related risk for trisomy 21 (Down syndrome), 18 (Edwards syndrome), and 13 (Patau syndrome)
 Second trimester anatomy scan (18 to 20 weeks) – screens for:
 Foetal abnormality
 Placental location
 Foetal growth
 Foetal wellbeing (amniotic fluid index – a marker of foetal renal health, or, biophysical profile – foetal activities)
 Doppler velocimetry (function of uterine, umbilical and foetal vessels)
Clinical screening
 Trisomy blood test (MSS1) (9 to 13 weeks) – β-hCG and PAPP-A (pregnancy-associated plasma protein A)
 Typically, used in conjunction with nuchal translucency (high sensitivity for trisomy detection)
 Quad screening (MSS2) (15 to 17 weeks) (only if MSS1 not conducted) – β-hCG, α-fetoprotein, inhibin A, and estriol
 Calculates maternal age-related risk for trisomy, open-neural tube defects , abdominal wall defects , foetal death
Quad screening
Β-HCG Α-FETOPROTEIN INHIBIN A ESTRIOL

Trisomy 21    

Trisomy 18    

Foetal abnormality testing

If the result of screening suggest a high risk of chromosomal abnormality , a foetal abnormality test can be obtained:
Types of foetal abnormality testing
CHORIONIC VILLUS SAMPLING AMNIOCENTESIS CELL-FREE FOETAL DNA

Gestation 10 to 14 weeks 15 to 20 weeks 10 weeks

Procedure Transcervical or transabdominal aspiration Transabdominal aspiration of amniotic Isolation of foetal DNA from blood
of placental tissue fluid using an ultra-sound guided needle sample obtained from mother

Advantages  Definitive  Definitive  Non-invasive

 Available at an earlier gestation

Disadvantages  Risk of miscarriage (1%)  Risk of miscarriage (0.5%)  May be limited by low concentration
 Does not detect open-neural tube defects of foetal DNA in maternal circulation

Miscarriage
MISCARRIAGE
Miscarriage is the most common complication of pregnancy (at least 25% of all pregnancies).
 Most miscarriage occurs in the first trimester of pregnancy
AETIOLOGY
 Chromosomal abnormalities – a factor in approximately 50% of miscarriages (particularly first trimester)
 Maternal factors – various, but particularly:
 Thrombophilia – most common cause in late trimester recurrent miscarriage
 Autoimmune issues (e.g. phospholipid syndrome)
 Anatomic issues (e.g. uterine or cervical abnormalities)
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 Endocrine issues (e.g. poorly controlled thyroid, diabetes, or PCOS)

 Environmental factors – tobacco, alcohol, caffeine (>500mg per day), medication
 Foetal factors – congenital malformation
 Maternal factors – various (e.g. thrombophilia, immunologic issues, anatomic issues)

Note: three or more miscarriages indicates work-up for investigation of recurrent pregnancy loss .
DIFFERENTIAL DIAGNOSIS OF BLEEDING IN EARLY PREGNANCY
 Idiopathic bleeding in a viable pregnancy
 Miscarriage
 Ectopic pregnancy
 Molar pregnancy
 Cervical or vaginal abnormality (e.g. infection, polyp, trauma, malignancy)
CLASSIFICATION
 Investigation of miscarriage – includes transvaginal ultrasound and serial β-hCG
Types of miscarriage
TYPE PRESENTATION DIAGNOSIS TREATMENT RISKS
Threatened Sx: bleeding ± pain hCG: increasing  Clinical monitoring  Progression to miscarriage
Os: closed U/S: viable foetus  Pre-term delivery
 PROM

Inevitable Sx: bleeding and pain hCG: plateaued/decreasing  Expectant or medical  Retained products
Os: open U/S: non-viable, POC in-utero  Surgical (if severe)

Incomplete Sx: bleeding and pain hCG: plateaued/decreasing  Expectant or medical  Retained products
Os: open (POC may be visible) U/S: non-viable, some POC in-  Surgical (if severe)
utero / some expelled

Complete Sx: POC expelled (no significant hCG: plateaued/decreasing  Expectant N/A
ongoing bleeding or pain) U/S: no POC in-utero
Os: closed

Missed Sx: asymptomatic (± bleeding) hCG: plateaued/decreasing  Medical  Retained products

Os: closed U/S: non-viable, POC in-utero  Surgical (gold standard)

Septic Miscarriage complicated by  Antibiotics  Sepsis

intrauterine infection  Prompt surgical evacuation

TREATMENT
 Expectant – supportive (in conjunction with clinical monitoring)
 Medical – mifepristone and misoprostol
 Surgical – aspiration curettage or dilatation and curettage (D&C)
 Additional:
 Anti-D (Rhesus) antibody – if mother is Rh negative

Normal labour and delivery

LABOUR

Definitions
 True labour – regular, painful, contractions of increasing intensity
 Associated with progressive dilation and effacement of cervix and descent of presenting part (or progression of station)
 Often preceded by a plug of cervical mucous (± light bleeding) – known as the ‘show’
 Classified as:
 Pre-term (<37 weeks gestation)
 Term (37-41 weeks gestation)
 Post-term (>42 weeks gestation)
 False labour – also known as Braxton-Hicks contractions
 Characterised by irregular contractions, with unchanged intensity and long intervals
 Not associated with any cervical dilation/effacement or descent
 Occur throughout pregnancy (but more common after 36 weeks gestation)

Cervix
 Cervical dilation – refers to diameter of cervical os, separated into the:
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 Latent phase (0-4cm)

 Active phase (4-10cm)
 Cervical effacement – refers to thinning of cervix (by percentage or length of cervix)

Foetus
 Foetal lie – orientation of the long axis of foetus relative to long axis of uterus (i.e. longitudinal, transverse, or oblique)
 Dependent on uterine shape in late gestation
 Foetal position – position of presenting part of foetus relative to maternal pelvis
 Occipitoanterior (OA) – common presentation (left OA is most common – occiput as reference point)
 Occipitoposterior (OP) – may cause prolonged second stage of labour (although most spontaneously rotate to OA)
 Occipitolateral (OL) – leads to arrest of dilatation
 Foetal presentation – foetal body part closest to the birth canal
 Breech (bottom or legs first)
 Cephalic (head first)
 Transverse (shoulder first)
 Compound (where a limb presents with another presenting body part)
 Attitude – flexion/extension of foetal head relative to shoulders
 Engagement – baby’s head engages when the maximum diameter is at or has passed through the pelvic brim (usually 34-36 weeks)
 Station – position of presenting part relative to ischial spines (as determined on vaginal examination)

Stages of labour
Labour is separated into four stages:
FIRST STAGE
 Latent phase – infrequent, irregular, uterine contractions
 Characterised by slow cervical dilatation (usually to 3cm) and effacement of cervix
 Active phase – painful, regular, uterine contractions (every two-to-three minutes, lasting up to a minute)
 Characterised by rapid cervical dilatation (approximately 1cm/hour)
 Contractions strongest at uterine fundus, and weakest at lower segment
 The commonest cause of arrest of active labour (after active stage) is incoordinate uterine action
 Associated with ROP position in primigravid women
 Requires augmentation of labour by oxytocin
SECOND STAGE
 Second stage occurs from full dilatation of cervix to delivery of baby
 Mother feels a desire to bear down and push with each contraction
THIRD STAGE
 Third stage occurs from delivery of baby to separation and expulsion of placenta
 Signs of placental separation:
 Cord lengthening  rush of blood (retroplacental haemorrhage)  fundus rising  uterus becomes globular as it contracts
 The contraction of placenta is essential to establish haemostasis; the absence of such is called uterine atony
 Oxytocin should be administered after delivery of the anterior shoulder in anticipation of placental delivery
 Significantly reduces the risk of post-partum haemorrhage
FOURTH STAGE
 Fourth stages is defined as the first postpartum hour
 An important stage for clinical management:
 Monitor vital signs
 Repair lacerations and bleeding
 Ensure uterus is contracted (to prevent bleeding)
 Inspect placenta for completeness (to prevent retained products of conception)
 Inspect umbilical cord for presence of two arteries and one vein
Stages of labour
STAGE NULLIPAROUS MULTIPAROUS
First 10 to 18 hours 6 to 12 hours

Second Less than 3 hours Less than 30 minutes

Third Less than 30 minutes Less than 30 minutes

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DELIVERY

Cardinal movements of foetus

PROCESS
 1) Flexion of head (reduces surface area of head relative to pelvic inlet)
 2) Internal rotation of the head (positions head into long axis of pelvic outlet)
 3) Extension and delivery of head (with face posterior relative to mother)
 4) Restitution of head (to realign head and shoulders)
 5) Delivery of shoulders and body
LABOUR MONITORING
During the active stage of labour (in a women without risk factors):
 Foetal heart monitoring every 15 minutes (by auscultation or electronically)
 Maternal general observations every 1 hour
OBSTETRIC PAIN
 Uterine contractions and cervical dilation result in visceral pain (T10-L1)
 Descent of foetal head (pressure on vagina and perineum) results in somatic pain (S2-S4)
 Pethidine (or other opiates ) is the main analgesic (if epidural is not considered)
 Epidural requires continuous CTG monitoring

Induction of labour
INDUCTION OF LABOUR
Induction of labour is the artificial initiation of labour in a pregnant women prior to spontaneous initiation to deliver foetus and
placenta.
 Indicated if risk of continuing pregnancy exceeds risks associated with inducing pregnancy
 Induction success depends on the cervix being soft, effaced, and dilated (‘cervical ripening’ – measured by the Bishop score)
METHOD
 Cervical ripening:
 Intravaginal prostaglandin (insert or gel) , or
 Foley catheter (mechanical)
 Stimulation of contraction:
 Amniotomy – artificial rupture of membranes stimulates prostaglandin synthesis and secretion (indirect)
 Oxytocin – stimulates uterine contraction (direct)
INDICATIONS
 Prolonged pregnancy (most common)
 Premature rupture of membranes
 Maternal health problems (hypertension, pre-eclampsia, diabetes)
 Foetal factors (e.g. foetal death or placental insufficiency)
COMPLICATIONS
 Failure to achieve labour and/or vaginal birth (progression to caesarean section)
 Uterine hyperstimulation (leading to foetal compromise or uterine rupture)
 Maternal side effects to medications
 Uterine atony (and post-partum haemorrhage)
AUGMENTATION OF LABOUR
Augmentation is the promotion of contractions if contractions are inadequate and descent of foetus fails to occur.
 Treatment: oxytocin
 Side effects are similar to induction

Operative obstetrics
OPERATIVE VAGINAL DELIVERY
Operative vaginal delivery is the use of instrumentation to assist in a vaginal delivery (if foetal head is positive in station).
INDICATIONS
 Foetal factors :
 Foetal compromise/abnormal foetal heart rate
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 Poor progression/prolonged second stage of labour (may be due to poor contractions or failure of foetal head to rotate)
 Maternal factors:
 Requirement to avoid voluntary expulsive effort (e.g. cardiac or cerebrovascular disease)
 Exhaustion or lack of co-operation
CLASSIFICATION

Operative obstetrics
FORCEPS VACUUM EXTRACTION (VENTOUSE)
Method Mechanical traction of presenting body part via forceps Suction of foetal head; aids maternal pushing

Advantages  Higher overall success  Easier

 Less anaesthesia required

Disadvantages  Greater incidence of maternal injury  Maternal pushing is required

Complications  Maternal: direct issue injury  Foetal: direct tissue injury

 Foetal: direct tissue injury

LACERATIONS

CLASSIFICATION
 First-degree – involves skin and vaginal mucosa but not underlying fascia or muscle
 Second-degree – involves fascia and muscles of perineal body but not the anal sphincter
 Third-degree – involves the anal sphincter but does not extend through it
 Fourth-degree – extends through the anal sphincter into the rectal mucosa
 Labial tears – common (heal quickly, and suturing is rarely helpful)

Note: controlling the extension of the head and holding the perineum during delivery helps to decrease laceration risk.
EPISIOTOMY
An episiotomy is an incision in the perineal body at the time of delivery (a controlled second-degree laceration).
 Midline – heals better but not as effective
 Mediolateral – more painful but reduced risk of extensive tear
INDICATIONS
 Routine use not recommended (considered in instrumental deliveries or deliveries that have a high risk of laceration – e.g. breech)
COMPLICATIONS
 Surgical risks
 Extension of incision into anal sphincter or rectum (and consequent fistula or incontinence)
CAESAREAN SECTION
A caesarean section is an abdominopelvic surgical procedure to deliver the baby extra-vaginally.
 Associated with surgical risks and maternal mortality (<0.1%)
INDICATIONS
 Maternal: obstruction, active herpes, cervical cancer, uterine surgery (e.g. previous CS), maternal illness (esp. eclampsia), death
 Maternal-foetal : cephalopelvic disproportion, failure to progress, placental previa/placental abruption, prolonged pregnancy
 Foetal: foetal distress, Rhesus incompatibility, cord compression/prolapse, malpresentation
CLASSIFICATION
 Skin
 Transverse (Pfannensteil) – slower entry but improved strength and cosmesis
 Vertical midline – rapid entry but increased dehiscence
 Uterine
 Classical (rare) – vertical incision in thick, contractile, segment of uterus
 Low vertical (rare) – vertical incision in lower segment of uterus (for very pre-term infants with poorly developed lower segment)
 Low transverse (most common) – transverse incision in thin, non-contractile, lower segment of uterus
Vaginal birth after caesarean (VBAC)
A trial of (normal) labour can be recommended after a previous low transverse incision.
 Success rate varies depending on the indication of the previous surgery (typically, 70% VBAC)
 There is a small risk of uterine rupture (<1% for low transverse incisions) – indication for continuous CTG throughout labour
 Contraindicated if increased stress on uterus (other uterine surgery, multiple gestation, non-vertex, placental previa)
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Medical complications of pregnancy

NAUSEA AND VOMITING IN PREGANCY
Morning sickness
Morning sickness affects the majority of pregnant women and is typically limited to the first trimester (although may persist).
Hyperemesis gravidarum
Hyperemesis gravidarum is a syndrome of persistent vomiting, acute starvation (with ketosis), and weight loss.
 As opposed to morning sickness, typically persists past the first trimester
 Associated with a multi-pregnancy and a significantly increased risk of IUGR
DIAGNOSIS
 Rule out molar pregnancy – β-hCG and U/S
 Assess for deficiencies: U&Es (esp. potassium), LFTs, TFTs, urinalysis (esp. ketones)
TREATMENT (AS FOR MORNING SICKNESS)
 Non-pharmacological – frequent small meals and stress reduction
 Pharmacological:
 In all patients – vitamin B6 (± thiamine)
 If mild-to-moderate – doxylamine (an antihistamine)
 If severe – metoclopramide , ondansetron, or promethazine
 If dehydrated – IV fluids and nutritional supplementation
HYPERTENSION IN PREGNANCY
Chronic and gestational hypertension
CLASSIFICATION
 Chronic (persistent) hypertension
 Present before conception and at less than 20 weeks gestation
 Up to 33% of patients develop super-imposed pre-eclampsia
 Gestational hypertension
 Present after 20 weeks gestation (without significant proteinuria )
 Up to 25% of patients develop super-imposed pre-eclampsia
TREATMENT
 Treat with appropriate antihypertensives (ABCs – α-blockers, β-blockers, CCBs)
 ACEI/ARBs – can cause uterine ischaemia (and are teratogenic)
 Diuretics – can cause low plasma volume (and uterine ischaemia)
Pre-eclampsia and eclampsia
Preeclampsia is a multi-system disorder characterised by hypertension and involvement of ≥1 other organ systems and/or the foetus.
CLASSIFICATION
 Pre-eclampsia – the presence of new onset hypertension (after 20 weeks gestation) and at least one of:
 Renal: proteinuria (after 20 weeks gestation), oedema, oliguria, or raised creatinine
 Liver: raised LFTs, or severe RUQ/epigastric
 Neurological: hyperreflexia, headache, visual disturbance (indicate imminent eclampsia)
 IUGR
 Eclampsia – new onset seizures in a women with pre-eclampsia
 HELLP syndrome – a variant of severe pre-eclampsia with poor prognosis
 Characterised by a thrombotic microangiopathy occurring in late pregnancy
 Defined by laboratory evidence of HELLP – Haemolysis, Elevated LFTs, Low Platelets
FEATURES
 Risk factors: nulliparity, multi-pregnancy, personal or family history, extremes of age, new sexual partner, chronic hypertension,
obesity, pre-existing renal disease
CLINICAL PRESENTATION
 Mild pre-eclampsia – asymptomatic
 Severe pre-eclampsia – headache, visual changes, RUQ/epigastric pain, and hyperactive reflexes
 Associated with acute fatty liver
 Eclampsia – seizures (typically preceded by symptoms of severe pre-eclampsia)
DIAGNOSIS
 Labs: CBC, U&E and uric acid, LFTs, urinalysis with ACR, coagulation (if anaesthesia planned)
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TREATMENT
 Pre-eclampsia:
 Mild – admission and expectant management with control of blood pressure:
 Agents: labetalol, nifedipine , hydralazine
 Delivery: when risk of pregnancy is greater than risk of delivery (around 34 to 36 weeks gestation)
 Severe – stabilise and deliver baby (induction of labour or caesarean section )
 Adjunct therapy – IV magnesium sulphate (neuroprotective for infant; anti-convulsant/anti-hypertensive for mother)
 Dose: 4g loading dose then 2g an hour (continue up to 24 hours post-delivery)
 Treat magnesium toxicity (weakness, flushing, cardiac and respiratory arrest) with IV calcium gluconate
 Prevention – aspirin (in pregnancies in patients with history of pre-eclampsia or patients at a high risk for pre-eclampsia)
 Eclampsia:
 First aid (ABCs)
 Supplemental oxygen if hypoxaemic
 Aggressive antihypertensives – labetalol , nifedipine , hydralazine
 Seizure prevention – IV magnesium sulphate ( diazepam) (continue up to 24 hours post-delivery/post-seizure))
 Definitive treatment – immediate delivery (irrespective of gestational age)
DIABETES IN PREGNANCY
Pre-gestational diabetes
Pre-gestational diabetes is the state of having diabetes prior to the onset of pregnancy.
CLINICAL NOTES
 If already on oral medication, typically switch to insulin therapy (continuing oral medication is controversial)
 Tight glycaemic control is essential (insulin dose may need adjustment throughout pregnancy)
 Poor control leads to risk of miscarriage, neonatal hypoglycaemia, congenital abnormality, macrosomia/IUGR, pre-term
labour, polyhydramnios
 Poor control associated with operative delivery , pre-eclampsia/eclampsia , DKA or HHS, infection in the mother
 Monitoring:
 Monthly HbA1c
 Oral glucose tolerance tests
 Foetal surveillance (esp. growth and congenital abnormality)
 Maintain normoglycemia during delivery and post-partum with insulin drip
 Induction of labour or caesarean section if poor maternal glucose control (or evidence of macrosomia or other morbidities)
 Insulin requirements dramatically drop with expulsion of placenta (source of insulin antagonists )
Gestational diabetes
Gestational diabetes is the onset of diabetes in pregnancy (typically in the third trimester).
 Anti-insulin factors produced by the placenta and high maternal cortisol lead to peripheral insulin resistance
CLINICAL PRESENTATION
 Typically, asymptomatic
 May present with oedema, polyhydramnios, or macrosomia
DIAGNOSIS
 Universal screening (antenatal bloods) – HbA1c
 All pregnant women between 24 and 28 weeks gestation:
 Screening with 1-hour 50g oral glucose tolerance test (‘polycose test’) , positive if:
 1hr post-glucose >11.1mmol/L
 Confirm with 2-hour 75g oral glucose tolerance test (or in high risk women), positive if either:
 Fasting glucose >5.5mmol/L
 2hr post-glucose >9mmol/L
TREATMENT
 First-line : diet, regular exercise, and strict glucose monitoring
 Second-line: insulin therapy (if glycaemic targets not met within two weeks of lifestyle changes)
 Foetal surveillance : ultrasound (esp. growth)
COMPLICATIONS
 Risk of recurrence
 More than 50% of patients develop T2DM later in life (screen post-partum)
GROUP B STREPTOCOCCUS IN PREGNANCY
Group B streptococcus (Streptococcus agalactiae) is found in the vagina (and rectum) in about 25% of all healthy pregnant women.
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 Not a risk factor for mother; however, can be vertically transmitted to foetus (neonatal sepsis, meningitis, pneumonia, and death )
FEATURES
 Risk factors (neonatal disease): preterm labour, PROM, positive GBS screen, previous infant with GBS disease
DIAGNOSIS
 Screening at 35-37 weeks gestation with vaginal and anorectal swabs for GBS culture
TREATMENT
 Antibiotics for GBS prophylaxis (at delivery) – penicillin G IV (or vancomycin if allergic)
 Indicated if: positive GBS screen (or unknown), GBS in urine, or previous infant with GBS disease
URINARY TRACT INFECTION
Urinary tract infection is the most common medical complication of pregnancy.
 Asymptomatic bacteriuria – should be treated in pregnancy due to increased risk of preterm labour and upper UTI
 For diagnosis and treatment see Nephrology (treated as a complicated lower or upper UTI )
COMMON INFECTIONS DURING PREGNANCY
Common infections during pregnancy
DISEASE TRANSMISSION NEONATAL PRESENTATION DIAGNOSIS TREATMENT/PREVENTION
Toxoplasmosis Transplacental  Classic triad: Serological  Pyrimethamine + sulfadiazine
(exposure via  Hydrocephalus  Avoid exposure to cat faeces
contact with cat  Intracranial calcification
faeces)  Chorioretinitis

Rubella Transplacental (1st  Sensorineural deafness Serological  Symptomatic

trimester)  Eye abnormalities (cataracts)  Immunisation (but not during pregnancy –
 Congenital heart disease (PDA) live attenuated virus)
 Purpuric rash (‘blueberry muffin’ lesion)
 Mental retardation

CMV Transplacental  Petechial rash Serological  Postpartum ganciclovir

 Periventricular calcification
 Hearing loss
 Seizures

HSV At delivery (if active  Skin/eye/mouth infection Serological  Acyclovir

lesions)  Life-threatening CNS/systemic infection  C/S (if active HSV lesions)

Chicken pox Transplacental  Congenital varicella (cutaneous scars Clinical (or  Varicella IG (VZIG) (if mother exposed
and IUGR; rarely limb aplasia, vesicle PCR) and non-immunised)
chorioretinitis, cataracts, mental
retardation)

HIV In utero, at  Often asymptomatic (or recurrent ELISA  HAART therapy

delivery, or via infections due to immunocompromise)  C/S (if viral load >1000)
breast milk  Avoid breastfeeding

Syphilis At delivery  Variable (often stillbirth) VDRL  Penicillin G

 Congenital syphilis
 Saber shins
 Saddle nose
 CNS involvement
 Hutchinson triad: peg-shaped central
incisors, deafness, interstitial keratitis

Listeria Transplacental  Premature delivery with amnionitis Blood, cervix,  Amoxicillin + gentamicin
(contaminated  Neonatal sepsis and placenta
milk, cheese, deli  Meningitis culture (consider
meats)  Disseminated granulomas neonatal LP)

TORCH syndrome
TORCH syndrome refers to infection of a developing foetus or new-born by any of a group of infectious agents:
 Toxoplasma gondii (parasite)
 Other (GBS, Listeria, Syphilis, Varicella Zoster, Parvovirus)
 Rubella
 Cytomegalovirus
 HSV
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CLINICAL NOTES
 In most cases, primary infection of the mother presents most risk of TORCH to the foetus
 Presents in neonates as fever, poor feeding , rash, small for gestational age , hepatosplenomegaly , and often jaundice
 The effects of congenital infections may not become apparent until the child is older
RH ISOIMMUNISATION

PATHOPHYSIOLOGY
 In Rhesus-negative women, exposure to Rhesus-positive foetus can lead to production of anti-Rhesus antibodies
 The risk of isoimmunisation is approximately 15% (only occurs after first trimester)
 These anti-Rhesus antibodies (IgG) can cross the placenta, leading to haemolysis of foetal RBCs in Rhesus-positive foetuses
 This is called erythroblastosis fetalis (and occurs only in Rhesus-negative women)
DIAGNOSIS
 Rhesus status of mother and antibody titre (>1:16 is positive)
 Kleihauer-Betke test – used to estimate extent of fetomaternal haemorrhage
 Estimates volume of foetal blood that has entered the maternal circulation
 Amniocentesis – for evidence of foetal haemoptysis (bilirubin)
 Ultrasound – MCA doppler (assess degree of anaemia)
TREATMENT
 In severe cases, initiate pre-term delivery when foetal lungs are mature
 Prior to delivery, consider intrauterine blood transfusion to correct low foetal haematocrit
PREVENTION
 All Rhesus-negative women (with negative antibody ) should be offered anti-D antibody if:
 28 and 34 weeks gestation (routine)
 Post-partum (and delivered a Rhesus-positive baby)
 Miscarriage, abortion, ectopic pregnancy, instrumentation, maternal trauma , or obstetric haemorrhage

Note: anti-D can be dose adjusted by quantification of fetomaternal haemorrhage .

COMPLICATIONS
 Hydrops fetalis (oedema in at least two foetal compartments due to foetal heart failure secondary to anaemia)
 Erythroblastosis fetalis (moderate to severe immune-mediated haemolytic anaemia)
 Foetal hypoxia , acidosis, kernicterus, prematurity , and death

Obstetric complications of pregnancy

ECTOPIC PREGNANCY
Ectopic pregnancy is defined as embryo implantation outside of the uterine cavity.
 Most commonly in the fallopian tube: ampullary (70%), isthmic (10%), fimbrial (10%)
 Can also be abdominal, ovarian, or cervical
FEATURES
 Occurs in 1% of pregnancies
 Leading cause of death in first trimester
AETIOLOGY
 Previous ectopic pregnancy
 Gynaecologic
 Current IUD use
 History of PID or salpingitis
 IVF pregnancies
 Anatomic abnormalities
CLINICAL PRESENTATION
 Classic triad ( PAVE) – Pain (abdominal ± peritonism),
Amenorrhoea, Vaginal Bleeding suggests Ectopic pregnancy
 Also associated with fever
 Examination: palpable adnexal mass, cervical motion tenderness
DIAGNOSTIC AND TREATMENT APPROACH
 β-hCG – absence of appropriate doubling
 U/S – empty uterus and/or fluid in rectouterine pouch
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 Laparoscopy – sometimes used for definitive diagnosis

 Medical options – methotrexate (if clinically stable, <3cm, and no foetal heart beat)
 Surgical options – typically, salpingectomy or salpingostomy
 Anti-D (Rhesus) antibody – if mother is Rh negative
COMPLICATIONS
 Tubal rupture and haemoperitoneum (an obstetric emergency)
PRETERM LABOUR
Preterm labour is the delivery of a baby at fewer than 37 weeks gestational age.
 Complicates approximately 10% of pregnancies and is the most common cause of neonatal mortality
FEATURES
 Most patients have no identifiable risk factors
 Risk factors: previous or family history, previous cervical instrumentation (LLETZ or biopsy), short cervical length (transvaginal
U/S)
AETIOLOGY
 Idiopathic (most common)
 Maternal: infection (upper UTI, untreated bacteriuria, chorioamnionitis, bacterial vaginosis), chronic illness, low SES, obesity
 Maternal-foetal: PROM (common), polyhydramnios, placenta previa/placental abruption, placental insufficiency (e.g. smoking)
 Foetal: multiple gestation, congenital abnormalities, foetal hydrops, stress
 Uterine: incompetent cervix, excessive enlargement, anatomic malformation
CLINICAL PRESENTATION
 Presents with menstrual-like cramps , onset of low back pain , pelvic pressure , and new vaginal discharge or bleeding
DIAGNOSIS
 Clinical diagnosis – requires:
 Symptoms: regular uterine contractions
 Signs: dilated/effaced cervix on examination
 Sterile speculum exam – to exclude PROM
 Ultrasound – to verify gestational age (and assess presentation, amniotic fluid, and exclude foetal or uterine abnormality)
 Infectious screen – laboratory and microbiology
TREATMENT
 Treatment of underlying cause
 Five-step protocol:
 Initial – transfer to appropriate facility; consider IV fluids, analgesia, and prophylactic antibiotics (for GBS/PROM)
 Tocolysis (suppression of labour) – CCB (nifedipine)
 Does not inhibit preterm labour completely, but may delay delivery for approximately 48 hours
 Neuroprotection – magnesium sulphate
 Enhancement of foetal pulmonary maturity – betamethasone valerate (corticosteroid)
 Reduces incidence and severity of respiratory distress syndrome
 Cervical cerclage (if cervical incompetence) – placement of cervical sutures at level of internal os
 Removed in the third-trimester to allow for vaginal delivery
OUTCOMES
 Prematurity is the leading cause of perinatal morbidity and mortality, although:
 >10% survival from 24 weeks  90% survival at 30 weeks or 1500 grams  99% survival at 33 weeks or 2000 grams
 Morbidity:
 Respiratory – asphyxia, hypoxia, RDS, bronchopulmonary dysplasia
 Cardiovascular – patent ductus arteriosus
 Other – intraventricular haemorrhage, thermal instability, retinopathy of prematurity, necrotising enterocolitis
PREMATURE RUPTURE OF MEMBRANES

DEFINITIONS
 Spontaneous ROM – occurs after or at the onset of labour
 Premature ROM (PROM) – rupture of membranes prior to labour at any gestational age
 Prolonged ROM – >24 hours elapsed between rupture of membranes and onset of labour
 Preterm ROM – ROM occurring before 37 weeks gestation
 Pre-term premature ROM (PPROM) – rupture of membranes before 37 weeks gestation and prior to onset of labour
 Associated with previous cervical surgery
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CLINICAL PRESENTATION
 Patients report a “gush” of clear or blood-tinged amniotic fluid (± uterine contractions)
DIAGNOSIS
 Sterile speculum exam – pooling of fluid in the vaginal vault
 May observe fluid leaking out of cervix on cough/Valsalva (‘cascade’)
 Nitrazine paper test – paper turns blue (indicating alkaline pH of amniotic fluid)
 Fern test – a ferning pattern is seen under microscopy after amniotic fluid dries on a glass slide
 Imaging – ultrasonography
 Amniosure/Partosure – non-invasive tests measuring PAMG-1 (protein in amniotic fluid – highly specific/sensitive for PROM)
 Foetal fibronectin test – non-invasive tests for foetal fibronectin (binds foetal sac to uterine lining – moderate utility for PROM)
TREATMENT
 Admit for clinical monitoring
 Monitor vitals and daily WBC count
 Minimise infection risk (do not conduct bimanual examination)
 Obtain vaginal cultures (to assess for GBS)
 Treatment (dependent on gestation):
 <26 weeks – individual consideration with counselling of parents regarding risks of preterm infants
 26-34 weeks – expectant management (as prematurity complications are significant)
 34-36 weeks – ‘grey zone’ (risk of death from RDS and neonatal sepsis is the same)
 >37 weeks – induction of labour (risk of death from sepsis is greater than RDS)
 Additional:
 Evidence of foetal pulmonary immaturity – betamethasone valerate (corticosteroid)
 Suggested by lecithin:sphingomyelin ratio of amniotic fluid (less than 2:1 indicates lung immaturity)
 Consider broad-spectrum antibiotics (controversial) – may delay time to onset of labour
 Deliver urgently if evidence of foetal distress and/or chorioamnionitis
OUTCOMES
 90% of women with PROM at 28-34 weeks gestation go into spontaneous labour within one week
 50% of women with PROM at <26 weeks gestation go into spontaneous labour within one week
COMPLICATIONS
 Pre-term labour, chorioamnionitis, placental abruption, cord prolapse
PROLONGED PREGNANCY
Prolonged pregnancy is defined as >42 weeks gestation.
 Typically, idiopathic (although associated with severe defects)
CLINICAL PRESENTATION
 Post-maturity syndrome (10-20% of cases)
 Characteristic appearance – dry, discoloured, skin; overgrown nails and scalp hair; reduced subcutaneous fat and soft tissue
 Associated with increased risk of : meconium aspiration, macrosomia, placental insufficiency, foetal distress, and NICU admissions
TREATMENT
 Induction of labour (offered after 41 weeks gestation) or expectant management (with increased clinical monitoring)
OUTCOMES
 Associated with 2-3 times higher risk of perinatal mortality (due to progressive uteroplacental insufficiency)
INTRAUTERINE FOETAL DEATH (STILLBIRTH)
A stillbirth is the death of a foetus that either:
 Occurred beyond 20 weeks gestational age , or
 Comprised of a foetus weighing greater than 400 grams
FEATURES
 Occurs in 1% of pregnancies
 Aetiology:
 50% idiopathic
 50% secondary to maternal or foetal complications
CLINICAL PRESENTATION AND DIAGNOSIS
 Presentation: decreased perception of foetal movement by mother
 Examination: fundal height and maternal weight not increasing; absent foetal heart on Doppler (although not diagnostic)
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 Ultrasound (diagnostic) : no foetal heart rate or movement; classical anatomic findings

TREATMENT
 Identify secondary causes and treat as indicated
 May require post-mortem investigation of the foetal death
 Induction of labour (as usual)
 Monitor for maternal coagulopathy (10% risk of DIC)
INTRAUTERINE GROWTH RESTRICTION (IUGR)
IUGR is defined as an infant weight <10th percentile (for gestation) or delivery at <2500g body weight.
AETIOLOGY
 Approximately 50% unknown
 Maternal – various (e.g. malnutrition, smoking, drug abuse, chronic disease)
 Previous IUGR is the most important risk factor
 Maternal-foetal – any disease that causes placental insufficiency (e.g. pre-eclampsia)
 Foetal – TORCH, multiple gestation, congenital abnormalities
CLINICAL PRESENTATION
 Symmetric – occurs early in pregnancy (associated with congenital abnormalities or TORCH infection)
 Asymmetric – occurs late in pregnancy (associated with placental insufficiency)
 Head is spared; therefore, more favourable prognosis than symmetric
DIAGNOSIS
 Fundal height
 Imaging:
 U/S – foetal measurement
 Doppler – analysis of umbilical cord blood flow
TREATMENT
 Prevention via risk modification prior to pregnancy is ideal (smoking, alcohol, nutrition, maternal illness)
 Foetal monitoring
 Enhancement of foetal pulmonary maturity – betamethasone valerate (corticosteroid)
 Assisted delivery ( induction of labour or Caesarean section is commonly indicated)
COMPLICATIONS
 Increased risk of perinatal morbidity and mortality
MACROSOMIA
Macrosomia is defined as an infant weight >90th percentile (for gestation) or delivery at >4000g body weight.
FEATURES
 Risk factors: maternal obesity, gestational diabetes, past history, prolonged gestation, multiparity
CLINICAL PRESENTATION
 Cephalopelvic disproportion and birth injuries (shoulder dystocia, foetal bone fracture)
 Increased risk of perinatal mortality
DIAGNOSIS
 Fundal height
 Imaging:
 U/S – foetal measurement
TREATMENT
 Prophylactic caesarean section is commonly indicated
Differential diagnosis for incorrect uterine size for dates
Differential diagnosis for incorrect uterine size
SMALL FOR DATES LARGE FOR DATES

 Date miscalculation  Date miscalculation

 IUGR  Multiple gestation
 Foetal demise  Macrosomia
 Oligohydramnios  Polyhydramnios
 Abnormal lie  Fibroids
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POLYHYDRAMNIOS AND OLIGOHYDRAMNIOS

Polyhydramnios versus oligohydramnios
POLYHYDRAMNIOS OLIGOHYDRAMNIOS
Definition Excessive amniotic fluid volume Inadequate amniotic fluid volume
 Amniotic fluid index (AFI) of >25cm  Amniotic fluid index (AFI) of <5cm

Aetiology Maternal: Maternal:

 Diabetes mellitus  Prolonged pregnancy
 Rhesus incompatibility  Placental insufficiency
Foetal:  Pre-eclampsia
 Congenital abnormalities  PROM
 Intrauterine infections (TORCH) Foetal:
 Twin-to-twin transfusion syndrome  Congenital abnormalities
 Intrauterine infections (TORCH)
 Twin-to-twin transfusion syndrome

Epidemiology 1% of pregnancy 5% of pregnancy (10% of prolonged pregnancy)

Clinical  Uterine size large for gestational age  Uterine size small for gestational age
presentation  Complications:  Complications:
 Pre-term labour  Foetal abnormality (up to 25% of cases – esp. pulmonary hypoplasia)
 Foetal malpresentation  Intrauterine growth restriction
 Cord prolapse  Intrauterine compression (Potter sequence)
 Pulmonary hypoplasia; craniofacial and limb anomaly
 Cord compression

Treatment  Treat the underlying cause  Treat the underlying cause

 Amnioreduction (drainage of fluid via amniocentesis)  Amnioinfusion (administer fluid via amniocentesis)
 Delivery if close to term

Outcome  2-5x risk of perinatal mortality  40x risk of perinatal mortality

Obstetrical haemorrhage
Obstetrical haemorrhage is defined as vaginal bleeding from 20 weeks gestation to term .
PLACENTA PREVIA
Placenta previa is abnormal placental implantation relative to the cervical os.
 Total – placenta covers cervical os
 Marginal – placenta extends to the margin of os
 Low-lying – placenta is in close proximity to os
FEATURES
 Occurs in 1 in 200 pregnancies
 Risk factors: personal history, multiple gestation, uterine abnormalities, previous uterine surgery, advanced maternal age
CLINICAL PRESENTATION
 PAINLESS vaginal bright red bleeding (recurrent) – may cease spontaneously, but can become catastrophic
 Not typically associated with foetal distress
DIAGNOSIS
 Transvaginal (or abdominal) U/S (do not perform a vaginal examination)
TREATMENT
 Goal – to keep pregnancy intrauterine until risk of delivery is less than risk of continued pregnancy
 If gestation less than 37 weeks and minimal bleeding :
 Expectant management (can admit to hospital for monitoring if accessibility is an issue)
 Limit physical activity and sexual intercourse
 Consider enhancement of foetal pulmonary maturity – betamethasone valerate (corticosteroid)
 Delivery (caesarean section ) at 37 weeks gestation or if haemorrhage
 If gestation past 37 weeks or significant bleeding :
 Treat as for hypovolaemic shock (if indicated)
 Caesarean section
COMPLICATION
 Risk of recurrence
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PLACENTAL ABRUPTION
Placental abruption is premature separation (before delivery) of a normally implanted placenta from the uterus.
CLASSIFICATION
 Total (foetal death inevitable) versus partial
 External/apparent (blood dissects downward to cervix) versus inward/concealed (blood dissects upward toward foetus)
FEATURES
 Occurs in 1 in 100 pregnancies (antenatal bleeding should be assumed abruption until proven otherwise)
 Risk factors: personal history, multiparity, pre-eclampsia, excessive uterine stimulation
CLINICAL PRESENTATION
 PAINFUL vaginal dark red bleeding – that doesn’t cease spontaneously (may be associated with shock)
 The pain is sudden onset, constant, and localised to lower back and uterus
 Must be distinguished from painLESS placental edge bleeding (the most common cause of antepartum haemorrhage)
 Associated with foetal distress
 Examination: uterine tenderness and hypercontractility
DIAGNOSIS
 Clinical diagnosis (U/S not sensitive)
TREATMENT
 Mild abruption and less than 37 weeks gestation – expectant management with admission and close monitoring
 If past 37 weeks gestation – induction of labour
 Moderate to severe abruption – immediate delivery
 Treat as for hypovolaemic shock (if indicated)
 Vaginal delivery with amniotomy – if mother and foetus are stable
 Caesarean section – if mother unstable or foetal distress
COMPLICATIONS
 Risk of recurrence
 Hypovolaemic shock
 DIC occurs in 10% of patients
VASA PREVIA
Vasa previa is bleeding at rupture of membranes from unprotected foetal vessels that pass over the cervical os.
 Associated with succenturiate placental lobe or velamentous insertion of cord into membranes of placenta
FEATURES
 Occurs in 1 in 5000 pregnancies (higher in twin pregnancies)
CLINICAL PRESENTATION
 PAINLESS vaginal bleeding (of FOETAL blood)
 Associated with foetal distress (bradycardia rather than tachycardia)
DIAGNOSIS
 Transvaginal U/S with Doppler – to visualise vessels over cervical os
 Apt test (NaOH mixed with blood) – can immediately determine if source of bleeding is foetal (pink) or maternal (yellow)
 Blood smear – look for nucleated red blood cells (in cord but not maternal blood)
TREATMENT
 Emergency caesarean section (since bleeding is from foetus – a small amount of blood loss has catastrophic consequences)
 If diagnosed prior to bleeding:
 Enhancement of foetal pulmonary maturity – betamethasone valerate (corticosteroid)
 Caesarean section at 35 weeks gestation
COMPLICATIONS
 50% perinatal mortality (increasing if ROM) – infant death from exsanguination
PLACENTAL INVASION

CLASSIFICATION
 Placenta accreta – placenta attach to myometrium (deeper than normal) (associated with  risk of heavy bleeding during delivery)
 Placenta increta – placenta penetrates myometrium
 Placenta percreta – placenta penetrates uterine serosa  Risk factors : previous caesarean section or placenta previa
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Abnormal labour and delivery

MULTIPLE GESTATIONS
Multiple gestations occurs when there is multiple foetuses in a single pregnancy.
 Dizygotic (fraternal) twins – more common (IVF is a risk factor)
 Monozygotic (identical) twins – less common (occurs at a constant rate
worldwide)
CLASSIFICATION
 Classified by the number of amniotic sacs and placentas (in twin pregnancies)
 Monoamnionic monochorionic
 Diamnionic dichorionic
 Diamnionic monochorionic
CLINICAL PRESENTATION
 Presents as rapid uterine growth or excessive maternal weight
DIAGNOSIS
 Labs: β-hCG, human placental lactogen, and MSAFP are elevated
 Imaging – ultrasound (definitive)
TREATMENT
 Antenatal foetal surveillance for IUGR
 Management by an obstetrician
 Typically, delivered by caesarean section (but vaginal delivery in certain cases)
COMPLICATIONS
 Maternal – much higher rate of obstetric complications (esp. placenta previa)
 Foetal – twin-to-twin transfusion syndrome, IUGR, preterm labour, and a higher incidence of congenital abnormality
 Spontaneous reduction to singleton occurs in one quarter of cases of twins diagnosed before seven weeks gestation
Twin-to-twin transfusion syndrome
Twin-to-twin transfusion syndrome affects monochorionic twins (10% of patients), where arterial blood from donor twin passes
through placenta into vein of recipient twin.
CLINICAL PRESENTATION
 Donor twin: IUGR, oligohydramnios, shock
 Recipient twin: fluid overload, polyhydramnios, jaundice
DIAGNOSIS
 Ultrasound with Doppler
TREATMENT
 Amnioreduction (of recipient twin)
 Amnioinfusion (of donor twin)
 Intrauterine blood transfusion (to donor twin)
 Laparoscopic occlusion of placental vessel s (to alleviate flow inequalities)
MALPRESENTATION
Malpresentation occurs when a foetal body part (other than the head) is the presenting part during delivery
 Most commonly a breech presentation – foetal buttocks or lower extremity (also face or transverse/shoulder presentations )
FEATURES
 Occurs in 5% of pregnancies (and is common in early pregnancy – typically, spontaneously resolves by 36 weeks)
 Risk factors: uterine shape abnormality, prematurity, oligohydramnios, placenta previa
CLASSIFICATION
 Breech presentation:
 Complete (10%) – hips and knees both flexed (buttocks presenting)
 Frank (60%) – hips flexed, knees extended (buttocks presenting)
 Incomplete (30%) – knee or feet presenting
TREATMENT
 Typically, spontaneously resolve
 External cephalic version (ECV) – repositioning of singleton foetus by transabdominal manipulation (if not in active labour)
 Trial of breach vaginal delivery (contraindicated if cord presentation or incompatible with vaginal delivery)
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 Elective caesarean section

OUTCOMES
 Regardless of delivery – associated with lower birth weights and higher perinatal mortality
SHOULDER DYSTOCIA
Shoulder dystocia occurs when the anterior foetal shoulder is impacted above the symphysis pubis (after the head has been delivered).
 Life threatening emergency (due to asphyxia)
FEATURES
 Risk factors : macrosomia, maternal obesity or diabetes, previous history of shoulder dystocia
CLINICAL PRESENTATION
 Prolonged second stage of labour
 Turtle sign – head retracts against perineum
 Lack of spontaneous restitution
TREATMENT
 In the event of dystocia, be the mother’s HELPER (not in order):
 Help reposition (into lithotomy position)
 Episiotomy
 Leg elevation (into McRobert’s position – hyperflexed lithotomy position)
 Pressure (suprapubic) (in McRobert’s position)
 Enter the vagina (and attempt rotation – Wood’s screw manoeuvre)
 Reach for foetal arm
 Other options:
 Cleidotomy (deliberate fracture of neonatal clavicle)
 Zavanelli manoeuvre (replacement of foetus into uterine cavity and emergent caesarean section )
 Symphysiotomy
COMPLICATIONS
 Maternal: perineal injury, post-partum haemorrhage, uterine rupture
 Foetal:
 Hypoxic ischaemic encephalopathy (chest compression by vagina or cord compression by pelvis)
 Brachial plexus injury (90% resolve within 6 months)
 Fracture
 Death
FAILURE TO PROGRESS (DYSTOCIA)
Failure to progress is when the descent of the presenting foetal body part fails to occur in an appropriate time frame.
CLASSIFICATION
 First-stage arrest (>4 hour of <0.5cm/hr) – labour that fails to produce adequate rates of progressive cervical change
 Second-stage arrest (>1 hour with no descent during active pushing) – arrest of foetal descent
AETIOLOGY
 3Ps:
 Power (leading cause) – poor contractions or inadequate maternal expulsive effort
 Passenger – foetal position, size, anomalies
 Passage – pelvic structure (CPD) or soft tissue factors (e.g. tumours, full bladder or rectum, vaginal septum)
TREATMENT
 First-stage arrest – expectant management versus induction of labour/augmentation
 Second-stage arrest – assisted vaginal delivery (instrumentation) or caesarean section
COMPLICATIONS
 Infection (chorioamnionitis or maternal infection)
 Foetal compromise (from uterine hyperstimulation)
 Uterine rupture (from uterine hyperstimulation)
 Post-partum haemorrhage
 Neonatal mortality
AMNIOTIC FLUID EMBOLUS
Amniotic fluid embolus is a maternal disease caused by amniotic fluid debris in the maternal circulation (an anaphylactoid response).
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 Accounts for 10% of maternal deaths (esp. induced abortions and miscarriages)
 Often occurs at end of first stage of labour or immediately post-delivery
CLINICAL PRESENTATION
 Sudden onset of respiratory distress, haemodynamic instability, coagulopathy, and seizures
TREATMENT
 ICU with intensive supportive measures
CHORIOAMNIONITIS
Chorioamnionitis is infection of the chorion, amnion, and amniotic fluid by ascending infection of the vaginal flora.
 Tetrad of fever, tachycardia (maternal or foetal) , tenderness (uterine) , and foul discharge (associated with prolonged labour)
 Treated with IV antibiotics
UTERINE RUPTURE

FEATURES
 Risk factors: previous uterine scarring (e.g. C/S), hyperstimulation with oxytocin, grand multiparity
 Highest incidence with ‘classical caesarean incision’
CLINICAL PRESENTATION
 Typically, presents with prolonged foetal bradycardia
 Associated with acute onset of constant lower abdominal pain, vaginal or intra-abdominal haemorrhage, and cessation of contractions
TREATMENT
 Rule out placental abruption
 Immediate delivery for foetal survival
 Maternal stabilisation (may require hysterectomy )
UMBILICAL CORD PROLAPSE
Umbilical cord prolapse occurs when the cord descends below the presenting part and compresses between this part and the pelvis.
 Typically, associated with foetal malpresentation
 Presents as visible or palpable cord and foetal heart rate changes
 Treated with emergency caesarean section (and alleviate pressure on cord by digit in the vagina and on knees/elbows position)
MECONIUM IN AMNIOTIC FLUID
Meconium in amniotic fluid occurs in up to 25% of all labours; but is usually not associated with poor outcome.
 Associated with cord compression or breech presentation
CLINICAL PRESENTATION
 Turns the amniotic fluid green or black in colour
 Associated with pneumonitis (due to meconium aspiration)
TREATMENT
 Multidisciplinary approach (respiratory therapy, neonatology, or paediatrics)
 Oropharynx suctioning upon delivery

Puerperium
POSTPARTUM HAEMORRHAGE
Postpartum haemorrhage is defined as a loss of >500ml of blood at the time of vaginal delivery or >1000ml with caesarean section .
 Can be early (within 24 hours postpartum) or late (after 24 hours but within first 6 weeks)
AETIOLOGY
4Ts:
 Tone (uterine atony) (most common)
 Avoided by giving oxytocin with delivery of anterior shoulder or placenta
 Due to:
 Overdistended uterus (polyhydramnios, multiple gestation, macrosomia)
 Uterine muscle exhaustion (prolonged or rapid labour, grand multiparity, oxytocin use, general anaesthetic)
 Uterine distortion (fibroids, placenta previa, placental abruption)
 Intra-amniotic infection (fever, prolonged ROM)
 Tissue (retained placenta or blood clots)
 Trauma
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 Thrombin (coagulopathy)
DIAGNOSIS AND TREATMENT
 Initial management: DRS ABCs, 2 large bore IV lines with IV fluid , CBC and coagulation , Foley catheter
 Local control: bimanual compression , uterine packing , Bakri balloon (for tamponade),
 Surgical therapy (refractory): uterine/internal iliac ligation , angiographic embolisation of uterine artery , or hysterectomy
Diagnosis and treatment of postpartum haemorrhage
UTERINE ATONY RETAINED TISSUE TRAUMA
Diagnosis  Palpation of soft, enlarged, boggy uterus  Manual and visual inspection of the  Manual and visual inspection of lower
placenta and uterine cavity for missing genital tract for any major laceration
cotyledons
 U/S may be used to inspect uterus

Treatment  Bimanual uterine massage  Manual removal of remaining tissue  Surgical repair of the physical defect
 Contractive agents  Curettage with suctioning
 Oxytocin infusion
 Ergotamine (if not hypertensive)
 Carbiprost (PGF-2α)

UTERINE INVERSION
Uterine inversion is inversion of the uterus through the cervix ± vaginal introitus.
 Can cause profound shock (disproportionate to maternal blood loss)
 Treated with manual replacement , tocolytic therapy , and rarely surgery
POSTPARTUM PYREXIA
Postpartum pyrexia is defined as a fever of >38 oC on the first ten days postpartum (except the first day).
 Diagnosis and treatment depends on underlying cause
AETIOLOGY
B-5W:
 Breast: engorgement, mastitis
 Wind: atelectasis, pneumonia
 Water: UTI
 Wound: episiotomy, caesarean section infection
 Walking: VTE
 Womb: endometritis
Endometritis
Endometritis is an infection of the uterine myometrium and parametrium (typically, GBS or mixed anaerobic/aerobic bacteria)
 Presents as fever, abdominal pain, uterine tenderness , and a foul-smelling lochia
 Occurs particularly after emergency caesarean section
 Treated with oral or IV antibiotics (e.g. IV clindamycin + gentamicin )
POSTPARTUM MOOD ALTERATION

CLASSIFICATION
 Postpartum blues – affects the majority of new mothers but is self-limiting
 Onset in first-week post-partum and settles by two weeks
 Postpartum depression – major depression occurring in a women within one months of childbirth
 Postpartum psychosis – psychosis within the first month of childbirth (rare but important)

Note: be aware of medication (e.g. fluoxetine) that is secreted in breast milk.

PHYSIOLOGICAL CHANGES IN PEURPERIUM
 Lochia – normal vaginal discharge postpartum (uterine decidual tissue sloughing), progresses through:
 Lochia rubra (red – contains erythrocytes) – over several days
 Lochia serosa (pale) – over several days
 Lochia alba (yellow – contains leukocytes) – over several weeks (abnormal if continues for >6 weeks)
 Ovulation
 Resumes in approximately 1 month for non-lactating women (or 3 to 6 months if lactating)
 Lactation is not an adequate form of contraception
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LACTATION AND BREASTFEEDING

Breast development
 Oestrogen – stimulates branching of breast ducts and fat deposition (esp. during puberty)
 Progesterone – stimulates alveolar development (esp. during pregnancy)
 Prolactin (and placental lactogen) – stimulates milk production
 Secreted in response to suckling stimulus (inhibits inhibitory dopamine secretion)
 Effects is blocked by high levels of oestrogen and progesterone (therefore not much milk produced in pregnancy)
 Oxytocin – stimulates milk ejection
 Secreted in response to suckling stimulus (pulsatile release)
Lactation failure
Lactation failure is inadequate milk production and/or failure of milk ejection.
 Inadequate production typically due to insufficient prolactin – e.g. Sheehan syndrome, obesity, medication (D2 agonists)
 Treated with domperidone (D2 antagonist)

Milk composition
 Colostrum (week 1) – rich in proteins, vitamins A/D/E/K, and immunoglobulins (esp. IgA)
 High IgA levels provides passive immunity for the infant
 Transitional and mature milk (week 2 onwards) – gradual change to increased lactose and fats as proteins decline
 Production occurs for months (dependent on suckling-induced stimulation of milk synthesis)
 Breastfeeding guidelines: exclusively for 6 months, and then up to two years (with introduction of solids at 6 months)
MASTITIS
Mastitis is a cellulitis of the breast tissue caused by nipple trauma from breastfeeding leading to infection of the nipple ducts .
 Typically, caused by S. aureus
CLINICAL PRESENTATION
 Symptoms are usually unilateral – breast tenderness, palpable mass , erythema, oedema, warmth, and purulent nipple drainage
 Associated with significant fever, chills, malaise

Note: non-tender lumpiness in the breast tissue is normal in the puerperium.

DIAGNOSIS
 Clinical diagnosis (differentiate from simple breast engorgement)
 Breast engorgement can be treated with cool compress and manual expression/pumping
 Labs:  WBC
TREATMENT
 Continued breastfeeding (prevents accumulation of infected material)
 Flucloxacillin
 Refractory – evaluate with breast ultrasound to assess for abscess (if present treat with I&D)

Foetal monitoring
FOETAL MOVEMENTS
Pregnant women will generally notice first foetal movement (quickening ) at around 18 weeks gestation .
 High risk women should be told to do foetal movement counts (≥6 movements in 2 hours expected)
 Causes of decreased foetal movement (DASH): foetal Death, decreased Amniotic fluid, foetal Sleep, Hunger/thirst
CARDIOTOCOGRAPHY
Cardiotocography (CTG) is used during pregnancy to monitor the foetal heart and contractions of the uterus .
 It is most commonly used intermittently in the third trimester
 Its purpose is to monitor foetal well-being and allow early detection of foetal distress
 Can be performed transabdominally or via foetal scalp (if obese mother)
 An abnormal CTG indicates the need for more invasive investigations and potentially emergency caesarean section
INTERPRETATION
DR C BRAVADO:
 DR – Define risk (high or low risk)
 C – Contractions
 BRA – Baseline rate
 Normal is 110 to 160bpm
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 V – Variability
 Normal is 5 to 25bpm
 A – Accelerations (>15bpm for 15 seconds)
 The presence of accelerations (even with reduced baseline variability) is generally a sign that the baby is healthy
 D – Decelerations (>15bpm for 15 seconds) – considered abnormal
 Early decelerations (occur during uterine contraction) – considered physiological (due to increased foetal intracranial pressure)
 Variable decelerations (no relationship to uterine contraction) – suggests umbilical cord compression
 Immediate reposition of the mother on her side can improve some variable decelerations
 Late deceleration (occur after uterine contraction) – suggests uteroplacental insufficiency (leading to foetal hypoxia and
acidosis)
 Prolonged deceleration (lasts greater than 2 minutes)
 O – Overall impression (normal or abnormal)

Foetal scalp blood sampling

Foetal scalp blood sampling is indicated when CTG demonstrates an abnormal or atypical foetal heart rate.
 Measures pH or foetal lactate (a pH <7.2 indicates foetal acidosis and emergency caesarean section )
PLACENTAL VARIATION

ANATOMICAL VARIATION OF PLACENTA

 Velamentous insertion – umbilical cord inserts into the foetal membranes, then travels
within the membranes to the placenta
 Succenturiate – accessory lobe
 Bilobate – two primary lobes
 Circummarginate – surrounded by thin rim of fibrous tissue
 Circumvallate – surrounded by large rim (cuplike) of fibrous tissue
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Paediatrics
Cardiology
BASIC PRINCIPLES

FOETAL CARDIOVASCULAR ANATOMY

 Umbilical vein – 80% oxygen saturation (PO2 of ~30mmHg)
 Umbilical artery – low oxygen saturation
 Three important shunts:
 1) Ductus venosus – umbilical vein  IVC (bypasses hepatic circulation)
 2) Foramen ovale – IVC/RA  LA (oxygenated blood to aorta bypassing lungs)
 3) Ductus arteriosus – pulmonary artery  aorta (low oxygenated blood from
SVC)
 Physiological changes at birth:
 After first breath, resistance in pulmonary vasculature decreases
 Foramen ovale closes from increased left atrial pressure (now called fossa ovalis)
 Oxygen from respiration and decreased prostaglandins from placental separation
cause closure of ductus arteriosus (the remnant is called ligamentum arteriosum)
Foetal-postnatal derivatives
FOETAL POSTNATAL NOTES

Umbilical vein Ligamentum teres Contained in falciform ligament

Umbilical arteries Medial umbilical ligaments

Ductus arteriosus Ligamentum arteriosum

Ductus venous Ligamentum venosum

Allantois Median umbilical ligament The allantois is a canal that drains the urinary
(urachus) bladder of the foetus that joins and runs
within the umbilical cord

CONGENITAL HEART DISEASE

Congenital heart disease is classified by the presence or absence of cyanosis:
 Acyanotic heart disease (‘pink babies’) – have left-to-right shunts
 Oxygenated blood from the lungs is shunted back to the pulmonary circulation
 Cyanotic heart disease (‘blue babies’) – have right-to-left shunts
 Deoxygenated blood is shunted into the systemic circulation
RISK FACTORS
 Maternal drug use (alcohol, lithium, thalidomide, phenytoin )
 Maternal infection (rubella)
 Maternal illness (diabetes mellitus, phenylketonuria)

Acyanotic heart disease

Septal defects
ASD versus VSD
ASD VSD
Associated conditions  Foetal alcohol syndrome  Foetal alcohol syndrome
 Trisomy 21  Trisomy 13, 18, and 21
 TORCH infections
 Cri du chat syndrome
 Apert syndrome

Clinical presentation  Small defect: asymptomatic  Small defect: asymptomatic

 Large defect: heart failure, recurrent respiratory infection  Large defect: as for ASD
 Presents later in childhood  Presents by 2 months

Diagnosis  Exam: pulmonic outflow murmur with widely-split fixed S2  Exam: holosystolic murmur at LLSB, mid-diastolic rumble
 CXR: cardiomegaly and increased vascular markings at apex (size of VSD inversely related to murmur intensity)
 ECG: RAD, RVH, RBBB  CXR: normal (similar to ASD if severe)
 Echo: definitive  ECG: normal (or LAD, LVH, LBBB if severe)
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 Echo: definitive

Treatment  Supportive (most close spontaneously)  Supportive (most close spontaneously)

 Treat heart failure  Treat heart failure
 If severe: catheter/surgical closure by 2 to 5 years of age  If severe: catheter/surgical closure by 1 year of age

Notes  Can lead to secondary pulmonary hypertension  Most common congenital heart defect (50%)
 Can lead to secondary pulmonary hypertension

Eisenmenger syndrome
Eisenmenger syndrome is a complication of long-standing cardiac septal defects (acyanotic defects).
 Characterised by pulmonary hypertension , and therefore shunt reversal (from left-to-right to right-to-left) causing cyanosis
Patent ductus arteriosus
Patent ductus arteriosus is failure of the ductus arteriosus to close in the first few days of life (leading to left-to-right shunt).
 Blood is shunted from aorta to pulmonary artery (as opposed to foetal circulation which is from pulmonary artery to aorta)
 Typically, functional closure occurs within the first 24 hours of life and anatomical closure within the first two weeks
 Delayed closure of ductus is common in premature infants
 Associated with congenital rubella syndrome
CLINICAL PRESENTATION
 Symptoms: typically, asymptomatic (may present with CHF or recurrent respiratory infection)
 Signs: continuous ‘machinery’ murmur (best heard in left infraclavicular area), tachycardia, wide pulse pressure, bounding pulse
DIAGNOSIS
 CXR: cardiomegaly and increased vascular markings
 ECG: LAD, LVH, LBBB
 Echo: definitive
TREATMENT
 Indomethacin (prostaglandin antagonist) – only effective in premature infants
 Catheter/surgical closure if symptoms persist for several months
Coarctation of the aorta
Coarctation of the aorta is a narrowing of the aorta (almost always at the level of the ductus arteriosus, just distal to left subclavian
artery).
FEATURES
 Associated with a bicuspid aortic valve (50%)
 Associated with Turner syndrome (one-third of patients have a coarctation)
CLINICAL PRESENTATION
 Symptoms : typically, asymptomatic (rarely can cause claudication, syncope, epistaxis, or headache)
 Signs:
 Blood pressure discrepancy between upper and lower extremities (upper extremity hypertension)
 Radial-femoral delay
 Systolic murmur across torso
 Pre- and post-ductal oximetry discrepancy in newborns (due to RL shunting via PDA)
 If severe, presents with shock in the neonatal period
DIAGNOSIS
 CXR:
 In younger children – cardiomegaly and increased vascular markings
 In older children – ‘3’ sign (pre- and post-dilation of aorta) and rib notching (collateral circulation through intercostal arteries)
 ECG: LVH
 Echo/MRI: definitive
TREATMENT
 Neonates – prostaglandins (to keep ductus arteriosus patent) followed by surgical correction
 Infants/children – balloon angioplasty or surgical correction

Cyanotic heart disease

Cyanotic heart disease is caused by the 5Ts:
 Truncus arteriosus
 Transposition of the great vessels (only condition that causes severe cyanosis in first few hours of life)
 Tricuspid atresia
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 Tetralogy of Fallot
 Total anomalous pulmonary venous return
DIAGNOSIS
 Hyperoxic test ( administer 100% O2 and monitor pre/post-ductal ABG) – differentiates between cardiac and lung causes of cyanosis
 If PaO2 improves to greater than 150mmHg cyanosis is likely not cardiac in origin
 Pre- and post-ductal pulse oximetry (>5% difference suggests RL shunt)
Truncus arteriosus
Truncus arteriosus is a congenital heart defect where a single large vessel (truncus arteriosu s) gives rise to the aorta, pulmonary, and
coronary arteries.
 Truncal valve overlies a large VSD
 Managed with surgical correction within first few weeks of life
Transposition of the great vessels
PATHOPHYSIOLOGY
 Characterised by parallel pulmonary and systemic circulations
 Systemic: body  RA  RV  aorta  body
 Pulmonary: lungs  LA  LV  pulmonary artery  lungs
 Survival is dependent on oxygenated blood mixing through PDA, ASD, or VSD
 A PDA alone is usually incompatible with life
FEATURES
 Most common cyanotic heart disease presenting in neonates
 Associated with DiGeorge syndrome (22q11 deletion) and diabetic mothers
CLINICAL PRESENTATION
 Dependent on presence of PDA or septal defect: ranges from cyanosis within first few hours of life to heart failure and death
 Examination: single loud S2 (or septal murmur)
DIAGNOSIS
 CXR: ‘egg shaped’ heart with narrow mediastinum
 ECG: RAD, RVH, RBBB
 Echo: definitive
TREATMENT
 Neonates – prostaglandins (to keep ductus arteriosus patent) followed by balloon atrial septostomy and then surgical correction
 Arterial switch performed in the first few weeks while the LV muscle is still strong
Tricuspid atresia
Tricuspid atresia is a form of congenital heart disease whereby there is a complete absence of the tricuspid valve .
 Therefore, there is no connection between the right atrium and ventricle (which becomes hypoplastic)
 An ASD must be present to fill the left ventricle with blood
 A VSD must be present to allow blood into the pulmonary arteries
Tetralogy of Fallot
PATHOPHYSIOLOGY
 Tetrad of VSD, right ventricular outflow tract obstruction (RVOTO), over-riding (biventricular) aorta, RVH
 The degree of RVOTO determines the extent of the cyanosis
 Early after birth, the right-to-left shunt may decrease due to decreasing pulmonary resistance
 However, RVOTO is progressive, leading to increasing right-to-left shunt over time (through VSD)
FEATURES
 Most common cyanotic heart disease presenting in children
 Associated with DiGeorge syndrome (22q11 deletion) and maternal phenylketonuria
CLINICAL PRESENTATION
 Typically, asymptomatic at birth but presents with cyanosis and heart failure within the first two years of life
 Children often squat for relief during hypoxaemic episodes (called ‘tet spells’ – occur during exercise or crying)
 Squatting increases systemic vascular resistance increasing blood flow to pulmonary vasculature and improving oxygenation
 Exam: single S2 (absence of pulmonary component), SEM pulmonic area radiating to back (RVOTO), left parasternal heave (RVH)
DIAGNOSIS
 CXR: ‘boot shaped’ heart and decreased pulmonary vasculature
 ECG: RVH
 Echo/cardiac catheterisation : definitive
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TREATMENT
 ‘Tet spells’ – oxygen, knee-chest position , IV fluids, propranolol, morphine (for dyspnoea)
 Curative – surgical correction (Blalock-Taussig shunt)
 Temporary palliation can be achieved through balloon atrial septostomy
 Severe RVOTO – prostaglandins (to keep ductus arteriosus patent) followed by immediate surgical correction
Total anomalous pulmonary venous return
Total anomalous pulmonary venous return is a congenital heart defect where all pulmonary veins drain into the right side of the heart
(i.e. no direct oxygenated pulmonary venous return to left atrium).
 An ASD must be present to fill the left ventricle with blood
 Managed with surgical correction within first few weeks of life
Ebstein’s anomaly
Ebstein’s anomaly is a congenital heart defect causing displacement of tricuspid valve leaflets (septal/posterior) into right ventricle.
 Associated with right ventricular dysfunction and Wolff-Parkinson-White syndrome
HEART MURMURS
Most children will have an audible heart murmur at some point in their childhood.
 Typically, these are functional (e.g. ‘innocent) without associated abnormality
 May be exacerbated by high output states – e.g. fever or anaemia
Differentiating childhood heart murmurs
INNOCENT PATHOLOGICAL

History Asymptomatic Symptoms and signs of cardiac disease

Timing SEM All diastolic, pansystolic, or continuous (except venous hum)

Quality Soft Harsh

Splitting Physiologic Fixed split or single S2

Extra sounds None May be present (thrills are pathological)

Change of position Murmur varies Unchanged

EXAMPLES
 Still’s murmur – flow across pulmonic valve (vibratory systolic murmur at LLSB between 3 to 6 years of age) (DDx – small VSD)
 Venous hum – altered flow in veins (murmur at infraclavicular area, R>L, between 3 to 6 years of age) (DDx – PDA)
HEART FAILURE IN CHILDREN
Heart failure in children can present differently than in adults.
CLINICAL PRESENTATION
 Symptoms:
 Infants – feeding difficulties, early fatigability, diaphoresis while sleeping or eating, respiratory distress, failure to thrive
 Children – similar to adults but can also present as frequent URTIs or ‘asthma’ episodes
 Orthopnoea, paroxysmal nocturnal dyspnoea, and oedema are uncommon in children
 Signs (2 tachy’s and 2 megaly’s ):
 Tachycardia
 Tachypnoea
 Cardiomegaly
 Hepatomegaly
 Also, failure-to-thrive

Respiratory
APPROACH TO DYSPNOEA IN CHILDREN
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UPPER RESPIRATORY TRACT DISEASE

CHARACTERISTICS
 Diseases above the thoracic inlet are characterised by: inspiratory stridor, hoarseness, and suprasternal/supraclavicular retraction
 Stridor is a high-pitched croaking sound caused by turbulent airflow in the larynx or upper airways
DIFFERENTIAL DIAGNOSIS OF STRIDOR
 Infective: croup, bacterial tracheitis, epiglottitis
 Congenital/acquired:
 Foreign body aspiration
 Subglottic stenosis (congenital or iatrogenic)
 Laryngomalacia/tracheomalacia (cartilaginous softening causing collapse of airway on inspiration)
Common Upper Respiratory Tract Infections in Children
CROUP (LARYNGOTRACHEOBRONCHITIS) BACTERIAL TRACHEITIS EPIGLOTTITIS

Anatomy Subglottic laryngitis Subglottic tracheitis Supraglottic laryngitis

Epidemiology Common (in children <6 years) Rare (in all age groups) Very rare (due to H. flu vaccination)

Aetiology Viral infection Bacterial infection Bacterial infection

 Parainfluenza (75%)  S. aureus  H. influenzae
 H. influenzae  S. pneumoniae
 GAS
 S. pneumoniae
 M. catarrhalis

Onset Prodrome Prodrome with acute decompensation Rapid

Clinical  URTI-like prodrome w/ low-grade fever  Like croup but more rapid deterioration  Respiratory distress:
presentation  Hoarse voice (intermediate fever, toxic appearance,  Toxic appearance
 Barking cough does not respond to croup treatment)  High-grade fever
 Inspiratory stridor  Rapid progression
 Worse at night  4D’s – Drooling, Dysphagia,
Dysphonia, Distress
 Inspiratory stridor
 Tripod position
 Hyperextended neck with protruding
chin (‘sniffing dog position’)

Investigations  Clinical diagnosis  Clinical diagnosis  Clinical diagnosis (avoid examining

 CXR – ‘steeple sign’ (subglottic  CXR – subglottic narrowing throat to prevent exacerbation)
narrowing)  Endoscopy – definitive diagnosis  CXR – ‘thumbprint sign’ (oedematous
epiglottis)

Treatment  No evidence for humidified O2 CLINICAL EMERGENCY CLINICAL EMERGENCY

 Oral/IM corticosteroids  Intubation (secure the airway)  Intubation (secure the airway)
 Nebulised racemic adrenaline  IV antibiotics (ceftriaxone)  IV antibiotics (ceftriaxone)
 Intubation if unresponsive

LOWER RESPIRATORY TRACT DISEASE

CHARACTERISTICS
 Diseases below the thoracic inlet are characterised by: wheeze ( expiratory sounds)
DIFFERENTIAL DIAGNOSIS OF WHEEZE
 Common:
 Bronchiolitis – first episode of wheezing (typically, <2 years old)
 Viral induced wheeze – recurrent wheezing episodes, associated with coryzal/cough symptoms (typically, 2-6 years old)
 Asthma – recurrent wheezing episodes, identifiable triggers (typically, >6 years old)
 Recurrent aspiration – associated with a history of neurological impairment
 Pneumonia – fever, cough, malaise
 Uncommon:
 Foreign body – acute unilateral wheezing and cough
 Pathognomonic sign – lung volume that does not change on expiratory CXR (normal lung appears smaller and denser)
 Cystic fibrosis – prolonged wheezing, unresponsive to therapy
 Bronchopulmonary dysplasia – typically occurs after a prolonged period of ventilation in new-borns
 Rare:
 Heart failure, mediastinal mass, bronchiolitis obliterans, tracheobronchial anomalies
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Bronchiolitis
Bronchiolitis is the most common LRTI in infants (affects 50% of children in first 2 years of life).
 Typically, wheeze in young children should be regarded as due to bronchiolitis (or other disorders) and not asthma
PATHOPHYSIOLOGY
 Most commonly due to viral infection (respiratory syncytial virus (RSV)) in >50% of cases
CLINICAL PRESENTATION
 Prodrome of URTI with cough, low-grade fever, and/or rhinorrhoea (if high fever is present, suspect pneumonia or other diagnoses)
 Symptoms : feeding difficulties, irritability, respiratory distress
 Signs: wheeze, fine crackles, tachypnoea, increased work of breathing, and tachycardia
 Classically, symptoms/signs peak at 3 to 4 days
DIAGNOSIS
 Clinical diagnosis in almost all cases
 Additional:
 Labs – CBC (however, WBC can be normal)
 NP swab – direct detection of viral antigen
 Imaging – CXR (if severe to rule out other pathology)
TREATMENT
 Typically, self-limiting disease that lasts 2 to 3 weeks (antibiotics and steroids have no benefit)
 Mild-to-moderate distress:
 Supportive care: PO/IV hydration, antipyretics , supplemental oxygen (NP or high-flow) , nasal drops/suctioning
 Severe distress (poor saturations, significant feeding problems, or comorbidity):
 As above ± intubation and ventilation
 Consider ribavirin (if high risk comorbidities)
 Prophylaxis (if high risk comorbidities) – RSV-Ig
OUTCOMES
 Persistent wheeze is experienced by ~40% of infants who are hospitalised due to bronchiolitis (typically, continues up to five years)
Respiratory medication delivery
CLINICAL NOTES
 An inhaler mask is necessary in young children (<2 to 3 years) who are obligate nose breathers or form inadequate mouthpiece seals
 However, the nasal route reduces lung deposition
 A dry powder inhaler is useful for children that do not tolerate a spacer
 However, they are less useful in acute attacks (require good inspiratory effort)

Gastroenterology
INTUSSUSCEPTION
Intussusception is a telescoping of a segment of bowel into a distal segment causing ischaemia and necrosis.
FEATURES
 Most common cause of bowel obstruction in children
 Typically, occurs between 3 months and 3 years old (male-to-female ratio is 3:1)
PATHOPHYSIOLOGY
 Usual site: ileocaecal junction
 Lead point of telescoping segment may be swollen Peyer’s patches , Meckel’s diverticulum , polyp, or other structural abnormality
CLINICAL PRESENTATION
 Classic triad (<25% of patients) – severe abdominal pain , palpable RUQ ‘sausage’ mass , red currant jelly stools
 Sudden onset of paroxysmal severe peri-umbilical pain with pain-free intervals
 Later – vomiting (may be bilious) and rectal bleeding (late finding)
 Often preceded by URTI
 Rarely, lethargy may be the only presenting symptom
DIAGNOSIS AND TREATMENT
 Initial test: abdominal U/S
 Definitive test and treatment: air enema fluoroscopy
 If refractory (10%): surgical correction of lead point
 Supportive: NPO, NGT, and antipyretic/analgesia/antiemetic
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PYLORIC STENOSIS
Pyloric stenosis is hypertrophy of the pyloric sphincter leading to gastric outlet obstruction.
 Associated with tracheoesophageal fistula and maternal erythromycin exposure
FEATURES
 Most common cause of GI tract obstruction in infancy
 Male-to-female ratio is 4:1
CLINICAL PRESENTATION
 Presents at six to eight weeks with:
 Projectile non-bilious vomiting (after feeds)
 Infants are always hungry ; they initially feed well, but eventually suffer from dehydration and malnutrition (variable severity)
 Examination: palpable olive-shaped non-tender gastric mass and visible gastric peristaltic waves
DIAGNOSIS
 Definitive test: abdominal U/S (demonstrate pyloric hypertrophy)
 Additional:
 Labs – U&E (classically hypochloraemic, hypokalaemic, metabolic alkalosis )
TREATMENT
 Supportive – IV fluids and correct electrolyte and acid-base abnormalities
 Curative – pyloromyotomy

Note: the differential diagnosis for bilious vomiting includes malrotation with volvulus , duodenal atresia , and Hirschsprung disease.
MECKEL DIVERTICULUM
Meckel diverticulum is caused by failure of the omphalomesenteric (vitelline) duct to obliterate, resulting in the formation of a true
diverticulum (containing all three layers of the gut wall).
 The omphalomesenteric duct connects the yolk sac to the primitive midgut
 The heterotopic gastric tissue present in most Meckel diverticula cause intestinal ulceration and painless haematochaezia
FEATURES
 Most common congenital malformation of the small bowel
 Meckel rule of 2’s :
 Occurs in 2% of the population
 Occurs 2 times as often in boys
 Contains 2 types of tissue (gastric and pancreatic)
 Typically, is 2 inches long
 Typically, found within 2 feet of ileocecal valve
CLINICAL PRESENTATION
 Typically, asymptomatic (often discovered incidentally)
 Classically, presents as painless haematochezia (in first five years of life)
 Complications include intestinal perforation or obstruction , shock, diverticulitis, and intussusception
DIAGNOSIS
 Definitive test : abdominal CT or Meckel scintigraphy scan (scan for ectopic gastric mucosa with technetium)
TREATMENT
 Surgical resection
HIRSCHSPRUNG DISEASE
Hirschsprung disease is a congenital absence of ganglion cells in the intestine (typically, distal colon – rarely, whole colon or small
bowel).
PATHOPHYSIOLOGY
 Defect in migration of neurocrest cells to intestine resulting in aganglionic bowel that:
 Results in failure of peristalsis, and
 Results in failure of sphincter relaxation (internal anal sphincter achalasia)
 This causes functional and partial mechanical obstruction respectively
 Always starts in the rectum, and variably involves proximal bowel
FEATURES
 Male-to-female ratio is 4:1 (but less if whole colon involved)
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 Associated with trisomy 21 , Waardenburg syndrome, and MEN-2

CLINICAL PRESENTATION
 Failure to pass meconium spontaneously within 48 hours of life is classical
 Symptoms of bowel obstruction – abdominal distension, constipation, bilious vomiting
 Associated with failure-to-thrive
 Exam: explosive discharge of stool following a rectal examination (squirt/blast sign) and hypertonic sphincter tone
DIAGNOSIS
 Rectal biopsy (gold standard – aganglionosis and neural hypertrophy)
 Barium enema (imaging study of choice – narrowed distal colon with proximal dilation)
 Anorectal manometry (only useful in older children – detects failure of anal sphincter to relax)
TREATMENT
 Surgical correction (resection and diverting colostomy followed by a ‘pull through’ procedure )
OUTCOMES
 Most have near-normal anorectal function
COMPLICATIONS
 Faecal incontinence, constipation, post-operative enterocolitis
MALROTATION WITH VOLVULUS
Malrotation is a congenital malrotation of the midgut, with variable risk for volvulus, that results in:
 Abnormal positioning of the small intestine
 Small intestine predominantly in the right abdomen, caecum in the RUQ, abnormal position of ligament of Treitz
 Formation of fibrous bands (Ladd bands) which predispose to obstruction and intestinal necrosis
CLINICAL PRESENTATION
 Classically, presents as bilious vomiting (in the first month of life) (esp. if abdomen non-distended)
 Bilious vomiting in ill child with distended abdomen is suggestive of volvulus
 May present late with rectal bleeding
DIAGNOSIS
 AXR – ‘bird-beak’ appearance and small bowel obstruction
 Upper GI series (definitive test) – abnormal location of the ligament of Treitz and ‘corkscrew appearance’ if volvulus present
TREATMENT
 Supportive: IV antibiotics , NPO, NGT, and IV fluids
 Curative: urgent laparotomy (Ladd procedure)
OUTCOMES
 Mortality related to length of intestinal necrosis
NECROTISING ENTEROCOLITIS
Necrotising enterocolitis is a condition where a portion of bowel undergoes necrosis.
FEATURES
 Most common cause of GI emergency in infancy
 Associated with premature infants , low birth weight , hypotension, and formula feeding
CLINICAL PRESENTATION
 Non-specific gastrointestinal symptoms within the first few days or weeks of life
 Can rapidly progress to severe rectal bleeding, intestinal perforation , peritonitis , DIC, and shock
DIAGNOSIS
 AXR (definitive) – pneumatosis intestinalis (intramural gas) is pathognomonic
 Serial AXR’s should be taken every 6 hours (to detect perforation)
 CXR can be performed to look for free abdominal air (i.e. perforation)
 Labs: non-specific (acidosis, neutrophilia, DIC)
TREATMENT
 Aggressive therapy: NPO, NGT, TPN, IV fluids, and supportive therapy
 IV antibiotics (vancomycin + gentamicin + metronidazole )
 Surgical resection if severe (perforation)
COMPLICATIONS
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 Intestinal strictures and short-bowel syndrome

MESENTERIC ADENITIS
Mesenteric lymphadenitis is inflammation of the mesenteric lymph nodes (especially in the right lower quadrant mesentery).
 Mainly affects adolescents, and is difficult to differentiate from acute appendicitis (esp. in children)
 The pathophysiology is thought to involve lymph node infection (esp. Yersinia enterocolitica)
CLINICAL PRESENTATION
 Clinical presentation similar to acute appendicitis
 Unlike appendicitis, is often preceded by URTI or nausea/vomiting
 Examination: as for appendicitis in addition to cervical lymphadenopathy and less marked peritonism
DIAGNOSIS
 Labs: CBC (leukocytosis), CRP, urinalysis ± septic workup
 Imaging: abdominal U/S followed by CT (enlarged mesenteric lymph nodes with ileocaecal wall thickening)
TREATMENT
 Supportive (after exclusion of appendicitis – may require surgical diagnosis)
 Antibiotics (co-trimoxazole ) if severe
GASTROESOPHAGEAL REFLUX
Gastroesophageal reflux is extremely common in infancy (up to 50% of all infants).
 Presents as vomiting post-feed (non-bilious, nil blood, small volume)
 Investigations are not required in a thriving baby
 Treatment includes:
 Frequent, thicker, and smaller feeds ( milk thickeners or sodium alginate)
 Short-term parenteral feeding
 Ranitidine/PPI (decreases oesophageal irritation)
 Domperidone or metoclopramide can be used in children with gastroparesis (although there are safety concerns)
 Surgical Nissen fundoplication if refractory
TODDLER’S DIARRHOEA
Toddler’s diarrhoea is the most common cause of chronic diarrhoea during infant/childhood.
 Diagnosis of exclusion in thriving child
CLINICAL PRESENTATION
 Several (4 to 6) loose bowel movements per day which may contain undigested food particles
 Diet history (excess juice is common – overwhelms small bowel resulting in disaccharide malabsorption)
 Associated with excoriated diaper rash
TREATMENT
 Reassurance (self-limiting – onset in first 3 years of life and ceases spontaneously before 5 years old)
 4Fs advice (adequate Fibre, normal Fluid intake, 35-40% Fat intake, discourage excess Fruit juice)
LACTOSE INTOLERANCE (LACTASE DEFICIENCY)

CLINICAL PRESENTATION
 Chronic, watery, diarrhoea and abdominal pain/bloating associated with dairy intake
 Can be associated with coeliac disease, IBD, and post-infection (secondary lactose intolerance)
DIAGNOSIS AND TREATMENT
 Trial of lactose-free diet
 Lactase-containing medication
MILK PROTEIN ALLERGY
Milk protein allergy is an immune-mediated (IgE or non-IgE) mucosal injury due to proteins in cow’s milk.
 Associated with a personal/family history of atopy
CLINICAL PRESENTATION
 Milk protein allergy can present as:
 Proctocolitis (bloody stool and mild diarrhoea)
 Enterocolitis (vomiting, diarrhoea, haematochaezia, anaemia) – can be severe (presents as shock)
 Enteropathy (chronic diarrhoea, hypoalbuminaemia)
 Associated with intolerance to soy protein (50% of cases)
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 Typically, self-limiting by 1 year old

TREATMENT
 Exclusion of milk protein from diet
 Continue breast feeding
 Dairy-free formula
GASTROENTERITIS
Gastroenteritis in young children is typically due to viruses (rotavirus and norovirus).
 Bacterial and parasitic causes are more common in older children
CLINICAL NOTES
 Do not encourage sugary fluids in gastroenteritis, as it causes osmotic diarrhoea, and hypernatraemic dehydration
 Most classical sign of hypernatraemia in children is a ‘doughy skin turgor ’
NUTRITIONAL ADVICE

ENERGY REQUIREMENTS
 Infants have the highest energy requirements per kilogram of any age (slowly decreases with age )
 180g - 220g per week is the expected weight gain for infants in the first 3 months of life
 A healthy neonate is expected to lose up to 10% of birth weight, but should regain this within the first 2 weeks after birth

 Infants having the highest growth velocity of any age (slowly decrease with age apart from a pubertal growth spurt )
 Plateaus out in mid-childhood around 5cm/year, before the pubertal growth spurt which may be up to 12 cm/yr
 Growth velocity below 5 cm/year should be carefully assessed
DIETARY REQUIREMENTS
 Diet for age:
 0 to 6 months – exclusive breast fed (with supplemental vitamin D ; also, fluoride or iron if low intake)
 >6 months – solid food introduction (meat  pureed vegetables  fruit)
 Introduce two-to-three new foods per week with a few days in between to allow for adverse reaction identification
 9 to 12 months – finger foods and switch to homogenized milk
COW VERSUS BREAST MILK
 Cow’s milk has, in comparison to breast milk:
 Higher quantity of solutes
 Higher level of casein
 Similar iron content (but not well absorbed)
 Iron deficiency anaemia is most common cause of anaemia in children (often due to excess cow milk intake)
 However, principle time for accumulating iron stores is the third trimester of pregnancy
 Vitamin C increases iron absorption (so is recommended with iron-rich foods)

Infectious disease
FEVER IN CHILDREN

MEASUREMENT
 The measurement of temperature should be completed by:
 Tympanic or rectal thermometer (tympanic is inaccurate if <6 months old)
TREATMENT ALGORITHM
 <6 weeks of age and any fever (>38 oC):
 High likelihood of bacterial infection (15%)
 Requires full sepsis workup: CBC, blood cultures, urinalysis (R&M/C&S), LP, CXR, BGL
 Treatment: immediate empiric IV antibiotics (amoxicillin + cefotaxime)
 <6 weeks to 3 months of age and any fever (>38 oC):
 Moderate likelihood of bacterial infection (5%)
 Requires full sepsis workup (but not LP if patient is well)
 Treatment: consider empiric IV antibiotics (amoxicillin + cefotaxime)
 >3 months to 2 years of age and high fever (>38.9 oC):
 Low likelihood of bacterial infection (unless clear infective focus)
 Requires full sepsis workup (only if unwell or unresponsive)
 Treatment: consider empiric IV antibiotics (cefotaxime)
 Supportive:
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 IV fluids – to replace fluid losses

 Antipyretics – not necessary in most cases (only for comfort)
PERTUSSIS
Pertussis is a respiratory infection by Bordetella pertussis (gram negative pleomorphic rod).
 Highly contagious via respiratory droplets (particularly in prodromal phase)
FEATURES
 Bimodal distribution – children less than one (not fully immunised) and adolescents (waning immunity)
 Adolescents serve as the primary reservoir for pertussis
CLINICAL PRESENTATION
 Prodromal ‘catarrhal’ stage (first week)
 URTI symptoms ± fever
 Paroxysmal stage (two to three months)
 Characterised by paroxysms of cough (‘100-day cough’) followed by inspiratory whoop (‘whooping cough’)
 Infants may present with post-tussive apnoea rather than inspiratory whoop
 Associated with post-tussive emesis
 Convalescent stage ( one to two weeks)
 Decreased frequency and severity of cough (non-infectious cough may last several months)
DIAGNOSIS
 NP swab culture (gold-standard)
 Labs: CBC (lymphocytosis)
TREATMENT
 Conservative:
 Supportive care
 Droplet isolation
 Aggressive:
 Hospital admission
 Supplemental oxygen
 Antibiotics (macrolides) (reduces infectivity but not duration)
 Prevention:
 Pertussis vaccination
 Antibiotics (macrolides) for household contacts
COMPLICATIONS
 Pressure-related: subconjunctival haemorrhage, epistaxis, rectal prolapse, hernias
 Respiratory-related: pneumonia, pneumothorax, bronchiectasis
 Neurological : seizures
 Death is a rare, but significant risk in infants
MUMPS
Mumps is an acute, self-limiting, viral infection caused by the mumps virus .
CLINICAL PRESENTATION
 Non-specific prodrome of fever, headache, malaise, myalgias (especially neck pain)
 Usually followed by tender parotid swelling secondary to parotitis (often ears are pushed up and out)
 One third of infections present only as an URTI with no parotid swelling
DIAGNOSIS
 Clinical diagnosis
TREATMENT
 Supportive
 Prevention – live attenuated vaccination (part of the MMR vaccine)
COMPLICATIONS
 Common: aseptic meningitis and orchitis (can cause infertility)
 Less common: arthritis, pancreatitis, hearing impairment
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URINARY TRACT INFECTION

DIAGNOSIS
 Labs – CBC, U&E, CRP, full sepsis screen (indicated if under 3 months old)
 Imaging – as for vesicoureteral reflux (indicated if under 3 months old, atypical UTI, or unresponsive to antibiotics for 48 hours)

 Urinalysis (R&M/C&S) – definitive test

 Urine bag – only useful as an exclusion test (should not be sent for culture)
 Clean catch – useful but difficult to obtain
 MSU – useful but only obtained from children who void on request (usually >3 years old)
 Catheter specimens – useful if positive urine bag or unable to provide MSU (preferred to suprapubic aspiration )
TREATMENT
 Initial IV therapy (consider for children under 6 months):
 Under 3 months of age (CNS sepsis not excluded) – IV amoxicillin + cefotaxime
 Under 3 months of age (CNS sepsis excluded) – IV amoxicillin + gentamicin
 Over 3 months of age – gentamicin
 Oral therapy (consider for children over 6 months in absence of atypical infection) – as for adults
Vesicoureteral reflux
Vesicoureteral reflux is retrograde projection or urine from the bladder to the ureters and kidneys.
PATHOPHYSIOLOGY
 Primary reflux – incompetent or inadequate closure of ureterovesical junction
 Secondary reflux – abnormally high intravesical pressure resulting in failure of ureterovesical junction closure
 Associated with posterior urethral valves (most common – only in males), urethral stenosis, or neurogenic bladder
CLASSIFICATION
 Mild reflux (grades I-II) – no ureteral or renal pelvic dilation (often resolves spontaneously)
 Moderate to severe reflux (grades III-IV) – ureteral dilation with associated caliceal blunting in severe causes
 However, the renal abnormalities found in conjunction with high grade reflux are now known to usually be congenital
CLINICAL PRESENTATION
 Typically, presents as recurrent urinary tract infections in childhood
DIAGNOSIS
 Initial test – pre- or post-natal U/S (may detect hydronephrosis and/or oligohydramnios)
 Definitive test (assess for renal scarring) – DMSA renal function scan (young children) or voiding cystourethrogram (older
children)
TREATMENT
 Treat infections aggressively – daily co-trimoxazole (or amoxicillin if <6 weeks of age)
 Surgical treatment (if severe) – ureteral reimplantation
OUTCOMES
 Associated with ESRD if inadequately treated

Neonatology
GESTIONAL AGE AND SIZE CONCERNS
Abnormalities of gestational age and size
ABNORMALITIES

Pre-term infants Respiratory: RDS, apnoea, bronchopulmonary dysplasia

<37 weeks Gastrointestinal: feeding difficulties, NEC, jaundice, hypocalcaemia, hypoglycaemia
Cardiovascular: PDA
Other: retinopathy of prematurity, anaemia, intraventricular/intracranial haemorrhage

Post-term infants Increased risk of stillbirth and neonatal death

>42 weeks Foetal ‘post-maturity syndrome’ – impaired growth due to placental dysfunction
Meconium aspiration

NEONATAL RESCUSCITATION
APGAR score
SIGN 0 1 2
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Activity (tone) Absent Flexion of limbs Active motion

Pulse (heart rate) Absent <100/min >100/min

Grimace (reflex) Flaccid Grimace Cough/cry

Appearance (colour) Blue/pale Body pink/extremities blue Completely pink

Respirations (effort) Absent Slow/irregular Good/crying

NEONATAL RESUSCITATION ALGORITHM

 The APGAR score is assessed at one and five minutes post-delivery
 Interpretation:
 Score 8-10 – good cardiopulmonary adaptation
 Score 4-7 – possible need for resuscitation
 Score 0-3 – immediate resuscitation required
 Resuscitation guideline:
 If <7 at five minutes , reassess every five minutes until >7
 Do not wait to assign APGAR score before initiating resuscitation
 Resuscitation method:
 Steps to take for all infants (before ABCs):
 Warm (radiant heater and warm towels) and dry the newborn (remove wet towels)
 Position and clear airway (‘sniffing’ position)
 Stimulate infant (rub lower back gently) EXCEPT if meconium present (in which case suction)
 Assess breathing and heart rate
 Airway
 If meconium present – intubate and suction trachea if baby is not vigorous
 If meconium absent – suction mouth followed by nose if required
 Breathing
 If apnoeic or HR <100/min – apply PPV (5 inflation breaths followed by ventilation breaths)
 Circulation
 If HR <60/min – start neonatal resuscitation protocol (3 compressions : 1 ventilation)
CONGENITAL MALFORMATIONS
Common congenital malformations
CLINICAL NOTES

Tracheoesophageal fistula Tracheoesophageal fistula is a fistula between the trachea and oesophagus.
 Associated with defects such as oesophageal atresia and VACTERL (vertebral, anal, cardiac, tracheal, oesophageal,
renal, and limb) abnormalities

 Presentation: polyhydramnios, inability to feed, gagging, recurrent pneumonia, cyanosis, respiratory distress,
bubbles of mucous from mouth and nose that return after suctioning
 Diagnosis: CXR showing NGT coiled in oesophagus (i.e. inability to advance NGT)
 Treatment: surgical

Congenital diaphragmatic hernia Congenital diaphragmatic hernias occur when components of the abdomen protrude into the thorax.
 Typically, posterolateral (left-side) (Bochdalek)

 Presentation: respiratory distress, sunken abdomen, bowel sounds over thorax

 Diagnosis: prenatal U/S or MRI confirmed by postnatal CXR (bowel loops in hemithorax)
 Treatment:
 Surgical (in-utero surgery to form tracheal obstruction can prevent pulmonary hypoplasia)
 Respiratory stabilisation (ventilation or ECMO)

Umbilical hernia Umbilical hernia is incomplete closure of peritoneal and fascial layers within umbilicus by 5 years of age.
 Relatively common (5%) but typically asymptomatic and self-resolving

Inguinal hernia Inguinal hernia in neonates are always indirect – intraabdominal descend through patent processus vaginalis.
 Relatively common (5%) – especially if pre-term (2x risk and more likely bilateral)
 20% risk of incarceration (more common in females)

 Presentation: painless intermittent mass in groin (may extend into scrotum) (symptoms if incarcerated)
 Diagnosis: physical exam (palpation along inguinal canal and testicular exam in males)
 Treatment:
 Manual reduction (to relieve acute symptoms)
 Immediate surgical treatment (herniorrhaphy) – due to risk of incarceration

Gastroschisis Gastroschisis is a defect in the abdominal wall with herniation of exposed intestine.
 Herniated viscera are not covered by a protective membrane
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 Not associated with genetic syndromes

 Presentation: exposed and inflamed hollow viscera (stomach or intestines) typically lateral to cord
 Diagnosis: prenatal U/S or elevated MS-AFP (or visualisation)
 Treatment: keep viscera moist and follow with surgical reduction

Omphalocoele Omphalocoele is a defect in the abdominal wall at the umbilicus with herniation of sac-covered viscera.
 Herniated viscera is covered by a protective membrane (peritoneum and amniotic membrane)
 Associated with genetic syndromes

 Presentation: exposed viscera (intestine, stomach, or liver) at the cord

 Diagnosis: prenatal U/S or elevated MS-AFP (or visualisation)
 Treatment: keep viscera moist and follow with surgical reduction

Intestinal atresia Intestinal atresia is failure of segments of the intestine to recanalize during gestational age weeks 8 to 10.
 Duodenal – associated with other anomalies such as trisomy 21
 Jejunal/ileal – associated with cystic fibrosis
 Colonic – unknown mechanism
 Anal – associated with VACTERL abnormalities

 Presentation: presents as neonatal bowel obstruction (gastric distension and bilious vomiting)
 Diagnosis: AXR (‘double-bubble’ sign for duodenal atresia) and contrast enema
 Treatment: NPO, NGT, and surgical correction

Biliary atresia Biliary atresia is atresia of the extra-hepatic bile ducts causing conjugated jaundice after the first week of life.
 Progressive obliterative cholangiopathy
 Associated with anomalies in one-third of cases (situs invertus, congenital heart defects, polysplenia)

 Presentation: conjugated hyperbilirubinaemia (persistent neonatal jaundice) and hepatomegaly

 Diagnosis: LFTs, abdominal U/S, liver biopsy
 Treatment: fat-soluble vitamin replacement and surgical correction (most require liver transplantation)

COMMON CONDITIONS OF NEONATES

Apnoea
DEFINITION
 Apnoea – similar to adults (i.e. central or obstructive) but the definition of an apnoeic/hypopnoeic event is different
 Periodic breathing – normal respiratory pattern in the newborn (rapid respiration alternating with pauses lasting 5 to 10 seconds )
AETIOLOGY
In term infants, apnoea requires a full septic workup (as it is associated with sepsis).
 Also, consider apnoea of prematurity (if <34 weeks) , aspiration, or CNS/CVS/metabolic issues
TREATMENT
 Supportive (supplemental oxygen , ventilatory support , and tactile stimulation )
 Apnoea of prematurity – caffeine is used to stimulate the CNS and diaphragm (typically, resolves by 36 weeks gestation )
 Prevention – betamethasone valerate (corticosteroid)

Hypoglycaemia
Hypoglycaemia in neonates is defined as a glucose level of <2.6mmol/L .
AETIOLOGY
 Decreased carbohydrate stores – premature or SGA
 Increased carbohydrate utilisation – neonatal sepsis or RDS
 Maternal factors – hypertension or diabetes
 Rarer causes – metabolic or endocrine (GH, cortisol, epinephrine deficiency) disorders
TREATMENT
 Monitor at-risk infants (measure BGL per hospital protocol)
 Start milk feeds ASAP after birth and continue regularly
 Treatment – buccal 40% dextrose gel (or IV glucose and IM glucagon if severe)

Jaundice
Jaundice is very common in newborns (up to 60% of term babies).
CLASSIFICATION

Causes of neonatal jaundice by age

<24 HOURS 24 HOURS TO 1 WEEK PROLONGED (>1WK)
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ALWAYS PATHOLOGIC  Physiologic  Prolonged physiologic (in pre-term)

 Haemolytic (Rh or ABO incompatibility)  Breast-feeding jaundice  Breast-milk jaundice
 Neonatal sepsis/congenital infection (TORCH)  Haemolytic anaemia  Neonatal hepatitis
 Haemorrhage  Neonatal sepsis/congenital infection (TORCH)  Hypothyroidism
 Conjugation defects (Gilbert/Crigler-Najjar)
 Metabolic disorder
 Biliary atresia

DIAGNOSIS
 Unconjugated (suspect haemolysis):
 First-line – LFTs, reticulocytes, blood grouping (ABO and Rh), and DAAT
 Second-line – TFTs, G6PD, blood smear, and septic workup
 Conjugated (always pathologic):
 First-line – LFTs and hepatic ultrasound
 Second-line – metabolic screen and TORCH/hepatitis screen
TREATMENT
 Treat underlying cause
 Monitor bilirubin levels as per published graphs based on age/gestation
 Unconjugated (to prevent kernicterus):
 Mild elevation – phototherapy (blue-green wavelength, not UV light) (not indicated if conjugated as it leads to skin bronzing)
 Severe elevation – exchange transfusion
Physiologic jaundice
Physiologic jaundice is very common and typically occurs in the first three days of life and resolves by ten days.
 May be prolonged in premature infants
PATHOPHYSIOLOGY
 Caused by decreased RBC lifespan, immature conjugation of bilirubin, and increased enterohepatic circulation
CLASSIFICATION
 Breast-feeding jaundice (common) – due to lack of milk production leading to dehydration and exaggerated physiologic jaundice
 Breast-milk jaundice (rare) – due to conjugation inhibitor found in breast milk (usually resolves by 6 weeks)
Kernicterus
 Clinical presentation varies from asymptomatic to acute encephalopathy and permanent neurological deficit

Respiratory distress in neonates

 Definitions:
 RDS – respiratory distress syndrome
 TTN – transient tachypnoea of newborn
 MAS – meconium aspiration syndrome
Common causes of respiratory distress in neonates
RDS TTN MAS
Aetiology Surfactant deficiency leads to atelectasis Delayed reabsorption of lung fluid leading Meconium is sterile, but aspiration causes
(reinflation causes respiratory distress) to tachypnoea (‘wet lung syndrome’) obstruction and chemical pneumonitis

Gestation Preterm Late pre-term/Term Post-term

Risk factors Pre-term delivery, maternal DM, male sex, Late pre-term delivery, maternal DM, male Meconium-stained amniotic fluid
second twin, caesarean section sex, macrosomia, caesarean section

Clinical Respiratory distress within first few hours Tachypnoea within first few hours of life Respiratory distress within first few hours
presentation of life with increased work of breathing with increased work of breathing (no of life with increased work of breathing
and hypoxia/cyanosis hypoxia or cyanosis) and hypoxia/cyanosis

CXR findings Ground-glass appearance with air Perihilar streaking Irregular infiltrates, hyperinflation, and
bronchograms occasionally pneumothorax

Treatment Prevention Prevention Prevention

 Betamethasone valerate  Avoidance of early caesarean section  Avoidance of post-term delivery
Treatment Treatment Treatment
 Intubation, ventilation, oxygenation  Oxygenation  Intubation, ventilation, oxygenation
 Artificial surfactant  CPAP  Suction
 Antibiotics

Outcomes Risk of chronic lung disease and Recovery by 72 hours Mortality up to 20%
retinopathy of prematurity
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Bronchopulmonary dysplasia
Bronchopulmonary dysplasia i s a form of chronic lung disease that affects newborns (mostly premature), defined as:
 An oxygen requirement for greater than 28 days of life, and/or
 Persistent need for oxygen and/or ventilatory support at 36 weeks corrected gestational age
PATHOPHYSIOLOGY
 Caused by barotrauma and oxygen toxicity from prolonged intubation or ventilation (typically, from RDS)
DIAGNOSIS
 CXR – demonstrates hyperinflation and atelectasis
TREATMENT
 No effective treatment
 Can prevent with steroids, surfactant treatment , gradual wean from ventilator , and nutritional optimisation )
OUTCOMES
 Chronic respiratory failure (with pulmonary hypertension, cor pulmonale, and failure-to-thrive)
 Lung impairment may persist into adulthood
 Associated with poor neurodevelopmental outcomes

Retinopathy of prematurity
Retinopathy of prematurity is a vasoproliferative retinopathy caused by high oxygen exposure after birth (i.e. in resuscitation).
 Can lead to retinal detachment and permanent visual loss
 Routinely screened in babies less than 30 weeks and/or less than 1250 grams
 Treated with laser therapy (but is associated with adverse visual outcomes despite treatment)

Bleeding disorders in neonates

CLASSIFICATION
 Haemorrhagic disease of the newborn
 Caused by vitamin K deficiency (poorly transferred across the placenta)
 Presents with prolonged bleeding and potentially severe internal bleeding (including intracranial haemorrhage) in the first
week
 Treated with IM vitamin K administration at birth to all newborns
 Intraventricular haemorrhage
 Caused by prematurity , small for gestational age , haemodynamic instability , or coagulopathy
 Typically, asymptomatic (subtle signs may include apnoea, bradycardia, changes in tone or activity)
 May be present catastrophically as bulging fontanelle, haemodynamic instability, acidosis, and seizures
 Routinely screened via head U/S in babies less than 32 weeks and/or less than 1500 grams
 Treatment – supportive
 Complications – major neurodevelopmental defect (mental retardation, cerebral palsy) and hydrocephalus
 Traumatic bleeding associated with prolonged second stage or instrumental delivery :
 Cephalohaematoma – subperiosteal skull bleeding
 Presents with well-defined haematoma that does not cross suture lines
 Subgaleal haemorrhage – supraperiosteal skull bleeding (surgical emergency due to potential space for blood loss)
 Presents with fluctuant boggy mass over the scalp that does cross suture lines
Haemoglobin in infancy
Haemoglobin decreases after birth to a low-point at 2-3 months (as low as 90, and lower in pre-term infants)
 Due to decreased EPO and red cell production (which slowly rises after this low-point)

Neonatal sepsis
CLASSIFICATION
 Early onset (<72hr) – almost exclusively vertical transmission (commonly GBS, E. coli, Listeria)
 Risk factors include maternal infection, maternal fever, prolonged rupture of membranes, preterm labour
 Associated with neonatal pneumonia
 Late onset (>72hr) – typically, acquired after birth (i.e. preterm infants in NICU) (commonly CONS)
TREATMENT
 Follow hospital protocol, but typically includes:
 Empiric IV antibiotics (amoxicillin + cefotaxime (+ gentamicin if normal CSF)) (acyclovir if HSV suspected)
 IV fluids (± inotropes )

Skin conditions of the newborn

 Milia – small pearly papules on nasal bridge, cheeks, and palate (self-resolving)
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 Capillary haemangioma – raised red lesion which increases after birth and involutes (90% resolves by age 9)
 Can be treated with β-blockers
 Erythema toxicum – yellow-white papules surrounded by erythema (palm/sole-sparing) (self-resolving by 2 weeks)
 Vernix caseosa – soft, creamy, white layer covering baby at birth

Genetic disease
COMMON GENETIC DISEASES
Common Trisomies
DISEASE GENETIC ABNORMALITY CLINICAL NOTES

Down syndrome Trisomy 21  Presentation - MED FAST

(most common)  Meiotic nondisjunction (95%)  Mental retardation
 Robertsonian translocation (4%)  Epicanthal folds (prominent)/Eye problems (upslanting with cataracts; Brushfield spots)
 Mosaicism (1%)  Duodenal atresia
 Flattened facies
Associated with:  Atrioventricular septal defect (or other cardiac defect)
 Advanced maternal age  Single palmar crease
 Balanced translocation in parent  Toe gap (1st and 2nd toe)
(greater recurrence risk than  Outcomes and complications:
maternal age)  Increased risk of AML/ALL, short stature, Alzheimer disease, and hypothyroidism
 Survival is typical into late adulthood

Edwards syndrome Trisomy 18  Presentation - EDWARDS

(2nd most common)  Eighteen (trisomy)
Associated with:  Digits overlap with a clenched fist
 Male sex (M:F 3:1)  Wide head (prominent occiput)
 Absent intellect (mental retardation)
 Rocker bottom feet
 Diseased heart (VSD, ASD, or PDA in 60% of cases)
 Small lower jaw (micrognathia)
 Outcomes and complications:
 Typically, death in the first year (profound retardation in survivors)

Patau syndrome Trisomy 13  Presentation - CRAMP

 Cleft lip/palate/Cardiac defects (VSD, ASD, or PDA in 80% of cases)
 Renal abnormalities
 Absent intellect (mental retardation)
 Microcephaly
 Polydactyly
 Outcomes and complications:
 Typically, death in the first year (profound retardation in survivors)

Common Sex Chromosome Abnormalities

DISEASE GENETIC ABNORMALITY CLINICAL NOTES

Klinefelter syndrome (male) 47, XXY Characterised by presence of inactivated X chromosome (Barr body).

Associated with:  Presentation

 Advanced maternal age  Tall, slim, long limbs, and underweight
 Post-pubertal gynaecomastia and lack of facial hair
 Mild intellectual disability
 Infertility due to hypogonadism/hypospermia
 Treatment: testosterone

Turner syndrome (female) 45, XO Characterised by absence of inactivated X chromosome (Barr body).

Not associated with:  Presentation - CLOWNS

 Advanced maternal age  Cardiac abnormality (coarctation and bicuspid aortic valve)
 Lymphoedema
 Ovarian insufficiency (and infertility)
 Webbed neck
 Nipples widely spaced
 Short stature
 + mild intellectual disability
Treatment:
 Oestrogen (secondary sexual characteristics)
 GH (short stature)
 Cardiac imaging (to screen for abnormality)

Noonan syndrome (both) 46, XX or 46, XY  Autosomal dominant (not a sex chromosome disorder)
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 Similar features to Turner syndrome (although also occurring in males)

Double Y (male) 47, XYY  Minimal symptoms (other than tall stature, acne, and learning problems)

Common Metabolic Disorders

DISEASE CLINICAL NOTES

Phenylketonuria  Autosomal recessive deficiency of phenylalanine hydroxylase prevents conversion of phenylalanine to tyrosine
(amino acid disorder) leading to build up of toxic metabolites
 Clinical presentation:
 Baby is normal at birth, but develops in the first few months:
 Musty odour, eczema, hypertonia, tremors, mental retardation, and hypopigmentation (fair hair, blue eyes)
 Can cause congenital abnormalities in children born to uncontrolled PKU mothers
 Treatment: special diet (decreased phenylalanine, increased tyrosine)

Maple syrup urine disease  Clinical presentation: similar to PKU but sweet-smelling urine and no hypopigmentation
(amino acid disorder)  Treatment: special diet (or liver transplantation)

Galactosaemia  Autosomal recessive disorder that prevents metabolism of galactose

(carbohydrate disorder)  Clinical presentation: vomiting after feeding, growth retardation, and infantile cataracts
 Treatment: special diet (avoid breast feeding)

MCAD  Autosomal recessive deficiency of medium chain acyl-CoA dehydrogenase prevents oxidation of medium-chain fatty
(fatty acid disorder) acids into acetyl-CoA
 Clinical presentation: hypoketotic hypoglycaemia and liver dysfunction, often preceded by fasting or vomiting
 Leads to infant death if untreated
 Treatment: special diet and avoidance of fasting

Lysosomal storage diseases  Examples: Hurler’s, Niemann-Pick, Tay-Sachs, Gaucher, Fabry, Krabbe
(invariably fatal)  Clinical presentation: developmental delay, epilepsy, encephalopathy
 Tay-Sachs disease is associated with Cherry-red spot on macula without hepatosplenomegaly

Other Genetic Diseases

DISEASE GENETICS CLINICAL NOTES

Fragile X syndrome X-linked dominant  Presentation

(triplet repeat disorder of  Large jaw, testes, and ears
FMR1 gene)  ADHD and/or autism
 Intellectual disability (most common heritable cause in boys)

DiGeorge syndrome Microdeletion of 22q11  Presentation - CATCH 22

(2nd most common genetic  Cyanotic congenital heart disease (esp. transposition of great vessels)
diagnosis after trisomy 21)  Anomalies (craniofacial – micrognathia, cleft palate, and low set ears)
 Thymic hypoplasia (immunodeficiency)
 Cognitive impairment
 Hypoparathyroidism
 22q11 microdeletions

Prader-Willi syndrome Loss of paternal  Presentation – H3O

contribution of the proximal  Hypotonia and weakness
part of the long arm of  Hypogonadism
chromosome 15  Hyperphagia (obsessive)
 Obesity (and T2DM) but short stature

Angelman syndrome Loss of maternal  Presentation

contribution of the proximal  Abnormal facies
part of the long arm of  Developmental and growth delay
chromosome 15  Seizures
 Characteristically smiling and laughing (‘angel’-like)

Cri-du-chat syndrome Deletion of short arm of  Presentation

chromosome 5  Microcephaly (with abnormal facies)
 High pitched cry (‘cry of the cat’)

Marfan syndrome Autosomal dominant Connective tissue disorder due to a mutation in FBN1 gene that encodes for fibrillin-1, an
essential component of ECM (typically, normal lifespan)

 Presentation
 Tall, thin, long arms and legs; also, arachnodactyly and pectus excavatum
 Flexible joints and scoliosis
 Complications: valvular heart disease (MR/AR), aortic aneurysm, lens dislocation

Ehlers-Danlos syndrome Various A group of connective tissue disorders (various genetic defects with different prognoses)

 Presentation – characterised by extreme joint laxity, stretchy skin, and scar formation
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Newborn Metabolic Screening Programme (Guthrie card)

 A newborn screening test via heel-prick blood sample that screens for 24 metabolic disorders , including:
 Amino acid disorders (e.g. PKU and MSUD)
 Carbohydrate disorders (e.g. Galactosaemia)
 Fatty acid oxidation disorders (e.g. MCAD)
 Cystic fibrosis (CF)
 Congenital adrenal hyperplasia (CAH)
 Biotinidase (vitamin B7) deficiency
 Severe combined immune deficiency (SCID)

Note: the sample should be taken between 48 and 72 hours of age for all babies regardless of medical conditions or prematurity.
Inheritance patterns

Development
MILESTONES
 For premature infants chronological age must be adjusted for gestational age
Developmental milestones
AGE GROSS MOTOR FINE MOTOR LANGUAGE SOCIAL/COGNITIVE

2 months Lifts head when prone Immature grasp Coos Social smile

4 months Rolls front to back; head control Grasp Laughs/squeals Laughs/squeals

6 months Sits unassisted (tripod) Raking grasp; transfers objects Babbles Start of stranger anxiety;
object permanence

9 months Crawls; cruises; pulls to stand; Pincer grip (3 fingers) Non-specific (e.g. ‘mama/dada’) Peak stranger anxiety;
sits unassisted (straight back) waves goodbye

12 months Walks Pincer grip (2 fingers); One-word phrase (few words) Separation anxiety;
throws ball follows 1-step command;
knows name

18 months Runs 3 cube tower One-word phrase (10 words) Pointing

2 years Jumps; kicks ball; 6 cube tower Two-word phrase 2-step command;
stairs (one step both feet) (50% intelligible) asks for things

3 years Stairs (one step one foot) Draws circle Three-word phase Brushes teeth with help
(75% intelligible)

4 years Hops Draws cross/square Colours/Numbers Co-operative play

(100% intelligible)
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5 years Skips Draw triangle Fluent speech Imaginative play

PRIMITIVE REFLEXES
Primitive reflexes are present up to six months and persistence after this may suggest abnormality (e.g. cerebral palsy).
 An upgoing Babinski reflex is normal up to two-years of age
EXAMPLES
 Moro – sudden dropping of infant from a semi-upright position
 Normal response – abduction and extension, followed by flexion and adduction, of the arms
 Grasp – placement of examiner’s finger in infant’s palm
 Normal response – flexion of infant’s fingers
 Stepping – holding the infant upright and placing the sole of foot onto a surface
 Normal response – a movement that resembles walking
 Rooting – tactile stimulus near mouth
 Normal response – infant turns head and tongue to side of stimulus (associated with suckling reflex )
GROWTH
Basics of growth
 Measurement of growth achieved by plotting of:
 Head circumference (up to 2 years of age)
 Increased – indicates space-occupying lesion or hydrocephalus
 Decreased – indicates microcephaly (e.g. TORCH infections)
 Weight and height (routinely into adulthood)
 Infants may lose up to 10% of their body weight in the first few days of life, but this should return by two weeks
Fontanelle
The fontanelle is an anatomical feature of the infant skull which is formed by membranous gaps (sutures) between the cranial bones.
 Allows for rapid stretching and deformation of the skull as the brain grows and flexing of skull during passage through the birth canal
 Anterior fontanelle (larger, diamond shaped) – persists until 18 months
 Bulging fontanelle – suggestive of increased intracranial pressure
 Sunken fontanelle – suggestive of dehydration of malnutrition
 Posterior fontanelle (smaller, triangle shaped) – persists for a few months (typically, less apparent)
Short stature
A short stature is defined as a height less than the 3 rd percentile for age and sex.
 Children are usually in a percentile between their parent’s height (i.e. the mid-parental height )
 Boys target height – (fathers height + mothers height + 13) divided by 2
 Girls target height – (fathers height + mothers height – 13) divided by 2
AETIOLOGY
 Any chronic disease can cause short stature, but short parents are the most common cause; consider, ABCDEFG if suspicious:
 Alone (neglect)
 Bone dysplasia (e.g. rickets)
 Chromosomal (e.g. Turner, CF, Down)
 Delayed growth (constitutional)
 Endocrine (e.g. Cushing, hypothyroid, low GH, panhypopituitarism)
 Familial
 GI malabsorption (e.g. coeliac, IBD)
TREATMENT
 Treat underlying cause
 Consider growth hormone therapy (effective if administered at an early age)
Tall stature
A tall stature is defined as a height greater than two standard deviations for age and sex.
 Typically, not a clinical ‘issue’ (due to societal perspective)
 If suspicious, consider other causes:
 Constitutional (e.g. tall parents)
 Endocrine (e.g. precocious puberty or gigantism)
 Genetic (e.g. Marfan or Klinefelter syndrome)
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Failure to thrive (FTT)

Failure to thrive is defined as a persistent weight less than the 5th percentile or falling across two major percentile curves on a weight
curve.
 The most common cause is inadequate caloric intake
CLASSIFICATION
 Non-organic FTT (90% of cases)
 Results from complex factors in parent-child relationship (e.g. poverty, poor diet, neglect, abuse)
 Organic FTT (10% of cases) – due to an underlying medical condition
 Inadequate intake (e.g. anorexia, oropharyngeal dysfunction)
 Excessive consumption (e.g. heart failure, cystic fibrosis, hyperthyroidism)
 Abnormal utilisation (e.g. metabolic disease)
 Excessive output (e.g. malabsorption, diarrhoea)
SEXUAL DEVELOPMENT

BASICS
 Female pubertal stages (Boobs, Pubes, Grow, Flow):
 Average age of puberty is 8 to 13 years
 Precocious puberty is common and often constitutional; but delayed puberty is rare (rule out organic causes)
 Usual sequence is as follows:
 Thelarche (Boobs) – breast development
 Pubarche (Pubes) – pubic and axillary hair development
 Growth spurt (Grow)
 Menarche (Flow) – onset of menstruation (usually following peak height velocity)
 Male pubertal stages (Ball, Shawl, Call, Tall ):
 Average age of puberty is 9 to 14 years
 Precocious puberty is rare (rule out organic causes); but delayed puberty is common and often constitutional
 Gynaecomastia is a common self-limiting condition of puberty (but discharge or fixed mass should be investigated)
 Usual sequence is as follows:
 Gonadarche (Balls) – testicles enlarge
 Pubarche (Shawl) – pubic hair development
 Adrenarche (Call) – axillary and facial hair, voice changes
 Growth spurt (Tall)
TANNER STAGING
Tanner staging is a scale used in paediatrics to assess sexual development.
 There are five stages (one, pre-adolescent, to five, adult)
ABNORMALITIES OF SEXUAL DEVELOPMENT
 Precocious puberty – defined as any sign of secondary sexual characteristics in females less than 8 or males less than 9
 Classified as central (GnRH-dependent) or peripheral (GnRH-independent)
 Delayed puberty – defined as no breast development/pubic hair in females by age 13 or no testicular enlargement in males by age 14
 Classified as central (GnRH-dependent) or peripheral (GnRH-independent)
 Constitutional growth delay – a normal variant and most common cause of delayed puberty
 Growth (and bone age) is delayed but remains consistent trajectory; typically, reaches height potential
CHILD ABUSE
Child abuse is an act of commission (physical, sexual, or psychological abuse) or omission (neglect) by a caregiver that harms a child.
 There is a legal obligation to report child abuse to the relevant parties if there is clinical suspicion
CLINICAL PRESENTATION
 Typically, presents as physical findings not explained or consistent with clinical history of injury or medical condition
 For example, a 2-month old infant cannot ‘roll off couch’ as they cannot roll yet
 TEN-4 rule – be aware of any bruising to the Torso, Ears, or Neck or bruising anywhere on a child 4 months old or younger
 Bruising is extremely rare in infants younger than 6 months
Common presentation and mimics of child abuse
TYPE OF ABUSE CLINICAL PRESENTATION AND DIAGNOSIS MIMICS

Bruises Most common physical finding Mongolian spots (flat, grey-blue, birthmarks with wavy
borders and irregular shape that resemble bruising and
disappear by five years old)

Burns Contact burns – e.g. cigarettes Scalded skin syndrome

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Immersion burns – buttocks or stocking-glove distribution

Abusive head trauma Changes in LOC, neurological symptoms, or retinal haemorrhage Accidental head trauma

Fractures Specific fractures very specific of child abuse: Osteogenesis imperfecta

 Bucket handle or Corner fractures (epiphyseal/metaphyseal)
 Ribs (especially posterior) – indicates squeezing
 Spiral fractures of humerus/femur

Sexual trauma Suspect if genital trauma, bleeding, or foul discharge; also, Vaginal foreign body
consider if preoccupation/knowledge of adult sexual behaviour

Other Torn frenulum Accidental injury

DIAGNOSIS
 Document all injuries on a body diagram (photography is ideal; although, do not use personal camera)
 Bruising – haematological workup (CBC, coagulation factors, vWF)
 Fractures:
 Orthopaedic workup (U&E with calcium/phosphate, LFTs, PTH, vitamin D)
 Bone density scans
 Skeletal survey (± bone scan)
 Abusive head trauma:
 Ophthalmological exam for retinal haemorrhage
 Non-contrast CT for subdural/epidural haematoma (consider MRI)
 Sexual trauma:
 Vaginal, anal, and/or oral swabs for STI and sperm (referral to sexual assault doctor for specialist testing)
TREATMENT
 Notify Child Protective Services (Police, Oranga Tamariki, or local DHB services)
 Treat injuries
 Consider admission for protection of child (or medical necessity)
 Exhaustive documentation
CHILDHOOD PSYCHIATRY

Developmental disorders
Global development delay
 Definition – performance significantly below average in two or more domains of development (gross/fine motor, language, or
social/cognitive) in a child less than 5 years old
Intellectual developmental disorder
 Definition – deficits in intellectual and adaptive functioning evident with onset before age 18
 Historically, defined as IQ <70
 Often preceded by diagnosis of global developmental delay
 Aetiology – typically, due to pre-natal causes (esp. TORCH and foetal-alcohol syndrome); consider Fragile X syndrome in males
 Foetal alcohol syndrome – characterised by:
 Facial anomalies (absent philtrum, thin upper lip, epicanthal folds, small palpebral fissures)
 Growth retardation (low birth weight or failure to thrive)
 CNS involvement (cognitive impairment or microcephaly)

Behavioural disorders
Disruptive behavioural disorders
Disruptive behavioural disorders are psychiatric diagnoses of children (under the age of 18) that are more common in males.
CLASSIFICATION
 Oppositional defiant disorder – a pattern of defiant, disobedient, and hostile behaviour towards authority figures for 6 or more
months (may progress to conduct disorder)
 Conduct disorder – a persistent pattern of violating the basic rights of others or age-appropriate societal norms or rules for 1
year or more (may progress to antisocial personality disorder in adulthood)
ADHD
Attention Deficit Hyperactivity Disorder is a disorder characterised by inattention, hyperactivity, and impulsivity.
PATHOPHYSIOLOGY
 Complex but demonstratable and reproducible pathology (with high heritability )
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FEATURES
 Up to 5% of school-aged children
 Male-to-female ratio of 4:1 (although girls may be underdiagnosed as they tend to have inattentive symptoms)
DIAGNOSTIC CRITERIA
 Three subtypes:
 Combined type – 6 symptoms from both inattentive and hyperactivity-impulsivity core symptoms
 Predominantly inattentive type – 6 symptoms from inattentive core symptoms
 Predominantly hyperactive-impulsive type – 6 symptoms from hyperactivity-impulsivity core symptoms
 Diagnostic requirements:
 Onset before age 12
 Symptoms for at least 6 months
 Symptoms present in at least two settings (i.e. home, school, work)
 Causes clinically significant impairment in social, occupational, or other functioning
 Diagnosis in older children and adults have a slightly different criteria (typically, 5 symptoms are required)

TREATMENT
 Non-pharmacological (little evidence) – parental management, behaviour modification, classroom intervention, omega-3 fatty acids
 Pharmacological:
 First-line – stimulants (methylphenidate – i.e. Ritalin and Rubifen)
 Second-line – atomoxetine (noradrenaline reuptake inhibitor)
 Third-line – non-stimulants (e.g. SSRIs) and α2-agonists (e.g. clonidine)
PROGNOSIS
 Typically, continues into adulthood but hyperactive symptoms decline
Autism
DIAGNOSTIC CRITERIA
 Persistent deficits in social communication and interaction, manifested in three areas:
 Social-emotional reciprocity
 Non-verbal communicative behaviours
 Developing, maintaining, and understanding relationships
 Diagnostic requirements:
 Onset in early development period
 Causes clinically significant impairment in social, occupational, or other functioning
 Restrictive, repetitive patterns of behaviour, interests or activities with at least two or more of the following:
 Stereotyped/repetitive speech or motor patterns
 Strict adherence to routine
 Highly restricted fixated interests
 Hyper/hypo-reactivity to sensory input
TREATMENT
 Multidisciplinary treatment is necessary:
 Psychosocial support
 Behavioural management
 Symptom-targeted medication (e.g. atypical antipsychotics for aggression, SSRIs for anxiety/depression, stimulants for ADHD)
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PROGNOSIS
 Variable prognosis (but improves with early intervention)
 Better prognosis if high IQ and communication is possible
Tourette syndrome
DIAGNOSTIC CRITERIA
 Presence of both multiple motor and vocal tics (only 15% of people have coprolalia – repetition of obscene words)
 Tics may wax/wane in frequency but have persisted for more than 1 year (with no tic-free periods greater than 3 months)
 Onset is before 18 years old
TREATMENT
 Clonidine
 Clonazepam
OUTCOMES
 Typically, begins in childhood and declines in severity with age
 Associated with ADHD, learning disorders, and OCD
ENURESIS
Enuresis is involuntary urinary incontinence by day and/or night in children older than 5 years old
 Daytime bladder control achieved 25% by 2 years of age and up to 99% by 3 years of age
 Up to 90% of children attain bladder control before bowel control
CLASSIFICATION
 Primary – nocturnal enuresis in children where bladder control has never been attained
 Typically, due to developmental disorder or maturational lag in bladder control while asleep
 Approximately 15% of children at school entry (males in particular) will have problems with bed wetting
 Treated by bed wetting alarm and reassurance (20% resolve spontaneously each year)
 Secondary – nocturnal enuresis in children after a sustained period of bladder control (>6 months)
 Typically, due to inorganic regression due to stress or anxiety or organic disease (e.g. UTI, DM, DI, neurogenic bladder)
 Treated by management of underlying cause
 Diurnal – daytime enuresis (although most also have nocturnal enuresis)
 Typically, due to micturition deferral (holding urine to last minute) due to psychosocial stressor or organic disease (as above)
 Treated by management of underlying cause and behavioural modification (scheduled toileting, double voiding, etc.)
ENCOPRESIS
Encopresis is faecal incontinence at least once per month in children older than 4 years old
 Typically, occurs in male school-aged children (very rare in adolescence)
Retentive encopresis
 Definition – child holds bowel movement  constipation  overflow incontinence
 Aetiology – typically, due to painful defaecation (often secondary to constipation)
 History – child resists urge to defecate and abdominal pain
 Examination – anal fissures (from passage of hard stools), palpable stool in LLQ, and faecal mass in rectal vault on DRE
 Management – complete clean-out of bowel and behavioural modification
ADOLESCENT MEDICINE

HEEADSSS framework
The HEEADSSS framework is a tool for adolescent history taking:
 Home: Who do you live with? What kind of place do you live in?
 Education/employment: What grade are you in? What are your favourite subjects?
 Eating: Tell me about your meals in a typical day. Have you ever gone on a diet?
 Activities: What do you do after school? On the weekends? Do you use social media?
 Drugs: What seems to be more popular at your school, alcohol or drugs? How often do you drink/smoke marijuana/take other drugs?
 Sexuality: Have you ever had sex with anyone? What do you do to prevent getting a STI/getting (someone) pregnant?
 Suicidality/depression: Have you ever thought seriously about suicide? Are you unhappy?
 Safety/violence: Are you being bullied at school? Has anyone ever touched you in an unwanted way?

Sudden infant death

SUDDEN UNEXPECTED DEATH IN INFNACY (SUDI)
Sudden unexpected death in infancy (SUDI) is defined as ‘sudden and unexpected death of an infant younger than 1 year of age’.
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CLASSIFICATION
 Unexplained - the cause of death cannot be found by history, examination, or a thorough post-mortem and death scene investigation
 Explained – clearly attributable to factors which on their own would be sufficient to cause death
 Unascertained – unclear (often due to incomplete information about the circumstances of death)
FEATURES
 In New Zealand, SUDI is the leading cause of infant mortality with a total population rate of 0.66 deaths per 1000 births (2015)
PREVENTION
 Non-modifiable risk factors:
 SES deprivation
 Young mothers (<25 years) or young infants (<6 months)
 Premature infants
 Māori or Pacific (62% of SUDI cases are Māori babies and 13% Pacific)
 Modifiable risk factors:
 Front (prone) sleeping (‘back to bed’) – main risk factor
 Preterm infants in NICU are often slept in the prone position as it improves respiratory function but they are monitored
 Maternal smoking (maternal smoking cessation ) – second most important risk factor
 Lack of breast feeding (breast feeding )
 Bed sharing (particularly in maternal smoking/alcohol) (use of Pepi-pod )
 Other preventative measures:
 Appropriate infant bedding (firm mattress that fits the bed; avoid loose bedding or pillows)

Oncology
BASICS OF PAEDIATRIC ONCOLOGY
 Some malignancies are more prevalent in paediatric age groups:
 Newborns – nephroblastoma, retinoblastoma, neuroblastoma
 Infancy and childhood – as above, but also leukaemia and CNS tumours
 Adolescence – primarily lymphoma, gonadal, germ cell, and bone tumours
 Prevalence: leukaemia > brain tumours > lymphoma > other malignancy (overall 1-2 cases/10,000 in 0 to 14 year age group)
 Unique treatment considerations because chemoradiation and surgery may impact development, endocrine function, and fertility
 Typically, paediatric malignancies have a good prognosis (>80% overall survival and cure rates)
WILM’S TUMOUR (NEPHROBLASTOMA)

FEATURES
 Most common primary renal neoplasm of childhood (typically, affects one kidney)
 Usually diagnosed between 2 and 5 years of age
 Associated with:
 WAGR syndrome (Wilm’s tumour, Aniridia, Genital anomalies, mental Retardation) with 11p13 deletion
 Beckwith-Wiedemann syndrome (characterised by enlargement of body organs)
 Neurofibromatosis
CLINICAL PRESENTATION
 Typically, asymptomatic unilateral abdominal mass
 May also present with hypertension, haematuria, abdominal pain, or vomiting
 May have pulmonary metastases at time of diagnosis (respiratory symptoms)
DIAGNOSIS
 Biopsy or FNA is required for definitive diagnosis
 Imaging: abdominal U/S (consider CT chest to detect metastases)
TREATMENT
 Nephrectomy ± chemoradiation
OUTCOME
 90% long-term survival
RETINOBLASTOMA

FEATURES
 Most common intraocular neoplasm of childhood (can affect one or both eyes)
 May have familial association (screening of family is essential)
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 Familial retinoblastoma is a risk factor for osteosarcoma

CLINICAL PRESENTATION AND DIAGNOSIS
 Typically, presents with leukocoria (absence of red reflex) or strabismus
DIAGNOSIS
 Clinical diagnosis (including ophthalmological exam under anaesthesia)
 Imaging: U/S and head MRI (may demonstrate calcified mass)
TREATMENT
 Ophthalmologic surgery (enucleation of eye) + chemoradiotherapy
OUTCOME
 Retinoblastoma has one of the best cure rates of all childhood cancers (>95%)
NEUROBLASTOMA
Neuroblastoma is an embryonal tumour of neural crest origin .
FEATURES
 Most common cancer occurring in the first year of life
 More than half of patients are <2 years of age
 70% have distant metastases at presentation
 Associated with neurofibromatosis , Hirschsprung disease , and the N-myc oncogene
CLINICAL PRESENTATION
 Can originate from any site in the SNS, presenting as mass in neck, chest, or abdomen (adrenal gland is most common)
 Signs and symptoms of disease vary with location of tumour:
 Thoracic – dyspnoea, Horner’s syndrome
 Abdomen – palpable mass
 Spinal – cord compression
 Metastasis is common at presentation (>50% present with advanced stage disease)
 Usually to bone/bone marrow (presents as bone pain or limp )
 Paraneoplastic syndromes:
 Excess catecholamines – hypertension, palpitations, sweating
 VIP secretion – diarrhoea or failure to thrive
DIAGNOSIS
 Diagnostic criteria (either of the following):
 Unequivocal histologic diagnosis from tumour tissue biopsy
 Evidence of metastasis to bone marrow (‘rosettes’) on aspirate analysis with elevated urine VMA/HVA level s (catecholamines)
 Staging: CT, bone scan, bone-marrow aspirate
TREATMENT
 Variable (may include surgery, chemoradiation, autologous stem cell transplant, immunotherapy)
OUTCOME
 Often, poor prognosis due to late detection (‘age and stage’ are primary determinants of better outcome)
BONE TUMOURS IN CHILDREN
The main importance of bone tumours in children is to distinguish between Ewing sarcoma and osteosarcoma.
Ewing sarcoma versus Osteosarcoma
EWING SARCOMA OSTEOSARCOMA
Pathophysiology  Sarcoma (neuroectoderm)  Osteoblasts (mesenchyme)
 Associated with chromosome t(11:22) translocation

Epidemiology Common in white male adolescents Common in male adolescents

Clinical presentation Local pain/swelling and systemic symptoms Local pain/swelling (systemic symptoms are rare)

Location Midshaft of long bones Metaphyses of long bones (typically, at knee)

Metastases to lung – 20% of cases

Diagnosis  Labs: leukocytosis, CRP/ESR (mimics infection)  Labs:  ALP

 CXR: moth-eating appearance with periosteal lamellated  CXR: characteristic periosteal reaction:
pattern (‘onion skinning’)  Codman’s triangle (new subperiosteal bone)
 ‘Sunburst’ spicule (tumour extension into periosteum)
 Chest CT: pulmonary metastases
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Treatment Local excision + chemoradiation (moderate prognosis) Local excision + chemotherapy (good prognosis)

Neurology
FEBRILE SEIZURE

FEATURES
 The most common cause of seizure in children (occurs in up to 5% of all children)
 Typically, occurs between 6 months and 6 years of age
CLINICAL PRESENTATION
 Often associated with illness with fever or family history
 By definition, there is no evidence of CNS infection/inflammation or previous history of non-febrile seizures
CLASSIFICATION
 Simple:
 Less than 15 minutes duration
 Generalised tonic-clonic
 No recurrence in a 24-hour period
 No neurological impairment before or after seizure
 Complex:
 Greater than 15 minutes duration
 Focal onset or focal features during seizure
 Recurrent seizures in a 24-hour period
 Neurological impairment before or after seizure
DIAGNOSIS
 Clinical diagnosis (thorough history and examination to exclude CNS inflammation/infection)
 Septic workup if suspicion of CNS inflammation/infection
 EEG/CT/MRI brain is not warranted unless atypical febrile seizure
TREATMENT
 Reassurance is the main treatment:
 Febrile seizures do not cause brain damage
 There is a very small risk for developing epilepsy (2% with typical seizures compared to 1% baseline population)
 There is a moderate chance of recurrence (33%)
 Supportive:
 Treat underlying cause of fever
 Tepid sponge bath
 Antipyretics and fluids for comfort (do not prevent seizure)
 Emergency:
 Seek medical attention if atypical (and treat as status epilepticus if prolonged)
CEREBRAL PALSY
Cerebral palsy is a spectrum of non-hereditary, non-progressive, disorders of movement and posture .
 The most common movement disorder in children
 Often results from prenatal neurologic insult (but in most cases the cause is known)
FEATURES
 Risk factors: SGA, prematurity, maternal infection, perinatal asphyxia, trauma, brain malformation, neonatal cerebral haemorrhage
CLASSIFICATION
 Pyramidal (spastic) – spastic paresis of any or all limbs (75% of cases)
 Intellectual disability are present in up to 90% of cases
 Extra-pyramidal (dyskinetic) – classified as ataxic, choreoathetoid, or dystonic
 Abnormal movements worsen with stress and disappear with sleep
CLINICAL PRESENTATION
 Commonly presents as delayed motor development
 Affected limbs may show hyperreflexia , pathologic reflexes , hypertonia , contractures, weakness , or underdevelopment
 Definitive hand preference before 1 year of age is a red flag
 Toe-walking and scissor gait are common
 Associated with seizure disorders , behavioural disorders , hearing/vision impairment , learning disability , and speech deficits
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DIAGNOSIS
 Clinical diagnosis
 Imaging – may be able to determine underlying case in some cases
TREATMENT
 No curative treatment
 Supportive:
 Special education
 Physiotherapy (and mechanical braces )
 Surgical release of contractures
 Anti-spastic agents (e.g. baclofen or dantrolene)
OUTCOME
 Life expectancy dependent on degree of mobility and intellectual impairment (not on severity of CNS lesion)
BREATH-HOLDING SPELLS
Types of breath-holding spells
BREATH-HOLDING ATTACKS ANOXIC SEIZURES

Trigger Vigorous crying triggered by pain, frustration, anger or fear Sudden unexpected fright or pain (excess vagal activity)
 May be relatively frequent
 Occur between 6-18 months of age

Clinical presentation  Child cries and has forced expiration  Child does not cry
 Loss of consciousness (± decorticate/decerebrate posture)  Seizure-like activity (although NORMAL EEG)
 No post-ictal phase  Post-ictal phase
 Cyanosis  Pallor (due to bradycardia/temporary asystole)

Treatment  Reassurance  Reassurance

 Iron supplements (if iron deficiency)  Iron supplements (if iron deficiency)

Outcome  Typically, self-limiting by school age  Typically, self-limiting by school age

 Does not cause adverse outcomes  Does not cause adverse outcomes

STURGE-WEBER SYNDROME
Sturge-Weber syndrome is a rare congenital neurological and skin disorder.
 Characterised by port-wine stain (in V1/V2 distribution ) with:
 Contralateral seizures
 Ipsilateral glaucoma
 Intracranial calcification (with seizures and developmental delay)
 Abnormal brain blood vessels

Note: port-wine stain is a vascular malformation that does not regress (typically, a birth-mark).

Neurosurgery
NEURAL TUBE DEFECTS
Neural tube defects occur in the first trimester of development and can be almost completely prevented with folic acid
supplementation .
 Spina bifida aperta can be detected via pre-natal blood tests or amniocentesis by detection of high level of α-fetoprotein (AFP)
 Neural tube defects are definitively diagnosed by imaging (CT, MRI, U/S, or X-ray)
Spina bifida occulta
DEFINITION
 Congenital absence of spinous process and a variable
amount of lamina
 Due to failure of fusion of the posterior neural arch
CLINICAL PRESENTATION
 No obvious clinical signs (and not associated with
high AFP)
 Presence of lumbosacral abnormalities (i.e. dimple,
port-wine stain, or hair tuft) is suggestive of
underlying anomaly (e.g. lipoma)
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TREATMENT
 Requires no treatment
Meningocele (spina bifida aperta)
DEFINITION
 Herniation of meningeal tissue and CSF through a defect in the spine but without associated herniation of neural tissue
 Due to primary failure of neural tube closure
CLINICAL PRESENTATION
 Commonly occurs in lumbosacral area
 Low incidence of symptoms or associated anomalies
TREATMENT
 Surgical repair (excellent results)
Myelomeningocele (spina bifida aperta)
DEFINITION
 Herniation of meningeal tissue and CSF through a defect in the spine but with associated herniation of neural tissue
 Due to primary failure of neural tube closure
CLINICAL PRESENTATION
 Sensory and motor changes distal to anatomic level producing varying degrees of weakness and anaesthesia
 Associated with walking difficulties, urinary and faecal incontinence , and proneness to urinary infection
 Almost always occurs in conjunction with hydrocephalus and type II Chiari malformation
TREATMENT
 Surgical repair (in utero closure has improved outcomes)
OUTCOMES
 Excellent operative mortality (close to 0%)
 Most patients have mild-to-moderate intellectual disability
 Early mortality usually due to complications of Chiari malformation
Encephalocele
 Encephalocele (cranium bifidum) is a neural tube defect characterised by sac-like protrusions of the brain through the skull
 Due to failure of rostral neural tube closure
Anencephaly
 Anencephaly is an absent skull vault and cerebral cortex
 Due to amniotic fluid erosion as a result of due to failure of rostral neural tube closure
HYDROCEPHALUS

AETIOLOGY
 Congenital – Dandy-Walker or Chiari malformation, TORCH infections, or aqueduct anomalies
 Acquired – post-meningitis, post-haemorrhage, or due to masses (vascular malformation of malignancy)
CLINICAL PRESENTATION
 Symptoms and signs are age-related
 Before suture closure : increased head circumference, bulging fontanelle, widened cranial sutures
 Before and after suture closure : irritability, lethargy, poor feeding, and vomiting
 Characteristic ‘sunset sign ’ (forced downward deviation of eyes) in severe hydrocephalus
DIAGNOSIS AND TREATMENT
 Diagnosis – skull imaging (X-ray, U/S, CT, MRI) and ICP monitoring
 Treatment – similar to adults
DANDY-WALKER MALFORMATION
Dandy-Walker malformation is a congenital atresia of the median and lateral apertures of the fourth ventricle.
 Associated with hydrocephalus and enlargement of the fourth ventricle (up to 5% of paediatric hydrocephalus)
 Associated with hypoplastic cerebellum and consequent ataxia and motor issues
CHIARI MALFORMATION
Chiari malformations are congenital malformations at the medullary-spinal junction .
Chiari malformation
TYPE I TYPE II
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Definition Cerebellar tonsils below the foramen More extensive cerebellar involvement (with inclusion of medulla and 4th
magnum ventricle) below the foramen magnum

Age of presentation Presents in adolescence Presents in infancy

Clinical presentation Typically, asymptomatic Brainstem and lower cranial nerve dysfunction
 Respiratory arrest is most common cause of mortality
 Associated with myelomeningocele and hydrocephalus

Diagnosis MRI MRI

Treatment Surgical Surgical

CRANIOSYNOSTOSIS
Craniosynostosis is defined as premature closure of the cranial suture(s).
 Classified by suture involvement (most commonly sagittal)
CLINICAL PRESENTATION
 Skull deformity
 Raised ICP ± hydrocephalus
 Ophthalmic issues (due to increased ICP or bony abnormality of orbit)
DIAGNOSIS AND TREATMENT
 Surgery for cosmesis or elevated ICP
 Must differentiate between positional plagiocephaly (head
malformation secondary to back sleeping)

Rheumatology
JUVENILE IDIOPATHIC ARTHRITIS
Juvenile idiopathic arthritis is a group of conditions characterised by persistent arthritis ( ≥6 weeks) in children less than 16 years old.
CLASSIFICATION

Juvenile idiopathic arthritis subtypes

SUBTYPE PRESENTATION RF/ANA STATUS NOTES

Pauci-articular (oligoarthritis)  Involves ≤4 joints (usually weight-bearing)  RF (-)  Most common type of JIA
 No systemic symptoms  ANA (+)  Usually occurs in young girls
 Uveitis is common (requires slit-lamp exam)

Polyarthritis  Involves ≥5 joints (usually symmetric)  RF (-) (unless severe)  Rheumatoid nodules may present in
 Systemic symptoms rare  ANA (+) severe disease (i.e. RF positive)

Systemic-onset (Still disease)  Recurrent ‘spiking’ high fever (>39C)  RF (-)  Joint inflammation may not occur
 Hepatosplenomegaly  ANA (-) for months to years after systemic
 Salmon-coloured macular rash symptoms appear

TREATMENT
 Multi-disciplinary approach:
 Non-pharmacological – physiotherapy
 First line pharmacological – NSAIDs and intra-articular steroids
 Second line pharmacological – DMARDs (e.g. methotrexate), corticosteroids , or biological agents (e.g. etanercept)
KAWASAKI DISEASE
Kawasaki disease is a multi-system acute medium-sized vasculitis of unknown aetiology with a predilection for coronary arteries.
 Most common cause of acquired heart disease after rheumatic fever (in New Zealand only) in children
FEATURES
 Typically, affects Asian children
 Typically, peak incidence between 3 months to 5 years old
CLINICAL PRESENTATION AND DIAGNOSTIC CRITERIA
 Clinical phases of Kawasaki disease:
 Acute phase (0 to 2 weeks) – see Diagnostic criteria; also, normochromic anaemia, leukocytosis, and elevated CRP/ESR
 Subacute phase (2 to 8 weeks) – thrombocytosis and elevated CRP/ESR
 Untreated children may develop coronary artery aneurysms (up to 25% of cases)
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 Chronic phase (>8 weeks ) – all clinical symptoms have settled and CRP/ESR is at baseline
 Untreated children are at risk of aneurysmal expansion and myocardial infarction
 Diagnostic criteria – ‘CRASH and BURN ’:
 Four or more classical symptoms/signs (CRASH), and
 Conjunctivitis
 Rash
 Adenopathy (unilateral)
 Strawberry tongue
 Hands and feet (oedematous, erythematous, flaky skin)
 Fever (>40oC for ≥5 days) (BURN)
DIAGNOSIS
 Labs – CBC and ESR/CRP
 Imaging – echocardiogram at time of diagnosis and screening thereafter (coronary artery morphology)
TREATMENT
 Initial therapy : IVIG (reduces risk of coronary artery aneurysm) and high dose aspirin (reduces cardiovascular risk)
 Long-term therapy : low-dose aspirin (usually for 6 weeks if low-risk; but long-term if coronary aneurysms)
 Patients on aspirin may be at risk of Reye syndrome

Immunology
IMMUNODEFICIENCY DISORDERS
Paediatric B-cell and T-cell deficiencies
CLASSIFICATION
 B-cell disorders (most common)
 Presentation – recurrent respiratory, gastrointestinal, and genitourinary infection with encapsulated organisms
 The main encapsulated organisms are H. influenza, S. pneumonia, N. meningitidis, N. gonorrhoeae
 Treatment – IVIG (except for IgA deficiencies – give IgA-depleted IVIG to prevent transfusion reaction)
 T-cell disorders
 Presentation – opportunistic and low-grade fungal, viral, and intracellular bacterial infections
 Associated with secondary B-cell dysfunction
 Treatment – bone marrow transplantation and antimicrobial prophylaxis
 Combined disorders
EXAMPLES
 B-cell disorders
 Bruton agammaglobulinaemia (X-linked recessive B-cell deficiency found only in boys – life threatening)
 Common variable immunodeficiency (all Ig levels are low – risk of respiratory tract infections, lymphoma, autoimmune
disease)
 IgA deficiency (low IgA – asymptomatic or recurrent respiratory or gastrointestinal infections) (most common)
 May present as anaphylactic transfusion reactions due to anti-IgA antibodies
 T-cell disorders
 Thymic aplasia in DiGeorge syndrome
 Combined disorders
 Severe combined immunodeficiency (X-linked recessive severe deficiency of B and T cells – life threatening)
Paediatric phagocytic disorders
Paediatric phagocytic disorders are characterised by mucous membrane infections, abscesses, and poor wound healing.
EXAMPLES
 Chronic granulomatous disease (deficient superoxide production in PMNs)
 Infecting organisms are catalase-positive (S. aureus, E. coli, Candida, Klebsiella, Pseudomonas, Aspergillus)
 Definitive diagnosis by dihydrorhodamine (DHR) test (supported by neutrophil function assays)
 Treated with daily co-trimoxazole and bone marrow transplantation
 Leukocyte adhesion deficiency (presents as omphalitis in neonatal period with delayed separation of umbilical cord )
 Associated with minimal pus and inflammation in wounds (due to chemotaxis deficit)
 Treated with bone marrow transplantation
 Job syndrome (hyper-IgE syndrome) (associated with recurrent abscesses)
Paediatric complement disorders
Paediatric complement disorders are characterised by recurrent infection by encapsulated organisms.
 Present in children with congenital asplenia or splenic dysfunction (sickle cell disease)
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EXAMPLES
 C1 esterase inhibitor deficiency ( see Haematology)
 Terminal complement deficiency (C5-C9 ) (inability to form membrane attack complex)
IMMUNISATION SCHEDULE

CLINICAL NOTES:
 MMR is a live-attenuated virus ; so, should NOT be given to immunocompromised or pregnant patients
 Pertussis is associated with prolonged inconsolable screaming (>3 hours)
 Egg allergic individuals may be safely vaccinated with the MMR and influenza vaccine

Miscellaneous
PAEDIATRIC TOXICOLOGY

CLINICAL NOTES
 Fuchsia berries are not poisonous
 In petrol ingestion , gastric lavage and charcoal are contraindicated due to the risk of aspiration and chemical pneumonitis
 Observation is the recommended management strategy
DEHYDRATION

CLINICAL NOTES
 Only proven signs of dehydration in children: decreased capillary refill, decreased skin turgor, and deep acidotic breathing
 The most objective sign of fluid loss or gain is weight
Dehydration in children
SEVERITY CLINICAL FEATURES TREATMENT

Mild (≤5% body weight loss)  Dry mucous membranes Water deficit can be calculated following an estimation of the
 Decreased peripheral capillary refill degree of dehydration expressed as % of body weight.
 Thirsty, alert, restless
No clinical dehydration:
Moderate (5-9% body weight loss)  As above (more pronounced)  Encourage oral intake
 Decreased skin turgor
 Decreased central capillary refill Mild-to-moderate dehydration:
 Rapid pulse (with normal blood pressure)  Oral rehydration
 Sunken eyes/sunken fontanelle  NGT rehydration (if unable to maintain oral intake)
 Oliguric  IV rehydration (if unable to maintain losses)
 Lethargic

Severe (≥10% body weight loss)  As above (more pronounced) Mild-to-moderate dehydration:
 Appearance: limp, cold, sweaty, cyanotic  IV rehydration (10-20ml/kg bolus followed by maintenance)
 Rapid pulse and hypotension
 Deep acidotic breathing

PAEDIATRIC CLINICAL PHARMACOLOGY

CLINICAL NOTES
 Compared with children and adults, neonates have:
 Higher volumes of extracellular fluid and total body water ( 75% compared to 55% in adults)
 This leads to a relatively larger volume of distribution and so they require a higher loading dose
 Lower proportions of adipose tissue
 Decreased muscle mass
 A child between 2 to 10 years of age will typically require higher doses/kg/day of medication compared to an adult
 Due to higher GFR and hepatic enzyme activity
 An infant will have lower requirements, due to lower GFR and hepatic enzyme activity
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SELECTED
TOPICS
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General practice
OBESITY

FEATURES
 In New Zealand, roughly 1/3 of adults are obese and a further 1/3 of adults are overweight
 More than ⅔ of Pacific adults and ½ of Maori adults are obese
DIAGNOSIS
 Clinical diagnosis (based on BMI)
 Assess for comorbidity:
 History – readiness and barriers to weight loss (also, eating or mood disorders)
 Examination – blood pressure
 Labs – U&E, LFTs, HbA1c, lipids
TREATMENT
 Goal – a modest weight loss of 5-10% body weight over long term
 Nutrition – have a diverse diet, reduce sugars and saturated fats, increase whole cereals and fibres (eat less, mainly plants )
 Physical activity – thirty-minutes moderate activity five times a week (increased to sixty-minutes most days)
 Green prescription is useful in this regard
 Psychological – cognitive behavioural therapy
 Advanced treatment (only if non-satisfactory progress):
 Pharmacotherapy – orlistat (lipase inhibitor)
 Surgery – bariatric surgery (requires lifelong medical monitoring)
Weight regain
 Hormones:
 Ghrelin (produced in stomach) – increases satiety
 Leptin (produced in adipose) – decreases satiety
 Set-point theory – with weight loss, ghrelin is increased and leptin is decreased (making weight-loss difficult)
 Bariatric surgery – with bariatric surgery, ghrelin is decreased and leptin is increased (increases effectiveness of surgery)
CARDIOVASCULAR RISK ASSESSMENT
Cardiovascular risk assessment utilises several risk factors to calculate a combined five-year cardiovascular event risk .
 Cardiovascular events – angina, acute coronary syndromes, stroke, peripheral vascular disease, or heart failure
 Risk assessment – begin at age 45 (30 if Maori/Pacific/South Asian) if male; age 55 (40 if Maori/Pacific/South Asian) if female
RISK PREDICTION
 Demographic – age, gender, ethnicity
 Family history
 Smoking status
 BMI
 Blood pressure
 Blood glucose (HbA1c)
 Cholesterol (TC/HDL ratio)
RISK REDUCTION
 Lifestyle modification
 Low risk (<5%) – medical management not indicated
 Intermediate risk (5-15%) – consider anti-hypertensives /statins
 High risk (>15%) – recommend anti-hypertensives /statins (also aspirin in low bleeding risk patients under 70)
RISK REDUCTION GOALS
 Lipid management:
 High-risk individuals – aim for LDL-C <1.8mmol/L
 Intermediate risk individuals – aim for LDL-C reduction of >40%
 Blood pressure management – aim for 130/80mmHg
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Emergency medicine and Critical care

Emergency medicine
ASSESSMENT OF PATIENT IN EMERGENCY SETTING

Primary Survey
DRS ABCDEFG
DRS
 Danger – check for danger to yourself and the patient
 Response – check to see if the patient is responsive (i.e. AVPU)
 Send for help – contact emergency services and gather necessary equipment as appropriate
Airway
 Check to see if airway normal
 Can the patient speak? – normal
 Is their noisy breathing? – obstruction until proven otherwise
 Silent with no air moving? – immediate treatment
 Airway management (establish an airway whilst protecting cervical spine):
 Triple airway manoeuvre – head tilt , chin-lift, and jaw-thrust (fixes 90% of compromised airways)
 Assisted airway – oropharyngeal or nasopharyngeal airway
 Definitive airway – laryngeal mask airway , endotracheal tube, or surgical airway Lethal six:
 Adjuncts – suctioning  Tension pneumothorax
 Oxygen therapy :  Open pneumothorax
 High-flow (15L/min) via reservoir mask  Massive haemothorax
 Continuous pulse oximetry (with titrated oxygen)  Cardiac tamponade
Breathing  Flail chest
 Check to see if patient breathing  Severe airway obstruction
 No – assist with bag valve mask
 Yes – assess whether patient is breathing normally (rate, work of breathing, gas exchange – SaO2, ETCO2, ABG)
 Assist with bag valve mask if not improving
 Assess for threats to life (inability to move air in and out of lungs) – presents as respiratory distress (lethal six )
Circulation
 Assess whether the patient is in shock and determine the cause
 Basic treatment of shock:
 Check for major external bleeding – control by direct pressure
 Check for obvious fractures – traction splint long bone fractures
 Optimise blood supply – raise legs or tip head down (for less than 10 minutes)
 Pharmacotherapy – insert two large bore IV lines (or IO if unable) ± volume challenge ± inotropic support
Disability (damage to brain or spinal cord)
 Stabilise any suspected spinal injury
 Assess GCS/AVPU and gross motor and sensory function
 Assess pupil reaction
 Consider treatment for seizure or raised ICP
Environment and Exposure
 Expose patient to assess for any further injuries/rashes
 Examine temperature:
 Hyperthermia – cool to <39 oC and give IV fluids
 Hypothermia – assess severity and re-warm appropriately
 Then maintain body temperature by adequate coverings
Forward planning and Fluids
 Is further back up from specialties required?
 Where is the best option for placement of this patient?
 Are any further fluids required?
Glucose
 Measure BGL
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Secondary Survey
The secondary survey is completed after the primary survey to identify major injuries or areas of concern.
 Consists of full history, physical examination, investigations , and initial management
 Also includes chart review and previous investigation review
HISTORY
 Brief history – SAMPLE:
 Signs and symptoms
 Allergies
 Medications (including when their last tetanus immunisation was)
 Past medical history
 Last meal / fluids
 Events and circumstances of the injury (e.g. blunt injuries, seat belts, airbags, fire, explosions, etc.)
PHYSICAL EXAMINATION
A brief top-to-toe examination should be completed (focused if indicated):
 General – inspection of whole body for blood / other injuries
 Head-and neck – palpation of facial bones / scalp
 Chest – inspect for 1) midline trachea, 2) flail segment, 3) auscultate lung fields
 CVS – murmur, arrhythmia
 Abdomen – brief abdominal exam; including genitalia and PR
 MSK – examine all extremities, checking for pulses and sensation
 Neuro – full cranial nerve examination and GCS
DIAGNOSIS
 Haemodynamically unstable – FAST scan (chest/abdomen free fluid) (laparotomy indicated if positive)
 Haemodynamically stable – consider non-contrast CT (head, face, spine, abdomen, pelvis), CXR, and/or ECG
 Additional labs (bloods, coagulation, cross-match, ABG, etc.)
BASIC RESUSCITATION

CPR
CLINICAL NOTES
 Adult – 30 compressions to 2 breaths (attach defibrillator if available)

Airway obstruction
CLINICAL NOTES
 Responsive – 5 back blows  5 chest thrusts
 Unresponsive – basic CPR

Anaphylaxis
CLINICAL NOTES
 Adult – adrenaline 0.5mg IM q5m up to 3 doses (upper outer thigh)
 IV 1L replacement bolus (if hypotensive)
 Children – adrenaline 10μg/kg IM q5m up to 3 doses (lateral thigh)
 IV 20ml/kg replacement bolus (if hypotensive)
 Persistent airway obstruction – nebulised adrenaline (if upper airway) or nebulised salbutamol (if lower airway)
TOXIDROMES

ABCD3EFG of toxicology
APPROACH TO TOXICOLOGY
 Airway – as normal
 Breathing – as normal
 Circulation – as normal
 Drugs (universal antidotes) (DONT) – dextrose, oxygen, naloxone, thiamine (must give before dextrose)
 Treatments that will not harm patients and may be essential
 Draw bloods – CBC, U&E, coagulation, LFTs, ABG, toxins and/or drug levels
 Decontaminate – dependent on the toxin (e.g. charcoal, gastric lavage, urine alkalinisation, haemodialysis)
 Expose – head-to-toe survey (with removal of clothes)
 Full vitals, ECG, catheter, X-ray – if indicated
 Give specific antidotes
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Common toxidromes
Common toxidromes
GROUP BP HR RR TEMP PUPILS SKIN

Sympathomimetic     Dilated Sweating and tremors

Anti-cholinergic +/-  +/-  Dilated Dry and flushed

Cholinergic +/- +/- +/- +/- Constricted Sweating

Opioid     Pinpoint Normal

Sedative-hypnotics     Variable Normal

Useful mnemonics
 Anti-cholinergic
 Hot as a hare – hyperthermia, Blind as a bat – mydriasis (and blurred vision), Dry as a bone – dry skin
 Red as a beet – vasodilation (flushing), Mad as a hatter – agitation/hallucination
 Bowel and bladder lose their tone – ileus and urinary retention, Heart goes on alone – tachycardia
 Cholinergic (SLUDGEMM) – salivation, lacrimation, urination, diaphoresis, GI upset (diarrhoea), emesis, miosis, muscle spasm

Common drugs/toxins and their antidotes

Common antidotes
DRUG/TOXIN ANTIDOTE DRUG/TOXIN (CONTINUED) ANTIDOTE

Paracetamol N-acetylcysteine Barbiturate Decontamination (as above)

Acid/alkali ingestion Upper endoscopy for stricture BZD Flumazenil

Anticholinesterase/organophosphate Atropine CO 100%/hyperbaric oxygen

Antimuscarinic/anticholinergic Physostigmine Cyanide Hydroxocobalamin

β-blockers Glucagon Lead Succimer or CaEDTA

Methanol/ethylene glycol Ethanol Methaemoglobin Methylene blue

Opioids Naloxone Aspirin Decontamination (as above)

Critical care
SHOCK
Shock is a clinical syndrome characterised by failure to adequately perfuse and oxygenate vital organs.
CLASSIFICATION

Classification of shock
TYPE OF SHOCK MAJOR CAUSES HR BP JVP SKIN TREATMENT

Hypovolaemic  Haemorrhagic fluid loss     Cold  Treat underlying cause

 Non-haemorrhagic fluid loss   Cap. refill  IV fluids/blood

Cardiogenic  Myocardial infarction ±    Cold  Treat underlying cause

 Arrhythmia   Cap. refill  Inotropic/vasopressor support
 CHF

Obstructive  Cardiac tamponade     Cold  Treat underlying cause

 Tension pneumothorax   Cap. refill
 Pulmonary embolism
 Constrictive pericarditis
 Restrictive cardiomyopathy

Distributive  Sepsis     Warm  Treat underlying cause

(includes septic,  Neurogenic (brain/spinal cord)   Cap. refill  IV fluids/blood
anaphylactic,  Anaphylaxis  Inotropic/vasopressor support
and neurogenic)
*Normal HR in neurogenic shock
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Inotrope/vasopressors
 Most ‘inotrope/vasopressor’ drugs have both vasopressor (vasoconstricting) and inotropic (increase cardiac contractility) effects
 Hence, they can be considered as the same class (and there is little evidence for difference in outcomes between differing drugs)
CLASSIFICATION
 Adrenergic drugs
 Non-synthetic – adrenaline and noradrenaline
 Synthetic – dobutamine and isoprenaline
 Non-adrenergic drugs
 PDE inhibitors – milrinone
 Others – vasopressin
DRUG CHOICE
 Septic shock – noradrenaline
 Neurogenic shock – noradrenaline
 Cardiogenic shock – dobutamine (typically, in conjunction with a vasoconstrictor )
 Anaphylactic shock – adrenaline
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Interpretation of investigations
Common investigations
ARTERIAL BLOOD GAS

INTERPRETATION
 Assess oxygenation (PaO2)
 Assess pH (acidosis or alkalosis)
 Assess the PaCO2 (rule in or out disturbance of respiratory system)
 Respiratory acidosis –  PaCO2,  pH
 Respiratory alkalosis –  PaCO2,  pH
 Metabolic disturbance – PaCO2 does not match corresponding pH change
 Standard base excess
 Normal base excess (normal HCO3 in blood) – pure respiratory disturbance
 Assess the HCO3
 Metabolic acidosis –  HCO3,  pH
 Assess anion gap
 If increased – indicates acid production or ingestion
 If decreased – indicates  acid excretion or  loss of HCO3 (e.g. diarrhoea or ostomy, RTA, Addison’s disease)
 Metabolic alkalosis –  HCO3,  pH
 Standard base excess
 Low base excess (or more negative) ( HCO3 in blood) – primary metabolic acidosis or compensated respiratory alkalosis
 High base excess ( HCO3 in blood) – primary metabolic alkalosis or compensated respiratory acidosis
 Assess for compensation (full versus partial)
 Respiratory acidosis w/ metabolic compensation –  PaCO2,  pH,  HCO3
 Respiratory alkalosis w/ metabolic compensation –  PaCO2,  pH,  HCO3
 Metabolic acidosis w/ respiratory compensation –  HCO3,  pH,  PaCO2
 Metabolic alkalosis w/ respiratory compensation –  HCO3,  pH,  PaCo2
 Rate of compensation:
 Respiratory – very quick
 Metabolic – several days

Special circumstances:
 Mixed acidosis/alkalosis (e.g. a respiratory and metabolic acidosis) – PaCO2 and HCO3 move in opposite direction
LACTATE
 Associated with increased mortality but not associated with secondary anaerobic metabolism
 Raised lactate is due to catecholamine excess under aerobic conditions (protective against acid production due to excess glycolysis)
SEROLOGY (ANTIBODIES)
Serology can be used to determine current or previous infection/exposure with an antigen/infective agent:
 IgM – indicates acute infection
 Cannot cross the placenta
 IgG – indicates previous infection or exposure
 Can cross the placenta
 An acute and convalescent phase titre may be required for diagnosis (a large rise is indicative of acute infection )
INTERPRETATION
 IgM (+) and IgG (-) – recent primary infection (or reactivation)
 Low-avidity IgG – primary infection
 High avidity IgG – reactivation
 IgM (-) and IgG (+) – previous infection/exposure
 Low-avidity IgG – recent infection
 High avidity IgG – chronic infection
 IgM (-) and IgG (-) – no primary infection
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Radiology
CHEST X-RAY INTEPRETATION
DRS ABCDE
 D – Details
 Check details of the CXR are correct (e.g. patient details, type of film, date and time of study)
 R – RIPE (assessing image quality)
 Rotation – medial clavicle ends equidistant from spinous processes
 Inspiration – 5-6 anterior ribs in MCL above diaphragm
 Picture – straight versus oblique, entire lung fields, etc
 Exposure – vertebrae and hemidiaphragm visible through cardiac shadow
 S – Soft tissue and bones
 Soft tissues – symmetry, swelling, loss of tissue planes, subcutaneous air, masses
 Breast shadows
 Calcification – great vessels/carotids
 Ribs, sternum, clavicles, spine – symmetry, fractures, dislocations, lytic lesions, density
 A – Airway and mediastinum
 Trachea – normally central or slightly deviated to right
 Hilum (pulmonary vasculature and major bronchi) – left generally higher than right, look for symmetry
 Mediastinum – width, masses
 B – Breathing
 Lung fields (three zones)
 Vascularity (base > apices; to within 2cm of pleura)
 Consolidation
 Pneumothorax
 Additional: horizontal fissure on right lung, atelectasis, bullae, masses
 Pleura
 Pleural reflections or thickening/plaques
 C – Circulation
 Heart – cardiomegaly (cardiothoracic ratio >0.5)
 Heart borders and shape
 Right atrium – right heart border
 Left ventricle – left heart border
 D – Diaphragm
 Hemidiaphragm – right lung higher than left lung
 Diaphragm shape/contour
 Cardiophrenic and costophrenic angles – clear and sharp
 Gastric bubble / colonic air / sub-diaphragmatic air (pneumoperitoneum)
 E – Everything else
 Tubes, pacemakers, implants, metal-work

Basic signs
 CXR Descriptors
 Right, left, bilateral
 Upper, middle, and lower zone
 Opacification (diffuse or localised)
 Silhouette signs
 If you lose the right heart border the right middle lobe is affected
 If you lose the right diaphragm the right lower lobe is affected
 If you lose the left heart border the lingula (left upper lobe) is affected
 If you lose the left diaphragm the left lower lobe is affected
 Pneumothorax signs
 Visible visceral pleural edge seen as a very thin, sharp white line
 Lung markings may be absent peripheral to this line due to air in the pleural cavity
 The lung may completely collapse
 The mediastinum should not shift unless a tension pneumothorax is present
 Atelectasis (lung collapse)
 Pleural effusion
 Blurring of costophrenic or cardiophrenic angles ± meniscus sign
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CT IV CONTRAST
CT IV contrast is an iodine solution that increases imaging information but has several risks.
RISKS
 Iodine allergy
 Contrast-induced nephropathy
 Prevention – pre- and post- IV fluid administration (normal saline)
 Drug risks
 NSAIDs or other nephrotoxic drugs – withdrawn in patients at risk (e.g. eGFR <60)
 Metformin (not directly nephrotoxic) – withdrawn for 48 hours (to prevent lactic acidosis)
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Clinical pharmacology
Basic principles
PHARMACOKINETICS
Pharmacokinetics is the study of ‘what the body does to the drug ’.
 Divided into four main areas of concern (ADME)
DEFINITIONS
 Half-life (t ½) – time taken for serum drug level to fall 50% during elimination
 Drugs with first-order kinetics take five half-lives to be eliminated once dosing is stopped
 Half-life is an important factor in dosing interval calculation
 Steady state (C SS) – drug concentration remains constant when amount of drug entering the system is equal to that leaving the
system
 Clearance (CL) – measurement of the body fluid volume from which a substance is removed per unit of time
 Clearance is constant with drugs with first-order kinetics
 Clearance determines the maintenance dose (MD) to achieve a given drug concentration

Absorption
Absorption is movement of the drug from site of administration into the plasma.
DEFINITIONS
 Bioavailability (F) – proportion of dose that reaches systemic circulation in an unchanged state (i.e. IV = 1)

Distribution
Distribution is movement of the drug between different body compartments and to the site of action.
DEFINITIONS
 Volume of distribution (V D) – the apparent volume of fluid into which a drug distributes
 Loading dose – dose required to achieve a target plasma concentration (Cp) as soon as possible
 Small V D – corresponds to drug that concentrate in plasma (hydrophilic) or binds plasma proteins to a high degree
 Large V D – corresponds to drugs that concentrate in tissues (lipophilic)

Metabolism
Metabolism is chemical transformation of a drug to enhance elimination.

Elimination
Elimination is removal of a drug from the body.
ROUTES OF DRUG ELIMINATION
 Kidney (main organ of elimination) – filtered or secreted
 Faecal
 Exhalation
 Saliva
ELIMINATION KINETICS
 First-order kinetics (most common) – constant fraction of drug eliminated per unit time
 Zero-order kinetics (less common) – constant rate of drug eliminated per unit time
PHARMACODYNAMICS
Pharmacokinetics is the study of ‘what the drug does to the body ’.

Dose-response relationship
DEFINITIONS
 Efficacy (measured by E max) – the maximal biological response produced by a drug
 Potency (measured by EC 50) – the concentration of a drug needed to produce 50% of Emax (i.e. lower is more potent)

Effectiveness and safety

DEFINITIONS
 Effectiveness (ED 50 ) – the dose of a drug needed to cause a therapeutic dose in 50% of the population
 Safety (TD 50 or LD 50) – the dose of a drug needed to cause a toxic/lethal dose in 50% of the population
 Therapeutic index (TD 50/ED 50 ) – reflects a ‘margin of safety’ for a drug (i.e. higher is safer)
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Public health
Determinants of health
DETERMINANTS OF HEALTH
Determinants of health are the socioeconomic factors that influence individual and group differences in health status.

Basic statistics
IMPORTANT CONCEPTS

Standard deviation
 Standard deviation – measures the variation in data (does not depend on sample size)
 68-95-99.7 rule – percentage of data that lies around the mean around a standard deviation of two, four, or six
 Standard error of the mean – measures the uncertainty of the mean (does depend on sample size – 𝑆𝐸 = 𝑆𝐷/√𝑛)

Confidence interval
 Confidence interval – the range within you can be confident, to a specified level, that the true value you are estimating lies (a
measure of robustness of results; does depend on sample size)
 Null hypothesis – that there is no difference in outcome between an intervention and control group
Reporting confidence interval
 If the confidence interval does not include the null hypothesis – we can reject the null hypothesis (statistically significant )
 If the confidence interval includes the null hypothesis – we cannot reject the null hypothesis (non-statistically significant )
 Null hypothesis – 0 for absolute risk and 1 for relative risk/odds ratio

P-values
 P-value – probability that a given value is likely to have arisen by chance (i.e. that the null hypothesis is true)
Reporting P-value
 If the P-value is less than 0.05 – we can reject the null hypothesis (statistically significant )
 If the P-value is greater than 0.05 – we cannot reject the null hypothesis (non-statistically significant )

Note: typically, the P-value is arbitrarily set at 0.05 (it can be set at other levels).
Error
 Type 1 error – the false rejection of a true null hypothesis (i.e. a false positive )
 Type 2 error – the false retention of a false null hypothesis (i.e. a false negative)
 Power – the probability a study will find a statistically significant difference when one is truly there (does depend on sample size)
 Power is determined by: 1 – type 2 error ( β)
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Study validity
INTERNAL VALIDITY
Internal validity is the extent to which the study results reflect the true situation in the study sample.

Chance
Chance is a random error appearing to cause an association between exposure and outcome.
 Typically, due to individual biological variation, sampling variability, and measurement errors

Bias
Bias is a systematic error appearing to cause an association between exposure and outcome.
 There are two main types of bias:
 Selection bias – bias introduced when selecting participants for a study
 Measurement/information bias – bias introduced when recording exposure and/or outcomes

Confounding
Confounding is when the association between exposure and outcome is distorted by another variable not on the causal pathway .
Confounding criteria
A confounder must:
 Be a risk or protecting factor for the outcome
 Be associated with the exposure of interest
 Not lie on the causal pathway
Controlling confounding
 Randomisation – confounders distributed evenly
 Restriction – sample restricted to people with/without confounders
 Matching – cases are matched to controls on known confounders
 Stratification or multivariable analysis – occurs in the statistical analysis phase
EXTERNAL VALIDITY
External validity is the extent to which the study is generalisable to the wider population.

Contingency tables
CONTIGENCY TABLE BASICS

DEFINITIONS
 Prevalence – number of existing cases in a population-at-risk during a specified time period
 Incidence – number of new cases in a population-at-risk during a specified time period
 Incidence rate – number of new cases divided by person-time risk during a specified time period

Basic calculations
 Relative risk – likelihood that exposed patients develop an outcome compared to those not exposed
 Odds ratio – the odds that cases were exposed to a factor compared to the odds that controls were exposed
 Attributable risk (risk difference) – the difference in risk between the exposed and unexposed group (AR = exposed – unexposed
risk)
 Number needed to treat – number of individuals that need to be treated for one patient to benefit (NNT = 1 / attributable risk)

Test characteristics
 Sensitivity – proportion of people with disease who test positive (rules OUT) (does not depend on sample size)
 Specificity – proportion of people without disease who test negative (rules IN) (does not depend on sample size)
 Positive predictive value – proportion of positive test results that are disease positive (does depend on sample size)
 Negative predictive value – proportion of negative test results that are disease negative (does depend on sample size)
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Study analysis
STUDY TYPES

CLASSIFICATION
 Observational
 Descriptive
 Case report/series
 Cross-sectional
 Ecological
 Analytic
 Cohort
 Case-control
 Interventional
 Randomised control trials
 Other specialised trials
Strength and weaknesses of different study designs
DESIGN DESCRIPTION STRENGTHS WEAKNESSES

Cross-sectional Exposures/outcomes are  Efficient  Cannot determine incidence

measured at a certain point in  Cannot determine causal relationship
time  Cannot determine temporality

Ecological Units of analysis are groups  Efficient  Subject to confounding

rather than individuals  Ecological fallacy

Cohort Compares the development of  Can measure multiple outcomes  Inefficient

outcomes in exposed versus  Can determine incidence  Subject to loss-to-follow-up
non-exposed patients over a  Can determine temporality  Not useful for rare outcomes
defined period of time  May determine causal relationship
 Useful for rare exposures

Case-control Compares the risk of previous  Efficient  Subject to recall bias

exposure in cases compared  Can measure multiple exposures  Not useful for rare exposures
to controls  Can determine temporality
 May determine causal relationship
 Useful for rare outcomes

RCT Compares the development of  Gold-standard of evidence  Inefficient

outcomes in randomised  Can measure multiple outcomes  Subject to poor generalisability
groups of patients over a  Can determine causal relationship  Subject to loss-to-follow-up
defined period of time  Can determine temporality  Subject to blinding issues
 Minimises bias/confounding (randomisation)  Ethical issues (clinical equipoise)
 Not useful for rare outcomes

CAUSALITY
The Bradford-Hill criteria (BEST CDS) is used to assess for study causality (that a true association exists between exposure and
outcome):
 B – biological plausibility
 E – experimental evidence (i.e. RCT)
 S – specificity of association
 T – temporality
 C – consistency (with other studies)
 D – dose-response relationship
 S – strength of association

Screening
SCREENING
Screening is the presumptive identification (not diagnosis) of unrecognized illness in the asymptomatic population .
Bias in screening programmes
 Lead-time bias – screening may recognise disease earlier so survival seems longer
 Length-time bias – screening may detect less aggressive disease because of longer latent period so survival seems longer
 Selection bias – screening may have a systematic bias in who presents for testing (i.e. ‘worried well’ or ‘known high risk’)
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 Overdiagnosis bias – screening may detect disease of questionable significant that would not have been diagnosed normally
Screening criteria
There are eight criteria which screening programmes should be assessed before they are established:
 Suitable condition – the condition should be suitable for screening
 Suitable test – there should be a suitable test to identify the condition
 Treatment – there should be effective treatment for the condition
 Evidence – there should be high quality evidence (i.e. RCT) that a screening programme reduces morbidity/mortality
 Benefit – the potential benefit of screening should outweigh the potential physical/psychological harm
 Support – the healthcare system should be capable of supporting the screening pathway
 Social/ethical issues – there should be consideration of social and ethical issues
 Cost – there should be consideration of cost-benefit issues

Prevention
PREVENTION
 Primordial – addresses determinants of health
 Primary (prevent) – prevents disease occurrence
 Secondary (screen) – prevents pre-clinical disease progression
 Tertiary ( treat) – prevents clinical disease progression

Maori health
TREATY OF WAITANGI
 Article 1 (participation ) – Kawanatanga (governance) – the Queen has governance over New Zealand
 Article 2 (partnership ) – Tino Rangatiratanga (Maori self-determination) – Maori maintain control over their land and people
 Article 3 (protection) – Oritetanga (equity) – the Queen will protect and give the same rights to all people of New Zealand
TE WHARE TAPA WHA
 Taha wairua – spiritual health
 Taha hinengaro – mental health
 Taha tinana – physical health
 Taha whanau – social health

Health promotion
OTTAWA CHARTER FOR HEALTH PROMOTION
There are five action areas for health promotion identified within the Ottawa charter:
 Building healthy public policy
 Creating supportive environments
 Strengthening community action
 Developing personal skills
 Re-orienting health services toward prevention of illness and promotion of illness
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Ethical, legal, and palliative medicine

Ethics
CORE ETHICAL PRINCIPLES

DEFINITIONS
 Autonomy – the right of a patient to make decisions for themselves
 Beneficence – the duty to provide health care that is of benefit
 Nonmaleficence – the duty to provide health care that does not cause harm
 Justice – fairness in healthcare in terms of its distribution
INFORMED CONSENT
Informed consent refers to the ethical right of a patient to make an informed decision whether to accept or refuse health care.
 In addition to an ethical right, it is also a legal requirement
FOUR DOMAINS OF INFORMED CONSENT
 Information
 Disclosure – of benefits, risks, and alternatives
 Comprehension – of information presented
 Consent
 Competence – of patient to make decision
 Voluntariness – of patient to be free of coercive influence
ABSENCE OF COMPETENCE
 Competence of minors (<16 years):
 HDC Code of Rights – presumption of competence in minors
 Care of Children’s Act – no statutory capacity to give/refuse consent (except with females in relation to termination)
 However, common law states that ‘mature minors’ may have legal capacity (e.g. Gillick competence)
 Furthermore, it is always encouraged to foster child-parent communication
 Non-competent patients:
 HDC Code of Consumers’ Rights – a doctor may make a decision for a non-competent patient, given:
 It is in the best interests of the patient
 Reasonable steps have been taken to ascertain the views of the patient
 Proxy competence:
 A designated EPOA, legal, or welfare guardian have capacity to make informed consent decisions
ADVANCED DIRECTIVE
Advanced directive is a statement be verbal or written that specifies in advance what someone wishes to happen to them.
 Advanced directives can be overruled by a patient’s current wishes given they are competent at the time of that decision
CONFIDENTIALITY

DEFINITIONS
 Confidentiality – protects communication within a relationship of confidence between persons
 Protected by New Zealand law
 A breach occurs regardless of harm resulting from that breach
 Privacy – protects an individual’s autonomy over their information
 Protected by the Health Information Privacy Code (adopted under the Privacy Act)
 A breach only occurs if it involves identifiable individual’s and harm results from that breach

Legal frameworks
HDC
The Health and Disability Commissioner Act 1994 established the HDC Code of Consumers’ Rights .
CODE OF CONSUMER’S RIGHTS
 Clause 1 – consumer’s (patients) have rights and providers have duties
 Clause 2 – ten consumer’s rights
 Clause 3 – no breach is found if providers take reasonable action to give effect to the rights and duties within the code
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Ten rights of the HDC Code of Consumers’ Rights

Ten rights of the HDC Code of Consumers’ Rights
NUMBER RIGHT TO… CONCEPT

1 Respect

2 Fair treatment Attitudinal rights

3 Dignity and independence

4 Services of an appropriate standard Non-negligent care

5 Effective communication

6 Full information (‘reasonable patient’ test) Autonomy

7 Informed choice and consent

8 Support persons
Support
9 Have the above rights extend to teaching and research

10 Complain (and be taken seriously) Accountability

Palliative medicine
PALLIATIVE FRAMEWORK
Palliative care is health care in people dying from advanced disease where curative/disease-modifying treatment is no longer appropriate.
GOALS OF PALLIATIVE CARE
 Affirms life and death as a normal process
 Aims neither to hasten or postpone death
 Provides relief from distressing symptoms using specialist techniques
 Provides a biopsychosocial approach to the care of the patient, their family, and carers
during illness and bereavement
 Represents a transition (rather than abandonment) from standard medical treatment
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Miscellaneous
SHOCK

Basics
 Shock is defined as perfusion that is inadequate to meet the metabolic demands of the cells
 Either due to falling cardiac output (from falling stroke volume or HR) or diversion of perfusion to the wrong areas
 4 main types:
 Hypovolemic
 Cardiogenic
 Obstructive
 Vasodilatory/distributive
 The microcirculation may become dysfunctional when shock is severe and prolonged regardless of the cause and it may be the site of
the primary lesion and thus the cause of the shock – eg:
 Septic shock:
 Microbial products activate endothelial cells and cellular and humoral elements of the innate immune system
 Initiates a cascade of events that lead to end-stage multiorgan failure
 Non-septic shock:
 Anoxia causes endothelial cell activation and then the same mechanisms as above
PATHOLOGY OF SHOCK EFFECTS ON ENDOTHELIAL CELLS
 Activation of endothelial cells results in expression of adhesion molecules, a pro-coagulant phenotype and secondary waves of cytokine
production. This causes three major sequelae:
 Thrombosis
 Increased vascular permeability
 Vasodilation
 Complement activation also occurs resulting in
the production of anaphylotoxins (C3a, C5a),
chemotaxic fragments (C5a), and opsonins
(C3b), all of which contribute to the pro-
inflammatory state
 Adrenal insufficiency occurs from depression of
the synthetic capacity of adrenal glands (adrenal
stress) or frank adrenal necrosis due to
disseminated intravascular coagulation. This
causes a relative glucocorticoid deficit
 The hyperinflammatory state produced can
paradoxically lead to a state of
immunosuppression from a variety of proposed
mechanisms
 Ultimately, systemic hypotension, increased
vascular permeability, tissue oedema, and small
vessel thrombosis all decrease the delivery of
oxygen and nutrients to the tissues and contribute to organ dysfunction

Hypovolemic Shock
PATHOPHYSIOLOGY
 Due to a decrease in the circulating volume – trauma, blood loss, dehydration, burns
 Cardiac output decreases due to decreased stroke volume from decreased pre-load
DIAGNOSIS
 Clinical diagnosis based on signs and symptoms:
 Mechanism of shock on history or signs on examination – bleeding, dehydration, etc
 HR increased, BP decreased
 JVP decreased
 Cold extremities
TREATMENT
 Treat cause
 Fluid resuscitation – isotonic solution and/or blood transfusion
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Cardiogenic Shock
PATHOPHYSIOLOGY
 Due to inadequacy of contractility of the myocardial muscle – CHF, arrhythmia, structural heart disease, MI
 This decreases the stroke volume
DIAGNOSIS
 Clinical diagnosis based on signs and symptoms:
 HR can vary (increased, decreased or normal)
 BP decreased
 JVP increased
 Cold extremities
 On auscultation of lung fields – bilateral crackles
TREATMENT
 Treat cause if possible
 Give inotropic support:
 If hypotensive – pressors (dopamine)
 If hypertensive – dobutamine

Obstructive
PATHOPHYSIOLOGY
 Due to obstruction of blood flow through heart or lungs – only 3 forms:
 Massive PE
 Cardiac tamponade
 Tension pneumothorax
 Causes an increased afterload (or a decreased preload), leading to a decreased stroke volume
DIAGNOSIS
 Clinical diagnosis based on signs and symptoms:
 HR increased
 BP decreased
 JVP increased
 Extremities normal or cold
 May see Kussmaul’s sign, pulsus paradoxus or tracheal deviation depending on cause
TREATMENT
 Treat the cause:
 Thrombolysis (PE)
 Pericardiocentesis (tamponade)
 Decompression (tension pneumothorax)

Vasodilatory/Distributive
PATHOPHYSIOLOGY
 Due to uncontrolled dilatation of the systemic circulatory system – neurogenic, endocrine, toxic
 Septic shock and anaphylactic shock combine this type along with hypovolaemic and cardiogenic shock mechanisms
 Causes uncontrolled distribution of blood flow leading to decreased afterload and hence stroke volume
DIAGNOSIS
 Clinical diagnosis based on signs and symptoms:
 HR can be increased or decreased
 BP decreased
 JVP decreased
 Extremities are warm
 Other obvious signs – such as infection or anaphylaxis signs
TREATMENT
 Manage the underlying cause:
 Antibiotics for sepsis
 Adrenaline for anaphylaxis
 Fluid resuscitation
 Pressor support
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Organ Effects of Shock

BRAIN
 3 different ranges of problems due to shock:
 Post-ischaemic confusional state :
 Temporary ischaemia - reversible
 Usually followed by complete recovery
 Global cerebral ischaemia/hypoxic-ischaemic
encephalopathy :
 Ranges from reversible mild injury to severe
generalised neuronal death leading to brain
death
 4-5 minutes of ischaemia can lead to irreversible damage
 Neurons more sensitive than glial cells because they have higher energy demands
 Some neurons more vulnerable – “selective ischaemia” – hippocampal and neocortical pyramidal cells, purkinje cells of
cerebellum and other watershed areas
 Greater length of ischaemia can damage thalamus and brainstem
 Acute ischaemic neurons become “red-dead” neurons:
 Cytoplasmic eosinophilia
 Nuclear pyknosis
 Shrinkage
 Border zone infarcts (watershed infarcts ):
 Watershed areas lie between arterial perfusion
territories – the most distal reaches of arterial
blood supply
 Are seen if enough time elapses before death so
that necrosis has time to occur
LUNGS
 The lungs suffer diffuse alveolar damage during shock –
so-called “shock lung”
 ARDS is seen in approximately 50% of cases
 Presents with dyspnoea and hypoxaemia
 Pathology steps:
 Pulmonary endothelial activation
 Pro-inflammatory state
 Increased vascular permeability and pneumocyte
necrosis
 Fibrin rich fluid exudate and necrotic debris
 Hyaline membrane formation
 Acute phase followed by granulation tissue formation
 Damage to type II pneumocytes also leads to surfactant
abnormalities – further compromising gas exchange
 Outcomes:
 Recovery – granulation tissue resolution and minimal
functional impairment
 Prolongation – fibrosis and thickening of alveolar walls
and resultant hypoxia
HEART
 Shock can lead to subendocardial infarction and resulting
cardiac myocyte necrosis
 The inner-most third/half of the myocardium is the least
perfused and most vulnerable – so can get circumferential
infarction
KIDNEYS
 3 outcomes of the effect of shock on the kidneys:
 Acute tubular injury (ATI):
 Always present, but may not be morphologically apparent
 The most common cause of acute kidney injury
 Pathology:
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 Tubular cells sensitive to ischaemia due to high metabolic rate and oxygen requirements
 Cells initially sustain reversible injury, with loss of polarity and detachment from basement membrane
 Loss of polarity leads to abnormal ion transport across cells
 Increased Na+ delivery to distal tubule
 Tubuloglomerular feedback occurs
 Leads to vasoconstriction and decreased GFR
 Acute tubular necrosis (ATN):
 Seen in around 20% of cases
 Due to sustained ischaemia of tubular cells
 Pathology:
 Ischaemic tubular cells express cytokines -> leukocyte
recruitment -> further damage
 Injured cells detach from BM -> luminal obstruction ->
increased intratubular pressure
 Necrosis/apoptosis eventually occurs -> fluid leakage into
interstitium
 Renal cortical necrosis :
 Rare
 Usually bilateral
 Partial or complete
LIVER
 Shock can lead to hepatocyte necrosis
 Principal hypoperfusion injury in centrilobular area (acinar zone
3) is seen after 24 hours
 This is because zone 3 is on the periphery of the microcirculation
of the portal triad – and hence has the lowest oxygen levels
 Presents clinically with:
 Jaundice and elevated transaminases
 Liver failure depending on the extent of the necrosis
BOWEL
 Hypoperfusion leads to haemorrhagic necrosis in bowel wall – extending from
mucosal aspect to transmural aspect depending on extent of shock
 Disruption of epithelium enables bacteria to access circulation -> sepsis
ADRENAL GLANDS
 Affected commonly in shock due to stress response:
 Stress-induced demand for corticosteroids causes increased production and
immediate transport of them
 This leads to cortical-cell lipid depletion - inactive cells become activated
and utilise stored vacuolated lipids for corticosteroid synthesis
 Adrenal medulla stressed due to production of adrenaline
 Adrenal cortex stressed due to production of corticosteroids
 Waterhouse-Friderichsen Syndrome may also occur:
 Vascular endothelial injury and DIC may cause massive bilateral adrenal
haemorrhage and insufficiency – leading to adrenal necrosis
 Adrenals converted to “sacs of blood”
 Mostly associated with Neisseria meningitidis septicaemia
SHOCK EFFECTS ON OTHER ORGANS
 Disseminated intravascular coagulation (DIC) can occur in shock:
 Fibrin-rich microthrombi may form in many organs
 Petechial haemorrhages occur on serosal surfaces and skin
 This causes a consumption coagulopathy
 DIC can still develop in anoxic damage due to shock, not just from sepsis
ORGAN RECOVERY
 Apart from neuronal and cardiac myocyte death, virtually all other tissues can recover from shock hypoperfusion if the patient survives
 The mortality rate for septic shock however is around 20%
 The outcomes from shock depend on the severity of the microcirculatory dysfunction and its duration