Medicine IM Platinum-1

CHAPTER 1
BASIC INFORMATION
I. Introduction to Internal Medicine
II. Core Skills in Internal Medicine
1. Electrocardiography
2. Chest Radiograph Interpretation
3. Arterial Blood Gas Interpretation
4. Thoracentesis
5. Paracentesis
6. Foley Catheter Insertion
7. Intravenous Line Insertion
III. Normal Laboratory Values and Conversion Factors
1. Complete Blood Count
2. Blood Chemistry
3. Urine Studies
4. Equivalent Values
IV. Intravenous Fluids
1. Intravenous Fluids and Common Indications
V. Commonly Used Drips
1. Formulation and Computation of Basic Drips
2. Other Commonly Used Drips
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SECTION 1
INTRODUCTION TO INTERNAL MEDICINE
I. INTRODUCTION
Internal Medicine (IM) can be quite overwhelming because of the complexity of cases and long work hours. Despite these
inherent toxicities, it remains one of the most rewarding fields in Medicine. Students and practitioners alike enjoy the
intellectual stimulation and experience of translating theoretical knowledge into direct patient care. As basic IM principles
cannot be dissociated from the cases we encounter, it is imperative for every practitioner to acquire the core
competencies and skills of an internist. The approach to patient encounter and chart writing are discussed in the
succeeding parts.
II. HISTORY AND PHYSICAL EXAMINATION
Complete history and physical examination are central to hypothetico-deductive reasoning in clinical medicine. Starting
from the chief complaint, problems are elicited from the in chronological order. After completing the details for acute
complaints, probe into the patient’s past medical history, including present medications and pre-morbid functional
capacity. Diseases in the family such as hypertension, diabetes, heart disease, early cardiac death and other
heredofamilial diseases should be elicited as part of the family medical history. History of allergic reactions to drugs and
food should always be elicited. Dietary habits, smoking history, alcohol intake and illicit drug use should also be included
in the personal and social history. Likewise, female patients should be asked about details on menstruation and
pregnancy.
The comprehensive history is followed by the systematic physical examination (PE). This starts with a general survey
followed by checking the patient’s vital signs. Permission should always be asked from the patient before doing any
maneuver, especially the more intrusive ones. A complete PE is carried out with special focus on certain procedures
pertinent to the identified problems of the patient.
III. WRITING THE ORDERS
With the information obtained from the history and PE, a prioritized problem list is then created, with the most urgent
conditions listed first. Based on the problem list, the management list is then outlined.
The orders for the patient usually contain the following:
Diet Dietary preparations (i.e., general liquids, soft diet, full diet) and specific dietary prescriptions
(i.e., low-salt, low-fat, low-purine, DAT)
Fluids and Drips Main IV lines (i.e., plain saline, D5-containing fluids) and side drips (i.e., vasopressors,
electrolyte solutions)
Monitoring BP, HR, RR, temperature, peripheral O2 saturation, neurologic vitals, etc.)
Frequency by which these parameters are checked (i.e., q hourly, q4h, q shift)
Diagnostics Prioritized list of diagnostic procedures such as imaging, blood tests and special procedures
Therapeutics Medications with corresponding doses, frequency of dosing, duration and side effects to
watch out for
Blood products, the amount to be transfused, rate of transfusion and interval between
transfusions
Transfusions Pre-medications and side effects to watch out for
Anticipatory measures: diuretics for possible congestion, anti-pyretics for febrile transfusion
reactions
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DATE/TIME PHYSICIAN’S ORDER SHEET
6/10/2015 Gen Med
7:30am
Diagnosis: Community acquired pneumonia, moderate risk
Hypertension, stage I, controlled
Diet: Low salt, low fat diet; limit oral fluid intake <1.5L day
IVF: PNSS 1L x 10 hours
Side drip1: MgSO4 2g in 250cc D5W x 24 hours
Dx: Chest X-Ray (PA and lateral views)

Complete blood count
Tx:
1. Ceftriaxone 2g IV q24h
2. Azithromycin 500mg/tab 1 tab OD for 3 days
3. Losartan 50mg/tab 1 tab PO OD
Monitor VS q4 with temp and O2 sat

Monitor I&O q shift and record
Refer to dietary for dietary prescription and advice
Watch out for desaturation and BT reaction
Jaime Aherrera MD
Lic. No. 123456
IV. PRESENTING THE CASE
A. General data – begin with the name, followed by the age, sex, chief complaint, reason for admission, and date of
admission or referral
“Juan dela Cruz, 28 years old male, admitted yesterday morning for dyspnea.”
B. History of present illness – review of systems and pertinent information from the past medical, family medical,
personal/social, and obstetric (if applicable) histories
C. Significant diagnostic findings and their interpretations, including pertinent normal findings to rule out the
differentials being considered by the team
D. Hospital course – emphasize the developments or important events that happened to the patient
E. Case summary – two or three sentences
F. Assessment/problem list
G. Plan – based on the assessment/problem list; detailed and specific. Orders for the patient should have their bases
and the expected laboratory findings or trends should be known
H. Entertain clarifications or questions from the audience
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SECTION 2
CORE SKILLS IN INTERNAL MEDICINE
ELECTROCARDIOGRAPHY
I. THE STANDARD 12-LEAD ELECTROCARDIOGRAM (ECG)
A. Limb leads
Standard limb (Bipolar) leads: I, II, III
Augmented limb (Unipolar) leads: aVF, aVR, aVL
B. Chest leads
V1 4th ICS, right parameter border
V2 4th IC, left parasternal border
V3 Between V2 and V4
V4 5th ICS, left midclavicular line
V5 5th ICS, left anterior axillary line
V6 5th ICS, left midaxillary line
II. THE P-QRST WAVES, SEGMENTS AND THE CARDIAC CYCLE
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III. BASIC STEPS IN ECG READING
Step 1: Determine rate

Step 2: Determine rhythm
Step 3: Measure intervals
Step 4: Determine axis
Step 5: Look for chamber enlargements
Step 6: Check for arrhythmias and other abnormalities
STEP 1: DETERMINE HEART RATE

Regular Rhythm
1500_____________
Heart Rate = # of small squares from R to R
Irregular Rhythm
Heart Rate = # of QRS complexes within 30 large boxes x 10
STEP 1: DETERMINE RHYTHM

Regular Sinus Rhythm
Rhythm is determined by the sinus node, which fires at 60-100 bpm
P-wave is normally upright in lead II (and usually in leads I, aVL and aVF)
Each p-wave is followed by a QRS complex, and each QRS complex is preceded by a p-wave
The distances between the R-R intervals should be equal
Sinus Tachycardia and Bradycardia

Tachycardia: HR >100bpm
Bradycardia: HR <60bpm
Sinus Arrhythmia
SA node discharges irregularly (sinus node rate varies with the respiratory cycle)
Rate: normal
Rhythm: varies with respiration, variation in the P-P interval and R-R interval >120 msecs
P-waves, PR interval and QRS: normal
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STEP 3: MEASURE INTERVALS
Normal Values
Wave/Interval Description Normal Values

P-wave Atrial depolarization < 0.12 sec or <120 msec (<3 small boxes)
PR interval Conduction within the AV node 0.12-0.20 sec or 120-200 msec (3-5 small boxes)
QRS duration Ventricular activation < 0.11-0.12 sec or <110-120 msec (<3 small boxes)
QT interval (QTc) Ventricular activation and recovery 0.35-0.43* (males) and 0.45* (females)
*may vary depending on reference
*Source: Kasper DL, et al. Harrison’s Principle of Internal Medicine, 19th edition
Corrected QT-interval (QTc) using the Bazett’s formula

Done to adjust for abnormal heart rates (HR <60 or >100 bpm)
QT actual
Corrected QT interval =
R-R interval in sec
STEP 4: DETERMINE AXIS

Computation of Frontal Axis
Deduct negative deflections form positive deflections in QRS complexes to derive the values for leads I and aVF.
If lead I is a negative integer, subtract the computed axis from 180 to get the final axis.
Note that the value for aVF in the denominator is the absolute value, while that in the numerator takes the sign
(positive or negative) into consideration. This is why a predominantly negative deflection in aVF will make the axis
negative.
____90 aVF____
Axis = | I | + | aVF
Interpretation
Normal Axis -30o to 100o
Right Axis Deviation (RAD) 100o to 180o
Left Axis Deviation (LAD) -30oto -90o
Extreme Axis Deviation -90o to -180o
“Eyeballing” method – can be used to estimate axis
INTERPRETATION LEAD I LEAD aVF

Normal QRS pointing UP QRS pointing UP
Left Axis Deviation QRS pointing UP QRS pointing DOWN
Right Axis Deviation QRS pointing DOWN QRS pointing UP
Extreme Axis Deviation QRS pointing DOWN QRS pointing DOWN
STEP 5: LOOK FOR CHAMBER ENLARGEMENTS

A. Atrial Enlargement
Peaked P-wave with > 2.5mm amplitude (> 2.5 small boxes)
Right Atrial Enlargement (RAE) in leads II, III or aVF
“P-Pulmonale” or peaked P-wave from pulmonary causes
Broad P-wave (> 120ms or > 3 small boxes)
Left Atrial Enlargement (LAE) Biphasic P wave in V1 with a broad negative component
Often notched P-wave in one or more limb leads
“P-Mitrale” or M-shaped P-wave
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B. Left Ventricular Hypertrophy (LVH)
SOKOLOW-LYON CRITERIA CORNELL CRITERIA
[S in V1] + [R in V5 or v6] > 35 mm (>35 small boxes) S in V3 + R in aVL:

Female > 20mm
OR Male > 28mm
R in aVL>11mm
C. Right Ventricular Hypertrophy (RVH)
Relatively tall R wave in lead V1 (R > S wave) with right axis deviation
R in V1 > 0.7mV
R/S in V1 > 1 with R > 0.5 mV
R/S in V5 or V6 < 1
IV. ARRYTHMIAS
JUNCTIONAL AND IDIOVENTRICULAR RHYTHMS
A. Junctional (Atrioventricular) Rhythm
Pacemaker: AV junction with a ventricular rate of 40 to 60 bpm

P wave: may appear before, after, or buried within the QRS complex
Rhythm (RR-interval): regular
QRS complex: narrow (<0.12 sec)
B. Idioventricular Rhythm
Pacemaker: Hiis-Purkinje system (HPS) with a ventricular rate between 15 to 40 bpm

P wave: absent
Rhythm (RR interval): regular
QRS complex: wide (>0.12 sec)
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DISORDERS OF SINUS RHYTHM
A. Sinus Pause
Temporary cessation of sinus node activity

May be synonymous with sinus “arrest” – which pertains to a prolonged sinus pause (definition is arbitrary)
Difference from sinus exit block: the supposed P-P interval of the dropped beat is not a multiple of the normal P-P
interval
B. Sinus Exit Block
Failure of impulse transmission

No visible P-QRS-T complex for >1 cycle, wherein the P-P interval of the pause is a multiple of the normal P-P
interval (differentiating it from sinus pause)
ATRIOVENTRICULAR (AV) BLOCKS

A. First Degree AV Block
Prolonged PR interval
(>0.20 sec or >5 small
boxes)
P-wave is followed by a
QRS complex
B. Second Degree AV Block, Mobitz Type I (Wenckebach)
PR interval progressively
lengthens, then the
impulse is blocked (P is
not followed by QRS,
resulting in a dropped
beat)
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C. Second Degree AV Block, Mobitz Type II
PR intervals of
conducted beats are
constant in length,
however, beats are
dropped with no warning
PR intervals may be
normal or prolonged
D. High Grade AV Block
2 out of every 3 or more

impulses from the atria
are blocked by the AV
node and fail to reach
the ventricles
PR intervals are
constant (in contrast to
complete heart block)
E. Third Degree (Complete) AV Block
P and QRS waves occur

regularly but are
independent of each
other
No consistent
relationship between
atrial and ventricular
activity (AV Dissociation)
PP intervals and RR
intervals are constant
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ATRIAL ARRHYTHMIAS
A. Premature Atrial Contractions (PAC)
Premature P-waves
(earlier than the next
expected sinus P-wave)
P-wave has a different
morphology compared to
the sinus P-wave since
this P-wave is coming
from a different atrial
focus
QRS is usually narrow
B. Atrial Fibrillation (AF)
Description: Rapid,
erratic electrical
discharge from multiple
atrial ectopic foci
Rate: atrial rate >350
bpm; ventricular rate
varies
Rhythm: irregularly
irregular
P-waves: no discernable
P-wave
QRS: usually normal
C. Atrial Flutter
Description: Re-entrant
circuit within the atria,
with variable conduction
of impulses through the
AV node to the ventricles
Rate: atrial rate is 250-
350 bpm; ventricular rate
varies
Rhythm: variable
(depending on
conduction)
P-waves: saw-tooth
appearance
QRS: usually normal
D. Wandering Pacemaker
Description: impulses
originate from different
foci in the atrium
Rate: normal
Rhythm: irregular
P-waves:> 3 different
forms
PR interval: variable
QRS: normal
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E. Multifocal Atrial Tachycardia (MFAT)
Rate: Fast; Irregular

atrial rate (> 100)
Rhythm: irregular
P-wave: >3 different
forms
PR interval: variable
QRS: normal
SUPRAVENTRICULAR TACHYCARDIA (SVT)
Arrhythmia has such a

fast rate that the P
waves may not be seen
Rate: 150-250 bpm
Rhythm: regular
P waves: frequently
buried in preceding T
waves
QRS: normal, but may
be wide if abnormally
conducted through
ventricles (aberrant
conduction)
Atrioventricular Nodal Reentrant Tachycardia (AVNRT)
Most common form of

SVT
Narrow QRS tachycardia
with a short RP interval –
P-waves buried in the
QRS complex
May have a “pseudo-S”
wave (which is actually a
retrogradely conducted
P wave) in inferior leads
or “pseudo-R prime” in
V1
VENTRICULAR ARRHYTHMIAS
Wide QRS tachycardias (>120 ms or 3 small squares): usually ventricular in origin
Differentials for wide QRS tachycardia
o Ventricular tachycardia (VT): more common
o Supraventricular tachycardia (SVT) with aberrancy
When faced with a wide-complex tachycardia and the morphology is in question, it is safer to treat as ventricular
tachycardia (the more life-threatening differential)
A. Premature Ventricular Contractions (PVC)
Prematurely occurring
QRS complex which is
wide and bizarre-looking
Usually no preceding P-
wave
T wave opposite in
Bigeminy: PVCs alternate with sinus beats
deflection to the QRS
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complex
Trigeminy: PVC occurs after every 2 sinus beats
Couplet: two successive PVCs (if three successive PVCs, it is already considered unsustained VT)
B. Ventricular Tachycardia (VT)

1. VT According to Morphology
a. Monomorphic Ventricular
Tachycardia
Rapid, bizarre wide QRS
complex (appearance of
all the beats match each
other in each lead)
No P-wave
Ventricular focus
produces a rapid
sequence of PVC-like
wide ventricular
complexes
b. Polymorphic Ventricular
Tachycardia (Torsades de
Pointes)
Beat-to-beat variations in
appearance
Baseline rhythm
demonstrates long QT
interval
Presents with an
oscillating pattern
mimicking the “turning of
the points” stitching
pattern
2. VT According to Duration
a. Sustained: ventricular tachycardia that lasts for more than 30 seconds

b. Non-sustained: ventricular tachycardia that self-terminates within 30 seconds (presence of at least >3
successive PVCs is considered VT)
3. VT Based on Symptoms
a. Pulseless VT: no effective cardiac output (no pulse, no BP) defibrillate (treat as ventricular fibrillation)
b. Unstable VT: with pulse, but unstable BP cardioversion
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C. Ventricular Fibrillation (VF)
Associated with coarse or fine chaotic undulations
No P-wave
No true QRS complexes
PACEMAKER RHYTHM
A. Ventricular Paced Rhythm
RR interval is regular
QRS complex is wide with an LBBB morphology
Pacemaker spike (“blip”) is followed by a wide QRS complex (good capture)
B. Atrial Paced Rhythm
Atrial pacing appears on the ECG as a single pacemaker stimulus followed by a P wave
PR interval and configuration of the QRS complex are similar to those seen in a sinus rhythm
C. Dual Pacemaker (Atrial and Ventricular)
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V. OTHER ABNORMAL FINDINGS
ISCHEMIA
Findings suggestive of ischemia(should be in 2 or The Contiguous Leads

more contiguous leads)
ST segment depression > 1mm (> 1 small box) II, III, aVF Inferior wall
Deep T-wave inversions > 5 mm (> 5 small I, aVL High lateral wall
boxes) V1, V2 Septal wall
V3, V4 Anterior wall
For example, if there are ST segment V5, V6 Lateral wall
depressions of >1mm in lead V5 and V6: then V1 – V3 Anteroseptal wall
we can say that there is lateral wall ischemia. If V3 – V6, I, aVL Anterolateral wall
ST segment depressions occur in V3 to V6: V5, V6, II, III, aVF Inferolateral wall
then we can say there is anterolateral wall Almost all leads Diffuse, massive
ischemia. V3R, V4R (right-sided Right ventricular wall
leads)
INFARCTION
A. Findings suggestive of injury or infarction
Significant ST elevation:manifestation of myocardial necrosis; the earliest sign of acute infarction

> 1 mm ST elevation in contiguous limb leads, or
> 2 mm ST elevation in contiguous chest leads
B. Pathologic Q-Waves
Indicate myocardial necrosis

Significant Q-wave: > 0.04 secs duration and > 25% of the R wave amplitude
Ignored in lead V1 unless with abnormalities in other precordial leads
Ignored in lead III unless with abnormalities in leads II and aVF
C. Classification as to Timing of Myocardial Infarction
CLASSIFICATION TIMING ECG FINDINGS

(A) Normal
(B) Acute MI Minutes to hours ST elevation + peaked or inverted T-waves + Q waves
(C) Recent MI Hours to days Q-waves +ST elevation + T-wave inversion
(D) Old MI Days to months Q-waves + Isoelectric ST-segment + T-wave inversion
D. Posterior LV wall involvement
Posterior wall ischemia, which is usually associated with lateral or inferior involvement, may be indirectly
recognized by reciprocal or “mirror-image” ST depressions in leads V1 to V3
The posterior LV wall electrical activity is not represented in a typical standard surface ECG
The anteroseptal leads (V1 to V3) are directed form the anterior precordium pointing towards the internal surface
of the posterior myocardium
E. Reciprocal Changes
Pertains to ST-depression in leads opposite those demonstrating ST-elevation
“Ischemia at a distance”
Anterior MI: reciprocal change in inferior wall
Inferior MI: reciprocal change in I, aVL, or anterior wall
Lateral MI: reciprocal change in V1 or inferior wall
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PULMONARY EMBOLISM (PE)
McGinn-White sign: S1Q3T3 pattern (large S-wave in lead I, Q-wave in lead III, and inverted T-wave in lead III)
indicating acute right heart strain
Sinus tachycardia: most commonly cited abnormality
T wave inversion on leads V1-V4: another most commonly cited abnormality (due to RV strain)
Right bundle branch block
Low amplitude deflections
ELECTRICAL ALTERNANS
Beat to beat variation in the QRS amplitude

Seen in massive pericardial effusion and/or cardiac tamponade
BUNDLE BRANCH BLOCKS
V1 V6
Normal
RBBB
LBBB
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A. Left Bundle Branch Block (LBBB)
QRS duration >0.12 sec (complete LBBB)

If <0.12 sec, then it is considered incomplete LBBB
Broad, notched, or slurred R-waves in leads I, aVL,
V5 and V6
Small or absent initial R-waves in right precordial
leads (V1 and V2) followed by deep S-waves
Absent septal Q-waves in leads I, V5 and V6
B. Right Bundle Branch Block (RBBB)
QRS duration >0.12 sec (complete RBBB)

If <0.12 sec, then it is considered incomplete RBBB
Slurred S-wave in leads I and V6
RSR pattern in V1 (“bunny ears”)
PERICARDITIS
Acute Pericarditis
A. Stages of Pericarditis
Stage 1: Widespread ST elevation and PR depression with reciprocal changes in aVR (first two weeks)
Stage 2: Normalization of ST changes; generalized T wave flattening (1 to 3 weeks)
Stage 3: Flattened T waves become inverted (3 to several weeks)
Stage 4: ECG returns to normal (several weeks onwards)
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B. Pericarditis versus Myocardial Infarction
PERICARDITIS MYOCARDIAL INFARCTION
Diffuse ST elevations which are concave upward ST elevations which are convex upward
ST elevation
T-waves T-wave usually not inverted unless ST is T-waves may begin to invert before ST
isoelectric becomes isoelectric
Q-waves Usually absent Present
Reciprocal Change Unusual Common
PR depression Usually present Absent
WOLFF PARKINSON WHITE (WPW) PATTERN
Pre-excitation pattern: atrial impulse activates the

ventricle earlier than would be expected if the
impulse traveled by way of the normal AV
conduction system
o Triad of WPW: PR interval <120 msec,
QRS >120 msec, (+) delta wave (slurred
upstroke or initial portion of QRS complex)
o Secondary ST-T wave abnormalities
opposite that of the delta wave and QRS
forces
ARRHYTHMOGENIC RV DYSPLASIA (ARVD)
Epsilon wave: a small positive deflection (‘blip’)

buried at the end of the QRS complex, representing
delay in depolarization of the right ventricular (RV)
free wall and outflow tract
Epsilon waves, found in 50% of patients with
ARVD, are due to the slowed intraventricular
conduction, hence the terminal notch in the last 1/3
segment of the QRS complex (which represents
the right ventricular activation)
BRUGADA ECG PATTERN
Type 1 Prominent coved ST-elevation displaying J-point amplitude or ST-elevation >2mm,

followed by a negative T-wave
Type 2 >2 mm J-point elevation, >1 mm ST-elevation and a saddleback appearance, followed by
a positive or biphasic T-wave
Type 3
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DEXTROCARDIA (“Right Sided Heart”)
Absent R-wave progression in the chest leads (dominant S-waves throughout)

Predominantly negative P-wave, QRS complex, and T-wave in lead I
Low voltage in leads V3-V6 (because these leads are placed on the left side of the chest)
Accidental reversal of the left and right arm electrodes may produce a similar ECG pattern in the limb leads but
with normal QRS morphology in the precordial leads
OTHER ECG FINDINGS

T-wave inversion, ST segment depression/elevation not fulfilling the
Non-specific ST-T wave changes criteria for ischemia or infarction (as outlined above): flattened or
slightly inverted T-waves, ST segments slightly above or below the
isoelectric line
Poor R wave progression R-wave in leads V1-V3 is < 3 small boxes
Normal R-wave in V4-V6
QRS complexes <5 small boxes in limb leads or < 10 small boxes in
Low voltage complexes chest leads
Example: COPD, anasarca, obesity, myocarditis, moderate-sized to
massive pericardial effusions
Hypokalemia Prominent U wave + flattened T wave
Hyperkalemia Peaked T-waves > 10 mm, wide QRS, sine
Electrolyte abnormalities wave pattern
Hypocalcemia Prolonged QT interval
Hypercalcemia Shortened QT interval
CHEST RADIOGRAPH INTERPRETATION

I. BASIC STEPS IN READING CHEST X-RAYS (CXR)
Step 1: Identify general data

Step 2: Determine view (PA, AP, lateral, decubitus)
Step 3: Assess quality of film
Step 4: Assess anatomy and determine abnormalities
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STEP 1: IDENTIFYING GENERAL DATA OF THE PATIENT
Patient name
Date/Time CXR was taken
Diagnosis of patient
Indication for CXR
STEP 2: DETERMINING THE VIEW
Postero-Anterior View (PA) Antero-Posterior View (AP)

Scapula winged out, ribs and clavicles more angulated Scapula not winged out; clavicles more horizontal
Arms at an angle with the body, with hands at waist Arms parallel to body
Mongolian hat sign appreciated
(formed by the C7 and T1 spinous + transverse Mongolian hat sign not appreciated
processes)
Heart not magnified Heart and other structures magnified
STEP 3: ASSESSING THE QUALITY OF THE FILM
Inclusion Apices of the lungs to the costophrenic angles should be adequately visualized
Inspiratory Effort One should count >8 intercostal spaces, 6-8 anterior ribs, 9-11 posterior ribs
Exposure Upper four thoracic vertebrae should be visualized
Obliquity Medial ends of both clavicles equidistant from midline
The spinous process of the thoracic vertebra should be in the midline
STEP 4: ASSESSING ANATOMY AND ABNORMALITIES

A. General Structure
Soft tissues and bones: soft tissue swellings, rib fractures, breast shadow, osteopenia/osteoporosis
Trachea and mediastinum: carinal angle, tracheal position, mediastinal widening, masses
Vessels: aortic knob and pulmonary arteries
Diaphragm: right hemidiaphragm is usually higher than the left
B. The Heart
Assess CT ratio: >0.50 in PA view suggests cardiomegaly
Cardiomegaly cannot be definitively ascertained on AP films, due to the possibility of magnification effects
CHAMBER PA FILM LATERAL FILM

Left ventricular Apex displaced inferiorly and laterally Obliteration of retrocardiac
enlargement (drooping apex) space
Right ventricular Apex displaced superiorly and Obliteration of retrosternal
enlargement laterally (uplifted apex) space
Prominence of left atrial appendage
Loss of cardiac waistline Posterior displacement of the
Left atrial enlargement Widening of carinal angle (>70o) left mainstem bronchus on
Double density sign on right cardiac lateral film
border
Bulging right heart border (height >1/2
Right atrial enlargement of right cardiac silhouette and width N/A
1/3 of right hemithorax)
C. The Lungs
CP angle: blunting suggests minimal pleural effusion
Pleura: check for pneumothorax, lesions
Parenchyma: check for opacities, densities, infiltrates
Lobes of the lungs:
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o Right Lung (3 lobes): Right upper lobe (RUL) + right middle lobe (RML) + right lower lobe (RLL)
o Left lung (2 lobes): Left upper lobe (LUL) + lingula + left lower lobe (LLL)
II. COMMON CHEST X-RAY PATHOLOGIES
Aortic Aneurysm Mediastinum >30% of thoracic diameter, or mediastinum >8-10 cm

Density in the area of the collapsed lung
Displacement of interlobular fissures (direct sign)
Atelectasis Surrounding structures deviated to the side of the collapsed lung (ipsilateral
mediastinal shift)
Crowding of vessels/bronchi
Ipsilateral diaphragmatic elevation
Bronchiectasis Appears as “bunches of grapes” (ring shadows)
Tram-track lines
Consolidation Inhomogenous opacities
Prominent air bronchogram sign
Hyperaerated lungs
COPD/Emphysema Flattened hemidiaphragms
Tubular heart
Occasionally, bullae
Decreased lung volume
Fibrosis Shift of mediastinum and surrounding structures towards fibrotic area
Blurred heart border or diaphragm with indistinct vascular markings in the areas
of fibrosis
Fungus Ball Homogenous round opacity with a crescent sign
Hamartoma Popcorn ball lesion
Pericardial Effusion Generalized enlargement of the cardiac shadow (“water bottle sign”) with
normal vascular markings
Pleural Effusion Blunting of costophrenic angles
Meniscus sign
Pneumomediastinum Presence of gas between the mediastinal structures
Pneumoperitoneum Presence of gas underneath the diaphragm
Hyperlucent pulmonary area
Pneumothorax Loss of vascular markings beyond the visceral pleural line
Mediastinal structures deviated to contralateral side (tension pneumothorax)
Prominent hilar vessels (hilar fullness) in a bat-wing distribution
Pulmonary edema Cephalization of vessels
Kerley B lines
Pulmonary Metastasis Cannon ball lesions
ARTERIAL BLOOD GAS (ABG) INTERPRETATION

I. BASIC STEPS IN ABG INTERPRETATION
Step 1: Determine the primary acid-base disorder and whether compensation is appropriate
Step 2: Check for secondary acid-base disorders
Step 3: Compute for anion gap and / when needed
Step 4: Check oxygenation status
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STEP 1: DETERMINE THE PRIMARY ACID-BASE DISTURBANCE AND APPROPRIATE COMPENSATION
A. Check the pH, HCO3 and pCO2 levels
NORMAL VALUES IN ARTERIAL BLOOD GAS

Arterial pH 7.40 + 0.05
pCO2 40 +2
HCO3 24 + 2
Anion gap 12 + 2
B. Determine Primary Problem

To assess whether primary problem is respiratory or metabolic in origin, compare changes of HCO 3and pCO2
from baseline
If the change in HCO3 from baseline is larger, then the problem is primarily metabolic and vice versa
Check pH Check HCO3& pCO2 PRIMARY DISTURBANCE

pH <7.4 HCO3> CO2 Metabolic acidosis
CO2>HCO3 Respiratory acidosis
pH >7.4 HCO3> CO2 Metabolic alkalosis
CO2> HCO3 Respiratory acidosis
C. Assess for appropriateness of compensation using the following formulas
PRIMARY DISORDER COMPENSATION

Metabolic acidosis For every 1 meq/L FALL in HCO3,pCO2will DECREASE by 1.2 mmHg
Metabolic alkalosis For every 1 meq/L RISE in HCO3,pCO2will INCREASE by 0.7 mmHg
Respiratory acidosis For every 10 mmHg RISE in pCO2, HCO3will INCREASE by 1 meq/L
Respiratory alkalosis For every 10 mmHg FALL in pCO2, HCO3will DECREASE by 2 meq/L
STEP 2: CHECK FOR SECONDARY ACID-BASE DISORDERS

A. In cases where there is inappropriate compensation, a secondary acid-base disorder should be considered
PRIMARY DISORDER COMPENSATION SECONDARY ACID-BASE DISORDER

Actual reduction of pCO2 from baseline is Secondary RESPIRATORY ALKALOSIS is
Metabolic HIGHER than that of calculated compensation present
Acidosis Actual reduction of pCO2 from baseline is LESS Secondary RESPIRATORY ACIDOSIS is
than that of calculated compensation present
Actual increase of pCO2 from baseline is Secondary RESPIRATORY ACIDOSIS is
Metabolic HIGHER than that of calculated compensation present
Alkalosis Actual increase of pCO2 from baseline is LESS Secondary RESPIRATORY ALKALOSIS is
Respiratory Actual increase of HCO3 from baseline is Secondary METABOLIC ALKALOSIS is
Acidosis HIGHER than that of calculated compensation present
Actual increase of HCO3 baseline is LESS than Secondary METABOLIC ACIDOSIS is
that of calculated compensation present
Respiratory Actual decrease of HCO3 from baseline is Secondary METABOLIC ACIDOSIS is
Alkalosis HIGHER than that of calculated compensation present
Actual decrease of HCO3 from baseline is LESS Secondary METABOLIC ALKALOSIS is
21
STEP 3: COMPUTE FOR ANION GAP AND / WHEN NECESSARY
A. Formula for Anion Gap
Anion gap = Na – (HCO3 + Cl) Normal anion gap is 8-12

High anion gap is >12
B. Usual Causes of Metabolic Acidosis are as follows:
HIGH-ANION GAP METABOLIC ACIDOSIS (HAGMA) NORMAL ANION GAP METABOLIC ACIDOSIS (NAGMA)
P: Paraldehyde H: Hyperalimentation
M: Methanol I: Isoniazid, Iron A: Acetazolamide
U: Uremia L: Lactic acidosis R: Renal tubular acidosis
D: Diabetic ketoacidosis E: Ethylene glycol, Ethanol D: Diarrhea
S: Salicylates U: Uretero-pelvic shunt
P: Post-hypocapnia
C. Check for /
1. For High-Anion Gap Metabolic Acidosis (HAGMA)

Anion Gap If=1, there is pure HAGMA
If <1, there is HAGMA + NAGMA
HCO3 If >1, there is HAGMA + metabolic alkalosis
2. For Normal-Anion Gap Metabolic Acidosis (NAGMA)

Chloride If=1, there is pure NAGMA
If <1, there is NAGMA + HAGMA
HCO3 If >1, there is NAGMA + metabolic alkalosis
D. Computing for Bicarbonate Deficit
HCO3 deficit = (desired HCO3– actual HCO3) x weight x 0.4
STEP 4: CHECK FOR OXYGENATION STATUS
STATUS PO2 LEVEL ON ABG

Hyperoxemia (more than adequate) >100 mmHg
Normoxemia 80-100 mmHg
Mild hypoxemia 60-79 mmHg
Moderate hypoxemia 45-59 mmHg
Severe hypoxemia
22
THORACENTESIS
MATERIALS METHOD
Thoracentesis set 1. Examine the patient and review available labs (CXR, CBC, blood chemistry,bleeding
Abbocath gauge #16 parameters)
3 way stopcock 2. Explain nature of procedure to patient and obtain consent
Macroset/IV tubing 3. Extract simultaneous serum specimen for LDH, albumin, total protein and glucose
Drapes 4. Position patient in sitting position with the mid-axillary line accessible for needle insertion
50cc syringe 5. Confirm and mark topmost site of insertion by counting ribs based on CXR and percussing
10cc syringe fluid level (usual site of insertion is at the 8th ICS posterior axillary line; alternatively, chest
UTZ with markings can be done)
Lidocaine 2% ampoules
6. Observe sterile technique including sterile gloves, betadine prep and drapes
Clean (non-sterile) gloves
7. Anesthetize skin over insertion site with 2% Lidocaine, including superior surface of the rib
Sterile gloves and pleura
Cotton 8. Insert thoracentesis needle perpendicularly through the anesthetized area to the same depth
Rubbing alcohol as the first needle and observe backflow of pleural fluid
Betadine 9. Once with backflow, leave catheter in place, remove needle and attach three-way stopcock &
Sterile gauze tubing
Micropore 10. Aspirate needed amount, then turn the stopcock and evacuate fluid through the tubing (do not
Sterile specimen remove more than 1.5L to avoid increased risk of re-expansionpulmonary edema or
vials/bottles hypotension)
11. Fill specimen tubes/containers and label properly
12. When draining of fluid is complete, have patient take a deep breath or ask patient to cough
and gently remove needle
13. Cover insertion site with sterile occlusive dressing
14. Send specimen for qualitative studies (pH, specific gravity, cell count and differentials,
protein, LDH, albumin, glucose), gram stain and culture, AFB smear and additional studies as
necessary (i.e., cytology for malignancy, amylase for pancreatitis, triglycerides for
chylothorax)
15. Monitor patient closely and watch out for untoward reactions (chest pain, dyspnea, cough,
infection)
16. Obtain upright CXR to evaluate lung expansion/fluid level and rule out pneumothorax
17. Provide post-procedural analgesics as necessary
18. Document procedure, patient response, side effects, nature of fluid drained and lab tests sent
PARACENTESIS
MATERIALS METHOD
Abbocath gauge #16 1. Examine the patient and review available labs (CXR, CBC, blood chemistry,bleeding
Macroset/IV tubing parameters)
Drapes 2. Explain nature of procedure to patient and obtain consent
50cc syringe 3. Have patient empty bladder prior to procedure
10cc syringe 4. Extract simultaneous serum specimen for LDH, albumin, total protein and glucose
Lidocaine 2% ampoules 5. Assemble materials and prepare sterile field
Clean (non-sterile) gloves 6. Position patient in supine position with the trunk elevated 45 degrees
7. Confirm and mark the site of access (usually midline 3-4 cm below umbilicus, halfway
Sterile gloves
between symphisis pubis and umbilicus)
Cotton
8. Anesthetize skin over insertion site with 2% lidocaine, down to and including the peritoneum
Rubbing alcohol 9. Insert paracentesis needle perpendicularly through the anesthetized area to the same depth
Betadine as the first needle and observe for backflow of fluid
Sterile gauze 10.Once with backflow, leave the catheter in place, remove needle and attach tubing draining into
Micropore specimen needles
Sterile specimen vials/ 11.Remove the necessary amount of ascetic fluid
bottles 12. Monitor the patient for hypotension during the procedure
13. When draining of fluid is complete, remove needle and cover insertion site with sterile
occlusive dressing
14. Fill specimen tubes/containers and label properly
15. Send specimens for qualitative studies (pH, specific gravity, cell count and differentials, LDH,
protein, albumin, glucose), gram stain and culture, AFB smear and additional studies as
necessary (i.e., cytology for malignancy)
16. Provide post-procedural analgesics as necessary
17. Document procedure, patient response, side effects, nature of fluid drained and lab tests sent
23
FOLEY CATHETER INSERTION
MATERIALS METHOD
Foley catheter with urine 1. Hand hygiene

bag 2. Prepare materials
Drapes 3. Identify patient by name and introduce self to patient
10cc syringe 4. Explain nature of procedure
1 vial syringe water 5. Provide as much privacy as possible
Clean (non-sterile) gloves 6. Position patient properly
Sterile gloves 7. Wash and rinse urethral area
Cotton 8. Open foley catheter package, put aside but maintain sterile zone around foley catheter
9. Wear clean gloves
Rubbing alcohol
10.Clean urethral opening aseptically:
Betadine
a. For male – in circular motions inside to out
Lubricant (KY jelly) b. For female – follow a “7” figure then drop
Micropore 11.Change to sterile gloves
Sterile specimen bottles 12. Lubricate tip of catheter liberally
(if for urine collection) 13. Attach drainage end of foley catheter to urine bag
14. Insert lubricated end of catheter into urinary meatus gently then push gently up until you are
sure you are inside the bladder (usually up to the port where you inject water and there is
urine backflow)
15. Observe for urine flow
16. Infuse 5-10ml of sterile water to inflate balloon
17. Pull foley catheter slowly until with some resistance
18. Secure foley catheter with tape
19. Dry patient’s perineum
20. Instruct patient on catheter care
21. Remove gloves
22. Hand hygiene
IV LINE INSERTION
MATERIALS METHOD
IV cathula 1. Hand hygiene

Macroset/IV tubing 2. Prepare materials
Clean (non-sterile) gloves 3. Identify patient by name and introduce self to patient
Tourniquet 4. Explain nature of procedure
Cotton 5. Wear clean gloves
Rubbing alcohol 6. Select position/site of venipuncture
Micropore 7. Swab puncture site with alcohol on concentric circles inside to out
8. Apply tourniquet
Splint (optional)
9. Stabilize the selected site
10.Insert needle bevel up
11.Observe for blood backflow
12. Remove needle while pushing cathula further into the vein
13. Attach infusion set quickly while pressing on vein to prevent excessive escape of blood
14. Release tourniquet
15. Try running the IV line to check that fluid infuses continuously and there is no bulging at the
insertion site
16. Cover the insertion site with a 1x1 sterile gauze and tape securely
17. Loop tubing and secure with tape
18. Apply splint
19. Instruct the patient on care of IV site
20. Discard sharps properly
21. Remove gloves
22. Hand hygiene
24
SECTION 3
NORMAL LABORATORY VALUES AND CONVERSION FACTORS
COMPLETE BLOOD COUNT (CBC)
Monocytes: Neutrophils:
0.02-0.09 Hemoglobin: 0.50-0.70
120-180g/L RBC 4-6 x 1012/L
Platelets: 12.0-18.0 g/dL WBC: (106/mm3)
150-450 x 109/L 4-11 x 109/L MCV 80-100 fL
MCH 27-31 pg
150-450 x 103/mm3 4-11 x 103/mm3 MCHC 320-360 g/L
Hematocrit:
RDW-CV 11-16%
Eosinophils: 0.37-0.54 Reticulocytes 0.005-0.015
0.00-0.06 Lymphocytes:
Basophils: 0.20-0.50
0.00-0.02
BLOOD CHEMISTRY
LABORATORY SI CONVENTIONAL
Glucose 3.9-6.1 mmol/L 75-100 mg/dL LABORATORY SI CONVENTIONAL
BUN 2.6-6.4 mmol/L 7-20 mg/dL Lipase 0.51-0.73 23-300 U/L
Creatinine 53-115 umol/L 0.6-1.3 ng/mL ukat/L
Sodium 136-146 136-146 mEq/L LDH 2.0-3.8 ukat/L 100-190 U/L
mmol/L CRP 0.2-3.0 mg/L 0.2-3.0 mg/L
Potassium 3.5-5.2 mmol/L 3.5-5.2 mEq/L RF < 30 kIU/L < 30 kIU/mL
Chloride 100-108 100-108 mEq/L Free T4 10.3-21.9 0.8-1.7 ng/dL
mmol/L pmol/L
Calcium 2.12-2.52 8.7-10.2 mg/dL Free T3 3.7-6.5 pmol/L 2.4-4.2 pg/mL
mmol/L TSH 0.34-4.25 0.34-4.25
Magnesium 0.70-1.00 1.5-2.3 mg/dL mIU/L uIU/mL
mmol/L PSA < 40 y/o 0.0-2.0 ug/L 0.0-2.0 ng/mL
Phosphorus 0.81-1.4 2.5-4.3 mg/dL PSA > 40 y/o 0.0-4.0 ug/L 0.0-4.0 ng/mL
mmol/L AFP 0.0-8.5 ug/L 0.0-8.5 ng/mL
Total protein 64-83 g/L 6.4-8.3 g/dL CA 125 0-35 kU/L 0-35 U/mL
Albumin 34-50 g/L 3.4-5.0 g/dL CA 19-9 0-37 kU/L 0-37 U/mL
Globulin 23-35 g/L 2.3-3.5 g/dL CEA 0-3.0 ug/L 0-3.0 ng/mL
AST (SGOT) 15-37 U/L 15-37 U/L (nonsmokers)
ALT (SGPT) 30-65 U/L 30-65 U/L CEA 0-5.0 ug/L 0-5.0 ng/mL
Alkaline 36-92 umol/L 36-92 umol/L (smokers)
phosphatase CK-total 55-170 U/L 55-170 U/L
Total bilirubin 0-17.1 umol/L 0.3-1.3 mg/dL CK MB 0-16 U/L 0-16 U/L
Direct bilirubin 0-5.00 umol/L 0.1-0.4 mg/dL CK MM 8-97 U/L 8-97 U/L
Indirect bilirubin 3.4-13.7 umol/L 0.2-0.9 mg/dL Troponin I 0-0.09 ng/mL 0-0.09 ug/L
Uric acid 0.13-0.44 3.1-7.0 mg/dL
umol/L
Ammonia 11-35 umol/L 19-60 ug/dL
Amylase 0.34-1.6 ukat/L 30-110 U/L
25
URINE STUDIES
URINALYSIS 24 HOUR URINE CHEMISTRY
Color Yellow, clear/hazy Total volume 500-2000cc
Specific 1.016-1.022 Creatinine 0.65-0.70 g/L or 8.8-14 mmol/d
gravity Total protein 0-0.1 g/24hr or < 100 mg/d
pH 4.6-6.5 Na+ 80-260 mmol/L
Sugar, (-) K+ 25-100 mmol/L
Albumin Cl- 80-340 mmol/L
RBC 0 / 0-2 / hpf Uric acid 4.42-5.9 mmol/24hr
WBC 0-2 / 0-5 / hpf CA2+ 2.5-7.5 mmol/24hr
Casts Hyaline, coarse, fine, granular, Phosphorus 22.4-33.6 mmol/24hr
waxy Amylase 64.75-490.25 U/L
Crystals Small amounts Mucus thread Small amounts
Epithelial cells Small amounts Microalbumin N: 0.0-0.03 g/d
Bacteria (-) Microalbuminuria: 0.03-0.30 g/d
Mucus thread Small amounts Clinical albuminuria: >0.3 g/d
EQUIVALENT VALUES
To convert to mg/dL Equivalent values of common interventions
PARAMETER FACTOR INTERVENTION EQUIVALENT

RBS (mmol/L) Multiply by 18 1 cc 10% oral KCl 1.33 meqs K+
BUN (mmol/L) Multiply by 2.8 15 cc 10% oral KCl 20 meqs K+
Creatinine (umol/L) Divide by 88.4 30 cc 10% oral KCl 40 meqs K+
Calcium (mmol/L) Divide by 0.25 Kaliumdurule 10 meqs K+
Magnesium (mmol/L) Divide by 0.411 (750mg)
Bilirubin (umol/L) Divide by 17.10 1 medium sized Roughly 7-10 meqs K+
Uric acid (umol/L) Divide by 59.48 banana
HDL or LDL (mmol/L) Divide by 0.0259 NaHCO3 50mL 45 meqs Na+
Triglycerides (mmol/L) Divide by 0.0113 NaHCO3GrX tab 7.7 meqs Na+per tab
(650 mg)
NaCl tab (1g) 17 meqs Na+ per tab
Normal saline 154 meqs Na+per liter
solution (1L)
26
SECTION 4
INTRAVENOUS FLUIDS
INTRAVENOUS FLUIDS AND COMMON INDICATIONS

I. BASIC TYPES OF INTRAVENOUS FLUIDS
IV FLUIDS DESCRIPTIONS EXAMPLES

Balanced salt / electrolyte solutions Normal saline (0.9% NaCl), lactated
Crystalloids which may be isotonic, hypertonic or Ringer’s, hypertonic saline (3, 5, 7.5%),
hypotonic Ringer’s solution
High-molecular weight solutions
which draw fluid into the Albumin, hetastarch, pentastarch,
Colloids intravascular component via oncotic plasma and dextran
pressure
Effective plasma expanders
Provide water that is not bound by D5W (5% dextrose in water), D10W,
Free H2O solutions macromolecules or organelles, thus D20W, D50W, D50-50, dextrose/
is free to pass through membranes crystalloid mixes
Blood products Essentially are also considered Whole blood, pRBC, FFP,
colloids cryoprecipitate, platelet concentrate
II. COMPOSITION OF INTRAVENOUS FLUIDS
IV FLUID Glucose Na+ Cl- K+ CA2+ HCO3 COMMENTS

Useful in dehydrated states and
D5W 50 gm/L hypernatremia
Can be used as diluents
D10W 100 gm/L Used to correct hypoglycemia
0.9 NSS 154 154 Fluid of choice for initial resuscitation
Can be used as diluents
Same as 0.9 NSS but with additional
D5 0.9 NSS 50 gm/L 154 154 glucose
Useful for patients on NPO
LR 130 109 4 3 28 Useful for trauma, surgery and burn
NR 140 98 5 patients
Routine fluid and electrolyte
D5NM 50 gm/L 40 40 13 maintenance with minimal
carbohydrate calories
D5NMK 50 gm/L 40 40 30 Same as D5NM but with additional
potassium content
III. USUAL INDICATIONS FOR IV FLUID ADMINISTRATION
Maintain normal blood pressure: normal or isotonic saline is the initial fluid of choice
Return the intracellular (ICF) volume to normal
o In patients with acute hyponatremia, the ICF volume in the brain rises and could become dangerous high
with more prominent decline in plasma sodium hypertonic saline usually given to raise the plasma
sodium
o When there is a large water deficit in the ICF compartment (e.g. severe hypernatremia), electrolyte-free
water (D5W) is given
Replace ongoing renal losses
Give maintenance fluids to match insensible losses
Provide glucose as fuel substrate for the brain, thereby useful for patients on NPO (dextrose-containing fluids)
27
IV. COMMONLY USED INTRAVENOUS FLUIDS
1. Normal Saline (0,9% NaCl, pNSS)

Least expensive and most commonly used resuscitative crystalloid
High Cl content imposes on the kidneys an excess Cl load that cannot be rapidly excreted risk of
hyperchloremic acidosis
The only solution that may be administered with blood products
Does not provide free water or calories
2. Lactated Ringer’s (LR) Solution

Lactate is converted readily to bicarbonate in the liver
Minimal effects on normal body fluid composition and pH
Most closely resembles the electrolyte composition of normal blood serum
Does not provide calories
3. D5W or ¼ Normal Saline

Provides 170 calories/L from 5% dextrose
Provides free water for insensible losses and some sodium to promote renal function and excretion
With added potassium, this is an excellent maintenance fluid in the immediate postoperative period
Prevents excess catabolism and limits proteolysis
4. Hypertonic Saline (3% NaCl)

1026 mOsm/L, 513 mEq/L Na+
Increases plasma osmolality and thereby acts as a plasma expander, increasing circulatory volume via
movement of intracellular and interstitial water into the intravascular space
Due to high sodium content, poses high risk of hypernatremia
Before proceeding to the next section, here are some general terminologies using drips:
cc/hr equal to mL/hr equal to ugtt/min
ugtt/min (microdrops/min) divided by 4 is EQUAL TO gtt/min (drops/min)
dose (mcg / kg / min) x BW in kg x 60 min

Infusion rate (cc / hr) = solution concentration (mcg / cc)
dose of drug (mcg)_

solution concentration (mcg / cc) = volume of diluent (cc)
28
SECTION 5
COMMONLY USED DRIPS
FORMULATION AND COMPUTATION OF BASIC DRIPS

I. DOPAMINE
Generally used to augment BP and cardiac output in patients with cardiogenic shock
Dopamine releases norepinephrine from nerve terminals, which itself stimulates A1 and B1 receptors
Usually started at an infusion rate of 2-5 mcg/kg/min
Dose is increased every 2-5 minutes to a maximum of 20-50 mcg/kg/min
A. Things to know about Dopamine:
Preparation One ampule contains 200 mg dopamine

Sample order Dopamine drip: 200mg dopamine (1 ampule) + 250 cc D5W to run
for ____ cc/hr
For a formulation of 1 ampule (200mg) in 250 cc D5W factor, used
is 13.3
For a formulation of 2 ampules (400mg) in 250 cc D 5W factor,
Dopamine factor used is 26.6
NOTE: A more concentrated dose is usually chosen for patients who

cannot tolerate fluid overload (e.g. patients with CHF, CKD)
B. Dopamine demonstrates varying Hemodynamic Effects based on the dose
DOSE MECHANISM OF ACTION EFFECT
< 2 mcg/kg/min Activates DA1 and DA2 Renal Vasodilation:

receptors Vasodilation of splanchnic and renal vasculature
Inotropic:
2-10 mcg/kg/min Activates B1-receptors Increase in cardiac output with little or no change in
HR or SVR
Effects on A1-receptors Vasoconstrictor:
> 10 mcg/kg/min overwhelm the dopaminergic Vasoconstriction, leading to increase in SVR, LV
receptors filling pressures, and HR
Source: Fauci, et.al, Harrison’s Principles of Internal Medicine 19th edition, 2015.
C. Computation of Dopamine Drip Rate based on Desired Dose
mcg
Desired dose kg min x Body Weight (kg)
Dopamine drip rate (ugtt/min) = Dopamine factor
D. Sample computation
55/F patient, 45kg, admitted for cardiogenic shock with BP of 80/50 mmHg
If our desired dose is 10mcg/kg/min (chronotropic/inotropic dose) and we decide to give 400mg (2 amps)
dopamine (factor is 26.6), the dopamine rate is computed as follows:
mcg
Dopamine drip rate (ugtt/min) =10 kg min x 45 (kg) = 16.9 = 17 cc/hr = 17 ugtt/min
26.6
Sample chart order:
29
Start dopamine drip: 400mg (2amps dopamine) + 250cc D5W x 17 cc/hr (dose of ~10 mcg/kg/min)
Titrate by 2-3 cc/hr to maintain BP > 90/60
E. Reverse computation: computing for the DOSE of dopamine being administered
Note that when reporting/endorsing a case, it is better to state the dose of dopamine that the patient is
being given and not the drip rate. To compute for the specific dose, use the following formula
Dopamine drip rate ugtt x Dopamine factor

mcg min = min________________
Dopamine dose kg body weight (kg)
Example:
Patient is a 45-kg, 55/F, given 2 amps of Dopamine (200 mg/amp) in 250cc PNSS at a rate of 19 ugtts/min (or
19cc/hr). QUESTION: What is the dose of dopamine being given to the patient?
Dose given (in mcg/kg/min) = rate (in ugtt/min) x 26.6 = 19ugtt/min x 26.6 = 11.23mcg/kg.min
45 kg 45 kg
Answer: 11.23 mcg/kg/min is the dose being given to the patient at a rate of 19 ugtts/min (or 19cc/hr). Since
we are giving 11.23 mcg/kg/min, we have a vasoconstricting effect which is beneficial in a patient with septic
shock. If the patient is still hypotensive, we can increase the ugtt/min (titrate) up 34 ugtt/min (20mcg/kg/min)
for a 45-kg patient (“dopa max”). If still with no response to maximal dopamine dosing, we can start another
inotrope like norepinephrine.
In the computation, we used 26.6 because 2 ampules of dopamine were used for the patient.
F. For quick reference:
1. Dopamine 200 mg + 250 cc D5W preparation
Drip Rate Body Weight in Kg

(ugtt/min or
cc/hr) 40 kg 50 kg 60 kg 70 kg 80 kg 90 kg
2.5 7.5 cc/hr 9.4 cc/hr 11.3 cc/hr 13.1 cc/hr 15.0 cc/hr 16.9 cc/hr
Dose 5.0 15.0 cc/hr 18.8 cc/hr 22.5 cc/hr 26.3 cc/hr 30.0 cc/hr 33.8 cc/hr
(mcg/ 7.5 22.5 cc/hr 28.1 cc/hr 33.8 cc/hr 39.4 cc/hr 45.0 cc/hr 50.6 cc/hr
kg/min) 10.0 30.0 cc/hr 37.5 cc/hr 45.0 cc/hr 52.5 cc/hr 60.0 cc/hr 67.5 cc/hr
2. Dopamine 400 mg + 250 cc D5W Preparation

(ugtt/min or
30
II. DOBUTAMINE
A synthetic sympathomimetic amine with positive inotropic action
Effects are due to selective stimulation of B1 adrenergic receptors
A. Things to know about Dobutamine:
Preparation One ampule contains 250 mg dobutamine

Sample order Dobutamine drip: 250mg dobutamine (1 amp) + 250 cc D5W to run for
___ cc/hr
For a formulation of 1 ampule (250 mg) in 250 cc D 5W, factor used is
16.6
For a formulation of 2 ampules (500 mg) in 250 cc D5W,factor used is
Dobutamine factor 33.2
NOTE: A more complicated dose is usually chosen for patients who cannot
tolerate fluid overload (e.g. patients with CHF, CKD)
B. Effects of Dobutamine (dose-dependent)

Minimal positive chronotropic activity at low doses(2.5 mcg/kg/min) and moderate chronotropic activity at
higher doses
Usually given at 10 mcg/kg/min, however, its vasodilatory effect at this dose precludes its use in patients
with decreased systemic vascular resistance
C. Computation of Dobutamine Drip Rate based on Desired Dose
Desired dose mcg min x Body weight (kg)

Dobutamine Drip Rate (ugtt/min) = kg_____________________
Dobutamine factor
D. Sample computation
60/M patient, 50 kg, in cardiogenic shock from decompensated heart failure with BP of 80/50 mmHg
If our desired dose is 5 mcg/kg/min and we decide to use 500 mg (2 amps) dobutamine (factor is 33.2)
5 mcg min x 50 (kg)

Dobutamine Drip Rate (ugtt/min) = kg_______________ = 7.5 = 8cc/hr = 8 ugtt/min
33.2
Sample chart order:

Start dobutamine drip: 500 mg (2 amps dobutamine) + 250 cc D5W x 8 cc/hr (dose of 5 mcg/kg/min)
Titrate by 2-3 cc/hr to maintain BP >90/60 until 15 cc/hr (~10 mcg/kg/min)
The maximum dose of 15 cc/hr was computed using the dose 10 mcg/kg/min
Note that when endorsing a case, it is better to state the dose of dobutamine that the patient is being
given and not the drip rate
To compute for the specific dose, use the following formula
Dobutamine drip rate ugtt x Dobutamine factor

Dobutamine Dose mcg min = min_____________________
kg body weight (kg)
31
E. For quick reference:
1. Dobutamine 250 mg + 250 cc D5W Preparation

(ugtt/min or
2. Dobutamine 500 mg + 250 cc D5W Preparation

(ugtt/min or
III. NORADRENALINE/NOREPINEPHRINE
A potent vasoconstrictor and inotropic stimulant
Despite non-significant improvement in survival compared to patients given dopamine, the relatively safer profile
of norepinephrine makes it a good initial vasopressor therapy
Usually started at a dose of 2 to 4 mcg/minand titrated upward as necessary
If systematic perfusion or systolic pressure cannot be maintained at >90 mmHg with a dose of 15 mcg/min, it is
unlikely that a further increase in dose will be beneficial
A. METHOD 1: Long Method

Step 1: Compute for concentration
EXAMPLE: For 4 mg norepinephrine + 250 cc D5W
stock (mg) x 1000 mcg

Concentration = 250 cc IVF 1 mg 4 mg x 1000 mcg
Concentration = 250 cc 1 mg
Step 2: Compute for infusion rate
mcg / min
Infusion rate cc = dose kg x weight (kg) x 60 min/hr
hr concentration (mcg/cc)
Sample chart order:

To start norepinephrine drip as follows: 4 mg norepinephrine + 250 D 5W x 38 cc/hr (0.2 mcg/kg/min or 10
mcg/min in a 50 kg patient)
Titrate by 5 cc/hr to maintain BP >90/60
32
To compute for the current dose given a certain infusion rate, use the following formula:
Dose mcg / min =Infusion rate (cc/hr) x concentration (mcg/cc)

kg weight (kg) 60 min/hr
B. METHOD 2: Short-Cut Method

Computation for Norepinephrine Drip Rate based on Desired Dose
Desired dose (mcg/min)____

Norepinephrine Drip Rate (ugtt/min) = Norepinephrine factor
Norepinephrine Factor
Norepinephrine drip: 2 mg (1 amp) + 250cc D5W (factor used: 0.133)
Norepinephrine drip: 4 mg (2 amps) + 250cc D5W (factor used: 0.266)
Norepinephrine drip: 8 mg (4 amps) + 250cc D5W (factor used: 0.532)
*A more concentrated dose is usually chosen for patients who cannot tolerate fluid overload
C. For quick reference:

Drip rate Dose (mcg/min)
(ugtt/min or cc/hr) Norepinephrine 2mg + 250 cc D5W Norepinephrine 4mg + 250 cc D5W
Preparation Preparation
5 cc/hr 0.7 mcg/min 1.3 mcg/min
IV. UNFRACTIONED HEPARIN (UFH)

A sulfated polysaccharide usually isolated from mammalian tissues rich in mast cells
Acts as an anticoagulant by activating antithrombin (AT III) and accelerating the rate at which antithrombin inhibits
clotting enzymes, particularly thrombin and factor Xa
A. Usual Formulation of Heparin Drip

Heparin drip: 10,000 units of UFH in enough pNSS to make 100 cc in a soluset (concentration of 10,000
units/100 cc or 100 units/cc)
B. Usual doses for Common Indications

Myocardial infarction = “60-12” 60 units/kg IV push as loading dose then start IV drip at 12 units/kg/hr
Deep vein thrombosis or 80 units/kg IV push as loading does then start IV drip at 18 units/kg/hr
pulmonary embolism = ’80-18”
33
C. Heparin Drip Adjustment:
PTT is ideally monitored every 6 hours (after a dose change) and IV drip adjusted accordingly to reach
target PTT of 1.5-2.5 times the control (46-70 sec)
Raschke’s Protocol
aPTT Heparin Adjustment

<1.2x control 80 u/kg IV bolus then add 4 u/kg/hr to infusion rate
1.2 to 1.5x control 40 u/kg IV bolus then add 2 u/kg/hr to infusion rate
1.5 to 2.3x control No change
2.3 to 3.0x control Decrease infusion rate by 2 u/kg/hr
>3.0x control Discontinue for 1 hour, then decrease infusion rate by 2 u/kg/hr
Mayo Clinic Protocol

aPTT (seconds) Heparin Adjustment
<35 80 u/kg bolus then increase drip rate by 4 u/kg/hr
35-45 40 u/kg bolus then increase drip rate by 2 u/kg/hr
46-70 No change
71-90 Reduce drip rate by 2 u/kg/hr
>90 Withhold heparin for 1 hour then reduce drip rate by 3 u/kg/hr
*Order a PTT 6 hours after any dosage change and adjust accordingly until PTT is therapeutic (~46-70). When two consecutive PTTs are
therapeutic, order PTT every 24 hours
V. INSULIN DRIP (Insulin regimen would depend on the indication)
A. For Hyperkalemia
Insulin causes K+ shift (extracellular potassium goes intracellularly)
Glucose-Insulin (GI) solution: 50 mL of 50% Dextrose in Water (D50-50) + 10 units Regular Insulin in 2-5
minutes
Sample order: Mix 1 amp D50-50 + 10 units Humulin-R IV stat, then q6h x 4 doses
B. For Hyperglycemia
1. Formulation of Insulin drip (depends on physician)
Example (drip 1) 20 units of Insulin (HR) in 100cc pNSS = concentration of 0.2unit/cc (20units/100cc)
Example (drip 2) 50 units of Insulin (HR) in 100cc pNSS = concentration of 0.5unit/cc (50units/100cc)
Example (drip 3) 100 units of Insulin (HR) in 100cc pNSS = concentration of 1unit/cc (100units/100cc)
2. Examples
Example 1: If we decide to give our patient 2 units of insulin per hour (via insulin drip):
For drip 1: give 10 cc per hour (10 cc/hr or 10 gtts/min)
For drip 2: give 4 cc per hour (4 cc/hr or 4 ugtts/min)
For drip 3: give 2 cc per hour (2 cc/hr or 2 ugtts/min)
Example 2: Start drip at 0.1 unit/kg/hr, titrate to desired blood glucose

If the patient is 50kg, start Insulin drip at 5 units/hr. if we decide to use drip #3 form the example
above, the order will be: Insulin drip 100 units HR + 100 cc pNSS at a rate of 5 cc/hr (to deliver 5
units/hr)
V. NICARDIPINE
An intravenous calcium channel blocker used as a first-line agent in the management of hypertensive crises
A. Things to know about Nicardipine:

Preparation One 10 mL ampule contains 10 mg Nicardipine
Drip: 10 mg Nicardipine + 90 mL D5W or pNSS in soluset
Usual formulation
Concentration: 0.1 mg/mL of Nicardipine
Dose Initial dose 5 mg/hr (ex. HPN emergency)
34
5mg/hr = 50 cc/hr (pr 50 ugtt/min)
0.1 mg/cc
Some would give an initial IV bolus prior to starting drip

Titration Titrate by 2,5 mg/hr q15 minutes until target BP is reached
Maximum dose: 15 mg/hr
B. Sample chart order:

Start Nicardipine drip as follows: 10 mg Nicardipine + 90 cc D5W in a soluset x 50 cc/hr, titrate by 2.5 mg/hr every
15 minutes until target BP is reached
VI. NITROGLYCERIN (GLYCERYL TRINITRATE)

Organic nitrate which causes systemic venodilation, decreasing preload and afterload and reducing myocardial
oxygen demand
Also improves coronary collateral circulation
A. Things to know about Nitroglycerin

Preparation One ampule contains 10 mg nitroglycerin
Drip: 10 mg + 90 cc D5W in soluset
Usual formulation
Concentration: 0.1 mg/cc of NTG
100 mcg/cc of NTG
Initial dose 5 mcg/min or 300 mcg/hr
Dose
300 mcg/hr = 3 cc/hr (or 4 uggt/min)
100 mcg/cc
Titration Titrate by 5 mcg.min q5min until pain relief is achieved or BP is controlled
B. Sample chart order:

Start nitroglycerin drip: 10mg nitroglycerin + 90cc D5W in a soluset x 3cc/hr, titrate by 3 cc/hr until chest
pain-free
35
OTHER COMMONLY USED DRIPS
DRUG NAME DOSE PREPARATION HOW TO TITRATE
Amiodarone Continuous infusion: 1 Bolus: 150 mg SIVP Goal is to load 1 g of
(Antiarrhythmic, mg/min for 6hrs, then 0.5 then drip: 150-600 amiodarone within 24
Class III) mg/min infusion mg + 250 cc D5W x hours
16-24 hours
Bolus: 0.5-1 mg SIVP over
Bumetanide 1-2 min Drip: 1 mg + 10 mL Depends on diuretic
(Loop diuretic) Continuous infusion: 1 NSS or D5W response and fluid status
mg/hr
(usually 1 mg/hr or higher)
Bolus: 2-40 mg SIVP x 1-2
Furosemide min Drip: 100 mg + 100 Depends on diuretic
(Loop diuretic) Continuous infusion: 1- mL diluents response and fluid status
10mg/hr
Loading dose: 1 mcg/kg x Drip: 2 mL of Titrate in 0.1 mcg/kg/hr
Dexmedetomedine 10min dexmedetomidine + increments to desired
(A2-Agonist) Continuous infusion: 0.2- 48 mL of 0.9 pNSS level of sedation (max
0.7 mcg/kg/hr (total of 50 mL) dose: 1.5 mcg/kg/hr)
Esmolol Continuous infusion: 50- Drip: 2500 mg + 250 Titrate in 50 mcg/kg/min
(Beta blocker) 200 mcg/kg/min mL diluents increments every four
minutes
May titrate by 1 mg
IsosorbideDinitrate Continuous infusion: 1-5 Drip: 10 mg + 90 mL every 15-30 mins until
(Nitrate) mg/hr diluents chest pain-free (as long
as patient’s BP is
normal)
Rate of infusion should
be reassessed as soon
as basic rhythm appears
Lidocaine Continuous infusion: 1-4 Drip: 1-2 grams + 500 to be stable or at the
(Anti-arrhthymic) mg/min mL diluents (NSS or earliest signs of toxicity.
D5W) It is rarely necessary to
continue IV lidocaine for
prolonged periods
Increase rate by 1 mg/hr
Midazolam Continuous infusion: 1-30 Drip: 125 mg + 125 based on sedation
(Benzodiazepine) mg/min mL diluents (titrate to lowest dose
possible)
Morphine Bolus: 2-4 mg SIVP Drip: 16 mg + 50 cc Depends on type of
(Opioid) Continuous infusion: 1-2 diluent sedation used
mg/hr
Omeprazole Bolus: 40-80 mg IV Bolus: 80 mg IV then Maintain the drip rate
(PPI) Continuous infusion: 8 drip: 40 mg + 90 cc continuously for 72
mg/hr pNSS x 5 hours RTC hours
Pamidronate Continuous infusion: 60-90 Drip: 60-90 mg in 250 Single dose usually
(Biphosphonate) mg IV infusion over 2-24hrs cc pNSS x 2-24 given every 3-4 weeks
hours
Somatostatin Bolus: 250 mcg IV Drip: 3 mg + 250 mL Maintain drip rate
(Splanchnic Continuous infusion: 250 D5W x 12 hours continuously for 72
vasoconstrictor) mcg/hr hours
36
CHAPTER 2
CARDIOLOGY
I. Introduction to Cardiology
II. Approach to Patients with Cardiovascular Conditions
1. Cardiovascular History
2. Cardiovascular Physical Examination
3. The Cardiac Diagnosis
III. Common Conditions in Cardiology
1. Atherosclerosis and Dyslipidemia
2. Hypertension
3. Heart failure
4. Chronic Stable Angina Pectoris
5. Acute Coronary Syndrome
A. Non-ST Elevation Acute Coronary Syndrome
B. ST-elevation Myocardial Infarction
6. Rheumatic Fever
7. Valvular Heart Disease
8. Pericarditis
9. Cardiac tamponade
10. Cardiomyopathy
11. Atrial Fibrillation
12. Peripheral Artery Disease
13. CorPulmonale
37
SECTION 1
INTRODUCTION TO CARDIOLOGY
CARDIOLOGY FORMULAS
STROKE VOLUME (SV)
Volume of blood pumped with each heart beat
Normal range is 55-100mL (for a 70kg man, normal
SV = EDV – ESV is ~70mL)
SV = stroke volume (mL/beat)
EDV = end diastolic volume (N: 65-240 mL)
ESV = end systolic volume (N: 16-143 mL)
EJECTION FRACTION (EF)
EF = SV Most useful index of LV function
Fraction of blood ejected by the LV during systole
EDV EF = ejection fraction
CARDIAC OUTPUT (CO)
Volume of blood being pumped by the heart per
minute
CO = HR X SV Normal CO = 5.0 – 5.5 L/min
CO = cardiac output (L/min)
HR = heart rate (bpm)
BLOOD PRESSURE (BP)
SVR = systematic vascular resistance (resistance

BP = CO x SVR to blood flow through vascular system)
BODY SURFACE AREA (BSA)
Better indicator of metabolic mass than body

BSA = Weight (kg) x Height (cm) weight
3600 BSA = body surface area (m 2)
CARDIAC INDEX (CI)

Marker of cardiac function in relation to BSA, thus
relating heart performance to the size of the
CI = CO individual
BSA Normal CI = 2.6 – 4.2 L/min/m2
If CI < 1.8 L/min/m2 suspect cardiogenic shock
MEAN ARTERIAL PRESSURE (MAP)
Defined as the average arterial pressure during a
single cardiac cycle
SV = EDV – ESV SBP = systolic blood pressure in mmHg
DBP = diastolic blood pressure in mmHg
Normal MAP = > 60mmHg can sustain organ
perfusion (normally 70-110 mmHg)
38
PULSE PRESSURE (PP)
Represents the force that the heart generates each
time it contracts
PP = SP – DP PP = pulse pressure: usually about 30-40 mmHg
SP = systolic pressure (mmHg)
DP = diastolic pressure (mmHg)
Normal PP: if PP < 25% of the systolic value (eg, Low stroke volume, blood loss, aortic stenosis, tamponade)
Wide PP: may reach up to 100mmHg (eg., exercise, atherosclerosis, aortic regurgitation, AV malformation,
hyperthyroidism, aortic dilatation / aneurysm, fever, anemia, pregnancy, anxiety, beri-beri)
MAXIMUM HEART RATE
Maximum HR = 220 – Age Highest HR an individual can achieve without
severe problems through exercise-induced stress
TARGET HEART RATE

Target HR = Maximum HR x 0.85 A specific age-based pulse rate to be maintained
during aerobic exercise to ensure optimal
cardiovascular function
39
SECTION 2
APPROACH TO PATIENTS WITH CARDIOVASCULAR CONDITIONS
CARDIOVASCULAR HISTORY
I. CARDINAL SYMPTOMS OF CARDIOVASCULAR DISEASE

Chest pain or discomfort
Dyspnea, orthopnea, paroxysmal nocturnal dyspnea (PND), wheezing
Palpitations, dizziness, syncope
Cough, hemoptysis
Fatigue, weakness
Pain in extremities with exertion (claudication)
II. COMMON CAUSES OF CHEST PAIN

CONDITION DURATION QUALITY LOCATION ASSOCIATED FEATURES
Cardiac Causes
Retrosternal Precipitated by
Pressure, tightness, Radiation to exertion, exposure to
Angina 2-10 mins squeezing, neck, jaw, cold, psychologic
heaviness, burning shoulders or stress
arms (left)
Similar to angina but Similar to angina but
Unstable Angina 10-20 mins often more severe Similar to angina occurs with low levels
of exertion or at rest
Unrelieved by
Similar to angina but nitroglycerin
Acute MI > 30 mins often more severe Similar to angina May be associated
with evidence of heart
failure or arrhythmia
As described for As described for Late-peaking systolic
Aortic Stenosis Variable angina angina ejection murmur
radiating to carotids
Retrosternal or Relieved by sitting up
toward apex and leaning forward
Pericarditis Hours to days Sharp Left shoulder Pericardial friction rub
and trapezius is present
radiation
Vascular Causes
Anterior chest, Associated with
Acute Aortic Sudden onset of Tearing or ripping often radiating to hypertension and/or
Syndrome unrelenting pain sensation; knife-like the back, underlying connective
(Dissection) between tissue disorder (e.g.,
shoulder blades Marfan syndrome)
Pulmonary Often unilateral, Dyspnea, tachypnea,
Embolism Sudden onset Pressure on the side of tachycardia,
embolism hypotension
Pulmonary Dyspnea
Hypertension Variable Pressure Substernal Signs of increased
venous pressure
Pulmonary Causes
Dyspnea, cough,
Pneumonia or Variable Pleuritic Unilateral, often fever, rales,
Pleuritis localized occasional pleural
friction rub
Spontaneous Sudden onset; Pleuritic Unilateral on Dyspnea
Pneumothorax several hours side of Decreased breath
40
pneumothorax sounds ipsilaterally
Non-Cardiopulmonary Causes
Worsened by
Esophageal 10-60 mins Burning Substernal, postprandial
Reflux epigastric recumbency
Relieved by antacids
Esophageal 2-40 mins Pressure, tightness, Retrosternal Can closely mimic
Spasm burning angina
Peptic Ulcer Prolonged Burning Epigastric. Relieved by food
Substernal intake or antacids
Gallbladder Epigastric, RUQ, May follow meals
Disease Prolonged Aching or colicky substernal Precipitated by fatty
meals
May be reproduced
Costochondritis Variable Aching Sternal by localized or
pinpoint pressure on
exam
Herpes Zoster Variable Sharp or burning Dermatomal Vesicular rash
distribution
Situational factors
Emotional/ Variable; may Variable; may precipitates
Psychiatric be fleeting Variable be retrosternal symptoms
Often with history of
anxiety/depression
CARDIOVASCULAR PHYSICAL EXAMINATION
I. COMMON FINDINGS ON INSPECTION

FINDING REMARKS
Central Cyanosis Cyanosis due to right-to-left shunting, allowing deoxygenated blood to reach
systemic circulation
Peripheral Cyanosis Cyanosis due to reduced extremity blood flow due to small vessel
vasoconstriction
Differential Cyanosis Isolated cyanosis affecting the lower extremities but not the upper (seen in
large PDA)
Homan’s Sign Posterior calf pain on active dorsiflexion of the foot against resistance
(suggestive of DVT)
Kussmaul’s Sign Rise or a lack of JVP with inspiration, associated with constrictive pericarditis
Normally, the venous pressure should fall by at least 3 mmHg with inspiration
Pressure over the upper abdomen (RUQ) for at least 10 seconds
Abdominojugular Reflux Positive response: sustained rise of >3 cm in JVP for at least 15 seconds after
release of the hand
II. COMMON FINDINGS ON PALPATION

FINDING REMARKS
Cardiac Findings
Located in the left 5th ICS, mid-clavicular line
Normal LV Apex Normal apex is a localized systolic outward thrust, less than 2.5 cm in
diameter
LV Enlargement Apical impulse is shifted laterally & downwards
RV Enlargement Sustained systolic lift / heave in the left parasternal area
Peripheral Pulses
PulsusParvus et Tardus A weak and delayed pulse that suggest severe aortic stenosis
Bifid Pulse Two systolic peaks can be appreciated, described in hypertrophic obstructive
cardiomyopathy (HOCM), with inscription of percussion and tidal waves
PulsusParadoxus Refers to a fall in SBP > 10mmHg with inspiration, seen in patients with:
41
pericardial tamponade, massive pulmonary embolism, hemorrhagic shock,
severe obstructive lung disease, tension pneumothorax)
PulsusAlternans Beat-to-beat variability of pulse amplitude seen in severe LV systolic heart
failure
III. COMMON FINDINGS ON AUSCULTATION
A. Heart Sounds
HEART SOUND REMARKS
First Heart Sound (S1) Coincides with closure of the mitral valve and tricuspid valve (Systolic
Pressure)
Caused by the closure of the aortic and pulmonic valves (Diastolic Pressure)
Indicates end of systole (or beginning of diastole)
Best heard at the base; splitting is normally heard
Second Heart Sound (S2) Variations include:
- Widened Interval: RBBB, severe MR
- Narrowly Split or Singular S2: Pulmonary arterial HPN
- Fixed Splitting: ASD secundum
- Paradoxical Splitting: LBBB, RV apical pacing, severe AS, HOCM, MI
Coincides with early diastole or rapid ventricular filling
Third Heart Sound (S3) It is caused by the flow of blood during rapid ventricular filling
Best heard after S2
Coincides with late diastole or atrial systole (atrial contraction/slow ventricular
Fourth Heart Sound (S4) filling)
Diminished ventricular compliance increases resistance to ventricular filling
More common in chronic LCH or active MI
B. Common Auscultatory Areas of the Heart

AREA LOCATION
Aortic Area From the 2nd to 3rd ICS at the right sternal border
Pulmonic Area From the 2nd to 3rd ICS at the left sternal border
Tricuspid Area From the 3rd to 5th ICS at the left sternal border
Mitral Area Near the apex of the heart at the 5th ICS in the left mid-clavicular line
C. Grading of Murmurs
GRADE VOLUME THRILL?
Grade 1 Faint; needs concentration No
Grade 2 Faint but can be heard readily by an experience observer No
Grade 3 Moderately loud No
Grade 4 Loud Yes
Grade 5 Very loud; heard with stethoscope lightly pressed on the skin Yes
Grade 6 Exceptionally loud; heard with stethoscope slightly above the chest wall Yes
D. Common Murmurs
POSSIBLE DIAGNOSIS DESCRIPTION OF MURMUR
Pulmonic / Aortic Stenosis Systolic ejection murmur
Aortic Regurgitation Early diastolic murmur
Tricuspid or Mitral Holosystolic (pansystolic) murmur if chronic
Regurgitation Early systolic murmur if acute
Murmur of TR usually increases with inspiration (Carvallo sign)
Tricuspid or Mitral Stenosis Late diastolic murmur / rumble
Mitral Valve Prolapse Systolic click with mid-to-late systolic murmur
E. Other Sounds
SOUND DESCRIPTION
Opening Snap (OS) High-pitched and occurs after a very short interval following S2
Pericardial Knock From the 2nd to 3rd ICS at the left sternal border
Tumor Plop From the 3rd to 5th ICS at the left sternal border
42
THE CARDIAC DIAGNOSIS
I. COMMON DIAGNOSTIC TESTS IN CARDIOLOGY
DIAGNOSTIC REMARKS
Chest Radiograph (CXR) Widely used to visualize the heart and lungs
12 Lead ECG Graphic recording of electric potentials generated by the heart to detect
arrhythmias, conduction disturbances and ischemia
Holter Monitoring Continuous ECG rhythm pattern for 24 hours or more to document
paroxysmal rhythm abnormalities
Non-invasive tool to evaluate the cardiovascular system’s response to stress
under controlled conditions:
Stress Testing o Exercise stress test: least invasive, makes use of a treadmill
o Pharmacologic stress test: drugs are used to induce stress (e.g.,
dobutamines)
Electrophysiological test of the heart involving intracardiac catheters with
Electrophysiology Study (EPS) electrodes probing the endocardium to test conduction pathways and
electrical activity
Transthoracic Uses ultrasound waves to visualize heart chambers and valves
Echocardiography (TTE) Using Doppler studies, it can visualize blood flow through the heart
Transesophageal Echocardiography that uses a specialized probe with an ultrasound
Echocardiography (TEE) transducer introduced into the esophagus to more accurately visualize
posterior structures
Cardiac Magnetic Resonance Differentiates soft tissues better than CT and allows comprehensive exams
Imaging (MRI) for assessment of size, morphology, function and tissue characteristics
Computed Tomography Displays vessels in the body (e.g., coronaries, aorta)
Angiography (CTA) May also be used to detect calcium in the coronary arteries
Uses radioisotopes (Technetium, Thallium) taken up by viable myocardial
Nuclear Imaging cells to assess myocardial perfusion, viability & function (ischemic
myocardium takes up less isotope)
Intravascular Ultrasound Percutaneous procedure that uses catheters to visualize the lumen and the
interior wall of blood vessels
Coronary Angiography Determines the patency and configuration of the coronary artery lumen by
injecting contrast material into the coronary arteries
Uses invasive monitoring and blood sampling through a catheter inserted into
Cardiac Catheterization the heart to determine function, pressures, oxygenation, flow and volume of
blood within the chambers and great vessels
II. MAKING A CARDIAC DIAGNOSIS

COMPONENT IMPORTANT QUESTIONS
1. Underlying Etiology Congenital, hypertensive, ischemic or inflammatory?
Which chambers are involved? Are they hypertrophied, dilated or both?
2. Anatomic Abnormalities Which valves are affected? Are they regurgitant and/or stenotic?
Is there pericardial involvement?
Has there been a myocardial infarction?
3. Physiologic Disturbances Is an arrhythmia present?
Is there evidence of congestive heart failure or of myocardial ischemia?
4. Functional Disability How strenuous is the physical activity required to elicit symptoms?
Example:
Ischemic Heart Disease, Chronic Stable Angina Pectoris, CCS 3
Congestive Heart Failure NYHA FC III, in Sinus Rhythm
43
SECTION 3
COMMON CONDITIONS IN CARDIOLOGY
ATHEROSCLEROSIS AND DYSLIPIDEMIA
I. THE LIPID PROFILE
A. Total Cholesterol
TC = HDL + Non HDL TC = total cholesterol in mg/dL

HDL = high density lipoprotein in mg/dL
TC = HDL + [LDL + VLDL] LDL = low density lipoprotein in mg/dL
VLDL = very low density lipoprotein in mg/dL (estimated by dividing TG
TC = HDL + LDL + TG level by 5)
5 TG = triglycerides in mg/dL
B. Individual Components
1. High Density Lipoproteins (HDL)
Removes cholesterol from peripheral tissues via the reverse cholesterol transport
Low HDL values < 40 mg/dL increased risk for heart disease
2. Non-High Density Lipoproteins (Non-HDL)

Includes low density lipoproteins (LDL) and very low density lipoproteins (VLDL)
Lower non-HDL cholesterol is desirable and is associated with a lower risk of heart disease
Value can be estimated from other lipid values when non-HDL level is not directly available:
NonHDL = TC – HDL
If VLDL values are not given, it can be
NonHDL = LDL + VLDL estimated by dividing triglyceride levels by 5
Non-HDL are ApoB-100 containing
NonHDL = LDL + TG atherogenic lipoproteins
5
C. The Lipoproteins
Composed of varying proportions of cholesterol, triglycerides and phospholipids
LDL and HDL carry most cholesterol
LIPOPROTEIN REMARKS
Chylomicron Delivers dietary triglyceride to peripheral tissues
Delivers cholesterol to the liver in the form of chylomicron remnants
Delivers hepatic triglycerides to peripheral tissues (TG > cholesterol
VLDL esters)
Secreted by the liver
Formed in the degradation of VLDL
IDL Delivers triglycerides and cholesterol to the liver, where they are
degraded into LDL
Delivers hepatic cholesterol to peripheral tissues
LDL Formed by lipoprotein lipase modification of VLDL in the peripheral
tissues
HDL Mediates reverse cholesterol transport (from periphery back to the liver)
II. THE ACC/AHA 2013 GUIDELINES ON THE TREATMENT OF BLOOD CHOLESTEROL

Statin therapy is recommended for individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk
who are most likely to experience a net benefit (benefit>harm)
There is insufficient evidence to support continued use of specific LDL-C and/or non-HDL-C treatment “targets”
Appropriate intensity of statin therapy should be used to reduce risk in those most likely to benefit
44
Non-statin therapies (e.g., fibrates, niacin), whether alone or in addition to statins, provide little benefit in risk
reduction
A. Four Major Statin Benefits Groups (ASCVD risk reduction outweighs risk of adverse events)
1. Acute coronary syndrome or history of MI
1 Patients with clinical ASCVD 2. Stable or unstable angina
3. Coronary or other arterial revascularization
4. Stroke, TIA or PAD
2 Primary elevations of LDL-cholesterol > 190mg/dL
3 Patients 40-75 years + LDL 70-189 mg/dL + Diabetes (without clinical ASCVD)
4 Patients 40-75 years + LDL 70-189 mg/dL + Estimated 10-year ASCVD risk > 7.5%
(without clinical ASCVD or diabetes)
B. Pooled Cohort Equations for ASCVD Risk Reduction

For the fourth group, risk prediction is done by using the pooled cohort equations for ASCVD risk prediction
(developed by the Risk Assessment Work Group)
Calculator is not appropriate for those with known ASCVD
Calculator is available online at http://tools.cardiosource.org/ASCVD-Risk-Estimator/
Computes for hard ASCVD events, including:
o Non-fatal MI
o Death due to coronary heart disease (CHD)
o Fatal or non-fatal stroke
Data includes:
o Age, sex and race
o Total cholesterol and HDL levels
o Systolic BP
o Treatment for hypertension
o Diabetes
o Smoking history
C. Major Recommendations for Statin Therapy for ASCVD Prevention
Clinical ASCVD LDL > 190 mg/dL Diabetes + 40-75
Age > 75 High Intensity Statin

(Class I) 10 year ASCVD risk >
7.5% and Age 40-75
Moderate Intensity Statin

(Class II) Moderate Intensity
Statin if risk is 5 to
<7.5%
(Class IIa)
High Intensity Statin if 10
year ASCVD Risk > 7.5%
(Class IIa)
45
D. Intensity of Statin Therapy
HIGH-INTENSITY THERAPY MODERATE-INTENSITY THERAPY LOW-INTENSITY THERAPY
Daily dose lowers LDL by > 50% Daily dose lowers LDL by 30 to <50% Daily dose lowers LDL by < 30%
Atorvastatin 10-20 mg
Rosuvastatin 10 mg Simvastatin 10 mg
Atorvastatin 40-80 mg Simvastatin 20-40 mg Pravastatin 10-20 mg
Rosuvastatin 20 mg Pravastatin 40 mg Lovastatin 20 mg
Lovastatin 40 mg Fluvastatin 20-40 mg
Fluvastatin XL 80 mg Pitavastatin 1 mg
Pitavastatin 2-4 mg
INDICATED FOR
Primary Prevention
For 40-75 yrs + LDL 70-189 For 40-75 yrs + LDL 70-189 mg/dL:
mg/dL: With diabetes* , or
With diabetes and > With 5 to <7.5% 10-year risk
7.5% 10-year risk* (without ASCVD or MI)
> 7.5% 10-year ASCVD risk Individualized (e.g., patients who
For LDL-C >190 mg/dL: (without ASCVD or DM); recover from mid-to-moderate
> 21 years + primary moderate-to-high intensity muscle symptoms with higher
LDL-C > 190 mg/dL (risk doses of statins)
estimation is not Individuals in whom high-density statin
required) therapy would be recommended but
have characteristics predisposing them
to statin-associated adverse effects**
Secondary Prevention
< 75 years + clinical > 75 years or safety concerns +
ASCVD clinical ASCVD
*For patients 40-75 years old with LDL 70-189 mg/dL and DM, moderate- (class I recommendation) or high-intensity (class Iia
recommendation if risk for ASCVD is >7.5%) may be considered, depending on the risk-benefit ratio.
**Multiple or serious comorbidities, including impaired renal or hepatic function; history of previous statin intolerance or muscle disorders;
unexplained alanine aminotransferase (ALT) elevations > 3 times the upper limit of normal (ULN); patient characteristics or concomitant use of
drugs affecting statin metabolism; age > 75 years
E. Monitoring
Fasting lipid profile within 4-12 weeks after initiation or dose adjustment and every 3-12 months thereafter
Indicators of anticipated therapeutic response to the recommended intensity of statin therapy (focus is on
the intensity of the statin therapy as an aid to monitoring):
o High-intensity statin therapy: LDL-C reduction of > 50% from the untreated baseline.
o Moderate-intensity statin therapy: LDL-C reduction of 30% to <50% from the untreated baseline.
III. MANAGEMENT
A. Non-Pharmacologic Management (ACC/AHA 2013 Guide for Lifestyle Management for Reducing CV Risk)
1. Diet
High in fruits and vegetables, whole grains; low fat; limit sweets
DASH diet (Dietary Approaches to Stop Hypertension):
o Rich in fruits, vegetables, whole grains, and low-fat dairy foods
o Meat, fish, poultry, nuts and beans
o Limited in sugar-sweetened foods and beverages, red meat, and added fats
2. Physical Activity
3-4 sessions a week, lasting 40 minutes per session
Moderate-to-vigorous intensity physical activity
46
B. Pharmacologic Management
DRUGS MECHANISM OF ACTION LABORATOTY FEATURES ADVERSE EFFECTS

HMG-CoA reductase 1st line of treatment
inhibitor 20-60% LDL reduction Myositis / myopathy
Statins Inhibits melavonate: Doubling of dose: 6% Reversible elevation of
cholesterol precursor additional lowering of AST / ALT
LDL
Ezetimibe Cholesterol absorption 15-20% LDL reduction May increase AST /
inhibitor ALT
Bile acid sequestrant Bad taste, GI
Prevents intestinal discomfort
reabsorption of bile Modest LDL reduction Decreased absorption
Cholestyramine acids, this forcing liver Can increase of fat-soluble vitamins
to use cholesterol to triglycerides Contraindicated if
make more bile acids triglycerides >200
as replacement mg/dL (relative) or 500
mg/dL (absolute)
Upregulates lipoprotein Myositis (increased
Fibrates lipase which increases 35-50% fasting risk if with concomitant
(Gemfibrozil, hydrolysis of VLDL and triglyceride reduction statin use)
Fenofibrate) chylomicrons Increase in AST / ALT
Most common: nausea
Reduces hepatic VLDL
Enhances activity of secretion into Flushing
lipoprotein lipase, circulation and Hyperuricemia
Niacin leading to decreased increases HDL Impaired glucose
VLDL and triglyceride significantly tolerance
levels Only agent proven to
raise HDL levels
Unclear, but it is
thought to decrease Primary use: lower
Omega-3-Fatty catabolism of triglyceride levels (by Bad / fishy taste
Acids (“Fish Oil”) chylomicrons and reducing triglyceride Dyspepsia
increase affinity of LDL synthesis in the liver)
uptake
Increases rate of LDL Reduces LDL levels Can reduce HDL
Probucol catabolism with strong Can reduce HDL levels QT interval
anti-oxidant properties
F. Potency Equivalence of Statins

DOSE OF AGENTS (mg) PERCENT REDUCTION
Rosuvastatin Atorvastatin Simvastatin Pravastatin Total Cholesterol LDL-C
10 20 22% 27%
10 20 40 27% 36%
5 20 40 32% 42%
10 40 80 37% 48%
20 80 42% 54%
Stained doses on same rows are equipotent
(e.g., Rosuvastatin 10 mg is equivalent to atorvastatin 40 mg and both reduce LDL by 48%)
47
HYPERTENSION
I. DIAGNOSIS OF HYPERTENSION
Two or more elevated readings on at least 2 clinic visits over a period of one to several weeks
Definition – adults with:
o SBP > 140 mmHg, or
o DBP > 90 mmHg
II. CLASSIFICATION OF HYPERTENSION
A. Classification as to Etiology
Primary / Essential (most common)
Secondary Hypertension
B. Clues for Suspecting Secondary Hypertension

Age of onset <20 or >50 years
No family history of HPN
DBP >100-120 mmHg
Sudden increase in BP in a patient with stable Stage I HPN
Poor BP control, despite good compliance
Systemic findings (e.g. weight loss/gain, potassium abnormalities)
C. Classification as to Stages
CLASSIFICATION SYSTOLIC (mmHg) DIASTOLIC (mmHg)
Normal <120 and <80
Pre-hypertension 120-139 or 80-89
Stage 1 Hypertension 140-159 or 90-99
Stage 2 Hypertension > 160 or > 100
Isolated Systolic Hypertension > 140 and <90
D. Definition of Terms
VARIATION DESCRIPTION
At least three separate clinic-based measurements >140/90 mmHg and at least
White Coat Hypertension two non-clinic-based measurements <140/90 mmHg in absence of any evident of
target organ damage
Resistant Hypertension Defined as high BP uncontrolled with three drugs or controlled with at least four
anti-hypertensive drugs (including a diuretic)
Orthostatic Hypotension Fall in SBP >20 mmHg or in DBP >10 mmHg in response to assumption of the
upright posture from a supine position within 3 minutes
III. THE EIGHT JOINT NATIONAL COMMITTEE (JNC-8): MANAGEMENT OF HYPERTENSION
A. Simplified Algorithm
Any Age Any Age

Age > 60 Age < 60 (+) Diabetes (+/-) Diabetes
(-) CKD (-) CKD
BP Goal BP Goal BP Goal BP Goal

<150 / <90 <140 / <90 < 140 / <90 < 140 / <90
Initial Drug Initial Drug

Thiazide, or ACEI ACEI or ARB
or ARB, or CCB 48
B. Summary of the JNC-8 Recommendations on Management of Hypertension
RECOMMENDATION PATIENT POPULATION INITIATE THERAPY WHEN GOAL BLOOD PRESSURE
No. 1 Patients > 60 years old SBP > 150 mmHg or SBP < 150 mmHg and
DBP > 90 mmHg DBP < 90 mmHg
No. 2 Patients < 60 years old DBP > 90 mmHg DBP < 90 mmHg
No. 3 SBP > 140 mmHg SBP < 140 mmHg
Patients > 18 years old with SBP > 140 mmHg or SBP < 140 mmHg and
No. 4 CKD DBP > 90 mmHg DBP < 90 mmHg
No. 5 Patients > 18 years old with SBP > 140 mmHg or SBP < 140 mmHg and
DM DBP > 90 mmHg DBP < 90 mmHg
RECOMMENDATION PATIENT POPULATION INITIAL ANTIHYPERTENSIVE AGENT OPTIONS
No. 6 Non-black population Thiazide-type diuretic
(including those with DM) Calcium channel blocker (CCB)
Angiotensin-converting enzyme inhibitor (ACEI)
Angiotensin receptor blocker (ARB)
No. 7 General black population Thiazide-type diuretic
(including those with DM) Calcium channel blocker (CCB)
Patients > 18 years old with Angiotensin-converting enzyme inhibitor (ACEI)
No. 8 CKD (regardless of race or Angiotensin receptor blocker (ARB)
DM status)
The main objective of hypertension treatment is to attain and maintain goal BP:
If goal BP is not reached within a month, increase the dose of the initial drug or add
a second drug (thiazide-type diuretic, CCB, ACEI or ARB)
No. 9 If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list
Do not use an ACEI and an ARB together in the same patient
If goal BP cannot be reached using only the drugs in recommendation 6 because
of a contraindication or the need to use more than 3 drugs to reach goal, other
classes can be used
IV. MANAGEMENT OF HYPERTENSION
A. Screening for Hypertension:

Us Preventive Services Task Force recommends screening for high blood pressure in adults > 18 years old
Screening:
o Every 2 years if BP < 120/80 (normal)
o Yearly if BP 120-139 / 80-89 (pre-hypertensive)
B. Non-Pharmacologic Management: Lifestyle Management for Hypertension

ASPECT GOAL
Weight Reduction Attain and maintain BMI < 25 kg/m 2
Dietary Salt Reduction < 6 g NaCl/day
Adapt DASH-type Dietary Plan Diet rich in fruits, vegetables, and low-fat dairy products
Reduced content of saturated and total fat
Moderation of Alcohol For those who drink alcohol, consume:
Consumption o < 2 drinks/day in men
o <1 drink/day in women
Physical Activity Regular aerobic activity (e.g., brisk walking for 30 mins/ day)
C. Common Drugs for Hypertension

REPRESENTATIVE
CLASS MECHANISM OF ACTION ADVERSE EFFECTS DRUGS WITH DOSE
RANGE
mg/day (doses per day)
Diuretics
Thiazide diuretics Selectively of Na/Cl Sexual impotence Hydrochlorothiazide
symporter which Hypokalemia 6.25-50 mg OD
49
acts on the distal Dyslipidemia Metolazone 2.5-5
convoluted tubules, Hyperuricemia mg OD
leading to enhanced Hyperglycemia Indapamide 1.5mg
NaCl excretion OD
Hypokalemia Furosemide 40-80
Acts on the thick Metabolic alkalosis mg OD
Loop diuretics ascending limb of Ototoxicity Bumetanide 0.5-2
the Loop of Henle Hypocalcemia mg OD
hypomagnesemia Ethacrynic Acid 25-
100 mg BID
Spironolactone Spironolactone
antagonizes action 12.5-100 mg OD
of aldosterone Hyperkalemia Amiloride 5-20 mg
Potassium-Saving Triamterene & Gynecomastia (only OD
diuretics amiloride inhibit Na- for spironolactone) Eplerenone 25-100
K exchange mg OD-BID
mechanism Triamterene 25-100
mg OD
Beta Blockers (BB)
Atenolol 25-100 mg
OD
Metoprolol 50-400
Selectively inhibits mg/day
Cardioselective BB (B1) B1-Receptors (less Metoprolol XL 50-
pulmonary effects) 200 mg OD
Bronchospasm Bisoprolol 2.5-20
Bradycardia mg OD
AV block Esmolol IV
Metabolic syndrome Propanolol 40-180
Non-Selective BB (B1/B2) Inhibits both B1 and Glucose intolerance mg BID-TID
B2 receptors Sleep disturbance Others: Pindolol,
Depression Timolol, Nadolol
Combined A1 & B- Cardvedilol 6.25-25
adrenergic receptor mg BID
Vasodilating BB (A1/B) blockade Nebivolol 5-10 mg
Nebivolol: additional OD
nitric oxide Others: Labetolol
potentiating effect
Calcium Channel Blockers (CCB)
Amlodipine 2.5-10
Blocks L-type Tachyarrhythmia mg OD
Dihydropyridine calcium channels Edema Felodipine 2.5-20
Vascular effect > Headaches mg/OD
AV-node effect Nifedipine 30-120
mg/day
Blocks L-type AV block (2nd and Diltiazem 120-360
calcium channels 3rd degree) mg/day
Non-Dihydropyridine AV node effect > Trifascicular block Verapamil 120-480
vascular effect Severe LV mg/day
dysfunction
Drugs Acting on the Renin-Angiotensin-Aldosterone-System (RAAS)
Captopril 25-150 mg
Inhibits ACE Cough BID-TID
Result: angiotensin- Angioedema Enalapril 2.5-20
ACE-Inhibitors I is not converted to Hyperkalemia mg/day
angiontensin-II Renal agenesis Lisinopril 5-20
mg/day
Perindopril 2.5-10
50
mg/day
Ramipril 2.5-10 mg
OD
Candesartan 8-32
mg OD
Irbesartan 150-300
mg OD
Hyperkalemia Losartan 25-100 mg
Angiotensin Receptor Competitive Renal agenesis OD
Blockers antagonism with Less cough and Olmesartan 5-40
angiotensin-II angioedema mg OD
Telmisartan 20-80
mg OD
Valsartan 80-320
mg OD
Directly inhibits Angioedema
Direct Renin Inhibitor rennin, the first Hyperkalemia Aliskiren 75-300 mg
enzyme in the Cough OD
RAAS Hyperuricemia
Other Anti-Hypertensives
Blocks the Prazosin 1-5
postsynaptic A1- Postural mg/day
Alpha Blockers receptors found in hypotension Terazosin 1-5
capacitance & Reflex tachycardia mg/day
resistance vessels Doxazosin 1-8 mg
OD
Sedation Clonidine 75-150
Activation of A2- Xerostomia mcg BID-TID
Central Sympatholytics receptors in the Impotence Methyldopa 250-
CNS CNS side effects 500 mg BID-TID
Rebound HPN on
withdrawal
Reflex tachycardia
Headache Hyrdrazaline 25 mg
Release of nitric Hypotension TID
Direct Vasodilators oxide, leading to Lupus-like Minoxidil 2.5-80
arterial vasodilation syndrome (for mg/day
hydralazine)
Hypertrichosis (for
minoxidil)
V. MANAGEMENT OF UNCONTROLLED HYPERTENSION
A. Differentiation Between Types of Uncontrolled Hypertension
SEVERE HYPERTENSION HYPERTENSIVE URGENCY HYPERTENSIVE CRISIS

Usual BP 180-220 / 110-130 mmHg >220/130 mmHg > 220/130 mmHg
Actual Target None (asymptomatic) None Present (brain, heart,
Organ Damage kidney, retina or vessels)
Long-acting oral medication can
Management simple be restarted (usually Short-acting oral medications Immediate reduction of BP
occurs in chronic hypertensives with intravenous medication
who stopped taking medication)
Monitoring Require outpatient follow-up Require outpatient follow-up Admit for monitoring (ICU)
within 24-72 hours within 24 to 72 hours
51
B. Common Intravenous (IV) Drugs for Hypertensive Emergencies
DRUG DOSE CONTRAINDICATIONS & SIDE EFFECTS
5-15 mg/hr as continuous infusion
Nicardipine Starting dose 5 mg/hr, increase q15- Liver failure
30 mins by 2.5 mg until goal BP
achieved
Nitroglycerin 5-200 ug/min Can cause headaches
5 ug/min increase q5 mins
0.3-10 ug/kg/min, increase by 0.5 Liver/kidney failure
Nitroprusside ug/kg/min q5 mins until goal BP Can cause cyanide toxicity
achieved
Esmolol 0.5-10 ug/kg/min as bolus 2nd or 3rd degree AV block, systolic
500-300 ug/kg/min as infusion heart failure, bradycardia, COPD
Labetalol 0.25-0.5 mg/kg; 2-4 mg/min until goal 2nd or 3rd degree AV block, systolic
BP is reached, thereafter 5-20 mg/hr heart failure, bradycardia, COPD
C. Recommended Treatment of Hypertensive Emergencies Based on End-Organ Involvement

TYPE OF EMERGENCY TIMELINE, TARGET BP THERAPY*
HPN Crisis with Several hours Labetalol, Nitroprusside,
Retinopathy or Acute Target MAP: decrease by 20% t0 25% Nicardipine
Renal Insufficiency
HPN Encephalopathy Immediate Labetalol, Nicardipine,
Target MAP: decrease by 20% to 25% Nitroprusside
Acute Aortic Dissection Immediate Nitroprusside + Metoprolol,
Target SBP < 110 mmHg Labetalol
Acute Pulmonary Edema Immediate Nitroprusside + Loop
Target MAP: 60-100 mmHg Diuretic, Nitroglycerin
Acute Coronary Syndrome 1 hour Nitroglycerin, Labetalol
Target MAP: 60-100 mmHg
Acute Ischemic Stroke and 1 hour Labetalol, Nicardipine,
BP > 220/120 mmHg Target MAP: decrease by 5% Nitroprusside
Cerebral Hemorrhage and 1 hour Labetalol, Nicardipine,
SBP > 180 mmHg or MAP > Target SBP: < 180 mmHg and MAP 130 Nitroprusside
130 mmHg mmHg
Several hours Phentolamine (after
Cocaine intoxication Target SBP: < 140 mmHg benzodiazepines),
Nitroprusside
Labetalol + MgSO4 and oral
Severe preeclampsia/ Immediate anti-HPN, Nicardipine
eclampsia Target BP: < 160/105 mmHg Emergency Delivery of
Fetus
*Those underlined: first-line therapy
VI. HYPERTENSION AND PREGNANCY

Four categories of hypertension in pregnancy:
1. Pre-eclampsia: severe progressive multisystem disorder diagnosed by hypertension accompanied by any one
of the following:
o Proteinuria
o BP of 160/110 mmHg or higher despite bed rest
o Thrombocytopenia
o Impaired liver function
o Progressive renal insufficiency
o Pulmonary edema
o New-onset cerebral or visual disturbance
2. Chronic hypertension: hypertension predating pregnancy
3. Chronic hypertension with superimposed preeclampsia
4. Gestational hypertension: BP elevation after 20 weeks gestation in the absence of the additional systemic
features listed above
52
HEART FAILURE (HF)
I. ETIOPATHOGENESIS
A clinical syndrome consisting of a constellation of clinical symptoms (dyspnea & fatigue) and signs (edema and
rales) that lead to frequent hospitalization, a poor quality of life, and a shortened life expectancy.
Etiologies:
o Coronary artery disease (CAD): most common cause of HF in industrialized countries (60-75%)
o Hypertension: cause of HF in 75% of patients
o Idiopathic cardiomyopathy: 20-30% of depressed EF HF
o Pulmonary heart disease: cor pulmonale, pulmonary vascular disorders
o High output states: thyrotoxicosis, nutritional disorders (beriberi), excessive blood flow requirements,
chronic asthma
II. CLASSIFICATION / STAGES OF HEART FAILURE (HF)
A. Classification Based on Function / Ejection Fraction (EF)

TYPE EJECTION DESCRIPTION COMMON EXAMPLES
FRACTION
Progressive disorder initiated by an
Systolic Heart Depressed HF index event (e.g., MI, volume CAD (e.g., MI)
Failure or HF with < 40% overload, chronic anemia) that leads Dilated cardiomyopathy
reduced EF (HfrEF) to a decline in the pumping capacity Valvular heart disease
of the heart
Proposed mechanisms include
Diastolic Heart diastolic dysfunction and extra- Pathologic hypertrophy
Failure or HF with Preserved EF cardiac mechanisms such as (HOCM, HPN)
preserved EF > 40-50% increased vascular stiffness and Aging, fibrosis
(HfpEF) impaired renal function (still Restrictive cardiomyopathy
undefined and evolving)
Occur when the body’s requirements Thyrotoxicosis
Normal at first, then for oxygen and nutrients are Beriberi
High-Output Heart may decrease over increased and the demand outstrips Chronic anemia
Failure time what the heart can provide Systemic arteriovenous
shunting
B. American College of Cardiology / American Heart Association (ACC/AHA) Stages of Heart Failure
STAGE DESCRIPTION EXAMPLES
A At high risk for HF but without structural heart Patients with HPN, CAD, DM or patients using
disease or HF symptoms cardiotoxins or with family history of cardiomyopathy
B Structural heart disease but without signs or Patients with previous MI, LV systolic dysfunction, or
symptoms of HF asymptomatic valvular disease
C Structural heart disease with previous or Patients with known structural heart disease with
current symptoms of HF shortness of breath, fatigue, reduced exercise tolerance
Refractory HF requiring specialized Patient who have marked symptoms at rest despite
interventions maximal therapy (e.g., patients with recurrent
D hospitalizations or cannot be safely discharged without
special interventions)
C. New York Heart Association (NYHA) Functional Classification

NYHA DESCRIPTION COMMENTS
I Symptoms occur with greater than ordinary No limitation of physical activity
physical activity Can climb > 2 flights of stairs with ease
II Symptoms occur with ordinary physical activity Slight limitation of physical activity
Can climb 2 flights of stairs but with difficulty
III Symptoms occur with less than ordinary Marked limitation of physical activity
physical activity Can climb <1 flight of stairs
IV Symptoms may be present even at rest Unable to carry on activity without symptoms
Dyspnea at rest
53
III. CLINICAL MANIFESTATIONS
A. Symptoms
Fatigue and Shortness of Cardinal symptoms
Breath Due to pulmonary congestion juxtacapillary J-receptors are activated
cardiac dyspnea
Orthopnea/Nocturnal Cough Redistribution of fluid from splanchnic and lower extremity into the central
circulation on recumbency
Paroxysmal Nocturnal Severe dyspnea that awakens patient from sleep 1-3 hours after patient retires
Dyspnea Increased pressure in the bronchial arteries
Cheyne-Stokes Respiration In 40% of advanced HF: series of apnea hyperventilation hypocapnia
Diminished sensitivity of the respiratory center to arterial PCO2
GI: anorexia, nausea, early satiety, abdominal fullness which may be due to
Others congested liver and/or bowels
CNS: confusion, disorientation, sleep and mood disturbance may be due to
reduced cerebral perfusion
B. Signs
General Appearance and Uncomfortable when lying flat, labored breathing
Vital Signs Normal or low BP
Cardiac cachexia
Although essential, frequently does not provide information on the severity of
HF
JVP may be > 8 cm H2O
Cardiovascular Sinus tachycardia due to increased adrenergic activity
Point of maximal impulse displaced due to cardiomegaly
S3 (protodiastolic gallop) at the apex: usually in volume overloaded patients
S4: usually in diastolic dysfunction
Crackles: transudation of fluid from intravascular space to alveoli
Pulmonary Expiratory wheezes: cardiac wheezing caused by peribronchial cuffing from
congestion
Pleural effusions: often bilateral; if unilateral, more often on the right
Hepatomegaly with pulsation (if with significant TR)
Abdomen Ascites: increased pressure in the hepatic veins
Jaundice: impairment of hepatic function due to congestion
Peripheral edema: ankles and pre-tibial region
Extremities Indurated and pigmented skin: long standing edema
Peripheral vasoconstriction: cool extremities
IV. DIAGNOSIS OF HEART FAILURE

The diagnosis of HF is straightforward when the patients presents with classic signs and symptoms
Key to diagnosis is a high index of suspicion
A. Framingham Criteria for Heart Failure

MAJOR CRITERIA MINOR CRITERIA
Paroxysmal nocturnal dyspnea (PND) or orthopnea Ankle edema
Neck vein distention Night cough
Rales Dyspnea on exertion
Cardiomegaly Hepatomegaly
Acute pulmonary edema Pleural effusion
S3 gallop Vital capacity decreased by 1/3 from maximal
Increased venous pressure > 16 cm H2O capacity
Hepatojugular reflux Tachycardia > 120 bpm
Major or Minor Criteria: Weight loss > 4.5 kg in 5 days in response to treatment
The diagnosis of HF requires simultaneous presence of at least:
1 Major Criteria, or
1 Major Criterion + 2 Minor Criterion
54
(use of minor criteria acceptable only if they cannot be attributed to another medical condition, such as pulmonary HPN, chronic lung disease, cirrhosis, ascites, nephrotic
syndrome)
B. Diagnostics in HF
DIAGNOSTICS DESCRIPTION
2D Echocardiography with Most useful test, evaluation of ejection fraction (EF)
Doppler Semi-quantitative assessment of LV size, function, wall motion abnormalities,
valvular defects
12-L ECG Assess cardiac rhythm, LV hypertrophy, prior MI
A normal ECG virtually excludes LV systolic dysfunction
Chest Radiography Assess the cardiac size and shape and state of pulmonary vasculature
Identify non-cardiac causes of symptoms
Cardiac Biomarkers (BNP) Relatively sensitive markers for the presence of HF
Increase with age and renal impairment
Complete Blood Count Look for anemia, signs of infection, and bleeding (may precipitate / worsen HF)
Serum Electrolytes, BUN, Assess for electrolyte disturbances, beginning cardiorenal syndrome, ischemic
Crea, AST, ALT hepatitis or chronic passive congestion of the liver
FBS, OGTT Assess for diabetes
Lipid Profile Assess for dyslipidemia
FT4, TSH Assess for thyroid hormone abnormalities
V. MANAGEMENT OF HEART FAILURE
A. Non-Pharmacologic Management and Basic Principles

Sodium restriction: limit Na+ intake to 2-3 g/day in all patients with HF; and to less than 2 g/day in patients with
moderate to severe HF
Fluid restriction: generally unnecessary unless with hyponatremia (< 130 mEq/L) and volume overload
Caloric supplement: for those with cardiac cachexia
B. Pharmacologic Management for Prevention and Treatment of Chronic Heart Failure

DRUG CLASS DESCRIPTION / MECHANISM DOSE
Cornerstone of modern HF treatment
Interferes with RAAS by inhibiting Captopril 25-50 mg TID
the conversion of angiotensin I to Enalapril 2.5-10 mg BID
ACE-Inhibitors angiotensin II Ramipril 2.5-10 mg OD
Inhibits kininase which may lead to Lisinopril 5-20 mg OD
increase in bradykinin (ACE-I
induced cough)
Angiotensin Receptor Use if ACEI intolerant (e.g., cough, Valsartan 40-160 mg BID
Blockers angioedema) Candesartan 8-32 mg OD
Losartan 25-50 mg OD
Another cornerstone of modern HF
treatment Carvedilol 3.125-25 mg BID
Beta Blockers Interferes with sustained activation of Bisoprolol 1.25-10 mg OD
the adrenergic nervous system, Metoprolol succinate 25-200 mg OD
particularly the deleterious effects of
B1 activation
Inhibits action of aldosterone in
Aldosterone Antagonist collecting duct Spironolactone 25-50 mg OD
May also be used for fluid retention Eplerenone 25-50 mg OD
(diuretic)
For symptomatic LV dysfunction +
Digoxin atrial fibrillation Digoxin 0.125-0.375 mg OD
Add-on to standard therapy
Reduces HR by inhibition of the Ivabradine 5-7.5 mg BID
Ivabradine “funny channel” (If) in the SA node
Primarily used for symptomatic
55
stable angina
May be used for HF with systolic
dysfunction in patients with sinus
rhythm and HR > 70 bpm
C. Management of Fluid Retention in Chronic HF

DRUG CLASS DESCRIPTION / MECHANISM DOSE
Act on the loop of Henle by reversibly Furosemide 20-40 mg OD-BID
Loop Diuretics inhibiting the reabsorption of Na+, K+, Cl in Bumetanide 0.5-1.0 mg OD-
the thick ascending limb BID
Reduce the reabsorption of Na+ and Cl in Hydrochlorothiazide 25 OD-
Thiazide and Thiazide- the first half of the distal convoluted tubule BID
Like-Diuretics Tend to lose their efficiency with moderate Indapamide 2.5 mg OD
to severe renal insufficiency (Crea > 2.5 Metolazone 2.5-5.0 mg OD
mg/dL)
Interfere with action at the vasopressin
Arginine Vasopressin receptors Tolvaptan 15 mg OD
Antagonists Primarily used for treatment of Satavaptan 25 mg OD
hyponatremia by stimulating free-water
excretion and improving plasma
Na+concentration
D. Indications for Use of Drugs in HF

CLASS ASYMPTOMATIC LV SYMPTOMATIC HF WORSENING HF END-STAGE HF
DYSFUNCTION (NYHA I) (NYHA II) (NYHA III-IV) (NYHA IV)
ACEI/ARB Yes yes Yes Yes
Diuretic No Yes, if with fluid retention Yes Yes
B-Blocker Yes, if Post-MI Yes Yes Yes
Aldosterone Yes, if Recent MI Yes Yes Yes
Antagonist
Digoxin May be considered* May be considered* Yes Yes
*Digoxin may be considered for patients with NYHA-I for rate control in AF or when improved from more severe HF and in sinus rhythm
E. Devices Used in HF
Cardiac resynchronization therapy (CRT) or biventricular pacing: device used to restore synchrony of the
left ventricle in patients with HF and a widened QRS complex
Implantable cardioverter-defibrillator (ICD): device to treat tachyarrhythmias for primary / secondary
prophylaxis against sudden cardiac death
VI. ACUTE DECOMPENSATED HEART FAILURE (ADHF)
A. Distinctive Phenotypes
ACUTE PRESENTATION MANAGEMENT
DECOMPENSATION
Typical Normo-hypertensive Vasodilators, diuretics
Usually not volume overloaded
Pulmonary Edema Severe pulmonary congestion with hypoxia Vasodilators, diuretics, opiates
O2 non-invasive ventilation
Hypoperfusion with end-organ dysfunction Inotropic therapy
Low Output Low pulse pressure, cool extremities Vasodilators
Cardiorenal syndrome, hepatic congestion Hemodynamic monitoring
Hypotension, low cardiac output, end-organ Inotropic therapy
Cardiogenic Shock failure Mechanical circulatory support
Extreme distress, pulmonary congestion,
renal failure
56
B. Parenteral Therapy for Acute Decompensated HF
DRUG CLASS SAMPLE DRUGS
Inotropic Therapy Dobutamine (2-20 mcg/kg/min)
Others: Milrinone, Levosimendan
Vasodilators Nitroglycerine (10-20 mcg/kg/min)
Others: Nesiritide, Nitroprusside, Serelaxin
Furosemide (20-240 mg/day)
Diuretics Bumetamide (0.5-5 mg/day)
Others: Torsemide, Metolazone, Chlorthalidone, Spironolactone, Acetazolamide
CHRONIC STABLE ANGINA PECTORIS (CSAP)
Patients with ischemic heart disease (IHD) fall into two large groups:
Chronic artery disease (CAD) who commonly present with chronic stable angina pectoris (CSAP)
Acute coronary syndromes (ACS), discussed in the next section, are composed of:
o Non ST-segment elevation acute coronary syndrome (NSTE-ACS)
o ST-segment elevation acute myocardial infarction (STEMI)
I. ETIOPATHOGENESIS
Inadequate supply of blood flow and oxygen to a portion of the myocardium causing inadequate perfusion of
myocardium supplied by an involved artery
Most common cause: atherosclerotic disease of an epicardial coronary artery
Obesity, insulin resistance, and T2DM are increasing and powerful risk factors for IHD
II. CLINICAL MANIFESTATIONS

A. Angina
Typical history involves a man >50 years old or woman >60 years old who complains of chest discomfort:
o Described as heaviness, pressure, squeezing, smothering or choking
o Crescendo-decrescendo in nature
o Usually lasts 2-5 minutes
o Associated with physical exertion or stress
o Radiation to either or both shoulders/arms, but does not radiate to the trapezius muscles
o Relieved within 5-10 minutes by rest and/or sublingual NTG
o Levine’s sign: hand placed over sternum with a clenched fist to indicate discomfort
B. Canadian Cardiovascular Society Classification of Angina

CCS CLASS DESCRIPTION
I Angina occurs with greater than ordinary physical activity
II Angina occurs with ordinary physical activity
III Angina occurs with less than ordinary physical activity
IV Angina may be present even at rest
III. DIAGNOSIS
A. Non-Invasive Diagnostics
DIAGNOSTIC TEST EXPECTED FINDINGS
May be normal at rest
ECG ST-segment and T-wave changes, LV hypertrophy, intraventricular
conduction disturbance (which may be non-specific)
Stress Testing Most widely used for both diagnosis of IHD and estimating prognosis
Involves recording the 12-lead ECG before, during and after exercise
Used to assess left ventricular function in patients with CSAP and
patients with a history of a prior MI, pathologic Q waves or clinical
2D Echo evidence of CHF
Assess for wall motion abnormalities, ejection fraction, presence of
thrombus, etc.
57
B. Indications for Coronary Angiography
Patients with CSAP who are severely symptomatic despite medical therapy and considered for revascularization
Patients with troublesome symptoms that present diagnostic difficulties in whom there is a need to confirm or R/O
the diagnosis of IHD
Patients with known or possible CSAP who have survived cardiac arrest
Patients with CSAP or evidence of ischemia on noninvasive testing with clinical or laboratory evidence of
ventricular dysfunction
Patients at high risk of sustaining coronary events on noninvasive testing, regardless of symptoms
IV. MANAGEMENT OF CSAP
A. Pharmacologic Treatment for Angina

DRUG CLASS EXAMPLES MECHANISM OF ACTION COMMENTS
Anti-Ischemic Drugs
None of the long-
acting nitrates are
as effective as SL
Isosorbide Dinitrate Systemic venodilation NTG for the acute
(ISDN) 10-40 mg BID- with reduction in LV relief of angina
TID end-diastolic volume Used for
Isosorbide Mononitrate and pressure, thereby symptomatic relief
(ISMN) 30-240 mg OD reducing myocardial May be
NTG 0.3-0.6 mg SL, as wall tension and O2 discontinued with
Nitrates needed up to 3 doses, requirements the disappearance
5 mins apart Dilation of epicardial of chest pain
NTG Transdermal coronary vessels Common side effect
Patch 0.2-0.8 mg/hr OD Increased blood flow limiting their use:
(remove at bedtime for in collateral vessels headache
12-14 hrs) At least 8 hour
nitrate-free interval
is recommended to
avoid nitrate
tolerance
Metoprolol 50-100 mg Reduced myocardial
BID-QID O2 demand by Cornerstone
Metoprolol XL 50-200 inhibiting increases in therapy for angina
B-Blockers (BB) mg OD HR, arterial pressure Shown to improve
Carvedilol 3.125-50 mg and myocardial life expectancy
BID contractility caused by following acute MI
Atenolol 50-100 mg OD adrenergic activation
Bisoprolol 5-20 mg OD
Indicated in patients
with:
o Inadequate
responsiveness to
Non-dihydropyridines the combination of
Verapamil 80-120 mg Coronary vasodilators BB and nitrates
TID-QID that produce variable o Adverse reactions
Diltiazem 30-90 mg and dose dependent to BB
Calcium TID-QID reductions in o Angina history of
Channel myocardial O2 asthma or COPD
Blockers (CCB) Dihydropyridines demand, contractility, o Sick sinus
Amlodipine 2.5-10 mg and arterial pressure syndrome or
OD significant AV
Felodpine 2.5-10 mg conduction
OD disturbances
o Prinzmetal’s angina
o Symptomatic
58
peripheral arterial
disease
Other Pharmacologic Agents for Angina
Inhibitor of the IF ion channel (principal determinant of Only works in
Ivabradine the SA node) patients who are in
2.5-7.5 mg BID Slows the heart rate through a mechanism that is not sinus rhythm
associated with negative inotropic effects
Dilates peripheral and coronary resistance vessels via Has anti-anginal
Nicorandil ATP-sensitive K+ channels efficacy similar to
10-20 mg BID Possess a nitrate moiety that promotes venous and BB, nitrates & CCBs
coronary dilation
B. Other Drugs for Stable Angina Pectoris

DRUG CLASS EXAMPLES MECHANISM OF ACTION COMMENTS
Irreversible inhibitor of Chronic administration
Aspirin platelet cyclooxygenase has been shown to
75-162 mg OD activity, interfering with reduce coronary events
platelet activation
Antiplatelets Oral agent that blocks May be substituted for
Clopidogrel ADP receptor-mediated aspirin in those with
75 mg OD platelet aggregation aspirin hypersensitivity
or those who cannot
tolerate aspirin
Can lower LDL
Act as HMG-CoA cholesterol (25-50%),
Rosuvastatin reductase inhibitor raise HDL cholesterol
10-20 mg OD Exhibit pleiotropic and lower triglycerides
Statins Atorvastatin effects: plaque High intensity statin
10-80 mg OD stabilization and anti- therapy should be given
Simvastatin inflammatory effects for patients with
10-40 mg OD established IHD who
are less than 75 years
old, in the absence of
contraindications
C. Coronary Interventions
INTERVENTION DESCRIPTION
Percutaneous Coronary Balloon dilatation usually accompanied by coronary stenting
Intervention (PCI) Most common indication: persistent or symptom-limiting angina pectoris,
despite medical therapy, accompanied by evidence of ischemia during a
stress test
Coronary Artery Bypass Indicated for those with three-vessel CAD or two-vessel CAD with
Grafting (CABG) involvement of the left anterior descending artery (LAD) or stenosis of the
left main coronary artery
ACUTE CORONARY SYNDROMES (ACS)
Operational term that refers to a spectrum of conditions compatible with acute myocardial ischemia and/or
infarction due to an abrupt reduction in coronary blood flow
Patients with ACS are composed of:
o Non-ST segment elevation acute coronary syndrome (NSTE-ACS):
Non-ST segment elevation myocardial infarction (NSTEMI)
Unstable angina (UA)
ST elevation acute myocardial infarction (STEMI)
59
I. UNIVERSAL DEFINITON OF MYOCARDIAL INFARCTION
A. Criteria for Acute MI

“Acute MI” should be used when there is evidence of myocardial necrosis in a clinical setting consistent with acute
myocardial ischemia. Under these conditions, any of the following criteria meet the diagnosis for MI:
Detection of a rise and/or fall in cardiac biomarkers (preferably cardiac troponins/cTn), with at least one value
above the 99th percentile with at least one of the following:
o Symptoms of ischemia
o New or presumed new significant ST-segment and/or T wave changes or new LBBB
o Development of pathologic Q waves on the ECG
o Imaging evidence of new loss of viable myocardium or new wall motion abnormality
o Identification of an intracoronary thrombus by angiography or autopsy
Cardiac death with symptoms suggestive of myocardial ischemia & presumed new ischemic ECG changes or
new LBBB (Type 3)
PCI-related MI (Type 4a)
Stent thrombosis associated with MI (Type 4b)
CABG-related MI (Type 5)
B. Criteria for Previous Myocardial Infarction (any of the following):

Pathologic Q waves with or without symptoms in the absence of non-ischemic causes
Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract in the absence of a
non-ischemic cause
Pathologic findings of previous MI
II. UNIVERSAL CLASSIFICATION OF TYPES OF MYOCARDIAL INFARCTION

TYPE OF MYOCARDIAL INFARCTION DESCRIPTION
(MI)
Type Related to atherosclerotic plaque rupture, ulceration, fissuring, erosion or
Spontaneous MI dissection with resulting intraluminal thrombus in one or more of the
1 coronary arteries that leads to decreased myocardial blood flow or distal
platelet emboli with ensuing myocyte necrosis
A condition other than CAD contributes to an imbalance between
MI secondary to myocardial oxygen supply and/or demand, e.g., coronary endothelial
Type Ischemic Imbalance dysfunction, coronary artery spasm, coronary embolism,
2 tachyarrhythmias/bradyarrhythmias, anemia, respiratory failure,
hypotension, and hypertension with or without LVH
Type MI resulting in Death Cardiac death with symptoms suggestive of ischemia and presumed new
when Biomarkers are ischemic changes (or new LBBB), but death occurring before blood
3 Unavailable samples could be obtained
MI associated with PCI defined by elevation of cTn values to >5x the 99th
percentile of the upper reference limit in those with normal baseline values
or a rise in cTn values >20% if baseline values are elevated and are stable
or falling; AND either:
Type MI related to PCI Symptoms suggestive of myocardial ischemia
4a New ischemic changes on the ECG or new LBBB
Angiographic loss of patency of a major coronary artery or a side
branch or persistent slow flow or no flow or embolization
Imaging demonstration of new loss of viable myocardium or new
regional wall motion abnormality
Type MI associated with stent thrombosis is detected by coronary angiography
MI related to Stent or autopsy in the setting myocardial ischemia and with a rise and/or fall in
4b Thrombosis cardiac biomarkers with at least one value >99th percentile of the upper
reference limit
MI associated with CABG – defined by elevation of cardiac biomarker
values >10x the 99th percentile of upper reference limit in patients with
Type MI related to CABG normal baseline values; AND either:
5 New pathologic Q waves or new LBBB, or
New graft or new native coronary artery occlusion on angiogram,
60
or
Imaging evidence of new loss of viable myocardium or new
regional wall motion abnormality
NON-ST ELEVATION ACUTE CORONARY SYNDROME (NSTE-ACS)

I. ETIOPATHOGENESIS
Most commonly caused by an imbalance O2 supply and demand, resulting from a partially occluding thrombus
forming on a disrupted atherothrombotic coronary plaque on eroded coronary artery endothelium
A. Four Basic Pathophysiologic Processes:

Most common cause: plaque rupture or erosion with superimposed non-occlusive thrombus
Dynamic obstruction (e.g., coronary spasm as in Prinzmetal’s variant angina)
Severe mechanical obstruction
Increased myocardial O2 demand (e.g., tachycardia) and/or decreased supply (e.g. anemia)
B. Definition of Terms
TERM DEFINITION
Angina or equivalent ischemic discomfort with at least one of the following:
Occurs at rest (or with minimal exertion), usually lasting >10 minutes
Unstable Angina (UA) Severe and of new onset (e.g., within the prior 4-6 weeks) of at least
CCS III severity
Occurs with crescendo pattern (e.g., distinctly more severe, prolonged
or frequent than previous episodes)
NSTEMI Clinical features of UA plus evidence of myocardial necrosis (elevated
cardiac biomarkers)
Ischemic pain that occurs at rest but not usually with exertion,
Prinzmetal Variant Angina associated with transient ST-segment elevation
Due to transient, focal spasm of an epicardial coronary artery
A. Typical Chest Pain

Chest discomfort is typically severe and has at least one of the following features:
o Occurs at rest (or with minimal exertion), lasting >10 minutes
o Relatively recent onset (within prior 2 weeks)
o Occurs with a crescendo pattern (e.g., more severe, prolonged or frequent)
B. Symptoms & Signs of NSTE-ACS

SYMPTOMS SIGNS
Chest pain radiating to the neck, left Pale cool skin
shoulder, and left arm Sinus tachycardia
Dyspnea S3 or S4
Diaphoresis Basilar rales
Anxiety, restlessness Hypotension
III. DIAGNOSIS OF NSTE-ACS
A. 12-Lead Echocardiogram (ECG)

ST-segment depression, transient ST-segment elevation or T-wave inversion
T-wave changes: sensitive for ischemia but less specific (unless new & deep T-wave inversions > 0.3 mV)
If initial ECG is not diagnostic – serial ECGs should be done to detect ischemic changes if patient remains
symptomatic with a high suspicion for ACS
B. Cardiac Biomarkers
Elevated levels distinguish patterns with NSTE-ACS from UA
61
Serial cardiac troponin I or T levels should be obtained at presentation and 3-6 hours after symptom onset to
identify a rising and/or falling pattern of values
Additional levels should be obtained beyond 6 hours in patients with normal levels on serial examination when
ECG and/or clinical presentation confer an intermediate or high index of suspicion for ACS
1. Advantages and Disadvantages of the Common Cardiac Biomarkers

CARDIAC TROPONINS CK-MB
Powerful tool for risk stratification Rapid, cost-efficient,
Greater sensitivity and specificity than accurate assays
Advantage CK Ability to detect early
Detection of recent MI up to 2 weeks reinfarction
after onset (remain elevated 7-10 days
after MI)
Low sensitivity in very early phase of Loss of specificity in setting
MI (<6 hours after symptom onset) of skeletal muscle disease of
and requires repeat measurement at injury, including surgery and
8-12hours if negative IM injections
Disadvantage Limited ability to detect late minor With contemporary troponin
reinfarction assays, CKMB is not useful
Minor troponin elevations can be for diagnosis of ACS
caused by azotemiz/CKD, CHF,
myocarditis or pulmonary embolism
2. Timing of Cardiac Markers

CARDIAC BIOMARKER TIME TO DETECTION PEAK DURATION
Troponin-T 3-12 hrs 24 hours 5-14 days
Troponin-I 3-12 hrs 24 hours 5-10 days
CK-MB 4-8 hrs 24 hours 2-3 days
C. Risk Stratification: TIMI SCORE for NSTE-ACS

Prognostication scheme, which categorizes patients based on risk of all-cause mortality, new or recurrent MI, or
severe ischemia requiring urgent revascularization
COMPONENTS POINTS INTERPRETATION

Age > 65 years 1 point
> 3 CAD factors 1 point Risk Total Score:
Known CAD (> 50% stenosis) 1 point 0-7 points
Aspirin use in the [ast 7 days 1 point
Severe angina in last 24 hours 1 point High Risk Score:
Elevated cardiac markers 1 point > 3 points
ST deviation > 0.5mm 1 point (13% mortality)
IV. MANAGEMENT OF NSTE-ACS
A. Standard and Anti-Ischemic Therapy

THERAPY DESCRIPTION
Non-Pharmacologic Bed rest with continuous ECG monitoring
Supplemental oxygen if O2 sat <94%
Avoid in:
SL nitrate (ISDN 5 mg/tab) q5 SBP <90 mmHg or >30 mmHg
mins x total of 3 doses below baseline
IV NTG in first 48 hours (5-10 Severe bradychardia <50 bpm
Nitrates mcg/kg/min, max 200 Tachycardia >100 bpm in
mcg/kg/min) for persistent absence of symptomatic HF
ischemia, HF or HPN Suspected RV infarction
Decrease in angina symptoms Those who received sildenafil
for the past 24 hours (may
potentiate hypotension)
62
Not given in patients with:
Signs of acute HF
Low output states (SBP <90,
Started within 24 hours HR <50)
Beta-Blockers (BB) Metoprolol succinate, PR interval > 0.24 secs, 2nd or
carvedilol or bisoprolol 3rd degree AVB without a
pacemaker
Active asthma or reactive
airway disease
Recommended for recurrent ischemia after appropriate use of BB and
Nondihydropyridine Calcium nitrates
Channel Blockers For those with contraindications to beta-blockers
Verapamil or diltiazem
Given orally within 24 hours in patients with congestion and/or LVEF <
ACE Inhibitors 40%
ARBs may be given if patient intolerant to ACE inhibitors
Captopril 6.25-12.5 mg PO q8
B. Anti-Platelet Therapy
Initial treatment should begin with aspirin
In the absence of a high risk of bleeding, patients with NSTE-ACS should also receive a P2Y12 inhibitor for up to
12 months (at least 12 months if patient is to undergo PCI with stenting): clopidgrel, ticagrelor, prasugrel
THERAPY DESCRIPTION
Platelet cyclooxygenase inhibitor
Aspirin Dose: 165-325 mg loading dose, then 80-162 mg OD maintenance dose
indefinitely
Thienopyridine
Clopidogrel Inactive prodrug that is converted into an active metabolite that causes
irreversible blockade of the platelet ADP P2Y12inhibitor
Dose: 300-600 mg loading dose, then 75 mg OD
Non-thienopyridine
Novel, potent, reversible platelet ADP P2Y12inhibitor
Ticagrelor May be used in patients who are treated either by an invasive or conservative
strategy
Dose: 180 mg loading dose, then 90 mg BID
Thienopyridine
Also a platelet ADP P2Y12 antagonist, but achieves a more rapid onset and
higher level of platelet inhibition than clopidogrel
Approved for ACS patients following angiography in whom PCI is planned (it
Prasugrel has not been found to be effective in patients treated by a conservative
strategy)
Contraindicated in patients with prior stroke / TIA or a high risk of bleeding
Dose: 60 mg loading dose, then 10 mg OD (if patient is to undergo early
invasive management)
C. Anticoagulation Therapy
THERAPY DESCRIPTION
Unfractioned Heparin Mainstay of therapy
(UFH) Target aPTT 50-70 seconds (ratio of 1.5-2.5)
Dose: 60 U/kg IV bolus (maximum 4,000 U), then 12 U/kg infusion (1000
units/hour) for 48 hours or until PCI is performed (most trials continued therapy
for 2-5 days)
Enoxaparin Superior to UFH in reducing recurrent cardiac events, especially in patients
managed conservatively
Dose: 30 mg IV loading dose, then 1 mg/kg SC q12 for the duration of
hospitalization or until PCI is performed
Fondaparinux Indirect factor Xa inhibitor
63
Equivalent in efficacy to enoxaparin, but with lower risk of major bleeding
Dose: 2.5 mg SC OD for duration of hospitalization or until PCI is performed
D. Statins
High intensity statin therapy should be initiated or continued
Early administration of statins (e.g., Atorvastatin 80 mg/day) has been shown to reduce adverse outcomes
E. Conservative versus Early Invasive Strategy
Conservative strategy (low risk patients): anti-ischemic therapy and antithrombotic therapy followed by “watchful
waiting” (close observation)
Early-invasive strategy (for high risk patients): following treatment with anti-ischemic and antithrombotic agents,
angiography is carried out within 48 hours, followed by coronary revascularization (PCI or CABG)
CONSERVATIVE MEDICAL MANAGEMENT EARLY INVASIVE MANAGEMENT
(Ischemia-Guided Strategy) (Revascularization)
Low risk score (TIMI 0 or 1) Recurrent angina or ischemia at rest or with low-
Low risk troponin-negative female patients level activities despite intensive medical therapy
Patient or physician preference in the Elevated cardiac biomarkers (TnT or Tnl)
absence of high-risk features New or presumably new ST segment depression
CHF symptoms, rales, MR
Reduced left ventricular function (LVEF < 40%)
Sustained ventricular tachycardia
PCI < 6 months or prior CABG
High-risk findings from noninvasive testing
Hemodynamic instability
Mild-to-moderate renal dysfunction
DM
High TIMI risk score > 3
IV. PRINZMETAL’S VARIANT ANGINA

Syndrome of severe ischemic pain that usually occurs at rest and associated with transient ST elevation
Caused by focal spasm of an epicardial coronary artery (most commonly the right coronary artery)
Diagnostic hallmark: coronary arteriography demonstrates transient coronary spasm
Main therapeutic agents: nitrates and calcium channel blockers
Aspirin may increase severity of ischemic episodes
ST-ELEVATION MYOCARDIAL INFARCTION (STEMI)

I. ETIOPATHOGENESIS
Acute plaque rupture is central to the pathogenesis of STEMI
Occurs when coronary blood blow decreases abruptly after a thrombotic occlusion of a coronary artery previously
affected by atherosclerosis

Diagnosed similarly as NSTE-ACS (e.g., clinical features, increased cardiac biomarkers) but with ECG findings
evolving in a temporal pattern (see ECG Reading in Chapter 1)
III. DIAGNOSIS AND RISK STRATIFICATION FOR STEMI

A. Killip Scoring for STEMI
CLASS DESCRIPTION RISK OF MORTALITY
Class No rales or signs of pulmonary or venous congestion
I Normal BP 0-5%
Moderate HF, bibasal rales
Class Normal BP
S3 gallop 10-20%
II
Tachypnea or signs of right-sided CHF (venous or hepatic
congestion)
Severe HF
64
Class (+) mid-basal rales and pulmonary edema 35-45%
III (+) S3 and S4
Normal BP
Shock with SBP <90 mmHg & evidence of peripheral
Class vasoconstriction 85-95%
Peripheral cyanosis
IV
Mental confusion and oliguria
B. TIMI Risk Score for STEMI

TIMI risk score for STEMI: predicts 30-day mortality
Designed for risk assessment early after patient presentation and thus does not incorporate noninvasive and
invasive data
COMPONENTS POINTS INTERPRETATION
Historical
Age 65-74 2 points
Age > 75 3 points
DM, Hypertension, Angina 1 point Risk Total Score:
Examination 0-14 points
SBP < 100 mmHg 3 points
HR > 100 bpm 2 points High Risk Score:
Killip II-IV 2 points > 5 points
Weight < 67 kg 1 point (12% mortality)
Presentation
Anterior ST elevation or LBBB on ECG 1 point
Time to Treatment > 4 hours 1 point
IV. MANAGEMENT OF STEMI
A. Pre-hospital Management of STEMI

Major components:
o Recognition of symptoms
o Rapid deployment of an emergency medical team capable of performing resuscitative maneuvers
o Expeditious transportation
o Expeditious implementation of reperfusion therapy
Most out-of-hospital deaths from STEMI are due to sudden ventricular fibrillation
Majority of deaths occur within 24 hours of the onset of symptoms (over half occur in the 1st hour)
B. Reperfusion Therapy: Primary Goal of Management

Reperfusion Therapy (fibrinolysis or PCI) should be administered to all eligible patients with STEMI with
symptom onset within the last 12 hours
o Primary PCI: recommended method of reperfusion when it can be performed in a timely fashion
o Fibrinolysis: administered at non-PCI-capable centers
FIBRINOLYSIS / THROMBOLYSIS INVASIVE STRATEGY (PCI)
Generally preferred if: Generally preferred if:
Early presentation (< 3 hours of symptom onset) Available PCI laboratory with surgical backup
Invasive strategy is not available: o Medical contact-to-balloon or door-to-balloon
Delay to invasive strategy: < 90 minutes
o Prolonged transport o Door-to-balloon minus door-to-needle < 1 hr
o Door-to-balloon minus door-to-needle High risk STEMI (cardiogenic shock, Killip > 3)
time >1 hr Contraindications to fibrinolysis
o Medical contact-to-balloon or door-to- Late presentation (symptom onset > 3 hours)
balloon time >90 minutes Diagnosis of STEMI is in doubt
Fibrinolytic agents: Percutaneous coronary intervention (PCI) or
o Streptokinase percutaneous transluminal coronary angioplasty
o Tissue plasminogen activators (PTCA): balloon angioplasty and stenting
Adjunct anti-platelet therapy with fibrinolysis: Anti-platelet therapy during Primary PCI:
Aspirin continued indefinitely
65
Clopidogrel for at least 14 days up to 1 o Aspirin indefinitely after PCI
year o One P2Y12-receptor inhibitor continued for 1 year
for those who receive a stent:
Adjunctive anticoagulant therapy with Clopidogrel
fibrinolysis: given for a minimum of 48 hours or Prasugrel (not used if + prior stroke/TIA)
until revascularization is performed (same dose Ticagrelor
as in NSTE-ACS)
o Unfractioned heparin (UFH) Anticoagulant therapy during primary PCI:
o Enoxaparin o UFH
o Fondaparinux o Bivalirudin
Fibrinolysis is still reasonable if symptom onset is within 12-24 hours as long as there is evidence of ongoing
ischemia (although primary PCI is preferred for this population)
CONTRAINDICATIONS TO FIBRINOLYSIS
ABSOLUTE CONTRAINDICATIONS RELATIVE CONTRAINDICATIONS
Previous intracranial hemorrhage History of chronic, severe, poorly controlled HPN
Structural cerebral vascular lesion (e.g., Significant HPN at initial evaluation (SBP > 180
AVM) mmHg or DBP > 110 mmHg)
Malignant intracranial neoplasm History of previous ischemia stroke > 3 months
Ischemic stroke within 3 months except Dementia
acute ischemic stroke within 4.5 hours Intracranial pathology not covered in absolute
Suspected aortic dissection contraindications
Active bleeding / bleeding diathesis (except Traumatic or prolonged (>10 minutes) CPR
mense) Major surgery (<3 weeks)
Closed-head or facial trauma within 3 months Recent (within 2-4 weeks) internal bleeding
Intracranial/intraspinal surgery within 2 Noncompressible vascular punctures
months Pregnancy
Severe uncontrolled hypertension Active peptic ulcer
(unresponsive to emergency therapy) Oral anticoagulant therapy
For streptokinase, previous treatment within
the previous 6 months
AVM: Arteriovenous malformation
CPR: cardiopulmonary resuscitation
C. Other Routine Medications for STEMI

THERAPY DESCRIPTION
Should be initiated in the first 24 hours, except if
with signs of HF, low output state, increased risk for
Beta Blockers cardiogenic shock, or other contraindications (PR
interval > 0.24, 2nd or 3rd degree AVB, active
asthma, reactive airway disease)
ACE-inhibitors should be initiated in the first 24
hours to all patients with anterior wall STEMI, HF or
RAAS Inhibitors EF < 40%
ARB may be used for those intolerant to ACE-
inhibitors
Statins High intensity statin therapy should be initiated or
continued
D. Supportive Care
THERAPY DESCRIPTION
First 12 hours: bed rest
Next 12 hours: dangling of feet at bedside and
Activity sitting in a chair
2nd and 3rd day: ambulation in the room with
increasing duration and frequency to a goal of 185
cm (600 ft) at least 3x a day
2 weeks: resumption of work and sexual activity
66
Nothing or only clear liquids (due to risk of emesis
Diet and aspiration) for the first 4-12 hours
Use of stool softener
Sedation Many require sedation during hospitalization to
withstand period of enforced inactivity
E. Secondary Prevention and Long Term Management

THERAPY DESCRIPTION
Smoking Complete cessation
BP Control BP <140/90 or <130/80 if CKD or DM
Lipid Management High dose statins
<7% of total calories as saturated fats and <200 mg/day total cholesterol
Physical Activity 30 minutes of moderate intensity aerobic exercise, 3 to 4 days per week
Weight BMI 18.5 – 24.9 kg/m2
Management Waist circumference: women <35 inches, men <40 inches
DM Management HbA1c <7%
Anti-platelets Aspirin or P2Y12-receptor inhibitors
RAAS Blockers ACEI in stable high-risk patients (anterior MI, previous MI, Killip > II, EF <40%)
Beta Blockers Continued indefinitely
IV. USUAL COMPLICATIONS OF STEMI

COMPLICATION FREQUENCY DESCRIPTION
Ventricular 1-3% in those who Bimodal peak (within 24 hours & 3-5 days; can range from 1-14 days)
Septal Rupture did not undergo Presents with chest pain, SOB and hypotension
(VSR) reperfusion Holosystolic murmur, S3, accentuated 2 nd heart sound, pulmonary
edema, RV and LV failure, cardiogenic shock
Bimodal peal (within 24 hours & 3-5 days; can range from 1-14 days)
Presents with angina, pleuritic or pericardial chest pain, syncope,
Ventricular Free 0.8-6.2% hypotension, arrhythmia, nausea, restlessness, hypotension and
Wall Rupture sudden death
JV distention (29%), pulsus paradoxus (47%), electromechanical
dissociation and cardiogenic shock
1% (posteromedial Bimodal peak (within 24 hours & 3-5 days; can range from 1-14 days)
Papillary Muscle more frequently Abrupt onset of dyspnea, pulmonary edema, and hypotension
Rupture affected than Soft murmur in most cases, no thrill, variable signs of RV overload,
anterolateral severe pulmonary edema, cardiogenic shock
muscle) Hypercontractile LV, torn papillary muscle or chordae tendinae, flail
leaflet and severe MR on echo with color flow
RHEUMATIC FEVER (RF)

I. ETIOPATHOGENESIS
Multi-system disease resulting from autoimmune reaction to infection with Group A Beta-Hemolytic
Streptococcus
In RF, antibodies against M-proteins of certain strains of Streptococcus cross-react with tissue glycoproteins in
the heart, joints and other tissues (“molecular mimicry”)

Latent period of 3 weeks (ranges from 1 to 5 weeks) between the precipitating infection and the appearance of
the clinical features of ARF with the exception of chorea and indolent carditis which may follow prolonged talent
period lasting up to 6 months
Most common clinical presentation: polyarthritis and fever
A. Major Manifestations
Carditis Pancarditis involving the pericardium, myocardium and endocardium
(up to 60%) Hallmark is valvular damage
67
Characteristic manifestation is mitral regurgitation
Migratory Typically migratory over a period of hours
Polyarthritis Most often asymmetric and affecting large joints (ankles, wrists, knees, elbows)
(75%) Highly responsive to salicylates and NSAIDs
Sydenham’s Involuntary jerking movements mostly affecting the head and upper limbs
Chorea (<10%) Commonly occurs in females and in the absence of other manifestations
Usually resolves completely within 6 weeks
Erythema Evanescent pink macular eruption with round borders and central clearing
Marginatum Usually concentrated on the trunk, sometimes on the limbs, but almost never on the
face
Subcutaneous Painless small lumps found over extensor surfaces of joints
Nodules Usually a delayed manifestation (2-3 weeks after onset)
Commonly associated with carditis
B. Minor Manifestations
Clinical Arthralgia (joint pains), fever
Laboratory findings Elevated acute phase reactants (ESR/CRP), prolonged PR interval on ECG
C. Supporting Evidence of a Preceding Streptococcal Infection within the last 45 days

Elevated or rising anti-streptolysin-O or other streptococcal antibody, or
A positive throat culture, or
Rapid antigen test for group-A Streptococcus, or
Recent scarlet fever
III. DIAGNOSIS
A. The Revised Jones Criteria: Diagnosis of Rheumatic Fever (RF) and Rheumatic Heart Disease (RHD)
DIAGNOSTIC CATEGORIES CRITERIA
Primary episode of RF Evidence of preceding group-A streptococcal infection; PLUS:
2 major criteria, or
1 major + 2 minor criteria
Recurrent RF in a patient Evidence of preceding group-A streptococcal infection; PLUS:
without established RHD 2 major criteria, or
1 major + 2 minor criteria
Recurrent RF in a patient with Evidence of preceding group-A streptococcal infection; PLUS:
established RHD 2 minor criteria
Rheumatic chorea Other major manifestations or evidence of group-A streptococcal infection not
Insidious onset rheumatic required
carditis
Chronic valve lesions of RHD
(patients presenting for the 1st
time with pure MS or mixed Do not require any other criteria to be diagnose as having RHD
MV disease and/or AV
disease)
B. Criteria for Echocardiographic Diagnosis of Rheumatic Heart Disease (RHD) in Individuals <20 years of age
Definite RHD (either A, B, C or D)
A. Pathologic MR + > 2 morphologic features of RHD of the mitral valve (MV)
B. MS mean gradient >4 mmHg
C. Pathologic AR + > 2 morphologic features of RHD of the aortic valve (AV)
D. Borderline disease of both the MV and AV
Borderline RHD (either A, B, C)
A. > 2 morphologic features of RHD of the MV without pathologic MR or MS
B. Pathologic MR
C. Pathologic AR
Normal Echocardiographic Findings (all of A, B, C and D)
A. MR that does not meet all four Doppler criteria (physiologic MR)
B. AR that does not meet all four Doppler criteria (physiologic AR)
68
C. An isolated morphologic feature of RHD of the MV (e.g., valvular thickening), without any associated pathologic
stenosis or regurgitation
D. Morphologic feature of RHD of the AV (e.g., valvular thickening), without any associated pathologic stenosis or
regurgitation
Definitions of Pathologic Regurgitation & Morphologic Features of RHD
Pathologic MR: all of the following – seen in 2 weeks; in at least 1 view, jet length 2 cm; peak velocity > 3 m/s;
pansystolic jet in at least 1 envelope
Pathologic AR: all of the following – seen in 2 views; in at least, jet length > 1 cm; peak velocity > 3 m/s’
pandiastolic jet in at least 1 envelope
Morphologic features of RHD in MV: anterior MV leaflet thickening > 3 mm; chordal thickening; restricted
leaflet motion; excessive leaflet tip motion during systole
Morphologic features of RHD in AV: irregular of focal thickening; coaptation defect; restricted leaflet motion;
prolapse
IV. MANAGEMENT OF RHEUMATIC FEVER
A. For Acute Management

Penicillin:
For Infection o PO: Pen V 500 mg BID or Amoxicillin 50 mg/kg daily x 10
days
o IM: single dose of 1.2 M units Benzathine Penicillin G
For Arthritis / Mild Carditis Aspirin 4-8 g/d in 4-5 divided doses up to 2 weeks
For Moderate-Severe Carditis May add prednisone 1-2 mg/kg/day up to 4 max of 3 weeks
For Severe Chorea Carbamazepine or valproic acid
B. For Prophylaxis of Rheumatic Fever

Primary prophylaxis for RH: to treat group-A streptococcal URTI and eradicate the organism to prevent an initial
attack of acute RF
Secondary prophylaxis for RF: to prevent colonization and/or infection in patients who had a previous attack of
RF to prevent recurrence of RF
1. Drugs Available for Secondary Prophylaxis

Benzathine Penicillin G 1.2 M units q 2-4 weeks (best)
Penicillin VK 250 mg/cap BID
Erythromycin 250 mg/cap BID (if allergic to Penicillin)
2. Duration of Secondary Prophylaxis

CATEGORY DURATION OF PROPHYLAXIS
RF without Carditis 5 years after last attack or until 21 y/o (whichever is longer)
RF with Carditis, but no residual 10 years after last attack or until 21 y/o (whichever is longer)
valvular disease
RF with persistent valvular disease 10 years after last attack or until 40 y/o (sometimes lifetime)
VALVULAR HEART DISEASE (VHD)

I. STAGES OF PROGRESSION OF VHD
CLASS STAGE A STAGE B STAGE C STAGE D
(At Risk) (Progressive) (Asymptomatic Severe) (Symptomatic Severe)
General Definition
Risk + + + +
Symptoms - - - +
Severity - Mild-to-Moderate Severe Severe
Individual Valvular Heart Disease Staging
Asymptomatic Severe Symptomatic Severe
AS At risk Asymptomatic C1: normal LVEF D1: high gradient
Progressive C2: low LVEF D2: low flow, low gradient, low
LVEF
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D3: low flow, low gradient,
preserved LVEF (paradoxical low-
flow severe AS)
Asymptomatic Severe
AR At risk Asymptomatic C1: normal LVEF Symptomatic Severe
Progressive C2: low LVEF or dilated
LVEF
MS At risk Asymptomatic Asymptomatic Severe Symptomatic Severe
Progressive
Asymptomatic Severe
MR At risk Asymptomatic C1: normal LVEF Symptomatic Severe
Progressive C2: low LVEF & dilated
LVEF
TR At risk Asymptomatic Asymptomatic Severe Symptomatic Severe
Progressive
II. INDIVIDUAL VALVULAR HEART DISEASES (VHD)
A. Aortic Stenosis (AS)

Most common cause: degenerative calcification of aortic cusps in adults
Most common congenital defect: bicuspid aortic valve (BAV)
Symptoms (dyspnea, angina, exertional syncope) are rarely present until valve orifice <1 cm 2
Death usually at 7th-8th decades, and may depend on the presence of symptoms:
o If with syncope I angina: death in 3 years
o If with dyspnea: death in 2 years
o If with CHF: death in 1.5-2 years
Pulsus parvus et tardus: weak and late pulse

Physical Exam Low pitched midsystolic ejection murmur at 2nd R ICS
Murmur may be transmitted to the apex, resembling murmur of MR (Gallavardin
effect)
Diagnostics CXR / ECG: LVH (with strain pattern on ECG)
2D Echo: calcified aortic valve with restriction in opening
Avoidance of strenuous activity and competitive sports
Diuretics for CHF
Caution with the use of nitrates and afterload unloaders (ACEI/ARBs) as these
Therapy may precipitate hypotension
Statins for slower progression of leaflet calcification
Intervention: Transcatheter Aortic Valve Implantation (TAVI), aortic valve
replacement (surgery)
B. Aortic Regurgitation (AR)

Austin Flint murmur: soft low-pitched rumbling mid-to-late diastolic murmur
De Musset sign: jarring of the body & bobbing of the head with each systole in
severe AR
Quincke’s pulse: visible capillary pulsations at the root of the nail with pressure
Physical Exam Traube sign: booming pistol shot sound over femoral arteries
Duroziez sign: to and from murmur when femoral artery is compressed
Water hammer (Corrigan’s) pulse: bounding and forceful pulse, rapidly
increasing and subsequently collapsing
Others: widened pulse pressure, absence of A2 in severe AR
ECG: LVH usually with ST depression and T wave inversion in I, aVL, V5-6 (lateral
Diagnostics leads)
2D Echo: mosaic color flow across the aortic valve during diastole
Therapy Diuretics, ACEI and vasodilators for CHF
Intervention: aortic valve replacement (surgery)
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C. Mitral Stenosis (MS)
Rheumatic heart disease is the leading cause
Poor prognosis for those >65 y/o, marked cardiac output depression, RV dysfunction and pulmonary
hypertension
Loud S1 and accentuated P2
Physical Exam Apical diastolic rumble and murmur
Opening snap
CXR: LAE, RAE, RVH
Diagnostics ECG: LAE, RAE, RVH; atrial fibrillation in severe cases
2D ECHO: doming motion of the mitral valve (anterior leaflet) during diastole
For fluid retention: sodium, restriction, diuretics
For rate control: beta-blockers, non-dihydropyridine calcium channel blockers,
digoxin
Therapy For secondary prophylaxis of rheumatic heart disease: penicillin
For prevention of stroke: warfarin (target INR 2-3)
Intervention: percutaneous transseptal mitral commisurotomy (PTMC) or mitral
valve replacement therapy (surgery)
D. Mitral Regurgitation (MR)

Soft S1; S4 in acute severe MR
Physical Exam Apical holosystolic murmur radiating to axilla (characteristic finding)
Hyperdynamic LV with brisk systolic impulse and laterally displaced apex beat
CXR: LAE, LVH
Diagnostics ECG: LAE, LVH; atrial fibrillation in severe cases
2D ECHO: mosaic color flow across the mitral valve during systole
For fluid retention: sodium, restriction, diuretics
Therapy For acute MR:vasodilators (decreases afterload and helps reduce severity of MR)
Intervention:mitral valve repair or replacement (surgery)
E. Mitral Valve Prolapse (MVP, Floppy Valve Syndrome, Barlow’s Syndrome)

More common in women 15-30 years old
More severe in men and >50 years old
Most patients are asymptomatic
Frequent finding in heritable connective tissue disease
Apical mid- or late non-ejection systolic click (characteristic finding)
Physical Exam High pitched late crescendo-decrescendo murmur after systolic click
Murmur is accentuated by standing and strain phase of Valsalva, diminished by
squatting and isometric exercises
CXR / ECG: usually normal; but may have biphasic or inverted T in II, III, aVF
Diagnostics (inferior leads) on ECG
2D ECHO: systolic displacement of MV leaflets (prolapse) at least 2 mm into LA
superior to mitral plane
IE prophylaxis for patients with prior endocarditis
Therapy Symptoms: beat-blockers for palpitations; warfarin if with AF
Intervention: mitral valve repair or replacement (surgery) if with severe MR
F. Tricuspid Stenosis (TS)

Generally rheumatic in origin; does not occur in isolation and usually associated with MS
Almost always accompanied by severe TR
Symptoms of right-sided CHF (ascites, edema, hepatosplenomegaly)
Physical Exam Opening snap of TV ~0.06 sec after PV closure
Diastolic murmur at LLSB, augmented during inspiration and reduced during
expiration & strain phase of Valsalva
Diagnostics ECG: RAE, RVH
2D ECHO: restriction in opening of the TV
Therapy Salt restriction, bed rest and diuretics
Interventions: surgery
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G. Tricuspid Regurgitation (TR)
Distended neck veins, hepatomegaly, ascites, (+) hepatojugular reflux
Physical Exam Prominent RV pulsation along left parasternal region
Carvallo sign: blowing holosystolic murmur at LPSB intensified by inspiration
Diagnostics ECG: RAE, RVH
2D ECHO: mosaic color flow across tricuspid valve during systole
Isolated TR is usually tolerated and does not require surgery
Therapy Intervention: valve annuloplasty or replacement for severe cases
H. Pulmonic Regurgitation (PR)

Most common acquired abnormality is regurgitation from severe pulmonary arterial HPN
Graham Steell murmur: high-pitched, decrescendo, diastolic blowing murmur along left sternal border
Intervention: percutaneous pulmonic valve replacement for severe PR
PERICARDITIS
I. ETIOPATHOGENESIS
Most common pathology affecting the pericardium and classified clinically and etiologically
May be infectious, non-infectious (MI, uremia, neoplasia, myxedema, cholesterol, chylopericardium, trauma, aortic
dissection, post-irradiation, acute idiopathic, sarcoidosis) or presumably related to hypersensitivity or
autoimmunity (rheumatic fever, collagen valvular disease, drug-induced, post-cardiac injury)
A. Acute Pericarditis (< 6 weeks)

Pain resembles that of acute MI
Chest pain: severe, pleuritic, may be retrosternal or left pericordial and may be referred to neck and, arms or
left shoulder
Pericardial pain may be relieved by sitting up and leaning forward and is intensified by lying supine
PE may reveal pericardial friction rub (85%): high-pitched and is described as rasping, scratching or grating
and heard most frequently at end-expiration with patient upright and leaning forward
B. Chronic (Constrictive) Pericarditis (> 6 months)

Results when the healing of an acute fibrinous or serofibrinous pericarditis or the resorption of a chronic
pericardial effusion is followed by obliteration of the pericardial cavity with formation of granulation tissue
Weakness, weight gain, fatigue, increased abdominal girth / ascites and edema
Common in the Philippines: tuberculosis, malignancy and radiation-induced
Kussmaul’s sign: increase in systemic venous pressure with inspiration (in normal conditions, there should
be a decrease in pressure with inspiration)
Pericardial knock: early diastolic sound in the left sternal border
III. DIAGNOSIS AND MANAGEMENT

DIAGNOSTICS ACUTE PERICARDITIS CHRONIC (CONSTRICTIVE
PERICARDITIS)
Cardiac biomarkers Modest increase May be normal-minimally
increased
Subepicardial inflammation displays: Low voltage QRS complexes
Stage 1: Diffuse SST-elevation Diffuse flattening or inversion
ECG with upward concavity and PR of T-waves
segment depression Atrial fibrillation in 1/3 of
Stage 2: ST segments patients
normalize
Stage 3: T-wave inversions
Stage 4: ECG returns to
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normal (weeks or months)
This is in contrast with ECG findings in

AMI wherein ST-elevations are
convex, QRS changes occur and T-
wave inversion is seen within hours
before the ST-segments become
isoelectric
Pericardial thickening
Septal bounce
Pericardial fluid or thickening Dilation of the IVC and hepatic
Differentiate pericarditis from veins
Echocardiography MI: assessment of wall motion Normal ventricular systolic
function
Flattening of the LV posterior
wall
CT/MRI Pericardial fluid collection Pericardial thickening (more
Pericardial thickening accurate)
Bed rest Pericardial resection /
NSAIDs, colchicine pericardectomy
Management Pericardiocentesis if with Sodium restriction & diuretics
tamponade Anti-Koch’s for TB patients
Steroids (uncertain benefi)
CARDIAC TAMPONADE
I. ETIOPATHOGENESIS
Accumulation of fluid in the pericardial space causes increased intracardiac pressures causing limited ventricular
filling and decreased cardiac output
Three most common causes are neoplastic disease, idiopathic pericarditis and renal failure

Dyspnea, orthopnea and fatigue
Beck’s triad: hypotension, neck vein engorgement and muffled heart sounds
Tachycardia, tachypnea and pulsus paradoxus (>10 mmHg decrease in SBP during inspiration)
A. Diagnostics for Cardiac Tamponade

DIAGNOSTICS COMMENTS/EXPECTED FINDINGS
12-L ECG Low voltage QRS complexes with electrical alternans
Chest Radiograph Multi-chambered cardiomegaly “water-bottle” sign
2D Echocardiography Large pericardial effusion
Right atrial and right ventricular diastolic collapse
B. Differentials for Cardiac Tamponade

CHARACTERISTIC CARDIAC CONSTRICTIVE RESTRICTIVE RV MI EFFUSIVE
TAMPONADE PERICARDITIS CMP CONSTRUCTIVE
Clinical Features
Pulsus Paradoxus +++ + + + +++
Jugular Veins
Prominent y-descent - ++ + + -
Prominent x-descent +++ ++ +++ + +++
Kussmaul’s sign - +++ + +++ ++
Third Heart Sound - - + + +
Pericardial Knock - ++ - - -
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Electrocardiogram
Low ECG voltage ++ ++ ++ - ++
Electrical Alternans ++ - - - +
Echocardiography
Thick pericardium - +++ - - ++
Pericardial effusion +++ - - ++
RV size Usually small Usually normal Usually normal Enlarged
Exaggerated +++ +++ - +++
Respiratory Variation
CT-MRI
Thick pericardium - +++ - ++
Equalization of Diastolic +++ +++ - ++
Pressure
Cardiac Biopsy Helpful? No No Sometimes No No
CMP: Cardiomyopathy; RVMI: right ventricular myocardial infarction
IV. MANAGEMENT
Emergency pericardiocentesis
Tube pericardiostomy with pericardial window (for recurrent, infectious, malignant and other chronic causes)
CARDIOMYOPATHY (CMP)
Heterogenous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that
usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of
causes that frequently are genetic
It excludes cardiac dysfunction that results from other structural heart diseases such as CAD, valvular disease or
severe hypertension
DILATED RESTRICTIVE HYPERTROPHY
CARDIOMYOPATHY CARDIOMYOPATHY CARDIOMYOPATHY
Cardiac enlargement, Endomyocardial scarring or Disproportionate
resulting in impaired systolic myocardial infiltration hypertrophy, typically
Pathophysiology function, HF, arrhythmia, resulting in restriction of involving the interventricular
emboli ventricular filling septum more than the free
wall
Ejection Fraction Usually <30% 25-50% >60%
LV Dimension Dilated >60mm >60mm (may be decreased) Often decreased
LV Wall Thickness Decreased Normal or increased Markedly increased
Atrial Size Increased Increased; may be massive Increased
Valvular Regurgitation Related to annular dilation Related to endocardial Related to valve-septum
involvement interaction
Common First Symptoms Exertional intolerance Exertional intolerance, fluid Exertional intolerance; may
retention early have chest pain
Congestive Symptoms Left before right Right often predominates Left-sided congestion may
develop late
Viral, parasitic Amyloidosis Most common abnormality
Common examples Peripartum Loeffler’s found at autopsy in young
Alcohol, MAP, cocaine Endomyocardial competitive athletes who die
Chemotherapy suddenly
Normal LVEF: > 50%
Normal LV dimension: < 55mm
ATRIAL FIBRILLATION (AF)

I. TYPES OF ATRIAL FIBRILLATION
TYPE DEFINITION
Lone AF AF in a patient <60 years old with the absence of clinical findings of other
cardiovascular disease, related pulmonary disease, or cardiac abnormalities
First Diagnosed AF Every patient who present with AF for the first time, irrespective of duration or
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presence / severity of symptoms
Self-terminating, usually within 48 hours
Paroxysms may continue for up to 7 days
Paroxysmal AF 48 hour time point is important: after this, likelihood of spontaneous conversion
is low
Anticoagulation must be considered
Persistent AF AF episode either lasts >7 days or require termination by cardioversion
Long-standing Persistent AF Lasted for > 1 year when it is decided to adopt a rhythm control strategy
Permanent AF Presence of arrhythmia is accepted by the patient – rhythm control interventions
are not pursued
II. STROKE PREVENTION IN AF

Efficacy of stroke prevention with aspirin is weak and the risk of major bleeding with aspirin is not significantly
different from oral anticoagulants (OACs)
Usually has two scoring systems:
o CHA2DS2-VASc Score: to determine the risk of having a stroke in the presence of AF
o HAS-BLED: to determine the risk of bleeding (since patients with AF will be given anticoagulants)
A. CHA2DS2-VASc Score
Estimates the risk of ischemic stroke in patients with non-rheumatic / non-valvular atrial fibrillation
Better than CHADS2 in identifying “truly low risk” patients with AF
Components and corresponding points:
VARIABLE SCORE (POINTS) RISK
C Congestive HF / left ventricular dysfunction 1 0: 0%
1: 1.3%
H Hypertension (>140/9 mmHg) 1 2: 2.2%
A2 Age > 75years 2 3: 3.2%
D Diabetes 1 4: 4.0%
S2 Prior stroke / TIA / thromboembolism 2 5: 6.7%
6: 9.8%
V Vascular disease (prior MI, PAD, aortic plaque) 1 7: 9.6%
A Age 65-74 1 8: 12.5%
Sc Female sex 1 9: 15.2%
B. HAS-BLED Score
Bleeding risk score to aid in decision-making for thromboprophylaxis (to balance the risk of stroke versus risk of
major bleeding)
High risk for bleeding: HAS-BLED score > 3 (regular monitoring and correction of potentially reversible risk factors
for bleeding)
VARIABLE SCORE (POINTS)
Hypertension (SBP > 160 mmHg) 1
Abnormal renal / liver function
Renal: Chronic dialysis or renal transplantation or creatinine > 200 umol/L 1
Liver: CLD, bilirubin >2x ULN with AST / ALT / Alk Phos >3x ULN 1
Previous Stroke 1
Bleeding history or predisposition (bleeding diathesis, anemia, etc) 1
Labile INR (unstable or high INR) 1
Elderly (age >65) 1
Use of Drugs predisposing to bleeding (e.g., antiplatelets, NSAIDs) 1
Alcohol use (>8 drinks per week) 1
CLD: Chronic Liver Disease
ULN: Upper Limit of Normal
III. MANAGEMENT OF ATRIAL FIBRILLATION

A. Drugs for Rate Control:
B-blockers: metoprolol, bisoprolol, atenolol, esmolol, propranolol, carvedilol
Non-dihydropyridine CCB: verapamil, diltiazem
Digitalis / Digoxin
Others: amiodarone, dronedarone
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B. Pharmacological Cardioversion:
If with structural heart disease: Amiodarone
If without structural heart disease: Flecainide, Ibutilide, Propafenone
C. Electrical Cardioversion:
Used for patients with recent-onset AF (<48 hours) and with hemodynamic instability
IV. ANTICOAGULATION FOR STROKE PREVENTION

POPULATION ANTITHROMBOTIC THERAPY FOR STROKE PREVENTION
Valvular AF (RHD, prosthetic valves) Warfarin only
Non-Valvular AF + <65 years old + Lone AF No antithrombotic therapy
Non-Valvulvar AF + CHA2DS2-VASc Score 0 No antithrombotic therapy
Non-Valvular AF + CHA2DS2-VASc Score 1 Class Iia: consider oral anticoagulant therapy (NOAC/warfarin)
Non-Valvular AF + CHA2DS2-VASc Score > 2 Class I: start oral anticoagulant therapy (NOAC or warfarin)
A. Warfarin (Vitamin-K Antagonist)

Considered for patients with AF with >1 stroke risk factor(s) provided there are no contraindications
Superior to antiplatelets in preventing stroke
Usual INR target: 2.0-3.0
B. Non-Vitamin K Oral Anticoagulants (NOACs)

Non-inferior to warfarin, but with better safety profile
Broadly preferably to warfarin in the vast majority of patients with non-valvular AF
Assessment of renal function is mandatory for all NOACs, especially for Dabigatran
Do not require dose adjustment on the basis of a specific coagulation test (in contrast to INR in warfarin)
Do not have specific antidotes, and management of bleeding is supportive
Not recommended in patients with severe renal impairment (creatinine clearance < 30 mL/min)
DRUG MECHANISM OF ACTION DOSE
Oral direct thrombin inhibitor
150 mg BID superior to warfarin 150 mg BID
with same risk as warfarin to cause 110 mg BID for> age > 80,
Dabigatran major bleeding concomitant interacting drugs,
110 mg BID non-inferior to warfarin HAS-BLED > 3, creatinine
with fewer major bleeds (compared clearance 30-40 mL/min
to warfarin)
Oral direct factor Xa inhibitor 20 mg OD
Rivaroxaban Non-inferior to warfarin in 15 mg OD if: HAS-BLED > 3,
preventing stroke creatinine clearance 30-49
mL/min
5 mg BID
Apixaban Oral direct factor Xa inhibitor 2.5 mg BID if : age > 80 years,
weight < 60 kg, or creatinine >
133 umol/L
PERIPHERAL ARTERY DISEASE (PAD)
I. ETIOPATHOGENESIS
Clinical disorder characterized by stenosis or occlusion in the aorta or arteries of the limbs
Atherosclerosis is the leading cause of PAD in patients >40 years old

A. History and Symptoms
More than half of patients with PAD are actually asymptomatic, though some may present with slow gait
Most common symptoms: intermittent claudication (pain, ache, cramp, numbness, or sense of fatigue in the
muscles which occurs during exercise and is relieved by rest)
Other symptoms are rest pain or feeling of coldness or numbness in the feet and toes
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B. Physical Examination
Decreased or absent pulses distal to obstruction
Bruits over narrowed artery
Muscle atrophy, hair loss, thickened nails, smooth and shiny skin
Reduced skin temperature
Pallor, cyanosis,, ulcers or gangrene
III. DIAGNOSIS
DIAGNOSTICS COMMENTS / EXPECTED FINDINGS
ABI: ratio of ankle to brachial artery pressure
ABI Assessment by Doppler o >1.0: normal individuals
o <0.9: in patients with PAD
o <0.5: signifies severe ischemia (at risk for critical limb ischemia)
Segmental pressure measurements: presence of pressure gradients between
sequential cuffs signify stenosis
Segmental pulse volume recordings: amplitude of pulse volume contour
Other Non-Invasive Tests becomes blunted in significant PAD
Duplex ultrasonography: images and detects stenosis
Transcutaneous oximetry
Treadmill testing: assesses functional limitations objectively
IV. MANAGEMENT
A. Non-Pharmacologic Management
Goals: reduce the risk of associated CV events, improve limb symptoms, prevent progression to critical ischemia,
and preserve limb viability
Risk factor modification: cigarette smoking cessation, BP control
Supportive: feet care, elastic supports should be avoided, regular exercise (walk until nearly maximum
claudication discomfort is experience, and then rest until symptoms resolve before resuming ambulation)
Revascularization is usually indicated for patients with disabling, progressive or severe symptoms despite medical
therapy and for those critical limb ischemia
B. Physical Examination
Antiplatelet Therapy Aspirin and clopidogrel dual therapy is not more effective than aspirin alone in
reducing CV morbidity and mortality in patients with PAD
Anticoagulant Therapy Not indicated to improve outcomes in patients with chronic PAD
ACE-Inhibitors Reduce CV risks in patients with PAD
Statins Target LDL <100 mg/dL
Increases claudication distance by 40-60% and improves measured quality of
Cilostazol life
Contraindicated in patients with CHF
Pentoxifylline Increases blood flow to the microcirculation and enhances tissue oxygenation
COR PULMONALE
I. ETIOPATHOGENESIS
Often referred to as “pulmonary heart disease”
Defined as altered RV structure and/or function in the context of chronic lung disease and is triggered by the
onset of pulmonary hypertension
Acute Cor Pulmonale Acute RV dilatation and failure occurs (e.g., massive pulmonary embolism) but RV does
not hypertrophy
Chronic Cor Pulmonale More slowly evolving and progressive pulmonary hypertension leads to both RV
hypertrophy and dilation

Dyspnea: most common symptom and occurs due to increased work of breathing
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Tussive or effort-related syncope happens due to inability of RV to deliver adequate blood volume to the LV
Abdominal pain and ascites: happens due to backflow from right-sided HF
Orthopnea and PND: uncommon and occurs only with concurrent LV failure
RV heave: points to RV volume and pressure overload
Carvallo’s sign: increase in the intensity of the holosystolic murmur of tricuspid regurgitation with inspiration
Cyanosis: a late finding and is secondary to low cardiac output
III. DIAGNOSIS
12-L ECG P pulmonale (p waves > 2.5 mV in leads II and/or V1)
Right axis deviation and RV hypertrophy
Chest Radiography Enlargement of main pulmonary artery, hilar vessels & descending right
pulmonary artery
2D Echocardiography Right-sided chamber enlargement with dysfunction; pulmonary hypertension
Spirometry Identifies obstructive and restrictive parenchymal diseases
CT scan Identifies thromboembolic diseases, interstitial diseases
IV. MANAGEMENT
Target the underlying pulmonary disease to decrease the underlying pulmonary valvular resistance and lessen
RV afterload
Non-invasive mechanical ventilation, bronchodilators and correction of respiratory acidosis
Correction of infection, anemia and polycythemia and other extra-cardiac problems
Pulmonary vasodilators: modest reduction of pulmonary pressure and RV afterload
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CHAPTER 3
PULMONARY MEDICINE
I. Introduction to Pulmonology
II. Approach to Patients with Pulmonary Conditions
1. Clinical History and Physical Examination
2. Diagnostic Procedures
III. Common Pulmonary Conditions
1. Bronchial Asthma
2. Chronic Obstructive Pulmonary Disease
3. Community-Acquired Pneumonia
4. Health Care-Associated Pneumonia
5. Pulmonary Tuberculosis
6. Pleural Effusion
7. Pneumothorax
8. Superior Vena Cava Syndrome
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SECTION 1
INTRODUCTION TO PULMONOLOGY
PULMONOLOGY FORMULAS AND REFERENCE VALUES
ALVEOLAR-ARTERIAL OXYGEN GRADIENT (Aa-Gradient)
To compute the A-a gradient appropriate for age:
age The normal A – a gradient for a young person

Normal A – a gradient = 4 + 4 is -5 -10 mmHg (normally increases with age).
Example: A 60 year old patient should have an
The A-a gradient is the difference between the alveolar oxygen (PAO 2) A-a gradient < 19.
and the arterial oxygen (PaO2)1 computed as follows:
An increased computed A-a gradient
A – a gradient = PAO2 – PaO2 (compared to the A-a gradient appropriate for
age) suggests defect in diffusion, V/Q
PaO2 is derived from patient’s ABG ; while PAO2 is computed as mismatch or right-to-lung shunting.
follows:
PaO2: arterial oxygen partial pressure: obtained
PaCO2 from ABG
PAO2 = FiO2(Patm- PH2O) – 0.8
PAO2: alveolar oxygen partial pressure
If FiO2 at room air is 21%, Patm at sea level is 760 mmHg and PH2O is 47
mmHg, the formula for A-a gradient can be simplified to: PaCO2: arterial carbo dioxide pressure: also
obtained from ABG
5
A – a gradient = 150 – 4 (PaCO2) - PaO2
PaO2 – FiO2 RATION (PFR)

PaO2: arterial oxygen partial pressure: obtained
PaO2 from ABG
PFR = FiO2 FiO2: fraction of inspired oxygen
DESIRED PaO2
If age < 60 years old:
Desired PaO2= 104 – (0.43 x age)

*Used for adjust for ventilator FiO2 settings
If age 60 years and above:
Desired PaO2= 80 – (age – 60)

DESIRED FiO2
Current FiO2 x Computed desired PaO2 Current PaO2: obtained from ABG
Desired FiO2 = Current PaO2 Computed desired PaO2: obtained using
previous formula
O2 FLOW SYSTEM OXYGEN FLOW RATES ESTIMATED FiO2 in %
1 24
2 28
Nasal cannula 3 32
4 36
5 40
6 44
5-6 40
Simple face mask 6-7 50
7-8 60
80
SECTION 2
APPROACH TO PATIENTS WITH PULMONARY CONDITIONS
CLINICAL HISTORY AND PHYSICAL EXAMINATION
I. DYSPNEA
A. Pathogenesis of Dyspnea
DESCRIPTION PATHOPHYSIOLOGY
Chest tightness or constriction Bronchoconstriction
Interstitial edema (asthma, myocardial ischemia)
Increased work or effort of breathing Airway obstruction (COPD, uncontrolled asthma)
Neuromuscular disease (myopathy, kyphoscoliosis)
Air hunger, need to breathe, urge to breathe Increased drive to breathe (CHF, pulmonary
embolism, moderate-severe airflow obstruction)
Hyperinflation (asthma, COPD)
Cannot get a deep breath, unsatisfying breath Restricted tidal volume (pulmonary fibrosis, chest
wall restriction)
Heavy breathing, rapid breathing, breathing more Deconditioning
B. Variations of Dyspnea
SYMPTOM COMMENTS
Common indicator of CHF, mechanical impairment
Orthopnea of the diaphragm associated with obesity, or
asthma triggered by esophageal reflux
Paroxysmal nocturnal dyspnea Highly suggestive of CHF
Acute, intermittent episodes of dyspnea More likely to reflect episodes of myocardial
ischemia, bronchospasm, or pulmonary embolism
Chronic persistent of dyspnea Typical of COPD, interstitial lung disease, and
chronic thromboembolic disease
Platypnea Left atrial myxoma or hepatopulmonary syndrome
II. COUGH
A. Duration of cough
DURATION COMMON CAUSES
Respiratory tract infection, aspiration
Acute cough <3 weeks event, inhalation or noxious chemicals
or smoke
Residuum from a tracheobronchitis,
Subacute cough 3-8 weeks duration such as in pertussis or “post-viral
tussive syndrome”
Chronic cough >8 weeks Inflammatory, infectious, neoplastic
and cardiovascular etiologies
B. Differential diagnoses for cough with normal chest physical examination and radiography
Cough-variant asthma
Gastroesophageal reflux
Nasopharyngeal drainage
Medications (angiotensin converting enzyme [ACE] inhibitors)
III. HEMOPTYSIS
70-90% due to bronchitis, bronchiectasis, necrotizing pneumonia, tuberculosis (owing to high prevalence and its
predilection to cavity formation)
“BATTLE CAMP”
o Bronchitis, Bronchiectasis
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o Aspergilloma
o Tumor
o Tuberculosis
o Lung abscess
o Emboli
o Coagulopathy
o Autoimmune disorders, AVM, Alveolar hemorrhage
o Mitral stenosis
o Pneumonia
The origin of blood can be identified by observing its color
o Bright-red, foamy blood: usually from the respiratory tract
o Dark-red, coffee-colored blood: usually from the gastrointestinal tract
Principles of management:
o Maintain airway patency and oxygenation
o Localize the source of bleeding
o Control hemorrhage: may give racemic epinephrine ET flushing (if intubated), concocted as 1 ampule of
epinephrine in 9 mL normal saline solution, as 2 mL flushing q6
IV. CHEST EXAMINATION FINDINGS

CONDITION PERCUSSION FREMITUS BREATH VOICE ADVENTITIOUS
SOUNDS TRANSMISSION SOUNDS
Normal Resonant Normal Vesicular Normal Absent
(lung bases)
Consolidation or Bronchophony,
Atelectasis (with Dull Increased Bronchial Egophony Crackles
patent airway)
Consolidation or
Atelectasis (with Dull Decreased Decreased Decreased Absent
blocked airway)
Asthma Resonant Normal Vesicular Normal Wheezing
Emphysema Hyperresonant Decreased Decreased Decreased Absent or
Wheezing
Pneumothorax Hyperresonant Decreased Decreased Decreased Absent
Pleural effusion Dull Decreased Decreased Decreased Absent or Pleural
Friction Rub
Pulmonary mass Dull normal Normal normal Decreased
(over the mass) (over the mass)
82
DIAGNOSTIC PROCEDURES
DIAGNOSTIC DESCRIPTION
Routine chest radiography (posterioanterior and lateral views)
Integral part of the diagnostic evaluation involving the parenchyma, pleura, airways
Chest Radiograph or and mediastinum
Chest X-Ray (CXR) Lateral decubitus: determine whether pleural abnormalities represent freely flowing
fluid
Apical lordotic views: visualize disease at the lung apices
Produces images using echoes or reflection of the US beam
Ultrasound (US) Can detect and localize pleural abnormalities
Quick and effective way of guiding percutaneous needle biopsy of peripheral lung,
pleural or chest wall lesions
Allows distinction between densities that would be superimpose on plain
Computed Tomography radiographs
(CT) Better in characterizing tissue density and providing accurate size assessment of
lesions
Commonly used for evaluation of pulmonary embolism (PE)
Ventilation-Perfusion PE produces 1 or more regions of VQ mismatch (e.g. regions in which there is a
(VQ) Lung Scanning defect in perfusion that follows the distribution of a vessel & that is not accompanied
by a corresponding defect in ventilation)
Helical CT and Helical CT: faster scans with improved contrast enhancement and thinner
Multidetector CT collimation
Multidetector CT: obtains multiple slices in a single rotation that are thinner
CT Pulmonary Allows simultaneous detection of parenchymal abnormalities
Angiography Test of choice for many clinicians in the evaluation of pulmonary embolism
Magnetic Resonance Role is less well defined than that of CT
Imaging (MRI) Poorer spatial resolutions and less detail of the pulmonary parenchyma
Pulmonary Angiography Radiopaque contrast medium is injected through a catheter placed in the pulmonary
artery
Bronchoscopy Direct visualization of the tracheobronchial tree
Performed usually with flexible fiberoptic instruments
Video-Associated Standard technique for diagnosis and management of pleural and parenchyma lung
Thoracoscopic Surgery disease
(VATS)
83
SECTION 3
COMMON PULMONARY CONDITIONS
BRONCHIAL ASTHMA
I. ETIOPATHOGENESIS
Syndrome characterized by airflow obstruction that varies markedly, both spontaneously and with treatment
Associated with airway hyperresponsiveness and airflow inflammation
Symptoms usually demonstrate reversibility and variability
o Reversibility applies to rapid improvements in FEV1 (or PEF)1 measured within minutes after inhalation of
a rapid-acting bronchodilator or more sustained improvement over days or weeks after controller
treatment
o Variability refers to improvement or deterioration in symptoms and lung function occurring over time
Mast cells, eosinophils, T-lymphocytes, and neutrophils all play a role in the pathogenesis

History of variable respiratory symptoms AND confirmed variable expiratory airflow limitation
III. History of Variable Respiratory Symptoms
Typical symptoms include cough, dyspnea, shortness of breath and wheezing
o May be worse at night and in the early morning hours
o Triggered by exercise, laughter, allergens and cold air
o Often appear or worsen with viral infections
Signs include rhonchi & wheezing throughout the chest but may be normal when asthma is controlled
III. Evidence of Variable Expiratory Airflow Limitation
At least once during the diagnostic process when FEV1 is low, confirm that FEV1 /FVC is reduced (it is normally
0.75-0.80 in adults)
Document that variation in lung function is greater than in healthy people (examples include the following):
o FEV1 increases by >12% and 200 mL after inhaling a bronchodilator (bronchodilator reversibility)
o Average diurnal PEF variability is >10%
o FEV1 increases by >12% and 200 mL from baseline after 4 weeks of anti-inflammatory treatment
PEF variability is calculated from twice daily readings (best of 3 each time), averaged over 1-2 weeks:
Day’s highest PEF – Day’s lowest PEF

PEF Variability = mean of the day’s highest and lowest PEF
III. DIAGNOSIS
A. Classification of Asthma Severity by Level of Control

CONTROLLED PARTYLY CONTROLLED UNCONTROLLED
(all of the following) (any measure present)
Daytime Symptoms None (2x or less/week) >2x/week
Limitation of Activities None Any
Nocturnal Symptoms None Any Three or more symptoms of
(Awakening) partly controlled asthma in
Need for Reliever None (2x or less/week) >2x/week any week
Lung Function Normal <80% predicted
Exacerbation None 1 or more per year One in any week
B. Asthma Phenotypes
PHENOTYPE DESCRIPTION
Most easily recognizable phenotype
Most often commences in childhood
Allergic Asthma Associated with a personal or family history of atopy
(eczema, allergic rhinitis, food and drug allergy)
Eosinophilic airway inflammation
Responds well to inhaled corticosteroids (ICS)
84
Non-allergic Asthma Neutrophilic or paucigranulocytic airway inflammation
Less responsive to ICS
Common in women, presenting symptoms usually in
Late-onset Asthma adulthood
Requires higher doses of ICS or are relatively refractory to
ICS
Asthma with Fixed Airflow Limitation Seen in patients with long-standing asthma who develop
fixed airflow limitation due to airway wall remodeling
IV. MANAGEMENT
Goals of asthma therapy:
o Minimal (ideally no) chronic symptoms, including nocturnal symptoms
o Minimal (infrequent) exacerbations
o No emergency visits
o Minimal (ideally no) use of as-required B2-agonist
o No limitations on activities, including exercise
o PEF circadian variation <20%
o (near) normal PEF
o Minimal (or no) adverse effects from medicine
A. Pharmacologic Therapy for Asthma

DRUG CLASS EXAMPLES MECHANISM OF ACTION COMMENTS/ADVERSE
EFFECTS
RELIEVERS
Stimulates adenylyl cyclase,
increasing cAMP, causing
Salbutamol bronchodilation Tremors and palpitations
Short Acting B2 Procaterol Rapid onset of (usually in the elderly)
Agonists Terbutaline bronchodilation Minimal decrease in serum
(SABA) Albuterol Best used to relief of K+
symptoms
No effect on chronic
inflammation
Muscarinic receptor
antagonists Dry mouth (most common)
Short Acting Ipratropium Inhibit only the cholinergic Urinary retention and
Anticholinergics reflex components and glaucoma may be
thereby less effective than observed in the elderly
B2-agonists
Inhibit phosphodiesterase Nausea, vomiting and
Methylxanthines Theophylline activity causing increase in headache (most common)
Aminophylline cAMP levels and Arrhythmia, seizures and
bronchodilation death at high concentration
CONTROLLERS
Most effective anti-
Inhaled Beclomethasone inflammatory agents for
Corticosteroids Budesonide asthma control Hoarseness / dysphonia
(ICS) Fluticasone Reduce inflammatory cell and oral candidiasis
numbers and eosinophils in
airway mucosa
Truncal obesity, easy
Prednisone bruisability, osteoporosis,
Systemic Methylprednisolone Useful for treatment of acute DM, HPN, gastric
Steroids Hydrocortisone exacerbations ulceration, proximal
myopathy, depression,
cataracts
Long Acting B2 Formoterol Improve asthma control and Should not be given in the
Agonists Salmeterol reduce inflammation when absence of ICS
85
(LABA) Bambuterol added to ICS, thereby
allowing lower doses of ICS
to be given
Less effective than ICS in
controlling asthma and
Leukotriene Montelukast Block leukotriene receptors have less effect on airway
Modifying Zafirlukast (montelukast, zafirlukast) or inflammation
Drugs Zileuton inhibit lipoxygenase Useful as an add-on
(zileuton) therapy in some patients
not controlled with low
doses of ICS
Very short duration of
Cromones Cromolyn sodium Inhibit mast cell and sensory action needing frequent
Nedocromil sodium nerve activation dosing
Favorable safety profile
Anti-IgE Omalizumab Inhibits IgE-mediated Very expensive
B. Initial Controlled Treatment

Asthma treatment is a continuous cycle: assess, adjust treatment and review response
For the best outcomes, regular controller treatment should be initiated as soon as possible after the diagnosis of
asthma is made
After starting initial controller treatment, review response after 2-3 months, or according to urgency
o Consider stepping up if: uncontrolled symptoms, exacerbations or risks
o Consider stepping down if: symptoms controlled for 3 months, low risk for exacerbations
Indicated only if:
Symptoms are rare
Step 1 As-needed SABA with no controller No night-walking due to asthma
No exacerbations in the last year
Normal FEV1
Step 2 Low-dose ICS + as-needed SABA
Step 3 Low-dose ICS/LABA + as-needed SABA or
ICS/Formoterol maintenance + reliever therapy
Step 4 Low-dose ICS/Formoterol maintenance + reliever therapy, or
Medium dose ICS/LABA + as-needed SABA
Step 5 Refer for expert investigation
Add-on treatments: anti-IgE (Omalizumab), low dose oral steroids
C. Non-Pharmacologic Therapy of Asthma

Smoking cessation
Regular physical activity
Occupational aspects
Breathing techniques
V. CLASSIFICATION AND MANAGEMENT OF EXACERBATIONS

MILD OR MODERATE SEVERE LIFE THREATENING
Clinical Talks in phrases Talks in words
manifestations Prefers sitting to lying Sits hunched forward
Not agitated Agitated
Respiratory rate Increased >30/min Drowsy,
Accessory Not used Used Confused,
muscles Silent chest
Pulse rate 100-120 bpm >120 bpm
O2 saturations 90-95% <90%
Peak Expiratory >50% predicted or best < 50% predicted or best
Flow (PEF)
SABA Transfer to acute care facility
Treatment Ipratropium bromide SABA
Prednisolone 1mg/kg PO Ipratropium bromide
86
Controlled oxygen Controlled oxygen
Oral or IV corticosteroids
Consider IV magnesium
Consider high dose ICS
CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD)
I. ETIOPATHOGENESIS
Characterized by expiratory airflow limitation that is not fully reversible (hallmark: airflow obstruction)
Unusual in the absence of smoking or prior history of smoking, except for patients with A1-antitrypsin deficiency
Elastase-Antielastase Hypothesis: remains a prevailing mechanism for its pathophysiology
A. The Pathological Changes include:

Chronic inflammation
Increased numbers of specific inflammatory cell types in different parts of the lung
Structural changes resulting from repeated injury and repair
B. Encompasses the Following Conditions:

Emphysema: anatomically-defined condition characterized by enlargement and destruction of alveoli “pink
puffers”)
Chronic bronchitis: clinical condition characterized by chronic cough and phlegm (“blue bloaters”)
Small airways disease: condition where bronchioles are narrowed

CARDINAL SYMPTOMS SIGNS
May be normal in early stages
Pink puffers (predominantly emphysema): thin, non-cyanotic,
prominent use of accessory muscles
Blue bloaters (predominantly chronic bronchitis): heavy and cyanotic
Most common symptoms: “Tripod position”: to facilitate use of accessory muscles
Cough, sputum production, exertional Signs of hyperinflation: barrel chest, enlarged lung volumes on
dyspnea percussion (hyperresonance)
Others: pursed-lip breathing, expiratory wheezing, systemic wasting,
weight loss
Signs of cor pulmonale (bipedal edema, ascites) in severe cases
Clubbing is not a sign of COPD and should alert the clinician to other
causes of clubbing
III. DIAGNOSIS
A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum
production, and a history of exposure to risk factors for the disease
Risk factors: tobacco smoke (including popular local preparations), smoke from home cooking and heating
fuels, occupational dusts and chemical
DIAGNOSTIC TEST COMMENTS/EXPECTED FINDINGS
Required to make the diagnosis
Post-bronchodilator FEV1/FVC <0.70 confirms presence of persistent
airflow limitation
Degree of reversibility of airflow limitation after bronchodilators /
steroids is no longer recommended (it has never been shown to add
Spirometry to the diagnosis, differential diagnosis, or to predicting the response
to long-term treatment with bronchodilators or corticosteroids)
FEV1, FEV1/FVC and all other measures of expiratory airflow are
reduced
TLC, FRC and RV may be increased indicating air trapping
DLCO may be reduced
Chest radiograph Useful for excluding other differential diagnoses
87
Low flattened diaphragms, increase in the volume of retrosternal
airspace (hyperinflation)
Hyperlucent lung zones with possible bullae formation and diminished
vascular markings
Not routinely requested
May be helpful when the diagnosis is in doubt to rule out concomitant
CT scan diseases
Useful if surgical procedure such as lung volume reduction is
contemplated
To evaluate a patient’s oxygen saturation and need for supplemental
oxygen therapy
Pulse oximetry Should be used to assess all stable patients with FEV1<35%
predicted or with clinical signs suggestive of respiratory failure or right
heart failure
If peripheral saturation is <92%, ABGs should be assessed
Resting or exertional hypoxemia
Increased alveolar-arterial oxygen tension gradient
Arterial blood gas (ABG) In long-standing disease, may have chronically increased arterial
PaCO2 but metabolic compensation (increased HCO 3) maintains pH
near normal
IV. CLASSIFICATION OF COPD

PATIENT CHARACTERISTIC SPIROMETRIC EXACERBATIONS PER mMRC
CLASSIFICATION YEAR
A Low risk GOLD 1-2 <1 0-1
Less symptoms
B Low risk GOLD 1-2 <1 >2
More symptoms
C High risk GOLD 3-4 >2 0-1
Less symptoms
D High risk GOLD 3-4 >2 >2
More symptoms
A. Classification based on Severity of Airflow Limitation in COPD using Spirometry (Post-Bronchodilator FEV1)
Spirometry should be performed after the administration of an adequate dose of a short-acting inhaled
bronchodilator (to minimize variability)
STAGE CLINICAL FINDINGS SPIROMETRY FINDINGS
FEV1/FVC FEV1
Chronic cough and
GOLD 1 sputum production FEV1> 80% predicted
Mild Patient unaware that lung
function is abnormal
Chronic cough and sputum
production
GOLD 2 Shortness of breath on FEV1 50 to <80%
Moderate exertion predicted
FEV1 / FVC
Stage patients typically seek
medical attention <0.70
Greater shortness of breath
GOLD 3 Reduced exercise capacity FEV130 to <50%
Severe Fatigue predicted
Repeated exacerbations
Signs or symptoms of
GOLD 4 respiratory failure (PaO2< 60 FEV1<30% predicted
Very Severe mmHg + PaCO2>50 mmHg)
Cor pulmonale
88
B. Classification Based on Exacerbation
Exacerbation of COPD: defined as an acute event characterized by worsening of the patient’s
respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication
Best predictor of having frequent exacerbations (2 or more per year) is a history of previously treated
events
C. Modified Medical Research Council (mMMRC) Questionnaire for Assessing the Severity of Breathlessness
mMMRC DESCRIPTION
0 I only get breathless with strenuous exercise
1 I get short of breath when hurrying of the level or walking up a slight hill
2 I walk slower than people of the same age on the level because of breathlessness, or I
stop for breath when walking on my own pace on the level
3 I stop for breath after walking 100 meters or after a few minutes on the level
4 I am too breathless or I am breathless when I’m dressing or undressing
V. OVERVIEW OF MANAGEMENT
A. Only Three Interventions have been demonstrated to influence the natural history of COPD
Biggest impact in the natural history of COPD
Nicotine replacement therapy (gum, inhaler, nasal spray, transdermal
Smoking Cessation patch) reliably increases long term smoking abstinence rates
Brief (3-minute) period of counseling to urge a smoker to quit results in
smoking cessation rates of 5-10%
Only pharmacologic therapy demonstrated to unequivocally decrease
Oxygen Therapy mortality rates in COPD
For chronically hypoxemic patients
>15 hours / day (long term oxygen therapy)
Lung Volume Reduction Surgery Segmentectomy or lobectomy of focal emphysematous areas of the
lung
B. Pharmacologic Therapy for Stable COPD

None of the existing medications for COPD have been shown to modify the long-term decline in lung function
Bronchodilator medications are central to the symptomatic management of COPD (principal bronchodilator
treatment includes B2-agonists, anticholinergics and methylxanthines)
MEDICATIONS COMMENTS ADVERSE EFFECTS
Alters airway smooth muscle tone improving
emptying of the lungs
Effects usually wear off within 4-6 hours (short Sinus tachycardia
acting) and >12 hours (long acting) Arrhythmias
Beta2 – Agonists Regular treatment with LABA is more effective Tremors
and convenient than treatment with SABA Hypokalemia
Appears to provide subjective benefit in acute
episodes but is not necessarily helpful in stable
disease
Blocks acetylcholine’s effect on muscarinic
receptors
Example: ipratropium, oxitropium, and Dryness of the mouth
Anticholinergics tiotropium bromide Bitter metallic taste
Bronchodilating effects of short-acting inhaled Arrhythmias
anticholinergics lasts longer than that of short-
acting B2-agonists
Tachycardia
Acts as nonselective phosphodiesterase Arrhythmias
Methylxanthines inhibitor Seizures
Examples: theophylline, doxofylline Headaches
Insomnia
Inhaled Addition of ICS to bronchodilator treatment Hoarseness
corticosteroids appropriate for: Oral candidiasis
89
o Symptomatic patients with FEV1<50%
predicted (Stages III and IV)
o Repeated exacerbations
Chronic treatment with systemic glucocorticoids
should be avoided
VI. MANAGEMENT OF STABLE COPD
A. Pharmacologic Management of COPD

PATIENT RECOMMENDED FIRST ALTERNATIVE CHOICE OTHER POSSIBLE
GROUP CHOICE TREATMENT
LAMA
SAMA pm or
A or LABA Theophylline
SABA pm or
SABA and SAMA
B LAMA SABA and/or SAMA
or LAMA and LABA Theophylline
LABA
LAMA and LABA
ICS + LABA or SABA and/or SAMA
C or LAMA and PDE-4 inhibitor Theophylline
LAMA or
LABA and PDE-4 inhibitor
ICS + LABA and LAMA
or
ICS + LABA ICS + LABA and PDE-4 inhibitor Carbocisteine
D and/or or SABA and/or SAMA
LAMA LAMA and LABA theophylline
or
LAMA and PDE-4 inhibitor
SAMA: Short acting muscarinic antagonist (e.g., Ipratropium)
SABA: Short acting beta agonist (e.g. Salbutamol)
LAMA: Long acting muscarinic agonist (e.g., Tiotropium)
LABA: Long acting beta agonist (e.g., Salmeterol)
ICS: Inhaled corticosteroid (e.g. Budesonide)
PDE-4 inhibitor (e.g., Roflumilast)
B. Non-Pharmacologic Management of COPD

PATIENT GROUP ESSENTIAL RECOMMENDED DEPENDING ON LOCAL
GUIDELINE
A Smoking cessation Physical activity Flu vaccination
Pneumococcal vaccination
B-D Smoking cessation Physical activity Flu vaccination
Pulmonary rehabilitation Pneumococcal vaccination
VII. MANAGEMENT OF ACUTE EXACERBATIONS

Exacerbation: event in the natural course of the disease characterized by a change in patient’s baseline
dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a
change in regular medication in patients with underlying COPD
Change in mental status is the most important sign of a severe exacerbation in patients with very severe COPD
A. Management of Severe but Not Life-Threatening Exacerbations of COPD at the ER

Assess severity of symptoms, blood gases, and CXR
Administer controlled oxygen therapy and repeat ABG after 30-60 minutes
Increase doses and/or frequency of bronchodilator use
Add oral or IV glucocorticoids
Consider antibiotics (oral or occasionally IV) when there are signs of bacterial infection
Consider non-invasive mechanical ventilation
90
B. Therapy for Acute Exacerbation
MANAGEMENT COMMENTS
Bronchodilators Inhaled B-agonists often with addition of anticholinergic agent
Frequency depends on severity of exacerbation
Bacteria frequently implicated in exacerbations: Streptococcus pneumoniae,
Antibiotics Haemophilius influenza, Moraxella catarrhalis
Most clinicians treat patients with moderate or severe exacerbations with
antibiotics, even in the absence of data implicating a specific pathogen
Reduces hospital stay, hastens recovery and reduces chances of subsequent
Glucocorticoids exacerbations / relapses
Prednisone 40 mg/day or its equivalent for 5 days
Most common acute complication for steroids: hyperglycemia
Oxygen Maintain O2 saturation > 90%
Administration of oxygen does not reduce minute ventilation
C. Indications for Ventilator Support

NON-INVASIVE VENTILATION INVASIVE MECHANICAL VENTILATION
Selection Criteria
Moderate to severe dyspnea with use of
accessory muscles and paradoxical abdominal Indications
motion Unable to tolerate NIV or NIV failure
Moderate to severe acidosis (pH <7.35) and/or Severe dyspnea with use of accessory muscles
hypercapnia (PaCO2>45mmHg) and paradoxical abdominal motion
RR >25/min RR >35/min
Exclusion Criteria (any may be present) Life-threatening hypoxemia
Respiratory arrest Severe acidosis (pH <7.25) and/or hypercapnia
Cardiovascular instability (PaCO2>60 mmHg)
Change in mental status; uncooperative patient Respiratory arrest
High aspiration risk Somnolence, impaired mental status
Viscous or copious secretions Cardiovascular complications
Recent facial or gastroesophageal surgery Other complications (e.g., metabolic abnormalities,
Craniofacial trauma sepsis, pneumonia, pulmonary embolism,
Fixed nasopharyngeal abnormalities barotrauma, massive pleural effusion)
Burns
Extreme obesity
D. Discharge Criteria
Inhaled beta-agonist use no more frequent than q4h
Patient is able to walk across room
Patient able to eat and sleep without frequent awakening by dyspnea
Patient has been clinically stable for 12-24 hours
ABG have been stable for 12-24 hours
Patient (or home caregiver) fully understands the use of meds
Follow-up plans have been finalized and home care arrangements have been completed
COMMUNITY-ACQUIRED PNEUMONIA (CAP)

I. ETIOPATHOGENESIS
Lower respiratory tract infection (pulmonary parenchyma) acquired in the community within 24 hours to less than
2 weeks
Results from the proliferation of microbial pathogens at the alveolar level and the host’s response to those
pathogens
Most common access of microorganisms to the lower respiratory tract is through aspiration from the oropharynx
Classic pneumonia (lobar pneumococcal) evolves through a series of changes
91
PHASE DESCRIPTION
Edema Initial phase with the presence of a proteinaceous exudate and often of bacteria
in the alveoli
Erythrocytes in the cellular intraalveolar exudate
Red Hepatization Neutrophil influx is more important from the standpoint of host defense
Bacteria are occasionally seen in pathologic specimens
No new erythrocytes are extravasating and those already present have been
lysed and degraded
Gray Hepatization The neutrophilis the predominant cell, fibrin deposition is abundant and bacteria
have disappeared
This phase corresponds with successful containment of the infection and
improvement in gas exchange
Resolution (Final Macrophage reappears as the dominant cell type in the alveolar space and the
Phase) debris of neutrophils, bacteria and fibrin has been cleared, as has the
inflammatory response

Commonly presents with acute cough, abnormal vital signs of tachypnea, tachycardia, and fever with at least one
abnormal chest finding of diminished breath sounds, rhonchi, crackles or wheezes
III. DIAGNOSIS
A. Classification and Disposition

LOW-RISK CAP MODERATE-RISK CAP HIGH-RISK CAP
Stable Unstable
RR <30/min RR > 30/min
Vital Signs PR <125bpm PR >12bpm
Temp 36-40oC Temp > 40oC or
BP > 90/60mmHg <36oC Any of the criteria under
BP < 90/60 mm/Hg Moderate Risk CAP, plus:
No altered mental Altered mental state Severe sepsis and
state of acute onset of acute onset septic shock
Features No suspected Suspected Need for
aspiration aspiration mechanical
No or stable Decompensated co- ventilation
comorbids morbidities
Localized infiltrates Multilobar infiltrates
Chest X-Ray No pleural effusion Pleural effusion
No abscess Abscess
Disposition outpatient ward admission ICU admission
B. Diagnostics for CAP

DIAGNOSTICS COMMENTS
Essential in the diagnosis of CAP, assessing
severity, differentiating pneumonia from other
Chest Radiography conditions and in prognostication
Best radiologic evaluation consists of standing
posterioanterior and lateral views of the chest
Does not predict the likely etiologic agent
Microbiologic Studies Optional in low-risk CAP
(sputum and blood cultures) Necessary in moderate- and high-risk CAP
Options for non-resolving pneumonia,
Invasive Procedures immunocompromised patients and in whom no
(e.g., transtracheal, transthoracic, biopsy, adequate respiratory specimens can be sent
bronchoalveolar lavage, protected brush specimen) despite sputum induction and routine diagnostic
testing
92
IV. MANAGEMENT
For patients requiring hospitalization, empiric therapy should be initiated as soon as possible after a diagnosis
Empiric microbial therapy for CAP:
RISK STRATIFICATION POTENTIAL PATHOGENS EMPIRIC THERAPY
Previously healthy:
Amoxicillin or extended macrolides
(suspected atypical pathogen)
Streptococcus pneumoniae
Haemophilus influenza With stable comorbid illness:
Chlamydphila pneumoniae β-lactam / β-lactamase inhibitor
Low-Risk CAP Mycoplasma pneumoniae combination (BLIC) or second-
Moraxella catarrhalis generation oral cephalosporin +
Enteric Gram-negative bacilli extended macrolides
(among those with co-morbids)
Alternative:
Third-generation oral cephalosporin
+ extended macrolide
Haemophilus influenza IV non-antipseudomonal β-lactam
Chlamydphila pneumoniae (BLIC, cephalosporin or carbapenem)
Moderate-Risk Mycoplasma pneumoniae + extended macrolide
Moraxella catarrhalis or
CAP Enteric Gram-negative bacilli IV non-antipseudomonal β-lactam +IV
Legionella pneumophila extended macrolide or IV respiratory
Anaerobes (risk of aspiration) FQ
No risk for P. aeruginosa:
Streptococcus pneumoniae IV non-antipseudomonal β-lactam +IV

Haemophilus influenza extended macrolide or IV respiratory
Chlamydphila pneumoniae FQ
Mycoplasma pneumoniae
Moraxella catarrhalis With risk for P. aeruginosa:
High-Risk CAP Enteric Gram-negative bacilli
Legionella pneumophila IV antipneumococcal antipseudomonal
Anaerobes (risk of aspiration) β-lactam + IV extended macrolide +
Staphylococcus aureus aminoglycoside
Pseudomonas aeruginosa or
IV antipneumococal antipseudomonal
β-lactam + IV ciprofloxacin/levofloxacin
(high-dose)
1. Extended macrolides: azithromycin dehydrate, clarithromycin
2. Oral β-lactam/β-lactamase inhibitor (BLIC): amoxicillin-clavulanic acid, amoxicillin-sulbactam, sultamicillin
3. Oral second-generation cephalosporin: cefaclor, cefuroxime axetil
4. Oral third-generation cephalosporin: cefdinir, cefixime, cefpodoxime proxetil
5. IV non-antipseudomonal β-lactam (BLIC, cephalosporin or carbapenem): amoxicillin-clavulanic acid, ampicillin-sulbactam, cefotiam,
cefoxitin, cefuroxime Na, cefotaxime, ceftizoxime, ceftriaxone, ertapenem
6. Respiratory fluoroquinolones: levofloxacin, moxifloxacin
7. IV antipneumococal, antipseudomonal β-lactam (BLIC, cephalosporin or carbapenem): cefoperazone-sulbactam, piperacillin-tazobactam,
ticarcillin-clavulanic acid, cefipime, cefpirome, imipenem-cilastatin, meropenem
8. Aminoglycosides: gentamicin, tobramycin, netilmicin, amikacin
V. PNEUMONIA RISK SCORE (CURB-65) PREDICTS MORTALITY IN CAP

C Confusion of new onset Interpretation:
U Urea (BUN) > 7 mmol/L (19 mg/dL) 0-1: treat as outpatient
R Respiratory rate > 30 bpm 2: admit patient
B Blood pressure <90/60 mmHg >3: consider ICU admission
65 Age >65 years old
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VI. ASSESSING RESPONSE TO THERAPY
A. Response to therapy is expected within 24-72 hours of initiating treatment:

Temperature, RR, HR, BP, sensorium, O2 saturation, and inspired oxygen concentration should be monitored
to assess response to therapy
A patient is considered to have responded to treatment if:
o Fever decreases within 72 hours;
o Temperature normalizes within 5 days; and,
o Respiratory signs, particularly tachypnea, return to normal
Follow-up cultures of blood and sputum are not indicated for patients who are responding to treatment
B. De-escalation of antibiotic therapy once the patient is improving, stable and has a functioning GI tract:
Resolution of fever more than 24 hours
Less cough and resolution of respiratory distress (normalization of RR)
Improving WBC count, no bacteremia
Etiologic agent is not a high-risk (virulent/resistant) pathogen (e.g. Legionella, S. aureus, or gram-negative
enteric bacilli)
No unstable comorbid condition or life-threatening complications such as MI, CHF, complete heart block, new
atrial fibrillation, supraventricular tachycardia, etc.
No sign of organ dysfunction such as hypotension, acute mental changes, BUN to creatinine ratio of >10:1,
hypoxemia, and metabolic acidosis
Patient is clinically hydrated, taking oral fluids and is able to take oral medications
C. Duration of Treatment
ETIOLOGIC ORGANISMS DURATION OF TREATMENT (days)
Most bacterial pneumonias 5-7
Enteric Gram-negative pathogens, S. aureus, and P. 14
aeruginosa
Mycoplasma and Chlamydophila 10-14
Legionella 14-21
D. Failure to improve after 72 hours of treatment is an indication of reassessment

Incorrect diagnosis or presence of complicating noninfectious condition (e.g., pulmonary embolism, CHF,
vasculitis, MI)
A resistant microorganism or an unexpected pathogen that is not covered by the antibiotic of choice
Antibiotic is ineffective or causing an allergic reaction
Impaired local or systemic host defenses (e.g., aspiration, endobronchial obstruction, bronchiectasis)
Local or distant complications of pneumonia (e.g., parapneumonic effusion, empyema, lung absecess, ARDS,
metastatic infection, endocarditis)
Overwhelming infection
Slow response in the elderly patient (S. pneumoniae and L. pneumophila)
Exacerbation of co-morbid illness
Nosocomial superinfection
E. Hospital Discharge
In the absence of any unstable coexisting illness or other life-threatening complication, the patient may be
discharged once clinical stability occurs and oral therapy is initiated
1. During the 24 hours before discharge, the patient should have the following characteristics:
Temperature of 36-37.5oC
Pulse <100/min
RR between 16-14/min
SBP >90 mmHg
Blood O2 saturation >90%
Functioning GI tract
2. Repeat Chest Radiograph
Not needed in patients who are clinically improving
Recommended during a follow-up visit, approximately 4 to 6 weeks after hospital discharge
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HEALTH CARE-ACQUIRED PNEUMONIA (HCAP)
I. ETIOPATHOGENESIS
Transition between classic CAP and typical HAP
A. Ventilator-Associated Pneumonia (VAP)

The greatest difference between VAP and HCAP/HAP is the return to dependence on expectorated sputum for a
microbiologic diagnosis of VAP, which is further complicated by frequent colonization by pathogens in patients
with HAP or HCAP
Common pathogenic mechanisms include oropharyngeal colonization with pathogenic bacteria, cross-infection
from other colonized patients, large volume aspiration, microaspiration around ET tub and altered lower
respiratory host defenses
Clinical manifestations: same in VAP as with any other forms of pneumonia: fever, leukocytosis, increase in
secretions, and pulmonary consolidation on PE, along with a new or changing radiographic infiltrate
NON-MDR PATHOGENS MDR PATHOGENS
Streptococcus pneumoniae Pseudomonas aeruginosa
Other Streptococcus spp. MRSA
Haemophilius 95nfluenza Acinetobacter spp.
MSSA Antibiotic-resistant Enterobacteraceae
Antibiotic-sensitive Enterobacteriaceae Enterobacter spp.
Escherichia coli ESBL-positive strains
Klebsiella pneumoniae Klebsiella spp.
Proteus spp. Legionella pneumophila
Enterobacter spp. Burkholderia cepacia
Serratia marcescens Aspergillus spp.
B. Hospital-Acquired Pneumonia (HAP)

HAP in non-intubated patients, both inside and outside the ICU, is similar to VAP save for the higher frequency of
non-MDR pathogens and better underlying host immunity in non-intubated patients the lower frequency of
MDR pathogens allows monotherapy in a majority of HAP cases
The only pathogens that may be more common in the non-VAP population are the anaerobes (due to a higher risk
of macroaspiration)
More difficult to obtain lower respiratory samples appropriate for culture in non-intubated patients
II. CLINICAL CONDITIONS ASSOCIATED WITH MDR PATHOGENS IN HCAP

Hospitalization for > 48 hours
Hospitalization for > 2 days in prior 3 months
Nursing home or extended-care-facility residence
Antibiotic therapy in preceding 3 months
Chronic dialysis
Home infusion therapy
Home wound care
Family member with MDR infection
III. MANAGEMENT
Once an etiologic diagnosis is made, broad-spectrum empirical therapy can be modified to address the known
pathogen specifically
Empirical antibiotic treatment of HCAP
WITHOUT RISK FACTORS FOR MDR PATHOGENS WITH RISK FACTIRS FOR MDR PATHOGENS
Standard recommendation is treatment with three
Majority can be treated with a single agent antibiotics: two directed at P. aeruginosa and one at
MRSA
Ceftriaxone 2g IV q24 A beta-lactam:
Moxifloxacin 400 mg IV q24 Ceftazidime 2g IV q8 or Cefepime 2g IV q8-12
Ciprofloxacin 400 mg IV q8 or
Levofloxacin 750 mg IV q24 Piperacillin/tazobactam 4.5g IV q6, Imipenem
Ampicillin/sulbactam 3g IV q6 500 mg IV q6 or 1g IV q8, plus
Ertapenem 1g IV q24
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A second agent against gram-negative bacteria:
Gentamicin or Tobramycib 7 mg/kg IV q24 or
Amikacin 20 mg/kg IV q24, or
Ciprofloxacin 400 mg IV q8 or Levofloxacin 750
mg IV q24, plus
An agent against gram-positive bacteria:

Linezolid 600 mg IV q12, or
Vancomycin 15mg/kg, up to 1 g IV q12
PULMONARY TUBERCULOSIS (PTB)
I. ETIOPATHOGENESIS
Caused by Mycobacterium tuberculosis
Most common site for the development of TB is the lungs (85% of patients)
Most commonly transmitted from person with infectious PTB to others by droplet nuclei, which are aerosolized by
coughing, sneezing or speaking. Aerosolized droplets are 1-5 µm in diameter. A single cough can generate 3000
infective droplets, with as few as 10 bacilli needed to initiate infection
Most infectious patients: those with cavitary pulmonary disease and laryngeal TB
Typical TB lesion: epitheloid granuloma with central caseation necrosis

In the Philippines, cough of two weeks or more should lead to high index of suspicion for PTB
Cough may be accompanied by night sweats, weight loss, unexplained fever and chills, chest pain, fatigue and
body malaise
Absence of fever does not exclude TB
Physical findings are of little utility in PTB
A. General Classification of Tuberculosis

CLASSIFICATION DEFINITIONS
Cough of at least 2 weeks in an adult (age > 15 y/o)
A child (< 15 y/o) fitting criteria for TB
Presumptive TB Radiologic imaging suggestive of tuberculosis
Any person who presents with symptoms or signs suggestive of TB
Cough of any duration in a high risk individual or a close contact of an
active TB case
Definite case A patient with MTB complex identified from a clinical specimen either by
culture or by a newer method such as molecular line probe assay
New case Patient who never had treatment for TB or who has taken anti-TB
medications for < 1 month
Retreatment case (patient previously treated with anti-TB drugs for at least 1 month in the past)
Patient who was previously treated for TB, and was declared cured for has
Relapse completed treatment; and is now bacteriologically or clinically diagnosed
TB
Patient who was previously treated for TB, and treatment failed at the end
of the most recent course:
o Sputum smear or sputum culture positive at 5 months or later
Treatment after failure during treatment
o Clinically diagnosed in a patient in whom sputum studies cannot
be done, without clinical improvement anytime during the course
of treatment
Treatment after lost to follow- A patient who returns to treatment with positive bacteriology (smear or
up (TALF) culture) or clinically diagnosed, following interruption of treatment for two
months or more
Previous treatment outcome A previously treated patient whose outcome was not known or not
unknown (PTOU) documented
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B. Classification of Tuberculosis based on Anatomical Site Affected
At least 1 (or 2) sputum

Smear-positive specimen positive for AFB,
with or without radiographic
abnormalities
Patient with sputum culture,
Bacteriologically- Culture-positive with or without radiographic
Confirmed abnormalities
Pulmonary TB Patient with positive sputum
Rapid Diagnostic test- for MTB using a rapid
positive diagnostic test (e.g. Xpert
MTB/Rif) with or without
radiographic abnormalities
Two sputum specimens negative for AFB or MTB; but with
Clinically-Diagnosed clinical or radiologic evidence consistent with active TB and
there is a decision by a physician to treat as tuberculosis
Bacteriologically- Smear/culture/rapid diagnostic test from an extra-
Extra-Pulmonary TB Confirmed pulmonary site positive for AFB
(EPTB) A patient with histologic and/or clinical or radiologic
Clinically-Diagnosed evidence consistent with active extra-pulmonary TB and
there is a decision by a physician to treat as tuberculosis
III. DIAGNOSIS
At least two sputum specimens should be sent
Sputum collection:
Sputum Microscopy for AFB o Two sputum specimens of good quality shall be collected, either
as frontloading (e.g., spot-spot one-hour apart) or spot-early
morning specimens, based on the patient’s preference
o The two specimens should be collected at most within 3 days
Primarily recommended for patients at risk for drug resistance
It is recommended in the following smear positive patients:
o All cases of retreatment
Sputum TB Culture o All cases of treatment failure
o All other cases of smear positive patients suspected to have one
or more multi-drug resistant TB
o All household contacts of patients with MDR-TB
o In patients with HIV
Recommended for patients suspected to have PTB whose sputum
Chest Radiograph smears are negative
Initiating TB treatment based on chest radiographs alone is discouraged
Rapid Diagnostic Test (Xpert Gene Xpert testing for the presence of Mycobacterium tuberculosis and
MTB/Rif Assay) Rifampicin resistance
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Presumptive TB
Cough of at least 2 years in an adult > 15 years old
CXR suggestive of tuberculosis
Cough of any duration in a high risk individual or close contact of an active TB case
Sputum smear microscopy
Positive* Negative or not done
Chest Radiograph
If not suggestive of TB Not TB
If suggestive of TB proceed to nest step
Bacteriology confirmed TB
MTB (+)
Rif-sensitive
Xpert MTB/Rif**
History of previous TB treatment? MTB Negative Not TB
MTB Positive Next step
No Yes MTB (+)

Rif-Resistant
Bacteriologically Bacteriologically
If no access to Xpert
confirmed TB confirmed TB
New Case Retreatment MTB/Rif:
Decision of MD or TBDC+?
Either “Not TB” or “Clinically
Clinically Diagnosed TB”
Refer to PMDT$ Diagnosed TB
Services for Retreatment
Evaluation
Yes
Category I Category II Treatment History of If clinically

previous TB diagnosed
Treatment (for Rif-sensitive)
treatment? TB
No
Clinically
Diagnosed TB
New Case
*Positive: at least 1 (of 2) specimen for acid fast bacilli

** Xpert MTB/Rif: Rapid diagnostic test for the presence of Mycobacteria tuberculosis and Rifampicin resistance
+ TBDC: Tuberculosis diagnostic committee
$ PMDT: Programmatic Management of Drug-Resistant Tuberculosis (possible MDR-TB treatment if Rifampicin Resistant TB)
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IV. MANAGEMENT
A. Treatment Regimen for TB

CATEGORY TB PATIENTS ALTERNATIVE TB TREATMENT REGIMEN
Initial Phase Continuation Phase
New pulmonary TB (bacteriologically-
confirmed or clinically diagnosed)
I New extra-pulmonary TB (bacteriologically- 2 HRZE* 4 HR or 4HRE*
confirmed or clinically-diagnosed), except
CNS / bones or joints
Ia New extra-pulmonary TB (CNS / bones or 2 HRZE 10 HR
joints)
Pulmonary or extra-pulmonary, previously
treated drug-susceptible TB (whether
bacteriologically-confirmed or clinically-
diagnosed), except CNS / bones or joints
o Relapse 2 HRZES and 1 5 HRE
II o Treatment after failure HRZE
o Treatment after lost to follow-up
(TALF)
o Previous treatment outcome
unknown (PTOU)
o Other
Extra-pulmonary (CNS / bones or joints),
previously treated, drug susceptible TB 2 HRZES and 1 9 HRE
IIa (whether bacteriologically-confirmed or HRZE
clinically-diagnosed)
Standard regime drug-resistant (SRDR):
Drug rifampicin resistant TB or multi-drug Individualized based on previous treatment
Resistant resistant TB courses and drug sensitivity testing
TB XDR TB regimen: extensively drug-
resistant TB
*if with cavitary disease, give streptomycin IM alternate days (60 days) instead of ethambutol
# based on the WHO guideline, in populations with known or suspected high levels of isoniazid resistance, new TB patients may receive HRE as
therapy in the continuation phase as an acceptable alternative to HR
B. Drugs used for Tuberculosis

DRUG DOSE MECHANISM OF ACTION
(daily)
Inhibits fatty acid synthase and mycolic acid synthesis
Isoniazid 5 mg/kg, Excellent bactericidal activity against both intracellular and extracellular
(H/INH) max 300 mg actively dividing MTB
Bacteriostatic against slowly dividing organisms
Binds to and inhibits mycobacterial DNA-dependent RNA polymerase
thereby blocking RNA synthesis
Rifampicin 10 mg/kg, Has both intracellular and extracellular bactericidal activity, both in
(R) max 600 mg dividing and non-dividing MTB
Also has sterilizing activity
Most active antimycobacterial agent available and therefore the
cornerstone of first-line TB treatment
Exact mechanism is unclear (fatty acid synthetase-) may be the primary
target)
Pyrazinamide 25 mg/kg, More active against slowly replicating organisms than against actively
(Z) max 2 g replicating organisms
Active only in acidic environment (pH<6.0) and are found within
phagocytes or granulomas
Ethambutol Inhibits arabinosyltransferases involved in cell wall synthesis, which
(E) 15 mg/kg probably inhibits the formation of arabinogalactan and
lipoarabinomannan
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Bacteriostatic antimycobacterial agent which provides synergy with
other drugs
Least potent against MTB
Inhibits protein synthesis by binding at a site in #)S mycobacterial
Streptomycin 15 mg/kg, ribosome
(S) max 1 g Bactericidal against dividing MTB but has only low-level early
bactericidal activity
C. Managing Side-Effects
SIDE EFFECTS DRUGS RESPONSIBLE WHAT TO DO?
Minor Side Effects (Patient should be encouraged to continue taking medications)
Gastrointestinal intolerance Rifampicin Give medication at bedtime
Mild skin reactions Any kind of drug Give antihistamines
Orange/red-colored urine Rifampicin Reassure the patient
Pain at injection site Streptomycin Apply warm compress
Give pyridoxine (Vitamin B6)
Burning sensation in feet IsoniazId 100-200 mg daily for
(peripheral neuropathy) treatment; 10 mg daily for
prevention
Give aspirin or NSAID
Arthralgia due to hyperuricemia Pyrazinamide If symptoms persist, consider
gout
Flu-like symptoms (e.g., fever, Rifampicin Give anti-pyretics
muscle pain)
Major Side Effects (discontinue taking the medications)
Severe skin rash Any drug (especially Discontinue anti TB drugs &
(hypersensitivity) streptomycin) refer
Discontinue anti TB drugs &
Jaundice due to hepatitis Any drug (especially isoniazid, refer
rifampicin, pyrazinamide) If symptoms subside, resume
treatment & monitor clinically
Impairment of visual acuity and Discontinue ethambutol &
color vision due to optic Ethambutol refer to an ophthalmologist
neuritis
Hearing impairment, tinnitus Discontinue streptomycin &
and dizziness due to damage of Streptomycin refer
CN VIII
Oliguria or albuminuria due to Streptomycin Discontinue anti TB drugs &
renal disorder Rifampicin refer
Psychosis and convulsion Isoniazid Discontinue isoniazid & refer
Thrombocytopenia, anemia, Rifampicin Discontinue anti TB drugs &
shock refer
D. Treatment Outcomes
OUTCOME DESCRIPTION
Cured A sputum smear positive patient who has completed treatment and is sputum smear
negative in the last month of treatment and on at least one previous occasion
Treatment completed A patient who has completed treatment, but does not meet the criteria to be
classified as “cured” or “failure”
Died A patient who dies for any reason during the course of the treatment
Patient who is sputum smear positive at five months o later during treatment
Treatment failure A sputum smear negative patient initially who turned out to be positive during
treatment
Lost to follow-up Patient whose treatment was interrupted for two consecutive months or more
Transfer out Patient who has been transferred to another facility with proper referral/transfer slip
for continuation of treatment
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Not evaluated A patient for whom no treatment outcome is assigned
Patients transferred to another treatment facility with outcome unknown
PLEURAL EFFUSION
I. ETIOPATHOGENESIS
Excess quantity of fluid in the pleural space
Most common cause of pleural effusion is left ventricular failure
Transudative effusion: occurs when systematic factors that influence the absorption of pleural fluid are altered
Exudative effusion: occurs when local factors that influence formation and absorption of pleural fluid are altered

Patients may present with pleuritic pain, cough and dyspnea
Findings include decreased breath sounds with decreased or absent tactile fremiti and dullness on percussion
Tracheal deviation and pleural rub may also be noted
III. DIAGNOSIS AND MANAGEMENT

First step: determine if effusion is exudative or transudative (use the Light’s criteria by obtaining LDH and protein
level from serum and pleural fluid)
Other diagnostics for exudative pleural effusions:
o Description of the appearance of the fluid
o Glucose & protein level
o Differential cell count
o Microbiologic studies and cytology
o Work up for tuberculosis
A. Light’s Criteria
Exudative pleural effusions meet at least one of the following criteria:

Pleural fluid protein / serum protein >0.5
Pleural fluid LDH/serum LDH >0.6
Pleural fluid LDH more than two-thirds normal upper limit for serum
These criteria misidentify -25% of transudates as exudates. If one or more of the exudative criteria arte met and the patient is
clinically thought to have a condition producing a transudative effusion, the difference between the protein levels in the serum and
the pleural fluid should be measured. If this gradient >31 g/L, the exudative categorization by these criteria can be ignored because
almost all such patients have transudative pleural effusion
B. Common causes of pleural effusion

Transudative Pleural Effusions
Most common cause of pleural effusion
Diagnostic thoracentesis should be performed:
o If effusions are not bilateral and comparable in
size
Effusion due to Heart Failure o If patient is febrile
o If patient has pleuritic chest pain, to verify that
the patient has a transudative effusion;
otherwise, the heart failure is treated
Pleural fluid N-terminal pro-brain natriuretic peptide
(NT-proBNP) >1500 pg/mL is virtually diagnostic
Liver cirrhosis may give rise to pleural effusion
Cirrhosis Usually on the right side (passage of fluid from
abdomen through diaphragm)
Other Transudative Effusions Nephritic syndrome, myxedema, urinothorax
Pulmonary embolism (may also be exudative)
Exudative Pleural Efusions
Parapneumonic Effusion Most common cause of exudative pleural effusion
Bacterial Pneumonia (in the US)
101
Lung Abscess Presents with acute febrile illness consisting of
Bronchiectasis chest pain, sputum production and leukocytosis
Empyema If free fluid separates the lung from the chest wall
by >10mm, a therapeutic thoracentesis should be
performed
The following factors indicate the need for a more
invasive procedure (e.g., CTT insertion)
o Loculated pleural fluid
o Pleural fluid pH <7.20
o Pleural fluid glucose <3.3 mmol/L (<60mg/dL)
o Positive gram stain or culture of the pleural fluid
o Presence of gross pus in the pleural space
If fluid recurs, a repeat thoracentesis should be
performed
If fluid cannot be completely removed, consider
CTT insertion and instilling fibrinolytics or
performing thoracoscopy to break own adhesions
If above procedures remain ineffective,
decortications should be considered
Three most common causes: lung CA, breast CA
and lymphoma
Diagnosis usually clinched by cytologic exam of
fluid if negative, thoracoscopy is the next best
procedure
Effusion secondary to Malignancy Glucose levels may be low if tumor burden is high
Patients with malignant effusions are treated
symptomatically for the most part
If patient’s QOL is compromised by dyspnea,
pleurodesis or insertion of a small indwelling
catheter may be considered
Diagnosis most commonly overlooked in the
differential diagnosis of a patient with undiagnosed
pleural effusion
Effusion secondary to Pulmonary Embolism Diagnosis is established by spiral CT scan or
pulmonary arteriography
If the pleural effusion increases in size after
anticoagulation, consider recurrent emboli,
hemothorax or a pleural infection
Most common cause of an exudative pleural
effusion in most parts of the world
Usually associated with primary TB and thought to
be primarily due to a hypersensitivity reaction to TB
Tuberculosis Pleuritis protein in pleural space
Cytology shows predominantly small lymphocytes
Diagnosis is established by high levels of
adenosine deaminase (>40 IU/L) or interferon
gamma (>140 pg/mL) in the pleural fluid
Treatment of pleural TB is identical to PTB
Hematocrit should be obtained on pleural fluid if
initial tap reveals bloody pleural fluid
If hematocrit is more than ½ of that in peripheral
Hemothorax blood, hemothorax should be considered and tube
thoracostomy should be inserted
If pleural hemorrhage >200 mL/h, consider
thoracoscopy or thoracotomy
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PNEUMOTHORAX (PTX)
Presence of gas in the pleural space
I. ETIOPATHOGENESIS
TYPE ETIOLOGY/PATHOGENESIS MANAGEMENT
Occurs in the absence of underlying
lung disease Simple aspiration: initial treatment
Primary Spontaneous Usually due to rupture of apical pleural If lung does not expand or PTX
PTX blebs recurs, thoracoscopic stapling of
Occurs almost exclusively in smokers blebs and pleural abrasion
(those with subclinical disease)
Occurs in the presence of underlying Tube thoracostomy or thoracoscopy
lung disease or thoracotomy with bleb stapling
Secondary PTX Mostly due to COPD (but have been and plural abrasion
reported in all lung disease) If patient refuses surgery,
pleurodesis is an option
Penetrating or non-penetrating chest Tube thoracostomy unless very small
injuries and can be managed with
Traumatic PTX Iatrogenic PTX is a subtype which is supplemental oxygen or aspiration
increasingly becoming more common If hemopneumothorax: two chest
tubes directed at each lesion
Medical emergency
Large-bore needle should be
Tension PTX Pressure in the pleural inserted into the pleural space
through the 2nd anterior ICS and
should be left in place until a
thoracostomy tube can be inserted
SUPERIOR VENA CAVA (SVC) SYNDROME

I. ETIOPATHOGENESIS
Clinical manifestation of superior vena caval obstruction with severe reduction in venous return from the heart,
neck and upper extremities
Most common etiologies are lung CA, lymphoma and metastatic tumors
o Lung CA (small cell and squamous cell) accounts for 85% of all cases of malignant origin
o Malignant lymphoma is the leading cause of SVCs in adults
The increasing use of intravascular devices has led to increasing prevalence of benign causes of SVC
Other benign causes: aneursyms, thyromegaly, thrombosis, fibrosing mediastinitis, histoplasmosis or Behcet’s
syndrome

SVCs usually present with neck and facial swelling (especially around the eyes), dyspnea and cough
Other symptoms are hoarseness, tongue swelling, headaches, nasal congestion, epistaxis, hemoptysis,
dysphagia, pain, dizziness, syncope and lethargy which are aggravated by bending forward or lying down
PE findings include dilated neck veins, increased number of collateral veins over the anterior chest wall, cyanosis
and edema of the face, arms and chest
More severe cases present with proptosis, glossal and laryngeal edema, obtundation and signs of cerebral
edema
Cardiorespiratory symptoms may occur at rest when significant airway and vascular obstruction occurs
Rarely, esophageal varices may develop
III. DIAGNOSIS OF SVC SYNDROME

Most significant finding is widening of the superior mediastinum (more
Chest Radiography commonly on the right side)
Pleural effusion occurs in 25% (often on the right side) - majority are
103
exudative and occasionally chylous
May be normal in some cases
Provides the most reliable view of the mediastinal anatomy
Chest CT Diminished or absent opacification of central venous structure with
prominent collateral venous circulation
Chest MRI No advantages over CT
Invasive Procedures
(e.g., broncoscopy, percutaneous Necessary for etiologic diagnosis / histologic diagnosis
core needle biopsy, mediastinoscopy
and thoracotomy)
IV. MANAGEMENT
Upper airway obstruction demands emergent therapy:
o Diuretics with low salt diet
o Head elevation
o Oxygen support
o Glucocorticoids for lymphoma (no benefit in lung CA)
Radiation therapy is the primary treatment for SVCs caused by NSCLC and other metastatic solid tumors
Chemotherapy is effective when the underlying CA is SCLS of the lung, lymphoma or germ cell tumor
Recurrent SVC may be palliated with use of intravascular self-expanding stents (however, may precipitate heart
failure and pulmonary edema)
The mortality with SVC does not relate to caval obstruction but rather to underlying cause
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CHAPTER 4
CRITICAL CARE
I. Shock in the Intensive Care Setting
1. Overview of the Types of Shock
2. Cardiogenic Shock
3. Sepsis and Septic Shock
4. Other Forms of Shock
II. Common Conditions Encountered in the ICU
1. Respiratory Failure
2. Acute Respiratory Distress Syndrome
3. Venous Thromboembolism
III. Overview of Mechanical Ventilation
1. Non-Invasive Ventilation (NIV)
2. Basic Modes of Mechanical Ventilation
3. Oxygen Delivery, Spontaneous Breathing Trial and
Weaning
105
SECTION 1
SHOCK IN THE INTENSIVE CARE SETTING
OVERVIEW OF THE TYPES OF SHOCK
TYPE OF SHOCK CVP & PCWP CARDIAC OUTPUT SYSTEMIC VASCULAR
(CO) RESISTANCE (SVR)
Cardiogenic Shock ↑ ↓ ↑
Septic Shock
Hyperdynamic phase (Early) ↑↓ ↑ ↓
Hypodynamic phase (Late) ↑↓ ↓ ↑
Hypovolemic Shock ↓ ↓ ↑
Hypoadrenal Shock ↓ ↓ ↓
Neurogenic Shock ↓ ↓ ↓
CVP: central venous pressure (N: 3-10 mmHg)
PCWP: pulmonary capillary wedge pressure (N: 4-12 mmHg)
CO: cardiac output (N: 4-8 L/min)
SVR: systemic vascular resistance (N: 700-1600 dynes.s/cm2)
CARDIOGENIC SHOCK
I. ETIOPATHOGENESIS
Characterized by systemic hypoperfusion due to severe depression of cardiac index (<2.2 L/min/m2) and
sustained systolic arterial hypotension (<90 mmHg) despite an elevated filling pressure (PCWP >18 mmHg)
Most common cause: severe LV dysfunction
II. MANAGEMENT OF PATIENTS WITH CARDIOGENIC SHOCK

ACUTE PULMONARY EDEMA LOW-OUTPUT ARRYHTMIA
CARIDOGENIC SHOCK
Furosemide IV 0.5-1 mg/kg SBP >100 mmHg:
Morphine IV 2-4 mg NTG 10-20 mcg/min IV
Oxygen/intubation as needed
NTG SL then 10-20 mcg/min IV if SBP 70-100 mmHg and no
SBP >100 mmHg signs/symptoms of shock: If with bradycardia or
Norepinephrine 0.5-30 mcg/min Dobutamine 2-20 tachycardia:
First Line of IV or Dopamine 5015 mcg/kg/min IV Manage accordingly
Action mcg/kg/min IV if SBP <100 based on ACLS
mmHg and signs/symptoms of SBP <100 mmHg or with guidelines
shock present signs/symptoms of shock:
Dobutamine 2-20 mcg/kg/min IV Norepinephrine 0.5-30
if SBP >70-100 mmHg and no mcg/min IV, or
signs/symptoms of shock Dopamine 5-15
mcg/kg/min IV
Second Line of If SBP >100 mmHg and not less than 20 mmHg below baseline: consider ACE-inhibitors such
Action as Captopril 1-6.25 mg
The following should be considered in non-hypovolemic shock
Third Line of o Diagnostics: pulmonary artery catheter, echocardiography, angiography for MI/ischemia
Action and other additional diagnostic studies
o Therapeutics: intra-aortic balloon pump, reperfusion/revascularization
SEPSIS AND SEPTIC SHOCK

I. ETIOPATHOGENESIS
TNF-alpha is a central mediator
Intravascular thrombosis is the hallmark of the local inflammatory response
106
Endothelial injury is the major mechanism of multi-organ dysfunction
II. DIAGNOSIS AND DEFINITIONS
A. Bacteremia Versus Septicemia

Bacteremia Presence of bacteria in blood, as evidenced by positive blood culture
Septicemia Presence of microbes or their toxins in blood
B. Definition in Terms
SYNDROME DEFINITION
Two or more of the following conditions (may have a noninfectional etiology):
Signs of Possible Harmful o Fever (oral temperature >38oC) or hypothermia (<36oC)
Systemic Response (SIRS) o Tachypnea (>24 breaths/min)
o Tachycardia (HR >90 bpm)
o Leukocytosis >12,000 or leukopenia <4,000 or >10% bands
The harmful host response is infection
Sepsis with one or more signs of organ dysfunction:
o CVS: arterial SBP < 90 mmHg or MAP <70 mmHg that responds to
administration of IV fluids
Sepsis o Renal: urine output <0.5 mL/kg/hr for 1 hour despite adequate fluids
(or Severe Sepsis) o Respiratory: PaO2/FiO2 <250 (or <200 if lung is the only dysfunctional
organ)
o Hematologic: platelet count <80,000/uL or 50% decrease in platelet count
from highest value recorded over precious 3 days
o Unexplained metabolic acidosis: a pH <7.30 or a base deficit >5.0 mEq/L
and a plasma lactate level >70 mmHg
Sepsis with hypotension (SBP <90 mmHg or 40 mmHg less than patient’s normal
Septic Shock BP) for at least 1 hour despite adequate fluid resuscitation, OR
Need for vasopressors to maintain SBP >90 mmHg or MAP >70 mmHg
Refractory Septic Shock Septic shock that lasts for >1 hour and does not respond to fluid or pressor
administration
Multiple-Organ Dysfunction Dysfunction of more than one organ, requiring intervention to maintain
Syndrome (MODS) homeostasis
SIRS: Systemic Inflammatory Response Syndrome
ULN: Upper Limit of Normal
“Adequate” fluid resuscitation: when the pulmonary artery wedge pressure is >12 mmHg or central venous pressure >8 mmHg
III. MANAGEMENT
A. Initial Resuscitation (first 6 hours)
CVP 8-12 mmHg
Resuscitation Goals MAP > 65 mmHg
Urine output >0.5 mL/kg/hour
Obtain appropriate blood cultures
Broad-spectrum IV antibiotics with good penetration into presumed source of infection
Antibiotic Therapy Combination therapy in Pseudomonas infections and neutropenic patients for at least
3-5 days and de-escalation following susceptibility studies
Duration of therapy typically 7-10 days; longer if response is slow or there are
undrainable foci of infection or immunologic deficiencies
B. Hemodynamic Support and Adjunctive Therapy

Fluid Therapy Crystalloids or colloid with target CVP of 8-12 mmHg (>12 mmHg if mechanically
ventilated)
Vasopressors Maintain MAP >65 mmHg
Norepinephrine and Dopamine are the initial vasopressors of choice
Inotropic Therapy Dobutamine in patients with myocardial dysfunction as supported by elevated cardiac
filling pressures and low CO
Steroids Consider IV hydrocortisone for adult septic shock when hypotension responds poorly
to adequate fluid resuscitation and vasopressors
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C. Other Supportive Therapy
RBC transfusion if hemoglobin is: Platelet transfusion if platelet count is:
<7.0 g/dL to target Hgb 7.0-9.0 g/dL <5000/mm3 (5x109/L) regardless of
in adults bleeding
Blood Transfusion Higher level required in special 5,000-30,000/mm3 (5-30x109/L) and
circumstances like MI, acute there is significant bleeding risk
hemorrhage, cyanotic CHD Higher platelet counts
(>50,000/mm3) are required for
surgery or invasive procedures
Target tidal volume of 6 mL/kg with an initial upper limit plateau pressure <30 cm
H2O (for ARDS)
Mechanical Ventilation Set PEEP to avoid extensive lung collapse at end-expiration
of Sepsis-Induced AL/ Maintain in a semi-recumbent position (bed raised to 45o) unless contraindicated
ARDS Noninvasive ventilation in patients with mild to moderate hypoxemic respiratory
failure with no contraindications for its use
Weaning protocol and an SBT regularly
Glucose Control May use IV insulin (e.g., drip) to control hyperglycemia
Low-dose UFH or LMWH, unless contraindicated
DVT Prophylaxis Compression stockings or an intermittent compression device, when heparin is
contraindicated
Sedation, analgesia, neuromuscular blockade (intermittent bolus or continuous
infusion)
Others Renal replacement therapy (intermittent hemodialysis & continuous veno-veno
hemofiltration)
Stress ulcer prophylaxis (H2 blocker or PPI)
Consideration for limitation of support (advanced care planning)
OTHER FORMS OF SHOCK

I. HYPOVOLEMIC SHOCK
Most common form of shock resulting from either the loss of RBC mass and plasma from hemorrhage or from
loss of plasma volume alone due to extravascular or GI, urinary and insensible losses
MILD MODERATE SEVERE

(<20% blood volume) (20-40% blood volume) (>40% blood volume)
Cool extremities Same as “mild”, PLUS: Same as “moderate”, PLUS:
Increased capillary refill time Tachycardia Hemodynamic instability
Diaphoresis Tachypnea Marked tachycardia
Collapsed veins Oliguria Hypotension
Anxiety Postural changes Mental status deterioration
II. HYPOADRENAL SHOCK/ADRENAL INSUFFICIENCY

Occurs in a setting where unrecognized adrenal insufficiency complicates the host response to the stress induced
by acute illness or major surgery
Can occur as a consequence of the chronic administration of high dose exogenous steroids
Shock is categorized by loss of homeostasis with reductions in systemic vascular resistance, hypovolemia and
reduced cardiac output
Diagnosis may be established by an ACTH stimulation test, but this may be inconsistent
Management:
o Hemodynamically unstable + diagnosis is not established Dexamethasone 4 mg IV (does not interfere
with the ACTH stimulation test)
o Diagnosis is established Hydrocortisone 100 mg IV q6-8h (leads to reduce mortality)
o Simultaneous volume resuscitation and pressor support are required
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SECTION 2
COMMON CONDITIONS ENCOUNTERED IN THE ICU
RESPIRATORY FAILURE
A condition in which the respiratory system fails in one or both of its gas exchanging functions
o Oxygenation
o CO2 elimination
I. TYPE I RESPIRATORY FAILURE

Acute hypoxemic respiratory failure (generally PO2 <55-60 mmHg)
Usually from alveolar flooding and subsequent intrapulmonary shunting
Alveolar flooding may be a consequence of:
o Pulmonary edema (cardiogenic or non-cardiogenic)
o Pneumona
o Alveolar hemorrhage
o ARDS (low pressure pulmonary edema)
II. TYPE II RESPIRATORY FAILURE

Hypercarbic respiratory failure (generally pCO2 >45-50 mmHg)
Result of alveolar hypoventilation and leads to the inability to eliminate carbon dioxide effectively
Mechanisms by which this occurs are categorized by:
Drug overdose
Diminished CNS drive Brainstem injury
to breathe Sleep-disordered breathing
Hypothyroidism
Impaired neuromuscular transmission
Reduced strength of o Myasthenia gravis
neuromuscular o Guillain-Barre syndrome
function o Amyotrophic lateral sclerosis
o Phrenic nerve injury
Respiratory muscle weakness (myopathy, electrolyte derangements, fatigue)
Increased resistive loads
o Bronchospasm
Loads due to reduced lung compliance
o Alveolar edema
o Atelectasis
Increased overall load o Intrinsic positive end-expiratory pressure (auto-PEEP)
on the respiratory Loads due to reduced chest wall compliance
system o Pneumothorax
o Pleural effusion
o Abdominal distention
Loads due to increased minute ventilation requirements
o Pulmonary embolus with increased dead space fraction
o Sepsis
III. TYPE III RESPIRATORY FAILURE

This form of respiratory failure occurs as a result of lung atelectasis
Also called perioperative respiratory failure: commonly found in the perioperative period (usually from pain)
IV. TYPE IV RESPIRATORY FAILURE

Results from hypoperfusion of respiratory muscles in patients in shock (respiratory muscles normally consume
<5% of the total cardiac output and O2 delivery)
Patients in shock often experience respiratory distress due to pulmonary edema (e.g., patients in cardiogenic
shock), lactic acidosis and anemia – up to 40% of CO may be distributed to the respiratory muscles
Intubation and mechanical ventilation can allow redistribution of the CO away from the respiratory muscles and
back to vital organs while the shock is treated
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ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
I. ETIOPATHOGENESIS
ARDS is a clinical syndrome of:
o Severe dyspnea of rapid onset
o Hypoxemia
o Diffuse pulmonary infiltrates
A. Etiology of ARDS
DIRECT LUNG INJURY INDIRECT LUNG INJURY
Pneumonia Sepsis
Aspiration of gastric contents Severe trauma (multiple bone fractures, flail chest, head trauma, burns)
Pulmonary contusion Multiple transfusions
Near-drowning Drug overdose
Toxic inhalation injury Pancreatitis
Postcardiopulmonary bypass
B. Three Phases in the Natural History of ARDS

Alveolar capillary endothelial cells and type I pneumocytes (alveolar epithelial cells)
are injured, leading to loss of the normally tight alveolar barrier to fluid and
Exudative Phase macromolecules
(Day 1-7) Edema fluid rich in protein accumulates in the interstitial and alveolar spaces
X-ray reveals alveolar and interstitial opacities involving at least three-quarters of
the lung fields
Most are liberated from mechanical ventilation during this phase
Proliferative Phase Histologically, the first signs of resolution are often evident in this phase
(Day 7-21) Lymphocyte-predominant pulmonary infiltrate
Approximately 3 weeks after the initial pulmonary injury, most patients recover
While many patients with ARDS recover lung function 3-4 weeks after the initial
Fibrotic Phase pulmonary injury, some will enter a fibrotic phase
Biopsy evidence for pulmonary fibrosis in any phase of ARDS is associated with
increased mortality
II. CLINICAL MANIFESTATIONS & DIAGNOSIS OF ARDS

OXYGENATION IN ARDS ONSET CHEST ABSENCE OF HIGH LEFT
PaO2 / FiO2 IMAGING ATRIAL PRESSURES
Mild 200 mmHg < PaO2/FiO2 < 300 mmHg Within 1 week Bilateral PCWP < 18 mmHg or no
Moderate 100 mmHg < PaO2/FiO2 < 200 mmHg of known alveolar or clinical evidence of
Severe PaO2/FiO2 < 100 mmHg clinical insult interstitial increased left atrial
infiltrates pressure
III. MANAGEMENT
Aim is to protect the lung and is basically done by decreasing tidal volume and giving adequate positive end-
expiratory pressure
A. Mechanical Ventilation
Frequently needed due to fatigue from increased work of breathing and progressive hypoxemia
However, mechanical ventilation can aggravate lung injury
Lower tidal volume (VT) would protect against ventilator-induced lung injury and improve clinical outcomes
o Low VT = 6 mL/kg predicted body weight (preferred in ARDS)
o Conventional VT = 12 mL/kg (8-10 mL/kg in Asians)
This improvement in survival represents the most substantial benefit in ARDS mortality demonstrated for any
therapeutic intervention in ARDS to date
B. Summary of Evidence-Based Recommendation for Management of ARDS

Management Level of Evidence
Low tidal volume Grade A – best evidence
Minimize left atrial filling pressures Grade B
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High-PEEP Grade C
Prone position Grade C
Recruitment maneuvers Grade C
ECMO Grade C
VENOUS THROMBOEMBOLISM (VTE)

Encompasses deep venous thrombosis (DVT) and pulmonary embolism (PE)
Virchow’s triad: inflammation + hypercoagulability + endothelial injury
I. DEEP VENOUS THROMBOSIS (DVT)

Presence of thrombus in one of the deep venous conduits that return blood to the heart
Most commonly involves the deep veins of the leg or arm, often resulting in potentially life-threatening emboli to
the lungs (e.g., pulmonary embolism) or debilitating valvular dysfunction and chronic leg swelling
A. Clinical Manifestations
Most frequent symptom: cramp in the lower calf
Leg swelling and pain
Patients at risk: older age, prolonged immobilization, paralysis, hyperviscosity syndromes, etc.
B. Diagnostic Tests
Venous duplex scan: best non-invasive diagnostic method which detects “vein incompressibility” (most definite
sign of thrombosis)
D-dimer: high negative predictive value (“rule out test”)
C. Padua Prediction Score for Identification of Hospitalized Patients at Risk for Venous Thromboembolism
Most widely used risk assessment tool to decide whether to administer VTE prophylaxis to hospitalized medical
patients (e.g., those at risk for venous thromboembolism)
High risk for developing PE: > 4 points
RISK FACTOR SCORING
Cancer 3
Previous VTE 3
Immobility 3
Thrombophilia 3
Trauma / surgery 2
Age > 70 years 1
Heart / respiratory failure 1
Acute MI or stroke 1
Infection / rheumatologic disorder 1
Obesity 1
Hormonal treatment 1
D. Common Regimens for VTE Prevention

UFH 5,000 units SC BID-TID
Enoxaparin 40 mg SC OD
Fondaparinux 2.5 mg SC OD
Compression stockings or intermittent pneumatic compression devices
II. PULMONARY EMBOLISM (PE)

Blockage of the main artery of the lung (or its branches) by a substance from elsewhere in the body (embolism)
Increase in pulmonary vascular resistance from pulmonary embolism causes increase in RV wall tension leading
to progressive right HF (the usual cause of death from PE)
One of the three major cardiovascular causes of death, along with MI and stroke
A. Sources of Embolism
Pelvic vein thrombosis or proximal leg DVT
Isolated calf thrombi (most common source of paradoxical embolism – e.g., through an ASD)
Upper extremity venous thrombosis (rarely embolize and cause PE)
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Others: air embolus, fat embolus, amniotic fluid
B. Pathophysiology
Most common gas exchange abnormalities:
o Hypoxemia (decreased arterial PO2)
o Increased alveolar-arterial O2 tension gradient (represents inefficiency of O2 transfer across the lungs)
Increase in anatomic dead space: because breathed gas does not enter gas exchange units
Increase in physiologic dead space: because ventilation to gas exchange exceeds venous blood
flow through pulmonary capillaries
C. Clinical Manifestations
PE: most frequent history is unexplained breathlessness
Dyspnea is the most frequent symptom of PE and tachypnea is the most frequent sign of PE
Clinical presentation depends on the size of PE
RISK FACTOR SMALL PE MODERATE PE MASSIVE PE
(70-75%) (20-25%) (5-10%)
Usual symptoms Pleuritic pain, cough, Varied Dyspnea, syncope
hemoptysis
Usual signs Varied Varied Hypotension, cyanosis
BP Normal Normal Low (<90 mmHg SBP)
RV on 2D Echo Normal right heart function RV hypokinesis / RV hypokinesis /
dysfunction dysfunction
Anticoagulation: IV anticoagulation; IV anticoagulation;
Management Heparin + Warfarin; or Controversy regarding consider advanced
Rivaroxaban advanced therapy therapy
*advanced therapy: systemic thrombolysis, catheter-directed therapy, surgical embolectomy, IVC filter
III. DIAGNOSIS OF VENOUS THROMBOEMBOLISM
A. Determine the likelihood of a venous thromboembolism (Well’s Scoring)

DEEP VENOUS THROMBOSIS PULMONARY EMBOLISM
Parameter Score Parameter Score
Active cancer 1
Paralysis, paresis or recent cast 1 Signs and symptoms of DVT 3
Bedridden for >3 days; major surgery <12 1 Alternative diagnosis less likely than PE 3
weeks HR >100bpm 1.5
Tenderness along distribution of deep veins 1 Immobilization >3 days; surgery within 4 weeks 1.5
Entire leg swelling 1 Prior PE or DVT 1.5
Unilateral calf swelling >3 cm 1 Hemoptysis 1
Pitting edema 1 Cancer 1
Collateral superficial non-varicose veins 1
Alternative diagnosis at least as likely as DVT -2
Low clinical likelihood of DVT: < 0 points
Moderate clinical likelihood of DVT: 1-2 points High clinical likelihood of PE: >4
High clinical likelihood of DVT: > 3 points
B. Approach to Diagnosis
1. Request for a D-Dimer (rule out test) if:
Likelihood for DVT is low
Likelihood for PE is not high
2. Request for an Imaging Test if:

Likelihood for DVT is not low
Likelihood for PE is high
C. Diagnostics for PE
Plasma D-dimer High sensitivity for PE
ELISA Useful rule-out test: patients with normal D-dimer do not have PE
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It is not specific as levels can increase with MI, pneumonia, sepsis, cancer, postoperative
state, 2nd and 3rd trimester of pregnancy
ABG Both PO2 and PCO2 may be decreased in PE
Most common abnormality in PE is T-wave inversion in leads V1 to V4
Most frequently cited abnormality in PE (in addition to sinus tachycardia): S1 Q3 T3
ECG o S wave in Lead I
o Q wave in Lead III
o Inverted T wave in Lead III
Cardiac May be increased in RV microinfarction
Biomarkers
Westermark’s sign: focal oligemia
CXR Hampton’s Hump: peripheral wedged-shaped density above the diaphragm
Palla’s Sign: enlarged right descending pulmonary artery
Chest CT Scan Principal imaging test for the diagnosis of PE
with IV Contrast Can image small peripheral emboli
(high-resolution)
Second-line diagnostic test for PE
Lung scanning High probability scan for PE: two or more segmental perfusion defects in the presence of
normal ventilation
Echocardiography McConnell’s Sign: hypokinesis of the RV free wall with normal motion of the RV apex
(best known indirect sign of PE on transthoracic echo)
Pulmonary Definitive diagnosis of PE depends upon visualization of an intraluminal filling defect in
angiography more than one projection
IV. MANAGEMENT OF VENOUS THROMBOEMBOLISM (DVT AND PE)
A. Anticoagulation
Foundation of successful treatment of DVT and PE
Parenteral agents are continued as a transition or bridge to stable, long-term anticoagulation with warfarin
ANTICOAGULANT REMARKS DOSE FOR VTE
Parenteral Anticoagulation
Binds and accelerates activity of
antithrombin, thus preventing additional
thrombus formation & permitting
Unfractioned Heparin endogenous fibrinolytic mechanisms to IV bolus 80 units/kg, then 18
(UFH) lyse the clot that has already formed units/kg/hour (maintain PTT ratio
Major advantage: short half-life 1.2-2.5x normal)
Major disadvantage: repeated sampling
for PTT and dose adjustment (every 4-6
hours)
Low Molecular Weight No monitoring or dose adjustment 1 mg/kg q12 SC
Heparin (LMWH) needed, unless obese or has CKD 0.5mg/kg if CrCl <30 mL/min
Fondarparinux Anti-Xa pentasaccharide 5-10 mg OD
Oral Anticoagulants
Vitamin-K antagonist which prevents
carboxylation activation of factors II, VII, 5 mg OD overlapped with
IX, X parenteral anticoagulation (to be
Full effect requires 5 days started on day 1-2 of LMWH or
Warfarin Overlapping UFH, LMWH, or UFH)
fondaparinux with warfarin for at least 5 Maintain overlap with parenteral
days can counteract early procoagulant anticoagulation for 5 days until
effect of unopposed warfarin INR is 2-3 for at least 24 hours
Monitor prothrombin time (PT) with a
target INR 2.5 (range of 2.0 to 3.0)
Direct thrombin inhibitor 150 mg BID (to be started on the
Dabigatran Indicated for DVT and PE in those who day after last dose of enoxaparin
have been treated with a parenteral is given)
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anticoagulant for 5-10 days
Rivaroxaban Factor Xa inhibitor 15 mg BID x 3 weeks, followed
by 20 mg OD
Apixaban Factor Xa inhibitor 10 mg BID x 7 days, then 5 mg
BID
DURATION OF ANTICOAGULATION
3 months Proximal or isolated distal provoked DVT (e.g., provoked by surgery or a non-
surgical transient risk factor)
3-6 months Unprovoked DVT (3 months if risk of bleeding is high)
Indefinite / Extended Idiopathic DVT
DVT with cancer, APAS, antithrombin III, protein C and protein S deficiencies
CONTRAINDICATIONS TO ANTICOAGULATION
Severe uncontrolled hypertension Cerebral lesions at high risk for bleeding
Acute bacterial endocarditis Major bleeding diathesis
Hemorrhagic stroke Allergy to anticoagulants
Active ulverative condition Severe liver and renal failure
Uncontrolled active bleeding Impaired bleeding parameters (platelet count
<50x109/L, INR >3, PTT >2x normal)
B. Fibrinolysis / Thrombolysis
The only FDA-approved indication for PE fibrinolysis is massive pulmonary embolism
Rapidly reverses right heart failure and may result in a lower rate of death and recurrent PE
Preferred agent: Recombinant Tissue Plasminogen Activator (r-tPA)
C. Other Modalities
Inferior vena cava (IVC) filters
Pulmonary embolectomy
Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension
Maintenance of adequate circulation (for patients with massive PE and hypotension)
Graduated compression stockings (30-40 mmHg) for DVT (if without significant peripheral arterial disease)
Emotional support
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SECTION 3
OVERVIEW OF MECHANICAL VENTILATION
NON-INVASIVE VENTILATION (NIV)
I. MECHANISM
Provided by using a tight fitting mask or nasal mask

Highly effective in patients with acute exacerbations of COPD
Uses bilevel positive airway pressure ventilation (“BiPAP”)
If there are contraindications to NIV, invasive ventilation should be used (e.g., may require intubation)
II. CONTRAINDICATIONS FOR NIV

Cardiac or respiratory arrest
Severe encephalopathy
Severe GI bleed
Hemodynamic instability
Acute coronary syndrome
Facial surgery or trauma
Upper airway obstruction
High-risk aspiration and/or inability to protect airways
Inability to clear secretions
NON-INVASIVE VENTILATION (NIV)

I. ASSIST/CONTROL MODE (A/C MODE)
The patient breathes at his own rate and the ventilator senses the inspiratory effort and delivers a preset tidal
volume of each patient effort
If patient’s RR decreases at preset rate, the ventilator delivers tidal breaths at the preset rate
Since every breath is assisted, tachypnea may result in significant hypocapnia and respiratory alkalosis
Uses initial mechanical ventilation settings
1. Tidal Volume (TV) 8-10 mL/kg of ideal body weight
“How much volume will the machine deliver?” 6 mL/kg for ALI/ARDS
10-12 mL/kg for neuromuscular disease
2. Back-up Rate (BUR)
Minimum number of breaths per minute
Usually set 2-4 counts below the spontaneous rate (this can be 14-22 breaths/min
adjusted depending on the desired PaCO2 or pH)
Faster RR = ↑ exhalation of CO2 ↓PaCO2 and ↑pH
3. Oxygen Concentration (FiO2)
Initial FiO2 should be 100% unless it is evident that a lower FiO2
will provide adequate oxygenation
We can start at 50% if with neuromuscular disease (e.g.,
myasthenia gravis) 100%
Eventually downtitrated based on desired PO2
Prolonged exposure to high oxygen concentrations is avoided
as it may lead to O2 narcosis and development of more free O2
radicals
4. Inspiratory Flow Rate (IFR)
“How fast do we deliver the air?”
This is the rate at which air is delivered to the patient to achieve
the set tidal volume 40-60 L/minute
Rate needs to be higher (80 L/min) in obstructive diseases such
as COPD or asthma to allow for a longer time for expiration
Rate needs to be lower in patients with severe hypoxemia to
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deliver air slower, prolonging inspiration time & allowing more
gas exchange
An IFR lower than the patient demand will increase the work of
breathing and is a common cause of patient-ventilator
discordance (fighting or bucking the ventilator)
5. Inspiratory Flow Pattern (IFP)
“How do you deliver the air?” Decelerating wave
How flow is distributed throughout the respiratory cycle
A normal person has a sine wave pattern
6. Positive End-Expiratory Pressure (PEEP)
“Physiologic PEEP” of about 5cm H2O should be added
regardless of FiO2 to prevent alveolar injury due to the shearing
effect of opening and closing the alveoli and therefore should
be increased in ARDS 5 cm H2O
Lower PEEP is usually given to patients with hypotension as
higher values increase intrathoracic pressures which can
impede venous return, thereby reducing preload and
subsequent CO
7. Sensitivity
Ranges anywhere from -5 to -0.5 cm H2O (pressure sensitivity)
or 1 to 5 liters (flow sensitivity)
The more sensitive (e.g., 0.5 cm or 1L), the easier for the
patient to trigger the ventilator which may lead to
hyperventilation
The less sensitive (e.g., 5 cm or 5L), the harder for the patient
to trigger the ventilator which may lead to increased work of
breathing and may cause patient-ventilator dyssynchrony
-2.0 cm or 2 L
a. Pressure Sensitivity
If set -1, the patient has to exert a -1cm Hg pressure for the
ventilator to deliver the tidal volume
b. Flow Sensitivity
If set at 1L, the patient has to exert an air flow of at least 1L
Advantageous in COPD since it affords less work of
breathing for patients
II. SYNCHRONIZED INTERMITTENT MANDATORY VENTILATION (SIMV)

Allows the patient to have spontaneous breaths around the intermittent synchronized ventilator breaths beyond
the set respiratory rate
Patient’s contribution to minute ventilation depends on the number of spontaneous breaths & inspiratory effort
EXAMPLE:
Patient’s MV set on SIMV mode; BUR set at 12; patient’s actual RR is 20
Only 12 of the 20 breaths are assisted in SIMV
o 12 will receive the complete (assisted) tidal volume set
o 8 will receive the tidal volume depending on the patient’s effort
In contrast, in AC mode all 20 breaths will be assisted
A. A/C Mode versus SIMV

A/C MODE SIMV MODE
Assist Total Partial
Work of Breathing Almost none Variable
Can be used for weaning? No Yes
Patient breathes at his own Allows patient to breathe on
rate his/her own if the RR exceeds
In simple terms Ventilator delivers a preset the preset back-up rate
tidal volume with each (all
effort)
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B. Advantages and Disadvantages of SIMV
ADVANTAGES DISADVANTAGES
Maintains respiratory muscle tone due to the
continued use of the inspiratory muscles Even with the same back-up rate as the A/C, there
preventing disuse atrophy is more work of breathing
There is decreased intrathoracic pressure as The increased work of breathing results in
compared to A/C which may lead to improved increased oxygen consumption which is deleterious
hemodynamics in patients with myocardial insufficiency
Useful for weaning because as the back-up This mode is not useful in patients with depressed
rate is decreased, the patient gradually respiratory drive or impaired neurologic status
assumes the bulk of breathing
C. Selection of Ventilator Settings for the SIMV mode

Rate: initial rate should be close to the patient’s inherent rate and eventually adjusted depending on patient
tolerance
VT, FiO2, IFR, IFP, PEEP selection is similar to that in A/C mode
III. NEWER MODALITIES OF MECHANICAL VENTILATION

Pressure Limited Ventilation Pressure Support Ventilation (PSV)
Pressure Controlled Ventilation (PC)
Combination of Volume-Cycled and Pressure-Limited SIMV with PSV
Ventilation
Inverse Ratio Ventilation PCV with Inverse Ratio
A/C with Very Low Flow Rates
OXYGEN DELIVERY, SPONTANEOUS BREATHING TRIAL & WEANING

I. OXYGEN DELIVERY
Indications:
o PaO2 <60 mmHg or SaO2 <90%
o Acute conditions where hypoxemia is suspected
o Severe trauma
o Acute MI
o Short-term, post-operative states
A. Nasal Cannula
FiO2 increases approximately 2-4%/L
Provides 23-45% of O2
Maximum flow rate of 6 lpm (flow rates >6 lpm do not augment the inspired gas)
High flows can dry the nasal mucosa
Humidification is recommended for flow rates >4 lpm
B. Simple Masks
Higher potential FiO2 (provides 31-61% O2)
Flow rates between 5-10 lpm
The reservoir is the space between the mask and the patient’s face
5 lpm is needed to flush exhaled CO2 from the mask (<5 lpm is not recommended)
II. SPONTANEOUS BREATHING TRIAL (SBT)

Consists of a period of breathing through endotracheal tube without ventilator support (both continuous
positive airway pressure [CPAP] of 5 cmH2O & an open T-piece breathing system can be used] for 30-120
minutes
A. If the following are present, the patient has passed the screening test and should undergo SBT:
Stable oxygenation (PaO2/FiO2 >200) and PEEP > 5 cmH2O
Cough and airway reflexes intact
No vasopressor agents or sedatives being administered
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B. SBT is declared a failure and stopped if any of the following occur:
RR >35/min for >5 minutes
O2 saturation <90%
HR >140/min or a 20% increase or decrease from baseline
SBP <90 mmHg or >180 mmHg
Increased anxiety or diaphoresis
If at the end of the spontaneous breathing trial, the rapid shallowing breathing index (RSBI) or ratio of the RR
to tidal volume in liters (f/VT) is <105: patient has higher chances of successful extubation
III. WEANING FROM MECHANICAL VENTILATION

Weaning is the process of abruptly or gradually withdrawing ventilator support when the cause of respiratory
failure is resolving (weaning is not synonymous with extubation)
Need for mechanical ventilation is not the same as the need for artificial airway
o Weaning failure is the inability to maintain adequate respiration through an artificial airway
o Extubation failure is the inability to maintain adequate respiration after removal of artificial airway
A. Removal of Mechanical Ventilator Support Requires that a Number of Criteria be met:
Upper airway function must be intact for a patient to remain extubated
RSBI <105
Reversal of underlying cause of respiratory failure
Adequate oxygenation:
o P/F ratio >150-200 at PEEP 5-8 cm H2O
o FiO2 40-50%
o pH > 7.25
o PO2 > 60 at FiO2 < 40%
Hemodynamic stability: HR < 140, stable BP, Hgb > 8-10
Capability to initiate inspiratory effort: GCS > 13
Acceptable electrolytes
B. Additional conditions which should be met for weaning
Cessation of sedative drugs
Cessation of neuromuscular blocking agents
Absence of sepsis or marked fever
No planned general anesthesia
Adequate gas exchange
Adequate respiratory pump capacity
C. Methods of Weaning
METHOD DESCRIPTION
Brief spontaneous breathing trials with supplemental O 2
Best tolerated by patients who have undergone M for brief periods and require little
T-Piece respiratory muscle reconditioning
Initiated for 5 minutes/hour followed by a1-hour interval of rest
Trials are increased in 5-10 min/hour increments until the patient can remain
ventilator independent for 60-120 minutes, and then extubation can be attempted
CPAP Mode of weaning where patient-initiated breaths are supported with preset
pressure that is eventually titrated down until discontinuation
Mandatory backup rate is decreased by 2 to 4 breaths per minute while monitoring
blood gas parameters & RRs until < 4-6 breaths per minute are achieved
Best for patients intubated for extended periods who are likely to require gradual
SIMV respiratory muscle reconditioning
Rates > 25/min on withdrawal of mandatory ventilator breaths generally indicate
respiratory muscle fatigue and the need to combine periods of exercise with rest
Shifting to PSV, CPAP, or T-Piece trial can then be attempted before extubation
Mode of ventilation that is patient-triggered, pressure-limited and flow-cycled to
Pressure Support augment spontaneous respiratory effort
Ventilation (PSV) Well tolerated by patients who are gradually being weaned by decreasing set
pressures until 4-6 cm H2O and eventual withdrawal of ventilator support
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CHAPTER 5
GASTROENTEROLOGY
I. Approach to Patients with Gastrointestinal Conditions
1. History Taking in Gastroenterology
2. Physical Examination in Gastroenterology
3. Gastrointestinal Endoscopy
4. Approach to Ascites
II. Common Conditions in Gastroenterology
1. Peptic Ulcer Disease
2. Gastrointestinal Bleeding
3. Overview of Liver Disease
4. Viral Hepatitis
5. Alcoholic Liver Disease
6. Liver Cirrhosis
7. Acute Pancreatitis
8. Surgical Causes of Right Upper Quadrant Pain
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SECTION 1
APPROACH TO PATIENTS WITH GASTROINTESTINAL CONDITIONS
HISTORY TAKING IN GASTROENTEROLOGY
I. COMMON GASTROINTESTINAL COMPLAINTS
TERM DEFINITION
Anorexia Loss or lack of appetite
Early satiety Inability to eat a full meal
Heartburn Retrosternal burning sensation resulting from excess gastroesophageal reflux
Dysphagia Difficulty in swallowing
Odynophagia Painful swallowing
Diarrhea Condition in which feces are discharged from the bowels frequently and in a liquid form
Constipation Condition in which there is difficulty in emptying the bowels, usually associated with hardened
feces
Obstipation Complete constipation with no passage of either feces or gas
Tenesmus Intense urge with straining but little or no result
Hematemesis Vomitus of red blood or coffee-ground material
Melena Black, tarry, foul-smelling stool which usually implies bleeding proximal to the ligament of Treitz
(upper GI bleed) and that blood has been in the GI tract for at least 14 hours
Hematochezia Passage of bright red or maroon blood form the rectum which usually implies bleeding from the
colon (lower GI bleed); may also come from an upper GI source, with rapid intestinal transit
Occult GI bleeding Identified in the absence of overt bleeding by a fecal occult blood test or the presence of iron
deficiency
Jaundice Yellowing of the skin or sclerae, arising from obstruction in bile duct, liver disease, hemolysis, etc.
Other complaints Indigestion, nausea, retching, regurgitation, vomiting, excessive gas, fullness, pain, weight loss
II. DIFFERENTIALS FOR THE COMMON GASTROINTESTINAL COMPLAINTS

ABDOMINAL PAIN DIARRHEA GI BLEEDING OBSTRUCTIVE JAUNDICE
Appendicitis Infection Ulcer disease Bile duct stones
Gallstone disease Poorly absorbed sugars Esophagitis Cholangiocarcinoma
Pancreatitis Inflammatory Bowel Disease Varices Cholangitis
Diverticulitis Microscopic Colitis Vascular lesions Sclerosing cholangitis
Ulcer disease Functional Bowel Disorders Neoplasm Ampullary stenosis
Esophagitis Celiac Disease Diverticula Ampularry carcinoma
GI obstruction Pancreatic Insufficiency Hemorrhoids Pancreatitis
Inflammatory Bowel Disease Hyperthyroidism Fissures Pancreatic tumor
Functional Bowel Disorders Ischemia Inflammatory Bowel Disease
Vascular disease Endocrine tumor Infectious Colitis
Gynecologic
Renal Stone
PHYSICAL EXAMINATION IN GASTROENTEROLOGY

I. INSPECTION
Violaceous Striae Usually seen in Cushing’s syndrome
Dilated Veins May be seen in portal hypertension and in inferior vena cava obstruction
Bulging Flanks Associated with ascites
Prominent Peristaltic May be seen in patients with intestinal obstruction
Waves Can also be seen in thin individuals
II. AUSCULTATION (done prior to percussion or palpation as these may alter frequency of bowel sounds)
Borborygmi Prolonged gurgles of hyperperistalsis, aka “stomach growling”
Bruits with audible systolic and diastolic components heard near the midline
Bruits almost midway between subxiphoid area and umbilicus may suggest renal artery
stenosis
Epigastric bruits heard only during systole may be present in normal individuals
120
III. PERCUSSION
Tympany Predominant percussion tone
Due to gas in the abdomen
Dullness Scattered all over the abdomen
Signifies presence of underlying mass, organ, fluid and/or feces
Obliterated Trauble’s Percussion of left lower anterior chest wall between lung resonance above and
Space the costal margin
Signifies splenomegaly
Change in the percussion note from tympany to dullness (over lowest interspace
Splenic Percussion Sign in left anterior axillary line) on inspiration
Also signifies splenomegaly
IV. PALPATION
Involuntary rigidity Associated with peritoneal inflammation
Rebound tenderness
Shifting dullness Dullness shifting to the more dependent side is seen in ascites
Fluid wave Easily palpable impulse on the side opposite the pressure (with hands pressed
firmly on the midline of the abdomen) suggest ascites
Pain in right lower quadrant during left-sided pressure suggests appendicitis
Rovsing’s sign Also associated with referred rebound tenderness (right lower quadrant pain on
withdrawal of pressure on left side)
Psoas sign Abdominal pain on hip flexion and/or extension secondary to irritation of psoas
muscle by an inflamed appendix
Obturator sign Right hypogastric pain on internal rotation of right hip suggests irritation of
obturator muscle by an inflamed appendix
Cutaneous Hyperesthesia May also be seen in appendicitis
Sharp increase in right upper quadrant tenderness with a sudden stop in
inspiratory effort (while pressure is applied under the costal margin lateral to the
Murphy’s sign border of the rectus muscle) is seen in acute cholecystitis
Same procedure may enhance hepatic tenderness (due to multiple causes) but
pain is usually less localized
V. DIGITAL RECTAL EXAMINATION (DRE)

Sphincter Tightness May be noted in anxiety, inflammation or scaring
Sphincter Laxity May be seen in some neurologic diseases
Induration May be due to inflammation, scarring or malignancy
Skin Tags Soft, pliable tags of redundant skin at anal margin seen in some individuals
121
GASTROINTESTINAL ENDOSCOPY
DIAGNOSTIC REMARKS COMMON INDICATIONS
Endoscope inserted through the mouth Dyspepsia despite treatment
Esophagogastroduo- into the esophagus, stomach, duodenal or with signs of alarm
denoscopy (Upper bulb, and second part of the duodenum UGIB, dysphagia, refractory
Endoscopy, EGD) Best method of examining the upper vomiting
gastrointestinal mucosa Anemia, weight loss,
malabsorption
Scope inserted through anal canal into Cancer screening
the rectum and colon LGIB
Colonoscopy Gold standard for diagnosis of colonic Anemia
mucosal disease Diarrhea
Obstruction
Visualizes only the rectum and a portion Primarily used for evaluation
Flexible Sigmoidoscopy of the left colon, typically up to 60 cm of diarrhea and rectal outlet
from the anal verge bleeding
Capsule endoscopy
Small Bowel Endoscopy Push enteroscopy Obscure GI bleeding
Single- or Double-Balloon Enteroscopy Suspected Crohn’s disease
or Spiral Enteroscopy
Scope passed through the mouth to the
Endoscopic Retrograde duodenum; the ampulla of Vater is Jaundice
Cholangiopancreatography identified and cannulated; and Cholangitis
(ERCP) radiographic contrast material is injected Gallstone pancreatitis
into the bile duct and pancreatic duct Pancreatic/biliary tumor
under fluoroscopic guidance
High-frequency ultrasound transducers
Endoscopic Ultrasound incorporated into the tip of endoscope
(EUS) Obtains images of the gut wall and Staging of malignancy
adjacent organs, vessels and lymph
nodes
APPROACH TO ASCITES
I. COMMON CAUSES OF ASCITES
CONDITION GROSS APPEARANCE OF ASCITIC FLUID PROTEIN (g/L) SAAG (g/dL)
Cirrhosis Straw-colored <25 > 1.1
CHF Straw-colored Variable
Neoplasm Straw-colored, hemorrhagic, mucinous or chylous >25
TB Peritonitis Clear, turbid, hemorrhagic, chylous >25
Pyogenic Peritonitis Turbid or purulent >25 < 1.1
Nephrosis Straw-colored or chylous <25
II. PERITONEAL FLUID ANALYSIS

LABORATORY FINDING ASSOCIATED CAUSE OF ASCITES
Absolute PMN count > 250/uL
Positive gram stain or culture Infection (e.g. spontaneous/primary bacterial peritonitis)
pH < 7.0
RBC count > 50,000 Hemorrhagic ascites
(malignancy, tuberculosis, trauma, ruptured omental varix)
Increased amylase Pancreatic ascites, pancreatitis
Increased triglycerides Chylous ascites
Positive malignant cells in cytology Malignancy
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III. SERUM ASCITES-ALBUMIN GRADIENT (SAAG)
Replaced the description of exudative or transudative ascitic fluid
The gradient correlates directly with portal pressures
SAAG = serum albumin – ascitic fluid albumin
SAAG > 1.1 g/dL (or 11 g/L) SAAG < 1.1 g/dL (or 11 g/L)
Portal Hypertension:
Cirrhosis Peritoneal carcinomatosis
Cardiac ascites Infection (peritonitis, TB)
Budd-Chari Syndrome Nephrotic Syndrome
Portal Vein Thrombosis Pancreatic or biliary ascites
Venoocclusive Disease
Fatty Liver of Pregnancy
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SECTION 2
COMMON CONDITIONS IN GASTROENTEROLOGY
PEPTIC ULCER DISEASE (PUD)
I. GASTRIC MUCOSAL DEFENSE SYSTEM
A. Preepithelial
Mucus-bicarbonate-phospholipid layer to neutralize/buffer gastric acid
B. Epithelial
Mucus production
Ionic transporters for maintaining intracellular pH and bicarbonate production
Intracellular tight junctions
Heat shock proteins prevent protein denaturation and protect cells
Restitution: epithelial cells bordering a site of injury migrate to restore a damaged region
C. Subepithelial
Microvascular system/bed
Capable of angiogenesis in the event of injury
Provides micronutrients and O2
Removes toxic metabolic by-products
II. OVERVIEW OF ULCERS

GASTRIC ULCER (GU) DUODENAL ULCER (DU)
Distal to the junction between First portion of the duodenum
Usual location antrum and acid secretory (within 3 cm of pylorus)
mucosa
Risk of malignancy Common (should be biopsied) Extremely rare
Usual etiology H. pylori, NSAID-induced H. pylori, NSAID-induced
injury injury
Gastric acid secretion appears
Pathophysiology Gastric acid output normal or to be increased
decreased HCO3 secretion is significantly
decreased
Burning or gnawing discomfort
Pain that awakens the patient
Character of abdominal pain Burning or gnawing discomfort from sleep (between midnight
and 3 AM) is the most
discriminating symptom
Occurs 90 minutes to 3 hours
Pain in relation to food intake Precipitated by food after a meal
Relieved by antacids or food
Bleeding: melena or coffee-ground emesis
Penetrating ulcer: pain becomes constant, no longer relieved by
Complications antacids, radiates to the back
Perforation: sudden severe, generalized abdominal pain
Gastric output obstruction: pain worsening with meals, vomiting of
undigested food
III. HELICOBACTER PYLORI AND NSAIDS
A. Helicobacter pylori
S-shaped gram-negative microaerophilic rod with multiple sheathed flagella which can transform into coccoid form
(dormant state)
Bacterial urease aids in infection by producing ammonia from urea, which then alkalinizes surrounding pH
124
RISK FACTORS FOR HIGHER COLONIZATION PLAYS A ROLE IN THE DEVELOPMENT OF
RATES
Poor socioeconomic status PUD
Low educational attainment Gastric mucosa-associated lymphoid tissue
Crowded and unsanitary conditions (MALT) lymphoma
Gastric adenocarcinoma
B. NSAID-induced Disease
Interruption of prostaglandin synthesis can impair mucosal defense and repair leading to mucosal injury
Established risk factors
o Advanced age
o History of ulcer
o Concomitant glucocorticoid/anticoagulant/clopigodrel use
o High-dose/multiple NSAIDs
o Serious/multisystem disease
IV. FORREST CLASSIFICATION OF ULCERS

Classification of Upper GI Bleed (UGIB) used for selecting patients for endoscopic treatment
CLASSIFICATION DESCRIPTION RISK OF REBLEED
Acute Hemorrhage
Type IA Arterial spurting 100%
Type IB Arterial oozing 50%
Signs of recent hemorrhage
Type IIA Visible vessel 43%
Type IIB Adherent clot 22%
Type IIC Pigmented flat spot 10%
Lesions without active bleeding
Type III No stigmata of recent bleed; or 5%
fibrin-coated clean ulcer base
V. DIAGNOSTICS
Commonly used as a first test for documenting an ulcer
Barium studies of o DU: appears as a well-demarcated crater, most often seen in the bulb
proximal GIT o GU: discrete crater with radiating mucosal folds originating from the ulcer
margin
Allows direct visualization of the mucosa
Endoscopy (EGD) Most sensitive and specific approach for examining the upper GIT
Facilitates documentation of a mucosal defect and tissue biopsy to rule out
malignancy (GU) or H. pylori
Invasive tests (Endoscopy/Biopsy required)
Rapid Urease (prone to false negatives with recent therapy)
Histology
Tests for detection of H. Culture
pylori Non-Invasive Tests
Urea Breath Test (test of choice for documenting eradication)
Serology
Stool antigen
125
VI. MANAGEMENT OF PUD
Relief of symptoms
Promote ulcer healing
Prevent ulcer recurrence and complications
A. Acid Neutralizing/Inhibitory Drugs

CLASS EXAMPLES MECHANISM OF ACTION SIDE EFFECTS
Aluminum hydroxide Constipation
Neutralizes intragastric Diarrhea
Antacids Magnesium hydroxide acidity Avoid in patients with
CKD
Cimetidine Competitive inhibition at Headache, fatigue,
H2 Receptor Ranitidine the parietal cell H2- myalgias
Antagonists Famotidine receptor, suppresses Relatively safe
acid secretion
Covalently bind and Headache, abdominal
Omeprazole irreversibly inhibit H+, pain, diarrhea,
Proton Pump Esomeprazole K+-ATPase flatulence, dermatitis,
Inhibitors Lansoprazole Most potent acid pruritus, dry mouth,
(PPIs) Rabeprazole inhibitory agent blurred vision,
Pantoprazole Maximum efficacy if angioedema
taken before a meal
B. Cytoprotective Agents
CLASS EXAMPLES MECHANISM OF ACTION SIDE EFFECTS
Becomes a viscous
paste within the stomach
and duodenum, binding
Sucralfate Sucralfate primarily to sites of Constipation
active ulceration
Act as a physiochemical
barrier
Black stools
Bismuth- Bismuth subsalicylate Constipation
Containing (BSS, Pepto-Bismol) Mechanism is unclear Darkening of the tongue
Preparations Neurotoxicity (long-
term)
Enhancement of Diarrhea
Prostaglandin Misoprostol mucosal defense and Contraindicate in
Analogues repair pregnancy
(Misoprostol)
C. Helicobacter pylori Eradication

Antibiotic resistant strains are the most common cause for treatment failure in compliant patients
Dual therapy and shorter regimens (7-10 days) are not as effective and are not recommended
1. Triple Therapy for 14 days
DRUG DOSE
Omeprazole 20 mg BID
Any Proton Pump Inhibitor (PPI), Lansoprazole 30 mg BID
plus Esomeprazole 40 mg OD
Pantoprazole 40 mg OD
Rabeprazole 20 mg BID
Either of the following, plus Clarithromycin (first line) 500 mg BID
Metronidazole 500 mg BID
2. Non-Bismuth Quadruple (Sequential) Therapy for 14 days
PPI plus Amoxicillin for 5-7 days, followed by
PPI plus Clarithromycin and Metronidazole for 5-7 days
126
VII. PUD-RELATED COMPLICATIONS
Gastrointestinal Bleeding Most common complication of PUD
Second most common ulcer-related complication
Penetration: form of perforation in which ulcer bed tunnels into
Perforation adjacent organ
o DU: tends to penetrate posteriorly into the pancreas, leading
to pancreatitis
o GU: tends to penetrate into the left hepatic lobe
Least common ulcer-related complication
Gastric Outlet Obstruction Relative obstruction secondary to ulcer-related inflammation and
edema in the prepyloric region
GASTROINTESTINAL BLEEDING
I. COMMON CAUSES OF UPPER GASTROINTESTINAL BLEEDING (UGIB)
Most common upper GI causes: ulcer disease, gastroduodenitis, and esophagitis
Usually presents with hematemesis or melena (massive UGIB can also present with hematochezia)
A. Bleeding Peptic Ulcer Disease (BPUD)

Most common cause of UGIB
Usually secondary to NSAID use or H. pylori infection
Ulcer: a break in the mucosal surface >5mm
ECG FINDINGS RISK OF RE- MANAGEMENT DISPOSITION
BLEEDING
Clean-based ulcer -/+ No IV PPI or endoscopic Discharge
treatment
Flat pigmented spots +
Ward for 3 days
Adherent clots covering ulcer base ++ IV PPI +/- endoscopic
treatment
Platelet plug protruding from a vessel +++
wall in the base of an ulcer (sentinel IV PPI + endoscopic ICU for a day then
clot) treatment ward for 2 more
Active spurting from an ulcer ++++ days
B. Bleeding Esophageal Varices (BEV)

Second most common cause of UGIB
Usually arises due to portal hypertension from liver cirrhosis
Poorer outcomes compared to patients with other sources of UGIB
C. Hemorrhagic and Erosive Gastropathy (“Gastritis”)

Endoscopically visualized subepithelial hemorrhages and erosions
Usually seen with NSAIDs, alcohol intake and stress (serious trauma, major surgery, extensive burns, major
intracranial disease, or severe medical illness)
D. Mallory-Weiss Tear
A linear mucosal rent near or across the gastroesophageal junction that is often associated with retching, vomiting
or incessant coughing
E. Dieulafoy’s Lesion
Large-caliber arteriole that runs immediately beneath GI mucosa and bleeds via a pinpoint mucosal erosion
Seen most commonly on the lesser curvature of the proximal stomach
II. COMMON CAUSES OF LOWER GASTROINTESTINAL BLEEDING (LGIB)

Most common lower GI causes: hemorrhoids, anal fissures, diverticula, neoplasms (adenocarcinoma), ischemic
colitis, and arteriovenous malformations
Usually presents with hematochezia
127
A. Hemorrhoidal Disease
Patients commonly present for two reasons: bleeding and protruding rectal mass
Severe pain may indicate a thrombosed hemorrhoid
STAGE CHARACTERISTICS TREATMENT
Fiber supplementation
I Enlargement with bleeding Cortisone suppository
Sclerotherapy
II Protrusion with spontaneous reduction Fiber supplementation
Cortisone suppository
Fiber supplementation
Protrusion requiring manual reduction Cortisone suppository
III Banding
Operative hemorrhoidectomy
IV Fiber supplementation
Irreducible protrusion Cortisone suppository
Operative hemorrhoidectomy
B. Diverticular Disease
Hemorrhage from a colonic diverticulum: most common cause of hematochezia in patients >60 years old
Bleeding more often seen from the right colon, usually abrupt and painless
Minor/occult bleeding is not characteristic
Localization of diverticular bleeding should include colonoscopy, which may be diagnostic and therapeutic
C. Anal Fissure
Most common cause of rectal bleeding in infancy
Acquired from trauma to the anal canal following defecation
More common in the posterior anal canal
Relative ischemia in the region of the fissure leads to poor healing
III. MANAGEMENT OF BLEEDING
A. Initial Resuscitation
1. Airway Protection (intubation to prevent aspiration)

Decreased sensorium (shock, hepatic encephalopathy)
Massive hematemesis
Active variceal bleeding
2. Restoration of Intravascular Volume

IV fluids: isotonic state; lactated Ringer’s solution
Transfusion with packed RBCs (or whole blood if necessary)
3. Correction of Coagulopathy (if present)

Discontinuation of offending anti-coagulants followed by infusion of FFP
Parenteral vitamin K for prolonged PT (INR) from warfarin, liver disease
Platelet infusion if with significant thrombocytopenia
128
B. Therapy for Specific Lesions
DISEASE TREATMENT
High-dose PPIs: Omeprazole 80 mg IV bolus followed by 8 mg/hour
infusion for 72 hours (See also chapter 1)
Therapeutic endoscopy (advantage of immediate treatment)
Peptic Ulcer Disease (PUD) Surgery for intractable or recurrent bleeding
H. pylori eradication if with evidence of infection (14-day antibiotic
regimens)
Avoidance of NSAIDs if possible
1. Vasoactive Agents
Reduce portal venous pressures acutely by splanchnic vasoconstriction
Somatostatin 275 mcg IV bolus followed by 3 mg infusion over 12 hours
Octreotide 50 mcg/hour infusion
2. Non-selective Beta-Blockers
Decrease rates of recurrent bleeding
β-blockade allows unopposed alpha-receptor mediated vasoconstriction of
splanchnic vessels
propranolol 10 mg PO TID (starting dose)
3. Antibiotics for Patients with Cirrhosis to Decrease Infections (7-day course)

Ceftriaxone 1 g IV OD
Ciprofloxacin 400 mg IV q12
Variceal Hemorrhage
Levofloxacin 500 mg IV OD
Norfloxacin 400 mg PO BID
4. Endoscopic / Surgical Options

Ligation or banding: endoscopic therapy of choice as it controls active
hemorrhage (lower rates of success for gastric compared to esophageal
varices)
Sclerotherapy
Cyanoacrylate “glue” injection
Balloon tamponade with a Sengstaken-Blakemore tube or Minnesota tube
Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Liver transplantation
5. Judicious Blood Transfusion (overtransfusion may further increase portal pressures)

Stress Ulcer Prophylactic therapy: PPIs, Histamine-Receptor Antagonists and
Sucralfate
Colonic Diverticulum Mesenteric angiography with coiling
Segmental resection of the colon
Sitz baths, high-fiber diet, stool softeners
Hemorrhoids Banding
Sclerotherapy
Hemorrhoidectomy (excisional vs stapled)
Sitz baths, high-fiber diet, stool softeners, topical anesthetics
Anal Fissures For chronic fissures (>6 weeks): nifedipine or NTG ointment applied TID,
botulinum toxin type A injections
Surgery: anal dilatation and lateral internal sphincterotomy
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OVERVIEW OF LIVER DISEASE
I. BASIC PATTERNS OF LIVER DISEASE
Hepatocellular (viral, alcoholic liver disease): features of liver injury, inflammation & necrosis predominate
Cholestatic (obstructive diseases): features of inhibition of bile flow predominate
Mixed (drug-induced liver diseases): features of both
II. MAJOR RISK FACTORS FOR LIVER DISEASE

Alcohol use, personal habits, sexual activity, travel, occupation, injection drug use
Medications (including herbal compounds, birth control pills, and over-the-counter medications)
Exposure to jaundiced or other high-risk persons
Recent surgery
Remote or recent transfusion with blood and blood products
Accidental exposure to blood or needle-stick
Familial history of liver disease

SYMPTOMS OF HEPATIC DISEASE
Constitutional Symptoms Fatigue, poor appetite, weakness, nausea and malaise
Fatigue: most common and most characteristic symptom of liver disease
Liver-specific Symptoms Dark urine, light stools, itching, abdominal pain and bloating
Jaundice: hallmark of liver disease and the most reliable marker of severity
SIGNS OF HEPATIC DISEASE
Icterus Check sclerae, skin, mucous membrane below the tongue
Palmar erythema Occurs in acute and chronic liver disease; prominent in persons with cirrhosis
Spider angioma Superficial tortuous arterioles seen on the arms, face, upper torso; fill outwards
from the center (unlike telangiectasis)
See in venoocclusive disease, infiltrative disorders, hepatic malignancy,
Hepatomegaly alcoholic hepatitis
Hepatic tenderness: the most reliable physical finding in examining the liver
Splenomegaly Subtle significant finding in liver disease
Ascites Best appreciated by percussing for shifting dullness
Peripheral edema Contributing factors: hypoalbuminemia, venous insufficiency, heart failure, and
medications
First signs: change in sleep patterns, change in personality, irritability, mental
Hepatic encephalopathy dullness
Confusion, disorientation, stupor and eventually coma supervene
Acute liver failure: excitability, mania
Fetor hepaticus Slightly sweet, ammonia-like odor in patients, especially if there is porto-
venous shunting of blood
Umbilical hernia Secondary to increased intraabdominal pressures from ascites
Caput medusa Results from recannulation of umbilical vein: collateral veins radiating from
umbilicus
Hyperestrogenemia For males: gynecomastia, testicular atrophy, loss of male-pattern hair
distribution
DISEASE-ASSOCIATED FINDINGS
Wilson’s disease Kayser-Fleischer rings (golden-brown copper pigment deposited in periphery
of cornea)
Alcoholic liver disease Dupuytren contracture and parotid enlargement
Hemochromatosis Slate-gray pigmentation of skin
130
IV. DIAGNOSTICS
TESTS BASED ON DETOXIFICATION & EXCRETORY FUNCTIONS
Unconjugated (indirect) bilirubin: seen in hemolytic disorders, Crigler-Najjar and
Gilbert’s syndrome
Serum Bilirubin Conjugated (direct) bilirubin: almost always implies liver or biliary tract disease
Higher levels indicate more severe hepatocellular damage/injury in viral
hepatitis and drug-induced liver disease
Enzymes that reflect damage to hepatocytes
ALT is more specific as an indicator of liver injury than AST
Elevations of >1000 U/L occur almost exclusively in:
o Viral hepatitis
o Ischemic liver injury (prolonged hypotension or acute heart failure)
Aminotransferases o Toxin- or drug-induced liver injury
o Acute phase of biliary obstruction caused by passage of gallstone into
CBD
Patterns of liver injury:
o AST:ALT<1 in chronic viral hepatitis, non-alcoholic fatty liver disease
o AST:ALT>2 in alcoholic liver disease
o Alkaline phosphatase > aminotransferases in cholestatic conditions
Alkaline Phosphatase (ALP) Enzymes that reflect cholestasis
5’Nucleotidase Elevations of ALP greater than 4 times seen in cholestatic liver disease,
y-glutamyl Transpeptidase infiltrative liver diseases, rapid bone turnover
(GGT) Elevations in both GGT and alkaline phosphatase indicative of biliary disease
TESTS THAT MEASURE BIOSYNTHETIC FUNCTION OF LIVER
Synthesized exclusively by the hepatocytes
Half-life of 18-20 days, therefore not a good indicator of acute or mild
Serum Albumin dysfunction
Hypoalbuminema is more common in chronic liver disorders such as cirrhosis,
reflecting severe liver damage and decreased albumin synthesis
y-globulins are increased in CLD due to increased antibody synthesis to fight off
Serum Globulins intestinal bacteria that the cirrhotic liver failed to clear from the hepatic
circulation
Single best acute measure of hepatic synthetic function
All clotting factors are synthesized in the liver except for factor VIII (produced by
endothelial cells)
Clotting Factors Prothrombin time measures factors II, V, VII, X
Vitamin K-dependent factors: II, VII, IIX, X
Marked prolongation of PT >5 sec above control not corrected by IV Vitamin K
is a poor prognostic sign
IMAGING AND OTHER TESTS
Most commonly employed for imaging of the liver
Ultrasound, CT, MRI Ultrasound is first-line if initial blood tests suggest cholestasis (to check for
dilated ducts/gallstones)
MRCP, ERCP Procedures of choice for visualization of the biliary tree
Doppler US and MRI Hepatic vasculature and hemodynamics
Doppler US is first test ordered if suspecting Budd-Chari syndrome
The criterion standard in the evaluation of patients with liver disease
Subject to sampling error in focal infiltrative disorders such as hepatic
Liver Biopsy metastasis
Should not be the initial procedure in the diagnosis of cholestasis
Contraindications to percutaneous approach: significant ascites and prolonged
INR (may use transjugular approach instead)
131
V. DISEASE-SPECIFIC LABORATORY TESTS
DISEASE DIAGNOSTIC TESTS AND EXPECTED FINDINGS
Autoimmune Hepatitis Antinuclear antibody (ANA) or anti-smooth muscle antibody (SMA)
Elevated IgG levels
Primary Biliary Cirrhosis AMA (anti-mitochondrial antibody); elevated IgM levels
Primary Sclerosing p-ANCA; cholangiography
Cholangitis
Wilson’s Disease Decreased serum ceruloplasmin and increased urinary copper
Increased hepatic copper level
Hemochromatosis Elevated iron saturation and serum ferritin
Genetic testing for HFE gene mutations
Hepatocellular Cancer Elevated alpha-fetoprotein level >500; US or CT image of mass
VI. OVERVIEW OF SEROLOGY FOR VIRAL HEPATITIS

HEPATITIS A (HAV)
Anti-HAV (IgM) Diagnosis of hepatitis A during acute illness and persists for several months
(Antibody to HAV) Detected when aminotransferase activity is elevated & fecal HAV shedding still
occurring
Anti-HAV (IgG) After acute illness, anti-HAV of the IgG class remains detectable indefinitely
(Antibody to HAV) Predominates during convalescence
Marker of immunity to reinfection
HEPATITIS B (HBV)
HBsAg (Hepatitis B Surface First virologic marker detectable in serum within 1-12 weeks after infection with
Agent) HBV
Chronic HBV infection: HBsAg remains detectable beyond six months
After HBsAg disappears, anti-HBsAg becomes detectable and remains
Anti-HBs detectable indefinitely thereafter (protective antibody)
Also seen after immunization with hepatitis B vaccine (anti-HBs would be the
only serologic marker to appear)
IgM anti-HBc: predominates during the first six months after acute infection,
Anti-HBc (IgM or IgG) including anti-HBc window period
IgG anti-HBc: predominant class of anti-HBc beyond six months
An isolated reactive anti-HBc can be seen in the gap or window period
Appears concurrently with or shortly after HBsAg
Qualitative marker on HBV replication and relative infectivity
HBeAg (Hepatitis B ‘e’ HBsAg-positive serum containing HBsAg is more likely to be highly infectious
Antigen) Its disappearance may be a harbinger of clinical improvement and resolution of
infection
Persistence beyond the first 3 months of acute infection is predictive of
development of chronic infection
Anti-HBe Its appearance coincides with a period of relatively lower infectivity
HBV DNA More sensitive and quantitative indicator of HBV replication
HEPATITIS C (HCV)
Anti-HCV Diagnosis of Hepatitis C
HCV RNA Most sensitive test for HCV infection: “gold standard” in establishing a diagnosis
of HCV
HEPATITIS D (HDV)
Anti-HDV Testing for anti-HDV is useful in those with hepatitis B and severe/fulminant
disease
HEPATITIS E (HEV)
Anti-HEV (IgM/IgG) Not routinely available
132
VII. SUMMARY OF TESTS FOR VIRAL HEPATITIS
DISEASE DIAGNOSTIC TESTS AND EXPECTED FINDINGS
Hepatitis A Anti-HAV IgM
Hepatitis B
Acute infection HBsAg, IgM anti-HBc
Chronic infection HBsAg, IgG anti-HBc
Markers of replication HBeAg, HBV DNA
Hepatitis C Anti-HCV and HCV RNA
Hepatitis D (Delta) HBsAg and anti-HDV
HBV/HDV coinfection IgM anti-HBc and anti-HDV
HDV superinfection IgG anti-HBc and anti-HDV
Hepatitis E Anti-HEV
VIRAL HEPATITIS
I. ACUTE VIRAL HEPATITIS
A. Overview of Clinical Profile

FEATURE HAV HBV HCV HDV HEV
Onset Acute Insidious or acute Insidious Insidious or Acute
acute
Predominant Percutaneous, perinatal, Percutaneous,
Mode/s of Fecal-oral sexual Percutaneous sexual Fecal-oral
Transmission
Severity Mild Occasionally severe Moderate Occasionally Mild
severe
Progression to None Occasional (common if Common Common None
Chronicity perinatal)
Prognosis Excellent Variable Moderate Variable Good
IG HBIG
Prophylaxis Inactivated Recombinant vaccine None HBV vaccine Vaccine
Vaccine
Interferon, Lamivudine, PEG-IFN +
Therapy None Adefovir, PEG-IFN, Ribavirin Interferon None
Entecavir, Telbivudine, Telaprevir,
Tenofovir Boceprevir
More Chronic liver Defective virus Usually from
symptomatic/ disease from that requires contaminated
severe The only hepatitis virus chronic helper water supply
Additional Notes infection in with a DNA genome (other hepatitis C is function of after monsoon
adults types have an RNA the most HBV for flooding in
compared to genome) frequent replication and endemic areas
children indication for expression
liver transplant
B. Clinical Manifestations
SYMPTOMS AND SIGNS
Prodromal Anorexia, nausea and vomiting, fatigue, malaise, arthralgias, myalgias, headache,
Symptoms photophobia, pharyngitis, cough & coryza may precede the onset of jaundice by 1-2
weeks
Jaundice With the onset of jaundice, the constitutional prodromal symptoms usually diminish
Complete clinical and biochemical recovery occurs:
o 1-2 months after hepatitis A and E
Recovery Phase o 3-4 months after the onset of jaundice in hepatitis B and C (among healthy
adults, acute hepatitis B is self-limited in 95-99% while hepatitis C is self-
limited in only 15%)
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LABORATORY FEATURES
AST and ALT Increase during the prodromal phase of acute viral hepatitis and precede the rise in
bilirubin level
Peak levels vary from 400-4000 IU or more
Bilirubin When jaundice appears, bilirubin typically rises
Prothrombin Time Prolonged values reflect a severe hepatic synthetic defect
Alkaline Normal or mildly elevated
Phosphatase
Hypoalbuminemia Uncommon in uncomplicated acute viral hepatitis
C. Diagnosis of Acute Hepatitis

DIAGNOSTIC INTERPRETATION HBsAg IgM Anti-HAV IgM Anti-HBc Anti-HCV
Acute hepatitis B + - + -
Acute hepatitis A superimposed on + + - -
chronic hepatitis B
Acute hepatitis A and B + + + -
Acute hepatitis A - + - -
Acute hepatitis A and B (HBsAg below - + + -
detection threshold)
Acute hepatitis B (HBsAg below - - + -
detection threshold)
Acute hepatitis C - - - +
D. Sequelae of Acute Viral Hepatitis
1. Fulminant Hepatitis
Most feared complication of viral hepatitis (massive hepatic necrosis)
Primarily seen in hepatitis B, E and D (mnemonic: B-E-D-ridden for fulminant hepatitis)
Signs and symptoms of encephalopathy that may evolve to deep coma
Terminal events: brainstem compression, GI bleeding, sepsis, respiratory failure, cardiovascular collapse,
renal failure
Management: restriction of protein intake, oral lactulose or neomycin, supportive (fluids, circulation,
respiration, correction of bleeding and hypoglycemia), liver transplantation may be life-saving
2. Chronic Liver Disease (CLD)

Hepatitis A or E Neither HAV nor HEV causes chronic liver disease
Hepatitis B Chronic: persistence of HBeAg for >3 months or HBsAg for >6 months after acute hepatitis
Hepatitis C After acute HCV infection, the likelihood of remaining chronically infected approaches 90%
II. CHRONIC VIRAL HEPATITIS
A. Interpretation of Hepatitis B Serologic Markers

INTERPRETATION HBsAg Anti-HBs Anti-HBc HBeAg Anti-HBe
Acute hepatitis B, high infectivity + - IgM + -
Chronic hepatitis B, high infectivity + - IgG + -
Chronic hepatitis B, low infectivity + - IgG - +
Anti-HBc “window” - - IgM +/- +/-
Hepatitis B in remote past - - IgG - +/-
Recovery from hepatitis B - + IgG - +/-
Immunization with HBsAg (after - + - - -
vaccination)
B. Sequelae
Liver cirrhosis (see separate section on Liver Cirrhosis for more information)
Hepatocellular carcinoma (hepatitis B and C), especially for individuals who acquired hepatitis B perinatally
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C. Management
FACTORS THAT AFFECT DECISION TO TREAT AND/OR DURATION OF TREATMENT
HEPATITIS B HEPATITIS C
Clinical status (presence of cirrhosis,
compensated vs. decompensated)
Family history of hepatocellular carcinoma Detectable HCV RNA in serum
HBsAg status HCV genotype
HBV DNA titers
ALT levels
TREATMENT
Pegylated interferon (PEG IFN) once weekly Pegylated interferon (PEG IFN) + Ribavirin
SC injection o Genotype 1: 48 weeks
Lamivudine 100 mg PO OD (first successful o Genotype 2: 24 weeks
oral antiviral agent) o Most pronounced side effect of ribavirin is
Entecavir 0.5 mg PO OD (most potent of the hemolysis
antivirals)
Tenofovir 300 mg PO OD
ALCOHOLIC LIVER DISEASE

I. ETIOPATHOGENESIS
Threshold for developing alcoholic liver disease
o Men: >60-80 g/day of alcohol for 10 years
o Women: >20-40 g/day of alcohol for 10 years
o >160 g/day has a 25x increased risk of alcoholic cirrhosis
The following all contain ~12 g of alcohol:
o One bottle of beer
o Four ounces of wine
o One ounce of 80% spirits

PATHOLOGY SYMPTOMS AND SIGNS SOME LABORATORY FINDINGS
Fatty liver RUQ pain, nausea, fatigue AST or ALT increased 2 to 7-fold
AST/ALT ratio >1
Fever, spider nevi, jaundice and Bilirubin may be markedly increased
abdominal pain in alcoholic hepatitis despite only
Alcoholic hepatitis Portal hypertension, ascites, or modest elevation in alkaline
variceal bleeding can occur in the phosphatase
absence of cirrhosis PMN >5500/uL predicts severe
alcoholic hepatitis when discriminant
function >32
RUQ pain, fever, nausea and vomiting,
diarrhea, anorexia and malaise
More specific complications: ascites,
edema or upper GI hemorrhage Hypoalbuminemia
Jaundice, encephalopathy, Prolonged PT
hepatomegaly, splenomegaly Increased bilirubin
Alcoholic cirrhosis Liver edge may be firm and nodular Anemia
Scleral icterus, palmar erythema, Thrombocytopenia (due to portal HPN
spider angiomas, parotid gland and hypersplenism)
enlargement, digital clubbing, muscle CT/UTZ: nodular liver, splenomegaly,
wasting, edema and ascites venous collaterals
Males: decreased body hair, testicular
atrophy, gynecomastia
Females: menstrual abnormalities
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III. MANAGEMENT
Complete abstinence from alcohol is the cornerstone in the treatment of alcoholic liver disease
Glucocorticoids may be used for severe alcoholic hepatitis (discriminant function >32 or MELD >20)
Discriminant function = 4.6 x [PT prolongation above control in seconds] +serum bilirubin mg
dL
o Steroid dosing: prednisone 40 mg/day or prednisolone 32 mg/day for 4 weeks, then tapered over 4 weeks
o Exclusion criteria: active GI bleeding, renal failure, pancreatitis
TNF inhibitor pentoxifylline (400 mg PO TID x 4 weeks) has demonstrated improved survival in severe cases
LIVER CIRRHOSIS
I. NATURAL HISTORY
Chronic liver disease compensated cirrhosis decompensated cirrhosis death

The presence of complications differentiates decompensated from compensated cirrhosis:
o Variceal hemorrhage
o Ascites
o Hepatic encephalopathy
o Jaundice
II. CAUSES OF CIRRHOSIS

Alcoholic cirrhosis
Chronic viral hepatitis B or C
Autoimmune hepatitis
Nonalcoholic steatohepatitis
Biliary cirrhosis
Cardiac cirrhosis
Inherited metabolic liver disease (e.g., hematochromatosis, Wilson’s Disease)
III. COMPLICATIONS OF CIRRHOSIS

Spontaneous bacterial peritonitis
Hepatic encephalopathy
Portal hypertension
Portopulmonary hypertension
Hepatorenal syndrome
Hepatopulmonary syndrome
Others: malnutrition, bone disease, coagulopathy, hematologic (thrombocytopenia, neutropenia)
A. Spontaneous Bacterial Peritonitis (SBP)

Spontaneous infection of the ascitic fluid without an intra-abdominal source
Usually occurs in the setting of liver cirrhosis
Clinical features of Spontaneous Bacterial Peritonitis

o Presents as fever, altered mental status, elevated WBC, and abdominal pain/discomfort
o Most common organisms are Escherichia coli and other gut bacteria
o Isolation/growth of more than 2 organisms should raise suspicion for perforated viscus (secondary
bacterial peritonitis)
o Diagnosis: fluid sample has an absolute neutrophil count >250/uL
Treatment: Cephalosporins or Quinolones

o Cefotaxime 2 g IV q8 x 5 days
o Ofloxacin 400 mg PO BID x 8 days
o Ciprofloxacin 200 mg IV q12 x 2 days followed by ciprofloxacin 500 mg PO q 12 x 5 days
o Ceftriaxone 1 g IV q8 x 5 days
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B. Hepatic Encephalopathy
Alteration in mental status and cognitive function occurring in the presence of liver failure
In acute liver injury, development of encephalopathy is a requirement for diagnosis of fulminant hepatic failure
Encephalopathy is more commonly seen in chronic liver disease
Symptoms are due to neurotoxins that are not removed by the liver because of vascular shunting
Clinical features of Hepatic Encephalopathy

o Symptoms: confused, changes in behavior, violent, difficult to manage, sleepy and difficult to rouse
o Asterixis or liver flap: sudden forward movement of the wrist after it is bent back on an extended arm
(cannot be elicited if already comatose)
o Cerebral herniation is a feared companion of brain edema
o Correlation between severity of liver disease and serum ammonia levels is often poor
GRADE LEVEL OF PERSONALITY AND INTELLECT NEUROLOGIC
CONSCIOUSNESS ABNORMALITIES
0 Normal Normal Normal
1 Inverted sleep pattern, Forgetful, mild confusion, agitation, Tremor, apraxia,
restless irritable incoordination, impaired
handwriting
Disorientation to time, amnesia, Asterixis, dysarthria,
2 Lethargic, slow responses decreased inhibitions, inappropriate hypoactive reflexes
behavior
Somnolent but can be Asterixis, hyperactive
3 aroused, confused Disorientation to place, aggressive reflexes, Babinski’s
sign, muscle rigidity
4 Coma Nil Decerebrate
Precipitating Events in Hepatic Encephalopathy

o Hypokalemia: hypokalemia causes increased ammoniagenesis (alkaline tide)
o Infection
o Increased dietary protein load
o Electrolyte disturbances
o GI bleeding
Treatment of Hepatic Encephalopathy

Nutrition Protein restriction is discouraged as it has negative impact on overall nutrition
Replace animal-based protein with vegetable-based protein in the diet
Mainstay of treatment for encephalopathy
Initial dose: 30-40 mL orally, once or twice daily (dose may be increased as
tolerated)
Lactulose Goal is to promote 2-3 soft stools per day
Mechanisms of action:
o Colonic acidification
o Catharsis
Adjunctive to lactulose
Poorly absorbed antibiotics:
Antibiotics o Neomycin 250 mg BID-QID
o Metronidazole 250-500 mg TID (given alternately to reduce individual side
effects)
Rifamixin 550 mg BID has been very effective as well, with a better safety profile
Supportive Management/correction of the above-mentioned precipitating factors
Zinc supplementation may be helpful
C. Portal Hypertension (HPN)

Elevation of hepatic venous pressure gradient >5 mmHg
Development of portal hypertension is usually revealed by the presence of thrombocytopenia, splenomegaly and
development of ascites, encephalopathy and/or esophageal varices with or without bleeding
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Classification of Portal Hypertension
PRE-HEPATIC HEPATIC POST-HEPATIC
Affects the portal venous system Most common: can be presinusoidal, Affects the hepatic veins and venous
before it enters the liver sinusoidal, postsinusoidal damage to the heart
Presinusoidal Budd-Chiari syndrome
Schistosomiasis Inferior vena caval webs
Portal vein thrombosis Congenital hepatic fibrosis Cardiac causes
Splenic vein thrombosis Sinusoidal Restrictive cardiomyopathy
Massive splenomegaly (Banti’s Cirrhosis Constrictive pericarditis
syndrome) Alcoholic hepatitis Severe CHF
Postsinusoidal
Hepatic sinusoidal obstruction
(venoocclusive syndrome)
Complications of Portal Hypertension

GASTROESOPHAGEAL VARICES
Resistance to portal flow leads to increased resistance in portal pressure
Mechanism Decreased splanchnic arteriolar resistance leads to increased splanchnic flow (increased
portal blood flow)
Treatment See table in separate section on Management on GI bleeding
ASCITES
Due to portal HPN, there will be vasodilation of the splanchnic arterial system, resulting in:
Increased splanchnic pressure due to increased portal venous flow ascites
Mechanism Underfilling of arterial system RAAS activation hyperaldosternism Na+/H2O
retention ascites
Decreased synthetic function of the liver hypoalbuminemia decreased oncotic
pressure ascites
Small amount of ascites: dietary sodium restriction (<2 g of sodium/day, avoid canned or
processed foods)
Moderate amount of ascites: diuretics with 100 mg spironolactone and 40 mg furosemide
Treatment as the isokalemic dose (up to a maximum of 600 mg/day and 160 mg/day, respectively)
Refractory ascites: repeated large-volume paracentesis with albumin infusion, TIPS
procedure (TIPS does not improve survival and may precipitate hepatic encephalopathy,
liver transplantation)
HYPERSPLENISM
Mechanism Hypersplenism with the development of thrombocytopenia is a common feature of
patients with cirrhosis and is usually the first indication of portal hypertension
Splenomegaly itself usually requires no specific treatment
Treatment Supportive transfusion with platelet concentrate as necessary during episodes of
bleeding
IV. RISK STRATIFICATION IN HEPATIC DISEASES
A. Child Pugh Score

Stratifies patients in risk groups
Predicts likelihood of major complications of cirrhosis (e.g., variceal bleeding, SBP)
PARAMETER 1 2 3
Serum Bilirubin umol/L <34 34-51 >51
mg/dL <2.0 2.0 – 3.0 >3.0
Serum Albumin g/L >35 30 - 35 < 30
g/dL >3.5 3.0 – 3.5 < 3.0
Prothrombin Time Seconds 0–4 4–6 >6
INR < 1.7 1.7 – 2.3 > 2.3
Ascites None Easily controlled Poorly controlled
Hepatic Encephalopathy None Minimal Advanced
Interpretation:
o Class A = scores 5-6
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o Class B = score of 7-9
o Class C = scores of 10-15
Decompensation indicates cirrhosis with a score of > 7 (this level has been the accepted criterion for listing a
patient for liver transplantation)
B. Model for End-Stage Liver Disease MELD) Score

Scoring system to predict prognosis of patients with liver disease and portal hypertension
This score is now used for prioritizing allocation for liver transplantation
Calculated using three non-invasive variables:
o PT-INR
o Serum bilirubin
o Serum creatinine
ACUTE PANCREATITIS
I. ETIOPATHOGENESIS
Inflammation of the pancreas due to activation of pancreatic enzymes within the pancreas
The pathologic spectrum of acute pancreatitis
o Interstitial pancreatitis: mild and self-limited disorder
o Necrotizing pancreatitis: more severe form
Common etiologies (G-A-T-E-D):
o Gallstones: most common cause
o Alcohol: 2nd most common cause
o HyperTriglycerides (usually with serum triglycerides >1000 mg/dL)
o Endoscopic retrograde cholangiopancratography (ERCP)
o Drugs
o Trauma
o Postoperative
o Sphincter of Oddi dysfunction
For recurrent attacks of pancreatitis, the two most common etiologies: alcohol and cholelithiasis
Autodigestion: currently accepted pathogenic theory
Proteolytic enzymes (e.g., trypsinogen, chymotrypsinogen, proelastase) are activated in the pancreas rather than
in the intestinal lumen
II. CLINICAL MANIFESTATIONS OF PANCREATITIS
A. Symptoms and Signs of Acute Pancreatitis

SYMPTOMS
Major symptom of acute pancreatitis
Quality: steady and boring in character
Abdominal pain Location: epigastrium and peiumbilical region
Radiation: back, chest, flanks, lower abdomen
More intense when supine
Relieved upon sitting with the trunk flexed and knees drawn up
Other symptoms Nausea, vomiting, and abdominal distention
SIGNS
General PE Distressed and anxious patient
Low-grade fever, tachycardia, and hypotension are fairly common
Hypovolemia secondary to exudation of blood and plasma proteins into
Shock the retroperitoneum
Systemic effects of proteolytic and lipolytic enzymes released into the
circulation
Abdominal Tenderness Compared with the intense pain, this sign may be unimpressive
Bowel Sounds Decreased or absent
Jaundice (infrequent) Due to edema of the pancreatic head with compression of the
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intrapancreatic portion of the common bile duct (CBD)
Pulmonary findings Basilar rates, atelectasis, pleural effusion (most frequently left sided)
Cullen’s Sign Blue discoloration around the umbilicus (results from hemoperitoneum)
Turner’s Sign Blue-red-purple or green-brown discoloration of the flanks (reflects tissue
catabolism of hemoglobin)
B. Revised Atlanta Definitions of Morphologic Features of Acute Pancreatitis

MORPHOLOGIC FEATURE DEFINITION
Interstitial Pancreatitis Acute inflammation of pancreatic parenchyma & peripancreatic tissues
No recognizable tissue necrosis
Necrotizing Pancreatitis Inflammation associated with parenchymal and/or peripancreatic necrosis
Peripancreatic fluid associated with interstitial edematous pancreatitis
Acute Pancreatic Fluid No associated necrosis
Collection Applies only to areas of fluid seen within the first 4 weeks after onset of
interstitial edematous pancreatitis and without features of a pseudocyst
Encapsulated collection of fluid with a well-defined inflammatory wall
Pancreatic pseudocyst usually outside the pancreas with minimal or no necrosis
Occurs > 4 weeks after onset of interstitial edematous pancreatitis
Acute necrotic collection Collection containing variable amounts of both fluid and necrosis
(ANC) associated with necrotizing pancreatitis
Mature, encapsulated collection of pancreatic and/or peripancreatic
Walled-off Necrosis (WON) necrosis that has developed a well-defined inflammatory wall
Usually occurs > 4 weeks after onset of necrotizing pancreatitis
C. Revised Atlanta Classification: Clinical Course, Definitions and Classifications
1. Phases of Acute Pancreatitis

Severity is defined by clinical parameters, rather than morphologic
findings
Early Most exhibit SIRS and are predisposed to organ failure
(<2 weeks) Three organ systems should be assessed to define organ failure:
respiratory, cardiovascular, and renal
Persistent organ failure (>48 hours): most important clinical finding with
regard to severity of the acute pancreatitis episode
Characterized by a protracted course of illness and may require imaging
Late to evaluate for local complications
(>2 weeks) Important clinical parameter of severity: persistent organ failure
May require supportive measures (dialysis, ventilator support, TPN)
2. Severity of Acute Pancreatitis

Without local complications or organ failure
Self-limited disease and subsides within 3-7 days after treatment is
Mild instituted
Oral intake may be resumed if patient is hungry, has normal bowel
function and has no nausea/vomiting
Moderately Severe Characterized by transient organ failure (resolves in <48 hours) or local or
systemic complications in the absence of persistent organ failure
Persistent organ failure (>48 hours)
Severe CT scan or MRI should be obtained to assess for necrosis and/or
complications
3. Imaging in Acute Pancreatitis

Two types of pancreatitis are recognized on imaging: interstitial or necrotizing
CT imaging: best evaluated 3-5 days into hospitalization when patients are not responding to
supportive care to look for local complications such as necrosis
III. DIAGNOSTICS
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Acute pancreatitis: increased level of serum amylase and lipase (more than 3-fold)
Amylase Returns to normal after 3-7 days
Amylase elevations in serum and urine occur in many conditions other than
pancreatitis
Acute pancreatitis: increased level of serum amylase and lipase (more than 3-fold)
Lipase Preferred test (more specific than amylase)
Elevated for 7-14 days
Complete blood count Leukocytosis (15,000-20,000/uL)
Hemoconcentration with hematocrit values >44%
Renal function Azotemia with BUN > 22mg/dL: due to loss of plasma into the retroperitoneal space
and peritoneal cavity
Hyperglycemia: due to decreased insulin release, increased glucagon release,
increase output of adrenal glucocorticoids and catecholamines
Hypocalcemia: saponification
Serum chemistry Hyperbilirubinemia
Serum alkaline phosphatase and aspartate aminotransferase levels are transiently
elevated
Markedly elevated serum LDH levels: poor prognosis
Hypertriglyceridemia
ABG Hypoxemia (arterial PO2 < 60 mmHg): may herald the onset of ARDS
Helpful in indicating the severity of acute pancreatitis and the risk of morbidity and
Abdominal CT Scan mortality
Aids in evaluating for complications of acute pancreatitis
Sonography Useful in acute pancreatitis to evaluate the gallbladder if gallstone disease is
suspected
IV. DEFINING SEVERE ACUTE PANCREATITIS

RISK FACTORS FOR SEVERE DISEASE
Age > 60 years
Obesity, BMI >30
Comorbid disease (Charlson Comorbidity Index)
MARKERS OF SEVERITY AT ADMISSION OR WITHIN 24 HOURS
SIRS
APACHE II
Hemoconcentration (Hematocrit > 44%)
Admission BUN (>22 mg/dL)
BISAP (> 3 of these factors: associated with increased risk for in-hospital mortality)
o B: BUN >25 mg/dL
o I: Impaired Mental Status (GCS <15)
o S: SIRS: > 2 of 4 present
o A: Age > 60 years
o P: Pleural effusion
Organ Failure (Modified Marshall Score)
o Cardiovascular: SBP < 90 mmHg, HR > 130 bpm
o Pulmonary: PaO2 < 60 mmHg
o Renal: serum creatinine > 2.0 mg/dL
MARKERS OF SEVERITY DURING HOSPITALIZATION
Persistent organ failure (>48 hours)
Pancreatic necrosis
V. MANAGEMENT
Usually, the disease is self-limited and subsides spontaneously
Resolution occurs within 3-7 days after treatment is instituted
Conventional Analgesics for pain
Measures No oral alimentation (NPO)
Fluid Resuscitation The most important treatment intervention: safe, aggressive IV fluid resuscitation
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Initial IVF: LR or pNSS at 15-20 cc/kg bolus, followed by 3mg/kg/hr to maintain urine
output >0.5cc/kg/hr
Targeted resuscitation strategy: measure hematocrit and BUN every 8-12 hours to
ensure adequacy of fluid resuscitation and monitor response to therapy
Antibiotics Prophylactic antibiotics have no role in either interstitial or necrotizing pancreatitis
ERCP For severe acute biliary pancreatitis with organ failure and/or cholangitis
No abdominal pain, nausea or vomiting
Resumption of Diet Patient is hungry
Normal bowel sounds
VI. COMPLICATIONS
LOCAL COMPLICATIONS SYSTEMIC COMPLICATIONS
Pulmonary: ARDS, effusion, pneumonitis
Necrosis (sterile or infected) Cardiovascular: hypotension, sudden death
Pancreatic fluid collections (pseudocyst, abscess) Hematologic: disseminated intravascular coagulation
Pancreatic ascites Gastrointestinal: ulcer formation, gastritis
Obstructive jaundice Renal: oliguria, azotemia, acute tubular necrosis
Metabolic: hyperglycemia, hypocalcemia
SURGICAL CAUSES OF RIGHT UPPER QUADRANT PAIN

I. DIFFERENTIALS FOR RIGHT UPPER QUADRANT PAIN
DIFFERENTIAL DESCRIPTION
Divided into two major types:
Cholelithiasis o Cholesterol stones (80%)
(“Gallstones”) o Pigment stones (< 20%)
Ultrasonography: very accurate in the identification of cholelithiasis
Most specific and characteristic symptom of gallstone disease: biliary colic
Passage of stones in the common bile duct (CBD)
CBD stones should be suspected in gallstone patients who have any of the following
Choledocholelithiasis risk factors:
o History of jaundice or pancreatitis
o Abnormal tests of liver function
o Ultrasonographic or MRCP evidence of a dilated CBD or stones in the duct
Acute inflammation of the gallbladder wall usually follow obstruction of the cystic duct
by a stone
Acute Cholecystitis Ultrasonography demonstrates calculi in 90-95% and is useful for detection of signs of
gallbladder inflammation: thickening of the wall, pericholecystic fluid and dilation of the
bile duct
Bacterial infection superimposed on an obstruction of the biliary tree most commonly
Ascending Cholangitis from a gallstone
Medical +/- surgical emergency
II. CLINICAL MANIFESTATIONS OF BILIARY TRACT PATHOLOGIES

Most specific and characteristic symptom of gallstone disease
Steady epigastric or RUQ pain, radiation to intrascapular area, right scapula or
shoulder
Begins quite suddenly and may persist with severe intensity for 15 minutes to 5 hours
Biliary colic Subsides gradually or rapidly
Persistence of pain beyond 5 hours should raise the suspicion of acute cholecystitis
May be precipitated by:
o Eating a fatty meal
o Consumption of a large meal following a period of prolonged fasting
o Eating a normal meal
Murphy’s sign Deep inspiration or cough during subcostal palpation of the RUQ usually produces
increased pain and inspiratory arrest
142
Usually in acute cholecystitis
Rare complication
Mirizzi’s Syndrome Gallstone becomes impacted in the cystic duct or neck of the gallbladder causing
compression of the common bile duct (CBD), resulting in CBD obstruction and
jaundice
Courvoisier’s Law A palpable enlarged gall bladder suggests that the biliary obstruction is secondary to
underlying malignancy
Triad of Acute Sudden RUQ tenderness
Cholecystitis Fever
Leukocytosis
Charcot’s Triad of Biliary (RUQ) pain
Acute Cholangitis Jaundice
Spiking fevers with chills
Biliary (RUQ) pain
Reynolds’ Pentad of Jaundice
Acute Cholangitis Fever
Shock
Altered mental status
Nausea and vomiting
Other symptoms Jaundice usually if with CBD obstruction
Fever or chills with biliary pain imply a complication: cholecystitis, pancreatitis,
cholangitis
III. DIAGNOSTICS
Bilirubin, Alkaline Elevated levels suggest common bile duct stone
Phosphatase
Rapid, accurate identification of gallstones (>95%)
Gallbladder Ultrasound Procedure of choice for detection of stones
Limitations: bowel gas, massive obesity, ascites
Pathognomonic findings in:
o Calcified gallstones
Plain Abdominal X-Ray o Limey bile, porcelain GB
o Emphysematous cholecystitis
o Gallstone ileus
Limitations: generally low-yield; contraindicated in pregnancy
Magnetic Resonance Useful modality for visualizing pancreatic and biliary ducts
Cholangiopancreatography Cannot offer therapeutic intervention
(MRCP)
Endoscopic Retrograde Best visualization of distal biliary tract
Cholangiopancreatography Cholangiogram of choice in: absence of dilated ducts, pancreatic or ampullary
(ERCP) disease, prior biliary surgery, endoscopic sphincterotomy is a treatment possibility
Can be complicated by pancreatitis, cholangitis or perforation
Pecutaneous Transhepatic Best visualization of proximal biliary tract
Cholangiogram Can provide biliary of drainage
Indicated when ERCP is contraindicated or has failed
IV. MANAGEMENT
A. Cholelithiasis (Gallstones)
Laparoscopic cholecystectomy: “gold standard” for treating symptomatic cholelithiasis
Ursodeoxycholic acid (UDCA) 10-15 mg/kg per day
o Used for cholesterol stones: therapy should be limited to radiolucent stones <5mm in diameter
o Mechanism: decreases cholesterol saturation of bile and retards cholesterol crystal nucleation
o Pigment stones are not responsive to UDCA therapy
o Relatively expensive and requires long-term treatment (up to 2 years for complete dissolution)
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B. Choledocholithiasis
Endoscopic biliary sphincterotomy (EBS) followed by spontaneous passage or stone extraction: treatment of
choice, especially in elderly or poor-risk patients
Laparoscopic cholecystectomy and ERCP have decreased the incidence of complicated biliary tract disease and
the need for choledocholithotomy and T-tube drainage of the bile ducts
C. Acute Cholecystitis
Cholecystectomy: mainstay of therapy for acute cholecystitis and its complications
Meperidine or NSAIDs: usually employed for analgesia because they may produce less spasm of the sphincter of
Oddi than drugs such as morphine
Intravenous antibiotic therapy for severe acute cholecystitis: guided by the most common organisms likely to be
present (E. coli, Klebseilla spp., and Streptococcus spp.)
D. Ascending Cholangitis
ERCP with endoscopic sphincterotomy: preferred initial procedure for both establishing a definitive diagnosis and
providing effective therapy
Endoscopic management of bacterial cholangitis is as effective as surgical intervention
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CHAPTER 6
INFECTIOUS DISEASES
I. Introduction to Infectious Diseases
1. Antibacterial Agents
2. Fever of Unknown Origin
3. Fever and Rash
II. Common Infectious Disease Conditions
1. Dengue
2. Malaria
3. Typhoid Fever
4. Leptospirosis
5. Schistosomiasis
6. Tetanus
7. Rabies
8. Infective Endocarditis
9. Human Immunodeficiency Virus: AIDS and Related
Disorders
10. Sexually Transmitted Infections
III. Immunization
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SECTION 1
INTRODUCTION TO INFECTIOUS DISEASES
ANTI-BACTERIAL AGENTS
I. BETA-LACTAMS
EXAMPLES MECHANISM ORGANISMS COVERED COMMON DOSAGES
OF ACTION
PENICILLINS
Narrow Spectrum Syphilis:
Penicillins: Highly effective against gram-positive cocci Pen G 2.4 Million units IM as
except penicillinase-producing bacteria, single dose (SD)
Penicillin G (IV form) meningococci, spirochetes, anaerobic
Penicillin V (Oral) cocci Prophylaxis for Recurrent
Rheumatic Fever:
Pen V 250 mg PO BID
Very Narrow
Spectrum Penicillins:
Active against most penicillinase-producing Cellulitis:
Nafcillin staphylococci Cloxacillin 500 mg QID
Oxacillin Inhibit cell wall
Cloxacillin synthesis:
Dicloxacillin
Extended-Spectrum Binds to
Penicillins: penicillin binding Effective against gram-positive cocci, Cellulitis:
proteins (PBP) enterococci and Listeria monocytogenes Amoxicillin 500 mg TIC
Ampicillin
Amoxicillin
Bone & Joint; Skin Structure
Antipseudomonal Sulbenicillin, Carbenicillin and Ticarcillin – Infections:
Penicillins: active against P. aeruginosa, P. vulgaris, Ticarcillin/Clavulanate 3.1 g IV
Providencia, Morganella and Enterobacter q4-q6
Sulbencillin sp. but less potent than the extended-
Carbenicillin spectrum penicillins against Streptococci Severe infections;
Ticarcillin and Enterococci Nosocomial Pneumonia:
Piperacillin Piperacilllin/Tazobactam 4.5 g
IV q6 (CrCl >40 mL/min)
CEPHALOSPORINS
Prophylaxis for
First-Generation: Cardiovascular and General
Active against most gram-positive cocci Surgeries (Biliary Tract,
Cefazolin including penicillin-resistant S. aureus but Esophageal, Appendectomy
Cephalexin not against enterococcus, Methicillin- or Laparoscopic Surgery):
Cephalothin resistant S. aureus (MRSA) and Methicillin- Usually Cefazolin 1-2 g IV pre-
Cefadroxil resistant S. epidermidis (MRSE) op (single dose)
Cephapirin
Inhibit cell wall Respiratory infections:
synthesis, but Cephalexin 250 mg PO q6
Second-Generation: are less Cefoxitin – resistant to beta-lactamase-
susceptible to producing gram-negative bacilli Prophylaxis for Non-
Cefoxitin penicillinase Perforated Appendicitis:
Cefaclor Improved activity against H. influenza, M. Cefoxicillin 1-2 g IV pre-op
Cefuroxime catarrhalis, Neisseria meningitides and N.
Cefamandole gonorrhea Pharyngitis/Tonsillitis:
Cefonizid Cefuroxime 250 mg PO q12 for
Cefotetan Enhanced activity against staphylococci, 10 days
Cefprozil non-enterococci streptococci and some
Enterbacteriaceae
146
Third-Generation: Effective against S. pneumoniae, S.
pyrogenes and other streptococci (with the
Ceftriaxone exception of Ceftazidime) and have CAP Mod risk:
Ceftazidime modest activity against Methicillin-sensitive Ceftriaxone 2g IV q24
Cefixime S. aureus (MSSA)
Ceftizoxime CAP High risk + Risk for P.
Cefpodoxime proxetil Excellent activity against N. gonorrhea, H. aeruginosa infection:
Cefotaxime influenza, M. catarrhalis and Ceftazidime 2 g Iv q8
Cefoperazone Enterobacteriaceae
Moxalactam
Active against both aerobic gram-positive
Fourth-generation: organisms (but not MRSA) and gram- CAP High risk + Risk for P.
(widest spectrum) negative organisms, including P. aeruginosa infection:
aeruginosa Cefepime 1-2 g IV q8-12 up to
Cefepime 21 days
Cefpirome Inactive against MRSA, MRSE,
Enterococcus sp., B. fragilis and ESBL
Specifically developed to target resistant
strains of bacteria
Ceftobiprole – active against MRSA,

Fifth-generation: Penicillin-resistant S. pneumoniae, P.
aeruginosa and enterococci Skin & soft tissue infections:
Ceftobiprole Ceftobiprole 500 mg IV
Ceftaroline fosamil Ceftaroline fosamil – for acute bacterial infusion q12
skin and skin structure infections (ABSSSI)
caused by MSSA, MRSA, S. pyrogenes, E.
coli, K. pneumoniae and CAP caused by S.
pneumoniae, S. aureus, H. influenxa, K.
pneumoniae and E. coli
CARBAPENEM
Nosocomial infections caused by multiple-
Inhibit cell wall resistant and complicated polymicrobial Intraabdominal infections:
Meropenem synthesis, and infections caused by aerobic gram-positive, Meropenem 1 g IV q8;
Imipenem are highly gram-negative organisms, anaerobic Imipenem 500 mg IV q6 or 1 g
Doripenem resistant to bacteria and ESBL-positive organisms. IV q8 for 4-7 days
Ertapenem degradation by
beta-lactamases All are recommended for pseudomonal Complicated skin/skin
infections except Ertapenem structure infections:
Meropenem 500 mg IV q8
MONOBACTAMS
Inhibit cell wall Activity limited to gram-negative bacilli
Aztreonam synthesis (binds including most Enterobacteriaceae, Pseudomonal infections:
to PBP3) Aeromonas sp., N. gonorrhea, H. influenza Aztreonam 2 g IV/IM q6-8
and P. aeruginosa
II. AMINOCYCLITOLS AND AMINOGLYCOSIDES

EXAMPLES MECHANISM OF ORGANISMS COVERED COMMON DOSAGES
ACTION
AMINOCYCLITOLS
Prophylaxis for Colorectal
Inhibit formation Active against aerobic gram-negative bacilli; Surgery:
of initiation most are active against P. aeruginosa, E. coli, Neomycin + Erythromycin
complex and Klebsiella and Proteus sp. base 1 g each PO at 1, 2,
Neomycin cause misreading and 11 pm on the day
of mRNA (30S Synergistic against staphylococcal, before surgery or Neomycin
inhibitor) streptococcal and enterococcal endocarditis 2 g + Metronidazole 2 g at 7
and 11 pm on the day
before surgery
147
AMINOGLYCOSIDES
In addition to an
Active against aerobic gram-negative bacilli; antipseudomonal beta-
Amikacin Inhibit formation most are active against P. aeruginosa, E. coli, lactam or carbapenem in
Streptomycin of initiation Klebsiella and Proteus sp. HAP:
Tobramycin complex and Useful combination treatment for serious Amikacin 20 mg/kg/day IV
Kanamycin cause misreading gram-negative infections
Netilmycin of mRNA (30S Tuberculosis:
inhibitor) Synergistic against Staphylococcal, Streptomycin 15 (12-18)
Streptococcal and Enterococcal endocarditis mg/kg IM per day (max 1
g/day)
III. BETA-LACTAMASE INHIBITORS

ACTION
Clavulanic acid
(usually with Inhibits beta- Exacerbation of chronic
Amoxicillin, Ticarcillin) lactamases which bronchitis:
then restores the Against Beta-lactamase producing strains of Co-amoxiclav 1 g BID
Sulbactam antibacterial staphylococci, gonococci, H. influenza, M.
(usually with activity of catarrhalis, Bacteroides, Klebsiella sp. and E. Severe infections;
Ampicillin) amoxicillin, coli Nosocomial Pneumonia:
ampicillin, Piperacillin/Tazobactam 4.5
Tazobactam ticarcillin and g IV q6 (CrCl >40 mL/min)
(usually with piperacillin
Piperacillin)
IV. CHLORAMPHENICOL
ACTION
Fully susceptible typhoid:
Inhibition of Aerobic and anaerobic bacteria
peptide bond Severe and complicated:
Chloramphenicol formation at the Standard therapy for typhoid fever, ampicillin- 100 mg/kg IV x 14-21 days
50S subunit resistant H. influenza and intraocular
infections Uncomplicated:
50-75 mg/kg x 14-21 days
V. MACROLIDES
ACTION
Acute bronchitis:
Azithromycin 500 mg PO
BID day 1 then 250 mg PO
Azithromycin OD for days 2-5
Cervicitis; Chancroid:
Azithromycin 500 mg PO
Prevents Active against aerobic gram-positive cocci single dose
translocation at and bacilli, Legionella, Mycoplasma, Chancroid:
the 50S subunit Chlamydia and some gram-negative Erythromycin 500 mg PO
organisms including Bordetella pertussis, H. QID for 7 days
ducreyi and C. jejuni
Erythromycin Alternative for
nongonococcal urethritis:
Erythromycin base 500 mg
PO QID for 7 days;
Erythromycin ethylsuccinate
800 mg PO QID for 7 days
148
Exacerbation of chronic
Newer Macrolides bronchitis:
Clarithromycin Clarithromycin 500 mg PO
Roxithromycin BID for 7 days
Josamycin
Telithromycin H. pylori: (together with
Fidaxomicin Bismuth and Amoxicillin)
Clarithromycin 500 mg BID
for 2 weeks
VI. GLYCOPEPTIDES
ACTION
Inhibit cell wall MRSA Infections:
mucopeptide Active against MSSA, MRSA, coagulase- Vancomycin 15-20 mg/kg IV
Vancomycin formation by negative staphylococci, enterococci, q12 (adjust accordingly
binding D-ala D- streptococci, C. diphtheria (JK Group), C. based on creatinine
ala portion cell difficile and Listeria clearance)
wall precursors
VII. LINCOSAMIDES
ACTION
CA MRSA:
Clindamycin 600 mg IV q6-8
Bacterial vaginosis: Clindamycin cream 2%,

Useful for aerobic and 1 full applicator (5g) intravaginally HS for 7
Clindamycin Blocks peptide anaerobic gram-positive days
Lincomycin bond formation at cocci, some anaerobic Alternative: Clindamycin 300 mg PO BID for 7
50S ribosomal gram-negative bacilli and days or Clindamycin ovules 100 mg
subunit protozoans intravaginally HS for 3 days
Add-on therapy to Aspiration Pneumonia

(except in B-lactams that already have
anaerobic activity):
Clindamycin 450-900 mg IV q8
VIII. NITROMIDAZOLES
ACTION
Bacterial Vaginosis:
Metronidazole 500 mg PO BID for 7 days or
Metronidazole gel 0.75%, 1 full applicator (5
g) intravaginally OD for 7 days
Forms toxic Trichomoniasis:

Metronizadole metabolites in the Excellent activity against Metronidazole 2 g PO SD
Secnidazole bacterial cell that anaerobes and protozoans Alternative: Metronidazole 500 mg BID x 7
damage DNA days
Acute gastroenteritis by B. hominis:

Metronidazole 750 mg PO TID x 10 days
Pseudomembranous colitis (C. difficile):

Metronidazole 500 mg PO TID for 10 days
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IX. OXAZOLIDINONES
ACTION
Protein synthesis Active against S. aureus, S.
Linezolid inhibitors: epidermidis, S. Soft tissue infections:
disrupts mRNA pneumoniae, E. faecalis, Linezolid 600 mg PO/IV q12
translation and E. faecium
X. QUINOLONES
EXAMPLES MECHANISM OF ORGANISMS COMMON DOSAGES
ACTION COVERED
First Generation:
Usually for UTI and
Cinoxacin diarrheal diseases Not available locally
Nalidixic acid among children
Oxolinic acid
Pipemidic acid
Alternative for acute uncomplicated cystitis:
Ciprofloxacin 250 mg BID PO for 3 days;
Second Generation: Active against Norfloxacin 400 mg BID PO for 3 days
Enterobacteriaceae and
Ciprofloxacin Haemophilus sp., N. Primary treatment for uncomplicated acute
Norfloxacin gonorrhea & M. pyelonephritis:
Ofloxacin catarrhalis, C. Ciprofloxacin 500 mg BID for 7-10 days
Lomefloxacin Blocks bacterial trachomatis, and H.
Pefloxacin DNA synthesis by ducreyi Salmonella gastroenteritis:
Rufloxacin inhibiting Ciprofloxacin 500 mg PO OD for 7-10 days
bacterial
topoisomerase II Shigellosis:
(DNA gyrase) Ciprofloxacin 750 mg PO OD for 3 days
and Add-on to an IV non-antipseudomonal beta-
topoisomerase IV lactam in Moderate or High Risk CAP:
Levofloxacin 500 mg PO/IV OD for 7-14 days or
Broadened activity 750 mg PO/IV for 5 days
Third Generation: against anaerobes,
intracellular pathogens & Primary treatment for uncomplicated acute
Levofloxacin some gram-positive and pyelonephritis:
gram-negative aerobes Levofloxacin 250 mg OD PO for 7-10 days or 750
mg OD PO for 5 days
Salmonella gastroenteritis:
Levofloxacin 500 mg PO OD x 7-10 days
Highly effective against
Fourth Generation: both typical and atypical
respiratory pathogens Add-on to an IV non-antipseudomonal beta-
Moxifloxacin lactam in Moderate or High Risk CAP:
Gatifloxacin Moxifloxacin – most Moxifloxacin 400 mg PO/IV OD x 10 days
potent against S.
pneumoniae
XI. NITROFURANS
ACTION COVERED
Inactivates
Nitrofurantoin bacterial Usually for the treatment Acute uncomplicated cystitis:
Nifuroxazide ribosomal of uncomplicated lower Nitrofurantoin monohydrate 100 mg BID PO x 5
Furazolidone proteins and UTI days or Nitrofurantoin macrocrystals 100 mg QID
other PO x 5 days
macromolecules
150
resulting to
inhibition of DNA,
RNA, protein and
cell wall
synthesis
XII. TETRACYCLINES
ACTION COVERED
Drug of choice for V.
cholera, V. vulnificus, B.
burgdorferi, some Cervicitis/Nongonococcal urethritis/
Aeromonas and Chlamydia infections:
Doxycycline Binds to 30S Xanthomas sp., Doxycycline 100 mg PO BID x 7days
Minocycline subunit to block Mycoplasmas
Oxytetracycline binding of Donovanosis:
Tetracycline aminoacyl-tRNA Penicillin allergic Doxycycline 100 mg PO BID x 3-4 weeks until all
Tigecycline to acceptor site patients with lesions have completely healed
ribosome-mRNA leptospirosis, syphilis,
complex actinomycosis, Lymphogranuloma venereum:
tularemia, meliodosis Doxycycline 100 mg PO BID x 21 days
and skin and soft tissue
infections
XIII. TRIMETHOPRIM/SULFONAMIDES
ACTION COVERED
Cotrimoxazole: Excellent activity against Pneumocystitis jiroveci Pneumonia
Trimethoprim- S. typhi, some strains of For prophylaxis:
Sulfamethoxazole Folic acid Shigella, V. cholera, H. TMP-SMX 160/800 mg 3x weekly, or
(TMP-SMX) synthesis influenza TMP-SMX 80/400 mg PO OD
inhibitors
Cotrimazine: Use in Pneumocystitis For treatment:
Trimethoprim- jiroveci infection TMP-SMX 15-20 mg TMP/kg/day PO or IV q6-q8
Sulfadiazine
FEVER OF UNKNOWN ORIGIN (FUO)

Any febrile illness without an initially obvious etiology
The term FUO should be reserved for prolonged febrile illness without an established etiology, despite intensive
evaluation & diagnostic testing
TYPE DEFINITION
Fever of Unknown Origin Temperature > 38.3oC on several occasions
(Petersdorf & Beeson Definition 1961) Duration of fever > 3 weeks on two occasions
Uncertain diagnosis despite 1 week of inpatient investigation
Fever > 38.3oC on at least two occasions
Illness duration of > 3 weeks
No known immunocompromised state
Diagnosis uncertain after a thorough history-taking, physical
exam and the following obligatory investigations:
o ESR, CRP
Recent Definition of FUO o Platelet count, leukocyte count and differential,
hemoglobin
o Electrolytes, creatinine, total protein
o Alkaline phosphatase, ALT, AST
o LDH, creatinine kinase
o Ferritin
o ANA and RF
o Protein electrophoresis
151
o Urinalysis
o Blood culture (x3), urine culture
o Imagine (CXR and abdominal ultrasound)
o Tuberculin skin test
FEVER AND RASH

Infectious diseases associated with a rash
DISEASE ETIOLOGY DESCRIPTION
Begins as erythematous macules behind the ears, neck and
Rubeola: hairline then progresses to face, trunk and extremities
Measles Paramyxovirus Koplik’s spots: pathognomonic for measles; bluish white
(1st disease) dots surrounded by erythema; appears first on the buccal
mucosa opposite the lower molars
Scarlet fever Group A Streptococcus Rash is made up of minute papules giving the “sandpaper”
(2nd disease) (pyrogenic exotoxin A, B, C) feel of the skin
Pastia’s lines: accentuation of the rash in skin folds
Rubella: Spreads from hairline downward, with clearing as it spreads
German Measles Togavirus Forschheimer spots: petechiae on the soft palate, present
(3rd disease) in 20% of patients
Erythema Erythematous macular rash that spreads to the extremities
infectiosum (5th Human parvovirus B19 in a lacy reticular pattern “Slapped-cheeks” disease;
disease) “Glove-and-socks” syndrome
Exanthema subitum: Diffuse maculopapular rash over trunk and neck
Roseola Human herpesvirus 6
(6th disease)
Infectious 5% of patients develop morbilliform or popular rash usually
Mononucleosis Epstein-Barr virus on the arms and trunk
Most patients given ampicillin may develop a macular rash
Macular rash usually presents on the fifth day, begins on
Epidemic Typhus Rickettsia prowazekii the upper trunk and becomes generalized sparing the face,
palms and soles
Endemic (Murine) Initial macular rash usually detected in the axilla or inner
Typhus Rickettsia typhi arm
Most patients given ampicillin may develop a macular rash
Scrub Typhus Orientia tsutsugamushi Maculopapular rash and presence of the characteristic
eschar (site where the chigger has fed)
Leptospirosis Leptospira interrogans Rash may be macular, maculopapular, erythematous,
petechial or ecchymotic
Lyme Disease Borrelia burgdorferi Presence of erythema migrans (central clearing, red outer
border and a target center) at the site of tick bite
Typhoid Fever Salmonella typhi Rose spots: faint, salmon-colored, blanching
maculopapular rash usually seen on the trunk and chest
Dengue virus (4 serotypes; Maculopapular rash beginning on the trunk and spreads to
Dengue Fever flavivirus) the extremities and face which usually presents near the
time of defervescence
Petechiae on the trunk, extremities and mucous
Relapsing Fever Borrelia species membranes seen in 18% of patients at the end of febrile
episode
African Trypanosoma rhodesiense Blotchy or erythematous maculopapular rash on the trunk
Trypanosomiasis (East Africa)/ gambiense Presence of a painful trypanosomal chancre in some
(West Africa) patients at the site of inoculation
Initially pale red or pink macules on the trunk and proximal
Secondary Syphilis Treponema pallidum extremities which progresses to popular lesions usually on
the palms and soles
Condyloma lata: papules that enlarged to form broad,
152
moist, pink or gray-white highly infectious lesions usually in
warm, intertriginous areas
Chikungunya Fever Chikungunya virus Maculopapular rash on upper extremities and face,
appearing at the time of defervescence
Hand-Foot-and- Coxsackie virus A16 Painful vesicles in the mouth; papules on hands and feet
Mouth Disease (most common cause)
Group A streptococcus
Streptococcal Toxic (associated with pyrogenic Scarlatiniform rash
Shock Syndrome exotoxin A and/or B or
certain M types)
Staphylococcal Toxic S. aureus (toxic shock Erythroderma of variable intensity
Shock Syndrome syndrome toxin 1, Desquamation of the skin occurs during convalescence
enterotoxin B or C)
Staphylococcal Localized blister formation and exfoliation of the skin
Scalded-Skin S. aureus, phagr group II Nikolsky’s sign: rupture of the lesions with gentle pressure
Syndrome
Varicella: Varicella-zoster virus Macules evolving into papules then vesicles on an
Chickenpox erythematous base (the classic “dew on a rose petal”)
Pseudomonas “hot- Pseudomonas aeruginosa Pruritic erythematous follicular, popular, vesicular or
tub” folliculitis pustular lesions
Primary Herpes Hallmark: painful grouped vesicles that may progress to
Simplex Virus (HSV) HSV pustules and ulcerate
infection
Initially pink maculopapular lesions and later evolves into
nonblanching petechial rash usually in the trunk and
Acute extremities
Meningococcemia Neisseria meningitides May have purpura fulminans (large ecchymoses with
sharply irregular shapes evolving into hemorrhagic bullae
and then into black necrotic lesions; reflects disseminated
intravascular coagulation)
Chronic Neisseria meningitides May have pink maculopapular, nodular, petechial and
Meningococcemia purpuric lesions with pale blue-gray centers; recurrent
Tularemia Francisella tularensis Ulceroglandular form: erythematous, tender papule
evolves into necrotic, tender ulcer with raised borders
Anthrax Bacillus anthracis Typically begins as a papule which evolves to a painless
vesicle then later on to a coal-black, necrotic eschar
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SECTION 2
COMMON INFECTIOUS DISEASES CONDITIONS
DENGUE
I. ETIOPATHOGENESIS
Acute febrile illness of 2-7 days duration (sometimes biphasic), with no identifiable focus of infection
Four (types 1 to 4) distinct viruses (type 2 is more dangerous)
Principal vector: Aedes aegypti, which breeds near human habitation
Macrophage/monocyte infection is central to the pathogenesis
Second infection with a serotype different from that involved in the primary infection leads to dengue hemorrhagic
fever (HF) with severe shock
Incubation period: 2-7 days

Classic symptoms: sudden onset of fever, headache, retro-orbital pain, and back pain along with severe myalgia
“break-bone fever”
Initial symptoms: macular rash, adenopathy, palatal vesicles and scleral injection
Other signs and symptoms: anorexia, nausea, vomiting, cutaneous hypersensitivity, maculopapular rash
beginning on the truck and spreading to extremities and face
Epistaxis and scattered peterchiae are often noted in uncomplicated dengue and preexisting gastrointestinal
lesions may bleed during the acute illness
III. DIAGNOSIS
A. Common Diagnostic Tests

Complete blood count Leukopenia, thrombocytopenia, elevated hematocrit
Dengue IgM and IgG (ELISA) IgM antibody: usually detected by day five of illness
IgG antibody: detects past dengue infection
Immunoassay for the detection of non-structural protein 1 (NS1) antigens
NS1 Antigen (Rapid) Test Aids in screening and diagnosis as early as 1 day post-onset of symptoms
(prior to the detection of IgM or IgG antibodies)
BP cuff is inflated midway between systolic and diastolic pressures for 5
Tourniquet test minutes
Considered positive if >20 petechiae per square inch, 1.5 inches from the
volar aspect of the antecubital fossa
B. WHO Classification of Dengue

DENGUE + WARNING SIGNS SEVERE DENGUE
DENGUE FEVER WARNING SIGNS
Probable Dengue Abdominal pain or Severe Plasma Leakage
Lives in/travels to dengue endemic area tenderness Leads to shock and fluid
Fever and any 2 of the following: Persistent vomiting accumulation with respiratory
Nausea, vomiting Clinical fluid collection distress
Rash Mucosal bleed
Aches and pains Lethargy, restlessness Severe Bleeding
Positive Tourniquet test Liver enlargement >2 cm As evaluated by physician
Leukopenia Increase in Hct concurrent
Any warning signs with rapid decrease in Severe Organ Involvement
platelet count Liver: AST or ALT > 1000
Laboratory-Confirmed Dengue CNS: impaired consciousness
Important when there are no signs *requiring strict observation and Heart and other organs
of plasma leakage medical intervention
154
IV. MANAGEMENT
GROUP A GROUP B GROUP C
DENGUE FEVER WITHOUT DENGUE FEVER WITH WARNING SEVERE DENGUE
WARNING SIGNS SIGNS
Patients with co-existing conditions*
May be sent home and have social circumstances** Require emergency treatment
Referred for in-patient management
Advise: Hydration: Initial resuscitation: isotonic crystalloid
Adequate bed rest Encourage OFI if tolerated. If not, solutions at 5-10 ml/kg/hr over 1 hour
Adequate fluid intake start IVF If patient improves: IVE may be
Paracetamol PRN (4g max per Start with 5-7 ml/kg/hr for 1-2 hrs reduced to 5-7 ml/kg/hr for 1-2
day) Reduce to 3-5 ml/kg/hr for 2-4 hours, 3-5 ml/kg/hr for 2-4 hrs and
hrs then reduced further depending
Patients with stable hematocrit can be Reduce to 2-3 ml/kg/hr or less on hemodynamic status; IVF can
sent home; advise return to hospital if according to clinical response be maintained over 24 to 48 hrs
with development of warning signs o If Hct remains the same or If unstable: recheck Hct after 1st IV
rises minimally, continue with bolus
Daily review for disease progression: 2-3 ml/kg/hr for another 2-4 o If Hct increases/still high
decreasing WBC, defervescence, hrs (>50%), repeat a second
warning signs until out of critical period o If with worsening of vitals and bolus of crystalloid solution or
rapidly rising Hct, increase 10-20 ml/kg/hr for 1 hour (if
rate to 5-10 ml/kg/hr for 1-2hrs there is improvement, reduce
Reduce IVF until adequate UO rate to 7-10 ml/kg/hr and
and/or fluid intake or Hct continue to reduce as above)
decreases below baseline value o If Hct decreases, this
indicates bleeding and need
Monitoring to cross-match & transfuse
VS q1-4 hrs until out of critical
phase Treatment of hypotensive shock:
Hct at baseline and q6-12 hrs initiate resuscitation with crystalloid or
Blood glucose and other organ colloid solution at 20 ml/kg as bolus for
function tests 15 mins
If patient improves, give IVF at 10
ml/kg/hr for 1 hr then reduce
gradually
If still unstable: review Hct, assess
need for further fluid resuscitation
(if persistently high) or need for
bllod transfusion
Treatment of hemorrhagic
complications:
Give 5-10 ml/kg of pRBC or 10-20
ml/kg fresh whole blood
*such as pregnancy, infancy and old age, obesity, diabetes, renal failure, chronic hemolytic disease, etc.
**such as living alone, or living far from health facilities
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MALARIA
I. ETIOPATHOGENESIS
A. Pathogenesis
Most important parasitic disease in humans
In humans, the erythrocytic cycle is responsible for disease
o Rupture of schizonts and release of merozoites present clinically as paroxysms of malaria
o Hypnozoites are responsible for disease relapses
B. Etiology
Protozoan disease caused by 4 species of Plasmodium (falciparum, vivax, ovale and malariae) and transmitted
by the bite of infected Anopheles mosquitoes (Anopheles flavirostris in the Philippines)
Plasmodium falciparum causes nearly all deaths and neurological complications
A. Classic Malaria Paroxysm: cold stage (chills), hot stage (fever spikes), sweating stage
Tertian Periodicity Cyclic fever occurring Plasmodium falciparum (malignant tertian)
every 48 hours Plasmodium vivac, ovale (benign tertian)
Quartan Periodicity Cyclic fever occurring Plasmodium malariae
every 72 hours
B. Symptoms Ranging from Mild Constitutional Symptoms to Organ Failure

MILD / NON-LIFE THREATENING MALARIA SEVERE FALCIPARUM MALARIA
Unarousable coma / cerebral malaria
Academia / acidosis
Nonspecific constitutional symptoms Severe normochromic, normocytic anemia
Headache without neck stiffness or photophobia Renal failure
Nausea and vomiting Pulmonary edema / ARDS
Classic malaria symptoms Hypoglycemia
Anemia Hypotension / shock
Hepatosplenomegaly Bleeding / disseminated intravascular coagulation
Mild jaundice (DIC)
Convulsions
Others: hemoglobinuria, extreme weakness,
hyperparasitemia, jaundice
III. DIAGNOSIS OF MALARIA

Thick and thin smear: gold standard for laboratory confirmation of Malaria
Microscopic Acute demonstration of the parasite in the smear
Examination o Thick smear: for quantification of parasitemia
o Thin smear: for species identification
Complete blood count Normocytic normochromic anemia, thrombocytopenia
(CBC)
Blood chemistry Decreased plasma glucose, ↓Na, ↓HCO3, ↓Ca2+, ↓phosphate, ↓albumin, ↑lactate,
↑BUN, ↑creatinine, ↑urate, ↑muscle & liver enzymes, ↑bilirubin (DB & IB)
ABG Metabolic acidosis (usually high anion gap)
PT/PTT Prolonged in severe cases
Lumbar tap (for Mean opening pressure ~180 mmHg of CSF
cerebral malaria) Normal or slightly ↑total protein and cell count
IV. MANAGEMENT OF MALARIA
A. Malaria is treated with Combination Drugs (due to widespread chloroquine resistance)

DRUG REGIMEN CLINICAL USE SIDE EFFECTS
Chloroquine + Sulfadoxine First line of treatment in Pyrimethamine: megaloblastic
156
Pyrimethamine (CQ + SP) probable and confirmed anemia, pancytopenia,
falciparum malaria that is not pulmonary infiltration
severe
Second line drug for cases
which did not respond to Artemether: anaphylaxis,
Artemether-Lumefantrine adequate CQ + SP therapy utricaria, fever
Not recommended for Lumefantrine: none identified
pregnant women and children
<8y/o
Quinine + Tetracycline/ Third line of drug for those
Doxycycline who did not respond to Co- Quinine: cinchonism, tinnitus,
(Quinine + Clindamycin for ArtemTM high-tone hearing loss,
pregnant women and children Drug of choice for severe hypoglycemia, very bitter taste
<8y/o) malaria
Given as single dose to
confirmed P. falciparum cases
to prevent transmission
Primaquine Given for 14 days to confirmed Massive hemolysis in G6PD
P. vivax to prevent relapse deficiency
The only drug which can
eradicate extrahepatic stages
of the parasite
Chloroquine Drug of choice for P. vivax Nausea, dysphoria, pruritus,
cases retinopathy (>100 g)
B. Drugs used for severe Falciparum malaria

Artesunate
Artemether
Quinine dyhydrochloride
Quinidine
C. Drugs for prophylaxis

Doxycycline, primaquine, atovaquone/proguanil, chloroquine
Mefloquine (only prophylaxis permitted in pregnancy)
TYPHOID FEVER (ENTERIC FEVER)

I. ETIOPATHOGENESIS
A potentially fatal multisystemic illness caused by gram-negative Salmonella typhi and Salmonella paratyphi
Hallmark: invasion and multiplication within the mononuclear phagocytic cells in the liver, spleen, lymph nodes
and Peyer’s patches of the ileum
Transmission: orally by contaminated food or water (humans are the only known hosts)
Incubation: varies with amount of infecting dose but averages 10-20 days (range of 3 to 55 days)

NON-SPECIFIC SYMPTOMS PHYSICAL FINDINGS FINDINGS NECESSITATING HOSPITAL
ADMISSION
Chills Persistent high fever Persistent vomiting / unable to take
Diaphoresis Relative bradycardia fluids
Anorexia Rose spots (rash at Severe dehydration
Myalgia trunk area) Spontaneous bleeding
Cough Abdominal tenderness Persistent abdominal pain
Weakness/malaise Hepatomegaly Listlessness
Sore throat Splenomegaly Changes in mental status
Dizziness Typhoid psychosis/ Weak, rapid pulse
Constipation/diarrhea encephalitis Cold, clammy skin
Abdominal pain Epistaxis Circumoral cyanosis
157
Abdominal distention Seizures
Hypotension or narrow pulse pressure
*complications include intestinal perforation leading to GI hemorrhage and peritonitis (3rd to 4th week of illness), pancreatitis, hepatic and splenic
abscess, DIC, myocarditis, meningitis and encephalitis
III. DIAGNOSIS OF TYPHOID FEVER

CBC Neutropenia / leukopenia / leukocytosis / thrombocytopenia
Normochromic anemia; hypochromia with blood loss
Blood culture Gold standard: should be taken from at least 2 different sites
Can be taken anytime during the illness but yield is highest during the first 2 weeks
Stool culture May be positive during the 3rd week of illness in untreated patients
Not usually done, but indicated in highly suspicious cases or of negative blood/stool culture
Bone marrow culture Can be done anytime during the illness
Yield is high (~90%): yield not reduced by up to 5 days of prior antibiotic therapy
Serology Several serologic tests, though available, are not sufficiently sensitive or specific to replace
culture-based methods for diagnosis of enteric fever
IV. MANAGEMENT OF TYPHOID FEVER

INDICATION AGENTS DOSAGE & ROUTE DURATION (DAYS)
Empirical Ceftriaxone 2 g/d IV 10-14
Treatment Azithromycin 1 g/d PO 5
Ciprofloxacin (first line) 500 mg BID PO or 400 mg q12h IV 5-7
Azithromycin 1 g/d PO 5
Fully Susceptible Amoxicillin 1 g TID PO or 2 g q6h IV 14
Chloramphenicol 25 mg/kg TID PO or IV 14-21
TMP-SMX 160/800 mg BID PO 7-14
Multidrug- Ceftriaxone 2 g/d IV 10-14
resistant Azithromycin 1 g/d PO 5
Quinolone- Ceftriaxone 2 g/d IV 10-14
resistant Azithromycin 1 g/d PO 5
LEPTOSPIROSIS
I. ETIOPATHOGENESIS
A. Etiology
Caused by the pathogenic spirochete Leptospira interrogans (zoonosis with a worldwide distribution)
Rodents (especially rats): most important reservoir (others are wild mammals, dogs, fish and birds)
Incubation period: 2-28 days
B. Transmission
Direct contact with urine, blood or tissue of an infected animal
Exposure to a contaminated environment
Human-to-human transmission is rare
Leptospires may persist in water for many months

SUSPECTED LEPTOSPIROSIS MILD OR ANICTERIC MODERATE-SEVERE LEPTOSPIROSIS
LEPTOSPIROSIS OR WEIL’S SYNDROME
Individual presenting with acute Any suspected case of leptospirosis Any suspected case of leptospirosis
febrile illness of at least 2 days, and presenting with acute febrile illness presenting with acute febrile illness with:
and various manifestations but Unstable vital signs
Residing in a flooded area or has with: Jaundice
high-risk exposure (wading in floods Stable vital signs Abdominal pain, nausea, vomiting,
and contaminated water, contact Aniceteric sclerae diarrhea
with animal fluids, swimming in Good urine output Oliguria/anuria
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flood water or ingestion of No evidence of Meningismus/mengineal irritation
contaminated water, with or without meningismus/meningeal Sepsis/septic shock or altered
cuts or wounds), and irritation, sepsis/septic sensorium
shock, difficulty of breathing Difficulty of breathing or hemoptysis
At least 2 of the following: or jaundice
Myalgia The following findings should alert the
Calf tenderness May have other nonspecific findings clinician to possible severe leptospirosis:
Conjunctival suffusion such as nausea/vomiting, diarrhea, WBC >12,000 with neutrophilia and
Chills non-productive cough and thrombocytopenia
Abdominal pain maculopapular rash Serum creatinine >3 mg/dL (or CrCl
Headache <20 ml/min) and BUN >23 mg/dL
Jaundice AST/ALT ratio >4x, Bilirubin >190
Oliguria umol/L
Prolonged PT <85%
Serum K+ >4 mmol/L
ABG: severe metabolic acidosis (pH
<7.2, HCO3 <10) and hypoxemia
(PaO2 <60 mmHg, SaO2 <90%, PF
ratio <250)
CXR: extensive alveolar infiltrates
ECG: heart block, repolarization
abnormalities
III. DIAGNOSIS OF LEPTOSPIROSIS

Microscopic Dark-field microscope or immunofluorescence or light microscopy after appropriate staining
Demonstration Only of value during the 1st 7-10 days of acute illness during leptospiremia
(Direct Detection) Insensitive and lacks specificity
Culture and Isolation Gold standard
(Direct Detection) Time-consuming, labor –intensive, requires 6-8 weeks for the result
Low diagnostic yield
Polymerase Chain Early confirmation of diagnosis especially during the acute leptospiremic phase before the
Reaction or PCR appearance of antibodies
(Direct Detection) Limited clinical use due to cost
Fourfold rise in titer from acute to convalescent sera is confirmatory
Microagglutination In endemic areas (like the Philippines), a single titer of at least 1:1600 in symptomatic
Test or MAT patients is indicative of leptospirosis
(Indirect Detection) Highly sensitive and specific but time-consuming and hazardous to perform
Cross-reacts with syphilis, viral hepatitis, HIV, relapsing fever, Lyme disease, legionellosis
and autoimmune disease
Specific IgM Rapid Quick detection of Leptospira genus-specific IgM antibodies in human sera
Diagnostics Sensitivity of 63-72% and specificity of 93-96% if tested in illness <7 days; if taken >7 days,
(Indirect Detection) sensitivity improves to >90%
Non-specific Rapid Detects leptospira antibody in human serum through agglutination reaction which may
Diagnostics persist for years
(Indirect Detection) A positive result should be confirmed with MAT
CBC Peripheral leukocytosis, neutrophilia, thrombocytopenia
Urinalysis Proteinuria, pyuria and often hematuria
Hyaline and granular casts may also be present during the first week of illness
Serum Creatinine Can be initially normal but can be elevated during the course (sign of acute kidney injury)
Serum Creatinine Elevated in patients with severe myalgia
Phosphokinase
Liver Function Tests Bilirubins, ALT, AST and alkaline phosphatase may show slight elevation
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IV. MANAGEMENT OF LEPTOSPIROSIS
Jarisch-Herxheimer reaction: dramatic, mild reaction consisting of fever, chills, myalgia, headache, tachycardia,
tachypnea, neutrophilia and vasodilation with mild hypotension after initiation of antibiotic therapy
A. Treatment of Leptospirosis
INDICATION DRUGS DOSE
Doxycycline (first line) 100 mg BID PO
Mild Cases Amoxicillin (alternative) 500 mg q6h or 1 g q8h PO
Azithromycin (alternative) 1 g initially, followed by 500 ng OD PO for 2 more days
Penicillin G (first line) 1.5 MU q6-8h IV for 7 days
Ampicillin (alternative) 0.5 to 1 g q6h IV for 7 days
Severe Cases Cefotaxime (alternative) 1 g q6h IV for 7 days
Ceftriaxone (alternative) 1 g q24h IV for 7 days
Azithromycin (alternative) 500 mg OD PO for 3-5 days
Renal replacement therapy for patients in uremia, increasing creatinine or K + levels,
Acute Kidney Injury fluid overload, pulmonary hemorrhage or ARDS, metabolic acidosis, intractable
oliguria
Patients should be admitted to the ICU for close monitoring and/or invasive
ventilation
Pulmonary Hemorrhage/ Bolus methylprednisolone within the first 12 hours of onset of respiratory involvement
ARDS may be considered
o Methylprednisolone 1 g IV/day for 3 days, then
o Oral prednisolone 1 mg/kg/day for 7 days
B. Chemoprophylaxis
Most effective measure is avoidance of high-risk exposure and use of appropriate protective equipment
Currently, there is no recommended pre-exposure prophylaxis that is safe for pregnant/lactating women
SINGLE EXPOSURE CONTINUOUS EXPOSURE

Low Risk: Moderate Risk: High Risk:
(-) wounds/cuts/skin lesions (+) wounds/cuts/skin lesions (+/-) wounds/cuts/skin lesions
Doxycycline 100 mg 2 caps single Doxycycline 100 mg 2 caps OD for 3- Doxycycline 100 mg 2 caps once
dose within 24-72 hours of exposure 5 days started immediately within 24- weekly until the end of exposure
72 hours of exposure
SCHISTOSOMIASIS
I. ETIOPATHOGENESIS
Parasitic disease endemic in 24 provinces In the Philippines; highest prevalence in children 5-15 years of age
Schistosoma japonicum: major species involved in the Philippines
Oncomelania hupensis quadrasi: snail vector
Transmission: requires skin penetration of the cercaria
Main pathology & manifestations caused by granulomatous reaction to eggs deposited in liver & other organs

ACUTE SCHISTOSOMIASIS CHRONIC SCHISTOSOMIASIS
Cercarial dermatitis / swimmer’s itch Liver cirrhosis
Katayama fever (serum sickness-like syndrome with fever, Portal hypertension
generalized lymphadenopathy and hepatosplenomegaly) Ascites
III. DIAGNOSIS
Liver Ultrasound Clay pipestem fibrosis with lacelike pattern
CBC High level peripheral eosinophilia in Katayama fever
Fecalysis (Kato Katz Method) Demonstration of parasite eggs
Rectal Imprint Biopsy of rectal tissue with the aid of proctoscopy
Circumoval Precipitin Test (COPT) Detects circulating schistosome antigens
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IV. MANAGEMENT
SPECIES MANAGEMENT
S. mansoni
S. haematobium Praziquantel 40 mg/kg/day PO in 2 divided doses in 1 day
S. intercalatum
S. japonicum Praziquantel 60 mg/kg/day PO in 3 divided doses in 1 day
S. mekongki
TETANUS
I. ETIOPATHOGENESIS
Acute disease manifested by hypertonia or muscle spasms with or without autonomic nervous disturbance
Caused by a powerful neurotoxin (tetanospasm) produced by Clostridium tetani, a gram-positive spore-forming
anaerobic rod which can enter the skin through abrasions, wounds or in neonates, the umbilical stump

Wound infection, multiplication of C. tetani No symptoms
↓ in 7 to 10 days
Tetanus toxin uptake into nervous system and VAMP Initial symptoms: muscle aches, trismus and myalgia
cleavage in GABA inhibitory neurons
↓ after 24 to 72 hours
Muscle spasm: local and generalized
Further toxin effects causing widespread disinhibition of Cardiovascular instability: labile BP, tachycardia or
motor and autonomic nervous system bradycardia
Pyrexia: increased respiratory and GI secretions
↓ after 4 to 6 weeks
Toxin degradation Cessation of spasms, restoration of normal muscle tone
Cardiovascular and autonomic control
III. DIAGNOSIS AND CLASSIFICATION OF TETANUS
A. RITM Classification
STAGE I STAGE II STAGE III
Incubation Period >14 days 10-14 days <10 days
Period of Onset >6 days 3-6 days <3 days
Trismus Mild Moderate Severe
Dysphagia Absent Present Present
Muscular stiffness Mild / localized Pronounced Severe/board-like
Paroxysmal spasm Absent Mild and short Frequent, violent, prolonged & with
asphyxia
Dyspnea of cyanosis Absent Absent Present
Unstable BP
Sympathetic overactivity Absent Absent or mild ↑↓Paroxysmal
tachycardia/arrhythmias
Profuse sweating, hyperpyrexia
B. Classification Based on Extent of Involvement

1. Localized Cephalic Tetanus
o Only isolated areas of the body are involved and only localized muscle spasms occur
o Prognosis is poor if cranial nerves are involved, leading to respiratory/pharyngeal muscle spasm with
consequent aspiration or airway obstruction
2. Generalized Tetanus
o Typical presentation involved face and jaw muscles first followed by generalized muscle spasm
IV. MANAGEMENT
161
Entry wound should be identified, cleaned and debrided of necrotic material to remove any remaining source of
anaerobic foci and prevent further toxin production
Secure airway early in severe cases; if necessary, mechanical ventilation should be instituted
Patients should ideally be nursed in calm, quiet, dark environments with close cardiovascular monitoring
Appropriate antibiotics Metronidazole 500 mg IV q6h for 7 days (preferred antibiotic)
Penicillin 100,000 – 200,000 IU/kg per day (alternative)
Tetanus Toxoid For cases of suspected tetanus
(e.g. Td vaccine) Can be given with or without tetanus immunoglobulin
Tetanus immunoglobulin (TIG) Human tetanus Ig (TIG) 3,000-6,000 IU, or
or Tetanus Antitoxin Equine antitoxin 10,000 – 20,000 U as single IM dose
Control of Spasms Sedatives (e.g., benzodiazepines) and muscle relaxants
C. Recommendations for Post-Exposure Tetanus Prophylaxis

VACCINATION HISTORY Clean, Minor Wounds All Other Wounds*
Td TIG Td TIG
Unknown number or < 3 doses received Yes No Yes Yes
For those with > 3 doses received:
> 10 years since most recent dose Yes No Yes No
5-9 years since most recent dose No No Yes No
<5 years since most recent dose No No No No
*wounds >1 cm, in depth, incurred >6 hrs earlier, or with stellate or avulsion configuration; crush injuries or burn injuries; devitalized tissue; and
wounds contaminated with dirt, feces or saliva
D. Prognosis: Factors Associated with a Worse Outcome in Adult Tetanus:

Age > 70 years
Incubation period < 7 days
Short time from first symptom to admission
Puerperal, IV, post-surgery and burn entry site
Period of onset < 48 hours
HR >140 bpm
SBP >14 mmHg
Severe disease or spasms
Temperature >38.5oC
RABIES
I. ETIOPATHOGENESIS
Rapidly progressive, acute infectious disease of the CNS, caused by the rabies virus (family Rhabdoviridae)
Incubation: 20-90 days
Transmission: via bite of an infected animal
Prognosis: recovery is rare

Combativeness, seizures, autonomic dysfunction (hypersalivation, gooseflesh,
Encephalithic (Furious) cardiac arrhythmia, priapism)
Rabies (80% Hydrophobia: involuntary, painful contraction of the diaphragm and accessory
respiratory/laryngeal/pharyngeal muscles in response to swallowing liquids
Aerophobia: same features cause by stimulation from a draft of air
Paralytic Rabies (20%) Early and prominent flaccid muscles weakness predominates
III. CATEGORIZATION OF EXPOSURE AND RESPECTIVE MANAGEMENT (WHO CLASSIFICATION)

EXPOSURE MANAGEMENT
Feeding/touching an animal Wash exposed skin immediately with soap and
Licking of intact skin water
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I Exposure to patient with signs of rabies by sharing No vaccine or RIG needed
or eating or drinking utensils Pre-exposure vaccination may be considered
Casual contact with patient with signs of rabies
Start vaccine immediately
o Complete regimen until day 28/30 if:
Animal is rabid, killed, died or unavailable for
Nibbling/nipping of uncovered skin with bruising 14 day observation and examination; or
Minor scratches / abrasions / abrasions without Animal under observation died within 14 days
II bleeding (includes wounds that are induced to and was IFAT positive or no IFAT testing was
bleed) done or has signs of rabies
Licks on broken skin o Complete vaccine regimen until:
Animal is alive and remains healthy after 14-
day observation period
Animal under observation died within 14 days
but had no signs of rabies and was IFAT
negative
Transdermal bites or scratches (includes puncture Start vaccine and RIG immediately:
wounds, lacerations and abrasions) o Complete regimen until day 28/30 if:
Contamination of mucous membranes with saliva Animal is rabid, killed, died or unavailable for
(e.g., licks) 14 day observation and examination; or
Exposure to rabies patient through bites, Animal under observation died within 14 days
III contamination of mucous membranes or open skin and was IFAT positive or no IFAT testing was
lesions with body fluids (except blood/ feces) done or had signs of rabies
through splattering, mouth-to-mouth resuscitation, o Complete vaccine regimen until day 7 if:
licks of eyes, lips, vulva, sexual activity, exchanging Animal is alive & remains healthy after 14 day
kisses on the mouth or other direct mucous observation period
membrane contact with saliva Animal under observation died within 14 days
Handling of infected carcass or ingestion of raw but had no signs of rabies and was IFAT
infected meat negative
INFECTIVE ENDOCARDITIS (IE)

I. ETIOPATHOGENESIS
Prototypic lesion: vegetation
The analogous process involving AV shunts, PDAs or coarctation of the aorta is called infective endarteritis
Endothelial injury may also lead to development of an uninfected platelet-fibrin thrombus called non-bacterial
thrombotic endocarditis (NBTE) or as a result of a hypercoagulable state called marantic endocarditis
II. DIAGNOSIS: THE MODIFIED DUKE’S CRITERIA
A. Criteria for Diagnosis

Two major criteria; or
Definite Endocarditis One major criteria and three minor criteria; or
Five minor criteria
Possible Endocarditis One major + one minor, or
Three minor criteria
Alternative diagnosis is established
Diagnosis of IE is Rejected Symptoms resolved & do not recur with < 4 days of antibiotic therapy
Surgery or autopsy after < 4 days of antimicrobial therapy yields no
histologic evidence of endocarditis
B. Major and Minor Criteria (from the Modified Duke’s Criteria)

Blood cultures: three 2-bottle sets separated from one another by at least 1 hour and obtained from different sites
over 24 hours
If cultures remain negative after 48-72 hours, 2 to 3 additional blood culture sets should be obtained
Predisposing heart conditions include: valvular disease with stenosis or regurgitation, prosthetic valves,
congenital heart defects, prior endocarditis, hypertrophic cardiomyopathy
163
MAJOR CRITERIA MINOR CRITERIA
1) Positive blood culture: Predisposing heart condition or
Typical organisms for IE from >2 cultures: injection drug use
o S. viridans
o HACEK Fever > 38.0oC
o S. gallolyticus (previously S. bovis)
o S. aureus Vascular phenomena: major arterial
o Enterococcus emboli, septic pulmonary infarcts, mycotic
OR, Persistently positive, defined as recovery of a aneurysms, intracranial hemorrhage,
microorganism consistent with IE from: conjunctival hemorrhages, Janeway
o Blood cultures drawn >12 hours apart, or lesions
o All of 3 or a majority of >4 separate cultures
with first and last drawn at least 1 hour apart Immunologic phenomena:
OR, Single positive blood culture for Coxiella burnetii or glomerulonephritis, Osler’s nodes, Roth’s
phase I IgG antibody titer of >1:800 spots, rheumatoid factor
2) Evidence of endocardial involvement:
Positive echocardiogram: Microbiologic evidence: positive blood
o Oscillating intracardiac mass culture but not meeting major criterion or
o Abscess serologic evidence of active infection with
o New dehiscence of prosthetic valve organism consistent of IE
Or, New valvular regurgitation
*HACEK: Haemophilius sp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella sp.
A. Acute Versus Subacute Endocarditis

ACUTE BACTERIAL IE SUBACUTE BACTERIAL IE
Streptococcus viridans
Usual S. aureus Enterococci
Etiology B-Hemolytic Streptococci Coagulase-negative staphylococcus (prosthetic
Pneumococci valve)
HACEK
Fever High grade fever (39.4-40oC) Low grade fever (rarely >39.4oC)
Course Rapid Indolent
Acute / decompensated heart failure common Rarely metastasizes
Hematogenously seeds extracardiac sites
Prognosis Poor (if untreated) Better prognosis
B. Non-Cardiac Manifestations
MANIFESTATION DESCRIPTION
Janeway lesions Nontender, slightly raised hemorrhages on the palms and soles (seen in endocarditis)
Osler’s nodes Tender, raised nodules on the pads of the fingers or toes (seen in endocarditis)
Splinter Small blood clots that run vertically under the nails
hemorrhages
Glomerulonephritis Caused by immune complex deposition at the glomerular basement membrane
Minor emboli: splinter hemorrhages, Janeway lesions, conjunctival hemorrhages
Embolic events Major emboli: arterial emboli, intracranial hemorrhage, pulmonary infarct, mycotic
aneurysm
Mycotic aneurysms Focal dilations in the artery wall that have been weakened by infection or septic emboli
IV. MANAGEMENT
ORGANISM RECOMMENDED REGIMEN
Penicillin G (2-3 mU IV q4h) for 4 weeks
Ceftriaxone (2 g/d IV OD) for 4 weeks
Streptococci Vancomycin (15 mg/kg IV q12h) for 4 weeks
(Penicillin-sensitive) Penicillin G (2-3 mU IV q4h) OR Ceftriaxone (2 g IV OD) for 2 weeks PLUS
Gentamicin (3 mg/kg IV or IM OD) as a single dose or divided into equal doses q8h for 2
weeks
164
Penicillin G (4-5 mU IV q4h) OR Ceftriaxone (2 g IV OD) for 6 weeks PLUS
Streptococci Gentamicin (3 mg/kg IV or IM OD) as a single dose or divided into equal doses q8h for 2
(Penicillin-resistant) weeks
Vancomycin (15 mg/kg IV q12h) for 4 weeks
Penicillin G (4-5 mU IV q4h) PLUS Gentamicin (1 mg/kg IV q8h) both for 4-6 weeks
Enterococci Ampicillin (2 g IV q4h) PLUS Gentamicin (1 mg/kg IV q8h) both for 4-6 weeks
Vancomycin (15 mg/kg IV q12h) PLUS Gentamicin (1 mg/kg IV q8h) both for 4-6 weeks
Staphylococci Nafcillin OR Oxacillin (2 g IV q4h) for 4-6 weeks
(Methicillin-sensitive) Cefazolin (2 g IV q8h) for 4-6 weeks
Vancomycin (15 mg/kg IV q12h) for 4-6 weeks
Staphylococci Vancomycin (15 mg/kg IV q8-12h) for 4-6 weeks
(Methicillin-resistant)
HACEK organisms Ceftriaxone (2 g/d IV OD) for 4 weeks
Ampicillin/sulbactam (3 g IV q6h) for 4 weeks
Culture Negative Ampicillin/sulbactam (3 g IV q6h) PLUS Gentamicin (1 mg/kg IV q8h) for 4-6 weeks
V. PROPHYLAXIS IN ADULTS WITH HIGH RISK CARDIAC LESIONS

Amoxicillin 2 g PO 1 hour before procedure (standard oral regimen)
Ampicillin 2 g IV or IM 1 hour before procedure (unable to take oral medication)
For Penicillin allergy:
o Clarithromycin or azithromycin 500 mg PO 1 hour before procedure
o Cephalexin 2 g PO 1 hour before procedure
o Clindamycin 600 mg PO 1 hour before procedure
o Cefazolin or Ceftriaxone 1 g IV or IM 30 minutes before procedure
HIGH RISK CARDIAC LESIONS
Prosthetic valves Completely repaired congenital defects
Prior endocarditis during the 6 months after repair
Unrepaired cyanotic congenital defects Incompletely repaired congenital defects
HUMAN IMMUNODEFICIENCY VIRUS: AIDS AND RELATED DISORDERS

I. ETIOPATHOGENESIS
A. Etiologic Agent
Etiologic agent: Human Immunodeficiency Virus (HIV)
Four retroviruses known to cause human disease
o Human T lymphotropic viruses (HTLV)-1 and HTLV-II: transforming retroviruses
o Human immunodeficiency viruses, HIV-1 and HIV-2: cause cytopathic effects
HIV-1 is the most common cause of HIV disease throughout the world
Hallmark of HIV disease: profound immunodeficiency resulting primarily from a progressive quantitative and
qualitative deficiency of helper T cells, occurring in a setting of polyclonal immune activation
B. Transmission
Primarily by sexual contact: worldwide, heterosexual transmission is still the most common mode
Blood and blood products
Occupational transmission of HIV
Infected mothers to infants intrapartum, perinatally or via breast milk
No evidence that HIV is transmitted by casual contact or that the virus can be spread by insect, such as by a
mosquito bite

ACUTE HIV SYNDROME ASYMPTOMATIC STAGE SYMPTOMATIC STAGE
(CLINICAL LATENCY)
Occurs 3-6 weeks after primary Median time: 10 years (for Symptoms can appear at any time
infection along with a burst of untreated patients) More severe and life-threatening
plasma viremia Ongoing and progressive HIV complications of HIV infection
165
Symptoms: fever, skin rash, disease with active virus occur in patients with CD4+ T cell
pharyngitis, myalgia replication counts <200/uL
Most patients recover Rate of disease progression is
spontaneously from this syndrome directly correlated with HIV RNA AIDS:
Many have only a mildly levels HIV + CD4+ T cell count <200/uL;
depressed CD4+ T cell count that or
remains stable for a variable HIV + HIV-associated diseases
period before beginning its decline indicative of a severe defect in cell-
mediated immunity
III. DIAGNOSIS OF HIV

A. Diagnostics Used
Standard blood screening test for HIV infection
ELISA or Enzyme Immunoassay Sensitivity of >99.5% (not optimal with regard to specificity)
(EIA) Commercial EIA kit contains antigens from both HIV-1 and HIV-2
Scored as positive (highly reactive), negative (nonreactive), or indeterminate
(partially reactive)
Most commonly used confirmatory test
Western blot Western blot demonstrating antibodies to products of all three of the major
genes of HIV (gag, pol and env) is conclusive evidence of infection with HIV
EIA-type assay: consists of antibodies to the p24 antigen of HIV
p24 Antigen Capture Assay Detects the viral protein p24 in the blood of HIV-infected individuals
Greatest use as a screening test for HIV infection in patients suspected of
having the acute HIV syndrome
B. Laboratory Monitoring of HIV Infection
Measured directly or calculated as the product of the percent of CD4 + T-cells and the
total lymphocyte count
Best indicator of and correlated with the level of immunologic competence
CD4+ T Cell Count o CD4+ T cell counts <200/uL: high risk of disease from P. jiroveci
o CD4+ T cell counts <50/uL: high risk of CMV, mycobacteria of the M. avium
complex (MAC), and/or T. gondii
Measured at the time of diagnosis and every 3-6 months thereafter
HIV RNA Determination Number of copies of HIV RNA per milliliter of serum or plasma
HIV RNA can be detected in virtually every patient with HIV infection
HIV Resistance Testing Drug resistance testing in the setting of virologic failure should be performed while
the patient is still on the failing regimen
IV. MANAGEMENT OF HIV AND AIDS
A. Clinical Settings where Initial Antiretroviral Therapy (ART) is recommended in the Philippines:
NNRTI-based regimen = 2 NRTI + 1 NNRTI
First line NNRTI Zidovudine (AZT) 300 mg BID + Lamivudine (3TC) 150 mg BID
Alternative first line NNRTI Tenofovir (TDF) 300 mg OD + Lamivudine (3TC) 150 mg BID
First line NRTI Nevirapine (NVP) 200 mg BID
Alternative first line NRTI Efavirenz (EFV) 600 mg OD HS (for patients with hypersensitivity to NVP)
NRTI: Nucleoside Reverse Transcriptase Inhibitor
NNRTI: Non-Nucleoside Reverse Transcriptase Inhibitor
166
SEXUALLY TRANSMITTED DISEASES (STD)
DISEASE/ETIOLOGY FEATURES TREATMENT
Treat gonorrhea (unless excluded)
Urethritis in Men Ceftriaxone 250 mg IM; or
N. gonorrhea Urethral discharge Cefpodoxime 400 mg Pol or
C. trachomatis Dysuria Cefixime 400 mg PO
M. genitalium Usually without frequency
U. urealyticum PLUS treatment for chlamydial infection
T. vaginalis Azithromycin 1 g PO; or
Doxycycline 100 mg BID PO for 7 days
Epididymitis Unilateral pain Ceftriaxone 250 mg IM + Doxycycline 100
C. trachomatis Swelling and tenderness of mg BID x 10 days
N. gonorrhea (less commonly) the epididymis Levofloxacin 500 mg OD x 10 days (for
Enterobacteriaceae)
Treat gonorrhea (unless excluded)
Ceftriaxone 250 mg IM; or
Mucopurulent cervicitis (MPC) Presence of yellow Cefpodoxime 400 mg PO; or
N. gonorrhea mucopurulent discharge from Cefixime 400 mg PO
C. trachomatis the cervical os
M. genitalium PLUS treatment for chlamydial infection
Azithromycin 1 g PO; or
Doxycycline 100 mg BID PO for 7 days
Outpatient
Ceftriaxone 350 mg IM once; PLUS
Doxycycline 100 mg PO BID for 14 days;
Acute PID Inpatient*

Lower abdominal pain <3 Regimen A
Pelvic Inflammatory Disease weeks duration o Cefotetan 2 g IV q12; or
N. gonorrhea Pelvic tenderness on o Cefoxitin 2 g IV q6; PLUS
C. trachomatis bimanual pelvic examination o Doxycycline 200 mg IV or PO q12
Evidence of lower genital tract Regimen B
infection o Clindamycin 900 mg IV q8; PLUS
o Gentamicin 1.5 mg/kg q8
Continued parenteral therapy until 48 hrs after clinical

improvement, then change to outpatient therapy
Vulvovaginal Infections
Vulvovaginal candidiasis Vulvar itching and/or irritation Fluconazole 150 mg PO single dose
C. albicans Scanty, white, clumped Azole cream, tab or suppository:
discharge miconazole, clotrimazole
Trichomonal vaginitis Vulvar itching
T. vaginalis Often profuse white or yellow Metronidazole 500 mg PO BID for 7 days
homogenous discharge
Malodorous
Slightly increased discharge
Bacterial vaginosis (+) Clue cells: vaginal Metronidazole 500 mg PO BID for 7 days
Gardnerella vaginalis epithelial cells coated with Topical: metronidazole gel, clindamycin
coccobacillary organisms
giving it a granular
appearance
Ulcerative Genital or Perianal Lesions
Sharply demarcated, elevated
Syphilitic Chancre and round ulcers Benzathine penicillin 2.4 million units IM as
T. pallidum Lymph nodes are bilateral, single dose
firm and non-tender
Herpes Acyclovir 400 mg PO TID x 7-10 days; or
167
HSV Erythematous ulcers Acyclovir 200 mg PO 5x a day x 7-10 days;
Lymph nodes are firm, tender, or
often bilateral Valacyclovir 1 g PO 2x a day for 7-10 days;
or
Famciclovir 250 mg PO TID for 7-10 days
Undermined, ragged &
Chancroid irregular ulcers Ciprofloxacin 500 mg PO as single dose; or
H. ducreyi Lymph nodes are tender, may Ceftriaxone 250 mg IM as single dose; or
suppurate, loculated & usually Azithromycin 1 g PO as single dose
unilateral
Elevated, round or oval ulcers
Lymphogranous venereum Lymph nodes are tender, may Doxycycline 100 mg PO BID for 21 days
C. trachomatis suppurate, loculated & usually
unilateral
Donovanosis Elevated, irregular ulcers Doxycycline 100 mg BID for at least 3
K. granulomatis Pseudobuboes weeks and until all lesions have completely
healed
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SECTION 3
IMMUNIZATION
VACCINE TYPE/ROUTE INDICATION SCHEDULE
Single dose
Comorbidities (chronic lung disease, asthma, Booster may be given to:

Pneumococcal cardiovascular disease, DM, liver disease) o > 65 years old if first
Polysaccharide (PPSV23): Immunocompromised (asplenia, HIV) dose >5 years ago and
IM or SC Residents of nursing homes or long-term care before age 65
Conjugate (PCV 13): IM facilities o <65 years old who
Smokers and alcoholics received vaccine >5
years ago and
immunocompromised
Human Papilloma Virus (HPV) Females:
Bivalent (Types 16, 18) for 3 doses at age 11 or 12 and those aged 13 3 doses
females only: IM through 26 if not previously vaccinated Bivalent – 0, 1, 6 months
Quadrivalent (Types 6, 11, Quadrivalent – 0, 2, 6
16, 18) for females and Males: months
males: IM 3 doses at age 11 or 12 and those aged 13
through 26, if not previously vaccinated
Meningococcal Two doses if immunocompromised (asplenia, HIV,
Polysaccharide vaccine complement deficiency) Single dose
(MPSV): IM or SC Single dose for unvaccinated students in (revaccination after 5
Conjugate vaccine dormitories, microbiologists routinely exposed to years if with risk of
(MCV4): IM Neisseria meningitides, military recruits, travelers exposure)
or inhabitants in endemic areas
ViPS
1 dose should be given >
2 weeks before exposure
Typhoid Travelers to outbreak areas Booster dose – 1 dose IM
Vi Polysaccharide (ViPS): Health care workers and lab technicians every 3 years for travelers
IM Exposed to S. typhi cases and patients
Live attenuated: Oral Those in refugee camps & disaster areas Live attenuated (oral)
Enteric-coated capsules
every other day for 1
week
Influenza
Trivalent inactivated All persons >6 months Single dose annually
vaccine: IM or intradermal
(microneedle)
MSM and illicit drug users
Persons working with HAV in a research Single dose
Hepatitis A laboratory setting Booster dose between 6-
Inactivated vaccine: IM Chronic liver disease and recipients of clotting 12 months after primary
factor concentrates course
Travelers to endemic countries
Sexually active persons not in a long-term,
mutually monogamous relationship and those with
STD
MSM and injection-drug users
Hepatitis B Exposed healthcare personnel 3 doses: 0, 1, 6 months
Inactivated vaccine: IM ESRD, chronic liver disease, HIV
Household contacts and sex partners of
chronically-infected persons
Clients and staff of institutions for developmental
disabilities
169
Close contact with persons at high risk for severe
disease (e.g., health personnel and family
contacts of immunocompromised persons) or at 2 doses: 0, 1-2 months
Varicella high risk for exposure or transmission (e.g. Single dose post-
Live attenuated vaccine: teachers, day care staff) exposure prophylaxis:
SC Residents and staff of correctional institutions within 72 hours of
Military personnel exposure
Adolescents and adults living in households with
children
Non-pregnant women of childbearing age
Measles, Mumps, Rubella Measles and mumps component: college
(MMR) students, health care workers, travelers 2 doses: 0, 1 month
Live attenuated: SC Rubella component: non-pregnant women of
childbearing age should be vaccinated
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CHAPTER 7
ENDOCRINOLOGY
I. Introduction to Endocrinology
II. Common Conditions in Endocrinology
1. The Metabolic Syndrome
2. Diabetes Mellitus
3. Gestational Diabetes Mellitus
4. Hyperglycemic Crises in Diabetes
5. Diabetic Foot Ulcer
6. Hypoglycemia
7. Hyperthyroidism
8. Thyroid Storm
9. Goiter and Nodular Thyroid Disease
10. Osteoporosis
11. Multiple Endocrine Neoplasia
12. Cushing’s Syndrome
13. Mineralocorticoid Excess
14. Pituitary Diseases
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SECTION 1
INTRODUCTION TO ENDOCRINOLOGY
I. GENERAL FORMULAS
BODY MASS INDEX
BMI = Weight in kg
(height in m)2
IDEAL BODY WEIGHT (IBW)
IBW Males = 106 lbs + (6 lbs per inch over 5 feet)
IBW Females = 100 lbs + (5 lbs per inch over 5 feet)
*Divide by 2.2 to convert to kilograms
WAIST-HIP RATIO (WHR)

WHR = Waist circumference in cm
Hip circumference in cm
Waist circumference should be measured at the midpoint between the lower margin of the last palpable rib and
the top of the iliac crest
Hip circumference should be measured around the widest portion of the buttocks
Used as an indicator or measure of the health of a person, and the risk of developing serious health conditions
Abdominal obesity: defined as a waist-hip ratio >0.90 for males and >0.85 for females
A1C APPROXIMATES THE FOLLOWING MEAN PLASMA GLUCOSE VALUES

HBA1C APPROXIMATE PLASMA GLUCOSE VALUE
6% 7.0 mmol/L (126 mg/dL)
7% 8.6 mmol/L (154 mg/dL)
8% 10.2 mmol/L (183 mg/dL)
9% 11.8 mmol/L (212 mg/dL)
10% 13.4 mmol/L (240 mg/dL)
11% 14.9 mmol/L (269 mg/dL)
12% 16.5 mmol/L (298 mg/dL)
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SECTION 2
COMMON CONDITIONS IN ENDOCRINOLOGY
THE METABOLIC SYNDROME
I. ETIOLOGY
Metabolic abnormalities that confer an increased risk of cardiovascular disease and diabetes mellitus
Insulin resistance: most accepted an unifying hypothesis in metabolic syndrome
Hypertriglycerides is an excellent marker of insulin resistance
Other associated conditions: non-alcoholic fatty liver, hyperuricemia, polycystic ovarian syndrome and obstructive
sleep apnea
II. DIAGNOSIS
A. BMI Classification
CLASSIFICATION OF BMI WHO INTERNATIONAL CLASSIFICATION IN ASIANS
(kg/m2) CLASSIFICATION
Underweight < 18.5 < 18.5
Normal 18.5 – 24.99 18.5 – 22.9
Overweight > 25 23 – 24.9
Obese I > 30 25 – 29.9
Obese II > 35 > 30
Obese III > 40
B. NCEP: ATP III 2001 Criteria for the Metabolic Syndrome (requires 3 or more of the following)
Central Obesity Waist circumference >102 cm (M) or >88cm (F)
Hypertriglyceridemia TG > 150 mg/dL or use of specific medication
Low HDL Cholesterol <40 mg/dL (M) or <50 mg/dL (F) or use of specific medication
Hypertension BP > 130 systolic or > 85 diastolic or use of specific medication
Fasting Glucose > 100 mg/dL or specific medication or preciously diagnosed T2DM
C. Harmonizing Definition for the Metabolic Syndrome (requires 3 or more of the following)
> 90 cm (M) or > 80 cm (F) in South Asian, Chinese, and Ethnic
South and Central American
Waist circumference > 85 cm (M) or > 90 cm (F) in Japanese
> 94 cm (M) or > 80 cm (F) in Europe, Sub-Saharan African, Eastern
and Middle Eastern
Hypertriglyceridemia TG > 150mg/dL or use of specific medication
Low HDL Cholesterol < 40 mg/dL (M) or < 50 mg/dL (F) or use of specific medication
Hypertension BP > 130 systolic or > 85 diastolic or use of specific medication
Fasting Glucose > 100 mg/dL or specific medication or previously diagnosed T2DM
TG: Triglycerides
M: Males; F: Females
III. MANAGEMENT OF OBESITY

TREATMENT BMI CATEGORY (kg/m2)
25 – 26.9 27 – 29.9 30 – 34.9 35 – 39.9 > 40
Diet & Exercise + if with + if with + + +
comorbids comorbids
Pharmacotherapy - + if with + + +
comorbids
Surgery - - - + if with +
comorbids
Dietary therapy: primary focus is reduction in overall calorie consumption

Diet and exercise: combination of dietary modification and exercise is the most effective behavioral approach
Pharmacotherapy: appetite suppressants (e.g., phentermine) and gastrointestinal fat blockers (e.g., orlistat)
Surgery: classified into three (restrictive, restrictive-malabsorptive, and malabsorptive)
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DIABETES MELLITUS
I. ETIOPATHOGENESIS
Group of metabolic disorders that share the common phenotype of hyperglycemia
DM is defined as the level of glycemia at which diabetes-specific combinations occur
A. Classification of Diabetes (based on the pathogenic process that leads to hyperglycemia)

Type 1 DM: result of interactions of genetic, environmental and immunologic factors that ultimately lead to
destruction of pancreatic beta cells and insulin deficiency
Type 2 DM: heterogenous group of disorders characterized by variable degrees of insulin resistance, impaired
insulin secretion and excessive hepatice glucose production
B. Risk Factors for Type 2 DM

Physical inactivity
Family history of diabetes (e.g., parent or sibling with T2DM)
Obesity (BMI > 25 kg/m2 or ethnically relevant definition for overweight)
High-risk ethnicity (e.g. African American, Latino, Native American, Asian American, Pacific Islander)
GDM or delivery of a baby > 9 lbs (4 kg)
History of cardiovascular disease or hypertension (> 140/90 mmHg)
HDL cholesterol < 35mg/dL (0.90 mmol/L) and/or triglycerides >250 mg/dL (2.82 mmol/L)
HbA1C 5.7-6.4%, IGT or IFG on previous testing
Conditions with insulin resistance (e.g. acanthrosis nigricans, polycystic ovary syndrome)
C. Classification of Glucose Tolerance

GLUCOSE FASTING PLASMA GLUCOSE GLUCOSE AFTER ORAL HbA1C
TOLERANCE (FPG) GLUCOSE CHALLENGE
Normal < 10 mg/dL (5.6 mmol/L) < 140 mg/dL (7.8 mmol/L) < 5.7%
Impaired Glucose 100-125 mg/dL (5.6-6.9 mmol/L) 140-199 mg/dL (7.8-11 mmol/L) 5.7-6.4%
Homeostasis Impaired Fasting Glucose (IFG) Impaired Glucose Tolerance (IGT)
Diabetes Mellitus > 126 mg/dL (7.0 mmol/L) > 200 mg/dL (11.1 mmol/L) > 6.5%
II. CLINICAL FEATURES OF DIABETES

Classic symptoms: polyuria, polydipsia, polyphagia, nocturia, weight loss
Others: fatigue, weakness, blurred vision, frequent superficial infections and poor wound healing
A. Acute Complications of DM
Diabetic Acidosis
Hypoglycemic hyperosmolar state
B. Chronic Complications of DM
MICROVASCULAR MACROVASCULAR OTHERS
Eye disease
Retinopathy (nonproliferative/ Gastrointestinal (gastroparesis, diarrhea)
proliferative) Genitourinary (uropathy, sexual dysfunction
Macular edema Dermatologic
Coronary artery disease Cataracts and glaucoma
Neuropathy Peripheral arterial disease Periodontal disease
Sensory and motor (mono-/ Cerebrovascular disease Hearing loss
polyneuropathy) Increased risk for infection
Autonomic Cheiroarthropathy (thick skin + reduced joint
mobility)
Nephropathy (albuminuria, declining
renal function)
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III. DIAGNOSIS OF DIABETES MELLITUS
A. Criteria for the Diagnosis of DM

Note:
Either of the following: Current criteria emphasize the HbA1C or the FPG as
Hemoglobin A1C > 6.5%, or the most reliable and convenient tests
FPG > 126 mg/dL (7.0 mmol/L), or Perform HbA1C with an assay-standardized method
2-hour plasma glucose > 200 mg/dL (11.1 mmol/L) “Fasting”: no caloric intake for at least 8 hours
during 75 g OGTT, or “Random”: without regard to time since last meal
Symptoms of DM + RBS > 200 mg/dL (11.1 In the absence of unequivocal hyperglycemia, these
mmol/L) criteria should be confirmed by repeat testing on a
different day
FPG: Fasting Plasma Glucose
OGTT: Oral Glucose Tolerance Test (performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water)
B. Screening for DM
Begin at age 45 years every 3 years
Earlier age if they are overweight (BMI > 23) + one additional risk factor for DM (see above)
May use A1C FPG, or 2-hour plasma glucose after 75 g OGTT for screening
IV. MANAGEMENT OF DIABETES
A. Insulin Therapy
Common side effects are hypoglycemia and weight gain
Adjust doses in renal insufficiency
INSULIN PREPARATION ONSET OF ACTION PEAK DURATION
Rapid and Short Acting Insulin
Lispro (Rapid)
Aspart (Rapid) < 15 mins 30-90 mins 2-4 hours
Glulisin (Rapid)
Regular (Short) 30-60 mins 2-3 hours 3-6 hours
Intermediate and Long Acting Insulin
Isophane/NPH (Intermediate) 2-4 hours 4-10 hours 10-16 hours
Glargine (Long) Minimal peak activity Up t0 24 hours
Detemir (Long) 1-4 hours
1. Three Major Components of Exogenous Insulin Therapy

Required to regulate metabolic processes even in the absence of meals
Basal Insulin Usual “basal insulin”: given as intermediate or long-acting insulin
Intermediate-acting insulin usually given in portions of 2/3 in AM and 1/3 in PM
Required to cover glycemic excursions following a meal
Bolus Insulin Usual “bolus insulin”: given as short or rapid-acting insulin
Rapid-acting insulin given within 15-20 minutes or immediately before meals
Short-acting insulin given within 30-45 minutes before meals
Correctional Insulin Supplemental doses of short or rapid-acting insulin given to correct elevations in
blood glucose that occur despite the use of basal and bolus insulin
2. Initiating Insulin Therapy in T1DM

Calculate total insulin requirement: usually 0.5-1 units/kg per day
50% of computed value given as basal insulin
3. Initiating Insulin Therapy in T2DM

Basal Insulin Calculate dose at 0.2 units/kg/day for insulin-naïve patients
Bolus Insulin Initiated if unable to achieve target A1C with basal insulin alone
Start with 4 units before each meal OR calculate each dose at 0.1 units/kg
Calculate dose at 0.3 to 0.5 units/kg/day:
Basal-bolus Insulin o 50% of dose will be given as basal insulin
NPH: 2/3 pre-breakfast, 1/3 pre-dinner
175
Glargine or Detemir: give at bedtime
o 50% of dose will be given as bolus insulin in equal divided doses pre-meals
Example:
Intermediate acting insulin: 20-0-10 (this means, 20 units given pre-breakfast +
Sample Order 10 units given pre-supper)
Regular acting insulin: 4-4-4 (this means, 4 units given pre-breakfast, 4 units
given pre-lunch, and 4 units given pre-supper)
B. Common Hypoglycemic Agents (OHAs)

DRUG CLASS SUBTYPES EXAMPLES GENERAL MECHANISM OF COMMON SIDE
ACTION EFFECTS
Gliclazide
Sulfonylureas Glibenclamide
Insulin Glimepride Increases insulin secretion Hypoglycemia
Secretagogues Glipizide Weight gain
Non-sulfonylureas Repaglinide
Nateglinide
Decreases hepatic
Biguanides Metformin glucose production and Weight loss
improves peripheral Lactic acidosis
Insulin glucose utilization
Sensitizers Decreases insulin Edema
Thiazolidinediones Rosiglitazone resistance, increases Weight gain
Pioglitazone glucose utilization Osteoporosis
Anemia
Intestinal Alpha-glucosidase Acarbose Inhibits intestinal Weight loss
Absorption Inhibitors Miglitol absorption of sugars Diarrhea
Inhibitors Lipase Inhibitors Orlistat Flatulence
Sitagliptin
DPP-IV Inhibitors Saxagliptin
Incretin- Linagliptin Prolongs endogenous Headache
Related Drugs Vildagliptin GLP-1 action Nasopharyngitis
GLP-1 Agonists Exenatide
(Parenteral) Liraglutide
Increases, urinary glucose Glucosuria
excretion Urinary tract &
Na+ -Glucose Dapagliflozin Inhibits subtype 2 Na+- vaginal infections
Co-Transporter-2 Canagliflozin glucose transport protein Dehydration
Others Inhibitors Empagliflozin which is responsible for at Hyperkalemia
least 90% of glucose (limited clinical
reabsorption in the kidney experience)
Amylin Agonists Pramlinitide Slows gastric emptying Nausea
(Parenteral) Decreases glucagon hypoglycemia
176
C. Drugs and their Primary Areas of Control
goals of treatment based on HbA1C
o If HbA1C is <7% Control PPG first
o If HbA1C is 7-9% Control both FPG and PPG
o If HbA1C is >9% Control FPG first
MONOTHERAPY COMBINATION THERAPY INSULIN
Sulfonylureas Sulfonylurea + Lispro

Metformin FPG Metformin FPG Aspart PPG
Thiazoldinediones Sulfonylurea + Regular
Meglitinides Thiazolidinedione NPH
GLP-1 agonists Sulfonylurea + GLP-1 FPG, Glargine FPG
Acarbose PPG agonist PPG Detemir
DPP-IV Metformin + Meglitinide
inhibitors
FPG: Fasting Plasma Glucose

PPG: Postprandial Glucose
D. Goals of Treatment
INDEX GOAL
Glycemic Control
HbA1C (primary goal) < 7.0%
Preprandial capillary plasma glucose 80-130 mg/dL (4.4 – 7.2 mmol/L)
Peak postprandial capillary plasma glucose* < 180 mg/dL (10.0 mmol/L)
Blood Pressure ** < 140/90 mmHg (130/80 for younger patients)
Lipids**
Low-density lipoprotein (LDL) < 100 mg/dL (2.6 mmol/L)
High-density lipoprotein (HDL) >40 mg/dL (1 mmol/L) [M] or > 50 mg/dL (1.3
Triglycerides mmol/L) [F}
< 150 mg/dL (1.7 mmol/L)
*Peak postprandial capillary plasma glucose: 1-2 hours after beginning a meal
**see JNC-8 and Dyslipidemia Guidelines in Cardiology Chapter (values indicated are from the ADA)
E. Self-Monitoring of Blood Glucose (SMBG): For patients on multiple-dose insulin or insulin pump
Prior to meals and snacks, occasionally postprandially, and at bedtime
Prior to exercise or critical tasks such as driving
When they suspect low blood glucose
After treating low blood glucose until they are normoglycemic
F. Monitoring Response
DRUG PEAK EFFECT WHEN TO MONITOR RESPONSE?
Sulfonylureas FPG at 2 weeks
HbA1C at 3 months
1-2 weeks FPG at 2 weeks
Meglitinides HbA1C at 3 months
PPG at initiation
Metformin 2-3 weeks FPG at 2 weeks
HbA1C at 3 months
Acarbose 2-4 weeks HbA1C at 3 months
PPG at initiation
Thiazolidinediones 1-2 months FPG at 4 weeks
HbA1C at 3-6 months
FPG at 2 weeks
DPP-IV Inhibitors 2 weeks HbA1C at 3 months
PPG at initiation
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V. ANTICIPATORY CARE
A. Recommended Annual Laboratories
LABORATORY FREQUENCY
HbA1C testing 2-4 times / year
Screening for Diabetic Neuropathy Annual
Lipid profile & Serum Creatinine Annual
B. Cornerstones of Anticipatore Care

Moderate weight loss of 7% of body weight
150 min/week moderate intensity aerobic exercise, spread over at least 3
Lifestyle Changes days/week, with no more than 2 consecutive days without exercise
Dietary fiber intake of 14 g of fiber/1,000 kcal; saturated fat intake <7%
Smoking cessation and moderation of alcohol intake
Hypertension Best treated with ACE inhibitor (ARB for ACEI intolerant patients)
DASH-style diet by reducing sodium and increasing potassium intake
Dyslipidemia Maximally-tolerated statin therapy regardless of baseline lipid levels for all
diabetics
Antiplatelet Agents Consider for primary prevention in men >50 years or women >60 years with
at least one major risk factor
Diabetic Kidney Disease Recommended daily protein allowance of 0.8 g/kg/day
Screening (comprehensive eye examination by an ophthalmologist or
Retinopathy optometrist)
o Type 1 diabetes: within 5 years after diagnosis
o Type 2 diabetes: shortly after diagnosis
Influenza vaccine to all diabetics > 6 months of age
Immunizations Pneumococcal vaccine if > 2 years old, revaccination if >64 years old
Hepatitis B vaccine in unvaccinated adult diabetic 19-59 years old
C. Approved Drugs for Management of Pre-diabetes (IGT, IFG, HbA1C 5.7-6.4%)

Metformin (strongest evidence)
Acarbose
Thiazolidinediones
GESTATIONAL DIABETES MELLITUS (GDM)

I. DEFINITIONS
Overt DM: pregnant woman who meets the criteria for diagnosis of DM
Pre-Gestational DM: diagnosed in a woman even before pregnancy
GDM: diagnosed in the 2nd and 3rd trimester of pregnancy that is not clearly overt DM
II. DIAGNOSIS (ONE-STEP STRATEGY)

Screen at first prenatal visit based on the International Association of the Diabetes and Pregnancy Study Groups
(IADPSG) criteria using the 75 g OGTT
Any of the following:
FPG: > 92 mg/dL (5.1 mmol/L)
1 hr PPG: > 180 mg/dL (10.0 mmol/L)
2 hr PPG: > 153 mg/dL (8.5 mmol/L)
III. MONITORING
Do SMBG before and 1 hr or 2 hrs after the start of each meal/after the first bite
Glycemic targets in pregnancy
GDM PREEXISTING TYPE 1 AND TYPE 2 DM
FPG < 95 mg/dL (5.3 mmol/L) FPG 60-99 mg/dL (3.3-5.4 mmol/L)
1-hr PPG < 140 mg/dL (7.8 mmol/L) PPG 100-129 mg/dL (5.4-7.1 mmol/L)
2-hr PPG < 120 mg/dL (6.7 mmol/L) HbA1C <6.0%
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IV. MANAGEMENT
A. Medical Nutrition Therapy (MNT)
1. Recommended Daily Caloric Intake and Weight Gain

PREGRAVID BMI CATERGORY Kcal/kg/day TOTAL WEIGHT GAIN
Low (BMI < 18.5) 36-40 <28-40
Normal (BMI 18.5-24.9) 30 25-35
High (BMI 25-29.9) 24 15-25
Obese (BMI >29.9) 12 11-20
2. General Diet Structure

3 meals and 3 snacks
o 50-60% complex high fiber carbohydrates
o 18-20% protein of high biologic value
o < 30% fats
Avoid concentrated sweets and convenience foods
B. Insulin Therapy
Implemented if glycemic goals not met after 1 week MNT
May use NPH, regular insulin, lispro or aspart insulin
V. POSTPARTUM SCREENING
Screen for persistent diabetes and prediabetes using FBS and 75 g OGTT
Done at 6-12 weeks postpartum and 1-3 years thereafter depending on risk factors
Use non-pregnancy criteria
HYPERGLYCEMIC CRISES IN DIABETES
I. ETIOPATHOGENESIS
Associated with absolute or relative insulin deficiency combined with counterregulatory hormone excess volume
depletion, and acid base abnormalities
Decreased insulin-glucagon ratio promotes gluconeogenesis, glycogenolysis and ketogenesis
A. Precipitating Factors
Infection: most common
Discontinuation of or inadequate insulin therapy
Comorbidities such as pancreatitis, MI, stroke
Restricted water intake (bedridden, altered thirst response of the elderly)
Drugs that affect carbohydrate metabolism: steroids, thiazides, sympathomimetic agents, pentamidine,
antipsychotics
B. Types of Hyperglycemic Crisis
1. Diabetic Ketoacidosis (DKA)

Results from increased gluconeogenesis and glycogenolysis and impaired glucose utilization by
peripheral tissues
Formerly a hallmark of DM type 1
Ketones (indicator of DKA) should be measured in individuals with T1DM when glucose > 300 mg/dL
2. Hyperosmotic Hyperglycemic State (HHS)

Greater degree of dehydration and higher endogenous insulin secretion compared with DKA
Primarily seen in individuals in T2DM
Insulin levels inadequate to facilitate glucose utilization by insulin-sensitive tissues but adequate to
prevent lipolysis and ketogenesis
179
A. Diagnostic Criteria for DKA and HHS

DKA HHS
Plasma Glucose (mg/dL) >250 >250 >250 >600
Arterial pH 7.25-7.30 7.00-7.24 <7.00 >7.30
Serum bicarbonate (mEq/L) 15-18 10 to <15 <10 >15
Urine ketones Positive Positive Positive Small
Serum ketones Positive Positive Positive Small
Effective serum osmolality (mOsm/kg) Variable Variable Variable >320
Anion gap >10 >12 >12 Variable
Alteration in Sensorium Alert Alert/drowsy Stupor/coma Stupor/coma
B. Differentiating Features of DKA and HHS

INDEX DKA HHS
CLINICAL FEATURES
Symptoms Nausea, vomiting, thirst, polyuria, Polyuria, weight loss, diminished oral
abdominal pain, dyspnea intake, mental confusion, lethargy, coma
Tachycardia, dehydration, tachypnea, Profound dehydration, hypotension,
Signs Kussmaul respirations, abdominal tachycardia, altered mental status (No
tenderness, decreased sensorium nausea, vomiting, abdominal pain or
Kussmaul respiration unlike DKA)
Development of Over 24 hours Several weeks
manifestations
LABORATORY VALUES
Glucose mmol/L (mg/dL) 13.9 – 33.3 (250-600) 33.3 – 66.6 (600-1200)
Na+ (mEq/L) 125-135 135-145
K+ Normal to increased Normal
Mg2+ Normal Normal
Cl- Normal Normal
Phosphate Decreased Normal
Creatinine Slightly increased Moderately increased
Osmolality (mOsm/mL) 300-320 330-380
Plasma ketones ++++ +/-
Serum bicarbonate < 15 mEq/L Normal to slightly decreased
(mEq/L)
Arterial pH 6.8 – 7.3 > 7.3
Arterial PCO2 (mmHg) 20-30 Normal
Anion Gap (Na- [Cl + High Normal to slightly high
HCO3])
III. MANAGEMENT
A. General Management
Admit to ICU
Measure capillary blood glucose (CBG) every 1-2 hours
Monitor BP, pulse, respirations, mental status and fluid I & O every 1-4 hours
Assess serum electrolytes, ABG and renal function
15-20 mL/kg/hr or 1-1.5 L of pNSS during the first hour (unless with risk of congestion)
Once CBG is ~200-250 mg/dL, shift fluids to D5-IVF (glucose-containing)
Fluid Therapy IVF replacement should correct estimated deficits within the first 34 hours
In renal/cardiac patients, monitor serum osmolality and cardiac, renal and mental status to
avoid iatrogenic overload
Regular insulin preferably by IV route (short half-life & easy titration): mainstay of therapy
Initial IV bolus (0.1 unit/kg) is given, then infusion started at 0.1 units/kg/hr (see algorithm)
Insulin Therapy If CBG does not decrease ~50-75 mg/dL/hr, increase insulin infusion rate (two to three-
fold) hourly until with a steady glucose decline
When CBG ~200 mg/dL in DKA or 300 mg/dL in HHS, may decrease insulin infusion rate
180
to 0.02-0.05 units/kg/hr to maintain CBG 150-200 mg/dL in DKA or 250-300 mg/dL in HHS
Potassium Despite depletion of total body potassium, mild-moderate hyperkalemia is common
Insulin therapy, correction of acidosis & volume expansion decrease serum K +
If pH <6.9, start 100 mmol HCO3 in 400 ml sterile water with 20 mEq KCl at 200 ml/h for 2
Bicarbonate hrs until venous pH >7.0
Repeat every 2 hours until pH reaches >7.0
181
Complete initial evaluation. Check capillary glucose and serum/urine ketones to confirm hyperglycemia and ketonemia/ketonuria. Obtain blood for metabolic
profile. Start IV fluids: 1.0 L of 0.9% NaCl per hour1
IV Fluids Bicarbonate Insulin: Regular Potassium
pH > 6.9 pH < 6.9 IV Route IV Route

Determine hydration status (DKA and HHS) (DKA and HHS) Establish adequate renal
function (urine output – 50
No 100 mmol in 0.1 U/kg/B. Wt. ml/hr)
Severe Cardiogenic
HCO3- 400 ml H2O as IV bolus
Hypovolemia Shock
+ 20mEq 0.14 U/kg
Mild KCL, infuse Bwt/hr as IV
dehydration for 2 hours 0.1 U/kg/hr IV continuous insul
Hemodynamic continuous infusion K+ <3.3 mEq/L K+ >5.2 mEq/L
Administer
0.9% Nacl monitoring/ insulin infusion
pressors Repeat
(1.0L/hr)
every 2
hours until Hold insulin and give Do not give K+, but
pH > 7. If serum glucose does not fall by 20 – 30 mEq/hr check serum K+ every 2
Monitor at least 10% in first hour, give 0.14 Until K+ >3.3 mEq/L hours
Elevated corrected serum
Na+ serum K+ U/kg as IV bolus, then continue
every 2 previous Rx
hours
Serum Serum Na+ Serum
Na+ high normal Na+ low DKA HHS
K+ = 3.3 – 5.2 mEq/L
When serum glucose reacges 200 When serum glucose reaches 300
mg/dL, reduce regular insulin mg/dl, reduce regular insulin
0.45% NaCl 0.9% NaCl infusion to 0.02-0.05 U/kg/hr IV, or infusion to 0.02-0.05 U/kg/hr
(250-500 ml/hr) (250-500 ml/hr) Give 20 – 30 mEq K+ in each
give rapid-acting insulin at 0.1 between 200 and 300 mg/dl until
depending on depending on liter of IV fluid to keep serum
U/kg SC every 2 hours. Keep patient is mentall alert. K+ between 4-5 mEq/L
hydration state hydration state serum glucose between 150 and
200 mg/dl until resolution of DKA.
When serum glucose reaches 200

mg/dl (DKA) or 300 mg/dl (HHS),
change to 5% dextrose with Check electrolytes, BUN, venous pH, creatinine and glucose every 2-4 hrs until stable. After
0.45% NaCl at 150-250 ml/hr resolution of DKA or HHS and when patient is able to eat, initiate SC multidose insulin regime.
To transfer from IV to SC, continue IV insulin infusion for 1-2 hrs after SC insulin begun to
ensure adequate plasma insulin levels. In insulin naïve patients, start at 0.5 U/kg to 0.8 U/kg
body weight per day and adjust insulin as needed. Look for precipitating cause(s).
182
B. Transition to Subcutaneous (SQ) insulin
Overlap 1-2 hours between IV and SQ insulin to prevent recurrence of hyperglycemia or ketoacidosis
If the patient remains on NPO, continue IV insulin
Patients with known DM may be given insulin at the dose they were receiving before the onset of DKA so long as
it was controlling glucose properly
For insulin-naïve patients, start insulin regimen at 0.5-0.8 units/kg/day
C. Criteria for Resolution

DKA HHS
Plasma glucose <200 mg/dL and two of the following: Normal serum osmolality
Serum bicarbonate level > 15 mEq/L Improvement of normal mental status
Venous pH >7.3
Calculated anion gap < 12 mEq/L
IV. COMPLICATIONS
A. Hypoglycemia and Hypokalemia

Due to overzealous treatment of DKA with insulin and bicarbonate
B. Hyperchloremic Non-Anion Gap Acidosis

Usually seen during the recovery phase of DKA
Caused by loss of ketoanions plus excess infusion of chloride-containing fluids during treatment
C. Cerebral Edema
Occurs in ~0.3-1% of DKA in children but rare in adults
Associated with 20-40% mortality rate
Symptoms: headache, gradual deterioration in level of consciousness, seizures, sphincter incontinence, pupillary
changes, papilledema, bradycardia, elevation in BP and respiratory arrest
Treated with mannitol and mechanical ventilation
DIABETIC FOOT ULCER

I. ETIOPATHOGENESIS
Diabetics are prone to foot ulcers
Development is attributed to: neuropathy, ischemia, infection and immune impairment
Neuropathy: most common underlying etiology of foot ulceration
II. CLASSIFICATION OF DIABETIC FOOT ULCERS

A. Wagner Classification System
Assesses ulcer depth and the presence of osteomyelitis or gangrene
o Grade 0: pre- or post-ulcerative lesion, completely epithelialized
o Grade 1: partial / full thickness ulcer; superficial wound
o Grade 2: penetrates the tendon or capsule
o Grade 3: deep with osteitis
o Grade 4: partial foot gangrene
o Grade 5: whole foot gangrene
B. University of Texas System

Assesses ulcer depth, presence of wound infection, and presence of signs of lower-extremity ischemia
Within each wound grade, there are four stages
Example: A superficial wound that is ischemic but not infected is classified as Grade 1, Stage C
DEPTH OF ULCER PRESENCE OF INFECTION / ISCHEMIA
Grade 0: pre- or post-ulcerative lesion, epithelialized Stage A: (-) infection, (-) ischemia
Grade 1: superficial wound Stage B: (+) infection, (-) ischemia
Grade 2: wound penetrates tendon or capsule Stage C: (-) infection, (+) ischemia
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Grade 3: wound penetrates bone and joint Stage D: (+) infection, (+) ischemia
III. DIFFERENTIALS FOR A FOOT ULCER

FOOT ULCER USUAL ETIOLOGY DESCRIPTION
Diabetic neuropathy (“DM Located at the sites of trauma, such as areas of callus
Neuropathic Ulcer foot”) formation, bony prominence or parts of foot exposed to mild
chronic trauma
Small, annular, pale, tender, circumscribed and dessicated
Arterial (Ischemic) Peripheral arterial Located on distal areas of limbs (e.g., toes, heels,
Ulcer occlusive disease fingertips)
(PAOD) May progress to tissue necrosis & gangrene
May co-exist in diabetic patients with PAOD
Large, irregular borders, erythematous & moist (shiny
Chronic venous appearance)
Venous Ulcer insufficiency (CVI) Located near the medial or lateral malleolus
Chronic venous edema may impart hemosiderin deposition
in the skin, giving rise to a “brawny appearance”
IV. MANAGEMENT
A. Screening & Surveillance

Screen for distal polyneuropathy at diagnosis and at least annually thereafter
Annual comprehensive foot examination
o Inspection
o Assessment of foot pulses and ankle brachial index (ABI)
o Tests for loss of protective sensation: 10-g monofilament plus either: vibration using 128-Hz tuning fork,
pinprick sensation, ankle reflexes, and vibration perception threshold
B. General Management
Medications for relief of symptoms from polyneuropathy or autonomic neuropathy are recommended
General foot self-care education
Use multi-disciplinary approach:
o Refer patients to foot care specialists for ongoing preventive care and surveillance
o Refer patients with significant claudication or positive ABI for further vascular assessment
HYPOGLYCEMIA
I. ETIOPATHOGENESIS
Defined as glucose levels <55 mg/dL with symptoms that are relieved promptly after the glucose level is raised
Recurrent hypoglycemia can induce a vicious cycle of hypoglycemia-associated autonomic failure
hypoglycemia unawareness and defective glucose counterregulation
Hepatic glycogen stores usually last only in 48 hours
A. Physiologic Response to Hypoglycemia

1ST line of defense Decreased insulin (primary glucose regulatory factor)
2nd line of defense Increased glucagon (primary glucose counterregulatory factor)
3rd line of defense Increased epinephrine (critical when glucagon is deficient)
Other defenses Increased cortisol and growth hormone
B. Common Causes of Hypoglycemia

Drugs used to treat DM (insulin/insulin secretagogues)
Alcohol intake
Critical illness (hepatic, renal, cardiac failure, sepsis, inanition)
Hormone deficiencies (cortisol, glucagon, epinephrine)
Endogenous hyperinsulinism (includes islet- and non-islet cell tumors)
Accidental, surrpetious or malicious hypoglycemia
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II. DIAGNOSIS (WHIPPLE’S TRIAD)
1. Symptoms consistent with hypoglycemia
o Neuroglycopenic symptoms: behavioral changes, confusion, fatigue, seizures, loss of consciousness
o Adrenergic symptoms: palpitations, tremors, anxiety, sweating
2. Low plasma glucose measured with a precise method (not a glucose monitor)
3. Relief of symptoms after the plasma glucose level is raised
III. TREATMENT
If awake initial dose of 20 g oral glucose
If unconscious or unwilling parenteral glucose 25 g, if not practical SC or IM glucagon (1.0 mg in adults)
Manage primary reason for hypoglycemia
HYPERTHYROIDISM
I. ETIOPATHOGENESIS
Consequence of excessive thyroid function
II. CLASSIFICATION
Thyrotoxicosis: clinical syndrome resulting from cellular responses to excessive thyroid hormone (may be
exogenous or endogenous)
Hyperthyroidism: clinical state resulting from increased production of thyroid hormones from the thyroid gland
itself (endogenous)
PRIMARY THYROTOXICOSIS SECONDARY THYROTOXICOSIS THYROTOXICOSIS WITHOUT
HYPERTHYROIDISM
Graves’ disease TSH-secreting pituitary adenoma Subacute thyroiditis
Toxic multinodular goiter Thyroid hormone resistance Silent thyroiditis
Toxic adenoma syndrome Thyroid destruction: amiodarone,
Functioning thyroid Ca Chorionic gonadotropin-secreting radiation, infarction of adenoma
metastasis tumors Ingestion of excess thyroid
Activating mutation of TSH Gestational thyrotoxicosis hormone (thyrotoxicosis factitia)
receptor or thyroid tissue
McCune-Albright syndrome
Struma ovarii
Drugs: iodine excess (Jod-
Basedow)
A. Graves’ Disease
Accounts for 60-80% of thyrotoxicosis
Typically occurs between 20 and 50 years of age; also occurs in the elderly
Caused by thyroid-stimulating immunoglobulin (antibodies to the receptor for TSH chronically stimulate TSH
receptor)
Diagnosis is straightforward in a patient with:
o Biochemically-confirmed thyrotoxicosis
o Diffuse goiter on palpation
o Ophthalmopathy
o Dermopathy
B. Toxic Multinodular Goiter (MNG)

Presence of functional autonomy (in contrast to nontoxic MNG)
Includes subclinical hyperthyroidism or mild thyrotoxicosis
C. Hyperfunctioning Solitary Nodule (Toxic Adenoma)

Mutations lead to enhanced thyroid follicular cell proliferation and function
Thyrotoxicosis is usually mild
Disorder is suggested by:
o Thyroid nodule: generally large enough to be palpable
o Absence of clinical features suggestive of Graves’ or other causes of thyrotoxicosis
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Radioiodine Ablation (RAI): treatment of choice

SYMPTOMS SIGNS
Hyperactivity, irritability, Weight loss with increased Tachycardia Warm, moist skin
dysphoria appetite Atrial fibrillation in the Muscle weakness, proximal
Heat intolerance and Diarrhea elderly myopathy
sweating Polyuria Tremor Lid retraction or lag
Palpitations Oligomenorrhea Goiter Gynecomastia
Fatigue and weakness Loss of libido
IV. DIAGNOSTICS
A. Common Diagnostics Used:

Sensitive TSH analysis Single best screening test for hyperthyroidism
TSH is suppressed
Free T4 RIA Elevated (isolated T4 toxicosis is occasionally seen when hyperthyroidism is
induced by excess iodine)
Free T3 RIA Elevated (may be the only thyroid hormone elevated T3 toxicosis)
Thyroid-Stimulating Elevated (not routinely necessary)
Antibodies
Graves’ Disease: enlarged gland and increased tracer uptake that is distributed
homogenously
Toxic Adenoma: focal areas of increased uptake with suppressed tracer uptake in
Radioactive Iodine the rest of the gland
Uptake and Thyroid Toxic MNG: gland is enlarged often with distorted architecture and multiple areas
Scan of relatively increased or decreased tracer uptake
Subacute Thyroiditis: very low uptake because of follicular cell damage and TSH
suppression
Thyrotoxicosis factitia: low uptake
B. Interpretation of Thyroid Function Test Results

RESULT DIFFERENTIALS
TSH FT4
Low High Primary thyrotoxicosis: Graves’ disease, multinodular goiter, toxic adenoma
Destructive thyroiditis, excess iodine intake, excess thyroid hormone
Low Normal Subclinical hyperthyroidism (if normal FT3)
T3 toxicosis (if high FT3)
Normal / High High Secondary thyrotoxicosis: TSH-secreting pituitary adenoma or thyroid hormone
resistance syndrome
V. MANAGEMENT
A. Medical Management
CLASS EXAMPLES MECHANISM SIDE EFFECTS
Inhibit thyroid peroxidase Common side effects: rash,
Propylthiouracil (PTU) 50- (TPO), reducing oxidation urticarial, arthralgia
150 mg PO q8h and organification of iodide Rare but major side effects:
Thionamides Methimazole 10-20 mg PO Reduce thyroid antibody hepatitis, SLE-like
q8-24h levels (unclear mechanism) syndrome, agranulocytosis
Carbimazole 15-40 mg PO PTU has added benefit in (sore throat, fever, oral
OD thyroid storm (see below) ulcers)
Control adrenergic
Beta- Propranolol 20-40 mg q6h symptoms, especially in the Bradycardia, AV block,
Blockers early stages before anti- bronchospasm, hypotension
thyroid drugs take effect
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B. Radioactive Iodine Therapy (RAI)
Damages gland through cytotoxic effects
Yields quickest resolution of the hyperthyroidism
Leads to post-procedural hypothyroidism and requires lifelong thyroid hormone replacement therapy
Carbimazole or methimazole must be stopped at least 2 days before RAI
PTU has prolonged radioprotective effect and should be stopped several weeks before RAI
Absolute contraindications: pregnancy and breast-feeding
C. Surgical Management
Now uncommonly performed, unless with coexistent thyroid cancer
Surgical candidates:
o Pregnant patients who are intolerant to medications
o Non-pregnant patients how refuse RAI
o Patients with very large goiters
o Pediatric patients
Complications include hypoparathyroidism and vocal cord paralysis
THYROID STORM
I. ETIOPATHOGENESIS
Extreme accentuation of hyperthyroidism, usually with Graves’ Disease or Toxic Multinodular Goiter
<10% of hospital admissions for thyrotoxicosis but reaches mortality rate of 20-30%
A. Pathophysiology
Point at which thyrotoxicosis transforms to storm is controversial
o No evidence that there is an increased production of T3 or T4 causing the storm
o Magnitude of increase in thyroid hormones does not appear to be critical
Increased catecholamine receptors have been noted
Decreased binding to thyroid-stimulating globulin (increased free T3/T4) is a possible mechanism
B. Precipitants of Thyroid Storm

Pre-existing thyrotoxicosis, untreated or partially treated
Surgery (e.g., poorly prepared thyroidectomy in a patient with diffuse toxic goiter)
Other conditions associated with a rapid rise in hormone levels
o Withdrawal of anti-thyroid drug therapy
o Radioiodine therapy
o Vigorous thyroid palpation
o Iodinated contrast dyes
o Salicylates (competes with albumin binding thus increasing free thyroid hormone levels)
Conditions associated with an acute or subacute non-thyroidal illness: infection, stroke, trauma, DKA
II. DIAGNOSIS (Burch and Wartofsky’s Criteria)

A. Thermoregulatory Dysfunction D. Cardiovascular Dysfunction
37.2 – 37.7oC 5 1. Tachycardia (bpm)
37.8 – 38.2oC 10 99 - 109 5
38.3 – 38.8oC 15 110 – 119 10
38.9 – 39.3oC 20 120 – 129 15
39.4 – 39.9oC 25 130 – 139 20
> 40.0oC 30 > 140 25
B. Central Nervous System Effects 2. Congestive Heart Failure / Atrial Fibrillation
Absent 0 Absent 0
Mild (agitation) 10 Mild (pedal edema) 5
Moderate (delirium, psychosis, extreme 20 Moderate (bibasilar rales) 10
lethargy)
Severe (seizure, coma) 30 Severe (pulmonary edema) 15
C. Gastrointestinal-Hepatic Dysfunction Atrial Fibrillation 10
Absent 0 3. Precipitant History
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Moderate (diarrhea, vomiting, abdominal 10 Negative 0
pain)
Severe (unexplained jaundice) 20 Positive 10
INTERPRETATION
<25 Storm unlikely 25-44 Impending Storm >45 Highly suggestive of storm
IV. MANAGEMENT
Goals of Management
o Stop synthesis of new thyroid hormones
o Halt release of preformed thyroid hormones
o Prevent conversion of T4 to T3
o Control adrenergic symptoms associated with thyrotoxicosis
o Control systemic decompensation
o Treat underlying cause
MECHANISM DRUG DOSE ACTION
Inhibits thyroid peroxidase (TPO)
Inhibition of 600-1000 mg LD and Inhibits peripheral conversion of T4 to T3 on
new PTU 200-300 mg q6h high doses
hormone PO/NGT/PR Decreases circulating TSI
production Restores normal suppressor cell activity
Methimazole 20-25 mg PO q6h Inhibits thyroid peroxidase (TPO)
Supersaturated 5 drops q6h 1 hour after
Inhibit Solution of PTU (Wolff-Chaikoff
preformed Potassium Iodide Effect) Blocks thyroid hormone release
hormone (SSKI) Decrease fractional turnover of thyroid iodine
release Lugol’s Solution 4-8 drops PO q6-8h and T4 secretion rate
Sodium ipodate 1-3 g PO QID
Iopanoic acid 1 g PO q8h
60-80 mg PO q4g or 80- Reduces sympathetic overdrive
Control of Propranolol 120 mg q6h High doses also decrease peripheral
adrenergic conversion of T4 to T3
symptoms Atenolol 50-200 mg PO QID Cardioselective
Metoprolol 100-200 mg (may be used in COPD and asthma)
Esmolol 50-100 mcg/kg/min
Acetaminophen 325-650 mg PO q4-6h
Supportive Hydrocortisone 100 mg IV q8 Decreases peripheral conversion of T4
management Addresses relative adrenal insufficiency
Glucose 5-10% solution
Mimics iodine
Lithium 300 mg PO q8h Inhibits coupling of iodotyrosinases and
Alternatives peripheral conversion of T4
Potassium 1 g PO QID
perchlorate
cholestyramine 4 g PO QID Hastens removal of T4 and T4 from serum
HYPOTHYROIDISM
I. ETIOPATHOGENESIS
Results from undersecretion of thyroid hormone
Iodine deficiency remains the most common cause worldwide
Most common causes in areas of iodine insufficiency: autoimmune disease (Hashimoto’s thyroiditis) & iatrogenic
Secondary causes include pituitary and hypothalamic disease
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SYMPTOMS SIGNS
Tiredness, weakness
Dry skin Dry coarse skin
Cold intolerance Cool peripheral extremities
Hair loss Puffy face, hands and feet (myxedema)
Difficulty concentrating and poor memory Diffuse alopecia
Constipation Bradycardia
Weight gain with poor appetite Peripheral edema
Dyspnea & hoarse voice Delayed tendon reflex relaxation
Menorrhagia (later oligomenorrhagia or amenorrhea) Carpal tunnel syndrome
Paresthesia Serous cavity effusions
Impaired hearing
Arranged in Decreasing Order of Frequency
III. COMMON DIAGNOSTICS
A. Common Diagnostics Used:

Sensitive TSH analysis Elevated in primary hypothyroidism
May be normal in secondary hypothyroidism (pituitary disease)
Free T4 Low in primary hypothyroidism
May be normal in mild hypothyroidism
Thyroid autoantibodies May be noted in autoimmune etiologies
Thyroid scan ultrasound To determine the specific cause of hypothyroidism
B. Interpretation of Thyroid Function Test Results

RESULTS DIFFERENTIALS
TSH FT4
High Normal Mild hypothyroidism
High Low Primary hypothyroidism
Autoimmune hypothyroidism (if thyroid autoantibodies are positive)
Normal Low Drug effects, sick euthyroid syndrome, pituitary disease
IV. MANAGEMENT: LEVOTHYROXINE (LT4)

A. Dosage
Start usually with 25-50 mcg/day (1.6 mcg/kg/day)
Use lower dosages of 12.5-25 mcg for patients >60 y/o and those with cardiac disease
B. Duration
Symptoms improve in weeks; lifelong treatment is necessary
Increase dose by 25-50mcg every 4 weeks until patient is clinically and biochemically euthyroid
C. Monitoring
Monitor plasma TSH q3-4 months (maintain in normal range)
For secondary hypothyroidism, monitor serum T4 and other pituitary hormones and give steroid replacement prior
to LT4
GOITER AND NODULAR THYROID DISEASE
I. ETIOPATHOGENESIS
Goiter is defined as an enlarge thyroid gland
Causes include biosynthetic defects, iodine deficiency, autoimmune disease and nodular diseases
II. CLASSIFICATION
A. Diffuse Non-Toxic (Simple or Colloid) Goiter

189
Diffuse enlargement of the thyroid occurs in the absence of nodules and hyperthyroidism
Thyroid function is preserved and most patients are asymptomatic
Pemberton’s sign: symptoms of faintness with facial congestion and external jugular venous obstruction when
arms are raised above the head
Levothyroxine can be started to suppress the TSH into the low-normal, but detectable, range
B. Non-Toxic MNG
Most are asymptomatic
Thyroid architecture is distorted and multiple nodules can be appreciated
C. Toxic MNG
Presence of functional autonomy in contrast to non-toxic MNG
TSH is low, T4 level is normal or minimally increased, and T3 is often elevated to a greater degree than T4
Antithyroid drugs often given with beta-blockers can normalize thyroid function
III. APPROACH TO A THYROID NODULE
Thyroid Ablate, resect or

Scan “Hot” Nodule medically manage
Surgery if further growth

or suspicious cytology
Low “Cold”
TSH Nodule
or
Released by
Intermediate Non inadequate “Hot”
Solitary or Diagnostic Monitor
Nodule
Suspicious TSH (17%) by US

Nodule
Normal Benign
TSH
(69%)
Consider
US Guided Cytopathology Thyroid
FNA Suspicious Scan
or Follicular “Cold” or
(10%) Intermediate
Surgery
Malignant
(4%)
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OSTEOPOROSIS
I. ETIOPATHOGENESIS AND DIAGNOSIS
A reduction in the strength of bone that leads to an increased fracture risk
Diagnosed based on WHO classification criteria for bone mass using dual-energy x-ray absorptiometry (DXA) as
gold standard
Presence of vertebral fractures on either radiograph or VFA examination confirms clinical diagnosis of
osteoporosis
Recommended DXA sites: femoral neck or total femur and/or lumbar spine (distal third of radius if cannot
evaluate spine/hips)
Peripheral BMD technologies (quantitative UTZ, CT scan, single x-ray absorptiometry) done in sites like the
calcaneus, wrist and metatarsals and bone turnover markers should not be used in the diagnosis of osteoporosis
(but can be used in fracture risk assessment and assessing adherence to and effectiveness of therapy)
BONE MINERAL DENSITY (T-Score)
Normal > -1 SD
Osteopenia / Low bone mass Between -1 and -2.5 SD
Osteoporosis < -2.5 SD
Severe osteoporosis < -2.5 SD and > 1 fragility fracture/s
II. SCREENING
A. Osteoporosis Screening Tool for Asian (OSTA)

Used to identify an individual’s risk for osteoporosis in areas where DXA is not widely available
Weight (kg) 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94
(lbs) 88-98 99-109 110-119 120-130 131-141 142-152 153-164 165-174 175-185 186-196 197-208
Age
40-44
45-49
50-54
55-59 LOW
60-64
65-69
70-74
75-79 MEDIUM
80-84
85-89 HIGH
90-94
95-99
A simple tool to identify Asian women at increased risk of osteoporosis.
B. Fracture Risk Assessment Tool (FRAX)

Used to assess fracture probability in all postmenopausal women with at least one WHO risk factor, prior to
undergoing central DXA:
o Low BMI
o Previous fragility fracture
o Parental history of hip fracture
o Glucocorticoid treatment
o Current smoking
o Alcohol intake (at least 3 units/day)
o Rheumatoid arthritis
o Other secondary causes of osteoporosis (e.g., CKD, liver disease, malabsorption, IBD, hypogonadism,
hyperparathyroidism, Cushing’s disease, COPD, androgen deprivation therapy, malignancies)
C. Indications for Bone Density Testing (consider BMD testing):

Women > 65 years and men > 70 years (regardless of risk factors)
Younger postmenopausal women, women in menopausal transition and men 50-69 years with risk factors for
fracture
Adults who have a fracture after age 50
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Adults with a condition associated with low bone mass or bone loss (e.g., RA, on steroids > 3 months)
III. MANAGEMENT OF OSTEOPOROSIS
A. Indications to Treat
IF WITH BMD MEASUREMENT, TREAT IF: IF WITHOUT BMD MEASUREMENT, TREAT IF:
Vertebral compression fracture evident on VFA or Belongs to high-risk category based on OSTA tool
confirmed through radiograph (clinical where central BMD cannot be done or not available
osteoporosis) 10-year probability of hip fracture >3% or any major
BMD T-score of < -2.5 SD osteoporosis related fracture >20% based on FRAX
estimates
B. Pharmacologic Therapies
Biphosphonates
Hormonal replacement therapy
Selective estrogen receptor modulators (SERM)
Strontium ranelate
Parathyroid hormone or its analog (teriparatide)
Calcitonin
Tibolone
RANKL inhibitor (denosumab)
Vitamin D or its analog, in combination with calcium, is used as mandatory adjunct
IV. PREVENTION
Calcium supplementation at least 750-800 mg daily for a minimum of 2 years to prevent bone loss
Calcium Vitamin D3 10-20 mcg to be given with 1000 mg calcium, especially for those with limited sun
exposure
Exercise Supervised high intensity resistance exercise (8-12 repetitions at least 2-3 days/week)
Moderate levels of walking (24 METs/week or 8 h/week of walking at an average pace)
Lifestyle Smoking cessation and limiting alcohol consumption
MULTIPLE ENDOCRINE NEOPLASIA (MEN)

MEN 1 MEN 2
MEN 2A MEN 2B
Parathyroid hyperplasia / adenoma Medullary thyroid carcinoma
Pancreatic islet cell hyperplasia / Pheochromocytoma Medullary thyroid carcinoma
adenoma / carcinoma Parathyroid hyperplasia/adenoma Pheochromocytoma
Pituitary hyperplasia / adenoma MEN 2A + cutaneous lichen Mucosal and gastrointestinal
amyloidosis neuromas
Less common manifestations: foregut MEN 2A + Hirschprung’s disease Marfanoid features
carcinoid, pheochromocytoma, Familial medullary thyroid carcinoma
subcutaneous or visceral lipomas
CUSHING’S SYNDROME
I. ETIOPATHOGENESIS
Constellation of clinical features that result from chronic exposure to excess glucocorticoids of any etiology
Iatrogenic use of glucocorticoids (for immunosuppression or treatment of inflammatory disorders) is the most
common cause
Cushing’s disease refers specifically to Cushing’s syndrome caused by a pituitary corticotrope adenoma
II. CLASSIFICATION
A. ACTH-Dependent
Means that Cushing’s syndrome is due to excess ACTH
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Possible sources of ACTH excess:
o Pituitary corticotrope adenoma (Cushing’s disease)
o Ectopic secretion of ACTH by nonpituitary tumor (paraneoplastic syndrome)
B. ACTH-Independent
Means that Cushing’s syndrome is not due to excess ACTH
Majority of patients with ACTH-independent cortisol excess harbor a cortisol-producing adrenal adenoma
Other causes include adrenocortical carcinoma and nodular adrenal hyperplasia
III. CLINICAL FEATURES

BODY COMPARTMENT/SYSTEM SIGNS AND SYMPTOMS
Body fat Weight gain, central obesity, rounded face, fat pad on back of neck (“buffalo
hump”)
Skin Facial plethora, thin and brittle skin, easy bruising, broad and purple stretch
marks, acne, hirsutism
Bone Osteopenia, osteoporosis (vertebral fractures)
Decreased linear growth in children
Muscle Weakness, proximal myopathy (prominent atrophy of gluteal and upper leg
muscles)
Cardiovascular System Hypertension, edema, atherosclerosis
Metabolism Glucose intolerance/diabetes, dyslipidemia, hypokalemia
Reproductive System Decreased libido, amenorrhea in women (duet to cortisol-mediated inhibition of
gonadotropin release)
Central Nervous System Irritability, emotional lability, depression, cognitive defects, paranoid psychosis
in severe cases
Blood and immune System Increased susceptibility to infections, leukocytosis with eosinopenia and
lymphopenia, hypercoagulability
MINERALOCORTICOID EXCESS
Excess activation of mineralocorticoid receptor leads to:
o Potassium depletion (hypokalemia)
o Increased sodium retention (expansion of extracellular and plasma volume hypertension)
Most common cause is primary hypertension
Clinical hallmark is hypokalemic hypertension
Conn’s Syndrome = aldosterone-producing adrenal adenoma
PITUITARY DISEASES
DISEASE PATHOPHYSIOLOGY CLINICAL MANIFESTATIONS TREATMENT
Frontal bossing Transphenoidal surgery (TSS)
Increased hand and Somatostatin analogs
mandibular enlargement with (Octreotidem, Lanreotide)
Acromegaly Growth hormone prognathism GH receptor antagonist
excess Widened space between (Pegvisomant)
lower incisors Dopamine agonists
Gigantism in children and (Cabergoline, Bromocriptine)
adolescents radiation
Prolactin-producing Galactorrhea Dopamine agonists
Hyperprolactinemia pituitary tumor Amenorrhea (Cabergoline, Bromocriptine)
(prolactinoma), stalk Infertility Surgery (TSS)
compression
Obesity Surgery (selective TSS)
Thick skin Pituitary irradiation
Cushing’s Disease ACTH-producing Moon facies Ketoconazole
adenoma Hypertension Metyrapone
Purple skin striae Mitotane
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Hirsutism
Menstrual disorders
Acne
Bruising
Truncal obesity
Proximal muscle weakness
Oligomenorrhea
Amenorrhea
Infertility
Decreased vaginal secretions
Gonadotropin Decreased libido and potency Hormone replacement
Hypogonadism deficiency Infertility, decreased muscle (testosterone, estrogen,
mass progesterone)
Reduced beard and body hair
growth
Soft testes
Fine facial wrinkles
III. TESTS OF PITUITARY INSUFFICIENCY

HORMONE TEST INTERPRETATION
Insulin Tolerance Test Insulin-induced hypoglycemia should normally induce a rise in GH;
Growth lack thereof suggest GH deficiency
Hormone GHRH test, L-arginine Normal response is a rise in GH
test, L-dopa test Lack thereof suggest GH deficiency
Prolactin TRH test TRH should normally induce a rise in prolactin levels
Insulin Tolerance Test Insulin-induced hypoglycemia induces a rise in ACTH and
subsequently cortisol
CRH test Lack of rise in both ACTH and cortisol suggests ACTH deficiency
Metyrapone blocks cortisol synthesis causing decreased cortisol and
ACTH Metyparone Test increased ACTH
Lack of rise in ACTH suggests ACTH deficiency
Standard ACTH Normal response is an increase in cortisol
Stimulation (Co-syntropin) Lack of rise in cortisol plus low ACTH suggests ACTH deficiency
Test
Basal Thyroid Function TSH normally induces a rise in T3 and T4 levels
Tests: T4, T3, TSH Low TSH with low free thyroid hormones indicate TSH deficiency
TSH Normal response is a rise in TSH (unless thyroid hormone levels are
TRH Test increased)
Lack thereof suggest TSH deficiency
Basal LH and FSH should normally be increased in postmenopausal
LH, FSH, Testosterone, women
LH, FSH Estrogen Low sex hormones in the setting of low LH and FSH indicate pituitary
insufficiency
GnRH Test Normal response is a rise in FSH and LH (most adults); lack thereof
suggests pituitary insufficiency
194
CHAPTER 8
NEPHROLOGY
I. Introduction to Nephrology
II. Fluids and Electrolytes
1. Water Balance
2. Sodium
3. Potassium
4. Calcium
5. Magnesium
6. Bicarbonate
III. Common Renal Conditions
1. Abnormalities in Nephrology
2. Acute Kidney Injury
3. Chronic Kidney Disease
4. Urinary Tract Infections
5. Nephrolithiasis
6. Renal Tubular Acidosis
7. Glomerular Diseases
195
SECTION 1
INTRODUCTION TO NEPHROLOGY
NEPHROLOGY FORMULAS
ANION GAP (SERUM)
Na+ = serum sodium
Anion Gap = Na – (Cl + HCO3) Cl- = serum chloride
HCO3 = serum bicarbonate
ANION GAP (URINE)
Na+ = urine sodium
Urine Anion Gap = Na + K – Cl K+ = urine potassium
Cl- = urine chloride
BUN CREATININE RATIO
BUN = serum BUN in mmol/L
Crea = serum creatinine in umol/L
BUN
BCR = Crea x 247 Interpretation:
Pre-renal azotemia: BCR > 20:1
Oliguric renal failure: BCR 10-15:1
ESTIMATED CREATININE CLEARANCE (COCKROFT – GAULT FORMULA)
(140 – age) x BW BW = body weight in kg
Crea = serum creatinine in mg/dL
CrCl = 72 x Crea *For females, multiply result by 0.85
SERUM OSMOLALITY
Balance between the water and the chemicals dissolved in blood
Find out if severe dehydration or overhydration is present
SERUM OSMOLALITY
Serum Osmolality = 2(Na + K) + RBS + BUN
Na+ = serum sodium; K+ = serum potassium; RBS = serum random blood sugar in mmol/L
BUN = serum BUN in mmol/L
Interpretation:
Normal osmolality: 280 – 295 mosmol/kg
Increased serum osmolality’ dehydration, poorly controlled DM (DKA, HHS), diabetes insipidus
Decreased serum osmolality: overhydration, diuretic use, SIADH
URINE OSMOLALITY (ESTIMATE)

Measure of urine concentration
Large values indicate concentrated urine (i.e., heart failure, dehydration, shock, SIADH)
Small values indicate diluted urine (e.g., diabetes insipidus, renal tubular necrosis, renal failure, pyelonephritis)
URINE OSMOLALITY (ESTIMATE)
Urine Osmolality = (Urine SG – 1) x Urine SG = urine specific gravity
Normal 24-hour urine osmolality = 50-800 mOsm/kg
40,000
FRACTIONAL EXCRETION OF SODIUM (FE Na)
Urine Na+ = urine sodium
Plasma Na+ = plasma sodium
Urine Na x Plasma Crea Urine Crea = urine creatinine
FE Na = Plasma Na x Urine Crea Plasma Crea = plasma creatinine
Interpretation:
FENa < 1%: seen in pre-renal azotemia
FENa > 2%: seen in oliguric acute renal failure
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WATER EXCESS
Water excess = (0.6 x BW in kg) - 0.6 x BW in kg x Actual Na BW = body weight in kg
Na+ = serum sodium
Desired Na
CORRECTED CALCIUM
Calcium must be “corrected” when the albumin is abnormal
This is to correct for the change in total calcium due to the change in albumin-bound calcium/
Corrected Calcium = Actual Ca + [(40 – Albumin) x 0.02] Actual Ca+ = serum calcium in mmol/L
Albumin = serum albumin in g/L
CORRECTED SODIUM
In marked hyperglycemia, ECF osmolality increases
Serum Na+ falls in proportion to ECF dilution, declining 1.6 mEq/L per 100 mg/dL increase in RBS
Corrected Sodium = Actual Na + 0.016 (RBS – 100) Actual Na+ = serum sodium
RBS = random blood sugar in mg/dL
OVERVIEW OF ELECTROLYTE CORRECTION

Hyponatremia
Na deficit = (Desired Na – Actual Na) x BW in kg x 0.6
Hypokalemia
Potassium deficit = Desired K – Actual K 100%
0.27
Hypernatremia (Water Deficit)
Water deficit = Na – 140 x TBW TBW in Males = 0.6 x Body Weight in kg
140 TBW in Females = 0.5 x Body Weight in kg
Bicarbonate Deficit
Bicarbonate deficit = (Desired HCO3 – Actual HCO3) x BW in kg x 0.4
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SECTION 2
FLUIDS AND ELECTROLYTES
WATER BALANCE
I. COMPOSITION OF BODY FLUIDS
Water is the most abundant constituent in the body [50% of body weight in women and 60% in men]
Total body water (TBW): 55-75% intracellular fluid (ICF) and 25-45% extracellular fluid (ECF)
ECF: 25% intravascular [plasma water] and 75% extravascular [interstitial]
Fluid movement between spaces determined by Starling forces
Osmolality: solute or particle concentration of a fluid (mosmol/kg of water)
o Major ECF particles: Na+, Cl-, HCO3
o Major ICF particles: K+, organic phosphate esters
o Effective osmoles: solutes restricted to ECF or ICF and thus determine the effective osmolality of that
compartment
o Ineffective osmoles: solutes that do not contribute to water shifts (e.g., urea) across most membranes
II. HYPOVOLEMIA
A. Causes of Hypovolemia
RENAL CAUSES EXTRARENAL CAUSES
Osmotic diuresis (e.g., mannitol)
Pharmacologic diuresis/natriuresis (e.g.,
furosemide) Fluid loss from GI tract (e.g., impaired GI reabsorption,
Hereditary defects in renal transport proteins, enhanced fluid secretion)
mineralocorticoid defects (e.g., deficiency, Insensible losses (evaporation of water from skin and
resistance) respiratory tract)
Tubulointerstitial injury (e.g., interstitial nephritis, Accumulation of fluid within specific tissue compartments
acute tubular injury, obstructive uropathy) (e.g., interstitium, peritoneum, GI tract)
Excessive renal water excretion (e.g., diabetes
insipidus)
Nonspecific: fatigue, weakness, thirst, postural dizziness, oliguria, cyanosis, abdominal and chest pain, confusion,
obtundation
May be accompanied by symptoms of additional electrolyte abnormalities
C. Physical Examination Findings

LESS RELIABLE MORE RELIABLE
Decreased jugular venous pressure (JVP)
Diminished skin turgor Orthostatic hypotension
Dry oral mucous membranes Orthostatic tachycardia
In severe cases: peripheral cyanosis, cold extremities,
oliguria, altered mental status
D. Diagnostics
DIAGNOSTICS EXPECTED FINDINGS
Increased due to a decrease in glomerular filtration rate (GFR)
Serum BUN, Creatinine Creatinine is more dependable since BUN is influenced by changes in
tubular reabsorption (prerenal azotemia), catabolic states, hyperalimentation,
GI bleeding and protein intake
Serum Aminotransferases May be elevate in hypovolemic shock from hepatic ischemia
(AST, ALT)
Cardiac Biomarkers May be elevated in hypovolemic shock from cardiac ischemia
Routine Chemistries and/or Will reveal acid-base disorders depending on the etiology and severity of
Arterial Blood Gases hypovolemia (e.g. normal anion gap metabolic acidosis from diarrheal illness,
elevated anion gap metabolic acidosis from lactic acidosis)
198
E. Management involves Restoration of Normovolemia and Replacement of Ongoing Losses
Mild hypovolemia: oral hydration and resumption of normal maintenance diet
Severe hypovolemia: IV hydration
CLINICAL SCENARIO APPROPRIATE MANAGEMENT
Normonatremic / Normal saline (0.9% NaCl) is the most appropriate resuscitation fluid
Hyponatremic Patients
Hypotonic solutions:
Hypernatremic Patients o 5% dextrose if water loss only (e.g. diabetes mellitus)
o Hypotonic saline if both water and Na+-Cl loss
Patients with Bicarbonate IV bicarbonate (150 mEq of NaHCO3 in 5% dextrose)
Loss and Metabolic Acidosis
Patients with Severe pRBC transfusions without increasing hematocrit beyond 35%
Hemorrhage or Anemia
SODIUM
Disorders are due to abnormalities in water homeostasis that lead to changes in the relative ratio of sodium to boy
water (the absolute plasma sodium concentration tells nothing about a patient’s volume status)
I. HYPONATREMIA
Defined as plasma Na+ <135 mM
Almost always due to increased circulating AVP and/or increased renal sensitivity to AVP combined with any
intake of free water (exception is hyponatremia due to low solute intake, e.g. beer potomania)
Causes generalized cellular swing
A. Approach to and causes of Hyponatremia

HYPOVOLEMIC HYPONATREMIA EUVOLEMIC HYPERVOLEMIC HYPONATREMIA
HYPONATREMIA
Decrease in total body sodium greater Subclinically volume Increase in total body water greater than
than decrease in total body water expanded patients increase in total body sodium
UNa >20 mM UNa <20 mM UNa >20 mM UNa >20 mM UNa <20 mM
Renal losses
Diuretic excess Extrarenal
Mineralocorticoid losses Glucocorticoid deficiency
deficiency Vomiting Hypothyroidism
Salt-losing deficiency Diarrhea Stress Nephrotic
Bicarbonaturia with Third Drugs Acute or chronic syndrome
RTA and metabolic spacing of Syndrome of renal failure Cirrhosis
alkalosis fluids inappropriate antidiuretic Cardiac failure
Ketonuria Burns hormone (SIADH)
Osmotic diuresis Pancreatitis secretion
Cerebral salt wasting Trauma
syndrome
B. Clinical Manifestations (primarily neurologic)

Early symptoms: nausea, headache and vomiting
Severe cases: seizures, brainstem herniation, coma and death
Key complication is normocapnic or hypercapnic respiratory failure (associated hypoxemia may amplify
neurologic injury)
C. Management
1. Clinical Assessment should Focus on the Underlying Cause:
Check for intake of drugs and supplements
Assessment of volume status (see above) is central to the diagnostic approach
Consider all possible causes of excessive circulating AVP
2. Major Considerations in Management

Presence/severity of symptoms determine the urgency and goals of therapy
199
Patients with chronic hyponatremia are at risk for osmotic demyelination syndrome (ODS) if plasma
Na+ corrected >8-10 mM within the first 24 hours and/or by >18mM within the first 48 hours
Response to therapy is unpredictable: ergo, frequent Na monitoring is needed
Once therapy instituted, focus on treatment or withdrawal of underlying cause
D. Correcting Sodium Deficit and Hyponatremia (Sample Problem)

CORRECT SODIUM DEFICIT SAMPLE CASE
1. Compute for the sodium deficit AP, 60/M, 60 kg, complaining of 3-day history of diarrhea.
Na deficit = (desired Na – actual Na) x BW in kg x 0.6 Serum Na+ 123. Ongoing losses of 200 cc/LBM, -8
*desired Na is usually pegged at 125-135 mEq/L
times/day [Na+ losses in LBM = 25-50 mEqs/L)
2. Compute for the time needed to infuse Na deficit = (133 – 123) x 60 x 0.6 = 360 + 80 mEqs/L
Desired Na – Actual Na
Time needed in infuse = 0.5 mEq / hr
*Desired Na of 133 was calculated by adding 10 mEqs to actual Na + (limit
L
to prevent ODS). We add another 80 mEqs/L deficit to our calculated
value since our patient has ongoing losses of 1.6L LBM/day, equivalent to
3. Compute for the amount of pNSS needed 80 mEqs per day.
Amount of pNSS needed = Computed Na deficit / 154
133 - 123
Time needed to infuse = 0.5 mEqs / hr = 20 hours
4. Calculate the drip rate L
Amount of pNSS needed
Drip rate = time needed to infuse
Amount of pNSS needed = 440 / 154 = 2.9 L
Drip rate = 2.9L / 20 hours = 145 cc/hour

Sample chart order: Start pNSS 1L x 145 cc/hr for a total of 3 liters, re-check serum sodium q6 to 12 hours
II. HYPERNATREMIA
Defined as an increase in plasma Na+ concentration to >145mM
Usually the result of a combined water and electrolyte deficit, with losses of water in excess of those of sodium
A. Causes
GI water loss / diarrhea: most common gastrointestinal cause
Insensible water loss
Renal water loss: osmotic diuresis from hyperglycemia, excess urea, post-obstructive diuresis, mannitol
Diabetes insipidus
B. Symptoms
Symptoms are explained by cellular shrinkage due to efflux of intracellular water
Primarily neurologic: change in sensorium is the most common manifestation
C. Management
Central to the management is correction of the underlying cause:
o Chronic hypernatremia (>48 hours): correction must be carried out slowly to avoid central cerebral edema
(e.g., correct deficit over 48 hours); plasma sodium should not be corrected >10 mM/d
o Acute hypernatremia due to sodium loading can be safely corrected at the rate of 1 mM/h
Water, as much as possible, must be administered per orem or by NGT
Alternatively, D5W can be used with corresponding CBG monitoring
D. Correcting Hypernatremia (Sample Problem)

CORRECT WATER DEFICIT SAMPLE CASE
1. Compute for the water deficit JR, 80/M, 50 kg, bedridden patient presented with
decrease in sensorium at the ER. Na was 155. 24-hour
Water deficit =Na – 140 TBW urine tests showed 1800 cc volume, urine Na+ of 35, urine
140 K+ 72.
Total body water (TBW) is 50% of body weight in
Water deficit = 155 – 140 x 50 x 0.6 = 3.2 L
women and 60% in men
140
2. Compute for ongoing water losses (optional) aka
electrolyte-free water clearance CeH2O = 1.8 (1 – 35 + 72) = 0.4 L
155
200
CeH2O = Urine Volume (1 – Urine Na + Urine K)
Insensible losses = 10 x 50 = 0.5 L
Plasma Na
3. Compute for insensible losses = ~10 mL/kg/day We therefore correct the water deficit of 3.2 L over 48 hours
(less if ventilated, more if febrile) which is roughly 67 cc/hr (1.6 L/day) of free-water
replacement + 0.9 L per day to account for ongoing water
4. Correct the deficit over 48-72 hours (incorporate losses and insensible losses.
insensible losses and ongoing water losses to daily
water replacement) avoiding correction of >10 mM/day
Sample chart order:

Choice 1: Replacement via enteral route: Give 270 cc free-water flushes q6 after feeding
Choice 2: Replacement via parenteral route: to start IVF D5W (or 0.3 NaCl) 1 L x 67 cc/hr
Please do serum sodium q6
POTASSIUM
I. HYPOKALEMIA
Defined as plasma K+ <3.6 mM
Long-standing hypokalemia may predispose to acute kidney injury and lead to ESRD
A. Causes of Hypokalemia
DECREASED INTAKE CELLULAR REDISTRIBUTION INCREASED LOSS
Metabolic alkalosis Non-renal
Insulin o Gastrointestinal loss (diarrhea)
B2-adrenergic activation o Integumentary loss (sweat)
(bronchodilators, tocolytics)
Alpha-adrenergic antagonists Renal
Thyrotoxic periodic paralysis o Increased distal delivery (diuretics,
Starvation Downstream stimulation of Na/K osmotic diuresis, salt-wasting
Clay ingestion ATPase pump (theophylline, nephropathies)
caffeine) o Increased potassium secretion
Anabolic state: vitamin B12 or folic Mineralocorticoid excess
acid administration, GM-CSF, TPN Distal delivery of
Familial hypokalemic periodic nonreabsorbed anions
paralysis (vomiting, NGT suction,
proximal RTA, DKA)
Magnesium deficiency
History: medications, diet, and/or symptoms pointing to a probable cause such as diarrhea and periodic weakness
Presents as cardiac, skeletal and intestinal disturbances
o Muscle weakness and paralysis due to hyperpolarization of skeletal muscles
o Ileus secondary to paralytic effects on intestinal smooth muscle cells
ECG changes include broad flat T waves, ST depression and QT prolongation (usually prominent at levels <2.7
mmol/L)
Predisposes to digoxin toxicity
C. Transtubular Potassium Gradient (TTKG)

TTKG >4 during hypokalemia points to renal loss
The transtubular potassium gradient (TTKG) can also be computed using the following formula
Urine K x Serum Osm

TTKG = Serum K Urine Osm
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D. Management
1. Goal of Therapy
Prevent life-threatening and/or chronic consequences
Replace the potassium deficit
Correct the underlying cause and/or mitigate future hypokalemia
2. Correcting the Potassium Deficit

Urgency of therapy depends on severity of hypokalemia, associated clinical factors & rate of decline
Oral replacement is the mainstay of therapy
Concomitant magnesium deficiency should always be corrected
E. Correcting Hypokalemia (Sample Problem)

CORRECTING POTASSIUM DEFICIT SAMPLE CASE
1. Calculate for potassium deficit JR, 24/M, presented at the ER with bilateral lower extremity
weakness. His siblings share the same symptoms, which
Desired K – Actual K 100% according to them occur usually after heavy meals. Serum
Potassium deficit = 0.27
K+ was noted to be 2.5 mM.
*This formula is used for non-redistributive hypokalemia. For other
cases, the potassium deficit is estimated as 400-800 mmol reduction 3.5 – 2.5
for a 2.0 mM fall in serum K. Potassium deficit = 0.27 100% = 370 mEqs
2. Target K+ for cardiac patients is usually 4.0; Since our patient can actually tolerate feeding, we prefer
otherwise a target of 3.5 is used. the oral route.
If we prefer to correct purely via the oral route we
3. Oral K correction is the preferred therapy for can provide the deficit using 10% oral KCl solution
hypokalemia. The IV route is limited to patients unable (30 cc = 40 mEqs K+). With this formulation, we can
to utilize the enteral route or in the setting of severe give 30cc of 10% oral KCl for a total of 9 doses at
complications (e.g., paralysis, arrhythmia). QID intervals.
Alternatively, to speed up the correcition, we can
4. Use saline solutions rather than dextrose since correct using the oral and IV route simultaneously
dextrose-induced increase in insulin can acutely o pNSS 1L + 30 mEqs KCl x 8 hrs x 3 cycles
exacerbate hypokalemia. (=90 mEqs/day)
o oral KCl 10% solution 30 cc TID x 7 cycles
5. The peripheral IV dose is usually 20-40 mmol of KCl (=120 mEqs/day)
per liter; higher concentrations can cause chemical
phlebitis, irritation and sclerosis. If hypokalemia is There are no hard and fast rules in choosing the method of
severe, IV KCl may be given through a central vein correction, always rely on clinical judgment!
(femoral veins are preferable) with cardiac monitoring
at rates of 10-20 mmol/hour.
6. Careful monitoring of serum K+ during correction.
II. HYPERKALEMIA
Defined as plasma K+ > 5.5mM
A decrease in renal potassium excretion is the most common cause
A. Causes
“PSEUDO” HYPERKALEMIA INTRA- TO EXTRACELLULAR SHIFT INADEQUATE EXCRETION
Acidosis Inhibition of the RAAS
Hyperosmolality (radiocontrast, ACE inhibitors / ARBs / direct renin
hypertronic dextrose, mannitol) inhibitors
Cellular efflux (thrombocytosis, Beta-adrenergic antagonists Blockade of mineralocorticoid
erythrocytosis, leukocytosis, in (noncardioselective agents) receptors (spironolactone,
vitro hemolysis) Digoxin and related glycosides eplerenone)
Hereditary defects in red cell Hyperkalemia periodic paralysis Blockade of ENaC (amiloride,
membrane transport Lysine, arginine, aminocaproic acid triamterene)
Succinylcholine, thermal trauma, Decreased distal delivery
neuromuscular injury, disuse CHF
atrophy, mucositis or prolonged Volume depletion
202
immobilization Hyporeninemic hypoaldosteronism
Rapid tumor lysis Tubulointerstitial disease
Diabetes
Drugs (NSAIDs, COX-2 inhibitors,
beta blockers, cyclosporine,
tacrolimus)
Advanced age
Renal resistance to mineralocorticoid
Tubulointerstitial diseases
Hereditary (defects in ENaC)
Advanced renal insufficiency (CKD,
ESRD, AKI)
Primary adrenal insufficiency
Clinical manifestations are predominantly cardiac in nature
Associated cardiac arrhythmias include sinus bradycardia, sinus arrest, slow idioventricular rhythms, ventricular
tachycardia, ventricular fibrillation and asystole
Classic ECG findings are:
o Tall peaked T waves (5.5-6.5 mM)
o Loss of P waves (6.5-7.5 mM)
o Widened QRS complexes (7-8 mM)
o Sinusoidal pattern (>8 mM)
C. Management
The first priority is assessment of need for emergency treatment followed by comprehensive workup:
o ECG manifestations should be considered as an emergency
o Patients with plasma K+ >6.5, even without ECG changes, should be managed aggressively
o Patients should be placed on continuous cardiac monitoring
The management of hyperkalemia is divided into stages:
1. Cardioprotection (from arrhythmic effects of hyperkalemia)

Calcium raises the action potential threshold and reduces excitability without changing the resting
membrane potential
10 mL of 10% calcium gluconate IV over 2-3 mins with cardiac monitoring
Effect starts in 1-3 minutes and lasts 30-60 minutes
Dose should be repeated if there is no change in ECG findings or if they recur
2. Cellular Redistribution (shifts K+ inside the cells)

TREATMENT DOSING PHARMACOKINETICS OTHERS
Hypoglycemia is a common side
10 units regular insulin + Effect in 10-20 mins effect, therefore follow with D10W
Insulin D50-50 Peaks at 30-60 mins at 5075 ml/h
Lasts for 4-6 hours If glucose > 250 mg/dL, insulin
should be given without glucose
Beta 10-20 mg nebulized Effect in 30 mins Use with caution in patients with
Agonists salbutamol in 4 ml pNSS Peaks at 90 mins cardiac disease
inhaled over 10 minutes Lasts for 2-6 hours
No role in routine treatment of
Bicarbonate hyperkalemia
(IV) 150 mEqs + 1 L D5W Reserved for patients with
hyperkalemia and concomitant
metabolic acidosis
3. Potassium Excretion
TREATMENT IMPORTANT POINTS
Cation Sodium polystyrene sulfonate (SPS) exchanges Na+ for K+ in the GI tract and increased
Exchange fecal K+ excretion
203
Resins Given as 15-30 g premade suspension with 33% sorbitol or 30 cc lactulose
Full effect only after 24 hours and usually requires repeated dosing every 4-6 hours
Diuretics Loop and thiazide diuretics can be utilized to reduce K+ in volume-replete or hypervolemic
patients with sufficient renal function
Dialysis Hemodialysis: most effective and reliable method to reduce plasma K+ concentration
CALCIUM
I. HYPOCALCEMIA
A. Causes
LOW PARATHYROID HORMONE LEVELS HIGH PARATHYROID HORMONE LEVELS (SECONDARY
(HYPOPARATHYROIDISM) HYPERPARATHYROIDISM)
Vitamin D deficiency or impaired 1,25(OH)2D production/action
Nutritional
Renal insufficiency
Parathyroid agenesis Vitamin D resistance
Isolated
DiGeorge syndrome Parathyroid hormone resistance syndromes
PTH receptor mutations
Parathyroid destruction Pseudohypoparathyroidism
Surgical
Radiation Drugs
Infiltration by metastases or systemic Calcium chelators
diseases Inhibitors of bone resorption (bisphosphonates,
Autoimmune plicamycin)
Altered vitamin D metabolism (phenytoin,
Reduced parathyroid function ketoconazole)
Hypomagnesemia
Activating CaSR mutations Miscellaneous
Acute pancreatitis
Acute rhabdomyolysis
Hungry bone syndrome after parathyroidectomy
Osteoblastic metastases (e.g., prostate cancer)
Patients may be asymptomatic (if decreases in calcium are relatively mild and chronic) or may present with life-
threatening complications
Moderate to severe hypocalcemia presents with paresthesias caused by neuromuscular activity
Chvostek’s Sign: twitching of circumoral muscles in response to tapping of the facial nerve anterior to the ear
Trousseau’s Sign: carpal spasms induced by inflation of BP cuff to 20 mmHg above the patient’s SBP for 3
minutes
Severe hypocalcemia can induce seizures, carpopedal spasm, bronchospasm, laryngospasm and prolongation of
QT interval in the ECG
C. Management
OVERVIEW OF CORRECTION (some examples)
Acute Symptomatic Calcium gluconate, 10 mL 10% wt/vol (90 mg or 2.2 mmol) IV, diluted in 50 mL of
Hypocalcemia 5% dextrose solution or pNSS, given IV over 5 mins
Calcium gluconate 10% solution 10 mL 1-2 amp SIVP (10-15 mins)
Continuing Constant IV infusion (10 amps calcium gluconate or 900 mg calcium in 1 L D 5W or
Hypocalcemia pNSS x 24 hours)
Chronic Hypocalcemia Elemental calcium 1,000-1,500 mg/day in divided doses (Calcium carbonate 500 mg
due to 1 tab BID-TID)
Hypoparathyroidism Vitamin D2 or D3 25,000-100,000 U daily or calcitriol [1,25(OH)2D] 0.25-2 mcg/day
(Calcitriol 0.25 mcg/cap OD-BID)
204
III. HYPERCALCEMIA
A. Causes of Hypercalcemia
COMMON CAUSES OF HYPERCALCEMIA
1. Excessive PTH production
Primary hyperparathyroidism (adenoma, hyperplasia, rarely carcinoma)
Tertiary hyperparathyroidism (long-term stimulation of PTH secretion in renal insufficiency)
Ectopic PTH secretion
Inactivating mutation in the CaSR
2. Hypercalcemia of malignancy
Overproduction of PTHrP (many solid tumors)
Lytic skeletal metastases (breast cancer, myoma)
3. Excessive 1,25(OH)2D production
Granulomatous diseases (sarcoidosis, tuberculosis, silicosis)
Lymphomas
Vitamin D intoxication
4. Primary increase in bone resorption
Hyperparathyroidism
Immobilization
5. Excessive calcium intake
Milk-alkali syndrome
Total parenteral nutrition
6. Other causes
Endocrine disorders (adrenal insufficiency, pheochromocytoma, VIPoma)
Medications (thiazides, vitamin A, antiestrogens)
SIGNS AND SYMPTOMS OF HYPERCALCEMIA
Usually asymptomatic and recognized only on routine calcium
Mild Hypercalcemia measurements
(up to 11-11.5 mg/dL) Vague neuropsychiatric symptoms (trouble concentrating, personality
changes, depression), peptic ulcer disease, nephrolithiasis or increased
fracture risk
More Severe Hypercalcemia Lethargy, stupor or coma
(>12-13mg/dL) GI symptoms (nausea, anorexia, constipation, pancreatitis)
ECG Changes Bradycardia, AV block, arrhythmias and shortened QT-interval
C. Mechanism of Hypercalcemia in Various Diseases

MECHANISM EXAMPLES
Excessive PTH Production Hyperparathyroidism, ectopic PTH secretion
Parathyroid Hormone Related Humoral hypercalcemia of malignancy
Peptide (PTHrP) Mediated
Excessive 1,25(OH)2D Tuberculosis, lymphoma, Vitamin D toxicity
Increased Bone Resorption Prolonged immobilization, hyperthyroidism, some malignancies
Drugs Thiazides, anti-estrogens, Vitamin A
Excessive Calcium Intake Iatrogenic, calcium supplements
D. Management
OVERVIEW OF MANAGEMENT
Volume Expansion First line treatment of hypercalcemia
(Hydration) pNSS x 8 hours (may go up to 1-4 L in 24 hours)
Furosemide 20-40 mg IV q8-12h
Forced Diuresis Loop diuretics may be used to enhance Ca excretion but should not be
initiated until volume status has been restored to normal
Diuresis in a dehydrated patient may worsen hypercalcemia
Bisphosphonates Pamidronate 60-90 mg IV over 2-4 hrs
May take up to 24-40 hrs to take effect
205
Acts within a few hours of its administration (used for life-threatening
Calcitonin hypercalcemia)
Principally acts through osteoclasts, blocking bone resorption
Steroids for malignancies (e.g., multiple myeloma, lymphoma)
Others Dialysis for severe hypercalcemia complicated by renal failure refractory to
medical management
MAGNESIUM
Second most abundant intracellular cation
Important in different processes which include:
o Energy transfer, storage and use
o Protein, carbohydrate and fat metabolism
o Maintenance of normal cell membrane function
o Regulation of PTH
I. HYPOMAGNESEMIA
May present with muscular weakness, tremors, seizures, paresthesias, tetany and nystagmus
ECG findings: nonspecific ST-T changes, prolonged QT interval, PVCs, torsades de pointes and ventricular
fibrillation
Usually coexists with hypokalemia and hypocalcemia
CORRECTING MAGNESIUM DEFICIT SAMPLE CASE
1. Calculate for magnesium deficit PR, 40/M, diagnosed cased of CHF, presented with Mg2+
of 0.5
Magnesium deficit = Desired Mg – Actual Mg
Magnesium deficit = 1 – 0.5 = 0.5
Target Mg2+ is usually 1.0 for patients with cardiac
conditions. Otherwise, a target of 0.8 is used Correct the deficit by starting MgSO4 drip as follows:
Start MgSO4 drip: 5g in 250cc D5W x 24 hours (faster drip
2. In correcting for the deficit, 1 g MgSO4 is given per rates can be used for patients with no volume overload)
0.1 mg Mg2+ deficit
BICARBONATE
Usually given in patients with severe metabolic acidosis (except hypercarbic acidosis)
Reacts with H+ ions to form water and carbon dioxide and acts as a buffer against acidosis by raising blood pH
CORRECTING BICARBONATE DEFICIT SAMPLE CASE
1. Compute for the estimated bicarbonate deficit PC, 56/M, 60 kg, diagnosed case of CKD V, lost to
follow-up after initiation HD, presented at the ER gasping
Bicarbonate deficit = (Desired HCO3 – Actual HCO3) x weight in kg x 0.4 ABG showed HCO3 of 9
Desired HCO3 is usually 20-23 in patients with CKD Bicarbonate deficit = (20 – 9) x 60 x 0.4 = 264 mEqs
2. Oral alkali supplementation may be initiated

Sample orders:
There is no hard and fast rule in choosing the method NaHCO3 50 mEqs IV bolus q6h x 3 doses, or
of correction, always rely on clinical judgment (caution NaHCO3 50 mEqs in 250 cc D5W x 8h x 3 cycles
with use of NaHCO3)! NaHCO3 GrX (650 mg) tabs can be given as well
206
SECTION 3
COMMON RENAL CONDITIONS
ABNORMALITIES IN NEPHROLOGY
I. DEFINITION OF TERMS
TERM DEFINITION
Azotemia Reduction in GFR
Abnormal excretion of serum protein
Proteinuria o Microalbuminuria: 30-300 mg/d (or mg/g)
o Macroalbuminuria: 300-3500 mg/d (or mg/g)
o Nephrotic range proteinuria: >3500 mg/d (or mg/g)
Polyuria 24 hour-urine output >3000 mL
Oliguria 24 hour-urine output <400 mL
Anuria Complete absence of urine formation (<100 mL in 24 hours)
Dysuria Pain that occurs during urination; perceived as burning or stinging in the urethra
II. CLUES FOR DIAGNOSIS OF RENAL DISEASES

TERM DEFINITION
Acute Renal Failure Anuria, oliguria, documented recent decline in GFR
Chronic Renal Azotemia > 3 months, prolonges signs of uremia, kidneys reduced in size, broad casts in
Failure urinary sentiment
Acute Nephritis Hematuria, RBC casts, azotemia, oliguria, edema, hypertension
Nephrotic Syndrome Proteinuria > 3.5g/24 h per 1.73m 2, hypoalbuminemia, edema, hyperlipidemia
Urinary Tract Bacteriuria >105 CFU/mL, infectious agent documented in urine, pyuria, leukocyte casts,
Infection frequency, urgency, tenderness
Nephrolithiasis Previous history of stone passage, stone seen on x-ray, renal colic
Renal Tubular Electrolyte disorders, polyuria, nocturia, rencal calcification, large kidneys, renal transport
Defects defects
ACUTE KIDNEY INJURY (AKI)
I. ETIOPATHOGENESIS
Sudden impairment of kidney function resulting in the retention of nitrogenous and other waste products
Defined by:
o Rise from baseline creatinine of at least 0.3 mg/dL within 48 hours or at least 50% higher within 1 week
o Reduction in urine output to less than 0.5 mL/kg per hour for longer than 6 hours
TYPE DESCRIPTION SOME EXAMPLES
Most common form Hypovolemia (e.g. GI losses, poor intake)
Due to inadequate renal plasma flow and Low cardiac output
intraglomerular hydrostatic pressure to Decreased effective circulating volume
Pre-renal support GFR (CHF, liver failure)
Involves no parenchymal damage to the Impaired renal autoregulation (NSAIDs,
kidney; rapidly reversed once ACEi, ARBs, cyclosporine)
intraglomerular hemodynamics are
restored
Most common causes are Glomerular (Acute GN)
o Sepsis Tubules and interstitium
o Ischemia o Ischemia
o Nephrotoxins o Sepsis/infection
Intrinsic Ischemia: hypoxia in the renal medulla o Nephrotoxins
leads to impaired autoregulation, Exogenous (iodinated
endothelial and vascular smooth muscle contrast, aminoglycosides,
damage and leukocyte-endothelial crisplatin, ampho B)
adhesion, vascular obstruction and Endogenous (hemolysis,
207
inflammation rhadbomyolysis, myeloma,
intratubular crystals)
Vascular
o Vasculitis
o Malignant hypertension
o TTP-HUS
Occurs when unidirectional flow of urine Bladder neck obstruction (most common)
Post-renal is acutely blocked, leading to increased Prostatic disease
retrograde hydrostatic pressure and Neurogenic bladder
interference with GFR Therapy with anticholinergics
II. MAJOR CAUSES, CLINICAL FEATURES AND DIAGNOSTICS

ETIOLOGY CLINICAL FEATURES LABORATORY FEATURES COMMENTS
Poor fluid intake / fluid loss BCR >20% Low FeNa, high SG and
Heart failure FeNa <1% urine osmolality may
Evidence of volume Hyaline casts in urine not be seen in CKD &
Pre-renal Azotemia depletion (tachycardia, Urine SG >1.018 diuretic use
hypotension, dry mucous Urine osmolality >500 Most diagnostic:
membranes) mOsm/kg Response to restoration
of hemodynamics
(+) culture from normally FeNa may be low
Sepsis-associated Overt hypotension not sterile body fluids particularly early in the
AKI always seen in mild to Granular casts and renal course but is usually
moderate AKI tubular epithelial cell >1% and osmolality
casts on urinalysis <500 mOsm/kg
Systemic hypotension, often Granular casts, renal
Ischemia-associated superimposed on sepsis tubular epithelial cell
AKI and those with limited renal casts
reserve such as old age and FeNa >1%
CKD
Nephroxtoxin-Associated AKI (Endogenous)
Elevated myoglobin and
Rhabdomyolysis Traumatic crush injuries, CK FeNa may be low
seizures, immobilization Heme (+) with few RBC
on U/A
Anemia FeNa may be low
Hemolysis Recent blood transfusion Elevated LDH Evaluation for
with transfusion reaction Low haptoglobin transfusion reaction
must be done
High turnover disease Hyperphosphatemia,
Tumor Lysis (leukemia, lymphoma) hypocalcemia,
Recent chemotherapy hyperyuricemia
Age > 60 years Monoclonal spike in Bone marrow or renal
Multiple myeloma Constitutional symptoms urine or serum biopsy can be
Bone pain electrophoresis diagnostic
Low anion gap
Nephrotoxin-Associated AKI (Exogenous)
Rise in serum creatinine
Contrast Exposure to iodinated in 1-2 days FeNa may be low
Nephropathy contrast Peak within 3-5 days
Recovery within 7 days
Granular casts, renal
Tubular injury Aminoglycosides, cisplatin, tubular epithelial cell
tenofovir, zoledronate casts
FeNa >1% typically
Recent medication exposure Eosinophilia Urine eosinophils of
Interstitial Nephritis Fever, rash, arthralgias Sterile pyuria limited diagnostic
accuracy
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Non-drug causes: Often non-oliguric Systemic signs of drug
tubulointerstitial nephritis- reaction often absent
uveitis syndrome, Legionella Kidney biopsy may be
infection helpful
Other causes of Intrinsic AKI
Variable features of skin ANA, ANCA, anti-GBM
rash, arthralgias, sinusitis antibody
Glomerulonephritis/ (anti-GBM disease), lung Hepatitis serologies, Kidney biopsy may be
Vasculitis hemorrhage (anti-GBM, cryoglobulins helpful
ANCA-associated, lupus), Blood culture
recent skin infection or Hypocomplementemia
pharyngitis ASO titer
Schistocytes on PBS
TTP/HUS Recent GI infection or use of Elevate LDH Kidney biopsy may be
calcineurin inhibitors Anemia, helpful
thrombocytopenia
Recent manipulation of the
aorta or other large vessels Hypocomplementemia
Atheroembolic May occur spontaneously or Eosinophiluria (variable) Skin or kidney biopsy
disease after anticoagulation Variable amounts of can be diagnostic
Retinal plaques, palpable proteinuria
purpura, livedo reticularis,
GI bleed
History of kidney stones, No specific findings Imaging with computed
Post-renal AKI prostate disease, other than AKI tomography or
obstructed bladder catheter May have pyuria or ultrasound
or pelvic neoplasm hematuria
III. MANAGEMENT
MANAGEMENT THERAPY
ISSUE
Reversal of Renal Insult
Ischemic AKI Restore systemic hemodynamics and renal perfusion through volume resuscitation and use
of vasopressors
Nephrotoxic AKI Eliminate nephrotoxic agents
Consider toxin-specific measures
Prevention and Treatment of Complications
Intravascular volume Salt and H2O restriction
overload Diuretics, ultrafiltration
Hyponatremia Please see selection on “Sodium”
Hyperkalemia Please see selection on “Potassium”
Metabolic acidosis Sodium bicarbonate (maintain serum HCO3 >15 mmol/L or arterial pH >7.2)
Dialysis in severe cases
Restriction of dietary phosphate intake
Hyperphosphatemia Phosphate-binding agents (e.g., calcium carbonate, calcium acetate, sevelamer
hydrochloride, aluminum OH)
Hypocalcemia Calcium carbonate or gluconate (if symptomatic)
Hypermagnesemia Discontinue Mg2+-containing antacids
Hyperuricemia Treatment usually not necessary if <890 umol/L or <15 mg/dL
Allopurinol for tumor lysis, forced alkaline diuresis for rhadbomyolysis
Nutrition Protein and calorie intake to avoid net negative nitrogen balance
Indicated when medical managements fails to control volume overload, hyperkalemia,
Dialysis acidosis and when there are severe complications of uremia (asterixis, pericardial rub or
effusion, encephalopathy, uremic bleeding)
Choice of agents Avoid other nephrotoxins: ACE inhibitors/ARBs, aminoglycosides, NSAIDs, radiocontrast
Drug dosing Adjust doses and frequency of administration for degree of renal impairment
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IV. R-I-F-L-E CRITERIA FOR AKI
STAGE GFR CRITERIA URINE OUTPUT CRITERIA
RISK Serum creatinine increased 1.5x; or Urine output <0.5 mL/kg/h x 6 hours
GFR decreased >25%
IINJURY Serum creatinine increased 2x; or Urine output <0.5 mL/kg/h x 12 hours
GFR decreased >50%
Serum creatinine increased 3x; or Urine output <0.3 ml/kg/h x 24 hours
GFR decreased >75%; or (oliguria); or
FAILURE Serum creatinine > 4 mg/dL; or Anuria x 12 hours
Acute rise > 0.5 mg/dL
LOSS Persistent acute renal failure; complete loss of kidney function >4 weeks
ESRD Complete loss of kidney function >3 months
CHRONIC KIDNEY INJURY (CKD)

I. ETIOPATHOGENESIS
Spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive
decline in GFR
Defined by the KDOQI as kidney damage for > 3 months, as defined by structural or functional abnormalities of
the kidney, with or without decreased GFR, manifested by either of the following or GFR <60 mL/min/1.73 m 2 for
> 3 months with or without damage
o Pathologic abnormalities
o Markers of kidney damage, including abnormalities in the composition of the blood or urine, or
abnormalities in imaging tests
A. Leading Categories of Etiologies of CKD
Diabetic nephropathy
Glomerulonephritis
Hypertension-associated CKD (vascular and ischemic kidney disease)
Autosomal dominant polycystic kidney disease
Other cystic and tubulointerstitial nephropathies
B. Pathophysiology of CKD
Initiating mechanism specific to the underlying etiology
Progressive mechanisms involving hyperfiltration & hypertrophy of the remaining viable nephrons
II. STAGING OF CKD
CKD is alternatively defined by KDIGO as abnormalities of kidney structure or function present for >3 months,
with implications for health and is classified (for prognostication/risk for outcome of CKD) based on case, GFR
category and albuminuria category (CGA)
ESRD: represents a stage of CKD where the accumulation of toxins, fluid and electrolytes normally excreted by
the kidneys results in the uremic syndrome
A. Prognosis of CKD by GFR and Albuminuria Categories: KDIGO 2013
PERSISTENT ALBUMINURIA CATEGORIES
A1 A2 A3
Normal to mildly Moderately Severely
increased increased increased
<30 mg/g 30-300 mg/g >300 mg/g
<3 mg/mmol 3-30 mg/mmol >30 mg/mmol
G1 Normal or high >90 Low risk Moderately High risk
increased risk
GFR G2 Mildly decreased 60-89 Low risk Moderately High risk
categories increased risk
(ml/min/ G3a Mildly to moderately decreased 45-59 Moderately High risk Very high risk
1.73m2) increased risk
G3b Moderately to severely decreased 30-44 High risk Very high risk Very high risk
G4 Severely decreased 15-29 Very high risk Very high risk Very high risk
G5 Kidney failure <15 Very high risk Very high risk Very high risk
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B. Previous Staging of CKD
STAGE DESCRIPTION GFR mL/min/1.73m2 ACTION
Diagnosis and treatment of
I Kidney damage with normal / increased GFR 90 comorbid, slowing progression,
CVD risk reduction
II Kidney damage with mildly decreased GFR 60 – 89 Estimating progression
III Moderately decreased GFR 30 – 59 Evaluating and treating

complications
IV Severely decreased GFR 15 – 29 Preparation for renal
replacement therapy
V Renal failure < 15 (or dialysis) Renal replacement
(if uremia is present)
III. DIAGNOSIS
A. Differentiating Acute Kidney Injury from Chronic Kidney Disease

ACUTE KIDNEY INJURY CHRONIC KIDNEY DISEASE
Kidney size Normal Small
Carbamylated Hemoglobin Normal High
Broad Casts on Urinalysis Absent Present
Histor of Kidney Disease, HPN, Absent Present
Abnormal Urinalysis
Anemia, Metabolic Acidosis, Often present Usually present
Hyperkalemia, Hyperphosphatemia
Reversibility with Time Usually complete Sometimes partial
B. Diagnostics
DIAGNOSTICS EXPECTED FINDINGS
Verifies presence of 2 kidneys, determines symmetry, estimates size and rules out
Renal Ultrasound masses/obstruction
Finding of bilaterally small kidneys supports CKD (expect for early DM
nephropathy, amyloidosis, HIV nephropathy, polycystic kidney disease)
Not advised for bilaterally small kidneys
Renal Biopsy Other contraindications: uncontrolled hypertension, active UTI, bleeding diathesis
(including ongoing anticoagulation) and severe obesity
Other Tests Perform specific tests to assess for specific target organ damage (see above)
IV. CLINICAL MANIFESTATIONS

Uremia leads to disturbances in the function of virtually every organ system
SYSTEMIC FINDINGS COMMENTS / TREATMENT
Fluid, Electrolyte and Acid-Base Disorders
Sodium and Water Homeostasis
o Total body content of Na+ and H2O are modestly
increased Hyponatremia responds to water restriction
o Hyponatremia not commonly seen Salt restriction if with evidence of ECFV
Potassium Homeostasis expansion
o Decline in urinary K+ excretion Diuretics +/- metolazone in CKD III-V
o Increase in K+ due to dietary intake, protein catabolism, Kaliuretic diuretics for hyperkalemia
hemolysis, hemorrhage, transfusion of RBC, acidosis Intractable hyperkalemia is an indication for
o Hypokalemia is uncommon (reduced dietary intake, dialysis
excessive diuretics, GI loss) Alkali supplementation when HCO3 falls below
Metabolic Acidosis 20-23 mmol/L
o Impaired ammoniagenesis
o NAGMA in early stages HAGMA in later stages
Disorders of Calcium and Phosphate Metabolism
Bone manifestations Optimal management is prevention
o High bone turnover with increased PTH levels: osteitis Low-phosphate diet
fibrosa cystica (classic lesion of secondary Use of phosphate-binding agents
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hyperparathyroidism) Calcitriol suppresses PTH secretion directly
o Low bone turnover with low or normal PTH levels:
adynamic bone disease and osteomalacia
Calcium, Phosphorus and Cardiovascular System
o Strong association between hyperphosphatemia and
increased CV mortality
Other complications
o Calciphylaxis (calcific uremic arteriolopathy): almost
exclusive to advanced CKD; livedo reticularis, patches
of ischemic necrosis especially on legs, thighs,
abdomen and breasts (warfarin treatment is at risk
factor)
Cardiovascular Abnormalities (leading cause of morbidity and mortality in CKD patients)
Ischemic Vascular Disease
o CKD is a major risk factor for ischemic CVD
Heart Failure In CKD + DM or proteinuria >1 g/day, BP goal
o Abnormal cardiac function from myocardial ischemia, left is <130/80 with salt restriction as first-line
ventricular hypertrophy and frank cardiomyopathy therapy
o “low-pressure” pulmonary edema in advanced CKD ACEi and ARBs may slow rate of decline of
Hypertension and Left Ventricular Hypertrophy kidney function but can precipitate AKI and
o Hypertension develops early in CKD hyperkalemia
o Absence of hypertension may signify a salt-wasting form Lifestyle changes
of CKD, effect of anti-HPN therapy, volume depletion or Management of hyperlipidemia using dietary
poor left ventricular function measures and statins
o Use of EPO can also increase BP Uremic pericarditis is an absolute indication for
Pericardial Disease urgent initiation or intensification of dialysis
o Chest pain with respiratory accentuation accompanied (heparin-free)
by friction rub
o Observed in advanced uremia (underdialyzed, non-
adherent patients)
Hematologic Abnormalities
Anemia
o Normocytic, normochromic anemia observed as early as
CKD III and universal in CKD IV
o Causes include:
Relative EPO deficiency
Diminished RBC survival Recombinant human EPO should be initiated
Bleeding diathesis once there are adequate bone marrow iron
Iron deficiency stores
Hyperparathyroidism/marrow fibrosis Iron supplementation
Chronic inflammation Vitamin B12 and folate supplementation
Folate or vitamin B12 deficiency Target hemoglobin of 100-115 g/L
Hemoglobinopathy Desmopressin, cryoprecipitate, IV conjugated
Co-morbids such as hypo/hyperthyroidism, estrogen and EPO for abnormal bleeding time
pregnancy, HIV, autoimmune disease and and coagulopathy
immunosuppressive drugs Optimal dialysis corrects prolonged bleeding
Abnormal hemostasis time
o Prolonged bleeding time, decreased activity of platelet
factor III, abnormal platelet aggregation and adhesion
and impaired prothrombin consumption
o Greater susceptibility to thromboembolism especially if
with nephrotic-range proteinuria
Neuromuscular Abnormalities
CNS, Peripheral and Autonomic Neuropathy Most resolve with dialysis
o Early signs seen at CKD III Successful renal transplantation may reverse
o Usually clinically evident at CKD IV residual neurologic changes
Gastrointestinal and Nutritional Abnormalities
Uremic Fetor: urine-like breath odor with dysgeusia Protein restriction may slow the rate of renal
(unpleasant metallic taste) decline at earlier stages
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Gastritis: peptic disease or mucosal ulcerations at any level o Daily protein intake 0.60-0.75 g/kg/day with
of the GI tract at least 50% provided by high-biologic
Anorexia due to retention of uremic toxins value proteins
Protein-Energy Malnutrition (PEM) o 0.90 g/kg/day for CKD IV and those with
PEM; daily total caloric intake of 35 kcal/kg
Calcium and iron supplements may aggravate
constipation and anorexia
PEM: indication for renal replacement therapy
Endocrine-Metabolic Disturbances
Glucose metabolism
o Slowed response to glucose loading Goals: FBS 90-130 mg/dL, HbA1Z <7%
o FBS normal or slightly elevated Reduction in insulin and hypoglycemic agent
o Diminished renal degradation of insulin doses
Sexual dysfunction Intensive dialysis and successful renal
Low estrogen, menstrual abnormalities, inability to carry transplantation may reverse sexual dysfunction
pregnancies to term
Reduced plasma testosterone, oligospermia
Dermatologic Abnormalities
Local moisturizers, mild topical steroids, UV
Pruritus, hyperpigmentation radiation
Nephrogenic fibrosing dermopathy: progressive Minimizing exposure to gadolinium in CKD II
subcutaneous induration especially on the arms and legs and avoidance in CKD III to V
associated with exposure to gadolonium Rapid removal of gadolinium by immediate
dialysis for patients in whom MRI is highly
necessary
IV. MANAGEMENT
A. Slowing Progression of CKD

MANAGEMENT REMARKS
Control of BP and Proteinuria Use anti-HPN therapy with a goal of <140/90 mmHg (see JNC-8 guidelines)
Use ACEi and ARBs for their proteinuria-lowering effects
Control of Blood Glucose FBS 90-130 mg/dL
HbA1C <7%
May slow rate of renal decline at earlier stages
Protein Restriction Daily protein intake 0.60-0.75 g/kg/day with at least 50% provided by high
biologic value proteins
For CKD V and those with PEM: may increase to 0.90g/kg/day
B. Hemodialysis or Renal Replacement Therapy

Relies on the principles of solute diffusion across a semipermeable membrane
Movement of waste products takes place down a concentration gradient from circulation into the dialysate
Clear indications for initiation of renal replacement therapy
o Uremic pericarditis
o Encephalopathy
o Intractable muscle cramping
o Anorexia and nausea not attributable to reversible causes such as peptic ulcer disease
o Evidence of malnutrition
o Fluid and electrolyte abnormalities refractory to other measures
URINARY TRACT INFECTIONS (UTI)

I. ETIOPATHOGENESIS
UTI may be asymptomatic (subclinical infection) or symptomatic (disease)
Both UTI and asymptomatic bacteriuria connote the presence of bacteria in the urinary tract, usually accompanied
by WBCs and inflammatory cytokines in the future
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A. Encompasses a Variety of Clinical Entities
Asymptomatic Bacteriuria Presence of bacteria in the urinary tract in the absence of symptoms attribute
(ABU) to the presence of bacteria and does not usually require treatment
Definition: > 105 bacterial CFU/mL in urine
Acute cystitis or pyelonephritis in premenopausal non-pregnant outpatient
women without anatomic abnormalities or instrumentation of the urinary tract
Acute uncomplicated cystitis (AUC): symptomatic infection in the urinary
Uncomplicated UTI bladder (acute onset dysuria, urgency, frequency, hematuria without vaginal
discharge)
Acute complicated pyelonephritis (AUP): symptomatic infection in the
kidneys (fever > 38oC, flank pain, costoverbal tenderness, +/- symptoms of
lower UTI)
Catch-all term that encompasses all other types of UTI, defined as:
o Presence of indwelling urinary catheter or intermittent catheterization
o Incomplete emptying of the bladder with >100mL retained urine post-
voiding
o Impaired voiding due to neurologic bladder or cystocoele, obstructive
uropathy, vesicoureteral reflux and toher urologic abnormalities including
surgical, ischemic or radiation injuries of the uroepithelium, peri-/post-
Complicated UTI operative UTI
o Intrinsic renal azotemia, renal transplantation, DM, immunosuppression
(febrile neutropenia, HIV/AIDS)
o UTI caused by unusual (M. tuberculosis, Candida spp) UTI or MDR
pathogens
o UTI in males except in young males presenting exclusively with lower UTI
symptoms
o Urosepsis
Recurrent UTI Not necessarily complicated
Catheter-Associated Can by symptomatic (CAUTI) or asymptomatic
Bacteriuria / UTI Definition: >102 bacterial CFU/mL in urine
B. Etiology
Uropathogens causing UTI: usually enteric gram-negative rods that have migrated to the urinary tract
Common pathogens
o E. coli
o Staphylococcus saprophyticus
o Klebsiella spp.
o Proteus spp.
o Enterococcus spp.
In majority of cases, bacteria establish infection by ascending from urethra to bladder
Bacteria can also gain access to the urinary tract by hematogenous spread

Cystitis Dysuria, urinary frequency, nocturia, hesitancy, suprapubic discomfort, gross
hematuria (without vaginal discharge)
Mild cases present with low-grade fever with or without lower-back or
costovertebral-angle pain
Pyelonephritis Severe cases present with high fever, rigors, nausea, vomiting and flank/loin pain
Urinalysis reveals pyuria (> 5 wbc/hpf of centrifuged urine) & bacteriuria (> 10,000
CFU of uropathogen/mL)
Emphysematous Severe form characterized by production of gas in renal and perinephric tissues
Pyelonephritis Almost exclusive in DM patients
Xanthrogranulomatous Occurs when chronic urinary obstruction, together with chronic infection, leads to
Pyelonephritis suppurative destruction of renal tissue
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III. DIAGNOSIS
DIAGNOSTIC EXPECTED FINDINGS
Urinalysis and Urine Urine microscopy reveals pyuria (~100%) and hematuria (~30%)
Dipstick Test Dipstick test for nitrite and leukocyte esterase test can be used in certain areas
Urine Culture Detection of bacteria in urine culture is the “gold standard” for UTI
Recommended in cases of pyelonephritis to facilitate cost-effective use of antibiotics
Blood Culture Not routinely recommended unless the patient presents with signs of sepsis
Biomarkers Procalcitonin, mid-regional pro-atrial natriuretic peptide and CRP all not
recommended
Not routinely recommended
Considered for patients with:
Radiologic Imaging o History of urolithiasis, urine pH > 7.0 or renal insufficiency
o Who remain febrile despite 72 hours of treatment
o Whose symptoms recur (to rule out nephrolithiasis, obstruction, abscess
formation or other complications of pyelonephritis)
Other tests Perform specific tests to assess for specific target organ damage (see above)
IV. MANAGEMENT OF UTI

A. Acute Uncomplicated Cystitis
Empiric antibiotic treatment: most cost-effective management approach (pre-treatment urine culture and
sensitivity is not recommended and urine microscopy and dipstick test are not prerequisites for treatment)
Patients whose symptoms worsen or do not improve after completion of initial treatment should have a culture
done and antibiotics empirically changed pending result of sensitivity testing
Patients in whom symptoms fail to resolve after treatment should be managed as complicated UTI
DRUG DOSE
Primary Nitrofurantoin macrocrystals (first line) 100 mg QID x 7 days PO
Treatment Fostomycin trometamol 3 g PO single dose
Fluoroquinolones
Ofloxacin 200 mg BID x 3 days PO
Ciprofloxacin 250 mg BID x 3 days PO
Levofloxacin 250 mg OD x 3 days PO
Alternative Norfloxacin 400 mg BID x 3 days PO
Treatment Beta-Lactams
Amoxicillin-clavulanate 625 mg BID x 7 days PO
Cefuroxime 250 mg BID x 7 days PO
Cefixime 200 mg BID x 7 days PO
Cefpoxodime proxetil 100 mg BID x 7 days PO
B. Acute Uncomplicated Pyelonephritis

Hospital admission (and IV antibiotic use, as necessary) is recommended for patients with:
o Inability to maintain oral hydration or take medications / concern with compliance
o Presence of possible complicating conditions
o Severe illnesses with high fever, severe pain, marked debility and signs of sepsis
ORAL PARENTERAL
Ciprofloxacin 500 mg BID x 7-10 days Ceftriaxone 1-2 g q24h
Ciprofloxacin 1000 mg BOD x 7 days Ciprofloxacin 400 mg q12h
Extended-Release
Levofloxacin 250 mg OD x 7-10 days Levofloxacin 250-750 mg q24h
750 mg OD x 5 days
Ofloxacin 400 mg BID x 14 days Ofloxacin 200-400 mg q12h
IV antibiotics can be shifted to any of the above oral antibiotics once Amikacin 15 mg/kg q24h
afebrile (day 3) and can tolerate drugs PO (guided by GS/CS results) Gentamicin +/- Ampicillin 3-5 mg/kg q24h
Multi-drug resistant organisms: ertapenem 1 g q24h or piperacillin-tazobactam 2.25-4.5 g q6-8h

Aminopenicillins and first-generation cephalosporins: not recommended (high prevalence of resistance)
TMP-SMX must be used only if the uropathogen is proven to be susceptible
Routine post-treatment culture in patients who are clinically improved is not recommended
215
C. UTI in Pregnancy
Screening should be done between 9th-17th week AOG, preferably on the 16th week for all pregnant women
The following are considered relatively safe in early pregnancy:
o Nitrofurantoin
o Ampicillin
o Cephalosporins
D. UTI in Males
Men with uncomplicated UTI 7 to 14 days of fluoroquinolone or TMP-SMX
Acute bacterial prostatitis Get cultures and tailor therapy and continue for 2-4 weeks
Chronic bacterial prostatitis 4-6 weeks of antibiotics
Recurrent bacterial prostatitis 12 weeks of antibiotics
Retreatment in the absence of 2 weeks
urologic abnormalities 4-6 weeks if repeat culture reveals same organism as initial infecting organism
NEPHROLITHIASIS
Calcium salts, uric acid, cysteine and struvite are the common constituents
May be asymptomatic and incidentally noted during radiographic studies undertaken for unrelated reasons
Common cause of isolated hematuria
As the stone traverses the ureter, it may present with pain (beginning at the flank, gradually increasing in severity
over the next 20-60 mins, may radiate to ipsilateral groin, testis or vulva) and bleeding
Stone <0.5 cm may pass spontaneously
Helical CT scan without radiocontrast is the standard diagnostic procedure
TYPE COMMON ETIOLOGIES DIAGNOSIS TREATMENT
Low-sodium and protein diet
Idiopathic hypercalciuria Serum and urine Thiazides (idiopathic
Calcium Stones Hypocitraturia calcium hypercalciuria)
(75-85%) Dietary hyperoxaluria Urine oxalate Alkali supplements (hypocitraturia)
Low-oxalate, normal calcium
(dietary hyperoxaluria)
Metabolic syndrome Glucose intolerance
Uric Acid Gout Obesity Alkali and allopurinol if daily urine
Stones (5-10%) Idiopathic Hyperlipidemia uric acid > 1000 mg
Clinical for gout
Cysteine Stone type Fluids and alkali
Stones (1%) Hereditary Elevated cysteine D-penicillamine if needed
excretion
Struvite Stones Infection Stone type (Mg2+, Antibiotics and judicious surgery
(5%) PO4-, NH3)
RENAL TUBULAR ACIDOSIS (RTA)

Disorder of renal acidification out of proportion to the reduction in GFR
Characterized by hyperchloremic metabolic acidosis with normal anion gap
TYPE CLINICAL FEATURES TREATMENT
Kidneys unable to acidify urine to pH <5.5 in
presence of systemic metabolic acidosis or after acid
loading Alkali replacement 1-3 mmol/kg/day in
Due to impaired hydrogen ion secretion or HCO 3 divided doses
Type 1 reabsorption in distal nephron Citrate tolerated better than sodium
Distal Features: hypokalemia, hypocitraturia, hypercalciuria, bicarbonate
nephrocalcinosis and/or nephrolithiasis
Most patients are asymptomatic; usually discovered
incidentally during evaluation for kidney stones
Type 2 Result of impaired bicarbonate reabsorption in the Alkali supplementation 5-15
Proximal proximal tubule where the bulk of filtered HCO 3 is mmol/kg/day with supplemental
216
recovered potassium
Features: hyperphosphaturia, hyperuricosuria,
hypercalciuria, non-selective aminoaciduria &
glycosuria
Distal tubule secretion of K+ and H+ ions are impaired,
Type 4 resulting in hyperchloremic acidosis with Correction of hyperkalemia
hyperkalemia Management of renal dysfunction
Most common form of RTA
GLOMERULAR DISEASES
Acute Nephritic Syndrome Pulmonary-Renal Syndromes Nephrotic Syndrome
1-2 g/24h proteinuria >3 g/24h proteinuria
Hematuria with RBC casts Hypertension
Pyuria RPGN with lung hemorrhage Hypercholesterolemia
Hypertension Hypoalbuminemia
Fluid retention Edema/anasarca
Rise in serum creatinine Microscopic hematuria
PROTOTYPE DISEASES
Post-streptococcal GN Minimal change disease
Subacute bacterial IE Goodpasture’s syndrome Focal segmental glomerulosclerosis
Lupus nephritis ANCA small-vessel vasculitis Membranous glomerulonephritis
Anti-GBM (Wegener’s, Churg-Strauss, Diabetic neuropathy
IgA nephropathy Microscopic polyangitis) AL and AA amyloidosis
ANCA small-vessel vasculitis HSP Light-chain deposition disease
Henoch-Schonlein purpura (HSP) Cryoglobulinemia Fibrillary-immunotactoid disease
Cryoglobulinemia Fabry’s disease
MPGN
Basement Membrane Syndromes Glomerular Vascular Symptoms Infectious Disease-Associated

Syndromes
Microscopic hematuria Vascular injury Variety of inflammatory reactions in
Mild to heavy proteinuria Hematuria glomerular capillaries
Hypertension with variable Moderate proteinuria Combination of hematuria and
elevations in serum creatinine proteinuria
PROTOTYPE DISEASE
Atherosclerotic nephropathy Post-streptococcal GN
Hypertensive nephropathy Subacute bacterial IE
Anti-GBM disease Cholesterol emboli HIV
Alport’s syndrome Sickle cell disease Hepatitis B and C
Thin basement membrane disease Thrombotic microangiopathies Syphilis
Nail-patella syndrome APAS Leprosy
ANCA small-vessel vasculitis Malaria
HSP schistosomiasis
Cryoglobulinemia
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CHAPTER 9
RHEUMATOLOGY
I. Approach to Patients with Joint Pains
II. Common Conditions in Rheumatology
1. Osteoarthritis
2. Gouty Arthritis
3. Systemic Lupus Erythematosus
4. Rheumatoid Arthritis
5. Infectious Arthritis
6. Antiphospholipid Antibody Syndrome
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SECTION 1
APPROACH TO PATIENTS WITH JOINT PAINS
I. HISTORY TAKING OF PATIENTS WITH JOINT PAIN
QUESTIONS TO ASK REMARKS
Monoarthritis: gout, septic arthritis, knee osteoarthritis (OA), reactive arthritis (ReA)
Oligoarthritis (2-4 joints involved): OA, reactive arthritis, gout
What is the number Polyarthritis (> 5 joints involved): rheumatoid arthritis (RA), systemic lupu erythematosus
of joints affected? (SLE), hand OA, chronic gout
Note: psoriatic arthritis has 5 types and can therefore be mono- to polyarticular
Acute versus chronic:
o Acute onset examples: gout, septic arthritis
What is the mode of o Chronic onset examples: OA; RA; TB arthritis; connective tissue disease (CTD)-related
onset? arthritis, e.g., SLE
Note: chronic diseases may have acute onset or “flares”, e.g., OA flare, while some acute
diseases can become chronic, e.g., chronic tophaceous gout
Inflammation usually presents with at least one of the following: dolor (pain), calor
Is there presence or (warmth), rubor (redness), tumor (swelling), and function laesa (loss of function)
absence of joint Inflammatory arthritis: pain and stiffness in involved joints; worse in the morning or after
inflammation? periods of inactivity (“gel phenomenon”); improves with mild to moderate activity
Non-inflammatory arthritis: pain that worsens with activity and improves with rest
Is it articular or non- Non-articular causes: bursitis, tendinitis, other soft tissue conditions
articular?
Pattern of onset: migratory, additive, intermittent
o Migratory: joints are sequentially affected where, as one joint settles, another
What is the pattern of becomes inflamed (e.g. acute rheumatic fever)
joint involvement? o Additive: subsequent joints are involved while preceding ones are still inflamed; most
common but least specific (e.g., RA)
o Intermittent: the same joint is involved in different episodes of inflammation, but the
joint is quiescent during intervening periods (e.g., gout)
Is there systemic Most commonly involves the eyes and skin, e.g., uveitis, scleritis, malar rash, oral ulcers,
involvement? photosensitivity
II. PHYSICAL EXAMINATION

Goal is to ascertain the structures involved, nature of the underlying pathology, functional consequences, and
presence of systemic or extraarticular manifestations
There are 28 easily examined joints (to be palpated):
o Proximal interphalangeal joints (PIPs)
o Metacarpophalangeal joints (MCPs)
o Wrists
o Elbows
o Shoulders
o Knees
A. Pain Differentiation Based on Range of Motion

SITE OF PATHOLOGY ACTIVE ROM PASSIVE ROM
Referred pain Normal Normal
Periarticular pain Decreased Can be normal
Intraarticular pain Decreased Decreased
B. Definition of Terms
SITE OF PATHOLOGY DEFINITION
Crepitus Palpable vibratory or crackling sensation elicited with joint motion
Subluxation Alteration of joint alignment such that articulating surfaces incompletely
approximate each other
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Dislocation Abnormal displacement of articulating surfaces such that the surfaces are
not in contact
Range of Motion For diarthrodial joints, the arc of measurable movement through which the
joint moves in a single plane
Contracture Loss of full movement resulting from bony hypertrophy, malalignment of
articulating structures, or damage to periarticular supportive structures
Deformity Abnormal shape or size resulting from bony hypertrophy, malalignment of
articulating structures, or damage to periarticular supportive structures
Enthesitis Inflammation of the enthuses (tendinous or ligamentous insertions in bone)
Epicondylitis Infection or inflammation involving an epicondyle
C. Grading of Muscle Strength (5-point scale)

0 No movement
1 Trace movement or twitch
2 Movement with gravity eliminated
3 Movement against gravity only
4 Movement against gravity and some resistance
5 Normal strength
III. DIAGNOSTICS
Cannot substitute for clinical evaluation and should never be used as a “screen” for disease
Positive predictive value of many rheumatologic tests is low when these tests are ordered indiscriminately
Add little to the evaluation of acute presentations of arthritis (except in cases of
Radiographs suspected trauma) but often critical for the assessment of chronic arthritis
Plain radiography is the imaging method of choice
Most reliable means of distinguishing between inflammatory and non-
inflammatory arthritis is analysis of the WBC in the synovial fluid
Arthrocentesis and Important diagnostic test to rule out septic arthritis and gout
Synovial Fluid Analysis Determine the WBC; detect bacteria by gram stain; look for uric acid crystals
under polarized light
Synovial fluid WBC count <2000/mcL in non-inflammatory arthritis
Useful in detection of soft tissue abnormalities (e.g., tendinitis, tenosynovitis,
Ultrasonography enthesitis, bursitis, rotator cuff lesions)
Preferred method for evaluation of synovial (Baker’s) cysts, rotator cuff tears,
tendinitis, and crystal deposition in cartilage
CT: provides detailed visualization of the axial skeleton, articulations, lung
disease
MRI: images musculoskeletal structures such as fascia, vessels, nerves,
CT or MRI muscle, cartilage, ligaments, tendons, pannus, synovial effusions and bone
marrow
MRI can better define the nature and the extent of joint, bone and surrounding
soft tissue changes
Erythrocyte Inflammatory marker; usually elevated in inflammatory arthritis
Sedimentation Rate (ESR) Can be elevated due to many other factors, e.g., menstruation, pregnancy
Inflammatory marker; usually elevated in inflammatory arthritis
C-Reactive Protein (CRP) Generally lacks specificity except when the value is >100 mg/dL, in which case
septic arthritis or gout should be excluded
Values range from 238-516 umol/L (4.0-8.6 mg/dL) in men; 178-351 umol/L
(3.0-5.9 mg/dL) in women
Hyperuricemia is associated with gout and nephrolithiasis but levels may not
Serum Uric Acid correlate with severity of articular disease
50% of patients with an acute gouty attack will have normal serum uric acid
levels
Monitoring may be useful in assessing response to therapy (target: <6 mg/dL)
Complete Blood Count Anemia is common in chronic inflammatory conditions
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Leukocytosis is common in septic arthritis, acute gout and juvenile arthritis
Leukopenia & lymphopenia in a patient with polyarthritis is suggestive of SLE
Reactive thrombocytosis is common with active chronic inflammatory arthritis,
e.g., RA and juvenile idiopathic arthritis
Thrombocytopenia can be a presenting feature of SLE
Histones: drug-induced lupus
ds-DNA: 50% of SLE (specific)
U1-RNP: >90% of mixed connective tissue disease
Sm: 30% of SLE (specific)
Antinuclear Antibody Ro (SS-A): 60% of Sjogren’s, subacute cutaneous lupus, neonatal lupus
(ANA) Patterns La (SS-B): 50% of Sjogren’s, 15% of lupus
Scl-70: 40% of diffuse scleroderma
PM-1: polymyositis, dermatomyositis
Jo-1: polymyositis with pneumonitis + arthritis
RNA polymerase I: 40% of progressive systemic sclerosis
Centromere / kinetochore: 75% of CREST (limited scleroderma)
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SECTION 2
COMMON CONDITIONS IN RHEUMATOLOGY
OSTEOARTHRITIS (OA)
I. ETIOPATHOGENESIS
Most common joint disease and a leading cause of disability in the elderly
Sine qua non is hyaline articular cartilage loss
o Commonly affected joints are the cervical and lumbosacral spine, hip, knee and first metatarsophalangeal
(MTP) joints
o In the hands, the distal and proximal interphalangeal joints (IPs) and base of the thumb are often affected
o Wrist, elbow and ankle are usually spared
Risk factors include age (most important), obesity, repeated joint use
Joint pain is activity-related, starting as episodic and progressing continuously with accompanying brief morning
stiffness (<30 min) that gradually resolves
II. DIAGNOSTICS
No blood tests are routinely indicated
Synovial fluid analysis reveals a non-inflammatory pattern
Joint imaging correlates poorly with presence and severity of pain:
o May be normal in early stages
o Advanced stages may show joint space narrowing, subchondral sclerosis, osteophytes
III. MANAGEMENT
Goal is relief of pain and prevention of disability
A. Non-Pharmacologic and Adjunctive Management

Exercise with brief periods of rest for the involved joint
Weight management (weight loss of 5 kg translates to 50% reduction in pain): core treatment for obese and
overweight adults with knee OA
Correction of possible malalignment (knee braces, orthotics)
Acupuncture
Concentrated standardized ginger preparation
MANAGEMENT COMMENTS
Maximum dose of 4 g daily
Paracetamol First-line drug therapy for reduction of mild knee OA pain
Close monitoring for upper GI adverse effects for doses >2 g per day
Low-dose NSAIDs or Up to 2 weeks duration
Selective COX-2 Inhibitors
Topical NSAIDs Less systemic side effects compared to oral preparations
Intra-articular Injections Steroids: should not exceed 3 times per year in the same joint
Hyaluronans: more effective: longer duration of pain control
Glucosamine and chondroitin sulfate
Others Opioids (tramadol)
Topical capsaicin
Surgery (arthroscopic debridement and lavage, meniscectomy, arthroplasty)
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GOUTY ARTHRITIS
I. ETIOPATHOGENESIS
Metabolic disease that usually affects middle-aged to elderly men and postmenopausal women
Results from increased body urate pool with hyperuricemia
Precipitants of gout: dietary excess, trauma, surgery, excessive ethanol ingestion, hypouricemic therapy and
comorbid illness (e.g., stroke, ACS)
Asymptomatic Defined as hyperuricemia in the absence of gouty arthritis and uric nephrolithiasis
Hyperuricemia Hyperuricemia; defined as serum uric acid >7 mg/dL (416 umol/L) in men and >6
mg/dL (357 umol/L) in women
Acute Gouty Arthritis Characterized by acute arthritis initially affecting the MTP of the first toe
(podagra) followed by recurring episodes of acute mono- or oligoarthritis
Intercritical Gout Referred to as “interval gout”: the asymptomatic periods between gouty attacks
Chronic Tophaceous Occurs in untreated gouty arthritis, characterized by persistent low grade
Gout (CTG) inflammation of joints with sporadic flares
Joint deformities: due to deposition of massive urate crystals forming visible tophi
II. DIAGNOSTICS
Strongly negative birefringent needle-shaped monosodium urate (MSU) crystals
Synovial Fluid Analysis both intra- and extracellularly
Thick chalky paste fluid; WBC 2,000-60,000/uL
Joint Imaging Joint swelling early in the disease; soft tissue masses
Cystic changes with well-defined erosions and overhanging sclerotic margins
Serum Uric Acid May be low or normal at the time of attacks
24h Uric Acid Urine >800 mg/24h (over-producers)
Collection <600 mg/24h (under-excretors)
III. MANAGEMENT
A. Non-Pharmacologic and Adjunctive Management
General Adequate hydration & increase oral fluid intake (at least 8 glasses of water per day)
Avoid diuretics unless benefits outweigh the risks
Hypouricemic Diet Low purine diet, avoid red meals, alcoholic drinks (especially beer)
Limit seafood, sweetened fruit juice / fructose-containing food and beverages
B. Medical Management
Asymptomatic Do not routinely treat with urate lowering medications
Hyperuricemia Indications for urate lowering therapy: serum uric acid >11-13 mg/dL, presence of
tophi, arthropathy on radiography, nephrolithiasis, tumor lysis syndrome, CKD 2-3
NSAIDS, glucocorticoids, ice compress
Acute Attacks Colchicine: unless contraindicated (e.g., renal insufficiency), colchicine 0.5 mg TID
may be given, then decreased to OD after the acute attack and maintained until uric
acid <6 mg/dL and at least 3 months without gout flare recurrence
Started 1-2 weeks after acute attacks and continued until uric acid is controlled
Treatment goal is to reduce uric acid to <6 mg/dL
Hypouricemic Uric acid under-excretion treated with uricosuric drugs (probenecid,
Therapy benzbromarone, sulfinpyrazone)
Uric acid over-production treated with xanthine oxidase inhibitors:
o Allopurinol 100 mg/tab PO OD initial dose (adjust accordingly)
o Febuxostat 40 mg/tab ½ tab PO OD initial dose (adjust accordingly)
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SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
I. ETIOPATHOGENESIS
Autoimmune disease in which organs and cells undergo damage mediated by tissue-binding autoantibodies and
immune complexes
Diagnosis is based on characteristic clinical features and autoantibodies
II. DIAGNOSTICS
A. 1982 Original American College of Rheumatology (ACR) Criteria
4 out of 11 criteria
Mnemonic: “SOAP BRAIN MD”
CRITERIA DESCRIPTION / REMARKS
Serositis Pleuritic, pericarditis
Oral/ Nephropharyngeal ulcers Observed by physician
Arthritis Non-erosive, 2 or more peripheral joints
Photosensitivity Sensitivity to UV rays from sunlight
Blood / Hematologic disorder Anemia, leukopenia <4000, lymphopenia <1500 or thrombocytopenia <100,000
Renal disorder +3 or >0.5 g/d proteinuria or cellular casts
Ana (+) Best screening test for SLE
Positive in >98% of patients during the course of the disease
Immunologic disorder Anti-dsDNA, anti-Sm, aPL
Neurologic disorder Cerebritis: seizures, psychosis
Malar Rash Butterfly rash: fixed erythema over the malar eminence which spares
nasolabial folds
Discoid Rash Erythematous circular patches with adherent keratotic scaling and follicular
plugging
B. 2012 Systemic Lupus International Collaborating Clinics (SLICC) Revised Criteria

4 criteria (at least 1 immunologic, 1 clinical) or biopsy-proven lupus nephritis
Presence of any 4 criteria (must have at least 1 in each category) qualifies patient to be classified as having SLE
with 93% specificity and 92% sensitivity
CLINICAL CRITERIA IMMUNOLOGIC CRITERIA
Skin
Acute, subacute cutaneous SLE
Chronic cutaneous SLE
Oral ulcers
Alopecia
Synovitis (arthritis) ANA (ANA > reference negative value)
Renal disorder Anti-dsDNA
Prot/Cr > 0.5 Anti-Sm
RBC casts Antiphospholipid antibodies
Biopsy Hypocomplementemia
Neurologic disorder Positive Direct Coombs test
Seizures, psychosis, mononeuritis, myelitis, peripheral
or cranial neuropathies, acute confusional state
hemolytic anemia
leukopenia <4,000 or lymphopenia <1,000
thrombocytopenia <100,000
III. MANAGEMENT
Analgesics and antimalarials are the mainstays of treatment for mild disease
Systemic steroids are the mainstays for severe disease
DRUG INDICATION ADVERSE EFFECTS / COMMENTS
NSAIDS Arthritis Increased risk for aseptic meningitis, renal insufficiency, elevated
transminases and cardiovascular events
Topical Steroids Dermatitis Skin atrophy, hypopigmentation, contact dermatitis
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Sunscreens Photosensitivity At least SPF 15 (SPF 30 preferred)
Reapply throughout the day
Bone health (to
Calcium and help counter
Vitamin D sun avoidance None when taken in appropriate doses
and steroid
intake)
Dermatitis, Hepatotoxicity, BM suppression, pulmonary fibrosis
Methotrexate arthritis Contraindicated in pregnancy; stop 3-6 months before trying to
conceive
Hydroxychloroquine Dermatitis, Potential retinal toxicity at high and prolonged doses
arthritis Helps prevent flares
Systemic Steroids/ Immunosuppression, hypertension, hyperglycemia, hypokalemia,
MPPT* acne, aseptic necrosis of bone/osteoporosis, fragile skin, mood
swings/psychosis, Cushing’s syndrome
Predisposition to infection, BM suppression, hemorrhagic cystitis,
Cyclophosphamide bladder CA, ovarian/testicular failure
Control of Contraindicated in pregnancy
disease activity Predisposition to infection, BM suppression, alopecia, GI symptoms,
Azathioprine hepatotoxicity, flulike illness
Contraindicated in pregnancy unless benefits outweigh risks
(evidence from prospective cohort studies suggests fetal safety)
Mycophenolate Predisposition to infection, BM suppression, lymphoproliferative
Mofetil disorders, GI symptoms, tremors, rash
Biologics Predisposition to infections, TB reactivation
**MPPT: Methylprednisolone Pulse Therapy
RHEUMATOID ARTHRITIS (RA)

I. ETIOPATHOGENESIS
Chronic inflammatory disease of unknown etiology marked by symmetric, peripheral polyarthritis
Most common form of inflammatory polyarthritis which may result in joint damage and physical disability
May result in a variety of extraarticular manifestations (e.g., fatigue, subcutaneous nodules, lung involvement,
pericarditis, peripheral neuropathy, vasculitis, and hematologic abnormalities)

MANIFESTATIONS REMARKS
Initially involves small joints of hands and feet
Early morning stiffness >1 hour easing with physical activity
Most frequently involved joints: wrists, MCP, PIP (DIP involvement usually a sign of
Joint Involvement coexistent OA)
Swan neck deformity: hyperextension of the PIP with flexion of the DIP joint
Boutonniere deformity: flexion of the PIP with hyperextension of the DIP joint
Z-line deformity: subluxation of the first MCP with hyperextension of 1st IP joint
Flexor tendon tenosynovitis: frequent hallmark of RA
Subcutaneous Nodules Seen in 30-40%
Usually benign, firm, nontender and adherent to periosteum, tendons or bursae
Pleuritic/Pericarditis Most frequent site of cardiac involvement in RA is the pericardium
Vasculitis Fever of >38.3oC during the clinical course should raise suspicion of systemic vasculitis
Others Weight loss, fever, fatigue, malaise, depression, cachexia in the most severe cases
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III. DIAGNOSIS
A. Classification Criteria for RA: Score > 6 fulfills the requirements for Definite RA
CRITERIA SCORE
1 large joint (shoulder, elbow, hip, knee, ankle) 0
2-10 large joints 1
Joint Involvement 1-2 small joints (MCP, PIP, thumb, IP, MTP, wrists) 2
4-10 small joints 3
>10 joints (at least 1 small joint) 5
Serology Negative RF and negative anti-CCP antibodies 0
Low-positive RF or low-positive anti-CCP antibodies (< 3 times ULN) 2
High-positive RF or high-positive anti-CCP antibodies (> 3 times ULN) 3
Acute-phase Normal CRP and normal ESR 0
Reactants Abnormal CRP or abnormal ESR 1
Duration of < 6 weeks 0
Symptoms > 6 weeks 1
B. Diagnostic Tests
Serum Markers (+) RF or anti-CCP, elevated acute phase reactants
CBC Normocytic normochromic anemia
Synovial Fluid Consistent with inflammatory arthritis
Analysis
Joint Imaging Juxtaarticular osteopenia (initial finding), soft tissue swelling, joint effusions, symmetric joint
space narrowing, joint subluxation & collapse in severe cases
III. MANAGEMENT
A. NSAIDS
Formerly viewed as the core of all other RA therapy
Now considered as adjunctive therapy
B. Glucocorticoids
Low-moderate doses for rapid disease control before the onset of fully effective DMARD therapy
1- to 2-week burst of glucocorticoids for acute disease flares
C. Disease-Modifying Anti-Rheumatic Agents (DMARDS)

Slow or prevent structural progression of RA
Cornerstone of therapy
DMARD DOSING ADVERSE EFFECTS / COMMENTS
Methotrexate 10-25 mg/week PO or SQ Hepatotoxicity, myelosuppression, infection, nauseam
(DMARD of choice) Folic acid 1 mg/day given to diarrhea, interstitial pneumonitis
reduce toxicities Contraindicated in pregnancy
Hydroxychloroquine 200-400 mg/day PO Irreversible retinal damage, rash, cardiotoxicity, blood
dyscrasia, nausea, diarrhea
Sulfasalazine 500-1500 mg BID PO Granulocytopenia, hemolytic anemia in persons with
G6PD deficiency, nausea, diarrhea
Hepatotoxicity, myelosuppression, infection, alopecia,
Leflunomide 10-20 mg/day diarrhea
Contraindicated in pregnancy
D. Biologics
Protein therapeutics designed mostly to target cytokines and cell-surface molecules
Share the common adverse effect of a potentially increased risk for infection
BIOLOGIC MECHANISM
Infliximab Chimeric (part-mouse, part-human) anti-TNF monoclonal antibody
Adalimumab, Fully humanized anti-TNF monoclonal antibody
Golimumab
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Certolizumab pegol Pegylated Fc-free fragment of a humanized monoclonal antibody with binding
specificity for TNF
Etanercept Soluble fusion protein comprising the TNF receptor-2 in a covalent linkage with the Fc
portion of IgG1
Anakinra Recombinant form 1L-1 receptor antagonist
Abatacept Soluble fusion protein consisting of a domain of human CTLA-4 linked to a portion of
human IgG
Rituximab Chimeric monoclonal antibody against CD-20
Tocilizumab Humanized monoclonal antibody against the IL-6 receptor
INFECTIOUS ARTHRITIS
I. ETIOPATHOGENESIS
A. Pathogenesis
Hematogenous route is the most common route in all age groups
The knee is the most commonly involved joint
Acute bacterial infection typically involves a single joint or a few joints
Subacute or chronic monoarthritis or oligoarthritis suggests mycobacterial or fungal infection
Polyarticular involvement may be seen in RA
B. Etiologic Agents
Infants: Group B Streptococcus, Gram (-) enteric bacilli, and Staphylococcus aureus
Young adults & adolescents: N. gonorrhea
Staphylococcus aureus accounts for most non-gonococcal isolates in adults of all ages

Fever (may be absent in immunosuppressed people)
Moderate-severe pain that is uniform around the joint
Musculoskeletal: joint effusion, muscle spasm, decreased range of motion
III. DIAGNOSTICS
Acute Phase Reactants Elevated ESR, CRP
CBC Elevated WBC counts with leftward shift
Cell counts averaging 100,000/uL with >90% PMN (acute bacterial infection)
Synovial Fluid Analysis 10,000-30,000/uL with 5-70% PMN and remainder lympchocytes (TB/fungal infection)
Elevated LDH and total protein; decreased glucose
Early findings: soft tissue swelling, joint space widening, displacement of tissue planes
Joint Imaging by distended capsule
Late findings: effusions, symmetric joint space narrowing, joint subluxation and
collapse in severe cases
Cultures Blood CS will be (+) for Staphylococcus aureus in 50% of cases
Synovial fluid CS will be (+) for Staphylococcus aureus in 90% of cases
IV. MANAGEMENT
Repeated arthrocentesis
Surgical drainage/arthroscopic lavage indicated for:
o Septic hip
o Concomitant osteomyelitis
o Prosthetic joint infection
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B. Pharmacologic (Antibiotics) Management
1. Recommended Antibiotics
EMPIRIC TREATMENT
Gram-positive smear Oxacillin 2 g IV q4; or Nafcillin 2 g IV q4
Gram-negative smear Cefotaxime 1 g IV q8; or Ceftriaxone 1-2 g IV q24
Pseudomonas suspect Add aminoglycoside or 3rd generation anti-pseudomonal cephalosporin
2. Duration of Treatment According to Organism

DURATION OF TREATMENT
Staphylococcus aureus 4 weeks
Pneumococcus/ 2 weeks Pen G 2M units q4 (penicillin-sensitive) or Cefotaxime/Ceftriaxone
Streptococcus (penicillin-resistant)
Enteric Gram-Negative 3-4 weeks 2nd/3rd generation cephalosporin IV or quinolone IV/PO
Bacilli
Pseudomonas At least 2 weeks of aminoglycoside plus extended spectrum penicillin or anti-
aeruginosa pseudomonal cephalosporin
ANTIPHOSPHOLIPID ANTIBODY SYNDROME (APAS)

I. ETIOPATHOGENESIS
Autoantibody-mediated acquired thrombophilia characterized by recurrent arterial or venous thrombosis and/or
pregnancy morbidity
Classification and nomenclature of antiphospholipid antibodies
o Antibodies against cardiolipin (aCL)
o Antibodies against B2GPI (anti-B2GPI)
o Lupus anticoagulant (LA)
II. DIAGNOSIS
Presence of at least 1 clinical + 1 laboratory criterion
CLINICAL CRITERIA LABORATORY CRITERIA
1. Vascular thrombosis defined as > 1 clinical episodes of
arterial, venous or small vessels thrombosis in any tissue
or organ
2. Pregnancy morbidity, defined as: Antiphospholipid antibodies on 2 occasions, 12 weeks
a. > 1 unexplained deaths of a morphologically normal apart:
fetus > 10th week of gestation 1. LA, and/or
b. > 1 premature births of a morphologically normal 2. Anticardiolipin (aCL), and/or
neonate before the 34th week of gestation because 3. Anti-B2GPI
of eclampsia, severe preeclampsia or placental
insufficiency
c. > 3 unexplained consecutive spontaneous abortions
before the 10th week of gestation
III. MANAGEMENT
Warfarin (INR 2.5-3.5) after the first thrombotic event
Pregnancy morbidity prevented by combination of heparin with aspirin 80 mg OD
IV immunoglobulin may be considered
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CHAPTER 10
ALLERGY AND
IMMUNOLOGY
I. Introduction to Allergology and Immunology
II. Common Conditions in Allergology and Immunology
1. Allergic Rhinitis
2. Atopic Dermatitis
3. Anaphylaxis
4. Primary Immune Deficiency Diseases
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SECTION 1
INTRODUCTION TO ALLERGOLOGY AND IMMUNOLOGY
THE IMMUNE SYSTEM
I. INNATE AND ADAPTIVE IMMUNE SYSTEM

INNATE IMMUNE SYSTEM ADAPTIVE IMMUNE SYSTEM
Recently evolved system of immune responses
mediated by T and B lymphocytes
Inherited from invertebrates Immune responses are based on specific antigen
Bears germ-line encoded pattern recognition receptors recognition by clonotypic receptors that are products of
(PRRs) that recognize pathogens and effect pathogen gene arrangements
elimination Consists of two limbs: cellular and humoral immunity
Takes longer to activate but generates more effective
defense which improves upon repeated exposure to the
same microbe
Major Components
Cell components Cellular Immunity Humoral Immunity
o Natural killer cell lymphocytes
o Monocytes / macrophages
o Dendritic cells
o Neutrophils
o Basophils B Lymphocytes and
o Eosinophils T Lymphocytes their product antibodies/
o Tissue mast cells immunoglobulins
o Epithelial cells
Classic and alternative complement pathways and
proteins that bind complement components
Antimicrobial peptides (defensins, cathelin, protegrin)
Cytokines
II. STAGES OF AN IMMUNE RESPONSE (i.e., generalized response to a bacterial skin infection: first time a particular microbe has infected the body)
1 Infiltration of microbes through a breach in the mirror
Activation of innate immune system
2 Bacterial lysis by membrane attack complex (from complement activation)
Opsonization (coating of bacteria with complement proteins that facilitate phagocytosis)
Phagocytosis and eventual digestion
Amplification of reactions leading to inflammation
Local vasodilation
3 Increase in vascular permeability
Adhesion of inflammatory cells to blood vessel wall
Chemotaxis (chemical attraction of inflammatory cells to the site of injury)
Immobilization of effector cells at site of infection
Activation of relevant cells and molecules to liberate lytic products
Generation of adaptive response (while innate response is being established)
Microbial antigens are captured and processed by antigen-presenting cells which are present in most tissues
a. Migration to draining lymph nodes
4 b. Antigen presentation to T cells
c. Activated T and B cells return blood circulation and enter inflamed, infected tissues together with antibodies
secreted by terminally differentiated B cells (plasma cells)
5 Secreted antibodies augment complement activation and phagocytosis
6 Cytokines released by T cells increase antimicrobial activity of phagocytes
Some activated T and B cells who are initially activated revert back to a resting state and constitute the body’s pool
7 of memory lymphocytes specific for the infecting microbe faster and bigger secondary response by lymphocytes
during subsequent infection with the same (or closely-related/antigenically similar) microbe
8 Containment of infection and deactivation of inflammatory response
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Nature of defense strategy that immune system employs in order to eliminate a microbe depends not only on the
biological nature of the microbe but also on the tissue compartment in which the infection is concentrated
EXTRACELLULAR INTRACELLULAR
In fluids or at the surfaces of the infected tissues Inside cytoplasm of cells
Sample Many types of bacteria Viruses
Pathogens Parasitic worms Some bacteria
Opsonization by antibodies and complement phagocytosis Interferons inhibit intracellular
by macrophages and neutrophils intracellular digestion viral replication
Defense Eosinophil attack (parasitic worms) Natural killer (NK) cells and
Strategy For microbes resistant to intracellular digestion and can cytotoxic T (Tc) cells
survive and replicate in cytoplasmic vesicles (e.g., deliberately kill infected cells
mycobacteria): macrophage activation by cytokines
III. OTHER IMMUNOLOGY CONCEPTS

Specificity: highly diverse repertoire of antigen receptors which enables recognition of a nearly infinite range of
pathogens
Memory: immune memory to enable rapid recall immune responses
Self-discrimination: immunologic tolerance to prevent immune damage to normal “self” tissue
IV. IMMUNOPATHOLOGY
Hypersensitivity or allergy: collateral damage to host tissues by immune system
Autoimmunity: immune recognition of self components (e.g. loss of self-discrimination)
Lymphoproliferative disease
Immunodeficiency
FOUR MAIN CATEGORIES OF TISSUE DAMAGE

Mechanism Physiology Pathology
Extrinsic Autoimmune
Extravascular recruitment Anaphylaxis
Type Immediate, of immunological Allergic asthma Chronic urticaria
I IgE-mediated components Allergic rhinitis
Parasite expulsion
Incompatible blood Thrombocytopenia
Lysis of pathogens by transfusion Pemphigoid
Type IgG, IgA or IgM- extracellular or intracellular Hemolytic disease of Goodpasture’s disease
II mediated veins the newborn Myasthenia gravis
Hyperacute graft Thyrotoxicosis
rejection Hemolytic anemia
Neutralization of pathogen- Local: arthus reaction,
derived factors (e.g. dermatitis Local: rheumatoid
Type Immune complex- toxins) herpetiformis, allergic arthritis
III mediated Transport of antigen to alveolitis Systemic: SLE,
germinal centers Systemic: serum widespread vasculitis
sickness, vasculitis
Tuberculosis Thyroiditis
Type Cell-mediated Defense against Leprosy Adrenalitis
IV intracellular parasites Contact dermatitis Pernicious anemia
Graft rejection diabetes
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SECTION 2
COMMON CONDITIONS IN ALLERGOLOGY AND IMMUNOLOGY
ALLERGIC RHINITIS (AR)
I. ETIOPATHOGENESIS
Characterized by a constellation of symptoms (sneezing; rhinorrhea; obstruction of the nasal passages;
conjunctival, nasal, and pharyngeal itching; and lacrimation) all occurring in a temporal relationship to allergen
exposure
Manifestations caused by sensitization of IgE-rich intraepithelial mast cells with allergens

Hallmarks of allergic rhinitis: episodic rhinorrhea, sneezing, obstruction of the nasal passages with lacrimation,
pruritus of the conjunctiva, nasal mucosa and oropharynx
Patients may have concurrent nasal polyps and may develop secondary sinusitis
III. DIAGNOSIS
Diagnosis depends on accurate history revealing symptoms coincident with potential triggers (pollen, animal
dander, house dust mite, work-related allergens)
Other laboratory findings include:
o CBC shows modest peripheral eosinophilia
o Positive skin test
IV. MANAGEMENT
Allergen avoidance is still the most effective form of management
Treatment options include:
o Intranasal steroids (most effective agents)
o Oral and nasal antihistamines
o Oral decongestants
o Leukotriene modifiers
o Cromones
o Topical ipratropium (for rhinorrhea)
o Anti-IgE (omalizumab)
o Immunotherapy (for intractable cases)
ARIA 2008 Algorithm
ALLERGEN AVOIDANCE
↓ ↓
Intermittent Symptoms Persistent Symptoms
Mild Moderate to Severe Mild Moderate to Severe
Not in preferred order Not in preferred order
Oral or intranasal H1- Oral or intranasal H1-antihistamine In preferred order
antihistamine And/or decongestant Intranasal steroids
And/or decongestant Or intranasal steroid H1-antihistamine or anti-leukotriene
Or antileukotriene Or antileukotriene (or cromone)
Review after 2-4 weeks
If improved: step down and continue for 1
month
o If failure: review compliance and
Review after 2-4 weeks diagnosis
If improved: continue for 1 month o Increase intranasal steroid dose
If failure: step up o If itch/sneeze: add H1-blocker
o If rhinorrhea: add ipratropium
o If blockage: add decongestant or
short course oral steroid
If failure: consider specialist referral
↓ ↓
CONSIDER SPECIFIC IMMUNOTHERAPY
232
ATOPIC DERMATITIS (AD)
I. ETIOPATHOGENESIS
Endogenous eczema: “the itch that rashes”
Typically begins in infancy with many patients outgrowing AD as they develop allergic respiratory symptoms
Pathogenesis: genetics, decreased skin barrier function, altered immunology

A chronic or relapsing disease characterized by pruritus and eczematous lesions with a distinctive morphology
and age-specific distribution
o Infantile (<2 years): face (prominent on cheeks with sparing of central face), scalp, extensors with sparing
of diaper area; features are more acute
o Childhood (2-12 years): flexural; more chronic lesions; more pronounced and widespread xerosis
o Adult (>12 years): also flexural with chronic lesions but can also present as chronic hand dermatitis, facial
dermatitis with severe eyelid involvement, extensive or erythrodermic diseases
Patients generally have dry lackluster skin with all three stages of skin reactions present:
o Acute lesions: erythematous papules with excoriations, vesicles over erythematous skin, serous exudates
o Subacute lesions: erythematous, excoriated, scaling papules
o Chronic lesions: thickened plaques of skin, lichenification, prurigo nodularis
III. DIAGNOSIS: BASED ON THE CONSTELLATION OF CLINICAL FINDINGS

DIAGNOSTIC FEATURES OF ATOPIC DERMATITIS (by Hanifiin and Rajka)
MAJOR FEATURES (3 of 4) MINOR FEATURES (3 of 23)
Xerosis
Ichthyosis/palmar hyperlinearity/keratosis pilaris
Immediate (type I) skin test reactivity
Elevated serum IgE
Early age of onset
Tendency toward cutaneous infections/impaired cell-
mediated immunity
Tendency toward non-specific hand or foot dermatitis
Nipple eczema
Cheilitis
Pruritus
Recurrent conjunctivitis
Typical morphology and distribution of skin lesions
Dennie-Morgan infraorbital fold
Chronically relapsing dermatitis
Keratoconus
Personal or family history of atopy
Anterior subcapsular cataract
Orbital darkening
Facial pallor/erythema
Pityriasis alba
Anterior neck folds
Pruritus when sweating
Intolerance to wool and lipid solvents
Perifollicular accentuation
Food intolerance
Course influenced by environmental/emotional factors
White dermographism/delayed blanch
IV. MANAGEMENT
Appropriate skin hydration and use of emollients: mainstay of management
Avoidance of irritants
Identification and avoidance of proven allergens
Identification and treatment of complicated/superimposed bacterial, viral or fungal infections
Anti-inflammatory therapy: topical glucocorticoids, topical calcineurin inhibitors
May give sedating antihistamines (hydroxyzine 25-50 mg tab OD HS)
233
ANAPHYLAXIS
I. ETIOPATHOGENESIS
Life-threatening response of a sensitized human after systemic exposure to specific antigen
Hallmark is the onset of some manifestation within seconds to minutes after introduction of the antigen (with the
exception of alpha-galactose allergy in beef, lamb or pork)
Angioedematous and urticarial manifestations are attributed to the release of endogenous histamine

ORGAN SYSTEM MANIFESTATIONS
Cutaneous Pruritus, urticarial, angioedema, flushing
Respiratory Dyspnea, hoarseness, “lump in the throat”, stridor, wheezing
Gastrointestinal Nausea, vomiting, crampy abdominal pain, diarrhea
Cardiovascular Hypotension
III. DIAGNOSIS
Diagnosis depends on a history revealing the onset of symptoms and signs within minutes after the antigen is
encountered
Other laboratory findings include:
o Acute emphysema and lung hyperinflation on chest radiography
o Eosinophilia
o ECG abnormalities reflecting a primary cardiovascular event mediated by mast cells or secondary to
blood volume reduction
o Elevation of serum tryptase (except for anaphylaxis from food)
IV. MANAGEMENT
Mild symptoms Epinephrine 0.3-0.5 ml of 1:1000 (1 mg/ml) SC/IM (repeat q5-20 min for
(pruritus and urticarial) severe reactions)
For injected material and insect Application of tourniquet proximal to the site
stings Epinephrine 0.2 ml of 1:1000 SC/IM
Removal without compression of insect stinger (if present)
Ancillary agents Diphenyhydramine 50-100 mg IM/IV for urticarial/angioedema
Aminophylline 0.25-0.5 g IV for bronchospasm
Fluids and pressors to maintain intravascular volume
Oxygen supplementation and intubation as needed
Supportive IV glucocorticoids:
o May alleviate delayed onset manifestations
o Hydrocortisone 200mg IV loading dose then 100mg IV q6h (for
late phase reactions)
PRIMARY IMMUNODEFICIENCY DISEASES (PID)

I. ETIOPATHOGENESIS
Genetic diseases with primarily Mendelian inheritance
Overall prevalence of PIDs: 5 per 100,000 individuals
Consequence of PIDs vary depending on the function of the molecules that are defective multiple levels of
vulnerability to infection by pathogenic and opportunistic microorganisms
o PID involving T cells generally have severe pathologic consequences
The most frequent PIDs are those that predominantly affect B lymphocytes (60-70% of cases)
INNATE IMMUNE ADAPTIVE IMMUNE SYSTEM REGULATORY DEFECTS
SYSTEM
Phagocytic Cells T Lymphocytes Innate Immunity Adaptive Immunity
Impaired production: Impaired Impaired Survival, Hemophagocytic
severe congenital Development Migration & Function Auto-inflammatory lymphohistiocyto-
neutropenia (SCN) Severe Severe combined syndromes sis (HLH)
Asplenia combined immunodeficiencies Severe colitis Autoimmune
immune Hyper-IgE syndrome lymphoprolifer-
234
Impaired adhesion: deficiencies CD40 ligand ation syndrome
leukocyte adhesion (SCID) deficiency (ALPS)
deficiency (LAD) DiGeorge Wiskott-Aldrich Autoimmunity and
Impaired killing: syndrome syndrome (WAS) inflammatory
chronic Ataxia-telangiectasia diseases (IPEX,
granulomatous and otjer DNA repair APECED)
disease (CGD) deficiencies
Innate Immunity
Receptors and Signal B Lymphocytes
Transduction
Defects in Toll-like Impaired Impaired Function
receptor signaling Development Hyper-IgM
Mendelian XL and AR syndrome
susceptibility to agammaglobu- Common variable
mycobacterial linemia immunodeficiency
disease (CVID)
Complement
Deficiencies
Classical, alternative
and lectin pathways
Lytic phase

Most frequent symptom is the presence of recurrent or unusually severe infections
May also present with recurrent allergic or autoimmune manifestations
DEFICIENCY EXAMPLE PATTERN OF INFECTION
T & B Cell SCID Viruses, fungi and bacteria
T Cell DiGeorge Syndrome Budding viruses, Candida, Pneumocystis
B Cell Hypogammaglobulinemia Pyogenic bacteria
Spleen Splenectomy Pneumococci, meningococci and Hemophilius influenza
Chronic granulomatous Catalase-positive organisms (e.g. staphylococcus and Aspergillus)
Phagocyte disease
Leukocyte adhesion Indolent infection with pyogenic bacteria
deficiency Poor wound healing
Complement C3 Pyogenic bacteria
C5, C6, C7, C8 or C9 Neisseria
III. DIAGNOSIS
Performance of laboratory tests should be guided to some extent by clinical findings
Neutrophils: decreased in SCN, increased in LAD
CBC and Cell Morphology Lymphocytes: to identify T cell deficits
Eosinophils: increased in WAS and Hyper-IgE syndrome
Howell-Jolly bodies in asplenia
Chest X-Ray Loss of thymic shadow in SCID and DiGeorge syndrome
Bone X-Ray Examine metaphyseal ends in cartilage hair hypoplasia
Immunoglobulin Serum Levels IgG, IgA, IgM: B cell immunodeficiencies
IgE: Hyper-IgE syndrome, WAS, T cell immunodeficiency
Lymphocyte Phenotype T and B lymphocyte counts for T cell immunodeficiency and
agammaglobulinemia
Dihydrorhodamine Fluorescence (DHR) To assess for reactive oxygen species production by PMNs which is
Assay decresed in chronic granulomatous disease
Nitroblue Tetrazolium (NBT) Assay
CH50, AP50 To assess classic and alternative complement pathways
Abdominal Ultrasound Assess asplenia
235
CHAPTER 11
HEMATOLOGY
I. Introduction to Hematology
1. Blood Components
2. Definition of Common Terms
3. Findings in Peripheral Blood Smear
4. Common Computations and Formulas in Hematology
5. Common Antiplatelets, Anticoagulants and Fibrinolytics
II. Transfusion Medicine
1. Blood Typing
2. Rational Use of Blood Products
III. Common Conditions in Hematology
1. Anemia
2. Thrombocytopenia
3. Bone Marrow Failure
4. Hematologic Malignancies
236
SECTION 1
INTRODUCTION IN HEMATOLOGY
BLOOD COMPONENTS
BLOOD COMPONENT DESCRIPTION
RBC / Erythrocytes Contain hemoglobin
Responsible for the O2-carrying capacity of the body
Integral part of the immune system
WBC / Leukocytes Responsible for removing old and aberrant cells and attacking infectious and
foreign substances
Polymorphonuclear Cells Most abundant WBC
(PMN) / Neutrophils Usually the first responders to microbial infection, especially bacterial
Three major types:
Lymphocytes o Natural killer/NK cells (cytotoxic innate immunity)
o T cells (cell-mediated adaptive immunity)
o B cells (humoral adaptive immunity)
Largest WBC
Monocytes Migrate from the bloodstream to other tissues and differentiate into resident
macrophages
Eosinophils Active in parasitic infections and modulate the allergic inflammatory response
Basophils Release histamine during the inflammatory response
Platelets/Thrombocytes Responsible for coagulation / thrombosis
DEFINITION OF COMMON TERMS IN HEMATOLOGY

TERM DEFINITION
Anemia Hemoglobin < 130 g/L in males; <120 g/L in females
Polycythemia Hemoglobin > 170 g/L in males; >150 g/L in females
Hematocrit >0.50 in males; >0.40 in females
Thrombocytopenia Platelet count <150 x 109/L
Tiny purple or red spots appearing on the skin as a result of tiny hemorrhages
Petechiae within the dermal or submucosal layers (result from ruptured blood vessels)
Less than 3mm in diameter
Purpura Purple skin blotch caused by bleeding beneath the skin (larger than petechiae)
Bluish discoloration of an area of skin caused by extravasation of blood into the
Ecchymosis subcutaneous tissues as a result of trauma to the underlying blood vessels
(“bruise”)
Hemarthosis The extravasation of blood into the joint
Hematoma Localized collection of blood outside the vessels, usually in liquid form within the
tissue
Icterus Pertaining to or resembling jaundice
FINDINGS IN PERIPHERAL BLOOD SMEAR (PBS)

I. ETIOPATHOGENESIS
PERIPHERAL BLOOD SMEAR FEATURES
Tear Drop Cells Seen in myelofibrosis, myeloid metaplasia
Schistocytes Broken, fragmented cells
Seen in DIC, HUS, TTP, prosthetic valves, severe burns
Burr Cells (Echinocytes) Same as schistocytes, but with longer sharp spicules
Seen in renal insufficiency, gastric ulcers
Spur Cells (Acanthocytes) Rounded spicules
Seen in liver disease, abetalipoproteinemia
Target Cells Dark staining on peripheral and central areas
237
Seen in thalassemia, post-splenectomy, liver disease
Elliptocytes (Ovalocytes) Elongated in shape
Seen in hereditary elliptocytosis, hereditary ovalocytosis
Spherocytes Sphere-shaped cells
Seen in hereditary spherocytosis (increased osmotic fragility)
Sickle Cells Crescent-shaped with fragile membranes
Seen in sickle cell anemia
Stomatocytes Slit-like central pallor
Seen in hereditary stomatocytosis, drug reactions
II. VARIATION IN SIZEZ (ANISOCYTOSIS)

Microcytic Chronic iron deficiency anemia, thalassemia, chronic disease
Macrocytic Megaloblastic anemia, chronic liver disease, chronic alcoholism, reticulosytosis,
myelodysplastic syndrome
III. VARIATION IN COLOR

Normochromic (RBC) Concentration of hemoglobin in the RBC is within normal range
Anemia Seen in aplastic, hemolytic, post-hemorrhagic, chronic disease
Hyperchromic (RBC) Anemia Anemia with increased hemoglobin in individual RBCs, but with reduced number of
RBCs
Hypochromic (RBC) Anemia RBCs are paler than normal
Most common causes are iron deficiency and thalassemia
IV. ERYTHROCYTE INCLUSIONS

Basophilic Stipplings Small, fine to coarse, dark blue granules
Seen in lead poisoning, megaloblastic anemia
Howell-Jolly Bodies Small, round, uniform black inclusions
Seen in megaloblastic anemia, post-splenectomy
Heinz Bodies Irregular, refractile, peripheral granules
Seen in toxic medications, post-splenectomy, sideroblastic anemia
Dark blue spots, aggregates of reticulum
Reticulocytes Index of RBC production: a decrease in number is a sign of slow or no production
of RBC
238
COMMON COMPUTATIONS AND FORMULAS IN HEMATOLOGY
RED BLOOD CELL INDICES
Mean Corpuscular Volume MCV = Hct x 100 N: 80-100 Micro- / Normo- / Macrocytic
RBC
Mean Corpuscular MCH = Hgb N: 27-31 Hypo- / Normo- /
Hemoglobin RBC Hyperchromic
Mean Corpuscular MCHC = Hgb N: 330-390
Hemoglobin Concentration Hct
ABSOLUTE NEUTROPHIL COUNT

ANC = WBC X (PMNs + stabs) x 1000 ANC: absolute neutrophil count
WBC: white blood cell count
RETICULOCYTE COUNT AND INDEX

COMPUTING PARAMETERS SAMPLE CASE
1. Compute for Absolute Reticulocyte Count (ARC) A 35/F presents with pallor, Hgb 91, Hct
25%, retic count of 0.015
ARC = Retic Count x 1000 x Hgb of patient_______
Expected Hgb for age and gender ARC =0.015 x 1000 x 91 = 11.375
120
2. Choose Maturation Time (MT)
Maturation Time (MT) Hematocrit of Patient MT = 2.0
1.0 45%
1.5 35% RI = 11.375 = 5.7
2.0 25% 2.0
2.5 15%
*See section on anemia to interpret
3. Compute for Reticulocyte Index (RI) reticulocyte index results
RI = ARC
MT
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COMMON ANTIPLATELETS, ANTICOAGULANTS AND FIBRINOLYTICS
DRUG MECHANISM OF ACTION DOSE SIDE EFFECTS
Irreversibly acetylates platelets Most common: GI
Aspirin cyclooxygenase (COX) 75-325 mg OD (dyspepsia, bleeding,
perforation)
Most common: GI
Selectively inhibit ADP-induced Most serious;
platelet aggregation by irreversibly Clopidogrel: 300 mg LD hematologic
Thienopyridines blocking P2Y12 then 75 mg OD (neutropenia,
Clopidogrel Prasugrel: more rapid onset of Prasugrel: 60 mg LD thrombocytopenia)
Prasugrel action and more predictable then 10 mg OD Prasugrel
inhibition compared to clopidogrel contraindicated in
patients with prior stroke
or TIA
Prophylaxis: 5000 u SC
BID-TID Most common: bleeding
Unfractioned Acts by activating antithrombin For ACS: 60 u/kg LD Thrombocytopenia,
Heparin (UFH) Monitored via aPTT levels then 12 u/kg/h infusion osteoporosis, elevated
For PE: 80 u/kg LD then LFT
18 u/kg/h infusion
Major complication:
Similar mechanism as UFH but Prophylaxis: 4000-5000 bleeding (lower than
Low Molecular has better bioavailability, longer u SC OD UFH)
Weight Heparin half-life and more predictable Treatment: 100-120 u/kg Risk for
(LMWH) response SC BID thrombocytopenia and
No need for aPTT monitoring osteoporosis also lower
with LMWH
Fondaparinux Catalyzes factor Xa inhibition by For ACS: 2.5 mg SC OD Major effect: bleeding
antithrombin For PE: 7.5 mg SC OD
Most common
Oral anticoagulant which interferes hematologic: bleeding
with the synthesis of vitamin K Started at 5-10 mg PO Most common non-
Warfarin dependent clotting factors (II, VII, once daily (goal: INR 2- hematologic: alopecia
IX, X) 3x normal) Skin necrosis (rare)
Monitored via PT/INR levels Contraindicated in
pregnancy
Stroke prevention in AF:
150 mg BID Not recommended in
Dabigatran Direct thrombin inhibitor VTE: 150 mg BID (start end-stage CKD or on
No need for PT/INR monitoring after 5-10 days of hemodialysis
parenteral
anticoagulant)
Stroke prevention in AF:
Factor Xa inhibitor 20 mg OD Caution in patients with
Rivaroxaban No need for PT/INR monitoring VTE: 15 mg BID x 21 CKD (dose adjustment
days then 20 mg OD for needed)
6 mos
Stroke prevention in AF: Caution in patients with
Apixaban Factor Xa inhibitor 5 mg BID CKD (dose adjustment
No need for PT/INR monitoring VTE: 15 mg BID x 7 needed)
days then 5 mg BID
Streptokinase: 1.5 Mu
Degrade thrombi by converting infusion over 30-60 min Rare allergic reactions
Fibrinolytics plasminogen to plasmin indirectly Alteplase: IV infusion and transient
(streptokinase) or directly over 60-90 min hypotension
(alteplase, tenecteplase, reteplase) Reteplase: two IV
boluses 30 min apart
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SECTION 2
TRANSFUSION MEDICINE
BLOOD TYPING
BLOOD TYPE ANTIGEN (Present on RBC) ANTIBODY (Present in Serum)
A A-Antigen Anti-B
B B-Antigen Anti-A
AB A and B Antigen None
O None Anti-A, Anti-B, Anti-AB
Donor with type-O can give to recipient with ANY blood type (Universal Donor)
Donor with type-A can give to recipient with type A or AB
Donor with type-B can give to recipient with type B or AB
Donor with type-AB can give only to recipient with type AB (Universal Recipient)
RATIONAL USE OF BLOOD PRODUCTS

I. PACKED RED BLOOD CELL (PRBC) TRANSFUSION
Increases O2-carrying capacity in the anemic patient
Usually given as a drip to run for 4-6 hours after proper typing and cross-matching
One unit of pRBC increases Hgb by 1 g/dL or Hct by 3%
The criteria for pRBC transfusion should be based on Hgb level, the patient’s clinical condition and the risk of
inadequate oxygenation
A. General Indications for pRBC Transfusion

HEMOGLOBIN LEVEL REMARKS
< 6 g/dL Almost always indicated in patients with this hemoglobin level
6 to 10 g/dL Transfusion should be based on inadequate oxygenation versus the
risks of complications
Rarely indicated, except for patients with:
o Disabling angina pectoris
> 10 g/dL o Myocardial infarction
o Congestive heart failure from severe anemia
o End-stage renal disorder
B. Surgical Indications for pRBC Transfusion

Acute blood loss >2L or 40% loss of blood volume (whole blood may be considered)
pRBS transfusion may be beneficial for normovolemic patients with acute anemia who have cardiac disease or
are at risk of cardiac disease
C. Indications for “Prophylactic” Medications

Paracetamol: given only if febrile
Anti-histamine: given only if with previous history of allergy
Treat as necessary
May opt to give leukocyte-depleted products
II. PLATELET TRANSFUSION

Cross-matching not required but should be ABO type-specific
Premedication is not necessary
A. Platelet Function at Different Levels of Thrombocytopenia

PLATELET LEVEL (cell/mm3) BLEEDING TENDENCY
At >100,000 Bleeding time is not affected
At 10,000 Bleeding time is prolonged
At <10,000 Bleeding time is >30 minutes and not related to platelet count
At <5,000 Spontaneous bleeding may occur
241
B. General Indications:
Ongoing massive bleeding to maintain platelet count >50,000/mm 3, if with CNS trauma or bleeding maintain
platelet count >100,000/mm 3
Massive blood transfusion and with platelet count <20,000/mm 3
Episodes of hemorrhage or during times of active treatment in chronic, stable, severe thrombocytopenia such as
aplastic anemia and myelodysplasia
Persistent mucosal bleeding in patients with hemolytic disorders
Adult patients receiving therapy for acute leukemia at a threshold of 10,000/mm 3
Patients with solid tumors receiving aggressive therapy as well as those patients with necrotic tumors to maintain
a threshold of 20,000/mm3
Patients with qualitative platelet dysfunction with bleeding or will be undergoing surgery
C. Dose and Response

POOLED/RANDOM DONOR SINGLE DONOR/APHERESED PLATELETS
PLATELETS
1 Unit (~50 cc) per 10 kg 1 Pack (~200-600 cc, equivalent to 4-8 Units of Random Donor
Dose body weight (contains Platelet)
>5.5x1010 platelets/bag) Advantage: may reduce the risk of infectious disease transmission
by reducing the number of donor exposures
1 Unit increases platelet Corrected Count Increment (CCI) >10,000 within 1 hour and >
Response concentrate by 5,000 – 7,500 within 24 hours post-transfusion
10,000 cells/mm 3 CCI = {(Posttransfusion count-Pretransfusion count)/(Number of
platelets transfused x 10)} x BSA
D. Platelets are NOT useful in the following conditions (thrombocytopenia is due to increased platelet destruction)
Drug-induced Thrombocytopenia
TTP, HUS, ITP
Heparin-induced Thrombocytopenia
E. Usual Thresholds for Platelet Transfusion

Platelet count <10,000/mm3 as prophylaxis as bleeding
Platelet count <50,000/mm3 for major surgeries
Platelet count <30,000/mm3 for minor surgeries
III. FRESH FROZEN PLASMA TRANSFUSION

Contains coagulation factors and plasma proteins including fibrinogen, antithrombin, albumin and proteins C/S
General indications:
o Multiple coagulation factor deficiencies associated with severe bleeding or disseminated intravascular
coagulation with bleeding
o Single coagulation factor deficiencies when no virus-safe fractionated product is available
o Severe bleeding due to warfarin or patients taking warfarin who will undergo emergency surgical
procedure (should not be given for reversal of warfarin anticoagulation in the absence of severe bleeding)
o Trauma casualties with 30% or more blood loss and who will be requiring massive transfusion
Usually given as 15-20 mL/kg or 4-7 units for an average-sized adult increases coagulation factors by ~2%
Has a shelf-life of 1 year when kept frozen at -30oC
IV. CRYOPRECIPITATE TRANSFUSION

Contains fibrinogen, factor VIII, factor XIII and von Willebrand factor (labile clotting factors)
Indicated for Hemophilia A with bleeding or anticipated bleeding, von Willebrand disease, fibrinogen deficiency in
DIC and factor XIII deficiency
Given in pools of 6 units increases fibrinogen by 30-60 mg/dL
Has a shelf-life of 1 year when kept frozen at -30oC
V. CRYOSUPERNATE TRANSFUSION
Contains plasma proteins and factors II, VII, IX and X (stable clotting factors)
Contains factor XIII and von Willebrand factor but is low in factor VIII
242
Indicated for patients with Hemophilia B, plasma exchange in TTP and rapid temporary warfarin reversal in
patients requiring emergency surgery
VI. GRANULOCYTE CONCENTRATE TRANSFUSION

Given for patients with markedly decreases ANC or in patients with gram-negative sepsis with ANC <500 and not
responding to antibiotics
Mostly replaced with granulocyte colony-stimulating factor (G-CSF) injections
VII. WHOLE BLOOD

Provides both O2-carrying capacity and volume expansion
Reserved for patients with massive bleeding and for exchange transfusion
Volume of 500 cc (contains 250 g iron)
Given at a dose of 20 mL/kg x 4 hours
243
SECTION 3
COMMON CONDITIONS IN HEMATOLOGY
ANEMIA
I. GENERAL APPROACH TO ANEMIA
In anemia, first get the reticulocyte index (RI)
o If RI <2.5: think of hypoproliferative anemias or maturation disorder
o If RI >2.5: think of hemolytic anemia (hemolysis) or hemorrhage
A. Anemias with Reticulocyte Index < 2.5

HYPOPROLIFERATIVE ANEMIAS MATURATION DISORDERS
(Normocytic, Normochromic) (Microcytic or Macrocytic)
Iron deficiency anemia Iron deficiency anemia (Micro)
Thalassemia Thalassemia (Micro)
Renal insufficiency Folic acid deficiency (Macro)
Inflammation / chronic disease Vitamin B-1 deficiency (Macro)
Marrow damage: aplasia, infiltration, fibrosis Drug toxicity
Sideroblastic anemia
B. Anemias with Reticulocyte Index > 2.5

Usually presents with indirect hyperbilirubinemia, elevated LDH, jaundice
o Blood loss
o Intravascular hemolysis
o Metabolic defects
o Membrane abnormality
o Hemoglobinopathy
o Immune destruction
o Fragmentation hemolysis
II. MAJOR CLASSIFICATION OF ANEMIA
A. Hypoproliferative Anemia
1. Differential Diagnosis of Microcytic Anemia
TESTS IRON INFLAMMATION THALASSEMIA SIDEROBLASTIC
DEFICIENCY ANEMIA
Smear Micro/hypo Normal/micro/hypo Micro/hypo with Variable
targeting
Serum Iron (mcg/dL) <30 <50 Normal to high Normal to high
Total Iron Binding >360 <300 Normal Normal
Capacity (mcg/dL)
Percent Saturation <10 10-20 30-80 30-80
Ferritin (mcg/dL) <15 30-200 50-300 50-300
Hemoglobin pattern on Normal Normal Can be abnormal Normal
electrophoresis
2. Differential Diagnosis of Hypoproliferative Anemias

TESTS IRON INFLAMMATION RENAL DISEASE HYPOMETABOLIC
DEFICIENCY STATES
Anemia Mild to severe Mild Mild to severe Mild
MCV (fL) 60-90 80-90 90 90
Morphology Normo-microcytic Normocytic Normocytic Normocytic
Serum Iron (mcg/dL) <30 <50 Normal Normal
TIBC (ug/dL) >360 <300 Normal Normal
Saturation (%) <10 10-20 Normal Normal
Serum Ferritin (g/L) <15 30-200 115-150 Normal
Iron Stores 0 2-4+ 1-4+ Normal
244
3. Features of Common Hypoproliferative Anemias
TYPE FEATURES TREATMENT
Most common form of anemia worldwide Oral iron suffices for most patients
Causes include: IV iron can be given to those who
o Increased iron demand (growth, cannot tolerate oral iron
Iron-deficiency pregnancy) Blood transfusion reserved for
anemia o Increased loss (bleeding, symptomatic and/or unstable patients
menstruation, phlebotomy) and those with continued/excessive
o Decreased intake or blood loss
malabsorption
Second most common form of anemia
worldwide
Anemia of Caused by inadequate iron delivery to Blood transfusion
chronic the marrow despite normal or increased Erythropoietin (should be withheld
inflammation stores when an infection intervenes)
Distinguished from IDA by high serum
ferritin levels
B. Megaloblastic Anemia
Group of disorders characterized by distinctive morphologic appearances of developing red cells due to defects in
DNA synthesis
Bone marrow is usually cellular
Anemia is due to ineffective erythropoiesis
Many asymptomatic patients are detected due to increased MCV on routine CBC; and macrocytes and
hypersegmented neutrophils on peripheral smear
Usually due to vitamin B12 deficiency or folic acid deficiency
DISEASE CAUSES TREATMENT
Major causes
o Malabsorption (pernicious anemia)
Vitamin B12 o Inadequate dietary intake (vegans)
(Cobalamin) Minor causes Usually requires lifelong regular
deficiency o Total/partial gastrectomy cobalamin injections
o Ileal resection
o Abnormalities of cobalamin
metabolism
Dietary deficiencies
Malabsorption
Folic acid Excess utilization/loss (pregnancy, co- Blood transfusion
deficiency morbidities) Erythropoietin (should be withheld
Use of antifolate drugs when an infection intervenes)
C. Hemolytic Anemia
Anemia due to increased destruction of RBCs
Main clinical signs are jaundice, pallor and splenomegaly
Laboratory features include increased MCV and MCH, reticulocytosis, increased LDH and unconjugated
hyperbilirubinemia
Can be either hereditary or acquired
1. Hereditary Hemolytic Anemia

DISEASE FEATURES TREATMENT
Autosomal dominant inheritance
Hereditary Deficiency of spectrin and Ankyrin Splenectomy is the definitive
Spherocytosis Increased MCHC on PBS treatment
Diagnosed by osmotic fragility test
Alpha thalassemia Supportive pRBC transfusions
Thalassemia o Thalassemia trait (1-2 gene deletion) Splenectomy if transfusion
Syndromes o Hb-H (3 gene deletion) requirement ↑ by 50% per year
o Hydrops fetalis with Hb-Barts (4 gene
245
deletion)
Beta thalassemia
o Thalassemia minor (↑ HbA2)
o Thalassemia major (Mediterranean or
Cooley anemia) (↑ HbF)
o Diagnosed by Hgb electrophoresis
Glucose-6- X-linked inheritance Avoidance of exposure to
Phosphate Usual triggers include fava beans, infection and triggering agents
Dehydrogenase drugs No specific treatment for most
(G6PD) Hemighosts, bite cells and Heinz bodie on PBS cases; blood transfusion for
Deficiency Diagnosed by G6PD assays emergency cases
2. Acquired Hemolytic Anemia

Warm type: involves IgG, reacts at body
Autoimmune temperature Steroids
Hemolytic Cold type: involves IgM, reacts at cold Some with spontaneous
Anemia (AIHA) temperature resolution
Diagnosed by Coomb’s antiglobulin test
Clinical triad Hematopoietic stem cell
Paroxysmal o Hemolytic anemia transplant (HSCT) is the definitive
Nocturnal o Venous thrombosis treatment
Hemoglobinuria o Deficient hematopoiesis Washed pRBC transfusions
(PNH) Due to complement hypersusceptibility as a Steroids
result of CD55 and CD59 deficiency Anticoagulation if with thrombosis
Diagnosed by flow cytometry
THROMBOCYTOPENIA
Most common cause: drug-induced
Most common non-iatrogenic cause: infection
Thrombocytopenia not usually severe (rarely Discontinuation of heparin
Heparin-induced 20,000/L) Direct thrombin inhibitors
Thrombocytopenia (HIT) Not associated with bleeding (in fact, Anticoagulation
increases risk of thrombosis)
Corticosteroids (mainstay in
treatment)
Idiopathic Splenectomy (long term)
Thrombocytopenia Bleeding diathesis with essentially normal PE High-dose IVIg
purpura (ITP) Immunosuppressants (e.g.,
rituximab)
Thrombopoietin receptor agonists
Pentad (FAT RN)
o Fever Plasmapheresis (mainstay in
o Microangiopathic hemolytic Anemia treatment)
Thrombotic o Thrombocytopenia Corticosteroids
Thrombocytopenic o Renal failure Immunomodulatory therapies
purpura (TTP) o Neurologic decline (rituximab, vincristine,
Inherited and idiopathic cases due to cyclophosphamide)
deficiency of ADAMTS13 that normally Splenectomy
cleaves vWF
Triad
o Microangiopathic hemolytic anemia Primarily supportive
Hemolytic Uremic o Thrombocytopenia Some patients may require short-
Syndrome (HUS) o Renal failure term dialysis
Predominantly seen in children
Most frequently caused by E. coli O157:H7
246
BONE MARROW FAILURE
Diagnosed by a combination of pancytopenia Hematopoetic stem cell transplant
with a fatty (hypocellular) bone marrow (HSCT): best treatment for young
Can be inherited or acquired patients with a fully compatible
Aplastic Anemia (AA) Biphasic peak (teens and older adults) sibling donor
Hepatitis: most common preceding infection Antithymocyte globulin (ATG) +
Bleeding: most common early symptom cyclosporine
Androgens (e.g., danazol)
Cytopenia associated with a dysmorphic and Only stem cell transplantation is
Myelodysplastic usually cellular bone marrow, and by curative
Syndrome (MDS) consequent ineffective blood cell production ATG + cyclosporine
Usually seen in older individuals Low doses of cytotoxic drugs (e.g.,
Anemia dominates the early course azacitidine, lenalidomide)
HEMATOLOGIC MALIGNANCIES
Goal is to quickly induce clinical
remission
Divided into two phases:
Etiology: heredity (e.g., Down’s syndrome), 1. Induction (cytarabine +
high-dose radiation, benzene exposure and anthracycline)
Acute Myeloid Leukemia drugs (e.g., anticancer drugs) 2. Consolidation (high dose
(AML) Chromosomal findings at diagnosis provide cytarabine)
the most important prognostic factor Allogeneic HSCT for patients who
Auer rods confirm myeloid lineage relapse
All trans retinoic acid (ATRA)
effective for acute promyelocytic
leukemia (APL)
Usually found in older individuals First-line therapy: tyrosine kinase
Caused by reciprocal translocation of inhibitors (e.g., imatinib, nilotinib,
Chronic Myeloid chromosomes 9 and 22 forming a BCR-ABL dasatinib)
Leukemia (CML) fusion gene (Philadelphia chromosome) Allogeneic HSCT for patients who
Mild to moderate splenomegaly: most develop drug resistance
common physical finding
Triad of B symptoms
o Fever (Pel Ebstein fever) Chemotherapy regimens
o Night sweats o ABVD (doxorubicin, bleomycin,
Hodgkin Lymphoma (HL) o Weight loss vinblastine, dacarbazine)
Most common presentation is palpable o MOPP (mechlorethamine,
lymphadenopathy vincristine, procarbazine,
Most common subtype is nodular sclerosing prednisone)
Staging is done using the Ann Arbor system
Diffuse large B cell lymphoma: most common CHOP (cyclophosphamide,
Non-Hodgkin Lymphoma subtype doxorubicin, vincristine,
(NHL) Burkitt’s lymphoma: most rapidly progressive prednisone) plus rituximab
human tumor
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CHAPTER 12
DERMATOLOGY
I. Approach to Patients – The Dermatology Lexicon
II. Common Outpatient Cases in Dermatology
1. Acne Vulgaris
2. Hansen’s Disease
3. Contact Dermatitis
4. Psoriasis Vulgaris
5. Topical Corticosteroids: Classes According to Potency
III. Common Inpatient Conditions in Dermatology
1. Epidermal Necrolysis (SJS / TEN)
2. Erythroderma / Exfoliative Dermatitis
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SECTION 1
APPROACH TO PATIENTS – THE DERMATOLOGY LEXICON
MORPHOLOGY
I. PRIMARY SKIN LESIONS
LESION DESCRIPTION USUALLY SEEN IN
Flat circumcised area of skin color change Solar lentigo, idiopathic guttate hypomelanosis,
Macule Non-palpable, can be ill-defined or well- macular exanthema
defined
Patch Similar to a macule, but >0.5 cm in diameter Melisma, vitiligo, Mongolian spot
Solid, elevated lesion in which a significant Acrochordion, keloid, lichen planus
Papule portion projects above the plane of the
surrounding skin
Plaque Similar to a papule, but >0.5 cm in diameter Psoriasis vulgaris, lichen simplex chronicus
Solid elevated lesion in which a significant Lipoma, nodular basal cell carcinoma, gumma of
Nodule portion is beneath the skin surface tertiary syphilis
Usually >0.5cm, depth of involvement
differentiates it from a papule/plaque
Cyst Encapsulated cavity or sac lined by true Epidermoid cysts
epithelium
Wheal Swelling of the skin that is characteristically Dermatographism
evanescent (disappearing within hours)
Vesicle Superficial, elevated, cavity containing clear, Dyshidrotic dermatitis, herpes simplex
serous, or hemorrhagic fluid
Bulla (Bullae) Similar to a vesicle, but >0.5cm in diameter Bullous pemphigoid, bullous drug eruption
Pustule Similar to a vesicle but containing purulent Folliculitis
fluid
II. SECONDARY SKIN LESIONS

LESION DESCRIPTION
USUALLY SEEN IN
Crust Dried serum (yellow-brown), blood (reddish-black), or pus (yellow-green) on ski surface
Example: classic honey-colored crusts of impetigo
Scale Flakes of stratum corneum
Example: psoriasis vulgaris, pityriasis rosea, ichthyosis vulgaris
Excoriation Surface excavations of the epidermis as a result of scratching
Fissure Linear loss of continuity of the skin surface, usually from excessive tension or decreased elasticity
Erosion Sharply defined, red, moist lesion resulting from partial loss of the epidermis
Ulceration Deeper defect, extending to at least the dermis
Scar Fibrous tissue replacement of a previous ulcer
Atrophy Diminution of some or all layers of the skin
Lichenification Reactive thickening of the skin with accentuation of skin markings due to repeated rubbing or
scratching
SHAPE OR CONFIGURATION
SHAPE DESCRIPTION
Annular Ring-shaped
Round/Nummular Discoid / coin-shaped
Polcyclic Coalescing circles or incomplete rings
Arcuate Arc-shaped
Linear May imply Koebner phenomenon
Reticular Net-like, lacy
Serpiginous Serpentine, snake-like
Targetoid Target-like with at least three distinct zones
Whorled Like a marble cake with two distinct colors interspersed in a wavy pattern
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SECTION 2
COMMON OUTPATIENT CASES IN DERMATOLOGY
ACNE VULGARIS
I. ETIOPATHOGENESIS
Onset at puberty (starts as comedones), peaks at middle to late adolescence
Pathogenesis:
o Follicular epidermal hyperproliferation
o Excess sebum production
o Inflammation
o Propionibacterium acnes: gram-positive, anaerobic, normal flora of sebaceous glands

Lesions are polymorphous
o Non-inflammatory lesions: close comedones (whiteheads), open comedones (blackheads)
o Inflammatory lesions: erythematous papules, pustules, fluctuant nodules
Type of acne scars: ice-pick, rolling, box-car, hypertrophic
Sites of predilection: face, back, chest, shoulders
ACNE VARIANT REMARKS
Neonatal acne Appears 2 weeks and resolves spontaneously at 3 months
Small inflamed papules on nasal bridge and cheeks, no comedones
Infantile acne Appears at 3-6 months and resolves, spontaneously at 1-2 years
Shows comedones, papules, pustules, nodules
Common in teenage males
Acne conglobate Severe form of nodular acne more prominent on the trunk
Often results in scarring and requires systemic treatment
Acne fulminans (acute Common in teenage males
febrile ulcerative acne) Severe form of nodular acne on the back (sparing the face) but more explosive in
onset, with lesions becoming ulcerative, and associated with systemic findings
Acne excoriee des Occurs in young women who are picking at their skin
jeunes filles Often with underlying depression, anxiety, OCD, personality disorder
Acne mechanica Occurring after repetitive rubbing or occlusion from clothing or sports equipment
Acne with solid facial
edema (Morbihan’s Disfiguring woody edema of the midthird of the face, requires systemic treatment
disease)
III. MANAGEMENT
Initiate treatment early and aggressively to prevent permanent sequelae
Application of a gentle cleanse twice daily
TOPICAL AGENTS SYSTEMIC THERAPY
Antibiotics (doxycycline 50-100 mg BID,
Salicylic acid minocycline 50-100 mg BID, clindamycin 150-
Azelaic acid 300mg QID)
Benzoyl peroxide (BPO) Oral contraceptives
Topical antibiotics (erythromycin, clindamycin) Isoretinoin 0.5-1 mg/kg/day (cumulative dose
Retinoids (adapalene, tretinoin at HS) 120-150mg/kg/day) + prednisone 40-60mg OD x
1-2 weeks

Comedronal Papular/Pustular Papular/Pustular Nodular Conglobate/
Fulminans
Topical retinoid Topical retinoid + Oral antibiotic + Oral antibiotic + Isoretinoin + oral
First + topical topical antibiotic topical retinoid + topical retinoid + corticosteroids
antibiotic BPO BPO
Second Topical dapsone Topical dapsone Oral antibiotic + Isoretinoin or High dose oral
250
or azelaic acid or or azelaic acid or topical retinoid + oral antibiotic + antibiotic +
salicylic acid salicylic acid BPO topical retinoid + topical retinoid +
BPO/azelaic acid BPO
- - + Oral + Oral + Oral
Female contraceptive / contraceptive/ contraceptive /
antiandrogen antiandrogen antiandrogen
Maintenance Topical retinoid Topical retinoid + Topical retinoid + Topical retinoid +
+ BPO BPO BPO BPO
HANSEN’S DISEASE (LEPROSY)

I. ETIOPATHOGENESIS
More common in males
Philippines remains to be a top contributer in Western Pacific Region (Endemic areas: Ilocos Region, Central
Visayas, NCR and SOCCSKARGEN)
Mycobacterium leprae: non-cultivable, gram-positive, obligate intracellular, acid-fast bacilli that requires cool
temperatures for growth (e.g., skin, superficial nerves, anterior chamber of eyes, testes)
Transmission: respiratory (nasal droplet) and hypothetically, skin-to-skin
Reservoir: humans and armadillos
Incubation: average of 2-5 years or even longer
A. Deformities in Leprosy
Facial Lagophthalmos, mask-face
Ulnar Claw hand
Radial Wrist-drop
Median Clawing of index and middle finger
Lateral popliteal Foot-drop
Posterior tibial Clawing of toes and collapse of arches
B. Classification of Leprosy (Ridley-Jopling and WHO Classification System)

Tuberculoid Borderline Borderline Borderline Lepromatous
(TT) Tuberculoid (BT) (BB) Lepromatous (BL) (LL)
Tuberculoid Borderline Lepromatous
Strong immunity to Low immunity to Low immunity
restrain infection restrain infection permits bacillary
but enough to dissemination
Strong immunity Multiple, asymmetric Immunologic induce
for self-cure (but midzone, easily inflammation Multiple,
still needs Annular plaque with upgrade or symmetric, poorly
treatment) sharply marginated downgrade Classic dimorphic defined nodules
borders lesions: annular
Usually solitary Annular plaque plaques with a Diffuse dermal
Ridley- Sharply marginated with sharply sharply marginated infiltration causes
Jopling Sharply satellite papules marginated inner border and enlargement of
marginated borders poorly marginated earlobes,
indurated Compared to TT, outer border widening of nasal
erythematous lesions are larger, but Large plaques root, fusiform
plaque, often less scaly, less with islands of Hyper/hypoesthetic swelling of
annular erythematous and less clinically normal skin lesions, fingers, skin
indurated skin within the multiple nerve thrown into folds
Scaly, dry, plaque or “Swiss trunk palsies, (producing
hairless, Hypoesthetic skin cheese” stocking-glove leonine facies)
anhidrotic, lesions with 1 or 2 nerve pattern of sensory
anesthetic trunk enlargement/ impairment Hair loss common
palsies in eyebrows
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Stocking-glove
pattern of sensory
impairment lead
to trophic
changes
Multibacillary
WHO Paucibacillary Any one of the ff: >5 skin lesions; >1 nerve trunk involved;
+AFB in skin smears
C. WHO Disability Grading

HANDS/FEET EYES
Grade 0 No anesthesia, deformity or damage No eye problems or evidence of visual
impairment
Grade 1 Anesthesia Eye problems
No deformity or damage Vision 6/60 or better, can count at 6 meters
Grade 2 Visible deformity or damage Severe visual impairment, lagophthalmos,
iridocyclitis, corneal opacities
III. DIAGNOSIS OF LEPROSY

An individual who has not completed a course of treatment and has one or more of the cardinal
Clinical signs:
Diagnosis o Hypopigmented or reddish skin lesion/s with definite sensory loss
(WHO) o Damage to peripheral nerves: nerve thickening, loss of sensation, weakness of muscles
hands/feet, face
o Positive slit skin smear for acid fast bacilli
Slit skin Take from the most active lesion (raised and red, usually the edge); if none, from a site that had
smears active lesions or previously positive smears
Skin biopsy Not required for diagnosis but can support a diagnosis of leprosy & rule out other diseases
IV. MANAGEMENT OF LEPROSY

FORM OF LEPROSY WHO-RECOMMENDED REGIMEN (1982)
Pacubacillary (6 months) Dapsone 100 mg OD + Rifampin 600 mg/month
Multibacillary (12 months or until skin smears Clofazimine 50 mg + Dapsone 100 mg OD; and
show no live bacilli) Rifampin 600 mg + Clofazimine 300 mg once a month
CONTACT DERMATITIS
Exogenous eczemas
Acute or chronic inflammatory reactions to substances that come in contact with the skin
IRRITANT CONTACT DERMATITIS (ICD) ALLERGIC CONTACT DERMATITIS (ACD)
Affects anyone exposed to the irritant substance Occurs in sensitized individuals
Epidemiology Most common occupational skin disease Uncommon in children and elderly (>70
years)
Nickel (metals, jewelry)
Neomycin sulfate (creams, ointments)
Balsam of Peru (topical meds)
Fragrance mix, cosmetics
Soaps, detergents, waterless hand cleaners Thimerosal (antiseptics)
Common Acids and alkalis Sodium gold thiosulfate (medication)
Causative Industrial solvents Formaldehyde (disinfectant, curing agents,
Agents Plants plastics)
Others: fiberglass, wool, rough synthetic clothing, Quaternium-15 (disinfectant)
fire-retardant fabrics, “NCR” paper Bacitracin (ointments, powder)
Cobalt chloride (cement, galvanization,
industrial oils, cooling agents, eyeshades)
Carba mix (rubber, latex)
Paraphenylenediamine (PPD) (hair dye,
252
textile dye, printer’s ink)
Thiuram (rubber)
MAJOR CRITERIA
Subjective
Onset of symptoms within minutes to hours of
exposure
Pain, burning, stinging or discomfort exceeding
itching early in the clinical course
Objective
Macular erythema, hyperkeratosis, or fissuring
predominating over vesiculation
Glazed, parched or scalded appearance of the
epidermis PATCH TESTING
Healing process begins promptly on withdrawal of Gold standard (to identify causal allergens)
exposure to the offending agent Indicated for patients with recurrent or
Diagnosis Patch testing is negative persistent dermatitis in whom ACD is
suspected
MINOR CRITERIA Standard test contains 28 allergens and 1
Subjective control
Onset of dermatitis within 2 weeks of exposure
Many people in the area affected similarly
Objective
Sharp circumspection of the dermatitis
Evidence of gravitational influence such as
dripping
Morphologic changes suggesting small
concentration differences or contact time produce
large differences in skin damage
Avoid irritants Identify and remove allergens
Emollients or occsluive dressings (petroleum jelly, Potent topical steroids, topical calcineurin
Management ceramide-containing lotions) inhibitors
In severe/chronic cases: potent topical steroids, For severe cases, systemic steroids for 1-2
topical calcineurin inhibitors, phototherapy weeks
PSORIASIS VULGARIS
I. ETIOPATHOGENESIS
More likely to appear between ages 15 and 30 years
T-cell driven disease
Production of epidermal cells is increased 28x
Triggers:
o Koebner phenomenon or isomorphic response (traumatic induction of psoriasis on non-lesional skin)
o Infections (especially streptococci, HIV)
o Drugs (e.g., lithium, beta blockers, interferons, antimalarials)
o Others: hypocalcemia, pregnancy, psychogenic stress, alcohol consumption, smoking, obesity

Psoriasis is a clinical diagnosis. A biopsy is indicated if the five classic features are not present:
o Symmetry of lesions
o Extensor distribution
o Auspitz sign (pinpoint bleeding when scale is gently removed)
o Sharply demarcated lesions
o Silvery scale
Most common forms:
o Chronic plaque type
o Guttate (eruptive) psoriasis usually triggered by streptococcal infection
o Erythrodermic/pustular psoriasis from worsening of chronic plaque or nontolerated treatment
253
Common related findings: nail pitting, oil spots, onychodystrophy, arthritis, metabolic syndrome
Characteristic histopathologic findings:
o Microabscess of Munro: collection of neutrophils in the stratum corneum
o Spongiform pustule of Kogoj: collection of neutrophils in the stratum spinosum
III. MANAGEMENT
Patient education
Modifying factors (obesity, infection, smoking, alcohol, drugs)
GUTTATE ERYTHRODERMIC/
PSORIASIS CHRONIC PLAQUE PSORIASIS PUSTULAR
PSORIASIS
Topical Systemic Phototherapy
1st line 1st line 1st line
Emollients Methotrexate NB UVB
Glucocorticoids Acitretin BB UVB Acitretin
No treatment Vitamin D3 analogs Biologicals Cyclosporine A
NB UVB 2nd line PUVA/NB UVB
Topical 2nd line Fumaric Acid 2nd line Methotrexate
-Vitamin D3 analog Salicylic acid Esters PUVA Anti-TNF agents
-Topical steroids Dithranol Cyclosporine A Excimer Systemic steroids
Tazarotene Hydroxyurea Climatotherapy
Tar 6-Thioguanine
Mycophenolate
Sulfasalazine
TOPICAL CORTICOSTEROIDS: CLASSES ACCORDING TO POTENCY

Higher potency for palms, soles, or thick lichenified lesions
Lower potency: non-halogenated for face, intertriginous areas, children, pregnant or involvement of large surface
areas
CLASS POTENCY EXAMPLES
Clobetasol propionate gel, ointment, cream, lotion, foam, spray and
Class 1 shampoo 0.05%
Superpotent Betamethasone dipropionate gel and ointment 0.05%
Fluocinonide cream 0.1%
Halobetasol propionate ointment and cream 0.05%
Betamethasone dipropionate cream, lotion, gel and ointment 0.05%
Class 2 Clobetasol propionate solution (“scalp application”) 0.05%
Fluocinonide gel, ointment, cream and solution 0.05%
Mometasone furoate ointment 0.1%
High potency Triamcinolone acetonide ointment 0.5%
Betamethasone dipropionate cream and lotion 0.05%
Class 3 Betamethasone valerate ointment 0.1%
Fluticasone propionate ointment 0.005%
Triamcinolone acetonide ointment 0.1% and cream 0.5%
Class 4 Fluocinolone acetonide ointment 0.025%
Mometasone furoate cream and lotion 0.1%
Betamethasone dipropionate lotion 0.05%
Medium potency Betamethasone valerate cream and lotion 0.1%
Class 5
Fluocinolone acetonide cream 0.025%
Fluticasone propionate cream and lotion 0.05%
Triamcinolone acetonide ointment 0.025% and lotion 0.1%
Betamethasone valerate lotion 0.1%
Class 6 Desonide gel, ointment, cream, lotion and foam 0.05%
Low potency Fluocinolone acetonide cream and solution 0.01%
Triamcinolone acetonide cream and lotion 0.025%
Class 7 Topicals with hydrocortisone, dexamethasone and prednisolone
254
LOCAL ADVERSE EFFECTS (MORE COMMON) SYSTEMIC ADVERSE EFFECTS
Atrophic changes
Acneiform reactions Glaucoma
Hypertrichosis Suppression of hypothalamic-pituitary-adrenal axis
Hypopigmentation Hyperglycemia, DM
Infections
Allergic reactions
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SECTION 3
COMMON INPATIENT CASES IN DERMATOLOGY
EPIDERMAL NECROLYSIS (STEVENS-JOHNSON SYNDROME AND TOXIC EPIDERMAL NECROLYSIS)
I. ETIOPATHOGENESIS
Acute life-threatening mucocutaneous reaction characterized by extensive necrosis & detachment of epidermis
60-80% due to drugs, 20% due to infection, 20% idiopathic
Mucous membrane involvement in 90% of cases and can precede or follow skin eruption
COMMONLY IMPLICATED MIEDCATIONS
Allopurinol Carbamazepine Sulfamethoxazole
Nevirapine Lamotrigine Sulfadiazine
Oxicam NSAIDs Phenobarbital Sulfapyridine
Thiacetazone Phenytoin Sulfadoxine
Phenylbutazone Sulfasalazine

Begins 8 weeks (usually 4 to 30 days) after exposure to a drug for the first time
Can have a prodrome of fever, headache, rhinitis, cough, malaise, pain on swallowing, burning or stinging of eyes
heralding mucous membrane involvement
Appear first on the trunk, spreading to the neck, face and proximal upper extremities with distal portions of the
arms and legs relatively spared
Can begin as morbiliform, target lesion-like, multiple erythematous dusky irregular macules confluence of
individual lesions leading to extensive and diffuse erythema (Nikolsky sign: dislodgement of the epidermis by
lateral pressure, is positive on erythematous zones) necrotic epidermis detaches from the dermis giving rise to
flaccid blisters (Asboe-Hansen sign: the extension of the blisters laterally by slight pressure of the thumb) and
sheets of necrotic epidermis resembling wet cigarette paper large denuded areas of red, oozing dermis similar
to a second-degree-thermal burn plateau phase but life-threatening complications may occur re-
epithelialization
Clues that this is SJS/TEN: rapid progression, severe pain, constitutional symptoms
III. DIAGNOSIS
Classification according to Extent of Skin Detachment (in % Body Surface Area involvement)
<10% BSA 10-30% BSA >30% BSA SJS – Steven-Johnsons Syndrome
SJS SJS/TEN TEN TEN – Toxic Epidermal Necrolysis
BSA – Body Surface Area
IV. SCORTEN: A PROGNOSTIC SCORING SYSTEM FOR PATIENTS WITH EPIDERMAL NECROLYSIS
PROGNOSTIC FACTORS POINTS INTERPRETATIONS
Age >40 years 1 Best done on day 3 of hospitalization
Hr >120 bpm 1 Points with their corresponding mortality rate (in %)
Cancer / hematologic malignancy 1 o 0-1 point: 3.2%
BSA involved >10% 1 o 2 points: 12%
Serum urea >10 mM 1 o 3 points: 36%
Serum bicarbonate >20 mM 1 o 4 points: 58%
Serum glucose >14 mM 1 o 5 points: 90%
V. MANAGEMENT
A. Early Recognition and Withdrawal of Offending Drug

Supportive measures : fluid and electrolyte replacement, optimal environmental temperature (28-30%), daily eye
exam and disruption of early synechiae by an ophthalmologist
B. Specific Treatment in the Acute Phase

Corticosteroids: still controversial dexamethasone IV 1.5 mg/kg/day for 3 days
Intravenous immunoglobulin 1g/kg/day for 3 days
Cyclosporine 3-4 mg/kg/day
256
Cyclophosphamide 100-300 mg/day
VI. COMPLICATIONS
Most common: sepsis from superimposed bacterial infection (S. aureus, Pseudomonas, Enterobacteriae)
Dehydration
Multiple organ system failure
Late complications of mucosal membrane involvement
ERYTHRODERMA / EXFOLIATIVE DERMATITIS

I. ETIOPATHOGENESIS
Diffuse erythema and scaling of the skin involving >90% of the total body skin surface area
52% from preexisting dermatoses (psoriasis, spongiotic dermatitis, immunobullous diseases), 20% idiopathic,
15% drug hypersensitivity reaction, 5% cutaneous T cell lymphoma

Erythematous patches that increase in size and coalesce into generalized erythema with a shiny appearance
fine white or yellow scaling dull red, edema, lichenification, skin induration
Other changes: ectropion, epiphora, palmoplantar keratoderma, nail changes, scaling of the scalp, diffuse
effluvium, alopecia
Systemic findings: tachycardia, hyperthermia/hypothermia, high-output cardiac failure, generalized
lymphadenopathy, hepatomegaly, splenomegaly, pedal edema, increased susceptibility to infections and sepsis
III. MANAGEMENT
GENERAL MEASURES DIRECTED THERAPY
(once underlying etiology is established)
Fluid and electrolyte replacement Prednisone 1-2 mg/kg/day with taper (for drug
Nutritional replacement (folate supplementation, diet reactions, immunobullous diseases, atopic dermatitis)
with 130% of normal dietary requirements of protein) Cyclosporine 4-5 mg/kg/day (for psoriasis, atopic
Keep in a warm humid environment (30-32oC) dermatitis)
Oatmeal baths, wet dressings on weeping or crusted Methotrexate 5-25 mg/week (for psoriasis, atopic
lesions, bland emollients dermatitis)
Low-potency topical corticosteroids Mycophenolate mofetil 1-3 g/day (for psoriasis, atopic
Sedating antihistamines (hydroxyzine 25-50 mg tab dermatitis, immunobullous diseases)
HS, diphenhydramine 25-50 mg cap q4-6h) Infliximab 5-10 mg/kg (for psoriasis)
Etanercept 25mg SC 2x/week (for psoriasis)
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CHAPTER 13
NEUROLOGY
I. Approach to Patients with Neurologic Conditions
II. Review of the Standard Neurologic Exam
III. Common Inpatient Cases
1. Cerebrovascular Disease
2. Subarachnoid Hemorrhage
3. Seizures and Epilepsy
4. CNS Infection
258
SECTION 1
APPROACH TO PATIENTS WITH NEUROLOGIC CONDITIONS
DIAGNOSTIC CATECHISM
I. DOES THE PATIENT HAVE A NEUROLOGIC PROBLEM?
NEUROLOGIC REMARKS
PROBLEM
Numbness of the face, arm, or leg especially on one side of the body
Focal Neurologic Hemiparesis/hemiplegia (weakness or paralysis on one side of the body)
Deficits Visual field problems like hemianopia or quadrantanopia
Trouble speaking or understanding
Problem with walking, balance and coordination
Increased Intracranial Main symptoms: headache, papilledema, vomiting
Pressure (ICP) Other symptoms: deteriorating sensorium, Cushing’s triad (hypertension, bradycardia,
irregular respiration), anisocoria
Presence of nuchal rigidity, Brudzinski’s, and Kernig’s signs
Meningeal Irritation Most common infectious cause of meningeal irritation: meningitis
Most common non-infectious cause of meningeal irritation: subarachnoid hemorrhage
Seizures Discussed in detail in next section
II. WHERE IS THE LESION? (ANATOMIC DIAGNOSIS: REMEMBER THE 3L’S)
A. Levelize
Central or peripheral?
If central, supratentorial or infratentorial?
o Supratentorial structures: cortex and subcortical structures
o Infratentorial structures: brainstem and cerebellum
B. Lateralize
Right, left or midline
Diffuse (no lateralizing signs, e.g., meningitis & subarachnoid hemorrhage unless with arteritis or vasospasm)
C. Localize
LESION DESCRIPTION
Cerebrum Discrete deficits, language disorders, intellectual impairment, seizures
Differentiate between cortical vs. subcortical lesions
Long tract signs (hemiparesis, hemisensory deficits)
Crossed signs (contralateral long tract signs, ipsilateral cranial nerve signs)
Cranial nerve signs:
III, IV, VI Diplopia
Brainstem V Facial sensation is decreased
Disease VII Facial muscle weakness
VIII Deafness and dizziness
IX, X Dysarthria and dysphagia
XI Decreased strength of SCM and trapezius muscles
XII Dysarthria and tongue deviation
Cerebellum Incoordination, clumsiness, ataxia, tremors on voluntary movements, nystagmus
Bilateral, often symmetrical deficit but normal neurologic function above the lesion
Spinal cord Presence of sensory level differences
Autonomic function disturbances (bowel and bladder problems)
Signs of upper motor neuron lesions: extensor toe sign, spasticity, hyperreflexia, clonus
Pain (hallmark): usually sharp, stabbing, shooting or radiating down the limb
Motor: weakness confined to muscles innervated by a nerve root, normal muscle tone,
Root Disease decreased or absent reflexes
Sensory loss in a dermatomal distribution
259
Maneuvers that stretch the root aggravate the pain
Distal sensorimotor deficit
May present as paresthesia or asymmetric weakness but can also be symmetrical like in
Peripheral Nerve GBS
Decreases muscle tone & reflexes, may have atrophy over time & fasciculations
Autonomic disturbances (trophic changes like smooth shiny skin or vasomotor changes like
temperature dysregulation)
Neuromuscular Purely motor; may involve both cranially and spinally innervated muscles
Junction Waxing & waning weakness (fatigable weakness: hallmark of MG)
Normal size and tone of muscles, intact reflexes, no fasciculations
Proximal and symmetrical weakness
Absent sensory signs except for pain and tenderness
Muscle Disease No fasciculations
Atrophy with normal or mildly decreased muscle tone and reflexes
Increased muscle enzymes
III. WHAT IS THE LESION? (ETIOLOGIC DIAGNOSIS: REMEMBER VITAMIN C&D)

CATEGORIES
Vascular Stroke (infarct, hemorrhage)
Infectious/Inflammatory Meningitis, encephalitis, brain abscess
Trauma Epidural/subdural hematoma, cerebral contusion
Autoimmune Demyelinating diseases like MS and GBS, MG
Metabolic Nutritional (e.g., Vitamin B12 or B6 deficiency), electrolyte problems, uremia, hyperglycemia,
toxic (e.g., lead), drug overdose
Idiopathic/Iatrogenic Iatrogenic: post-procedural complications
Neoplastic Primary (e.g., meningioma, glioma) versus metastatic
Congenital Arteriovenous malformation, muscle dystrophies
Degenerative Parkinson disease, Alzheimer’s disease
IV. WHAT TESTS SHOULD BE DONE TO ESTABLISH THE DIAGNOSIS?
A. Lumbar Puncture (LP)
1. Indications and Contraindications

Obtain pressure measurements and procure a sample of the CSF for examination
Indications Aid in therapy by the administration of spinal anesthetics and occasionally, antibiotics
or antitumor agents, or by reduction of CSF pressure
Increased ICP from suspected or known intracranial mass lesion (order imaging
before doing an LP)
Contraindications Infection of the lumbar skin or deeper tissues through which the needle must pass
Coagulopathies (platelet count should be > 50,000 & INR <1.5 before LP)
Cervical cord lesions (removal of CSF from lumbar region may cause the cord to shift
against the lesion, resulting in quadriplegia, apnea and death)
2. Cerebrospinal Fluid Profiles in Normal Individuals and in Various Diseases

Conditions Color Pressure Cells/mm2 Cell Type Culture Glucose (% Total
of blood) Protein
Normal Adult Sparkling clear 80-180 <5 Mononuclear Negative -66% of 10-40
mmH2O blood mg %
Bacterial Cloudy ↑ 500-1000 Polymorpho- Bacteria present <50% of ↑
Meningitis (↑) nuclear blood (↓)
Tuberculous Cloudy, Normal or 10-500 Mostly Bacteria present <50% of ↑
xanthochromic ↑ mononuclear blood (↓)
Fungal Cloudy, Normal or < 500 Mostly Fungi present <50% of ↑
xanthochromic ↑ mononuclear blood (↓)
Clear to fairly Normal or Mononuclear Negative skin; Normal
Encephalitis cloudy ↑ < 500 after first culture may be Normal to ↑
hours positive
Subarachnoid Erythochromic
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Hemorrhage or Normal or 100-1000 RBCs Negative Normal Varies
xanthochromatic ↑
B. Neuroimaging
CRANIAL CT SCAN CRANIAL MRI
CT’s wider availability shorter scanning time and lower cost
make it suitable as MRI substitute in some cases
CT often shows intracranial bleeding better than MRI Procedure of choice for imaging the brain
Substitute CT for MRI when: and spinal cord
o Time is critical (e.g., acute intracranial bleeding)
o Has metal or electronic device in body (e.g., pacemaker)
C. Electroneurodiagnosis
Electroencephalography (EEG)
Electromyography (EMG)
Nerve conduction velocity (NCV)
Evoked responses: visual, auditory and somatosensory
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SECTION 2
REVIEW OF THE STANDARD NEUROLOGIC EXAM
THE NEUROLOGIC EXAMINATION
I. MENTAL STATUS EXAMINATION
A. General Behavior and Appearance

Attitude: cooperative, hostile, evasive, threatening, aggressive
Behavior: psychomotor agitation or retardation
B. Stream of Talk
Rate: rapid, slow, pressured
Volume: loud, soft, monotonous, histrionic
Quality: fluent, neologisms, word salad, lacking in inflection and spontaneity
Tangential, discursive, or unable to reach the conversational goal
Check for the 4D’s of speech
Dysphonia Difficulty in producing voice sounds (phonating)
Dysarthria Difficulty in articulating the individual sounds or the units of speech (vowels,
consonants, labials, gutturals and lingual)
Dysprosody Difficulty in melody and rhythm of speech, the accent of syllables, the inflections,
intonations, and pitch of the voice
Dysphasia Difficulty in expressing or understanding words as the symbols of communication
C. Mood and Affective Disorders

Mood: pervasive and sustained emotion that colors the person’s perception of the world
Affect: patient’s present emotional responsiveness; may or may not be congruent with mood
D. Content of Thought
Thought process: disorganized, illogical, loose associations, tangential, circumstantial, flight of ideas
Though content: preoccupations, obsessions, ideas of reference, delusions, suicidal or homicidal ideation
Perception:
o Delusions: false belief that reason cannot dispel
o Illusion: false sensory perception base on natural stimulation of a sensory receptor
o Hallucination: false sensory perception not based on natural stimulation of a sensory receptor
E. Intellectual Capacity
Bright, average, dull
F. Levels of Consciousness
Awake State of full awareness of one’s self and one’s relationship to the environment
Drowsy Can usually be aroused easily but promptly falls asleep when left alone
Stupor Can be aroused only with vigorous and continuous stimulation
Coma Cannot be aroused to respond appropriately to stimuli, even with vigorous stimulation
Glasgow Coma Scale

Eye (E) Opening Verbal (V) Response Motor (M) Response
4 = opens spontaneously 5 = normal conversation 6 = normal
3 = opens to voice 4 = disoriented conversation 5 = localizes to pain
2 = opens to pain 3 = incoherent speech 4 = withdraws to pain
1 = none 2 = incomprehensible speech 3 = decorticate posturing
1 = none 2 = decerebrate posturing
1 = none
G. Higher Cortical Function

Test higher cortical functions if the history or mental status examination suggests a cerebral lesion
Includes test for the 3A’s: Agnosia, Apraxia, Aphasia
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Agnosia “Not knowing” Inability to understand the meaning, importance or symbolic significance
of ordinary sensory stimuli even though the sensory pathways and
sensorium are intact
Apraxia “Inability to act” Inability to perform voluntary acts even though motor and sensory
systems and sensorium are intact
Inability to understand or express words as symbols for communication,
Aphasia “Lack of speech” even though the primary sensorimotor pathways and sensorium are
relatively intact
II. CRANIAL NERVES

CN NAME FUNCTION TESTS
I Olfactory Sensory Use aromatic, non-irritating substance and test each nostril
separately with the patient’s eyes closed
II Optic Sensory Visual acuity, visual field cuts by confrontation, pupillary light reflex
(together with CN III), fundoscopy
III Oculomotor Motor Primary gaze, movements of the extra-ocular muscles (EOMs)
IV Trochlear Motor Ptosis and accommodation for CN III
Doll’s eye maneuver in patients with altered sensorium
V Trigeminal Mixed Corneal reflex, somatic sensation on V1 to V3 distribution of the
face, muscles of mastication
VI Abducens Motor Test together with CN III and IV (ocular motility)
Test forehead wrinkling (differentiates central and peripheral facial
palsy), eyelid closure, mouth retraction, whistling or puffing out of
VII Facial Mixed cheeks, and wrinkling of skin over the neck
Listen to labial articulations, test taste on anterior 2/3 of the tongue
using salt and sugar
VIII Otoscopy and hearing tests (Weber, Rinne, Schwabach)
Vestibular tests (e.g., Barany chair test,, tilt tests for postural
Vestibulocochlear Sensory vertigo and nystagmus)
Vestibule-ocular reflex tested with doll’s eye maneuver or caloric
irrigation
IX Glossopharyngeal Mixed Listen for phonation and articulations (palatal sounds)
X Vagus Mixed Check swallowing, palatal elevation, and gag reflex
XI Spinal Accessory Motor Inspect sternocleidomastoid and trapezius contours
Test strength of head movements and shoulder shrugging
Check for lingual articulation, midline tongue protrusion, lateral
XII Hypoglossal Motor movement
Inspect for tongue atrophy and fasciculations
III. SOMATIC MOTOR SYSTEM

A. Muscle Testing
GRADE BMRC GRADING OF MUSCLE STRENGTH GRADING OF MUSCLE
STRETCH REFLEXES
0 Complete paralysis Areflexia
1 Only a flicker of muscle contraction but cannot move joint Hyporeflexia
2 Moves part only when positioned to eliminate gravity Normal
3 Moves part full range against gravity but not against any resistance Hyperreflexia
4 Moves joint through full range against resistance greater than gravity Clonus present
but examiner can overcome the action
5 Normal strength
B. Reflexes
SKIN AND MUSCLE (SUPERFICIAL) REFLEXES MUSCLE STRETCH (DEEP) REFLEXES
1. Abdominal skin and muscle reflexes (Beevor’s sign) 1. Jaw jerk Afferent: CN V
Upper quadrants T8-9, lower quadrants T11-12 Efferent: CN V
2. Biceps reflex C5-6
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Elicited by scraping the skin tangential to or towards 3. Brachioradialis reflex C5-6
the umbilicus 4. Triceps reflex C7-C8
5. Finger flexion reflex C7-T1
2. Cremasteric reflex 6. Quadriceps reflex (knee L2-L4
Afferent: L1, efferent: L2 jerk)
Elicited by scratching the skin of the medial skin 7. Medical Harmstrings reflex L5-S1
Elicited by scratching the skin of the medial thigh 8. Triceps surae reflex (ankle S1-S2
jerk)
3. Anal pucker reflex (S4-5) and bulbocavernous reflex (S3-S4) 9. Toe flexion reflex S1-S2
if suspecting sacral or cauda equine lesions
4. Plantar reflex
Afferent: S1, efferent: L5-S1-2 Proper documentation
Babinski and Babinski-like maneuvers: of MSRs, abdominal,
o Babinski: stimulate along lateral aspect of
cremasteric, and plantar
bottom of the foot
o Chaddock: stimulate the lateral side of the foot reflexes
o Oppenheim: knuckles over the shin and move
them down
o Gordon: grip the gastrocnemius (calf)
o Schaeffer: squeeze the Achilles tendon
o Gonda: grasp the fourth digit
C. Clinical Syndrome of UMN versus LMN lesions

SIGN UPPER MOTOR NEURON LOWER MOTOR NEURON
Atrophy Atrophy of disuse only (late and slight) Atrophy of denervation (early and severe)
Fasciculations and Absent Present
fibrillations
Tone Spastics (clasp-knife spasticity) Flaccid
Pyramidal / Regional Distal / Segmental
Distribution (Hemiplegic, paraplegic, quadriplegic) (individual or set of muscles in a root or
peripheral nerve distribution)
Tendon Reflexes Hyperactive Hypoactive / Absent
Clonus and Present Absent
Babinski’s sign
IV. SOMATIC SENSORY SYSTEM

Superficial Sensory Light touch over hands, trunk & feet
Modalities Temperature discrimination & pain perception over hands, trunk & feet
Vibration perception at fingers and toes
Position sense of fingers and toes by using the fourth digits
Deep Sensory Modalities Astereogenesis
Directional scratch test
Romberg (swaying) test
Determine Distribution Dermatomal, peripheral nerve(s), plexus, central pathway or nonorganic
Pattern of any Sensory Loss
V. CEREBELLAR SYSTEM
Check for nystagmus, hypotonia, incoordination and ataxia
Do finger-to-nose, rapid alternating movements, heel-to-shin movements and assess tandem gait
VI. MENINGEALS
True nuchal rigidity is when the neck resists only flexion and moves freely through rotation and extension
Brudzinski’s sign: adduction and flexion of the legs when you flex the neck
Kernig’s sign (bent-knee and straight-knee leg-raising tests of Kernig and Lasegue): passively flex one hip and
knee 90 degrees, meningeal irritation causes the patient to resist movement when you straighten the bent knee
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SECTION 3
COMMON NEUROLOGIC CONDITIONS
CEREBROVASCULAR DISEASE (CVD)
CVD includes ischemic stroke, hemorrhagic stroke and cerebrovascular anomalies such as intracranial
aneurysms and arteriovenous malformations
I. ETIOPATHOGENESIS
Stroke Sudden onset of focal (or global) neurologic deficit due to an underlying vascular pathology
Transient episode of neurological dysfunction caused by a focal brain, spinal or retinal ischemia,
Transient Ischemic without evidence of infarction (normal cranial imaging) in which symptoms typically last less than
Attack (TIA) an hour
*The risk of stroke after a TIA is 10-15% in the first 3 months, with most events occurring in the first 2 days
*Use ABCD2 score to assess risk of stroke following TIA
A. Ischemic Stroke
Acute occlusion of an intracranial vessel causes reduction in blood flow to the brain region supplied
Most cases are atherothrombotic strokes, while others result from cardioembolism (commonly non-rheumatic
atrial fibrillation), artery-to-artery embolism and lacunar infarcts
Treatment focuses on saving the ischemic penumbra
B. Hemorrhagic Stroke
Causes: SMASH-U
o Structural lesions (e.g., cavernomas, AVMs)
o Medications (e.g., anticoagulant-induced)
o Amyloid angiopathy
o Systemic diseases (e.g., coagulopathy from liver disease, thrombocytopenia from leukemia)
o Hypertension
o Undetermined cause
Most common cause: hypertension resulting to spontaneous rupture of small penetrating arteries of Circle of
Willies (possibly secondary to weakened vessel walls & formation of Charcot-Bouchard aneurysms)
Most common sites: basal ganglia (especially putamen and internal capsule), thalamus, cerebellum, pons and
lobar areas
A. Ischemic vs Hemorrhagic Strokes (no reliable clinical findings to conclusively distinguish ischemia vs hemorrhage)
ISCHEMIC HEMORRHAGIC
Deficit maximal at onset Headache, vomiting, SBP >220 mmHg, impaired
Atherothrombotic stroke: usually during sleep consciousness and evolution of focal deficits over a
Cardioembolic stroke: sudden onset of maximal period of minutes to hours
deficits (<5 min) with rapid improvement of initially Hypertensive ICH: develops over 30-90 minutes
massive symptoms (“spectacular shrinking of Anticoagulant-induced ICH: may evolve for as long as
deficits”) 24-48 hours
B. Anterior vs Posterior Circulations Strokes

PARAMETERS ANTERIOR CIRCULATION STROKES POSTERIOR CIRCULATION STROKES
Incidence More frequent (represent 80% of strokes) Less frequent
Internal carotid, middle cerebral, anterior Vertebrobasilar artery and its
Arteries Involved cerebral and anterior communicating branches
arteries
Site of Ischemia Cerebral hemispheres Brainstem and cerebellum
Bilateral signs frequently present
Laterality Usually unilateral, contralateral to the
side of the hemispheric lesion *crossed signs for brainstem lesions (contralateral
long tract signs + ipsilateral cranial nerve deficit)
*ipsilateral signs for cerebella hemisphere lesions
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Bulbar signs: dysarthria, dysphagia,
Monocular blindness (amaurosis fugax) dysphonia, dizziness, diplopia
Cortical dysfunctions Facial paralysis involving all muscles
Facial weakness (sparing the frontalis of facial expression ipsilateral to the
Clinical Features and corrugator muscles) contralateral to side of the lesion
the side of the lesion Eye deviation looking toward side of
Eye deviation looking away from side of hemiparesis (or away from side of
hemiparesis (or toward side of lesion) lesion)
*Pontine (PPRF lesion) – pointing to paretic side

Extensive ischemia of the brain may More complete neurologic recovery for
result to less complete neurologic small infarcts
Prognosis recovery Large infarcts are often fatal because
of the vital centers located in the
brainstem
C. Major Clinical Findings based on Arterial Involvement

ICA Sudden onset transient monocular blindness
UE > LE weakness
MCA Dominant hemisphere: aphasia (e.g., global, Wernicke’s, Broca’s)
Non-dominant hemisphere: neglect syndrome, topographical difficulty, apraxia,
constructional impairment
ACA LE > UE weakness
Abulia, muteness, perseveration, disinhibition
PCA, Peripheral Memory deficits
Branches Cortical blindness, ocular apraxia and other visual deficits
PCA, Central Thalamic syndrome
Branches Can also present with cranial nerve deficits and other manifestations of dysfunction in
the brainstem and diencephalon
Brainstem stroke syndrome (crossed signs: ipsilateral cranial nerve deficits and
Vertebrobasilar contralateral long tract signs)
Cerebellar manifestations
D. Lacunar Strokes (<1.5 cm in size)

Infarct involving deep brain structures: cerebral subcortical white matter, basal ganglia, thalamus, pons, and
cerebellum
Risk factors: diabetes, hypertension
There should be no cortical signs in these syndromes
LACUNAR SYNDROMES SITE OF LESION CLINICAL FINDINGS
Internal capsule posterior Weakness (usually equal) of contralateral
Pure Motor Hemiplegia limb, base pontis, medullary face, arm and leg with dysarthria, no
pyramids sensory deficits
VPL, VPM nuclei of the Numbness, paresthesias or hemisensory
Pure Sensory Stroke thalamus deficits of contralateral face and limbs, no
motor deficits
Sensorimotor Stroke Junction of internal capsule & Weakness and numbness of contralateral
thalamus face, arm, leg
Central (supranuclear), facial weakness,
Basis pontis or in genu of tongue deviation, dysphagia and
Dysarthria / Clumsy Hand internal capsule dysarthria associated with clumsy but
strong contralateral arm
No sensory deficits
Posterior limb internal Ipsilateral hemiparesis with marked
Ataxic Hemiparesis capsule, basis pontis, red ipsilateral limb ataxia (out of proportion to
nucleus or in thalamocapsular the motor deficit)
region
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III. CLASSIFICATION
A. May be classified by
ETIOLOGY ICTUS SEVERITY
(TIME FROM STROKE ONSET)
Ischemic (80-85%) Hyperacute (0-6 hours) Mild (NIHSS 0-5)
o Atherothrombotic Acute (6-72 hours) Moderate (NIHSS 6-21)
o Embolic (cardiac or artery- Subacute (3 days to 3 weeks) Severe (NIHSS >22)
to-artery) Chronic (>3 weeks)
o Lacunar *NIHSS: National Institute of Healthy
Hemorrhagic (10-15%) Stroke Scale
B. TOAST (Trial of Org 10172 in Acute Stroke Treatment)

Widest accepted subtyping system for stroke based on likely pathophysiology using advanced diagnostics
Classifies ischemic stroke into 5 categories:
CLASSIFICATION DESCRIPTION
Large Artery Atherosclerosis Cortical or subcortical infarcts >1.5 cm
Cardioembolism Embolus originating from the heart
Small Artery Occlusion Subcortical or brainstem infarcts <1.5 cm
Other Determined Causes E.g., hematologic disorders, hypercoagulable states, non-atherosclerotic
vascular diseases – inflammatory, non-inflammatory, infectious, hereditary
Either no cause was found despite extensive evaluation, or a most likely
Undetermined Causes cause could not be determined because more than one plausible cause was
found
IV. DIAGNOSTICS
A. Cranial CT-Scan
Plain cranial CT: initial neuroimaging of choice to differentiate ischemic and hemorrhagic stroke and exclude
stroke mimickers
Highly sensitive in detecting hemorrhage
CT findings in the hyperacute phase (0-6 hours) [Look for early sign of infarction]
o Loss of gray-white matter differentiation
o Insular ribbon sign
o Hyperdense middle cerebral artery or “dot sign”
o Obscuration of the lentiform nucleus
o Sulcal effacement
Estimating volume of bleed in CT scan (Kothari Method): A: Largest diameter of hematoma (in cm)
B: Diameter perpendicular to A (in cm)
A x B x C C: Number of slices on CT scan with
hemorrhage x slice thickness (in cm)
Volume in cc = 2
In counting CT slices with hemorrhage:
If >75% of largest hematoma size: count as 1 slice
If 25-75%: count as 0.5 (1/2 slice)
If <25%: disregard that CT slice
*In some hospitals with a 5 mm slice thickness, you can change the denominator to 4 instead of 2 (since you will
multiply the slice thickness by 0.5 instead of 1)
B. Cranial MRI
Better imaging for posterior circulation ischemic strokes because CT poorly visualizes lesions of the posterior
fossa (dense petrous bone degrades the image)
The areas of infarction are seen as bright signals in DWI while ADC maps depict the areas of restricted
diffusion as low intensity signals (observed as early as 30 minutes after onset of ischemia)
Disadvantages of MRI:
o Not sensitive in detecting acute hemorrhages
o More expensive
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o Longer acquisition time compared to CT
o Less widely available
o Contraindicated in those with metallic implants
V. MANAGEMENT
A. Early Specific Management of Ischemic Stroke
1. Thrombolytic Therapy
IV recombinant tissue plasminogen activator (r-tPA)
Give within 3 hours of stroke onset at 0.9 mg/kg (max of 90 mg), 10% of total dose given as IV bolus then
the rest as infusion over 60 minutes
Patients given r-tPA should not receive antiplatelets or anticoagulants within 24 hours of treatment
Contraindications to thrombolytic therapy (from SSP Guidelines 2014):
ABSOLUTE CONTRAINDICATIONS RELATIVE
CONTRAINDICATIONS
Evidence of intracranial hemorrhage on pretreatment scan Major surgery or serious
Evidence of multi-lobar infarction (>1/3 cerebral hemisphere) on trauma (excluding head
neuroimaging trauma) within previous 14
Only minor or rapidly growing stroke symptoms days
Clinical presentation suggestive of subarachnoid hemorrhage Gastrointestinal or urinary
(SAH), even with normal CT tract hemorrhage within
Significant head trauma or prior stroke within 3 months previous 21 days
History of prior intracerebral hemorrhage (ICH) MI within the past 3 months
Known arteriovenous malformation or aneurysm Only minor and rapidly
Arterial puncture at a non-compressible site within 7 days improving neurological signs
Recent intracranial or spinal surgery (resolving spontaneously)
Active internal bleeding Seizures at the time of onset
Known bleeding diathesis, including but not limited to: of stroke symptoms with post-
o Platelet count <100,000/mm 3 ictal neurological impairment
o Heparin use in previous 48 hours or prolonged PTT >1.5x pregnancy
normal
o Current / recent use of oral anticoagulants with PT >15
seconds or INR >1.7
Blood glucose <50 mg/dL or >400 mg/dL
Sustained pretreatment SBP >185 mmHg or DBP >110 mmHg
(those requiring aggressive treatment to lower BP)
Use of novel oral anticoagulants (NOACs)
2. Antithrombotic Therapy
Noncardioembolic ischemic stroke or TIA
o Start ASA 160-325 mg/day as early as possible and continue for 14 days
o Long-term ASA 80-100 mg/day monotherapy for secondary stroke prevention
o Acceptable options for initial therapy:
Clopidogrel 75 mg OD
Aspirin 25 mg plus extended release (ER) Dipyridample 200 mg BID
Cilostazol 100 mg BID
Trifusal 300 mg BID
o Choice of antiplatelet should be individualized
o Patients with recurrent stroke while on antithrombotic therapy should be re-evaluated for risk
factors (no evidence that increasing the dose will provide additional benefits for those who are
already taking Aspirin)
o Use of LMWH and heparinoids associated with significant reduction in venous thromboembolism
but no significant effect on mortality and disability at 6 months
Cardioembolic stroke (see Cardiology Chapter 2 for further discussion)

o Compute for the CHA2DS2-VASc and HAS-BLED score of patients with AF
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o Benefit of anticoagulation in acute stroke within the first 14 days would be weighed carefully
against the risk of hemorrhagic conversion (large infarctions, severe strokes or neurologic deficits
and uncontrolled HPN)
3. Neuroprotection (the 5 “H” principle)

Target mean arterial pressure (MAP): 110-130 mmHg
Permissive hypertension during the first 7 days EXCEPT in cases of:
o Acute MI
o CHF
o Aortic dissection
Avoid o Acute pulmonary edema
Hypotension o ARF
o Hypertensive encephalopathy
Treat if SBP >220 mmHg, DBP >120 mmHg and MAP >130 mmHg
Do not use rapid-acting sublingual agents
Use easily titratable IV or short-acting antihypertensive agents
o IV Nicardipine (alternatives: hydralazine, labetalol, esmolol)
Avoid Target O2 sat: >94%
Hypoxemia Monitor O2 saturation via pulse oximeter and/or check ABGs
Avoid Target CBG: 140-180 mg/dL
Hypoglycemia No benefit with intensive glycemic control after stroke
or Use isotonic saline (0.9% NaCl) and avoid glucose-containing (D5) IVFs
Hyperglycemia
Avoid Target: normothermia
Hyperthermia Relative risk of death or disability increases twofold for every 1 oC increase in body temp
Treat fever with antipyretics and cooling blankets; work-up for source of fever
4. Role of Neuroprotective and Neurorestorative drugs

Remains a matter of preference of the attending physician
Examples: citicholine, cerebrolysin
B. Early Specific Management of Hemorrhagic Stroke
1. Medical Treatment
Treat if SBP >180 mmHg since the absence of ischemic penumbra allows for more aggressive BP
treatment in ICH
Acute lowering of SBP <140 mmHg within 7 days is safe in patients with small- to moderate-sized ICH
(not requiring surgical intervention)
Manage IICP
MANAGEMENT OF INCREASED INTRACRANIAL PRESSURE
Head Elevation Elevate head 30-45o
Osmotic Therapy Mannitol 20% IV infusion (0.5-1.5 g/kg q3-6h)
Hypertonic saline (Target Na: 145-155 mmol/L)
Serum Osmolality Maintain serum osmolality at 300-320 mosmol/kg
Hyperventilation Target pCO2 of 30-35 mmHg (effect last ~6 hrs)
Only for impending herniation and not as prophylaxis
Others: control seizures, ensure neuroprotection, maintain adequate nutrition, ensure proper fluid &
electrolyte balance, stool softeners, DVT prophylaxis, early rehabilitation if stable, bedsore precautions
2. Surgical Treatment
Immediate surgical candidates:
o Cerebellar hemorrhage >3cm who are neurologically deteriorating or have brainstem
compression and hydrocephalus from ventricular obstruction
o Bleed associated with structural lesions (aneurysms, AVM) if surgically accessible and patient
has good overall prognosis
o Clinically deteriorating young patients with moderate or large lobar hemorrhage
o Ventricular drainage for patients with intraventricular hemorrhage with moderate to severe
hydrocephalus
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Other patients which may benefit from surgery:
o Basal ganglia or thalamic hemorrhage
o GCS 5 and above
o Supratentorial hematoma with volume >30cc
C. Primary and Secondary Prevention of Stroke

Hyertension Most important modifiable risk factor; 3-4x higher risk of stroke
Degree of BP reduction is more important than the specific agent
Diabetes Mellitus Target HbA1C <7%
Dyslipidemia Statin therapy reduces all stroke types
Atrial Fibrillation 3-4x higher risk of stroke (regardless of whether paroxysmal or sustained)
If patients unable to take oral anticoagulants, ASA 160-325 mg/day is recommended
ACS with LV Oral anticoagulation if persistent AF, decreased LV function or if with LV thrombi
Thrombus
Mass screwing for carotid stenosis is not cost-effective
Carotid endarterectomy (CEA) for asymptomatic stenosis > 70% if life expectancy is
Carotid Stenosis at least 5 years and perioperative risk is <3%
CEA combined with medical treatment for recent TIA or non-disabling stroke with
ipsilateral severe carotid artery stenosis (70-99%) if perioperative risk is <6%
Risk of recurrent ipsilateral stroke highest if 70-99% stenosis and those with recent of
symptoms within 2 weeks
Intracranial Stenosis Screening for intracranial stenosis by vascular studies is recommended for ischemic
stroke or TIA
Optimal medical therapy with ASA and high-intensity statins
Smoking Smoking cessation
Light to moderate intake of alcohol (1 drink per day for non-pregnant women and 2
Excessive Alcohol drinks per day for men; “one drink” defined as 12 oz of regular beer (5% alcohol), 5
oz of wine (12% alcohol), or 1.5 oz of 80 proof (40% alcohol) distilled spirits
Nutrition Limit Na+ intake to <2.4g/day (<1.5g/day associated with greater BP reduction)
Obesity Goals: BMI 18.5 kg/m 2, waist-hip-ratio < 1 (men) or 0.85 (women), waist
circumference < 35 inches (men) or 31 inches (women)
Physical Inactivity At least 3-4 sessions per week (average of 40 minutes/session) of moderate to
vigorous intensity aerobic physical exercise
SUBARACHNOID HEMORRHAGE (SAH)

I. ETIOPATHOGENESIS
Most common cause: trauma
Most common cause of non-traumatic SAH: ruptured aneurysm
Most common site of aneurysm: ACom-ACA Junction
Other causes include bleeding from a vascular malformation (AV malformation or dural AV fistula) and extension
into the subarachnoid space from a primary intracerebral hemorrhage

Patients usually present with sudden severe headache (“the worst headache of my life”) in ~80% of cases
May be accompanied by nausea/vomiting, loss of consciousness, neck stiffness, photophobia, focal neurologic
deficits and seizures
Clinical findings of subarachnoid hemorrhages depending on the site of the aneurysms
LOCATION OF ANEURYSM CLINICAL FINDINGS
ICA, Posterior communicating 3rd nerve palsy
artery
Middle cerebral artery Contralateral hemiparesis (mainly face and hands)
Aphasia or contralateral visual neglect
Anterior communicating artery Bilateral leg paresis, abulia
Intracranial vertebral artery/ Vertigo, elements of the lateral medullary syndrome
Posterior inferior cerebellar artery
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Delayed neurologic deficits may be due to re-rupture, acute hydrocephalus or vasospasm
III. DIAGNOSIS
Plain cranial CT scan remains the cornerstone of diagnosis of SAH
Lumbar puncture may show xanthochromia after 5-7 days when the rate of negative CT increases sharply
Cerebral angiography: gold standard in determining the cause of SAH
A. Clinical Classification of SAH
GRADE HUNT AND HESS CLASSIFICATION WFNS SCALE
GCS Motor Deficits
Grade I Asymptomatic or mild headache, slight nuchal rigidity 15 (-)
Grade II Moderate-severe headache, nuchal rigidity, no neurologic 13-14 (-)
deficit other than cranial nerve palsy
Grade III Mild alteration in mental status 13-14 (+)
Mild focal neurologic deficit
Grade IV Stupor, moderate to severe hemiparesis 7-12 (-) or (+)
Grade V Comatose, decerebrate posturing 3-6 (-) or (+)
WFNS: World Federation of Neurological Surgeons
Note: Follow the higher grade. In a patient who is awake but with significant hemiplegia, the grade is IV.
B. Fisher Scale (based on CT scan appearance)

SCORE CT SCAN FINDINGS
1 No blood detected
2 Diffuse deposition of subarachnoid blood but clots and layers of blood <1 mm in thickness (look
at the interhemispheric fissure, insular cistern, ambient cistern)
3 Localized clots and/or vertical layers of blood > 1 mm in thickness
4 Diffuse or no subarachnoid blood, but with intracerebral or intraventricular clots present
III. MANAGEMENT
A. General Symptomatic Treatment

Complete bed rest without bathroom privileges until aneurysm is secured
May start feeding unless with planned immediate surgical intervention
Analgesics for headache. Avoid NSAIDs and aspirin.
PPIs or H2 blockers for GI prophylaxis for stress gastritis.
Anti-emetics for nausea and vomiting
Stool softeners
Sedatives for restlessness and agitation
Antipyretics and/or cooling blankets for fever
DVT prophylaxis with pneumatic compression devices with or without thigh-high anti-embolic stockings
B. Early Specific Treatment

Nimodipine 30mg/tab 2 tabs PO q4h x 3 weeks to prevent vasospasm
Short-term anticonvulsants for patients with documented seizures
Manage increased ICP (as discussed in ICH)
Optimal BP management (IV nicardipine to maintain SBP<150 in unsecured aneurysm)
Correction of hyponatremia and maintenance of euglycemia and euvolemia
C. Timing of Surgery
Early surgery (ideally within 72 hours from ictus) is recommended for good to moderate grade SAH
Poor grade SAH may warrant early surgery in the presence of hematoma and hydrocephalus
Clipping: MCA aneurysms and large parenchymal clots
Coiling: poor clinical grades, those with vasospasm, elderly, posterior circulation aneurysms
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SEIZURES AND EPILEPSY
I. DEFINITION OF TERMS
Seizures: manifestations of excessive or hypersynchronous (epileptic) neuronal activity in the brain that is usually
self-limited
Epilepsy: condition characterized by recurrent (two or more) epileptic seizures, unprovoked by any immediate
identified cause
II. SYNCOPE VERSUS SEIZURES

FEATURES SEIZURE SYNCOPE
Immediate Precipitating Factors Usually none Emotional stress, Valsalva maneuver,
orthostatic hypotension, cardiac etiologies
Premonitory Symptoms None or aura Tiredness, nausea, diaphoresis, tunneling of
(e.g., odd odor) vision
Posture at Onset Variable Usually erect
Transition to Unconsciousness Often immediate Gradual over seconds
Duration of Unconsciousness Minutes Seconds
Duration of Tonic Clonic Movements 30-60 sec Never more than 15 sec
Facial Appearance during Event Cyanosis, frothing at mouth Pallor
Post-Ictal Sleepiness / Confusion Many minutes to hours <5 minutes
Aching of Muscles after Event Often Sometimes
Biting of Tongue Sometimes Rarely
Incontinence Sometimes Sometimes
Headache Sometimes Rarely
III. CLASSIFICATION OF SEIZURES
A. Generalized Seizures
Originating at some point within, and rapidly engaging, bilaterally distributed networks
Most common seizure type resulting from metabolic derangements
Begins abruptly without warning, although some with vague premonitory symptoms in
the hours prior
Initial Phase (Tonic Phase):

o Eyes open and roll up, elbows flex, arms pronate, incontinence, moaning, cyanosis
and apnea
o Increased HR, BP and pupillary size
Generalized Tonic
Clonic Seizures Clonic Phase:
(Grand Mal) o After 10-20 sec, tonic phase evolves into the clonic phase
o Generalized clonic movements, atonic between jerks, tongue biting, cyanosis
o Periods of relaxation progressively increase until the end of the ictal phase, which
lasts <1 min
Postictal state:
o Regular respiration resumes, may have headache and muscle soreness, patients
gradually regain consciousness over minutes to hours, with postictal confusion
Drop attacks lasting seconds
Atonic Seizures Consciousness is briefly impaired, but there is usually no post-ictal confusion
Spectrum: from head drop to complete loss of tone in entire body
Sudden brief muscle contraction that may involve one part or the entire body (shock-
Myoclonic Seizures like jerks)
Most common type: symptomatic or secondary (non-epileptic) myoclonus resulting from
an underlying neurological or non-neurological disorder
Usually occur in children with normal intelligence
Absence Seizures Generalized 3-Hz spike-and-wave electroencephalogram (EEG)
(Petit Mal or Brief duration, usually a few seconds
Pyknoepilepsy) Abrupt recovery (consciousness returns as suddenly as it was lost)
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No postictal phase
Have features that deviate from typical absence seizures:
Atypical Absence o Longer duration – may last several minutes
Seizures o Less abrupt onset and offset
o More prominent loss of postural tone
B. Focal Seizures
Originating within networks limited to one hemisphere
Previously called partial seizures and used to be classified as simple partial (consciousness fully preserved during
the seizure) or complex partial (with impaired consciousness and more complex symptomatology)
Describe aura, motor, sensory or autonomic features, and awareness/responsiveness (altered or retained)
Can evolve to a bilateral convulsive seizure
IV. DIAGNOSIS
A. Basic Laboratory Tests

CBC, random blood sugar, BUN, crea and electrolytes
12-L ECG
Septic work-up if warranted (e.g., chest x-ray, urinalysis)
B. Neurodiagnostic Procedures
Most important diagnostic procedure for patients with epilepsy
Electroencephalogram A normal EEG does not totally rule out epilepsy
An abnormal EEG does not always mean epilepsy
Indications:
Cranial MRI or Cranial CT o Focal seizures (except if caused by hyperglycemia)
Scan o Intractable seizures
o Progressive neurologic disease or structural lesions that may warrant
surgical intervention
Lumbar Puncture Done if CNS infection is suspected
V. MANAGEMENT
A. Indications for Prescribing Antiepileptic Drugs (AEDs) in a Single Unprovoked Seizure

Focal seizures
Signs of a focal lesion on neurologic evaluation
Abnormal neuroimaging or abnormal EEG (e.g., focal slowing, epileptiform activity)
B. General Principles in Initiating AEDs

Goal: seizure freedom without adverse drug reactions
Monotherapy is the mainstay of treatment
Start a low dose and gradually increase until seizures are controlled or adverse effects appear
Consider seizure type, pharmacologic properties (efficacy, safety, pharmacokinetics, tolerability), patient
characteristics (comorbidities, gender and age), availability, potential adverse effects and interactions with other
medications
C. Choice of Antiepileptic Drugs

SEIZURE TYPE CONVENTIONAL AEDS NEWER AEDS
Generalized Seizures
Lamotrigine (LTG)
Carbamazepine (CBZ) Oxcarbazepine (OXC)
Tonic Clonic Phenytoin (PHT) Topiramate (TPM)
Phenobarbital (PB) Carbamazepine (CBZ)
Valproic Acid (VPA) Levetiracetam (LEV)
Zonisamide (ZNS)
LTG
Myoclonic VPA LEV
Clonazepam (CZP) TPM
ZNS
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Absence VPA LTG
Ethosuximide TPM
Atonic VPA
Tonic VPA
Focal Seizures
Gabapentin (GBP)
Focal Seizures (with or without PHT TPM
evolution to bilateral convulsive PB OXC
seizure) CBZ LEV
VPA LTG
ZNS
CENTRAL NERVOUS SYSTEM (CNS) INFECTIONS

Meningitis: infection predominantly involves the subarachnoid space (meninges)
Encephalitis: infection diffusely involves brain tissue
Cerebritis: focal infection of brain tissue with no capsule formation
Abscess: focal infection of brain tissue with capsule formation
I. BACTERIAL MENINGITIS
Most common form of suppurative CNS infection
Most common meningeal pathogens are normal inhabitants of the nasopharynx
o S. pneumoniae, N. meningitides, H. influenza
Most likely pathogen depends on patient’s age and risk factors
o Adults (in order of frequency): S. pneumoniae and N. meningitides, L. monocytogenes, Staphylococci,
gram-negative bacilli (including E. coli, Klebsiella, Enterobacter, P. aeruginosa) and H. influenza
o Trauma or neurosurgical procedures: Staphylococci, gram-negative bacilli, S. pneumoniae
o Immunocompromised: S. pneumoniae, L. monocytogenes, gram-negative bacilli
May arise from: hematogenous spread, parameningeal infection (sinusitis, otitis media, mastoiditis, brain
abscess), abscess rupture into CSF space, trauma or surgery with disruption of the blood-brain barrier
A. Clinical Presentation
Subacute onset, rapid progression of symptoms within hours to days
Presents with classic triad: fever, headache and nuchal rigidity
Other cerebral symptoms: seizures, confusion, cranial nerve palsies, possible focal deficits
Other symptoms: nausea/vomiting, photophobia, rash (in N. meningitides)
B. Diagnostics
Cranial CT scan with contrast
Lumbar puncture (see prior section for interpretation of results):
o Febrile patients with lethargy, headache, stiff neck or confusion of sudden onset should generally
undergo lumbar puncture if no alternative explanation for the state is evident
o CSF profile:
Opening pressure: increased (>180 cm H2O)
Leukocytes 250-100,000/mm3 with neutrophilic predominance (85-95% of total) but increasing
mononuclear cells may be seen as infection continues for days especially if partially treated
Protein >45 mg/dL
Glucose < 40 mg/dL or <40% of serum glucose (measured concomitantly or previous hour)
Gram stain and culture are positive in >70-90%
C. Management
Bacterial meningitis is a medical emergency!
Treatment should begin while awaiting the results of diagnostic tests
Reduction in mortality and improved overall outcome if dexamethasone 10 mg is given just before the first dose of
antibiotics and then repeated q6h for 4 days
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AGE OF PATIENT EMPIRIC THERAPY FOR BACTERIAL MENINGITIS
0-4 wk Cefotaxime plus ampicillin
4-12 wk Third-generation cephalosporin plus ampicillin (plus dexamethasone)
3 mo-18 y Third-generation cephalosporin plus vancomycin (+ ampicillin)
18-50 y Third-generation cephalosporin plus vancomycin (+ ampicillin)
>50 y Third-generation cephalosporin plus vancomycin plus ampicillin
Immunocompromised State Vancomycin plus ampicillin and ceftazidime
Basilar Skull Fracture Third-generation cephalosporin plus vancomycin
Head trauma; Neurosurgery Vancomycin plus ceftazidime
CSF Shunt Vancomycin plus ceftazidime
SPECIFIC ANTIMICROBIAL THERAPY FOR ACUTE BACTERIAL MENINGITIS

Haemophilus influenzae
Beta-lactamase-negative Ampicillin
Beta-lactamase-positive 3rd generation cephalosporin
Neisseria meningitides Penicillin G or 3rd generation cephalosporin
Penicillin MIC <0.11 ftg/mL (sensitive) Penicillin G or ampicillin
Penicillin MIC 0.1-1.0 ftg/mL (intermediate) 3rd generation cephalosporin
Penicillin MIC > 2.0 ftg/mL (highly resistant) Vancomycin plus 3rd generation cephalosporin
Enterobacteriaceae 3rd generation cephalosporin
Pseudomonas aeruginosa Ceftazidime or cefepime
Listeria monocytogenes Ampicillin or penicillin G
Streptococcus agalactiae Ampicillin or penicillin G
Staphylococcus aureus
Methicillin-sensitive Nafcillin or oxacillin plus 3rd generation cephalosporin
Methicillin-resistant Vancomycin plus 3rd generation cephalosporin
Staphylococcus epidermidis Vancomycin
II. TUBERCULOUS (TB) MENINGITIS

Most fatal form of extrapulmonary TB
A. Clinical Presentation
Subacute to chronic presentation
Usually with prodrome of 2-4weeks: nonspecific symptoms of fatigue, malaise and possibly fever
Fever, meningismus, headache, nausea, vomiting, seizures and cranial nerve palsies (CN VI most commonly
affected)
Complications: hydrocephalus and cerebral infarctions
B. Grading and Staging of Tuberculous Meningitis
GRADE VELLORE GRADING SYSTEM MODIFIED VELLORE GRADING SYSTEM
Headache, vomiting, fever + neck stiffness Headache, vomiting, fever + neck stiffness
I Normal sensorium GCS 15
(-) neurological deficit (-) Neurological deficit
II Normal sensorium GCS 15
(+) Neurological deficit (+) Neurological deficit
III Altered sensorium, but easily arousable GCS 9-14
(+) or (-) Dense neurologically deficit (+) Neurological deficit
IV Deeply comatose GCS 3-8
Decerebrate or decorticate posturing (+/-) Neurological deficit
MRC STAGE FINDINGS
1 Fully conscious, no paresis
2 Decreased sensorium, localizing pain
3 Deeply comatose
C. Diagnostics
Cranial CT with contrast to demonstrate triad of:
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Imaging Studies o Basal enhancement
o Communicating hydrocephalus
o Multiple vasculitic infarcts
CXR to identify: lymphadenopathy, Ghon’s complex, military lesions
Lumbar Puncture Lymphocytic pleocytosis, decreased glucose and increased protein
Seldom (+) on AFB smear, thus specimen should be sent for culture
Others Work up for possible disseminated TB (pulmonary, GI, GU, etc)
D. Treatment Regimen
2 months HRZE then 10 months HR for a total of 12 months
Role of corticosteroids: reduction of mortality and disabling neurological deficits among survivors
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CHAPTER 14
BOARD CORRELATES
I. Cardiology
II. Pulmonology
III. Gastroenterology
IV. Nephrology
V. Endocrinology
VI. Infectious Diseases
VII. Allergy and Rheumatology
VIII. Hematology
IX. Oncology
X. Dermatology
XI. Neurology
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SECTION 1
CARDIOLOGY
HIGH-YIELD PHYSIOLOGY CONCEPTS IN CARDIOLOGY
Most efficient extractor of oxygen from the blood Heart
Intracellular junctions responsible for the cardiac syncytium Gap Junctions
Substance that dilates upstream blood vessels Endothelium-Derived Relaxing Factor (EDRF) aka Nitric
Oxide (NO)
Most potent vasoconstrictor ADH (can increase levels of Endothelin-1)
An increase in venous return will increase the HR Bainbridge Reflex
An increase in venous return will increase the stroke
volume, Basis: stretching of cardiac sarcomeres will Frank-Starling Mechanism
increase contraction
Hypertension, irregular respiration and bradycardia due to
activation of the CNS ischemic response and baroreceptor Cushing Reflex
reflex in increased ICP
BP = CO x Total Peripheral
Formula for BP based on Ohm’s Law Resistance (TPR) = (HR x Stroke Volume) x TPR
TPR is synonymous with Systemic Vascular Resistance
and increases when arterioles vasoconstricted
Large Arteries: <120/80 mmHg
Systemic Capillaries: 17 mmHg
Normal pressure at various parts of the adult circulation Vena Cava: 0 mmHg
Pulmonary Artery: 25/8 mmHg
Pulmonary Capillaries: 7 mmHg
HIGH-YIELD TERMS IN EXAMINATION OF THE CARDIOVASCULAR SYSTEM

Abdominojugular Reflux At least 10 second pressure over the upper abdomen (RUQ)
Positive responses rise of >3 cm in JVP for at least 10-15 sec after release of the hand
Carvallo’s Sign Pansystolic murmur of tricuspid regurgitation
Louder during inspiration and diminishes during forced expiration
High-pitched, diastolic, decrescendo blowing murmur along the left sternal border due to
Graham Steell Murmur dilation of the pulmonary valve ring: occurs in mitral valve disease and severe
pulmonary hypertension
Gallavardin Effect Condition where the murmur of aortic stenosis may be transmitted downward and to the
apex and may be confused with the systolic murmur of mitral regurgitation
Broadbent’s Sign Apical pulse is reduced and may retract in systole in constrictive pericarditis
Peripheral Signs in Aortic Regurgitation
Corrigan’s Pulse A rapidly rising “water-hammer” pulse that collapses suddenly as arterial pressure falls
rapidly during late systole and diastole, seen in aortic regurgitation
Quincke’s Pulse Capillary pulsations manifest as alternate flushing and paling of the skin while pressure
is applied to the tip of the nail, seen in aortic regurgitation
Traube’s Sign A blooming “pistol-shot” sound heard over the femoral arteries, seen in aortic
regurgitation
Duroziez Sign To-and-fro murmur audible if the femoral artery is lightly compressed with a
stethoscope, seen in aortic regurgitation
DIAGNOSTIC PROCEDURES USED IN CARDIOLOGY

Major noninvasive marker of increased CV morbidity / mortality risk Left Ventricular Hypertrophy (LVH)
Cornerstone in the diagnosis of acute and chronic ischemic heart Electrocardiogram (ECG)
disease
Ideal imaging modality for cardiac emergencies 2D echocardiography
Gold standard for imaging valve morphology and motion, detection
of pericardial effusion and cardiac tamponade, and assessment of 2D echocardiography
LV cavity size, systolic function, and wall thickness
Gold standard for assessing LV mass & volumes MRI
278
Imaging modalities of choice for the evaluation of suspected aortic
aneurysm or aortic dissection, and in distinguishing between CT scan and MRI
restrictive cardiomyopathy & constrictive pericarditis
Gold standard in assessing the anatomy & physiology of the heart Cardiac catheterization and coronary angiography
& associated vasculature
HIGH-YIELD TRIADS IN CARDIOLOGY

Left flank pain
Triad of Ruptured Aneurysm Hypotension
Pulsatile mass
Wide QRS complex
Diagnostic Triad of Wolff-Parkinson-White (WPW) ECG Pattern Relatively short PR interval
Slurring of the initial part of the QRS complex (delta
wave)
Peaked T waves (hyperkalemia)
Triad of chronic renal failure in ECG Long QT due to ST segment lengthening
(hypocalcemia)
LCH (systemic hypertension)
Hypotension
Three principal features of tamponade (Beck’s Triad) Soft / absent heart sounds
Jugular venous distention with a prominent x-
descent but an absent y-descent
Thin fibrous caps
Plaques that have caused fatal thromboses tend to have Relatively large lipid cores
High content of macrophages
Heart rate
Major determinants of myocardial O2 demand (MVO2) Myocardial contractility
Myocardial wall tension (stress)
Claudication of the affected extremity
Triad of Buerger’s disease Raynaud’s phenomenon
Migratory superficial vein thrombophlebitis
Stasis
Virchow’s Triad Vascular/endothelial damage
Hypercoagulability
Fever
Dressler’s Triad (post-MI pericarditis) Pleuritic pain
Pericardial effusion
CARDIAC PHARMACOLOGY
Drugs for Heart Failure
Digoxin1
Increases Contractility Dobutamine2
Milrinone2
Diuretics (e.g. furosemide)1
Reduces Preload Vasodilators (e.g., nitrates, hydralazine)
ACE inhibitors/ARBs3
Diuretics (e.g., furosemide)1
Reduces Afterload Vasodilators (e.g., nitrates, hydralazine)
ACE inhibitors/ARBs3
Beta blockers (e.g., metoprolol succinate, bisoprolol, carvedilol)3
1 2 3
used for symptomatic treatment used in acute decompensated HF proven to have mortality and morbidity benefits
Drugs for Heart Failure

CLASS MECHANISM OF ACTION CLINICAL USE EXAMPLES
Binds to activated sodium channels and blocks Atrial fibrillation Quinidine
IA the flow of sodium ions into the cardiac Atrial flutter Procainamide
myocyte (Prolongs action potential) Ventricular tachycardia Disopyramide
IB Binds to both activated and inactivated sodium Post-ischemic arrhythmia Lidocaine
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channels and blocks the flow of sodium ions in Ventricular fibrillation Tocainide
the cardiac myocyte (Shortens action potential) Ventricular tachycardia Mexiletine
Binds to activated sodium channels and blocks Treatment of severe refractory Flecainide
IC the flow of sodium ions into the cardiac ventricular arrhythmia Encainide
myocyte (No effect on action potential) Propafenone
II Blocks beta-adrenergic receptors Numerous Propranolol
Metoprolol
Binds to potassium channels and blocks the Sotalol
III flow of K in the myocyte (Prolongs action Atrial and ventricular arrhythmias Ibutilide
potential) Bretylium
Amiodarone1
Blocks voltage-gated calcium channels thereby Supraventricular tachycardia Verapamil
IV blocking the flow of calcium into the cell Rate reduction in patients with Diltiazem
atrial fibrillation
1amiodarone has Class I-IV anti-arrhythmic actions
Drugs in Hypertension
Causes Na excretion and reduction in blood volume Diuretics
Calcium Channel Blocker that exerts more effect in the vessels than the heart Dihydropyridines
(Nifedipine, Felodipine, Amlodipine)
Calcium Channel blocker that exerts more effect on the heart than the vessels Nondihydropyridines
(Verapamil, Diltiazem)
Decreases the work load of the heart Beta-blockers
Blocks the AT1 receptor of angiotensin II ARBs
Notorious for drug-induced cough by increasing bradykinin ACE inhibitors
Blocks aldosterone action in the collecting tubules Spironolactone, Eplerenone
Hypertension with Benign Prostatic Hyperplasia (BPH) Alpha-1 antagonists (Prazosin)
Maintenance medication for pre-eclampsia Methyldopa
CARDIOVASCULAR DISEASES
High-Yield Concepts in Cardiac Dysrhythmias
P-wave: atrial depolarization
Physiologic basis for normal ECG tracing QRS complex: ventricular depolarization
T wave: ventricular repolarization
Master pacemaker of the heart Sinoatrial (SA) Node
Calcium influx (Sodium influx will merely
Causes depolarization of the SA node bring potential closer to threshold;
however, sodium is still the determinant
of heart rate)
Failure to increase HR during exercise,
alternatively defined as:
Unable to achieve 85% of
predicted maximal HR at peak
Chronotropic Incompetence exercise
Unable to achieve a HR >100
bpm with exercise
Maximal HR with exercise <2 standard
deviations below that of an age-
matched control population
The only electrical connection between the atria and ventricles AV node
Most common arrhythmia mechanism Reentry
Only reliable therapy for symptomatic bradycardia in the absence of extrinsic Permanent pacemaking
and reversible etiologies
Most rapid conduction in the heart His bundle and bundle branches
Most expeditious technique in the management of AV conduction block Transcutaneous pacing
Most common arrhythmia identified during extended ECG monitoring Atrial Premature Complexes
280
Most common sustained arrhythmia Atrial Fibrillation
Has prolongation of PR interval before
dropped QRS complex
Mobitz Type I Mnemonic: think of the Roman Numeral
I that gets taller PR prolongation in
Mobitz I
Has no prolongation of PR interval
before dropped QRS complex
Mobitz Type II Mnemonic: think of the Roman Numeral
II with equal heights between the two
letter “I”s no PR prolongation in
Mobitz II
Duration that distinguishes sustained from nonsustained ventricular >30 seconds
tachycardia
Most common arrhythmia post-MI Premature Ventricular Contraction
(PVC)
Most common lethal arrhythmia post-MI Ventricular Fibrillation
High-Yield Concepts in Heart Failure (HF)

Most common cause of systolic dysfunction that leads to L-sided HF Coronary Artery Disease (CAD)
Most common cause of diastolic dysfunction that leads to L-sided HF Concentric LVH due to HPN
Most common cause of R-sided HF L-sided HF
Earliest cardinal symptom of L-sided HF Dyspnea
Earliest cardinal sign of L-sided HF L-sided S3
Dyspnea, left-sided S3, PND,
orthopnea, Mitral regurgitation,
increased Brain Natriuretic Peptide
Presentation of L-sided HF (BNP), Siderophages (hemosiderin-
laden macrophages or HF cells),
pulmonary edema (septal edema,
peribronchiolar edema)
Peripheral ankle edema (hallmark of R-
Presentation of R-sided HF sided HF), NVE, tricuspid regurgitation,
ascites, chronic passive congestion of
the liver (nutmeg liver), cardiac cirrhosis
Most sensitive index of cardiac function Ejection fraction
Single most important bedside measurement to estimate volume status JVP (internal jugular vein is preferred)
Cardinal symptoms of HF Fatigue and shortness of breath
Pulmonary congestion with
Most important mechanism of dyspnea in HF accumulation of interstitial or intra-
alveolar fluid, which activates
juxtacapillary J receptors
Only pharmacologic agents that can adequately control fluid retention in Diuretics
advanced HF
Major problem of Aldosterone Antagonists Development of life-threatening
hyperkalemia
Cornerstones of modern therapy for HF with a depressed EF ACE-I/ARBs and Beta Blockers
Most common side effect of all vasodilating agents Hypotension
Most commonly used inotropic agent for acute HF Dobutamine
First choice for therapy in which modest inotropy & pressor support are Dopamine
required
Most common reason for rehospitalization in HF Failure to meet criteria for discharge
Most common symptom of cor pulmonale Dyspnea
High-Yield Concepts in Valvular Heart Disease

Murmurs that always signify structural heart disease Diastolic murmurs (Grade I-II systolic
murmurs are usually benign)
Opening Snap, mid-Late Diastolic Murmur, typical tethering and diastolic Mitral stenosis (MS)
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doming on 2D Echo, Atrial Fibrillation
Leading cause of MS Rheumatic Heart Disease
Pansystolic Murmur; may be due to Mitral Valve Prolapse (MVP) Mitral Regurgitation (MR)
Papillary muscle involved more frequently in acute MR because of single blood Posteromedial papillary muscle
supply
Most prominent complaints in chronic severe MR Fatigue, exertional dyspnea &
orthopnea
Most important finding on auscultation in MVP Mid- or late (non-ejection) systolic click
Most common ECG finding in MVP Normal
Most common cause of midsystolic murmur in an adult Aortic Stenosis (AS)
Most common congenital heart valve defect Bicuspid Aortic Valve Disease
Exertional Dyspnea
Three cardinal symptoms of AS Angina Pectoris
Syncope
IE in IV Drug Abusers, pulsating Liver, giant C-V Wave in Jugular Venous Tricuspid Regurgitation
Pulses
Carcinoid Heart Disease Pulmonary Stenosis
High-Yield Concepts Cardiomyopathies and Myocarditis

Young adult with progressive dyspnea
Typical clinic picture of myocarditis and weakness days to weeks after a
viral syndrome with fever and myalgia
from skeletal muscle inflammation
Third most common parasitic infection in the world, a cause of dilated Chagas’ Disease
cardiomyopathy
Trypanosoma cruzi is transmitted by the bite of the Reduviiid Bug
African Trypanosomiasis is caused by Tsetse Fly Bite
Most common cause of death in Diphtheria Myocarditis
Time frame of Peripartum Cardiomyopathy Lasts trimester or within the first 6
months after pregnancy
Most common toxin in chronic dilated cardiomyopathy Alcohol
Temporary dilated cardiomyopathy due to stress Tako-Tsubo Cardiomyopathy a.k.a.
“Broken-Heart” Syndrome
Most common reason for thyroid abnormalities in HF Use of amiodarone
Least common of the triad of cardiomyopathies (dilated, hypertrophic, Restrictive Cardiomyopathy
restrictive)
Best characterized genetic cardiomyopathy and the common lesion found at Hypertrophic Cardiomyopathy (HCM)
autopsy of young athletes dying suddenly
Most common presenting symptom of HCM Dyspnea on exertion
Classic finding on the ECG of HCM Systolic anterior motion (SAM) of the
mitral valve
Most commonly used initial therapy for HCM Beta-blockers and verapamil
High-Yield Concepts in Pericardial Diseases

Most common pathologic process involving the pericardium Acute Pericarditis
Typical pain in pericarditis Worse when supine and relieved by
sitting upright and leaning forward
Pericardial friction rub in acute pericarditis is heard not frequently at End-expiration with patient upright and
leaning forward
Most common ECG finding in acute pericarditis Diffuse ST-Segment Elevation
(except V1, aVL, aVR)
Neoplastic disease
Three most causes of tamponade Idiopathic pericarditis
Renal failure
Important clue to the presence of cardiac tamponade consisting of a greater Paradoxical Pulse (Pulsus Paradoxus)
than normal (10 mmHg) inspiratory decline in systolic arterial pressure
Most common causes of bloody pericardial fluid Neoplasm in the US
Tuberculosis in developing nations
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Pericardial effusion in HIV is usually due to Infection (mycobacterial)
Neoplasm (most frequently lymphoma)
Extension or invasion of metastatic
tumors
Most common causes of pericarditis due to neoplastic disease Carcinoma of Lung and Breast
Malignant Melanoma
Hematologic (Lymphoma,
Leukemia)
Neoplasm
Grossly sanguineous pericardial fluid in chronic pericarditis results most Tuberculosis
commonly from Renal failure
Slow leakage from an aortic aneurysm
Basic physiologic abnormality in chronic constrictive pericarditis Inability of ventricles to fill because of
limitations imposed by the rigid,
thickened pericardium
Most prominent deflection in constrictive pericarditis (absent/diminished in y descent
tamponade)
The only definitive treatment of constrictive pericarditis Pericardial Resection
High-Yield Concepts in Cardiac Tumors and Trauma

Secondary to malignant neoplasms from
Most common tumor of the pericardium or invading the mediastinum (e.g.,
carcinoma of the bronchus and breast,
lymphoma, melanoma)
Most common primary malignant pericardial tumor Mesothelioma (e.g., from asbestosis)
Most common type of primary cardiac tumor in all age groups and occurring at Myxomas (90% are sporadic)
all ages
Most common tumors of the cardiac valves Papillary Fibroelastomas
Most common cardiac tumors in infants and children Rhabdomyomas
Almost all primary cardiac malignancies are Sarcomas (commonly involve the right
side of the heart)
Most common primary originating sites of cardiac metastases Cancer of the breast and lung
Most often involved in metastasis to the heart Pericardium > Myocardium >
Endocardium or Cardiac Valves
Central role in the diagnostic evaluation of cardiac metastases and cardiac Cardiac MRI
tumors
Most common form of non-penetrating cardiac injury Myocardial contusions
Most common valves that rupture in non-penetrating cardiac injury TV or MV (heralded by the development
of a loud murmur)
Most serious consequence of non-penetrating injury Myocardial rupture
Most common vascular deceleration injury Rupture of the aorta
Most common cause of sudden death in contact sports (e.g., American Commotion Cordis
football)
High-Yield Concepts in Congenital Heart Diseases (CHD)

Most common congenital heart disease; CXR shows biventricular enlargement Ventricular Septal Defect (VSD)
& dilated left atrium; most common type is membranous
Most common congenital heart disease diagnosed in adults; CXR shows Atrial Septal Defect (ASD)
dilated right atrium and right ventricle
Mnemonic: All CHDs that start with “T”:
Tetralogy of Fallot (TOF)
Tricuspid Atresia
CHD with Early Cyanosis (R L shunt) Truncus Arteriosus
Total Anomalous Pulmonary
Venous Connection (TAPVC)
Transposition of the Great
Arteries (TGA)
CHD with Late Cyanosis (L R shunt) ASD, VSD, PDA, AVSD
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Conversion of an initial L R shunt into a R L shunt Eisenmengerization
CHD associated with Congenital Rubella Syndrome; “continuous machinery Patent Ductus Arteriosus (PDA)
like murmur”; needs indomethacin to close and PGE1 to remain open
CHD associated with Turner’s Syndrome Preductal Coarctation of the Aorta
(CoA)
CHD associated with Down Syndrome ASD, Endocardial Cushion Defect
CHD associated with Marfan Syndrome MVP, Aortic Dissection
CHD associated with offspring of diabetic moms TGA
CXR shows boot-shaped heart (Coeur en Sabot); Components: subpulmonic TOF
stenosis (main determinant of severity), RVH, VSD, overriding of the aorta
CXR shows egg-shaped silhouette or egg-on-its-side appearance TGA
CXR shows snowman sign/cottage-loaf heart TAPVC
CXR shows figure of 3 sign CoA (rib-notching is seen in the adult or
post-ductal form)
High-Yield Concepts in Ischemic Heart Disease (IHD)

Most common underlying cause of myocardial ischemia and injury Obstruction of coronary arteries by
atherosclerosis
Most common cause of anterior chest musculoskeletal pain Costochondral and chondrosternal
syndromes
Myocardial perfusion occurs during this time Diastole
Major cause of death and premature disability in developed societies Atherosclerosis
Represents the initial lesion of atherosclerosis Fatty Streak
Central obesity
Hyperglycemia
Major features of metabolic syndrome Hypertriglyceridemia
Hypertension
Low HDL cholesterol
All adults > 20 years (fasting lipid
Age when lipid screening should start (based on current ATP III guidelines) profile: total cholesterol, triglycerides,
LDL and HDL) repeated every 5 years
First maneuver to achieve LDL goal Therapeutic lifestyle changes (TLC)
Ultimately causes the gravest complications of atherosclerosis Thrombosis
Key feature of the metabolic syndrome Central adiposity
Most accepted & unifying hypothesis to describe pathophysiology of metabolic Insulin resistance
syndrome
Driving force behind the metabolic syndrome Obesity
Primary approach to metabolic syndrome Weight reduction (caloric restriction:
most important component)
Drug of choice to lower LDL HMG-CoA reductase inhibitors (Statins)
Drug of choice to lower fasting TG Fibrates
Only currently available drug with predictable HDL-raising properties Nicotinic acid
Most common cause of myocardial ischemia Atherosclerotic disease of epicardial
coronary artery
Major site of atherosclerotic disease Epicardial arteries (most common: Left
Anterior Descending Artery)
Sites of predilection for atherosclerotic plaques to develop due to increased Branch points in the epicardial arteries
turbulence
Time frame for reversible damage in myocardium <20 minutes for total occlusion in the
absence of collaterals
Most widely used test for both the diagnosis of IHD and estimating the Electrocardiographic Stress Testing
prognosis
Route of administration where absorption of nitrates is most rapid and Sublingual/through mucus membranes
complete
Most common route in administration of nitroglycerin Sublingual
Most common pathophysiologic cause of unstable angina Plaque rupture or erosion with
superimposed non occlusive thrombus
Only absolute contraindications to nitrate use Hypotension
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Sildenafil or other drugs in that class in
previous 24-48 hours
Most important adverse effect of all antithrombotic agents Excessive bleeding
Most common artery involved in focal spasms of Prinzmetal angina Right Coronary Artery
Main agents for acute episodes and to abolish recurrent episodes of Nitrates & Calcium Channel Blockers
Prinzmetal’s angina (Nifedipine)
Type of necrosis seen in MI Coagulation Necrosis (preserved
architecture, faded details)
Time frame where gross changes in MI occur 12 hours after the onset of symptoms
Mottling: 4 hours
Bright yellow: 1 wk
Color changes in MI Surrounding red granulation tissue: 2
weeks
Gray-white scar: 2 months
Full-thickness/Transmural; ECG: ST-elevation, Q-waves; associated with Q-wave infarction (equivalent to STEMI
increased early mortality in Clinical Medicine)
Partial-thickness/Subendocardial; involves inner third of the myocardium; ECG; Non-Q-wave Infarction (equivalent to
ST-depression; increased risk of infarction and sudden cardiac death post-MI NSTE ACS in Clinical Medicine)
Fibrinous Pericarditis (bread & butter pericarditis) post-MI Dressler’s Syndrome
Myocardial rupture post-MI occurs in patients who are 1st time MI patients (cardiac scar in
those with previous MI prevents rupture)
Pivotal diagnostic and triage tool because it is at the center of the decision 12-Lead ECG
pathway for management in STEMI
Most common presenting complaint in STEMI Chest pain
Preferred biochemical markers for MI Cardiac-Specific Troponin T & Cardiac-
Specific Troponin I
Primary cause of out-of-hospital deaths from STEMI Ventricular Fibrillation
Primary cause of in-hospital deaths from STEMI Pump Failure
Most common clinical signs of pump failure Pulmonary rales; S3 and S4 gallop
sounds
Greatest delay usually occurs between Onset of pain and the patient’s decision
to call for help
Principle goal of fibrinolysis Prompt restoration of full contrary
arterial patency
Door-to-needle time < 30 min
Most frequently and potentially the most serious complication of fibrinolysis Hemorrhage (Hemorrhagic Stroke: most
serious complication)
Standard antiplatelet agent for STEMI Aspirin
Standard anticoagulant agent for STEMI Unfractionated Heparin
Extent of LV involvement that usually results in cardiogenic shock Infarction > 40%
Usual duration of hospitalization for an uncomplicated STEMI 5 days
Most common complication of angioplasty Restenosis
Most common thrombi found in NSTEMI (composed mainly of platelets) White Thrombi
Most common thrombi found in STEMI (composed of cells and fibrin) Red Thrombi
High-Yield Concepts in Hypertension

Most common cause of death in hypertensive patients Cardiac
Second most frequent cause of death in the world Stroke
Strongest risk factor for stroke Hypertension
Reliable marker of Chronic Kidney Disease (CKD) severity and is a predictor of Proteinuria
its progression
Classic symptom of Peripheral Artery Disease (PAD) Intermittent Claudication
ABI cut off diagnostic of PAD and associated with >50% stenosis in at least ABI <0.90
one major lower limb vessel
ABI cut off associated with elevated BP, particularly systolic BP ABI <0.80
Time of the day where myocardial infarction and stroke are more frequent Early morning hours
Gold standard for evaluation and identification of renal artery lesions Contrast Angiography
Most common congenital cardiovascular cause of hypertension CoA
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BP cut off where drug therapy is recommended <140/90 mmHg
Single most effective intervention for slowing the rate of progression of BP control
hypertension-related CKD
Most common vascular deceleration injury Rupture of the aorta
Most common cause of sudden death in contact sports (e.g., American Commotio Cordis
football)
High-Yield Concepts in Rheumatic Fever

Other name for Strep. pyogenes Group A Beta-Hemolytic Strep (GABHS)
Polyarthritis, Carditis, Subcutaneous
Signs and symptoms of Rheumatic Fever Nodules, Erythema Marginatum,
Sydenham Chorea
Most common initial presentation of Rheumatic Fever Polyarthritis
Most specific presentation of Rheumatic Fever Sydenham Chorea
Most serious presentation of Rheumatic Fever Carditis
Pericardial Friction Rub, Weak Heart
Manifestation of carditis in Rheumatic Fever Sounds, Tachycardia, Arrhythmias,
Mitral Regurgitation
Anitschkow Cells/Caterpillar Cells
(Macrophages containing abundant
cytoplasm and round nuclei with
Pathologic lesion in Rheumatic Heart Disease slender, wavy ribbon of chromatin)
May coalesce to form Aschoff Giant
Cells that together with T Cells and
Plasma Cells form Aschoff Bodies
Fibrinoid Pericarditis (bread-and-butter
pericarditis)
Other pathologic findings in Rheumatic Heart Disease MacCallum Plaques: irregular thickening
of the subendocardium
Fish-mouth/Buttonhole stenosis
Mitral stenosis
High-Yield Concepts in Aortic and Ventricular Pathologies

Most common pathologic condition associated with degenerative aortic Atherosclerosis
aneurysms
Location of 90% of syphilitic aneurysms Proximal Ascending Aorta, particularly
the aortic root
Typical location of Tuberculous Aneurysms Thoracic Aorta
Aneurysms associated with Takayasu’s Arteritis Aneurysms of the aortic arch and
descending thoracic aorta
First test that suggests the diagnosis of a thoracic aortic aneurysm Chest X-Ray (findings: Widened
Mediastinum)
Harbinger of rupture and represents a medical emergency Aneurysmal pain
Most common presenting complaint of aortic dissection Sudden onset of severe sharp pain
Usual location of aortic dissection Right lateral wall of the ascending aorta
Pathology of Takayasu’s Arteritis Panarteritis
Pathology of Giant Cell Arteritis Focal granulomatous lesions involving
the entire arterial wall
Initial lesion of Syphilitic Aortitis Obliterative endarteritis
Buerger’s Disease (Thromboangitis Obliterans) has a definite relationship with Cigarette smoking (especially in young
males Jewish smokers)
Major predisposing cause of venous thrombosis Immobilization
Most common cause of secondary lymphedema Filariasis
Most common symptom attributable to pulmonary HPN Exertional dyspnea
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SECTION 2
PULMONOLOGY
HIGH-YIELD CONCEPTS IN PULMONARY PHYSIOLOGY
Respiratory bronchiole
Areas of gas exchange in the respiratory tract Alveolar ducts
Alveoli
Inspiratory Reserve Volume (IRV)
4 basic lung volumes Tidal Volume (TV)
Expiratory Reserve Volume (ERV)
Residual Volume (RV)
Amount of air inhaled/exhaled with each normal breath TV (~0.5L)
Amount of air remaining in the lungs after full exhalation RV (maintains oxygenation between breaths)
Maximum amount of air that one can inhale/exhale Vital capacity (IRV + TV + ERV)
Anatomic dead space volume Area with no gas exchange from nose to terminal
bronchiole (~150 mL)
Physiologic dead space volume Anatomic dead space volume + alveolar dead space
volume
Alveolar ventilation per minute Respiratory Rate x (TV – Physiologic Dead Space
Volume)
Minute respiratory volume TV x RR
Stimulates central chemoreceptors in the medulla Carbon dioxide (as CSF H+)
Zone 1 (no blood flow)
Lung zones Zone 2 (intermittent blood flow)
Zone 3 (continuous blood flow)
Increase in the following factors would cause shift to the right of Mnemonic: CADET face RIGHT:
the O2-Hgb dissociation curve (unloading of O2 from Hgb) CO2, Acidosis, 2,3-DPG, Exercise, Temperature
Increase in the following factors would cause shift to the left of Carbon monoxide, fetal hemoglobin
the O2-Hgb dissociation curve (increased binding of O2 to Hgb)
Percentage of blood that gives up oxygen as it passes through Utilization coefficient (25% at rest, 75-85% during
the tissue capillaries exercise)
Central control of inspiration; sends inspiratory ramp signals Dorsal respiratory group (DRG) of the medulla
Central control of both inspiration and expiration; sends Ventral respiratory group (VRG) of the medulla
overdrive mechanism in exercise
Limits inspiration and increases RR Pneumotaxic center of the pons
Stimulates inspiration and decreases RR Apneustic center of the pons
Receptors in ventral medulla; stimulated by CSF H+ from blood Central chemoreceptors (made up of DRG and VRG)
CO2; adapts within 1-2 days
Receptors in carotid bodies (CN IX) and aortic bodies (CN X); Peripheral chemoreceptors
activated when PO2 <70mmHg and to a lesser event, CO2
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PULMONARY DISEASES
High-Yield Concepts in Bronchial Asthma
>12% and 200 mL increase in FEV1: 15 minutes after
Reversibility in asthma (spirometry) is demonstrated by an inhaled short-acting B2-agonist; or
After a 2 to 4 week trial of oral corticosteroids
(prednisone or prednisolone 30-40 mg daily)
Physiologic abnormality of asthma Airway hypperresponsiveness
Pathogenesis behind asthma Imbalance favoring TH2 production over TH1
increases 1L-1, IL-5 increased eosinophils
Putative mediators of asthma SRS-A (made up of leukotrienes C4, D4, E4)
Whorls of shed epithelium in mucus plugs in asthma Curschmann’s Spirals
Crystalloid made up of eosinophil membrane protein seen in Charcot-Leyden Crystals
both asthma & amoebiasis
Predominant key cell involved in asthma None
Characteristic feature of asthmatic airways Eosinophil infiltration
Most common allergens that trigger asthma Dermatophagoides (house dust mites)
Most common triggers of acute severe asthma exacerbations URTI: rhinovirus, respiratory syncytial virus (RSV),
coronavirus
Mechanism of exercise-induced asthma (EIA) Hyperventilation
EIA is best prevented by regular treatment with Inhaled corticosteroids (ICS)
Confirms airflow limitation with a reduced FEV1, FEV1/FVC Spirometry
ratio, and PEF
Confirms diurnal variations in airflow obstruction Measurements of PEF twice daily
Primary action of B2-agonists Relax smooth muscle cells of all airways, where they
act as function antagonists
Most common side effects of B2-agonists Muscle tremor and palpitations
Most common side effect of anticholinergics Dry mouth
Most common side effects of theophylline Nausea, vomiting, headaches
Most effective controllers for asthma ICS
Indicates the need for regular controller therapy Use of a reliever medication >3x a week
Most common reason for poor control of asthma Noncompliance with medications, usually ICS
Short acting B2-agonists
Drugs that are safe for asthma in pregnancy ICS
Theophylline
High-Yield Concepts in COPD

Asthma and COPD are variations of the same basic disease Dutch hypothesis
Asthma (allergic phenomenon) and COPD (smoking-related British hypothesis
inflammation and damage) are fundamentally different diseases
Pathogenesis behind emphysema Imbalance between Protease (Elastase) and Anti-
Protease (Alpha-1-Anti-Trypsin)
First symptom of emphysema Progressive dyspnea
Ratio of mucus thickness gland layer thickness to the thickness
of the wall between the epithelium and the cartilage of the Reid’s Index (>0.4 in Chronic Bronchitis)
trachea and bronchi
Most highly significant predictor of FEV1 Pack-years of cigarette smoking
Important causes of COPD exacerbations Respiratory infections
Most common form of severe α 1-AT deficiency PiZ: two Z alleles or one Z and one null allele
Most typical finding in COPD Persistent reduction in forced expiratory flow rates
Accounts for essentially all of the reduction in PaO2 that occurs Ventilation-perfusion mismatching
in COPD
Major site of increased resistance in COPD Small airways <2 mm diameter
Type of emphysema frequently associated with cigarette Centriacinar emphysema: prominent in the upper lobes
smoking, characterized by enlarged air spaces found (initially) and superior segments of lower lobes and often focal;
in association with respiratory bronchioles involves the respiratory bronchiole (Mnemonic:
SENTROacinar, Smoking)
Type of emphysema usually observed in patients with α 1-AT Panacinar emphysema: predilection for lower lobes and
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deficiency, characterized by abnormally large air spaces evenly involves the entire respiratory unit (respiratory
distributed within and across acinar units bronchiole, alveolar duct, alveoli)
Type of emphysema associated with spontaneous Distal acinar emphysema: predilection for upper lobes
pneumothorax and involves the alveoli
Most common type of emphysema with irregular involvement Irregular emphysema
and often asymptomatic
Major physiologic change in COPD Airflow limitation
Newly-developed clubbing of the digits (not a sign of COPD) Lung cancer
should alert an investigation for
The only pharmacologic therapy demonstrated to unequivocally Supplemental O2
decrease mortality rates
Strong predictor of future COPD exacerbations History of prior exacerbations
Streptococcus pneumonia
Bacteria frequently implicated in COPD exacerbations Haemophilus influenza
Moraxella catarrhalis
The only three interventions shown to influence the natural Smoking cessation
history of COPD Oxygen therapy
Lung volume reduction surgery
High-Yield Concepts in Pneumonia and Other Pulmonary Infections

Most common pathogenesis of pneumonia Aspiration
Most common etiology of community-acquired pneumonia Streptococcus pneumoniae
Most common etiology of atypical pneumonia Mycoplasma pneumoniae
Most common cause of nosocomial pneumonia and pneumonia Pseudomonas aeruginosa
in cystic fibrosis patients
Most common viral cause of atypical pneumonia and Respiratory Syncytial Virus (RSV)
bronchiolitis in children
Main purpose of the sputum gram stain Ensure suitability of sample for culture
To be adequate for culture, a sputum sample must have >25 neutrophils; and
<10 squamous cells per low power field
Most frequently isolated pathogen in blood cultures of Streptococcus pneumoniae
community-acquired pneumonia
High-Yield Concepts in Bronchiectasis

Irreversible airway dilation that involves the lung in either a Bronchiectasis
focal or a diffuse manner
Most common form of bronchiectasis Cylindrical or tubular
Most widely called mechanism of infectious bronchiectasis Vicious Cycle Hypothesis
Most common clinical presentation of bronchiectasis Persistent cough with production of thick sputum
Imaging modality of choice for confirming bronchiectasis Chest CT
High-Yield Concepts in Pleural Effusion and Pneumothorax

First step in the diagnostic approach to pleural effusion Determine whether effusion is a transudate or exudate
Leading causes or transudative pleural effusion LV failure and cirrhosis
Leading causes of exudative pleural effusion Bacterial pneumonia, malignancy, viral infection,
pulmonary embolism
Most common cause of chylous pleural effusion Malignancy
Three tumors that cause ~75% of all malignant pleural Lung carcinoma
effusions Breast carcinoma
Lymphoma
Benign ovarian tumors producing ascites and pleural effusion Meig’s syndrome
The only symptom that can be attributed to the malignant Dyspnea
effusion itself
Condition most commonly overlooked in the differential Pulmonary embolism
diagnosis of a patient with an undiagnosed effusion
Most common cause of chylothorax Trauma (most frequently thoracic surgery)
Treatment of choice for most cases of chylothorax Insertion of a chest tube plus administration of
octreotide
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Population at risk for spontaneous pneumothorax Tall thin men 20-40 y/o, smoker
Tracheal deviation in spontaneous pneumothorax Ipsilateral tracheal deviation
Tracheal deviation in tension pneumothorax Contralateral tracheal deviation
High-Yield Concepts in Hypoventilation Syndrome and Sleep Apnea

Coexistence of unexplained excessive daytime
Obstructive Sleep Apnea sleepiness with at least five obstructed breathing
events (apnea or hypopnea) per hour of sleep
Apnea Breathing pauses lasting >10 seconds
hypopnea >10 second events where ventilation is reduced by at
least 50% from the previous baseline
High-Yield Concepts in Mediastinal Masses

First step in evaluating a mediastinal mass Place it in one of the three mediastinal compartments
Mnemonic: Terrible T’s!
Thymomas
Most common lesions in anterior mediastinum Teratomatous neoplasms
Thyroid masses
Terrible Lymphomas
Vascular masses
Most common masses in the middle mediastinum Lymphadenopathy from metastases or granulomatous
disease
Pleuropericardial and bronchogenic cysts
Neurogenic tumors
Meningocoeles
Most common masses in the posterior mediastinum Meningomyelocoeles
Gastroenteric cysts
Esophageal diverticula
High-Yield Concepts in DVT and Pulmonary Embolism

One of the three major cardiovascular causes of death, along Venous Thromboembolism (VTE)
with MI and stroke
Causes of pulmonary embolism Fat, foreign body, air, DVT, bone marrow, amniotic
fluid, tumor
Population at risk for pulmonary infarcts Patients with pre-existing heart/lung diseases (occurs
in the lower lobes)
Usual cause of death from pulmonary embolism Progressive right HF
Most frequent history in DVT Cramp in the lower calf that persists and worsens for
several days
Most frequent history in PE Unexplained breathlessness
Classic signs of PE Tachycardia, low-grade fever, neck vein distention
Most frequent symptom of PE Dyspnea
Most frequent sign of PE Tachypnea
Useful rule out test: >95% of patients with normal levels Quantitative plasma D-dimer ELISA
(<500ng/mL) do not have PE
Most frequently cited ECG abnormality in PE (in addition to S1 Q3 T3 sign
sinus tachycardia) (specific but insensitive)
Most common ECG abnormality in PE T-wave inversion in leads V1 to V4
Principal imaging test for the diagnosis of PE Chest CT Scan with IV contrast
Second-line diagnostic test for PE, used mostly for patients who Lung scanning
cannot tolerate IV contrast
Best known indirect sign of PE on transthoracic echo McConnell’s sign: hypokinesis of the RV free wall with
normal motion of the apex
Definite diagnostic test for PE which visualizes an intraluminal Pulmonary Angiography
filling defect in more than one projection
Foundation for successful treatment of DVT and PE Anticoagulation
Massive pulmonary embolism Systemic arterial hypotension with usually anatomically
widespread thromboembolism
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Moderate to large pulmonary embolism RV hypokinesis with normal systemic arterial pressure
Normal RV function and normal systemic arterial
Small to moderate pulmonary embolism pressure (excellent prognosis with adequate
anticoagulation)
High-Yield Concepts in ARDS

Acute onset (<24 hours)
Definition in ARDS Bilateral patchy airspace disease
Absence of left atrial hypertension (PCWP <18 mmHg)
Profound shunt physiology (PaO2/FiO2 <200)
Top 3 causes of ARDS Gram-negative sepsis, gastric aspiration, severe trauma
Short-term morphology of ARDS Waxy hyaline membranes
Long-term morphology of ARDS Intra-alveolar fibrosis
Histologic manifestation of ARDS Diffuse alveolar damage
High-Yield Concepts in Acute Respiratory Failure

Hypoxic respiratory failure
Pulmonary edema
Type 1 Pneumonia
Alveolar hemorrhage
ARDS
Hypercarbic respiratory failure
Type 2 Central hypoventilation
Neuromuscular asthenia
Increased respiratory load
Type 3 Respiratory failure due to atelectasis (aka post-operative respiratory
failure)
Type 4 Hypoperfusion of respiratory muscles usually secondary to shock
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SECTION 3
GASTROENTEROLOGY
HIGH-YIELD PHYSIOLOGY CONCEPTS IN GASTROENTEROLOGY
Gastrin Secreted by G cells (antrum), stimulates parietal cells in fundus
Cholecystokinin (CCK) Secreted by I cells (duodenum), contracts gallbladder &
prolongs gastric emptying time
Secretin Secreted by S cells (duodenum), inhibits acid secretion
Glucose-dependent insulinotropic Peptide (GIP) Secreted by K cells (duodenum), stimulates insulin secretion
Gastrin, Histamine, Acetylcholine Stimulates gastric acid secretion (synergistic effects)
Motilin Stimulates motility during fasting
Mucus Neck Cells Secretes mucus in the stomach
Parietal Cells Secretes HCl and Intrinsic Factor (IF) in the stomach (HCL =
parietal)
Chief Cells Secretes pepsinogen in the stomach
Enterochromaffin Cells Secretes serotonin in the stomach
Enterochromaffin-Like Cells Secretes histamine in the stomach
Interstitial cells of Cajal Pacemaker cells of the GI tract (generate slow waves)
Liver Acinus Model (Zones 1-3) Preferred functional unit of the liver
Ito Cells Store vitamin A in the liver
Enterokinase Intestinal enzyme that triggers conversion of pancreatic
trypsinogen to trypsin
Main mechanism for Bile Salt Reabsorption Enterohepatic circulation
Triglyceride Absorption Lumen Intestinal Cells as Micelles
Intestinal Cells Lymph Vessels (Lacteals) aa Chylomicrons
Carbohydrates Mouth (salivary amylase/ptyalin)
Start of Digestion Fats Stomach (lingual lipase)
Proteins Stomach (pepsin and denaturation by HCl)
Duodenum Iron, vitamin C
Absorption of Nutrients Jejunum Carbohydrates, fats, proteins, water
Ileum Vitamin B12, IF, bile salts, vitamins ADEK
GASTROINTESTINAL DISEASES
High-Yield Classic Disease Patterns in the Gastrointestinal System
2% of the population
2 years old
Rule of 2s in Meckel’s Diverticulum 2:1 male: female ratio
2 types of tissue involved
2 inches long
2 feet from ileocecal valve
Recurrent abdominal pain or discomfort at least 3 days per
month in the last 3 months associated with 2 or more of the
Diagnostic Criteria for Irritable Bowel Syndrome following:
(IBS) Improvement with defecation
Onset associated with a change in frequency of stool
Onset associated with a change in appearance of stool
Charcot’s Triad for Ascending Cholangitis FPJ – Fever, abdominal Pain, Jaundice
Charcot’s Neurologic Triad for MS SIN – Scanning speech, Intention tremor, Nystagmus
Reynold’s Pentad Charcot’s Cholangitis Triad + Shock and Confusion
Liver disease
Triad of Hepatopulmonary Syndrome Hypoxemia
Pulmonary Arteriovenous Shunting
Sudden RUQ tenderness
Triad of Acute Cholecystitis Fever
Leukocytosis
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Triad of Choledochal Cyst Abdominal pain
Jaundice
Abdominal pain
Biliary Pain
Type of Hemobilia Obstructive Jaundice
Melena
Typical abdominal pain
Diagnosis of Acute Pancreatitis 3x or greater elevation in serum amylase and/or lipase levels
Confirmatory findings on cross-sectional abdominal imaging
Increase in the size of the mass
(Requires at least 2 of the 3) A localized bruit over the mass
Sudden decrease in hemoglobin and hematocrit without
obvious external blood loss
Increase in the size of the mass
Triad of Hemorrhage from Pancreatic Pseudocyst A localized bruit over the mass
Sudden decrease in hemoglobin and hematocrit without
obvious external blood loss
High-Yield Concepts in Esophageal Disorders

Classic symptoms of GERD Water brash and substernal heartburn
Most common cause of Esophageal Chest Pain Gastroesophageal reflux
Most sensitive test for diagnosis of GERD 24-hour ambulatory pH monitoring
Globus Hystericus Perception of a lump or fullness in the throat that is felt
irrespective of swallowing
Characteristic symptom of Infectious Esophagitis Odynophagia
Common cause of Steakhouse Syndrome Schatzki ring in the lower esophagus (meat usually instigates
intermittent food impaction)
Bird’s beak appearance Radiographic sign in achalasia
Corkscrew or rosary bead esophagus Seen radiographically in diffuse esophageal spasm (DES) or
spastic achalasia
Esophageal Manometry Detects impaired LES relaxation and absent peristalsis in
achalasia
Best test for evaluation of the proximal GIT Endoscopy/esophagogastroduodenoscopy (EGD)
Cobblestone appearance of esophagus Crohn’s disease (on endoscopy or barium radiography)
Gold standard for confirmation of Barrett’s Endoscopic biopsy
Esophagus
Typical presentation Progressive solid food dysphagia and weight loss
Squamous Cell CA Middle third of the esophagus, associated with smoking
Esophageal Cancer Distal third of the esophagus, associated with GERD & Barrett’s
Adenocarcinoma Esophagus (metaplasia from squamous to columnar
epithelium)
High-Yield Concepts in Gastrointestinal Bleeding

Most common cause of UGIB Peptic ulcers
Most common cause of LGIB overall Hemorrhoids
Most common cause of Rectal Bleeding in infancy Anal fissure
Most common cause of significant LGIB in children Meckel’s diverticulum
Most common colonic causes of significant GIB in IBD and juvenile polyps
children and adolescents
Most common cause of hematochezia in the elderly Hemorrhage from a colonic diverticulum
Majority of obscure GIB Small intestinal sources of bleeding
Boerhaave Syndrome Full-thickness esophageal tear (rupture)
Mallory-Weiss Tear Partial-thickness esophageal tear
Classic history of Mallory-Weiss Tear Vomiting, retching, coughing, hematemesis in an
alcoholic/bulimic patient
Most important causes of Hemorrhagic and Erosive NSAIDs, alcohol and stress
Gastropathy (Gastritis)
Best way to initially assess a patient with GIB HR and BP
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Procedure of choice in UGIB Upper endoscopy
Procedure of choice in LGIB Colonoscopy after an oral lavage solution
Initial test for massive obscure GIB Angiography
High-Yield Concepts in Peptic Ulcer Disease (PUD)

Key enzyme in rate-limiting step of prostaglandin synthesis Cylooxygenase (COX)
Most common causes of gastric/duodenal ulcers (GU/DU) H. pylori and NSAIDs
Most common location of DUs 1st portion of the duodenum
Most discriminating symptom of DUS Pain that awakens the patient from sleep (between
midnight and 3AM)
Most frequent finding in patients with GU/DU Epigastric tenderness
PUD-related complications GI bleeding > perforation > gastric outlet obstruction
(in order of decreasing frequency)
Most potent acid inhibitory agents PPIs
Most common toxicity with Sucralfate Constipation
Most common toxicity with Prostaglandin Analogues Diarrhea
Most feared complication with Amoxicillin, Clindamycin Pseudomembranous colitis (treat with oral vancomycin
or IV metronidazole)
Refractory Peptic Ulcers GU: failure to heal after 12 weeks of therapy
DU: failure to heal after 8 weeks of therapy
Most common cause of treatment failure in compliant agents Antibiotic-resistant H. pylori strains
Test of choice for documenting eradication of H. pylori Urea breath test (UBT)
Vagotomy and drainage
Most commonly performed operation for DUs Highly selective vagotomy
Vagotomy with antrectomy
Higher ulcer recurrence rate, but lowest complication rate Highly selective vagotomy
Lowest ulcer recurrence rate, but highest complication rate Vagotomy with Antrectomy
Surgery of choice for an Antral Ulcer Antrectomy (including the ulcer) with a Billroth I
anastomosis
Cornerstone of therapy for Dumping Syndrome (DS) Dietary modification
Severe peptic ulcer diathesis secondary to gastric acid
hypersecretion due to unregulated gastrin release from Zollinger-Ellison Syndrome (ZES)
gastrinomas
Most common location of Gastrinomas Pancreas >> duodenum
Superior border: cystic and common bile ducts
Gastrinoma Triangle (contains over 80% of these tumors) Inferior border: junction of the 2nd and 3rd portions of
duodenum
Medial border: junction of neck and body of pancreas
Most common clinical manifestations of Gastrinoma Peptic ulcer, followed by diarrhea
First step in the evaluation of Gastrinoma Obtain a fasting gastrin level
Most sensitive/specific Gastrin Provocative Test Secretin study
Treatment of Choice for Gastrinoma PPIs
Most common presentation of Stress-Related Mucosal Injury GI bleeding
(SRMI)
Treatment of choice for Stress Prophylaxis PPIs (preferably oral if tolerated)
Most common causes of Acute Gastritis Infectious
Important predisposing factor for Gastric Cancer Intestinal metaplasia
Type A Gastritis (“Autoimmune”: anti-parietal cell antibodies) Involves primarily the fundus and body, with antral
sparing
Type B Gastritis (“Bacteria”: H. pylori-associated) Antral-predominant
More common type
Menetrier’s Disease Large, tortuous gastric mucosal folds (not a form of
gastritis)
High-Yield Concepts in Inflammatory Bowel Disease (IBD)

Ulcerative Colitis (UC) Mucosal disease that usually involves all the rectum &
extends proximally to involve all or part of the colon
Crohn’s Disease (CD) Can affect any part of the GIT from mouth to anus, but
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rectum is often spared (in contrast to UC)
Toxic Megacolon Transverse or right colon with diameter of >6 cm and
loss of haustrations in severe attacks of UC
pANCA Positivity (Perinuclear Anti-neutrophil Cytoplasmic UC >> CD
Antibodies)
ASCA Positivity (Anti-Saccharomyces cerevisiae Antibodies) CD >> UC
Markers of Intestinal Inflammation Fecal lactoferin and calprotectin (leukocyte-derived
proteins)
Appendectomy Protective against UC, increased risk of CD
Earliest lesions in CD Aphthoid ulcerations and focal crypt abscesses
Pathognomonic feature of CD Granulomas
Most common site of inflammation in CD Terminal ileum
Earliest radiologic change of UC seen on barium enema Fine mucosal granularity
Most dangerous local complication of UC Perforation
Most common ocular complications of IBD Conjunctivitis, anterior uveitis/iritis, and episcelritis
Most common genitourinary complications of IBD Calculi, ureteral obstruction, and fistulas
Mainstay of therapy of mild to moderate UC and Crohn’s Colitis Sulfasalazine and other 5-ASA agents
Treatment of moderate to severe IBD Glucocorticoids (no role as maintenance therapy)
First biologic therapy approved for CD Infliximab (TNF-alpha antibody)
Operation of choice for UC Ileal Pouch Anal Anastomosis (IPAA)
Most frequent late complication of IPAA Pouchitis
High-Yield Concepts in Irritable Bowel Syndrome (IBS)

Key symptom / prerequisite clinical feature for Abdominal pain of discomfort
the diagnosis of IBS
Most consistent clinical feature in IBS Altered bowel habits (most common pattern is constipation alternating
with diarrhea)
Evidence of anemia
Laboratory features that argue against IBS Elevated sedimentation rate
Presence of leukocytes or blood in stool
Best management for postprandial pain Antispasmodics 30 minutes before meals
Initial therapy of choice for IBS-D (Diarrhea Peripherally acting opiate-based agents
Predominant)
Only antibiotic for IBS with sustained benefit Rifaximin
beyond therapy cessation
High-Yield Concepts in Diverticular Diseases

True Diverticulum Sac-like herniation of entire bowel wall
False Diverticulum (Pseudodiverticulum) Only a protrusion of the mucosa through the muscularis propria of the
colon (where the vasa recti penetrates)
Diverticulitis Inflammation of a diverticulum
Air-fluid level in the LLQ on plain abdominal Giant diverticulum of the sigmoid colon
film
Hinchey Classification System Staging system for predicting outcomes after surgery for perforated
diverticulitis
Sigmoid diverticula
Diagnosis of Diverticulitis is best made with Thickened colonic wall >4 mm
these CT findings Inflammation within the pericolic fat + the collection of contrast material
or fluid
Safety window for barium enema or 6 weeks after an attack of diverticular disease
colonoscopy (should not be performed in acute setting due to higher risk of
perforation)
Best management for massive Diverticular Angiography + coiling (if patient unstable or has had a 6-unit bleed
Bleeding in a stabled patient within 24 hours, emergent surgery should be performed)
Best management for asymptomatic Diet alterations
Diverticular Disease
Initial treatment for symptomatic Antibiotics and bowel rest
Uncomplicated Diverticular Disease
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High-Yield Concepts in Anorectal Disorders
Procidentia (Rectal Prolapse) Circumferential, full-thickness protrusion of the rectal wall through the
anal orifice
Fecal Incontinences Involuntary passage of fecal material >10 mL for at least 1 month
Anismus The result of attempting to defecate against a closed pelvic floor (a.k.a.
nonrelaxing puborectalis)
Mucosal vs Full-thickness Rectal Prolapse Radial vs circumferential grooves around anus
Mainstay of Therapy for Rectal Prolapse Surgical correction
3 Hemorrhoidal Complexes in the Anal Canal Left lateral, right anterior, and right posterior
Most common presentation of Hemorrhoids Bleeding and/or protrusion
Hallmarks of an Anorectal Abscess Perianal pain and fever
Most common location of Anorectal Abscess Perianal, followed by ischiorectal
Most common location of Anal Fissures Posterior position, followed by anterior (lateral fissure is worrisome, and
systemic disorders should be ruled out)
Most common location of Internal Opening of Dentate line
Fistula in Ano (FIA)
Most common type of FIA Intersphincteric, followed by transsphincteric
Anterior fistula: straight tract to nearest crypt
Goodsall’s Rule for FIA Posterior fistula: curved tract to enter anal canal at posterior midline
Exception:
Best Management for Newly-Diagnoses FIA Seton (vessel loop or silk tie placed through the tract)
High-Yield Concepts on Mesenteric Vascular Disease

Most common form of Acute Intestinal Strangulated small bowel obstruction, followed by ischemic colitis
Ischemia
Most prevalent gastrointestinal disease Ischemic colitis
complicating cardiovascular surgery
Griffith’s point: splenic flexure
Most common locations for Colonic Ischemia
Sudeck’s point: descending/sigmoid colon
Gold standard for diagnosis and management Laparotomy
of Acute Arterial Occlusive Disease
Gold standard for confirmation of Mesenteric
Arterial Occlusion in Chronic Intestinal Mesenteric angiography
Ischemia
Intervention of choice to maintain
hemodynamics in Nonocculsive/Vasopastic Fluid resuscitation
Mesenteric Ischemia
Optimal treatment for Ischemic Colitis Resection of ischemic bowel & formation of a proximal stoma
Most significant indicator of survival in Timeliness of diagnosis and treatment
Mesenteric Ischemia
Best prognosis of all Acute Intestinal Ischemic Mesenteric venous insufficiency
Disorders
Marker of Intestinal Nonviability Area of nonfluorescence >5mm in diameter under UV illumination with
Woods lamp
High-Yield Concepts in Intestinal Obstruction

Main differentials for Acute Intestinal Adynamic Ileus
Obstruction Primary Intestinal Pseudo-Obstruction
Most common cause of Small-Intestinal Adhesions
Obstruction
Most common cause of Colonic Obstruction Colon cancer
Most irritating substances to the peritoneum Hydrochloric acid, colonic contents and pancreatic enzymes
Hallmark of all forms of Intestinal Obstruction Abdominal distention (more prominent in more distal sites of
obstruction)
Pathognomonic signs for Small-Bowel Fluid- and gas-filled loops of small intestine
Obstruction on plain abdominal film “Stepladder” pattern with air-fluid levels
Absence or paucity of colonic gas
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Most commonly used modality to evaluate Abdominal CT (can differentiate between adynamic ileus, partial
postoperative patients for Intestinal Obstruction obstruction, and complete obstruction)
Cecal diameter that increases likelihood of >10 cm on plain abdominal film
perforation
Most featured complication of Acute Intestinal Closed loop: lumen is occluded at two points by a single mechanism
Obstruction (such as fascial hernia or adhesive band), also often with occlusion of
blood supply, leading to high pressures and gangrene
High-Yield Concepts in Appendicitis and Peritonitis

Most common abdominal surgical emergency Appendicitis
Most common cause of appendiceal luminal Fecalith
obstruction leading to Acute Appendicitis (AA)
Pathognomonic in AA Sequence of abdominal discomfort and anorexia
Most useful test in excluding genitourinary Urinalysis
conditions that may mimic AA
Most common extrauterine condition requiring Appendicitis
abdominal operation during pregnancy
Most common period of occurrence of AA Second trimester
during Pregnancy
Best diagnostic exam of AA during pregnancy Ultrasound
Cardinal manifestations of Peritonitis Acute abdominal pain and tenderness, usually with fever
Most common causes of localized Peritonitis Uncomplicated appendicitis and diverticulitis
High-Yield Concepts in Evaluation of Liver Disease

Hepatocellular pattern of liver disease Liver injury, inflammation and necrosis predominate
Cholestatic pattern of liver disease Inhibition of bile flow predominates
Histologic assessment of necroinflammatory activity:
Grading of liver disease Acute or chronic
Active or inactive
Mild, moderate or severe
Level of progression of the disease, based on the degree of hepatic
Staging of liver disease fibrosis:
Early or advanced
Precirrhotic or cirrhotic
Criterion standard in evaluation of liver disease
and most accurate means of assessing grade Liver biopsy
and stage
Prognostication for cirrhosis and provides
standard criteria for listing for liver
transplantation (Class B & C); utilizes serum Child-Pugh Score
bilirubin, serum albumin, PT-INR and severity
of ascites and hepatic encephalopathy
More objective means of assessing disease
severity; utilizes serum bilirubin, serum Model for End-Stage Liver Disease (MELD) Score
creatinine, and PT-INR
Indicates cirrhosis with a Child-Pugh score > 7 Liver decompensation
(Class B or C)
Occurrence of signs or symptoms of hepatic
encephalopathy in a person with severe acute Hepatic failure
or chronic liver disease
Hepatic inflammation and necrosis that Chronic hepatitis
continue for at least 6 months
Most common and most characteristic Fatigue
symptom of liver disease
Hallmark of liver disease and most reliable Jaundice
marker of severity
Most reliable physical finding in examining the Hepatic tenderness
liver
Best physical exam maneuver to appreciate Shifting dullness on percussion
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ascites
Major criterion for diagnosis of Fulminant Hepatic encephalopathy during acute hepatitis (indicates poor
Hepatitis prognosis)
Screening test for Hepatopulmonary Syndrome Oxygen saturation by pulse oximetry
Most commonly used Liver Function Tests Serum bilirubin, serum albumin, prothrombin time (PT)
Rate-limiting step in bilirubin metabolism Transport of conjugated bilirubin into the bile canaliculi (not conjugation
itself)
Any bilirubin found in urine Conjugated/direct bilirubin (water-soluble)
Exclusive site for synthesis of serum albumin Hepatocytes
Only clotting factor not produced in liver Factor VIII
Single best acute measure of hepatic synthetic Protime (PT)
function (PT prolongation >5 secs not corrected by parenteral vitamin K
administration is a poor prognostic sign in acute viral hepatitis)
Most helpful in recognizing Acute Elevated aminotransferases/transaminases
Hepatocellular Diseases
Viral hepatitis
Differentials for striking elevations in Ischemic liver injury
aminotransferases (>1000U/L) Toxin- or drug-induced liver injury
Acute phase of biliary obstruction caused by passage of gallstone into
CBD
↑ AST > ↑ ALT Alcoholic liver disease (AST for San Miguel Beer)
↑ ALT > ↑ AST Viral hepatitis (ALT is a more specific indicator of liver injury)
Key events in hepatic fibrinogenesis Stellate cell activation and collagen production
First indication of worsening hepatic fibrosis Mild thrombocytopenia
Most commonly employed imaging tests for the Ultrasound, CT, MRI
liver
First-line imaging tests for suspected Ultrasound and Ct (high sensitivity for biliary duct dilatation)
Obstructive Jaundice
First test for suspected Budd Chiari Syndrome Ultrasound with Doppler Imaging
(Hepatic Vein Thrombosis)
Budd-Chiari Syndrome (BCS) vs Cardiac Extravasation of RBCs in BCS (but not in cardiac cirrhosis)
Cirrhosis
High-Yield Concepts in Complications of Liver Cirrhosis

Portal Hypertension (HPN) Elevation of hepatic venous pressure gradient (HVPG) to >5 mmHg
Most common cause of Portal HPN in the US Cirrhosis
Gastroesophageal varices with hemorrhage
3 primary complications of Portal HPN Ascites
Hypersplenism
First indication of Portal HPN in Liver Cirrhosis Hypersplenism with thrombocytopenia
Palliative procedure to Portal HPN Transjugular Intrahepatic Portosystemic Shunt (TIPS)
First-line treatment to control Acute Variceal Endoscopic intervention
Bleeding
Most common cause of ascites Portal HPN related to cirrhosis
Laterality of Hepatic Hydrothorax More common on the right side
Recommended Sodium Restriction for Small <2 g of sodium per day
Amounts of Ascites
Most common organisms causing Escherichia coli and other gut bacteria
Spontaneous Bacterial Peritonitis (SBP)
Presumed mechanism for development of SBP Bacterial translocation
Most common antibiotic for SBP Cefotaxime
Hepatic Encephalopathy (Portosystemic Alteration in mental status and cognitive function occurring in the
Encephalopathy) presence of liver failure
Asterixis or Liver Flap Sudden forward movement of the wrist after it is bent back on an
extended arm; cannot be elicited if patient already comatose
Mainstay of treatment for Hepatic Lactulose, to promote 2-3 soft stools per day
Encephalopathy
Hepatorenal Syndrome (HRS) Functional renal failure without renal pathology in patients with
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advanced cirrhosis or acute liver failure
Type 1 HRS Progressive impairment in renal function and significant reduction in
creatinine clearance within 1-2 weeks
Type 2 HRS Reduction in GFR with an elevation of serum creatinine level, but failry
stable (better outcome than Type 1 HRS)
Best therapy for HRS Liver transplantation
Phenotype of A1AT Deficiency with Greatest ZZ phenotype
Risk for Developing Chronic Liver Disease
High-Yield Concepts in Viral Hepatitis

Only human Hepatitis Virus that is a DNA Virus Hepatitis B (other as RNA viruses)
First detectable marker HBs Antigen (HBsAg)
Qualitative marker for high HBe Antigen (HBeAg, disappearance is a harbinger of critical
infectivity/replication improvement & resolution of infection)
Quantitative marker for high HBV DNA (also correlates with level of liver injury)
infectivity/replication
HBV First antibody to rise Anti-HBc antibody (1-2 weeks after HBsAg)
Serology Positive during window period IgM anti-HBc antibody
Protective antibody and the only
marker to appear after Anti-HBs antibody
immunization
Criteria for chronic HBV infection HBsAg remains delectable beyond 6 months
Nonpercutaneous routes of HBV transmission Intimate (especially sexual) contact
with the greatest impact Perinatal transmission
Most important mode of HBV perpetuation in Perinatal transmission (particularly at time of delivery; not related to
the Far East and Developing Countries breastfeeding)
Most important risk factor for progression to Level of HBV replication
Cirrhosis and HCCA in Hepatitis B
Most frequent indication for liver transplantation Hepatitis C
Most common symptom in Hepatitis C Fatigue (jaundice is rare)
Most common risk factor for Hepatitis C Injection drug use
The most common genotype of Hepatitis C Genotype 1
worldwide
Gold standard for establishing a diagnosis of HCV RNA
Hepatitis C (most sensitive indicator)
Best prognostic indicator in chronic Hepatitis C Liver histology
Defective RNA virus that coinfects with and Hepatitis D (HDV)
requires helper function of HBV
Distinguishing serologic feature of chronic Presence of antibodies to liver-kidney microsomes (anti-LKM3)
Hepatitis D
Most common cause of acute Hepatitis in India, Hepatitis E
Asia, Africa and Central America
Most feared complication of Viral Hepatitis Fulminant Hepatitis (massive hepatic necrosis)
Acute Yellow Atrophy The striking postmortem finding in massive hepatic necrosis, referring to
a small, shrunken, soft liver
First approved therapy for chronic Hepatitis B IFN-alpha (although no longer used for treatment)
First nucleoside analogue to be approved for Lamivudine
Hepatitis B
Most potent of the HBV antivirals Entecavir
First-line drugs for Hepatitis B PEG-IFN, entecavir or tenofovir
PEG-IFN + ribavirin
Best treatment regimen for chronic Hepatitis C 24 weeks for genotypes 2 and 3
48 weeks for genotype 1
Most pronounced side effect of Ribavirin Hemolysis
Single most important clinical variable Duration of infection
determining IFN responsiveness in Hepatitis C
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High-Yield Concepts in Alcoholic Liver Disease (ALD)
Most commonly used drug in the US Alcohol
3 major lesions of ALD Fatty liver, alcoholic hepatitis, cirrhosis
Initial and most common histologic response to Fatty liver
hepatotoxic stimuli
Most important risk factors for ALD Quantity and duration of alcohol intake
Threshold for developing ALD Men: >60-80 g/day of alcohol for 10 years
Women: 20-40 g/day
Major enzyme responsible for alcohol Alcohol dehydrogenase
metabolism
Hepatocyte injury characterized by ballooning degeneration, spotty
Hallmark of Alcoholic Hepatitis necrosis, polymorphonuclear infiltrate, and fibrosis in the perivenular
and perisinusoidal space of Disse
Zieve’s Syndrome Hemolytic anemia with spur cells and acanthrocytes in patients with
severe alcoholic hepatitis
Cut-off poor prognosis in Alcoholic Hepatitis Discriminant function > 32
Cornerstone of ALD treatment Complete abstinence from alcohol (liver biopsy should not be performed
until abstinence maintained for at least 6 months)
High-Yield Concept in Non-Viral Hepatitis

Cause of most drug hepatotoxicity Phase I toxic metabolite (cytochrome P450)
Examples of direct hepatotoxins Carbon tetrachloride, acetaminophen, tetracycline, Amanita phalloides
(deathcap mushroom)
Examples of idiosyncratic hepatotoxins Halothane, isoniazid, chlorpromazine
Drugs wherein hepatotoxicity is more frequent Aspirin, methotrexate, isoniazid, antiretrovirals
in patients with underlying CLD
Acetaminophen dose producing clinical 10-15 grams
evidence of liver injury
Acetaminophen dose usually associated with > 25 grams
fatal fulminant disease
Last resort for Acetaminophen Hepatotoxicity Liver transplantation (if with progressive hepatic failure despite NAC
therapy)
Most important adverse effect of Erythromycin Cholestatic reaction (infrequent)
Hepatotoxic component of Trimethoprim- Sulfamethoxazole
Sulfamethoxazole (TMP-SMX)
Chronic disorder characterized by continuing hepatocellular necrosis
Autoimmune Hepatitis (AIH) and inflammation, usually with fibrosis, which can progress to cirrhosis
and liver failure
Classic syndrome in young women
Type I AIH
ANA antibodies (and p-ANCA)
Often seen in children, common in Mediterranean
Type II AIH
Anti-LKM antibodies
Anti-LKM1 Type II AIH & hepatitis C
Anti-LKM2 Drug-induced hepatitis
Anti-LKM3 Chronic hepatitis D
Mainstay of treatment for AIH Glucocorticoid therapy
High-Yield Concepts in Gallbladder and Biliary Diseases

2 major types of Gallstones Cholesterol stones (>80%)
Pigment stones (<20%)
Most important mechanism in the formation of Increased biliary secretion of cholesterol
lithogenic bile
A marked increase in cholesterol saturation of bile during the 3rd
2 key changes during pregnancy that trimester
contribute to a cholelithogenic state Sluggish gallbladder contraction in response to a standard meal
impaired gallbladder emptying
300
Most frequently isolated organisms in Escherichia coli, Klebsiella spp., Streptococcus spp., Clostridium spp.
gallbladder bile
Most frequently cultured bacteria in Anaerobes, such as Clostridium welchii or Clostridium perfringens
Emphysematous Cholecystitis Aerobes, such as E. coli
Most frequent demographic for Elderly men and diabetics
Emphysematous Cholecystitis
Radiographic diagnosis of Emphysematous Gas within the gallbladder lumen on plain abdominal film, dissecting
Cholecystitis within the gallbladder wall to form a gaseous ring
Deep inspiration or cough during subcostal palpation of the RUQ
Murphy’s Sign produces increased pain and inspiratory arrest, suggestive of acute
cholecystitis or cholangitis
Gallstone becomes impacted in the cystic duct or neck of the
Mirizzi’s Syndrome gallbladder causing compression of the CBD, resulting in obstruction
and jaundice
Presence of a palpably enlarged gallbladder suggests that the biliary
Courvoisier’s Law obstruction is secondary to an underlying malignancy rather than to
calculous disease
Sonographic criteria for identifying gallstones Acoustic “shadowing” of opacities that are within the gallbladder lumen
Change with the patient’s position (by gravity)
Most common site of fistula formation in Fistula into the duodenum
Cholecystitis
Usual site of obstruction in Gallstone Ileus Ileocecal valve
Calcium salt deposition within the wall of a chronically inflamed
Porcelain Gallbladder gallbladder; associated with gallbladder carcinoma, so cholecystectomy
is advised
Usual analgesics for Acute Cholecystitis Meperidine or NSAIDs (produce less spasm of sphincter of Oddi than
morphine)
Gold standard for treating symptomatic Laparoscopic cholecystectomy
Cholelithiasis
Treatment of choice for Acute Cholecystitis Early cholecystectomy (within 72 hours)
Overall medical condition imposes an unacceptable risk for early
Delayed surgical intervention in Cholecystitis surgery
Diagnosis of acute cholecystitis in doubt
Most common cause of persistent Overlooked symptomatic nonbiliary disorder (reflux esophagitis, peptic
Postcholecystectomy Symptoms ulceration, pancreatitis, or most often, irritable bowel syndrome)
Most common biliary anomalies in infancy Biliary atresia and hypoplasia
Caroli’s Disease Congenital biliary ectasia involving the major intrahepatic radicles
Most common type of Cholangitis Nonsuppurative acute cholangitis (vs suppurative)
Procedure of choice for Cholangitis ERCP with endoscopic sphincterotomy (both diagnostic and
therapeutic)
Most common associated entity in patients with Biliary tract disease
Nonalcoholic Acute Pancreatitis
Risk factors for concomitant CBD stones in History of jaundice or pancreatitis
patients with Gallstones Abnormal tests of liver function
Ultrasonographic or MRCP evidence of a dilated CBD
Preferred approach if CBD stones in patients
are suspected prior to Laparoscopic Preoperative ERCP with endoscopic papillotomy and stone extraction
Cholecystectomy
Treatment of choice for Cholelithiasis Endoscopic biliary sphincterotomy (EBS)
Most common cause of benign strictures if the Surgical trauma
extrahepatic bile ducts
Most common cause of extrinsic bile duct Carcinoma of the pancreatic head
compression
Organisms most commonly involved in Trematodes or flukes, including Clonorchis sinensis, Opisthorchis
Hepatobiliary Parasitism viverrini or O. felineus, Fasciola hepatica
Earliest lesion in Primary Biliary Cirrhosis Chronic nonsuppurative destructive cholangitis
(PBC)
Antibodies associated with PBC Antimitochondrial antibodies (AMA)
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Main symptoms of PBC Fatigue and pruritus
Only approved treatment for PBC Ursodeoxycholic acid (UDCA) can slow the rate of progression of
disease (but cannot reverse or cure)
Treatment of choice for decompensated Liver transplantation
cirrhosis due to PBC
Imaging technique of choice for initial
evaluation of Primary Sclerosing Cholangitis MRCP (but ERCP is the traditional gold standard diagnostic test)
(PSC)
Typical cholangiographic findings in PSC Multifocal structuring and beading involving both the intra- and
extrahepatic biliary tree
Ultimate treatment for PSC Liver transplant
Dreaded complication of PSC Development of cholangiocarcinoma
High-Yield Concepts in Pancreatic Disorders

Most common cause of Acute Pancreatitis Gallstones, followed by alcohol
Currently accepted pathogenic theory for Autodigestion
Pancreatitis
Major Symptom of Acute Pancreatitis Abdominal pain (more intense when supine, relieved by sitting up)
Cullen’s Sign Blue discoloration around the umbilicus from hemoperitoneum
Turner’s Sign Blue-red-purple or green discoloration of the flanks from tissue
catabolism of hemoglobin
Laterality of pleural effusion in Pancreatitis Most frequent on the left
Recommended screening tests Serum lipase and amylase levels
Single best enzyme to measure for the Lipase (more specific)
diagnosis
Pancreatitis for Hypertriglyceridemia Serum triglyceride levels usually >11.3 mmol/L (>1000 mg/dL)
Risk factors for severe disease and mortality in Hematocrit >44%
Acute Pancreatitis Azotemia with BUN >22 mg/dL
Best imaging study for initial evaluation of
suspected pancreatic disorder and for Abdominal CT Scan
complications of pancreatitis
Imaging study if gallstone disease is suspected Ultrasonography
in Acute Pancreatitis
Diagnostic tests of choice to evaluate the EUS and MRCP (but ERCP still needed for treatment of biliary and
pancreatic duct pancreatic duct lesions)
Best way to prevent ERCP-induced Avoidance of ERCP for diagnostic purposes in high-risk patients
Pancreatitis
Hallmark of treatment in Acute Pancreatitis Bowel rest, intravenous hydration with crystalloid, analgesia
Preferred method of nutritional support in Acute Enteral-feeding with a nasojejunal tube (vs TPN)
Pancreatitis
Diagnosis of Pancreatic Infection CT-guided needle aspiration with Gram stain and culture
Most common organisms in Pancreatic Gram-negative bacteria of intestinal origin
Infection
Most common location in Pancreatic Pancreatic body or tail (only 15% in the head)
Pseudocysts
Usual presenting complaint of Pseudocyst Abdominal pain
Usual cause of death from Pancreatic Rupture and hemorrhage of the pseudocyst
Pseudocyst
Most frequently involved artery in Splenic artery, followed by inferior and superior pancreatic duodenal
Pseudoaneurysms arteries
Most common cause of Chronic Pancreatitis in Alcoholism
US adults
Most common cause of Chronic Pancreatitis in Cystic fibrosis
US children
Predominant symptoms of Chronic Pancreatitis Abdominal pain or maldigestion and weight loss
Diagnostic test with best sensitivity/specificity Secretin stimulation test (abnormal once >60% of pancreatic exocrine
for Chronic Pancreatitis function has been lost)
Most reproducible measurement in the Secretin Maximal HCO3 concentration
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Test
Most common cause of pancreatic calcification Alcohol
Cornerstone of pancreatic therapy Pancreatic enzymes
Most common congenital anatomic variant of Pancreas divisum
the pancreas
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SECTION 4
NEPHROLOGY
HIGH-YIELD PHYSIOLOGY CONCEPTS IN NEPHROLOGY
Site of erythropoietin (EPO) production Interstitial cells of the peritubular capillaries
1,25-dihydroxycholecalciferol (calcitriol)
Active form of Vitamin D 1st hydroxylation happens in the liver (via 25-alpha hydroxylase)
2nd hydroxylation happens in the kidney (via 1-alpha hydroxylase)
Contains vasa recta and has longer loops of Juxtamedullary nephrons (less common than cortical nephrons)
Henle
Macula densa (walls of the distal tubule; detects changes in BP)
Components of the juxtaglomerular apparatus JG cells (walls of the afferent arteriole; secretes renin)
Lacis cells (unknown function)
Physiologic function of renin None
(merely converts angiotensinogen from the liver to angiotensin I)
Physiologic function of angiotensin I None
(merely converted to angiotensin II due to ACE in the lungs)
Vasoconstricts afferent and efferent arteriole (efferent>afferent)
Physiologic functions of angiotensin II Systemic vasoconstriction
Stimulates thirst
Increases ADH, cortisol, epinephrine, norepinephrine and aldosterone
Site of aldosterone production Zona glomerulosa of the adrenal cortex
Aldoesterone actions Increases Na+ reabsorption, K+ secretion, H+ secretion
ADH actions Insertion of aquaporins (AQP-2) in the collecting ducts
Increased plasma osmolarity
Triggers for ADH secretion Decreased blood volume
Decreased blood pressure
Increases GFR Afferent arteriolar vasodilation
Moderate efferent arteriolar vasoconstriction
Afferent arteriolar vasoconstriction
Decreases GFR Efferent arteriolar vasodilation
Severe efferent arteriolar vasoconstriction
Principal cells Absorb Na+ and secrete H+
Intercalated cells Absorb K+ and secrete H+
Macula densa feedback
Tubuloglomerular feedback “Constant load delivered to the distal tubule”
Primary mechanism for autoregulation of GFR
Glomerulotubular balance “Percentage of solute reabsorbed is held constant”
Substances with no transport maximum and Sodium and all passively transported solutes
renal threshold (exhibits gradient-time transport)
Ascending limb of the loop of Henle is Solutes (Mnemonic: asinding limb is permeable to solutes)
permeable to Impermeable to water
Descending limb of the loop of Henle is Water
permeable to Impermeable to solutes
Arterial blood: 7.4
Venous blood, interstitial blood: 7.35
Normal pH in various fluid sites Intracellular fluid: 6.0-7.4
Urine: 4.5-8.0
Gastric HCl: 0.8
Vaginal secretions: 3.5-4.5
Acid-base abnormalities caused by diuretics Metabolic acidosis: acetazolamide (Mnemonic: acidazolamide)
Metabolic alkalosis: loop diuretics, thiazide diuretics
Decreases in the number of functioning nephrons causes remaining
Intact Nephron Hypothesis by Neil Bricker nephrons to carry a larger burden of transport, systemic function and
regulatory function
Bricker’s Trade-Off Hypothesis Some physiologic adaptations to nephron loss also produce unintended
clinical consequences
Hyperfiltration Hypothesis by Barry Brenner Some adaptations accelerate the deterioration of residual nephrons
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CLINICAL NEPHROLOGY
Diagnostic Procedures in Nephrology
Standard test for measurement of albuminuria Accurate 24-hour urine collection
Most useful renal imaging study Renal ultrasound
The only test to establish etiology in early-stage CKD in Renal biopsy
the absence of a clinical diagnosis
Most sensitive test for renal vein thrombosis (RVT) CT angiography
Imagint test for diagnosis of nephrolithiasis Helical computed tomography (CT) scanning without
radiocontrast enhancement
High-Yield Concepts in Renal Replacement Therapy

Most common form of renal replacement therapy for AKI Hemodialysis
1. Uremic pericarditis
2. Encephalopathy
Clear indications for initiation of renal replacement 3. Intractable muscle cramping, anorexia and nausea not
therapy in patients with CKD attributable to reversible causes
4. Evidence of malnutrition
5. Fluid & electrolyte abnormalities (principally hyperkalemia or
ECF volume overload) refractory to other measures
Best potential for complete renal rehabilitation Kidney transplantation
Educational programs should be commenced No later than stage 4 CKD
Most common therapeutic modality for ESRD Hemodialysis
Leading cause of ESRD DM
Dialysis access with highest long-term patency rate Fistula
Most important complication of arteriovenous grafts Thrombosis of the graft and graft failure
Most common acute complication of hemodialysis, Hypotension
particularly among DM patients
Preferred buffer in peritoneal dialysis solutions Lactate
Heparin
Most common additives to peritoneal dialysis solutions Antibiotics
Insulin
Most common organisms in peritoneal dialysis-related Gram-positive cocci including Staphylococcus (reflecting the
peritonitis origin from the skin)
Absolute indication for the urgent initiation of or Uremic pericarditis
intensification of dialysis prescription
High-Yield Concepts in Acute Kidney Injury (AKI)

A rise of at least 0.3 mg/dL within 48 h or 50% higher than
Definition of AKI baseline within 1 week; or
Reduction in urine output to <0.5 mL/kg/h for >6 hours
Definition of oliguria <400 mL/24h
Associated with multiple myeloma Renal amyloidosis
Most common cause of Acute Renal Failure (ARF) Acute Tubular Necrosis (ATN)
(from Robbin’s Pathology)
Most common form of AKI Prerenal Azotemia (from Harrison’s IM)
Patchy necrosis, PCT & LH affected, relatively short Ischemic-type ATN (e.g. in hypovolemia)
lengths of tubules affected
Extensive necrosis, PCT and DT affected, relatively Toxic-type ATN (e.g. in use of aminoglycosides, radiocontrast
longer lengths of tubules dyes)
Prerenal Azotemia
Three broad categories of AKI Intrinsic Renal Parenchymal Disease
Post-renal Obstruction
Hypovolemia
Most common clinical conditions associated with Decreased cardiac output
prerenal azotemia Medications that interfere with renal autoregulatory responses
such as NSAIDs and inhibitors of angiotensin II
Most common causes of intrinsic AKI Sepsis, ischemia and nephrotoxins
305
A rise in SCr beginning 24-48 hours following exposure
Most common clinical course of contrast nephropathy Peak within 305 days
Resolution within 1 week
Most common protein in urine and produced in the thick Uromodulin/Tamm-Horsfall Protein
ascending limb of the loop of Henle
Hallmark of AKI Buildup of nitrogenous waste products, manifested as an
elevated BUN concentration
High-Yield Concepts in Chronic Kidney Disease

Diabetic nephropathy
Causes of large kidney observed in CKD HIV-associated nephropathy
Infiltrative diseases
Occasionally acute interstitial nephritis
Can provide definitive diagnostic and prognostic Kidney biopsy
information about CKD
Definitive treatment of the hepatorenal syndrome Liver transplantation
Continuous Renal Replacement Therapy is often Severe hemodynamic instability
preferred in patients with Cerebral edema
Significant volume overload
Chronic renal failure typically corresponds to Stage 3-5 CKD
ESRD refers to Stage 5 CKD (<15% GFR)
Screening test for early detection of renal disease Microalbuminuria (especially in DM)
Major side effects of calcium-based phosphate binders Total-body calcium accumulation and hypercalcemia
Leading cause of morbidity and mortality in patients at Cardiovascular disease (CVD)
every stage of CKD
Major risk factor for ischemic CVD Presence of any stage of CKD
Among the strongest risk factors for cardiovascular Left ventricular hypertrophy and dilated cardiomyopathy
morbidity and mortality in CKD
Salt-wasting form of renal disease
Absence of hypertension in CKD may signify Effect of antihypertensive therapy
Volume depletion
Poor left ventricular function
Stage of CKD where normocytic, normochromic anemia As early as stage 3 CKD
appears Almost universal by stage 4 CKD
Primary cause of anemia Insufficient production of EPO by the diseases kidneys
Target hemoglobin concentration in CKD 100-115 g/L
Stage of CKD where peripheral neuropathy usually Stage 4 CKD
becomes clinically evident
Stages of CKD where assessment for protein-energy Stage 3 CKD
malnutrition should begin
Indication for therapy with ACE inhibitors or ARBs Protein excretion >300 mg
(especially in DM nephropathy)
Derives from the breakdown of urea to ammonia in
saliva and is often associated with an unpleasant Uremic fetor
metallic taste (dysgeusia)
Most important initial diagnostic step in the evaluation of To distinguish newly diagnosed CKD from acute or subacute
a patient presenting with elevated serum creatinine renal failure
Classic lesion of secondary hyperparathyroidism; high Osteitis fibrosa cystica
bone turnover with increased PTH levels
Low bone turnover with low or normal PTH levels Adynamic bone disease and Osteomalacai
Devastating condition seen almost exclusively in Calciphylaxis (calcific uremic arteriopathy)
patients with advanced CKD
Seen in patients with CKD who have been exposed to Nephrogenic fibrosing dermopathy
gadolinium
High-Yield Concepts in Glomerular Diseases

“Thyroidization” (appearance similar to thyroid follicles of Chronic glomerulonephritis (GN)
the kidney) Chronic tubulointerstitial nephritis (TIN)
306
Chronic pyelonephritis
RBC casts or dysmorphic RBCs seen in the sediment GN
Most common causes of glomerulonephritis throughout Malaria and schistosomiasis (closely followed by: HIV, chronic
the world (save for subacute bacterial endocarditis in the hepatitis B and C)
Western hemisphere)
Prototypical for acute endocapillary proliferative GN Poststreptococcal GN (PSGN)
Streptococcal strains associated with impetigo M types 47, 49, 55, 2, 60 and 57
Streptococcal strains associated with pharyngitis M types 1, 2, 4, 3, 25, 49 and 12
Kidneys have subcapsular hemorrhages with a “flea- Endocarditis-associated GN
bitten” appearance
Primary treatment for endocarditis-associated GN Eradication of the infection with 4-6 weeks of antibiotics
May produce nephrotic or nephritic signs and symptoms
Large, hypercellular glomeruli, increased mesangial
matrix Membranoproliferative GN (MPGN)
BM thickening and appears as two layers; “tram-
track/train track” appearance on EM
Type I MPGN characteristics Presenceof subendothelial deposits; low C3
Type II MPGN characteristics Intramembranous deposits, ribbon-like pattern, IgG
autoantibody; low C3
Most proliferative of the three types of MPGN Type I MPGN
Glomeruli located at the corticomedullary junction (if the renal
Pathologic changes of FSGS are most prominent in biopsy specimen is form superficial tissue, the lesions can be
missed, leading to a misdiagnosis of MCD)
Has the highest reported incidences of renal vein
thrombosis, pulmonary embolism, and deep vein Membranous Nephropathy (MGN)
thrombosis
Sensitive indicator for the presence of diabetes but
correlates poorly with the presence of absence of Thickening of the GBM
clinically significant nephropathy
Earliest manifestation in ~40% of patients with diabetes Increase in albuminuria detected by sensitive
who develop diabetic nephropathy radioimmunoassay
Potent risk factor for cardiovascular events and death in Microalbuminuria
patients with T2DM
Most renal amyloidosis is the result of Fibrillary deposits of immunoglobulin light chains
Lesion in HIV-associated nephropathy FSGS
GN caused by Hepatitis B MGN: more common in children
MPGN: more common in adults
Schistosoma species most commonly associated with Schistosoma mansoni
clinical renal disease
Nephrotic versus Nephrotic Syndrome

Mnemonic: EPAL
Edema
Signs and symptoms of nephrotic syndrome Proteinuria >3.5 g/day (patho) or >3.0 g/day (IM)
HypoAlbuminemia
HyperLidemia
MCD
MGN
Diseases presenting with nephrotic syndrome DM Nephropathy
Renal Amyloidosis
FSGS
Most common cause of nephrotic syndrome in Adults Focal-Segment GS (FSGS)
Most common cause of nephrotic syndrome in Children MCD
Mnemonic: OHHA
Signs and symptoms of nephritic syndrome Oliguria
Hematuria
HPN
Azotemia
Diseases presenting with nephritic syndrome PSGN
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Rapidly-Progressive GN (RPGN)
Goodpasture syndrome
Alport syndrome
Lupus nephropathy
Key finding in nephritic syndrome RBC cast
Summary of Nephrotic Glomerular Diseases

Effacement of foot processes
MCD Highly-selective proteinuria, good response to steroids,
excellent prognosis
Idiopathic but may be caused by SLE, hepatitis B, syphilis,
gold, penicillamine, malignancy
MGN Diffuse capillary and BM thickening, “spike & dome
appearance” with subepithelial IgG and C3 deposits
Non-selective proteinuria, poor response to steroids, indolent
course
DM Nephropathy Microangiopathy leading to BM thickening
2 types: diffuse and nodular (has Kimmelsteil-Wilson Nodules)
Subendothelial/mesangial amyloid deposits
Renal Amyloidosis PAS-negative, apple-green birefringence on Congo red stain
Increasing severity may lead to renal failure
Summary of Nephritic Glomerular Diseases

Caused by GABHS; marked by high ASO titer
Most common pediatric cause of nephritic syndrome
PSGN Hypercellular glomeruli, “lumpy-bumpy” deposits of IgG and
C3, subepithelial humps on electron microscopy
Self-resolving
Poststreptococcal etiology in 50%
Renal failure within weeks or months
RPGN Type I RPGN: anti-GBM antibody-induced disease
Type II RPGN: immune complex-mediated disease
Type III: RPGN: pauci-immune type
Rupture of the basement membrane seen in the EM
Anti-GBM antibodies and anti-alveolar BM antibodies
Goodpasture Syndrome Linear pattern of IgG on IF
Hematuria and hemoptysis
Appears before age 20
Alport Syndrome Hereditary structural defect in collagen IV
Leaky BM (BM splitting on electron microscope)
Hematuria, hearing loss, blindness
High-Yield Concepts in Lupus Nephritis

Wire-loop appearance Lupus nephritis
Correlate best with the presence of renal disease in Anti-dsDNA
lupus nephritis
The only reliable method of identifying the morphologic Renal biopsy
variants of lupus nephritis
Has the most varied course of lupus nephritis Classic III Nephritis
Describes global, diffuse proliferative lesions involving Classic IV Nephritis
the vast majority of glomeruli
Has the worst renal prognosis without treatment Patients with crescents on biopsy
Predisposed to renal-vein thrombosis and other Class V Nephritis
thrombotic complications
Diseases with Prominent Renal Vascular Injury

Henoch-Schonlein purpura is distinguished clinically Prominent systemic symptoms
from IgA nephropathy by Younger age (<20 years old)
Preceding infection
308
Abdominal complaints
Berger’s Disease
IgA deposits in the mesangium
IgA Nephropathy Usually follows infection
Mesangial cell proliferation
Most common cause of asymptomatic glomerular hematuria
Recurrent episodes of macroscopic hematuria often
Two most common presentations of IgA nephropathy accompanied by proteinuria during or immediately following an
upper respiratory infection, OR
Persistent asymptomatic microscopic hematuria
More common in granulomatosis with polyangiitis Anti-PR3 antibodies
(Wegener’s)
More common in microscopic polyangiitis or Churg- Anti-MPO antibodies
Strauss
Necrotizing vasculitis
Necrotizing triad of Wegener’s granulomatosis Necrotizing glomerulitis
Necrotizing granulomas
Classically present with fever, purulent rhinorrhea, nasal
Characteristics of Wegener’s granulomatosis ulcers, sinus pain, polyarthralgias/arthritis, cough hemoptysis,
shortness of breath, microscopic hematuria, and 0.5-1g
proteinuria per 24h
Most clinical atheroembolic events Follow angiographic procedures, often of the coronary vessels
Definitive diagnosis of atheroembolic renal disease Kidney biopsy demonstrating microvessel occlusion with
cholesterol crystals that leave a “cleft” in the vessel
Prototypes of Microangiopathic Hemolytic Anemia Hemolytic Uremic Syndrome (HUS) and
(MAHA) Thrombotic Thrombocytopenic Purpura (TTP)
Most common variant of HUS D+ HUS referring to its association with bacterial
gastroenteritis
Most common Shiga-toxigenic E. coli (STEC) strain 0157:H7
Most severe manifestation of scleroderma characterized by
Characteristics of scleroderma renal crisis (SRC) accelerated hypotension, rapid decline in renal function,
nephrotic proteinuria and hematuria
Renal lesion in SRC Onion-skinning
First-line therapy in SRC unless contraindicated Treatment with ACE inhibitor
Goal in SRC Reduce SBP by 20 mmHg and DBP by 10 mmHg every 24
hours until BP normalized
Anticardiolipin (aCL): IgG, IgM, or IgA
Antiphospholipid antibodies are mainly Lupus anticoagulant (LA)
Anti-β-2 glycoprotein I (antiβ2GPI)
HELLP SYNDROME (Hemolysis, Elevated Liver Third trimester
Enzymes, Low Platelets) commonly occurs in
More commonly involved in renal vein thrombosis (RVT) Left renal vein
High-Yield Concepts in Polycystic Kidney and Tubulointerstitial Diseases

Most common genetic cause of ESRD in childhood and Nephronophthisis
adolescence
Most common renal abnormality in tuberous sclerosis Angiomyolipomas
Gitelman’s syndrome is distinguished from most forms Severe hypomagnesemia
of Bartter’s syndrome by the presence of Hypocalciuria
The mainstay of treatment for cystinuria Hydration to achieve a urine output of 2.5 L/d
Acute TIN most often presents with Acute renal failure
Predominant pathology in chronic TIN Interstitial fibrosis
Hallmark feature of TIN with uveitis Painful anterior uveitis
Bartter’s syndrome Due to mutations affecting any of the five ion transport proteins
in the TAL
Clinical syndrome mimics the effects of chronic ingestion of a
loop diuretic
Due to mutations in in the thiazide-sensitive Na-Cl co-
309
Gitelman’s syndrome transporter (NCTT) in the DCT
Mimics the effects of thiazide diuretics
Severe form of Bartter’s syndrome in which neonates present
Hyperprostaglandin E syndrome with pronounced volume depletion and failure to thrive, fever,
vomiting and diarrhea from PGE2 overproduction
Mimics a state of aldosterone excess with early and sever
Liddle’s syndrome hypertension, hypokalemia and metabolic alkalosis, but
plasma aldosterone and renin levels are low
Saturnine gout
Triad of heavy metal (lead) nephropathy Hypertension
Renal insufficiency
Analgesic nephropathy Results from the long-term use of compound analgesic
preparations containing phenacetin, aspirin and caffeine
Renal biopsy of chronic TIN Interstitial fibrosis & tubular atrophy out of proportion to degree
of glomerulosclerosis or vascular disease
High-Yield Concepts in Nephrolithiasis

Normal points of narrowing in the urinary tract and Ureteropelvic and ureterovesical junctions
common sites of stone obstruction: Bladder neck
Urethral meatus
Most common type of urolithiasis Calcium stones
Associated with Proteus mirabilis, forming staghorn Struvite stones (magnesium ammonium phosphate stones)
calculi
Hereditary, contains sulfur Cystine stones
Size of most ureteral stones which pass spontaneously <0.5 cm in diameter
Radiopaque stones on standard x-rays Calcium, cysteine and struvite stones
Radiolucent stones on standard x-rays Uric acid stones
Most common metabolic abnormality found in patients Idiopathic hypercalciuria
with nephrolithiasis
Major risk factor for uric acid stone formation Persistently acidic urine
Two goals of treatment for uric acid stones To raise urine pH
To lower excessive urine acid excretion to <1 g/d
Cornerstone of therapy for cystinuria and cysteine High fluid intake, even at night
stones
Complete removal of the stone with subsequent sterilization of
Treatment of choice for struvite stones the urinary tract (Percutaneous nephrolithotomy is the
preferred surgical approach for most patients)
High-Yield Concepts in Urinary Tract Infections (UTI)

The only consistently documented behavioral risk Frequent sexual intercourse
factors for recurrent UTI Spermicide use
Common etiologic agents in acute uncomplicated cystitis E. coli accounts for 75-90% of isolates (Mnemonic: KEPS –
Klebsiella, E. coli, Proteus, Staphylococcus aureus)
Dysuria
Typical symptoms of cystitis Urinary frequency
Urgency
Generally an indication that the upper urinary tract is Unilateral back or flank pain
involved
Indication of invasive infection of either the kidney or the Fever
prostate
Main feature distinguishing cystitis and pyelonephritis Fever (fever of pyelonephritis exhibits a high, spiking “piket-
fence” pattern & resolves over 72 h of treatment)
Fluoroquinolones commonly used for UTI include Ofloxacin, ciprofloxacin and levofloxacin
(moxifloxacin is not effective)
Drugs considered relatively safe for UTI in early Nitrofurantoin
pregnancy Penicillin
Cephalosporins
The standard of care for pregnant women with overt Parenteral B-lactam with or without aminoglycosides
310
pyelonephritis
Treatment of asymptomatic bacteriuria (ABU) does not Pregnant women
decrease the frequency of symptomatic infections or Persons undergoing urologic surgery
complications except in Neutropenic patients and renal transplant recipients
Most common isolate in candiduria C. albicans
Most common cause of bilateral hydronephrosis in boys Posterior urethral valves
Most common cause of urinary tract obstruction in adults Acquired defects
Pathognomonic of vesicoureteral reflux Flank pain that occurs only micturition
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SECTION 5
ENDOCRINOLOGY
HIGH-YIELD PHYSIOLOGY CONCEPTS IN NEPHROLOGY
High-Yield Physiology Concepts in Endocrinology
Most common 2nd messenger system cAMP system (e.g., glucagon)
2nd messenger system for insulin Tyrosine kinase (also used by IGF-1, EPO)
2nd messenger system for thyroid hormone None (acts like a steroid hormone; does not need
2nd messenger)
Hormones delivered from proopiomelanocortin (POMC) MSH, ACTH, B-lipoprotein, B-Endorphin
Other name for growth hormone Somatotropin
Other name for insulin-like growth factor 1 (IGF-1) Somatomedin
Antagonizes prolactin Dopamine (and dopamine analogs like
bromocriptine)
Main site of ADH/vasopressin synthesis Supraoptic nuclei of the anterior hypothalamus
Main site of oxytocin synthesis Paraventricular nuclei of the anterior hypothalamus
Mnemonic: PARA sa Voovs!)
Site of oxytocin & ADH/vasopressin storage and secretion Posterior pituitary
Predominant form of thyroid hormone in the blood T4
Active form of thyroid hormone T3
From outer to inner: G-F-R
3 parts of the adrenal cortex Zone Glomerulosa (Aldosterone secretion)
Zona Fasciculata (Cortisol Secretion)
Zona Reticulans (weak androgen secretion)
2 products of the adrenal medulla Epinephrine (80%), norepinephrine (20%)
Effect of insulin on potassium Increased potassium uptake in muscles and adipose
tissue (decreases plasma K+)
Marker for insulin secretion; allows discrimination of endogenous
and exogenous sources of insulin in the evaluation of C-peptide
hypoglycemia
Responsible for tensile strength of the bone Collagen fibers (make up 95% of the organic matrix)
Responsible for compressional strength of the bone Bone salts
Decreases calcium and phosphate excretion but increases urinary
calcium; increases intestinal calcium absorption; calcium Vitamin D
deposition at RDA levels and calcium resorption at toxic levels
Decreases calcium excretion and increases phosphate excretion; PTH
increases 1-alpha hydroxylase; increases bone resorption
Stimulated by LH, releases the “libido” hormone testosterone Leydig Cells
(Mnemonic: LLL: LH, Leydig, Libido hormone
Stimulated by FSH, nurse cell for sperm Sertoli cells
(Mnemonic: SSS: FSH, Sertoli cells, Sperm)
Site of sperm formation Seminoferous tubules
Site of sperm motility Epididymis
Site of sperm storage Vas deferens
Production of fructose and prostaglandins Seminal vesicle
Contributes to semen alkalinity Prostate gland
Supplies mucus to semen for lubrication Bulbourethral glands (Cowper’s glands)
Main hormone of the follicular phase Estrogen
Main hormone of the luteal phase Progesterone
Causes ovulation LH surge
Cells of the blastocyst that digest and liquefy the endometrium for Trophoblast
invasion
Nutrient-rich endometrium invaded by trophoblast Decidua
Beta-HCG is produced by Syncytiotrophoblast
Promotes growth of the fetus and insulin resistance and lipolysis in Human chorionic somatomammotropin (HCS)
the mom formerly known as HPL (human placental lactogen)
Prevents pregnancy during breastfeeding Inhibition of GnRH by prolactin
312
ENDOCRINE PATHOLOGY
High-Yield Concepts in Pituitary Pathology
Most common functioning pituitary adenoma Prolactinoma
Second most common pituitary adenoma Somatotroph adenoma
Postpartum necrosis of anterior pituitary gland presenting as Sheehan syndrome
sudden cessation of lactation
Headache, diplopia and hypopituitarism Pituitary apoplexy
High-Yield Concepts in Thyroid Pathology

Thyroid Malignancies
Papillary Thyroid CA Most common type: good prognosis; Orphan Annie
eye nuclei
Follicular Thyroid CA Hurthle cells, invades blood vessels
Medullary Thyroid CA Derived from C cells, MEN-associated
Anaplastic Thyroid CA Giant cells and spindle cells seen; poor prognosis
Other Thyroid Gland Disorders
Most common cause of hypothyroidism in iodine sufficient areas Hashimoto’s thyroiditis
Most common cause of hypothyroidism worldwide Iodine deficiency
Chronic inflammatory infiltrate of the thyroid gland with Subacute thyroiditis
multinucleate giant cells
Most common cause of painful thyroid gland; associated with viral Subacute, granulomatous, De Quervain’s thyroiditis
infection (Coxsackie)
Lymphocytic infiltration of the thyroid gland with hyperplastic
germinal centers; patchy disruption and collapse of thyroid Lymphocytic thyroiditis
follicles; no fibrosis and Hurthle cells metaplasia
Condition where normal thyroid tissues re replaces by fibrous Reidel thyroiditis
tissue; usually associated with sclerosing mediastinitis
Presents with hyperthyroidism, ophthalmology, dermopathy Graves’ disease
Histopathologic finding of Grave’s disease Diffuse thyroid hypertrophy and hyperplasia
Most common primary thyroid cancer in adults and children Papillary Thyroid Cancer
Diseases associated with PSaMMoma Bodies Papillary Thyroid Cancer; Serous Cystadenoma of
the ovaries; Mesothelioma; Meningioma
High-Yield Concepts in Parathyroid Pathology

Most common cause of primary hyperparathyroidism Parathyroid adenoma
Elevated PTH, normal calcium levels Pseudohypoparathyroidism/Tertiary
hyperparathyroidism
Elevated PTH occurring in CKD patients Secondary hyperparathyroidism
High-Yield Concepts in Adrenal Pathology

Difficult-to-treat hypertension associated with hypokalemia Hyperaldosteronism
Most common cause of primary hyperaldosteronism Idiopathic Hyperaldosteronism
Adrenals are converted to sacs of clotted blood, which virtually Waterhouse-Friedrichsen Syndrome (causes acute
obscures are underlying detail adrenal insufficiency)
Neoplasms composed of chromaffin cells, which synthesize and Pheochromocytoma
release catecholamines and in some instances peptide hormones
DISEASES OF THE ENDOCRINE SYSTEM

High-Yield Concepts Related to the Hypothalamus-Pituitary Axis
Tropic hormone failure associated with pituitary compression or GH > FSH > LH > TSH > ACTH
destruction usually occurs in this sequence
Most common presentation of tropic hormone failure in childhood Growth retardation
Earliest symptom of tropic hormone failure in the adult Hypogonadism
Most common cause of hypopituitarism in children associated with Craniopharyngoima
WNT signaling pathway
313
Most common cause of pituitary hormone hypersecretion and Pituitary adenomas
hyposecretion syndromes in adults
Cut-off size for microadenoma < 10 mm diameter
Most common mechanism where suprasellar extension can lead to Compression of the optic chiasm
bitemporal hemianopsia
Early sign of optic tract pressure Loss of red perception
Surgical approach for most pituitary tumors Transsphenoidal surgery
Treatment of choice for prolactinomas Dopamine agonists (Cabergoline and Bromocriptine)
Most common pituitary hormone hypersecretion syndrome in both Hyperprolactinemia
sexes
Hallmarks of hyperprolactinemia Amenorrhea, galactorrhea, infertility
Most abundant anterior pituitary hormone and major determinant GH
of hepatic IGF-synthesis
Major source of circulating IGF-I Liver
Most validated test to distinguish pituitary-sufficient patients from Insulin-induced hypoglycemia
AGHD
Most serious manifestation of Graves’ ophthalmopathy Compression of optic nerve at apex of the orbit
Most frequent site of thyroid dermopathy Anterior and lateral aspects of the lower leg
(Pretibial myxedema)
Time of major risk for relapse in Graves’ disease in pregnancy Postpartum period
Duration of Carbimazole or methimazole – free period prior to At least 2 days before
radioiodine therapy
Duration of PTU-free period prior to radioiodine therapy Several weeks before
Absolute contraindications to radioiodine Pregnancy and breastfeeding
Most common cause of acute thyroiditits in children and young Presence of a pyriform sinus (predominantly left-
adults sided)
Most common clinically apparent cause of chronic thyroiditis Hashimoto’s thyroiditis
Major cause of sick euthyroid syndrome Release of cytokines
Most common pattern of sick euthyroid syndrome Decrease in total and unbound T3 levels (low T3
syndrome) with normal levels of T4 and TSH
Clinical manifestations of most goiters Asymptomatic
Venous distention over the neck and difficulty breathing especially Pemberton’s Sign
when the arms are raised (in large restrosternal goiters)
Most frequent cause of acquired hypoparathyroidism in the past Surgery for hyperthyroidism
Hypoparathyroidism now usually occurs after Surgery for hyperparathyroidism
High-Yield Concepts Related to Thyroid Malignancies

Sonographic characteristics of thyroid nodules suggestive of Microcalcifications, hypoechogenicity, increased
malignancy vascularity
Benign thyroid neoplasms where risk of malignancy is very low Macrofollicular (colloid)
Normofollicular (simple)
Benign thyroid neoplasms where risk of malignancy is higher and Microfollicular (fetal)
histology is more difficult to interpret Trabecular (embryonal)
Hurthle cell variant (oncocytic)
Most common malignancy of the endocrine system Thyroid CA
Most common type of thyroid cancer Papillary Thyroid Carcinoma
More common in iodine-deficient regions Follicular Thyroid Carcinoma
Surgical treatment in almost all patients with well-differentiated Near-Total Thyroidectomy
cancer
Mainstay of thyroid cancer treatment Levothyroxine suppression of TSH
Most common type of thyroid lymphoma Diffuse large-cell lymphoma
Provides a marker of residual or recurrent disease in medullary Elevated serum calcitonin
thyroid carcinoma
Primary management of medullary thyroid carcinoma Surgery
Main goal in the approach to thyroid nodule Identify in a cost-effective manner the small
subgroup of malignant lesions
Size of most palpable thyroid nodules > 1 cm
314
High-Yield Concepts Related to the Adrenal Cortex
Cushing’s Syndrome
Hypercortisolism due to exogenous steroids Cushing’s syndrome
In the overwhelming majority of patients, Cushing’s syndrome is ACTH-producing corticotrope adenoma of the
caused by pituitary
Most common cause of Cushing’s syndrome overall Medical use of glucocorticoids for inflammatory or
immunosuppressive treatment
In at least 90% of patients with Cushing’s disease, ACTH excess Corticotrope pituitary microadenoma (often only a
is caused by few millimeters in diameter)
Ectopic ACTH production is predominantly caused by Occult carcinoid tumors (usually lung)
Majority of patients with ACTH-independent cortisol excess Cortisol-producing adrenal adenoma
caused by
Most prominent features in Cushing’s syndrome are caused by Upregulation of gluconeogenesis, lipolysis and
protein catabolism
Signs of proximal myopathy become most obvious when Trying to stand up from a chair without the use of
hands or when climbing stairs
Majority of patients experience psychiatric symptoms mostly in the Anxiety or depression
form of
Most important first step in the management of suspected Establish the correct diagnosis
Cushing’s syndrome
Investigation of choice in ACTH-dependent cortisol excess MRI of the pituitary
Oral agents with established efficacy in Cushing’s syndrome Metyrapone and Ketoconazole
Hyperaldosteronism and Conn’s Syndrome
Most common cause of mineralocorticoid excess Primary hyperaldosteronism
(Conn’s syndrome)
Clinical hallmark of mineralocorticoid excess Hypokalemic hypertension
Concurrent measurement of plasma renin and
Accepted screening test for primary hyperaldosteronism aldosterone with subsequent calculation of the
aldosterone-renin ratio (ARR)
Most straightforward test for primary hyperaldosteronism Saline infusion test
Imaging of choice for hyperaldosteronism Fine-cut CT scanning of the adrenal region
Preferred approach for unilateral lesions Laparoscopic adrenalectomy
Medical treatment for hyperaldosteronism Spironolactone
Adrenal Malignancy
Most solitary adrenal tumors Monoclonal neoplasms
Majority of adrenal nodules Inactive adrenocortical adenomas
Most common cause of malignant adrenal mass Metastasis originating from another solid tissue
tumor (frequently breast and lung)
Characteristics of benign adrenal lesions Rounded and homogenous
Characteristics of malignant adrenal lesions Lobulated and inhomogeneous
Most common histopathologic classification for adrenocortical Weiss Score
carcinoma
Highly sensitive for the detection of malignancy and can be used
to detect small metastases or local recurrence that may not be 18-FDG PET
obvious on CT
Site of metastasis in adrenocortical carcinoma Liver and lung
Capsule violation during primary surgery
Major determinants of poor survival in adrenal carcinoma Metastasis at diagnosis
Primary treatment in a nonspecialist center
Adrenal Insufficiency
Characterized by the loss of both glucocorticoids and Primary adrenal insufficiency (AI)
mineralocorticoid secretion
Only glucocorticoid deficiency is present Secondary AI
Most frequent origin of AI Hypothalamic-pituitary
Most common cause of primary AI Autoimmune adrenalitis
Excluding iatrogenic suppressions, majority of secondary AI are Pituitary or hypothalamic tumors, or their treatment
caused by by surgery or irradiation
Distinguishing feature of primary AI Hyperpigmentation
315
Characteristic feature in primary AI Hyponatremia (80%)
Diagnosis of AI is established by Short cosyntropin test
Monitoring of glucocorticoid replacement History and PE for signs and symptoms
1 mg hydrocortisone
1.6 mg cortisone acetate
Equipotency of steroids can be assumed for 0.2 mg prednisolone
0.25 mg prednisone
0.025 mg dexamethasone
Congenital Adrenal Hyperplasia
Increased adrenal androgens, decreased aldosterone, decreased 21-beta hydroxylase deficiency (virilizing)
cortisol
Increased aldosterone, decreased adrenal androgens, decreased 17-alpha hydroxylase deficiency (non-virilizing)
cortisol
Pheochromocytoma
Classic triad in pheochromocytoma Episodes of palpitations, headaches, profuse
sweating
Dominant sign of pheochromocytoma Hypertension
10% are bilateral
10% are extraadrenal
“Rule of 10s” in pheochromocytoma 10% are malignant
10% calcify
10% in children
10% familial
First step in diagnosis of pheochromocytoma Measurement of catecholamines
Cornerstone for the diagnosis Elevated plasma & urinary catecholamines
Most tumors continuously leak this metabolite, which are detected O-methylated metabolites
by measurements of metanephrines
Most sensitive test which is less susceptible to false-positive Measurements of plasma metanephrine
elevations from stress, including venipuncture
Ultimate therapeutic goal for pheochromocytoma Complete tumore removal
Before surgery, blood pressure should be Consistently <160/90 mmHg, with moderate
orthostasis
Method of choice for pheochromocytoma Atraumatic endoscopic surgery
First-described pheochromocytoma-associated syndrome Neurofibromatosis Type 1 (NF 1)
Best-known pheochromocytoma-associated syndrome Multiple endocrine neoplasia (MEN) type 2A and
type 2B
Summary of Hypercortisolism
LABORATORY TEST PITUITARY CS ADRENAL CS ECTOPIC CS
Serum cortisol ↑ ↑ ↑
Urine free cortisol ↑ ↑ ↑
Low-dose dexamethasone Cortisol not suppressed Cortisol not suppressed Cortisol not suppressed
High-dose dexamethasone Cortisol suppressed Cortisol not suppressed Cortisol not suppressed
Plasma ACTH N to ↑ ↓ Markedly ↑
High-Yield Concepts Related to the Parathyroid Gland and Calcium Homeostasis

Hyperparathyroidism and Hypercalcemia
Primary regulator of calcium physiology Parathyroid hormone (PTH) from chief cell of
parathyroid gland
Primary function of PTH Maintain the extracellular fluid (ECF) calcium
concentration within a narrow normal range
Major source of calcitonin Thyroid (C cells/parafollicular cells)
Most common cause of hypercalcemia Hyperparathyroidism
Second most common cause of hypercalcemia Malignancy
Inadvertent hemoconcentration during blood
False-positive hypercalcemia is usually the result of collection or elevation in serum proteins such as
albumin
Serve as the principal laboratory test in establishing the diagnosis Immunometric PTH assays
316
of hypercalcemia
Bones (bone pain), Groans (abdominal pain),
Symptoms of hypercalcemia Psychiatric Overtones (decreased sensorium,
psychosis)
Severe hypercalcemia and medical emergency 3.7-4.5 mmol/L or 15-18 mg/dL
Most common presentation of parathyroid tumors Isolated adenomas without other endocrinopathy
Most common location of parathyroid adenomas Inferior parathyroid glands
Primary manifestations of hyperparathyroidism involve the Kidneys and the skeletal system
Most prevalent form of hyperparathyroidism Asymptomatic
Definitive therapy of hyperparathyroidism Surgical excision of abnormal parathyroid
Responsible humoral agent in most solid tumors that cause PTH-related protein (PTHrP)
hypercalcemia
Treatment of hypercalcemia of malignancy Control of tumor
Striking feature of malignancy-associated hypercalcemia Rapidity of the course
First principle of treatment of hypercalcemia Restore normal hydration
Treatment of choice for severe hypercalcemia complicated by Dialysis
renal failure
Tapping along facial nerve induces contractions of eye, mouth or Chvostek sign
nose muscles
Carpal spasms produced by occlusion of the circulation to the Trousseau sign
forearm
Osteoporosis
Bone density that falls 2.5 standard deviations (SD) below the WHO definition of osteoporosis
mean for young healthy adults of the same sex (T-score)
Compare individual results to those in a young population T-scores
Compare individual results to those of an age-matched population Z-scores
that is also matched for race and sex
Chief clinical manifestations of osteoporosis Vertebral and hip fractures
Final common pathway in osteoclast development & activation Activation of RANK by RANKL
Time when resorption and formation processes become After age 30-45
imbalanced, wherein resorption exceeds formation
Most common estrogen-deficient state Cessation of ovarian function at the time of
menopause (average at age 51)
Fractures occur earliest in these sites Sites where trabecular bone contributes most to
bone strength
Most common early consequence of estrogen deficiency Vertebral fractures
Most common cause of medication-induced osteoporosis Glucocorticoids
Highly accurate X-ray technique that is the standard for measuring Dual Energy X-Ray Absorptiometry (DXA)
bone density
Sites of DXA determinations Lumbar spine and hip
Tend to falsely increase bone density of the spine and are a Bone spurs
particular problem in measuring the spine in older individuals
Amenable for use as a screening procedure for osteoporosis Ultrasound
Guidelines further recommend that bone mass measurement be All women by age 65
considered in
Indication for radiography or vertebral fracture assessment by DXA
to rule out asymptomatic vertebral fractures, as is the presence of Height loss >2.5-3.8 cm (>1-1.5 in)
significant kyphosis or back pain, particularly if it began after
menopause
Primary use of biochemical markers Monitoring response to treatment
Preferred source of calcium Dairy products and other foods
Calcium supplement best taken with food (since they require acid Calcium carbonate
for solubility)
Calcium supplement taken anytime Calcium citrate
Primary therapeutic agent for prevention or treatment of Estrogen
osteoporosis
SERM approved for the prevention and treatment of osteoporosis Raloxifene
SERM approved for the prevention and treatment of breast cancer Tamoxifen (but increases risk of uterine cancer in
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postmenopausal women)
Osteonecrosis of the jaw is found mostly in cancer patients given Zoledronic acid or pamidronate
high doses of
First bisphosphonate to be approved; initially for use in Paget’s Etidronate
disease and hypercalcemia
Preferred site for bone mineral density (BMD) scan due to larger Hip
surface area and greater reproducibility
Fully human monoclonal antibody to RANKL Denosumab
An exogenous PTH analog Teripararide (1-34hPTH)
By far the most common form of glucocorticoid-induced Therapeutic use of glucocorticoids
osteoporosis
Affected more severely in glucocorticoid-induced osteoporosis Trabecular bone
Should have measurement of bone mass at both the spine and hip Patients on long-term (>3 months) glucocorticoids
using DXA
If only one skeletal site can be measured, it is best to assess the Spine in individuals < 60 years
Hip in individuals > 60 years
Demonstrated in large clinical trials to reduce the risk of fractures Only bisphosphonates
in patients being treated with glucocorticoids
Summary of Bone Disorders

DISEASE Ca2+ PO4 ALP PTH NOTES
Osteoporosis - - - - ↓ Bone Mass
Osteopetrosis - - - - Thickened, dense bones
Osteomalacia/rickets ↓ ↓ - ↑ Soft bones
Osteitis fibrosa cystica ↑ ↓ ↑ ↑ “Brown tumors”
Paget’s Disease - - ↑ - Abnormal bone architecture
High-Yield Concepts in Diabetes

Leading cause of ESRD, nontraumatic lower extremity amputation DM
and adult blindness
Differentiate Type 1a and Type 1b Type 1a: Autoimmune destruction of beat cells,
Type 1b: Non-autoimmune destruction of beta cells
Most reliable and convenient tests for identifying RM in HbA1C or FPG
asymptomatic individuals
Key regulator of insulin secretion Glucose
Glucose level that stimulates insulin synthesis >70 mg/dl (3.9 mmol/L)
Glucokinase (liver; higher Km, lower affinity, higher
Rate-limiting step that controls glucose-regulated insulin secretion Vmax)
Hexokinase (everywhere else; lower Km, higher
affinity, lower Vmax)
Most potent incretin Glucagon-like peptide 1 (GLP-1)
Major portion of postprandial glucose utilized by Skeletal muscle
Features of diabetes do not become evident until how much beta 70-80%
cells are destroyed
Major susceptibility gene in T1DM HLA region on chromosome 6
Central to the development of T2DM Insulin resistance and abnormal insulin secretion
Predominantly accounts for increased FPG levels Increased hepatic glucose output
Results in postprandial hyperglycemia Decreased peripheral glucose usage
All individuals >45 years old every 3 years;
Screening for DM screening at an earlier age if overweight (BMI >25)
and have one additional risk factor for DM
Honeymoon phase Time when glycemic control is achieved with modest
doses of insulin
Classic sign of diabetic ketoacidosis (DKA) Kussmaul respiration and fruity odor (secondary to
metabolic acidosis and increased acetone)
Acetoacetate (excreted in the urine)
3 ketone bodies β-hydroxybutyrate
Acetone (not used as source of energy)
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Extremely serious complication of DKA seen most frequently in Cerebal edema
children
Necessary for DKA to develop Both insulin deficiency and glucagon excess
Preferred method for detecting ketones that more accurately Serum or plasma assays for β-hydroxybutyrate
reflect the true ketone level
Synthesized at a 3-fold greater rate than acetoacetate in DKA β-hydroxybutyrate
Preferentially detected by a commonly used ketosis detection Acetoacetate
reagent (nitroprusside)
Consistent finding in DKA and distinguishes it from simple ketonemia
hyperglycemia
False-positive reaction with nitroprusside tablet or stick (test for Captopril or penicillamine
DKA)
Careful monitoring and frequent reassessment to
Central to successful treatment of DKA ensure that patient and metabolic derangements are
improving
Acceptable potassium level wherein insulin drip can be started Initial serum K+ > 3.3 mEq/L
Underlying cause of hyperglycemic hyperosmotic state (HHS) Relative insulin deficiency and inadequate fluid
intake
Elderly with T2DM and history of polyuria, weight
Prototypical patient of HHS loss, and diminished oral intake leading to mental
confusion, lethargy or coma
Prominent features of both HHS and DKA Volume depletion and hyperglycemia
Confirms a patient’s need for insulin Low C-peptide level
Symptoms of diabetes usually resolved when glucose is < 200 mg/dL (11.1 mmol/L)
Primary goal in treatment of adults with DM HbA1C < 7.0%
Recommendations on exercise 150 min/week (distributed over at least 3 days) of
moderate aerobic physical activity
Standard of care in diabetes management Self-monitoring of blood glucose
Standard method for long-term glycemic control Measurement of HbA1C
Primary predictor of long-term DM complications HbA1C
Can be used as an alternative indicator of glycemic control when Albumin
the HbA1c is inaccurate (hemolytic anemia, hemoglobinopathies)
Measurement of glycated albumin that reflects glycemic status Fructosamine assay
over the prior 2 weeks
Glucose-lowering agents other than insulin are ineffective in type 1 Except amylin analogs and alpha-glucosidase
DM and should not be used for glucose management of severely ill inhibitors
individuals with type 2 DM
Major toxicity of metformin Lactic acidosis
Major side effects of GLP-1 agonists Nausea, vomiting and diarrhea
Major side effects of alpha-glucosidase inhibitors Diarrhea, flatulence, abdominal distention
Most common side effects of bile acid-binding resins Gastrointestinal
Effectively raises HDL, but high doses (>2 g/d) may worsen Nicotinic acid
glycemic control and increase insulin resistance
Should not be used if hypertriglyceridemia is present Bile acid-binding resins
Most serious complication of therapy for DM Hypoglycemia
Predictor of poor outcome in hospitalized patients Hyperglycemia
Preferred in ICU or in a clinically unstable setting (absorption of Insulin infusions
SC insulin is variable)
Preferred over insulin analog for IV insulin infusion (less expensive Regular insulin
and equally effective)
Preferred method for managing patients with T1DM in the Insulin infusion
perioperative period or when serious concurrent illness is present
Most crucial period of glycemic control in pregnancy Soon after fertilization
Type 1 vs Type 2 Diabetes Mellitus

CHARACTERISTICS TYPE 1 TYPE 2
Usually occurs in those <30 y.o. +
Postulated to occur due to autoimmune causes +
319
DKA is the most common complication +
Strong polygenic genetic predisposition +
HLA-DR3, -DR4 +
Depleted beta cells +
Islet leukocytic infiltrate +
Islet amyloid deposit +
High-Yield Concepts in DM Complications

Microvascular manifestations of DM Retinopathy, neuropathy, nephropathy
Macrovascular manifestations of DM Coronary heart disease, peripheral arterial disease,
cerebrovascular disease
Leading cause of blindness between ages 20 and 74 DM retinopathy
Blindness is primarily the result of Progressive diabetic retinopathy and clinically significant
macular edema
Non-proliferative DM retinopathy Retinal vascular microaneurysms, blot hemorrhages and
cotton wool spots
Hallmark proliferative DM retinopathy Neovascularization in response to retinal hypoxia
Best predictors of development of retinopathy Duration of DM and degree of glycemic control
Duration of DM in patients with non-proliferative DM >20 years
retinopathy
Most effective therapy for DM retinopathy Prevention
Treatment of proliferative retinopathy Panretinal laser photocoagulation
Treatment of macular edema Focal laser photocoagulation
Microalbuminuria 30-299 mg/d in a 24-h collection or 30-299 ug/mg creatinine in
a spot collection (preferred)
Fibrin caps, capsular drops, Kimmelstiel-Wilson nodules DM nephropathy (nodular glomerulosclerosis)
Optimal therapy of DM nephropathy Prevention by control of glycemia
Preferred therapy for DM nephropathy Renal transplantation from a living related donor
Pigmented pretibial papules or diabetic skin spots DM dermopathy
Most common site of foot ulcers Great toe or metatarsophalangeal (MTP) areas
Optimal therapy for foot ulcers and amputation Prevention
Most common site of ulceration Plantar surface of the foot
Most helpful diagnostic for infected foot ulcer Culture from debrided ulcer base or from purulent drainage or
aspiration of wound
Most specific modality for osteomyelitis MRI of the foot
Osteomyelitis best treated by Prolonged antibiotics (IV then oral) and possible debridement
of infected bone
Most common form of diabetic neuropathy Distal symmetric polyneuropathy (frequently presents with
distal sensory loss)
Most commonly involved nerve in mononeuropathy CN III (heralded by diplopia)
Most prominent GI symptoms in DM Delayed gastric emptying and altered small- and large-bowel
motility
Primary goal in gastrointestinal and genitourinary Improved glycemic control
dysfunction in DM
Most common pattern of DM dyslipidemia Hypertriglyceridemia and reduced HDL
High-Yield Concepts in Hypoglycemia

Limiting factor in the glycemic management of diabetes Hypoglycemia
Most common cause of hypoglycemia Drugs used to treat DM or by exposure to other drugs,
including alcohol
Second only to drugs as causes of hypoglycemia Serious illnesses such as renal, hepatic or cardiac failure,
sepsis and inanition
1. Symptoms consistent with hypoglycemia
Whipple’s Triad (in insulinoma) 2. Low plasma glucose measured with a precise method (not a
glucose monitor)
3. Relief of symptoms after the plasma glucose level is raised
Critical diagnostic findings when plasma glucose is <55 Plasma insulin concentration >3 uU/mL (>18 pmol/L),
mg/dL (with symptoms of hypoglycemia) Plasma C-peptide concentration >0.6 ng/mL (>0.2 nmol/L),
320
and
Plasma proinsulin concentration >5.0 pmol/L
Lower limit of the fasting plasma glucose concentration Approximately 70 mg/dL (3.9 mmol/L)
Obligate metabolic fuel for the brain under physiologic Glucose (may also use ketones in prolonged fasting after 2
conditions weeks)
Major site of endogenous glucose production Liver
Hepatic glycogen stores are able to sustain glucose Approximately 8-12h
needs for
Glycemic maintenance goals in hospitalized patients 140-180 mg/dL
First defense against hypoglycemia Decreased insulin
Second defense against hypoglycemia Increased glucagon
Third defense against hypoglycemia Increased epinephrine
Compromises physiologic defense against
hypoglycemia (particularly decrements in insulin and Defective glucose counterregulation
increments in glucagon and epinephrine)
Compromises behavioral defense against hypoglycemia Hypoglycemia unawareness
(ingestion of carbohydrates)
Hypoglycemia in non-beta cell tumors is due to Overproduction of insulin-like growth factor II (“big IGF-II”)
Prototypical cause of endogenous hyperinsulinism Insulinoma
Ingestion of an insulin secretagogue Causes hypoglycemia with increased C-peptide levels
Exogenous insulin Causes hypoglycemia with low C-peptide levels
High-Yield Concepts Related to the Gonads

Defined as the inability to conceive after 12 months of Infertility
unprotected sexual intercourse
Probability of achieving pregnancy in one menstrual Fecundability (normal value in young couples: 20%)
cycle
Emerging as the method of choice for testosterone Liquid chromatography tandem mass spectrometry (LC-
measurement MS/MS)
Most important step in the evaluation of male infertility Semen analysis
Volume = 2-6 mL
Normal ejaculate Sperm counts >20 million/mL
Motility of >50%
>15% normal morphology
Most common cause of androgen deficiency in acute Hypogonadotropic hypogonadism
illness
Most common chromosomal disorder associated with Klinefelter Syndrome (47 XXY)
testicular dysfunction and male infertility
Glandular breast tissue that is >4 cm in diameter and True gynecomastia
often tender
Most effective therapy if gynecomastia is of long Surgery
duration
Most common cause of female infertility Abnormalities in menstrual function
Most widely used form of hormonal contraception Oral contraceptives
Midcycle pelvic discomfort that is thought to be caused
by the rapid expansion of the dominant follicle at the Mittelschmerz
time of ovulation
Precocious puberty in boys Before age 9
Delayed puberty in boys Absence of secondary sexual characteristics by age 14
Precocious puberty in girls Before age 8
Delated puberty in girls Absence of secondary sexual characteristics by age 13
ENDOCRINOLOGY AND BIOCHEMISTRY CORRELATION

Basic Biochemistry of Lipids
Long chain of carboxylic acid with no double bond Saturated fatty acid
Long chain of carboxylic acid with one double bond Monounsaturated fatty acid
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Long chain of carboxylic acid with two or more double bonds Polyunsaturated fatty acid
Fatty acids associated with increased risk of atherosclerosis Trans-fatty acids and Saturated fatty acids
Essential fatty acids Linoleic acid and Linolenic acid
Immediate precursor of prostaglandins Arachidonic acid
End product of fatty acid synthesis Palmitic acid
2 primary bile acids Cholic acid and Chenodeoxycholic acid
(Mnemonic: Starts with a letter “C”: Primary)
2 secondary bile acids Deoxycholic acid and Lithocholic acid
2 molecules conjugated to bile acids to convert them to bile salts Taurine and Glycine
Clinical manifestation of lipid malabsorption Steatorrhea
Spherical macromolecular complexes composed of a neutral lipid core
surrounded by a shell of amphipathic lipoproteins, phospholipid and non- Lipoproteins
esterified cholesterol
Protein moiety of lipoproteins Apoproteins
Transport dietary triglycerides and cholesterol from intestine to tissues Chylomicrons
Transports triglycerides from liver to tissues VLDL
Delivers cholesterol into cells LDL
Reverse cholesterol transport HDL
Shuttles Apo C-II and Apo E in the blood HDL
Mediates chylomicron secretion Apo B-48
Activates lipoprotein lipase Apo C-II
Mediates uptake of chylomicron remnant Apo E
Binds to LDL receptor and mediates VLDL secretion Apo B-100
Activates LCAT to produce cholesteryl esters in HDL Apo A-1
Degradation of TAG stored in adipocytes Hormone sensitive lipase
Pancreatic lipase
Degradation of dietary TAG in small intestine Lipoprotein lipase
Degradation of TAG circulating in chylomicrons Hepatic TAG lipase
Degradation of TAG remaining in IDL
Major component of lung surfactant Dipalmitoylphosphatidylcholine (Lecithin)
Only glycerophospholipid that is antigenic Cardiolipin
Reservoir for arachidonic acid in the membranes and precursor for IP3 Phosphatidylinositol
and DAG
Important constituent of myelin Sphingomyelin
Diseases involved in Lipid Metabolism

Alcohol leads to fat accumulation in the liver Fatty liver
Cerebrohepatorenal syndrome Zellweger Syndrome
Accumulation of phytanic acid due to deficiency of alpha-hydroxylase Refsum’s Disease
Hypoglycin from unripe fruit of the akee tree inactivates medium- and Jamaican Vomiting Sickness
short-chain acyl CoA dehydrogenase
Genetic absence of lipoprotein lipase leads to excess TAGs and Type I Hypertriglyceridemia
chylomicrons that deposit in the liver, skin and pancreas
LDL receptor deficiency leads to elevated LDL cholesterol with increased Type IIA Hypercholesterolemia
risk for atherosclerosis and coronary artery disease
Accumulation of fat in intestinal enterocytes and hepatocytes, with Abetalipoproteinemia
deficiency in fat-soluble vitamins and essential fatty acids
Mental retardation from accumulation of GM2 ganglioside Tay-Sachs Disease
Mental retardation from accumulation of sphingomyelin Niemann-Pick Disease
Mental retardation with enlarged liver and spleen from accumulation of Gaucher’s Disease
glucosylceramide
Diseases Involved in Carbohydrate Metabolism

Flatulence, cramps and diarrhea after ingestion of dairy products Lactose intolerance
Severe fasting hypoglycemia, hepatomegaly, elevated glycogen in the Von Gierke Disease (Glucose 6-phosphatase
liver deficiency)
Cardiomegaly and heart failure from impaired glycogen metabolism Pompe (“Pump”) Disease (Lysosomal acid
maltase deficiency)
322
Hepatomegaly, milder form of Von Gierke Disease Cori Disease (Debranching enzyme
deficiency)
Myoglobinuria with strenuous exercise McArdle Syndrome (Skeletal muscles
glycogen phosphorylase deficiency)
Decreased NADPH in RBCs leads to hemolytic anemia due to poor RBS G6PD deficiency
defense against oxidizing agents (rate limiting enzyme of pentose phosphate
pathway)
Recurrent pyogenic infections due to impairment of respiratory burst of Chronic Granulomatous Disease
neutrophils and monocytes (NADPH oxidase deficiency)
Cataracts within a few days of birth, vomiting and diarrhea after milk Classic Galactosemia (Galactose 1p-
ingestion, lethargy, hypotonia, mental retardation uridyltransferase deficiency)
Galactosemia, galactosuria, cataracts in early childhood Galactokinase deficiency
Benign fructosuria Fructokinase deficiency
Fructosuria, severe hypoglycemia, lactic acidosis, liver damage, jaundice Fructose intolerance (Aldolase B deficiency)
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SECTION 6
INFECTIOUS DISEASES
COMMON INFECTIOUS DISEASES
Two Important Mosquito Borne Infections

Influenza-like syndrome with maculopapular rash and severe pains in Dengue
muscles and joints (breakbone fever)
Most important parasitic disease in man Malaria
Comparison of the Different Malaria Species

P. FALCIPARUM P. VIVAX P. MALARIAE P. OVALE
Asexual Cycle 48 hours 48 hours 72 hours 48 hours
Periodicity Malignant Tertian Benign Tertian Benign Quartan Benign Tertian
RBC preference All ages Young RBCs Old RBCs Young RBCs
Parasitemia Highest Low Lowest Low
Merozoites 0 12-24 6-12 8
Gametocytes Banana-shaped Large round Compact Small round
Cerebral malaria Yes No No No
Recrudescence Yes No Yes No
Relapse No Yes No Yes
Drug resistance Many Few Few Few
High-Yield Concepts in Malaria

Recurrence of symptoms after a temporary abatement (2-4 weeks) Recrudescence
Return of disease after its apparent cessation (1-6 months) due to Relapse
reactivation of hypnozoites
Screens for presence of malarial organisms Thick smears
For species identification in malaria Thin smears
Highest yield of thick and thin smears Blood sample taken during fever 2-3 hours
after peak
Punctuate granulation present in RBCs invaded by P. ovale and P. Schuffner dots (Schuffner dots = P. Ovale &
vivax Vivax, SOVrang daming dots!)
Coarse granulations present in RBC invaded b P. falciparum Maurer dots (Mnemonic: coMMa-shaped = P.
falciparuM)
Fine dots present in RBCs invaded by P. malariae Ziemann dots
Malarial or Durck granulomas are seen in Cerebral malaria
Acute renal failure in malaria Blackwater fever
Septic shock in malaria Algid malaria
Areas of high endemicity in malaria Palawan, Kalinga Apayao, Ifugao, Agusan del
Sur
Areas of chloroquine-resistance in malaria Palawan, Davao del Norte, Compstela Valley
Natural Course of Typhoid Fever

WEEK PRESENTATION CULTURE SOURCE
1 Stepwise fever, anorexia, malaise, relative bradycardia and bacteremia Blood, bone marrow
2 Abdominal pain, bloating, constipation, rose spots, hepatosplenomegaly Urine, rose spots, bone
jaundice marrow
3 Bleeding, ileitis, pneumonia Stool, bone marrow
4 Recover or death Bone marrow
POST Chronic carrier state Bile, stool, bone marrow
High-Yield Concepts Related to Leptospirosis

Most severe form of leptospirosis Weil’s Syndrome (presents with severe jaundice)
Most common cause of death in leptospirosis Massive pulmonary hemorrhage leading to respiratory failure
Drug of choice against severe leptospirosis Ceftriaxone
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Prophylaxis for leptospirosis exposure Doxycycline
Comparison of Trematode Infections

TREMATODE TRANSMISSION SITES AFFECTED INTERMEDIATE HOSTS TREATMENT
S. japonicum Penetrates skin Liver Snail Praziquantel
P. westermanii Ingested with raw crab Lung Snail and crab Praziquantel
C. sinensis Ingested with raw fish Liver Snail and fish Praziquantel
High-Yield Concepts Related to Schistosomiasis

Intermediate host of S. japonicum Oncomelania quadrasi (snail)
Intermediate host of P. westernii Sundathelphusa philippina (mountain crab)
Systemic hypersensitivity in schistosomiasis Katayama fever
resembling serum sickness
Areas of endemicity of schistosomiasis Sorsogon, Samar, Leyte, Oriental Mindoro, Bohol & all of
Mindanao except Misamis Oriental
High-Yield Concepts Related to Tetanus & Rabies

Anaerobic, gram-positive, spore-forming rods Clostridium tetani (spore is at one end so organism looks like a
tennis racquet)
Histopathologic finding in Rabies Negri bodies (not colored black!)
Rabies is invariably fatal when encephalitis develops Early brainstem dysfunction
because of
ANTI-INFECTIVES
Antibiotic Classification Based on Action

Very Finely Proficient At Murder!
Vancomycin
Bactericidal Antibiotics Fluoroquinolones
Penicillins
Aminoglycosides
Metronidazole
We’re ECSTaTiC about bacteriostatics!
Erythromycin
Clindamycin
Bacteriostatic Antibiotics Sulfamethoxazole
Trimethoprim
Tetracycline
Chloramphenicol
Penicillins
DRUG CHARACTERISTIC SIDE EFFECT
Penicillin G Narrow spectrum penicillins Hypersensitivity
Methicillin Penicillinase-resistant penicillins Interstitial Nephritis
Ampicillin Extended-spectrum penicillins Pseudomembranous Coloitis
Ticarcillin/Piperacillin Antipseudominal penicillins Hypertension, Hypervolemia, Bleeding
Carbenicillin
Remembering the Penicillins

Pen V is Oral, ipinapasok sa Vunganga
Pen G is IV: You inGect Pen G
Use naf (nafcillin) for Staph
AMPicillin = AMPed up penicillin
amOxicillin = greater Oral bioavailability
325
Organisms Susceptible to Amoxicillin
Amoxicillin HELPS kill Enterococci
Haemophilus influenza
Escherichia coli
Listeria monocytogenes
Proteus mirabilis
Salmonella spp.
enterococci
Cephalosporins
DRUG DESCRIPTION SIDE EFFECT
Cefazolin 1st generation cephalosporin, high bone penetration, surgical Hypersensitivity reaction
prophylaxis, greatest gram positive coverage
Cefamandole 2nd generation cephalosporin, added gram negative coverage Disulfiram reaction
Cefoperazone 3rd generation cephalosporin, Pseudomonas coverage Disulfiram reaction
Ceftazidime Most efficacious cephalosporin for Pseudomonas aeruginosa
Cefepime 4th generation cephalosporin, broad spectrum activity
(both gram positive and gram negative)
Ceftriaxone Best CNS penetrance
Some important points about Cephalosporins

Microbes covered by 1st generation cephalosporins
KEPs
Klebsiella spp.
E. coli
Proteus spp.
Remembering 1st Generation Cephalosporins

FADer, help me FAZ my PHarmacology boards!
CeFADroxil
CeFAZolin
CePHalothin
CePHapirin
CePHradine
CePHalexin
Organisms Susceptible to Second Generation Cephalosporins

HEN has KEPS
Haemophilus influenzae
Enterobacter aerogenes
Neisseria spp.
Klebsiella pneumoniae
Escherichia coli
Proteus mirabilis
Serratia marcescens
Remembering Second Generation Cephalosporins

In a FAMily gathering, you see your FOXy cousin wearing a FUR coat and drinking TEa.
CeFAMandole
CeFOXitin
CeFURoxime
CefoTEtan
or
FAC! LORA the PROfessional AZhOLE is still on the FONe.
CeFAClor
LORAcarbef
CefPROzil
CefmetAZOLE
CeFONicid
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Cephalosporins causing Disulfiram Reaction
Cefamandole Cefotetan
Cefmetazole Cefoperazone
Remembering Third Generation Cephalosporins

FEnge PO ng PERA to FIX my TTTTTV!
CeFEtamet CefTazidime
CefPOdoxin CefoTaxime
CefoPERAzone CefTizoxime
CeFIXime CefTibuten
CefTriaxone
Protein Synthesis Inhibitors

DRUG REMARKS SIDE EFFECT
Chloramphenicol Binds to 50S subunit Aplastic Anemia
Gray Baby Syndrome
Tetracycline Binds to 30S subunit Tooth Enamel Discoloration
Photosensitivity
Erythromycin Binds to 50S subunit, Drug of choice for Diarrhea, cholestatic jaundice
penicillin-allergic patients
Azithromycin Binds to 50S subunit, highest volume of distribution,
single dose administration for certain indications
Clindamycin Binds to 50S subunit, anaerobic coverage
Linezolid Binds to 50S subunit, for Vancomycin-resistant organisms
Aminoglycosides
Prototype aminoglycoside Nephrotoxicity
Gentamicin Bactericidal Ototoxicity
Binds to 50S subunit
Tobramycin Treatment of ocular infections
Streptomycin Tuberculosis
Spectinomycin Treatment of drug-resistant gonorrhea
Widest spectrum of activity
Amikacin Has pseudomonal coverage
Narrow therapeutic window
Neomycin Treatment of hepatic encephalopathy
Remembering Aminoglycosides
Mean GiANTS canNOT kill anaerobes.
Gentamicin Streptomycin
Amikacin Nephrotoxicity
Neomycin Ototoxicity
Tobramycin Teratogen
AminOglycosides require O2 for transport.
They won’t work under anaerobic conditions.
Sulfonamides
DRUGS REMARKDS SIDE EFFECT
Sulfamethoxazole Blocks Dihydropteroate Synthase
Sequential blockade in folate synthesis Hypersensitivity (SJS, TEN),
TMP-SMX Commonly used for UTI kernicterus, hemolysis in patients with
G6PD deficiency
Fluoroquinolones
Ciprofloxacin 2nd generation quinolone Tendinitis
Used for UTI and GIT infections
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Levofloxacin 3rd generation quinolone
Used for pulmonary infection
4th generation quinolone
Moxifloxacin Broad spectrum of activity, anaerobic coverage
Treatment of ocular infections
Gatifloxacin 4th generation quinolone Diabetes mellitus
Anti-Mycobacterial Agents
Isoniazid Bactericidal Neurotoxicity, hepatotoxicity, sideroblastic anemia,
Inhibits mycolic acid synthesis drug-induced lupus, potent CYP450 inhibitor
Rifampicin Bacteriostatic
Inhibits DNA-dependent RNA polymerase Red orange urine, hepatotoxicity
Ethambutol Bacteriostatic Visual dysfunction (retrobulbar neuritis, color
Inhibits arabinogalactan synthesis blindness)
Pyrazinamide Bacteriostatic but bactericidal on actively dividing Hyperuricemia, most hepatotoxic
MTB
Streptomycin Bactericidal, binds to 30S Nephrotoxicity, ototoxicity
Other Important Things to Remember About Anti-Mycobacterials

INH Injures Neurons and Hepatocytes
R = Rifampicin (RNA polymerase inhibitor, Red-orange body fluids, Rapid development of resistance, Revs up
cytochrome P450 (inducer)
Hepatotoxicity: Iso a Red Pyre! [Isoniazid < Rifampin < Pyrazinamide]
Drugs Used for Leprosy

Dapsone Most active drug against M. leprae Methelmoglobinemia
Inhibits folate synthesis
Rifampicin Inhibits DNA-dependent RNA polymerase Red-orange urine
Delays onset of dapsone resistance
Clofazimine Phenazine dye Skin discoloration
Binds to guanine bases
Other Antimicrobials
Aztreonam Silver bullet against gram-negative bacteria
Clavulanic Beta-lactamase inhibitor
Acid
Meropenem Drug of last resort CNS toxicity
Broad spectrum of activity
Metronidazole Anaerobic and antiprotozoal coverage Disulfiram reaction, metallic taste, neurotoxicity
Treatment of pseudomembranous colitis
Nitrofurantoin Treatment of urinary tract infections Pulmonary fibrosis
Antibiotics Drugs of Last Resort

I AM your Last Shot at Victory!
Imipenem
Amikacin
Meropenem
Linezolid
Streptogramins
Vancomycin
Antifungals
Amphotericin B Most efficacious antifungal drug Nephrotoxicity (RTA, ATN)
Forms artificial pores
328
Ketoconazole Topical treatment of dermatophytosis and Gynecomastia
candidiasis CYP450 inhibitor
Fluconazole Prophylaxis and treatment of candidiasis and cryptococcosis
Griseofulvin Interferes with fungal microtubules Potent CYP450 inducer
Nystatin Treatment of candidiasis (oropharyngeal, esophageal, vaginal)
Swish and swallow or suppository preparations
Antivirals
Acyclovir Treatment of HSV and VZV Crystalluria
Requires activation by viral thymidine kinase
Ganciclovir Treatment of CMV
Requires activation by viral thymidine kinase
Foscarnet Treatment of HSV, VZV and CMV
Does NOT require viral thymidine kinase activation
Amantadine Prevents viral uncoating Cerebellar dysfunction,
Influenza A coverage Livedo reticularis
Oseltamivir Neuraminidase inhibitor
Drug of choice for influenza
Lamivudine Treatment of hepatitis B infection
Ribavirin Treatment of hepatitis C and RSV infection
Some Important Points about FOScarnet and AMANTADINE

FOScarnet
pyroFOSphate analog
AMANTADINE
A man to dine takes off his coat.
Amantadine prevents uncoating.
Blocks influenza A and rubellA
Causes problems with the cerebellA
Anti-Retroviral Drugs
Nucleoside reverse transcriptase inhibitor (NRTI)
Zidovudine Requires phosphorylation Lactic acidosis
Primary drug for HIV
Prevents vertical transmission of HIV
Non-nucleoside reverse transcriptase inhibitor
Delavirdine (NNRTI) Hepatotoxicity
No phosphorylation required
Indinavir Protease inhibitor Fat redistribution syndrome, hyperlipidemia,
insulin resistance
Enfuvirtide Fusion inhibitor, binds gp41 subunit
Maraviroc Binding inhibitor, CCR5 antagonist
Remembering NNRTIs
Never Ever Deliver Nucleosides
Nevirapine
Efavirenz
Delavirdine
Remembering Protease Inhibitors

All protease inhibitors end with –navir
NAVIR (never) TEASE a PROTEASE
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Anti-Malarial Drugs
Chloroquine Primary drug for malaria Retinal damage, hearing loss
Prevents heme polymerization into hemozoin
Quinine For chloroquine-resistant and severe malaria Hypoglycemia, cinchonism
Drug of choice for pregnant patients with malaria
Primaquine Eradication of hypnozoites of P. vivax and ovale
Mefloquine, Chemoprophylaxis (chloroquine-resistant areas)
Malarone
Doxycycline Chemoprophylaxis (multi-drug resistant areas)
Artemether- Drug of choice for malaria in the Philippines (P. falciparum)
Lumefantrine
Anti-Protozoal Drugs
DRUG REMARKS
Dioxanide Asymptomatic cyst carriers of E. histolytica
furoate
Metronidazole Amoebic dysentery
Trichomoniasis
Bacterial vaginosis
Nitazoxanide Cryptosporidium parvum infection
TMP-SMX Pneumocystis jirovecii pneumonia
Pyrimethamine- Toxoplasmosis
Sulfadiazine
Suramin + African sleeping sickness
Melarsoprol
Nifurtimox Chagas disease
Stibogluconate Leishmaniasis
Anti-Helminthic Drugs
DRUG REMARKS
Mebendazole Inhibits helminthic microtubules
Ovicidal
Inhibits helminthic microtubules
Albendazole Ovicidal and larvicidal
Drug of choice for hydatid disease (echinococcosis)
Diethylcarbamazine Drug of choice for filarial disease and Loa loa
SE: filarial fever
Ivermectin Drug of choice for Strongyloides and Onchocerca
SE: Mazzotti reaction
Pyrantel pamoate Drug of choice for Enterobius infection
Thiabendazole Drug of choice for Trichinosis
Praziquantel Drug of choice for trematodes and cestodes except echinococcosis
Niclosamide Back-up drug to Praziquantel
BASIC BACTERIOLOGY
Steps in Gram Staining (remember V-I-A-S)
STEP PROCEDURE REAGENT
1 Primary stain Crystal Violet
2 Mordant Iodine
3 Decolonizing Agent Acetone
4 Counterstain Safranin
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Atypical Bacteria (based on gram staining)
NAME REASON ALTERNATIVE
Mycobacteria Too much lipid in cell so dye cannot penetrate Acid-fast stain
Spirochetes Too thin to see Dark field microscopy
Mycoplasma No cell wall Non
Use serologic studies
Legionella Poor uptake of counterstain Silver stain
Chlamydiae Intracellular Locate for inclusion bodies
Rickettsiae Intracellular Giemsa/Tissue stains
Generalization in Bacteria
All bacteria have cells compose of peptidoglycan except Mycoplasma pneumoniae
All gram-positive bacteria have NO endotoxin except Listeria monocytogenes
All bacterial capsules are composed of polysaccharide except Bacillus anthracis
All exotoxins are heat-labile except Staphylococcal enterotoxin
Bacterial Oxygen Metabolism

Obligate Aerobes Nocardia, Bacillus cereus, Neisseria, Pseudomonas, Bordetella. Legionella,
Brucella, Mycobacterium
Facultative Anaerobes Staphylococcus, Bacillus anthracis, Corynebacterium, Listeria, Actinomyces,
Mycoplasma
Microaerophiles Streptococcus, spirochetes (Borrelia, Leptospira, Treponema), Campylobacter
Obligate Anaerobes Clostridium, Bacteroides
Bacterial Culture Media

Clostridium perfringens Egg yolk
Corynebacterium diphtheria Tellurite
Group D streptococci Bile esculin
Staphylococcus spp. Mannitol salts
N. meningitides, Chocolate
N. gonorrhoeae from sterile sites
N. gonorrhoeae from nonsterile sites Thayer-Martin
Haemophilus influenzae Chocolate + factors X and V
Mycobacterium tuberculosis Lowenstein-Jensen
Vibrio cholera Thiosulfate citrate bile salts (TCBS)
Bordatella pertussis Bordet-Gengou
Legionella pneumophila Charcoal-yeast extract
Campylobacter jejuni Skirrow
Borrelia burgdorferi Barbour-Stoenner-Kelly (BSK)
Mycoplasma pneumoniae Eaton
Pseudomonas aeruginosa Cetrimide
Salmonella, Shigella Xylose-Lysine-Deoxycholate (XLD)
Leptospira interrogans Ellinghausen-McCullough-Johnson-Harris (EMJH)
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SECTION 7
ALLERGY AND RHEUMATOLOGY
High-Yield Concepts in Basic Immunology
B cell surface marker and EBV receptor CD21 (other B cell markers: CD19 and 20)
Most potent and effective APCs (antigen presenting cells) in the body Dendritic cells
Major receptor for antigen in B cells IgM and IgD
Majority of total serum immunoglobulins, able to cross the placenta IgG
Antibody secreted in mucosal surface as dimer, most produced IgA
antibody overall
First immunoglobulin to appear in the immune response and initial IgM
antibody synthesized by neonates
Protein molecules capable of activating up to 20% of T-cell pool Superantigen
resulting in widespread immune response
Binding of an opsonized target cells to an FC receptor bearing effector ADCC (antibody dependent cellular
cell resulting in the lysis of the target cytotoxicity)
Rapid, first-line immunity involving neutrophils, macrophages, dendritic Innate immunity
and natural killer cells
Learned, high-specific immunity involving T and B cells and antibodies Adaptive immunity
and utilizing memory cells
Expressed in all nucleated cells, presents endogenous intracellular MHC (Major Histocompatibility Complex) 1
antigens to CD8 cytotoxic T-cells
Expressed only on APCs and present exogenous or extracellularly MHC 2
engulfed antigens to CD4 T-helper cells
Involved with MHC1 – activates CD8 and macrophages via IFN-y TH1 (T-Helper 1)
Involved with MHC2 – secretes IL4, 5, 6, 13 recruiting eosinophils TH2 (T-Helper 2)
stimulating antibody production
Release cytotoxic granules (perforin, granzyme) and activates Cytotoxic T cells
apoptosis
Facilitates phagocytosis by coating antigen Opsonins (IgG and C3b)
Acute phase reactants that are increased during inflammation Serum Amyloid A, CRP, Ferritin, Fibrinogen,
Hepcidin
Proteins that are decreased during inflammation Albumin, Transferrin
Classigcal – IgG or IgM mediated
Alternative – Microbial surface proteins Complement Pathways
Lectin – Mannose or other sugars
Complement proteins involved in anaphylaxis (anaphylatoxins) C3a, 4a, 5a
Induces neutrophil chemotaxis C5a
The key effector cell in the biologic response in allergic rhinitis, asthma Mast cells
and anaphylaxis and urticarial
Neutrophil chemotaxis Leukotriene LTB4
Components of Slow Reacting Substance of Anaphylaxis (SRS-A) Leukotriene LTC4, LTD4, LTE4
Most effective means of controlling allergic disease Allergen avoidance
Common Cytokines and Their Function

IL1 Fever, activates osteoclasts
IL2 Stimulates all types of T cells
IL3 Stimulates bone marrow stem cells
IL4 Induces B cell growth and IgE production
IL5 Induces eosinophil growth and IgA production
IL6 Fever, stimulates acute phase proteins
IL8 Major neutrophil chemotactic factor
IL10 Modulates inflammatory response (together with TGF-B)
IL12 Differentiates T cells into TH1; activates NK cells
TNF alpha Stimulates septic shock, vascular leakage, recruitment of
leukocytes
IFN gamma Activates macrophages; increases antigen presentation
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Common Autoantibodies and Associated Diseases
Anti-Ach Receptor MG
Anti-Basement Membrane Goodpasture’s Syndrome
Anti-Glutamate Decarboxylase Type DM
Anti-Jo-1, Anti-SRP, Anti-Mi-2 Dermatomyositis, Polymyositis
Anti-Microsomal, Anti-Thyroglobulin, Anti-TPO (Thyroid Hashimoto’s Thyroiditis
Peroxidase)
Anti-Mitochondrial Primary Biliary Cirrhosis (PBC)
Anti-Smooth Muscles Autoimmune Hepatitis
TSI (TSH-Receptor Stimulating Immunoglobulin), Anti-TPO Graves’ Disease
Anti-U1 RNP (Ribonucleoprotein) Mixed Connective Tissue Disese (MCTD)
Anti-Centromere Limited Scleroderma, CREST Syndrome
Anti-Scl-70, Anti-Topoisomerase 1 Diffuse Syndrome
High-Yield Concepts in Systemic Lupus Erythematosus (SLE)

Female, joint pains, pleural or pericardial effusions,
photosensitive rash, hematuria or proteinuria, oral ulcers, SLE
anemia, leukopenia or thrombocytopenia, seizures or
psychosis, headache, fever, myalgias, autoantibodies
Best screening test for SLE (most sensitive) ANA
SLE-specific antibodies that correlate with level of disease Anti-dsDNA
activity, nephritis and vasculitis
SLE-specific antibodies with no clinical correlations Anti-Sm
Antibodies associated with Sicca syndrome, subacute Anti-Ro (SS-A)
cutaneous lupus, neonatal lupus with congestive heart
block and decreased risk for nephritis
Antibodies in drug-induced lupus Anti-Histone
Antibodies predisposing to recurrent fetal loss, thrombosis, Anti-Phospholipid Antibody
detected by ELISA for Cardiolipin and B2G1 and DRVVT
Most serious manifestation of SLE Nephritis
Immunosuppressive therapy for Class 3 to 5 lupus nephritis Steroids + Cyclophosphamide/Mycophenolate Mofetil
Most common pulmonary manifestation of SLE Pleuritic with or without effusion
Most frequent cardiac manifestation of SLE Pericarditis
Fibrinous vegetations and endocarditis in SLE Libman-Sacks Endocarditis (LSE)
Most frequent hematologic manifestation of SLE Normocytic Normochromic Anemia
Most common manifestation of diffuse CNS lupus Cognitive Dysfunction
Most common chronic dermatitis in SLE Discoid lupus erythematosus
High-Yield Concepts in Rheumatoid Arthritis (RA)

Most common form of chronic inflammatory arthritis RA
Most common cardiac and valvular manifestation in RA Pericarditis and mitral regurgitation
Most common cause of death in patients with RA Cardiovascular disease
Environmental factor most implicated in RA Smoking
Triad of neutropenia, splenomegaly and nodular RA Felty’s Syndrome
Triad of keratoconjunctivitis sicca, xerostomia and RA Sjogren’s syndrome
Length of time for joint symptoms to be suggestive of RA 6 weeks or more
Synovial inflammation and proliferation, focal bone
Pathologic hallmarks of RA erosions, thinning of the articular cartilage and pannus
formation
IgM against the Fc portion of IgG Rheumatoid factor
Serum marker with higher specificity for RA than RF Anti-CCP
Initial radiological finding in RA Juxta-articular osteopenia (other findings: soft tissue
swelling, symmetric joins space loss
Test with greatest sensitivity for detecting synovitis, joint MRI
effusion and early bone and marrow changes in RA
DMARD of choice for RA Methotrexate
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High-Yield Concepts in Osteoarthritis (OA)
Obese, elderly, female complaining of unilateral knee pain OA
exacerbated by exertion and relieved by rest and NSAIDs;
no warmth, no swelling, nor redness; (+) crepitus
Most common type of arthritis OA
2 major factors contributing to the development of OA Joint loading and joint vulnerability
Most potent risk factor for OA Age
Nodes found on the PIP joint in OA Bouchard’s nodes (Mnemonic: B of Bouchard comes first
in the alphabet before H of Heberden’s)
Nodes found on the DIP joint in OA Heberden’s nodes
Fulcrum of the longest lever arm in the body Knee
Radiographic hallmarks of OA Asymmetric joint space narrowing, subchondral sclerosis
and osteophytes
Initial analgesic of choice for OA Acetaminophen or Paracetamol
High-Yield Concepts in Gouty Arthritis and Pseudogout

50 year old alcoholic male patient complaining of severe
joint paint starting last night with noted swelling and Gouty arthritis
redness on his right first metatarsophalangeal (MTP) joint
Inflammation of the first MTP joint in gout Podagra
Needle-shaped crystals that are negatively birefringent
(yellow under parallel light and blue under perpendicular Gouty arthritis
light)
Rhomboid-shaped crystals that are weakly positively Pseudogout
birefringent
Mainstay of treatment during acute attack of gout NSAIDs (Indomethacin)
Conditions leading to overproduction (tumor lysis
syndrome, tophi or chronic gouty arthritis, uric acid stones,
Indications for initiating urate-lowering therapy serum uric acid >9 mg/dl or 535 mmol/l, repeated acute
attacks of gouty arthritis, patient willingness to commit to
long term therapy and not during acute attacks)
Indications for uricosuric agents Under excretors of uric acid (<600 mg in 24 hour urine
sample)
Most commonly used hypouricemic and best drug to use in Allopurinol
urate overproducers, urate stone formers and renal disease
Target therapeutic blood uric acid level for gout Less than or equal to 6 mg/dl
Joint most frequently affected in CPPD or pseudogout Knee
Radiograph findings of punctate or linear radiodense
deposits in fibrocartilaginous joint menisci or articular Chondrocalcinosis
hyaline cartilage suggestive of CPPD
High-Yield Concepts in Psoriatic Arthritis

Arthritis presenting with predominant DIP involvement,
asymmetric or symmetric, involving one or more joints, Psoriatic arthritis
dactylitis, shortening of digits and nail changes with or
without silvery scaly skin lesions
Nail pitting, horizontal ridging, oncholysis, yellowish
Nail changes in psoriasis/psoriatic arthritis discoloration of margins (oil spots), dystrophic thick
subungal hyperkeratosis, salmon patches (nailbed
psoriasis)
Uveitis in psoriatic arthritis Bilateral chronic posterior uveitis
1. Symmetric polyarthritis
5 patters of psoriatic arthritis (from most to least common) 2. Asymmetric oligoarthritis 3. DIP predominance
3. Axial arthropathy
4. Arthritis mutilans
Pencil-in-cup deformity, “whiskering”, small joint ankylosos,
Radiographic characteristics of psoriatic arthritis osteolysis, periostitis, new bone formation, telescoping of
digits
Ideal treatment for psoriatic arthritis Anti-TNF-alpha agents (Infliximab, Adalimumab,
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Golimumab)
High-Yield Concepts in Reactive Arthritis (ReA)

Acute nonpurulent arthritis complicating an infection ReA
elsewhere in the body
Triad of arthritis, urethritis and conjunctivitis Reiter’s syndrome
Common organisms implicated in ReA Shigella, Salmonella, Yersinia, Campylobacter, Chlamydia,
HIV
Initial treatment of choice for ReA Indomethacin and other NSAIDs
High-Yield Concepts in Ankylosing Spondylitis (AS)

Young adult male, insidious onset of dull pain in the lower
lumbar or gluteal region, lumbar morning stiffness lasting a AS
few hours that improves with activity and returns after
inactivity with nocturnal exacerbation
Genetic marker prominent in AS and other HLA-B27
spondylarthropathies (SpA)
Earliest manifestation in AS Sacroiliitis
Inflammation in the fibrocartilaginous regions where a
tendon, ligament or joint capsule attaches to bone Enthesitis
characteristic of SpA
Most common extra-articular manifestation of AS Acute anterior uveitis
First line pharmacologic management for AS NSAIDs
High-Yield Concepts in Infectious Arthritis

Patient with pneumonia presenting with sudden onset
moderate to severe pain on the right knee, with muscle Infectious or septic arthritis
spasm, decreased range of motion, swelling and redness,
high fever, leukocytosis
Most common site of infectious arthritis Knee
Most common route of infection for infectious in all age Hematogenous
groups
Most common etiologic agent for infectious arthritis among Neisseria gonorrhea
young adults and adolescents
Most common nongonococcal cause of infectious arthritis in Staphylococcus aureus
adults of all ages
Most common etiologic agent for infectious arthritis after Staphylococcus aureus
surgery or penetrating injuries
Subset of patients with highest incidence of infectious RA patients
arthritis
Most common presentation of infectious arthritis Monoarthritis
Sites of infectious arthritis common among IV drug abusers Vertebral, sacroiliac and sternoclavicular joints
Other than antibiotics, essential treatment needed for a Timely drainage of pus and necrotic debris
favorable outcome on joint function in infectious arthritis
Late manifestation of congenital syphilis manifesting as
chronic painless synovitis with effusion of large joints, Clutton’s joint
particularly the knees and elbows
Reactive symmetric form of polyarthritis that affects Poncet’s disease
persons with visceral or disseminated tuberculosis
High-Yield Concepts in Vasculitides

Antibodies directed against proteinase-3 detected as cANCA (cytoplasmic anti-neutrophil cytoplasmic
diffuse granular cytoplasmic staining pattern in neutrophils antibodies)
Antibodies directed against myeloperoxidase with pANCA (perinuclear antineutrophil cytoplasmic antibodies)
perinuclear or nuclear staining in neutrophils
First step in the workup of a patient with suspected Exclude other diseases
vasculitis
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Palpable purpura, pulmonary infiltrates, microscopic
Symptoms suggestive of vasculitis hematuria, chronic inflammatory sinusitis, mononeuritis
multiplex, unexplained ischemic events and
glomerulonephritis
Granulomatous necrotizing vasculitis of the triad of upper
and lower respiratory tract and kidney (sinusitis, lung Wegener’s granulomatosis
involvement, glomerulonephritis), (+) cANCA
Non-granulomatous inflammation of small arteries and
veins including venules, glomerulonephritis, usually with no Microscopic polyangitis
upper airway involvement and no pulmonary nodules, (+)
pANCA
Asthma, peripheral and tissue eosinophilia, extravascular
granuloma and vasculitis of multiple organ systems Churg-Strauss
(predominant pulmonary findings)
Necrotizing vasculitis, renal and visceral artery involvement
with aneurysmal dilatations, no pulmonary artery Polyarteritis nodosa
involvement, associated with Hepatitis B
Elderly female presenting with fever, anemia, headaches,
temporal tenderness, jaw claudication, high ESR and Giant cell/temporal arteritis
accompanying stiffness and muscle pains of the neck,
shoulders, hip and thighs
Syndrome characterized by stiffness aching and pain in the
muscles of the neck, shoulders, lower back, hips and thighs Polymyalgia rheumatic
associated with giant cell arteritis
Dreaded complication of giant cell arteritis Ischemic optic neuropathy
Y=young female, systemic symptoms, arm claudication, Takayasu’s arteritis (also known as Aortic Arch Syndrome
diminished pulses on one arm, vasculitis of medium to large or Pulseless Disease)
arteries involving the aortic arch and branches
Child with glomerulonephritis, palpable purpura over the
buttocks and lower extremities, gastrointestinal symptoms, Henoch Schonlein Purpura (HSP)
arthralgias, and history of recent respiratory infection
Most commonly encountered vasculitis in clinical practice Cutaneous vasculitis
So far the most effective therapy for the systemic Cyclophosphamide
vasculitides
Cutaneous vasculitis, arthritis, peripheral neuropathy,
membranoproliferative glomerulonephritis, Hepatitis C, Cryglobulinemic vasculitis
cold-precipitated agglutinins or immunoglobulins
Drugs implicated in vasculitis syndromes Allopurinol, Thiazides, Gold, Sulfonamides, Phenytoin,
Penicillin, Hydralazine, PTU
Other High-Yield Concepts in Rheumatology

Malar rash, Gottron’s papules, erythematous periorbital rash (heliotrope
rash), shawl and face rash, mechanic’s hands, high creatine kinase, (+) Dermatomyositis
ANA, (+) anti-Jo-1, anti-SRP and anti-Mi-2
Calcinosis
Raynaud’s phenomenon CREST Syndrome
Esophageal dysmotility (limited scleroderma)
Sclerodactyl
Telangiectasia
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SECTION 8
HEMATOLOGY
High-Yield Physiology Concepts in Hematology
Sites of hematopoiesis Yolk sac, liver, spleen, bone marrow
Heme precursors Succinyl CoA (TCA intermediate)
Glycine (an amino acid)
Source of energy by the RBC Anaerobic glycolysis (net of 2 ATPs)
Vitamin B12 and folic acid deficiency Megaloblastic anemia
Last stage of RBC with a nucleus Orthochromatic erythroblast
Premature RBCs, increase in hemolysis Reticulocytes
Hemoglobin with 2 alpha chains, 2 beta chains Adult hemoglobin (HbA)
Hemoglobin with 2 alpha chains, 2 gamma chains Fetal hemoglobin (HbF)
Transfers iron in the blood Transferrin
Stores iron in the liver Ferritin
For additional iron storage Hemosiderin
Basophils
Granulocytes Eosinophils
Neutrophils
Release histamine and heparin, involved in allergies Basophils
Increased in allergies and parasitic infections Eosinophils
Involved in bacterial infections; last 8 hours Neutrophils
Osteoclasts (bones)
Kupffer cells (liver)
Tissue macrophages Histiocytes/Langerhans cells (skin)
Microglia (brain)
Alveolar macrophages (lungs)
Derived from megakaryocytes; last 7-10 days Platelets
Requires glycoprotein 1g and von Willebrand Factor Platelet adhesion
Requires glycoprotein IIb-IIIa and fibrinogen Platelet aggregation
Secrete immunoglobulins (Ig) Plasma cells (derived from B cells)
Ig involved in the primary response; largest IgM
Ig involved in the secondary response; smallest (can penetrate placental IgG
barrier)
Ig in secretions (e.g. saliva, Peyer’s patches) IgA
Ig involved in allergies, parasitic infections IgD
MHC I, CD8 T-Killer Cell
MHC II, CD4 T-Helper Cell
Histopathologic Findings in Systemic and Hematologic Diseases

DESCRIPTION MARKER DISEASE
Abnormal azurophilic Toxic granules Severe infection
(primary) granules
Patches of dilated endoplasmic reticulum that appear Dohle bodies Severe infection
as sky blue cytoplasmic puddles
Distinctive needle-like azurophilic granules found in Auer rods Acute Myelogenous Leukemia
myeloblasts
Scattered macrophages with abundant wrinkled green Sea-blue histocytes Chronic Myeloid Leukemia
blue cytoplasm
Small lymphocytes disrupted in the process of making Smudge cells Chronic Lymphoid Leukemia
smears
Large cells with multiple nuclei or a single nucleus with Reed-Sternberg (RS) cells Hodgkin’s lymphoma
multiple lobes
Cells found in adult T-cell lymphoma which appear to Cloverleaf or flower cells Adult T-cell lymphoma
have multi-lobulated nuclei
Destructive plasma cell tumors involving axial skeleton Plasmacytoma Multiple myeloma
Fiery red cytoplasm Flame cells
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Pink globular cytoplasmic inclusions Russell bodies
Blue globular nuclear inclusions Ditcher bodies
M proteins causing RBCs to stick in linear arrays Rouleaux conformation
Erythroblasts with iron-laden mitochondria visible as Ringed sideroblasts Sideroblastic anemia
perinuclear granules
Neutrophils with only two nuclear lobes Pseudo-Pelger-Huet cells Myelodysplastic syndrome
Megakaryocytes with single nuclear lobes or multiple Pawn ball megakaryocytes
separate nuclei Primary myelofibrosis
Premature release of nucleated erythroid and early Leukoerythroblastosis
granulocyte progenitors
Cells that were probably damaged during the birthing Teardrop cells or dacrocytes
process in the fibrotic marrow Langerhans cell histocytosis
Pentalaminar tubules, often with a dilated terminal end Birbeck granules
(tennis racket-like appearance)
Small yellow-brown, brown or rust-colored foci in the Gandy-Gamna nodules Congestion of the spleen
spleen
Hodgkin’s (HL) versus Non-Hodgkin’s Lymphoma (NHL)

HL NHL
Reed-Sternberg cells +
Associated with HIV and immunosuppression +
Multiple peripheral nodes; extranodal involvement +
common, non-contiguous spread
Low-grade fever, night sweats, weight loss +
EBV association; bimodal distribution +
Types of Hodgkin’s Lymphoma

Most common type; lacunar variant RS cells Nodular Sclerosis
Lymphocytes make up the vast majority of cellular infiltrate; mononuclear variant RS Lymphocyte-rich
cells; best prognosis
Relatively good prognosis; contains popcorn cells Lymphocyte predominant
Worst prognosis Lymphocyte-depleted
Types of Non-Hodgkin’s Lymphoma

Most common type Diffuse large B-cell
Translocation on chromosome 8; presents with starry-sky pattern Burkitt’s lymphoma
Biopsy reveals homogenous population of small lymphocytes, does not have Mantle cell lymphoma
centroblasts and proliferation centers
Plasma Cell, Thymus and Spleen Disorders

Excess light or heavy chains along with complete Ig synthesized by neoplastic plasma Bence-Jones proteins
cells
Tumor of the thymus associated with MG and pure red cell aplasia Thymoma
Most important monoclonal gammopathy usually presenting as tumorous masses Multiple myeloma
scattered throughout the skeletal system
Histopathologic Findings in RBC-Related Disorders

DESCRIPTION MARKER ASSOCIATED DISEASE
Small hyperchromic RBC lacking central pallor Spherocytes Hereditary spherocytes
Small dark nuclear remnants in RBCs of asplenic Howell-Jolly bodies Asplenia
patients
Membrane-bound precipitates on denatured globin Heinz bodies
chains G6PD deficiency
RBCs with damaged membranes due to removal of Bite cells
Heinz bodies by splenic macrophages
RBCs shaped like curved blades Sickle cells Sickle cell anemia
Dehydrated RBCs with bull’s eye appearance Target cells (codocytes) Sickle cell anemia
Thalassemia
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Fragmented RBCs; also called helmet cells if cut in half Schistocytes RBC trauma, certain drugs,
HUS
RBCs with spikes Burr cells or echinocytes RBC trauma
High-Yield Concepts in Hemolytic Anemia

Triad of hemolytic anemia Pallor, jaundice and splenomegaly
Differentiates intravascular from extravascular hemolysis Presence of splenomegaly in extravascular hemolysis
Autosomal dominant disorder caused by intrinsic defects in Hereditary Sphetocytosis
the red cell membrane: increased MCHC
X-linked recessive disorder that reduces protection of RBCs G6PD deficiency
from oxidative injuries, leading to hemolysis
Intravascular hemolysis due to increased complement- Paroxysmal Nocturnal Hemoglobinuria
mediated RBC lysis
Hemolytic anemia seen in DIC, TTP-HUS, SLE and Microangiopathic Hemolytic Anemia
malignant hypertension
Caused by trauma to RBCs in individuals with cardiac valve Macroangiopathic Hemolytic Anemia
prosthesis
Summary of Hemolytic Anemia
Hereditary Spherocytosis Intrinsic Extravascular

G6PD Deficiency Intrinsic Intravascular
Sickle Cell Anemia Intrinsic Extravascular
Thalassemia Intrinsic Extravascular
Paroxysmal Nocturnal Hemoglobinuria Intrinsic Intravascular
Autoimmune Hemolytic Anemia Extrinsic Intravascular
Microangiopathic Hemolytic Anemia Extrinsic Intravascular
Macroangiopathic Hemolytic Anemia Extrinsic Intravascular
*Generally, all extrinsic hemolytic anemias are lysed intravascularly. All intrinsic hemolytic anemias are lysed in the spleen
with the exception of G6PD and PNH
Summary of Bleeding Disorders

PLATELET BLEEDING PT PTT
TIME
Ehlers-Danlos Syndrome Normal Normal Normal Normal
Immune Thrombocytopenic Purpura (ITP) Decreased Prolonged Normal Normal
TTP Decreased Prolonged Normal Normal
Bernard-Soulier Syndrome Decreased Prolonged Normal Normal
Glanzmann’s Thromboasthenia Normal Prolonged Normal Normal
Von Willebrand Disease Normal Prolonged Normal Prolonged
Hemophilia Normal Normal Normal Prolonged
Vitamin K Deficiency Normal Normal Prolonged Prolonged
Disseminated Intravascular Coagulation (DIC) Decreased Prolonged Prolonged Prolonged
Anemias of Decreased Erythropoeisis

Megaloblastic Anemia Impairment of DNA synthesis that leads to distinctive
morphologic changes
Iron Deficiency Anemia Most common nutritional disorder in the world
Microcytic hypochromic anemia
Anemia of Chronic Disease Most common cause of anemia among hospitalized patients
Aplastic Anemia Syndrome of chronic primary hematopoietic failure and
attendant pancytopenia
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HEMATOLOGY AND BIOCHEMISTRY CORRELATION
Difference between Hemoglobin and Myoglobin
DESCRIPTION HEMOGLOBIN MYOGLOBIN
Heme-containing + +
Contains fibrous components - -
Level of structure exhibited quaternary Tertiary
Tissues in th body where it is mostly found Blood Heart and muscles
Number of maximum bound oxygen molecules 4 1
Oxygen binding affected by pH and CO2 Yes No
Function in relationship with oxygen O2 transporter O2 reservoir
Has taut and relaxed forms Yes No
Curve exhibited in terms of O2 dissociation Sigmoidal Hyperbolic
High-Yield Concepts about Hemoglobin

Most abundant form in adults Hemoglobin A
Used to determine levels of glucose by non-enzymatic HbA1C1
addition of glucose to hemoglobin
Oxidation of the heme component of hemoglobin to iron Methemoglobin
which cannot bind oxygen
Form of hemoglobin where CO binds tightly but reversibly Carboxyhemoglobin
Tetramer consisting of two alphas and gamma chains Fetal Hemoglobin
Gamma-tetramers in the newborns Hemoglobin Bart’s
Cirrhosis
Clinical syndrome of hemochromatosis Diabetes
Hypogonadism
1Can be used to diagnose T2DM, cut off value is >6.5%
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SECTION 9
ONCOLOGY
High-Yield Concepts in Oncology
Most significant risk factor for cancer Age
overall
Most common cancer worldwide Lung cancer
Second most common cancer Breast cancer
worldwide
Most common cause of cancer death Lung cancer
Growth involved in restraining cell
growth and requiring both alleles to be Tumor suppressor genes
mutated for tumorigenesis
Genesis involved in cellular growth
wherein mutation of one allele may lead Oncogenes
to tumorigenesis
Most effective means of treating cancer Surgery
Deliver of radiation therapy from a Teletherapy
distance
Encapsulated sealed sources of
radiation implanted directly or adjacent Brachytherapy
to tumor
Radionuclides targeted to the site of the Systemic radiation therapy
tumor
Most significant risk factor for head and Alcohol and smoking
neck cancer
Most commonly used treatment for head Chemoradiotherapy
and neck cancers
Most effective drugs against highly Serotonin receptor antagonists (i.e., ondansetron)
emetogenic agents
General Cancer Screening Recommendations for Asymptomatic Average-Risk Patients

SCREENING PROCEDURE RECOMMENDED FREQUENCY
Sigmoidoscopy Adults > 50 years old: screen every 5 years
FOBT (fecal occult blood testing) Adults > 50 years old: screen every year
Colonoscopy Adults > 50 years old: screen every 10 years
Begin 3 yrs after first intercourse or by age 21
Pap smear Done yearly for standard pap smear and every 2 years for liquie-based test
May screen every 2-3 years if last 3 tests are normal
Women >65-70 years old may stop screening if no abnormal pap smears
Mammography Women > 50 years old: screen annually (ACS)
Women 50-74 years old: screen every 2 years (USPSTF)
Men > 50 years old: screen annually
DRE and PSA Men > 45 years old if African-American or with first degree relative <65 years
old with prostate cancer, even younger at age 40 years old if with multiple
relatives with prostate cancer
Most Commonly Used Tumor Markers

hCG (human chorionic gonadotropin) Trophoblastic diseas; gonadal germ cell tumor, choriocarcinoma,
dysgerminoma
Calcitonin Medullary thyroid cancer
Catecholamines Pheochromocytoma
AFP (alpha fetoprotein) Hepatocellular, gonadal cell tumor, yolk sac or endodermal sinus tumor
CEA (carcinoembryonic antigen) Colon, pancreatic, breast, lung and ovarian cancer
Prostatic acid phosphatase, prostate Prostate cancer
specific antigen (PSA)
Neuron-specific enolase Small cell lung cancer, neuroblastoma
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Lactate dehydrogenase (LDH) Lymphoma, Ewing’s sarcoma, dysgerminoma
Monoclonal immunoglobulins Myeloma
CA-125 Ovarian cancer, lymphoma
CA 19-9 Colo, pancreatic, and breast cancer
S-100 Cancers of neural crest origin (melanomas, schwannomas, Langerhans cell
histiocytosis)
Oncogenes and Associated Malignancies

BRAF Melanoma, lung, colorectal cancer
BCR-ABL CML, ALL
BCL-2 Follicular lymphoma
C-myc Burkitt’s lymphoma
L-myc Lung and bladder cancer
N-myc Neuroblastoma, lung cancer
RAS Colon, lung, pancreatic cancer
RET Multiple endocrine neoplasia (MEN) 2A and 2B
Tumor Suppressor Genes and Associated Malignancies

APC Colon cancer (FAP)
BRCA1, BRCA2 Breast and ovarian cancer
DCC Colon cancer
MEN1 MEN 1
NF1, NF2 Neurofibromatosis 1 and 2
p53 (guardian of the genome) Li-Fraumeni Syndrome
Rb Retinoblastoma, osteosarcoma
VHL Von Hippel Lindau Syndrome
WT1, WT2 Wilm’s Tumor
Suspected Carcinogens and Associated Malignancies

Alkylating agents and benzene AML
Aromatic dyes and Schistosoma hematobium Bladder cancer
Asbestos, arsenic Lung cancer, mesothelioma
Epstein-Barr virus Burkitt’s lymphoma, nasopharyngeal cancer
Diethylstilbestrol (DES) Vaginal clear cell cancer (in daughters exposed to it during
fetal development)
HIV Lymphoma, Kaposi’s sarcoma (HHV-8 Virus)
Human Papilloma Virus (HPV) Cervical cancer, head and neck cancer
HTLV-1 Adult T-cell leukemia
UV radiation (sunlight) Skin
Vinyl chloride Liver angiosasrcoma
Smoking Bladder, lung, esophageal, kidney, head and neck and
pancreatic cancers
H. pylori Gastric adenocarcinoma and MALT lymphoma
HBV, HCV, aflatoxin-1, ethanol Hepatocellular carcinoma
High-Yield Concepts in Lung Cancer

Primary cause of lung cancer worldwide Smoking
Types of lung cancer implicated with smoking which tend to Small cell and squamous cell lung cancer
present centrally
Most prevalent type of lung cancer among women, young Adenocarcinoma of the lung
adults and non-smokers presenting peripherally
Subtype of lung adenocarcinoma that grows aking alveoli
without invasion (lepidic growth), may present with classic Bronchioalveolar carcinoma
ground glass appearance on CT
Results from local extension of tumor growing in the apex
involving C8 and T1-T2 nerve roots with shoulder pain Pancoast syndrome or superior sulcus tumor
radiating to the ulnar distribution and Horner’s syndrome
Most common life threatening metabolic complication of Hypercalcemia from ectopic PTH/PTH-related protein
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malignancy associated with squamous cell cancer of the production
lung
Paraneoplastic syndromes associated with small cell lung SIADH, Cushing’s Syndrome, Lambert Eaton Syndrome
cancer
Treatment of choice for small cell lung cancer Chemotherapy
Treatment of choice for early (stage 1 or 2) non-small cell Surgical resection
lung cancer
Location of majority of hamartomas Lungs
High-Yield Concepts in Breast Cancer

Three dates in a women’s life with major impact on breast Age of menarche
cancer risk First full term pregnancy
Age at menopause
Best time for breast examination Days 5-7 of the menstrual cycle
Most important prognostic variable in breast cancer Tumor stage
Hormonal treatment for breast cancer which increases the Selective estrogen receptor modulators (SERM)
risk of endometrial cancer
Treatment that increases breast cancer risk but decreases Oral contraceptive pills
ovarian and endometrial cancer risk
Monoclonal antibody directed against the erb/her2-neu Trastuzumab
receptor used for breast cancers
Premalignant lesion that suggests elevated risk of breast Lobular neoplasia
cancer
High-Yield Concepts in Gastric and Esophageal Cancers

Esophageal cancer related to smoking and alcohol, arising Squamous cell carcinoma
in the middle 1/3
Esophageal cancer related to acid reflux and Barrett’s Adenocarcinoma
esophagus arising in the distal 1/3
Initial symptoms of esophageal cancer in majority of Progressive dysphagia and weight loss
patients
Threshold of dysphagia >60% of esophageal circumference is infiltrated
Type of gastric carcinoma with loss of cell cohesion
developing throughout the stomach resulting to loss of Diffuse type
distensibility (linitis plastic or leather bottle appearance)
Type of gastric carcinoma frequently ulcerative and
involving the antrum and lesser curvature, often initiated by Intestinal type
H. pylori
Low socio-economic class, H. pylori infection, ingestion of
Implicated risk factors for gastric cancer high concentrations of nitrates in preserved foods,
Menetrier’s disease (hypertrophy of rugal folds), blood
group A
Gastric cancer metastatic to the ovary Krukenberg tumor
Gastric cancer metastatic to the periumbilical region Sister Mary Joseph nodes
Gastric cancer metastatic to the peritoneal cul-de-sac Blumer’s nodes
Gastric cancer metastatic to the supraclavicular lymph Virchow’s nodes
nodes
Most common site for hematogenous spread of gastric Liver
cancer
Only chance of cure for gastric cancer Complete surgical removal of the tumpr with resection of
adjacent lymph nodes
Most frequent site of extra-nodal lymphoma Stomach
Primary treatment of gastric lymphoma Eradication of H. pylori
High-Yield Concepts in Colorectal Neoplasms

Characteristics of colonic polyps most associated with Villous sessile adenomatous polyps, >2.5 cm in size
malignancy
Familial autosomal dominant condition with multiple polyps FAP (familial adenomatous polyposis)
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(polyposis coli)
Multiple polyps in the small and large intestines with
osteomas, fibromas and congenital hypertrophy of the Gardner’s Syndrome
retinal pigment epithelium
Multiple polyps in the large intestine with brain tumors Turcot’s Syndrome
Multiple small and large intestinal polyps (hamaromatous/
juvenile), mucocutaneous pigmentation, tumors of the Peutz-Jeghers syndrome
ovary, breast and pancreas
Hereditary autosomal dominant predisposition to colon,
ovarian and endometrial cancers caused by defects in DNA Hereditary nonpolyposis colon cancer (Lynch syndrome)
mismatch repair
Most effective class of agents to reduce the risk of colon Aspirin and NSAIDs
adenomas and carcinomas
Usually non-obstructive, discovered late, with iron- Right-sided colon cancers
deficiency anemia
Usually with obstructive symptoms and apple-core or Left-sided colon cancers
napkin ring deformity on barium studies
Hematochezia, tenesmus, narrowing of stool caliber Rectosigmoid cancers
Period of time when most recurrenecs after surgical Within the first 4 years
resection of large bowel cancer occur
Number of sampled lymph nodes necessary to accurately Minimum of 12 lymph nodes
defin tumor stage during surgery
Most frequent visceral site of metastasis for colon cancer Liver
Backbone chemotherapeutic agent for colon cancer and 5-fluorouracil (5-FU)
acts as a radiosensitizer for treatment of rectal cancer
Major side effect of irinotecan used in FOLFIRI regimen for Diarrhea
colon cancer
Common side effect of oxaliplatin used in FOLFOX regimen Dose-dependent sensory neuropathy
for colon cancer
High-Yield Concepts in Hepatic, Pancreatic and Biliary Malignancies

Most common location of pancreatic cancer Pancreatic head
Most common environmental risk factor for pancreatic Smoking
cancer
Most common physical sign in hepatocellular carcinoma Hepatomegaly
(HCC)
Non-cirrhotic or Child-Pugh A cirrhosis
Candidates for resection in HCC Single lesion
No metastasis
Criteria for orthotopic liver transplant (Milan criteria) Single lesion < 5 cm or < 3 nodules each < 3 cm, no gross
vascular invasion
Variant of HCC associated with younger females, elevated Fibrolamellar HCC
blood neurotensin levels, no cirrhosis
Most common benign liver tumor among women Hemangioma
Benign liver mass associated with contraceptive use, with Adenoma
low potential for malignant change and risk of bleeding
Benign liver mass with characteristic central scar,
hypovascular on arterial phase and hypervascular on Focal nodular hyperplasia
delayed phase CT
Most useful diagnostic tool in differentiating between Triphasic CT scan
benign and malignant liver masses
Mucin-producing adenocarcinomas that arise from the bile
ducts, majority of which are located in the hilar or central Cholangiocarcinoma
area
Nodular tumors arising at the bifurcation of the common bile Klatskin tumors
duct
Adenocarcnimoa arising within 2 cm of the distal end of the Ampullary carcinoma
common bile duct
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Palpable gallbladder associated with obstructive biliary Courvoisier’s sign
malignancy
Standard surgical procedure for pancreatic head and Pylorus preserving pancreaticduodenectomy (modified
uncinate tumors Whipple’s procedure)
High-Yield Concepts in Genitourinary Malignancies

Most common site of malignancy in the urinary tract Urinary bladder
Most common source of gross hematuria Urinary bladder
Most common presentation of bladder, renal pelvis and Painless hematuria
ureteric cancer
Vaccine component used as intravesicular therapy in BCG
bladder cancer
Most common environmental risk factor for bladder and Smoking
renal cell carcinoma
Most common histopathologic type of renal carcinoma Clear cell carcinoma
Hematuria
Classic triad of renal cell carcinoma Abdominal pain
Flank or abdominal mass
Site where most prostate cancers develop Peripheral zone
Predominant therapy to reduce future risk of prostate 5-alpha reductase inhibitors (finasteride/dutasteride)
cancer diagnosis
Free PSA <10%, PSA density >0.15 ng/ml/cm 3
PSA levels suggestive of cancer requiring biopsy PSA levels >4 ng/ml with PSA velocity or rise of >0.75
ng/ml/year
Levels <4 ng/ml with rate of rise >0.5 ng/ml/year
Test to establish prostate cancer diagnosis Transrectal ultrasound-guided needle biopsy
Scoring used to measure histologic aggressiveness of the
dominant and secondary glandular histology of prostate Gleason scoring
cancers
High-Yield Concepts in Soft Tissue Malignancies

Most common site of metastasis of soft tissue sarcomas Lungs
Mainstay of treatment for Ewing’s sarcoma, PNET and Chemotherapy
rhabdomyosarcoma
Most common malignant tumor of bone Plasma cell tumors
Account for majority of bone sarcomas, predominant in
young males, usually occurring on the metaphysis of long Osteosarcoma
bones, distal femur, proximal tibia and humerus
Moth-eaten appearance
Radiographic hallmarks of osteosarcoma Speculated periosteal reaction (sunburst appearance)
Cuff of periosteal new bone formation (Codman’s triangle)
Most important prognostic factor for long-term survival in Response to chemotherapy
osteosarcoma
Site most commonly involved in bone metastasis Vertebrae
High-Yield Concepts on Skin Malignancies

Lack of an endonuclease necessary for thymidine dimer Xeroderma pigmentosa
repair increased susceptibility to skin cancers of all types
One or few small waxy, semitranslucent nodules forming
around a central depression that may be ulcerated, crusted Basal cell carcinoma
or bleeding, edge is rolled or pearly with rodent ulcer, rarely
metastasizes
Most common site of basal cell carcinoma Face/head and neck area
Most common type of basal cell carcinoma Classical or nodular type
Dome-shaped, elevated, hard infiltrating lesion (deeply
nodular), may eventually develop an ulcer, occurs on sun- Squamous cell carcinoma
exposed areas
In situ form of squamous cell carcinoma Bowen’s Disease
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Major risk factor for squamous cell carcinoma of the skin Chronic lung term sun exposure
Known precursor lesion of squamous cell carcinoma of the Actinic keratosis
skin
Most common type of melanoma Superficial spreading
Asymmetry.
Characteristics of a malignant lesion melanoma (versus Border irregularity,
benign nevus) Color variegation,
Diameter >6mm,
ChangE in the lesion
Single greatest determinant of metastasis of melanoma Depth of invasion (Breslow thickness)
Single greatest risk factor for melanoma Personal history of melanoma
Most common type of melanoma in dark-skinned Acral-lentiginous Melanoma
individuals and Asians
Single most important prognostic factor for melanoma Regional lymph node metastasis
Most important determinant of outcome in melanoma Early excision
Primary lesion of erythematous edematous evanescent Wheal
rash
Thickening of skin with accentuation of skin fold markings Lichenification
Loss of epidermis without loss of dermis Erosion
Loss of both epidermis and dermis Ulcer
Common Paraneoplastic Syndromes

PARANEOPLASTIC SYNDROME ASSOCIATEED MALIGNANCY
PTHrP: squamous cell carcinoma (lung, head & neck, skin,
Hypercalcemia breast, GU, GI)
Increased vitamin D: lymphomas
SIADH Small cell carcinoma of the lung, carcinoid tumors, GI, GU,
ovarian cancer
Cushing’s Syndrome Ectopic ACTH: small cell lung cancer, carcinoid, pancreatic
islet cell tumors
Hypoglycemia from IGF-2 excess Mesenchymal tumors, hepatocellular and adrenal
carcinomas
Erythrocytosis Renal and hepatocellular cancer, cerebellar
hemangioblastomas
Trousseau’s Syndrome Pancreatic cancer
(migratory thrombophlebitis)
Myasthenia gravis, pure red cell aplasia Thymoma
Lambert-Eaton myasthenic syndrome (LEMS) Small cell carcinoma of the lung
Common Chemotherapy Drugs: Actions and Adverse Effects

ALKYLATING AGENTS (INTERCALATE DNA: NON-CELL-CYCLE SPECIFIC)
Cyclophosphamide Alopecia, bone marrow toxicity, gonadal failure;
Metabolized to acrolein can cause hemorrhagic cystitis give mesna (antidote)
Cisplatin Ototoxicity, nephrotoxicity, neuropathy give ammifostine (antidote)
Busulfan Pulmonary fibrosis
Nitroureas Neurotoxicity
Oxaliplatin Neurotoxicity
Procarbazine Disulfram-like reaction
ANTITUMOR ANTIBIOTICS (INTERCALATE DNA; NON-CELL-CYCLE SPECIFIC)
Bleomycin Pulmonary fibrosis
Dactinomycin/Actinomycin D Myelosuppression
Doxorubicin/Adriamycin Cardiotoxicity give dexrazoxane (antidote)
ANTIMETABOLITES (INTERFERE WITH DNA SYNTHESIS; S-PHASE SPECIFIC)
Methotrexate Inhibits dihydrofolate reductase Myelosuppression give leucovorin (antidote)
5-FU Inhibits thymidylate synthase Myelosuppression give uridine (antidote)
Azathioprine and 6- Purine analogue Myelosuppression, increased toxicity with intake of
Mercaptopurine (6-MP) allopurinol (because these drugs are metabolized
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by xanthine oxidase)
Cytarabine Pyrimidine analogue Pancytopenia
Hydroxyurea Inhibits ribonucleotide reducatse Myelosuppression, GI upset
MICROTUBULE INHIBITORS (M-PHASE SPECIFIC)
Hyperstabilize polymerized
Taxanes microtubules preventing their Alopecia, hypersensitivity, myelosuppession
break down during anaphase
Attach to B tubulin and inhibit Vinblastine: myelosuppression (Mnemonic: “blast
Vinblastine and Vincristine polymerization the bone marrow”)
Vincristine: neurotoxicity
TOPOISOMERASE INHIBITORS
Etoposide, Teniposide Inhibit topoisomerase II Alopecia, GI irritation, myelosuppession
Irinotecan, Topotecan Inhibit topoisomera I Diarrhea, severe myelosuppression
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SECTION 10
DERMATOLOGY
Erythematous Non-Scaly Papules
Erythematous papules, pustules, cysts, nodules, open and closed comedones on the Acne vulgaris
face, chest and upper back
Comedones (closed:
Primary lesion of acne whiteheads, open: blackheads
black due to oxidation)
Most important consideration before initiating isotretinoin (vitamin A) therapy for severe Rule out pregnancy (isotretinoin
acne is extremely teratogenic)
Erythematous pruritic or painful papules with central punctum Insect bites
Erythematous macules papules more pruritic at night located a the groin, axillae, webs
of fingers, toes, elbows and wrists, other family members with similar lesions Scabies
Imaginary circle intersecting site of involvement in scabies Circle of Hebra
Slightly elevated tortuous lines in the skin with a vesicle or pustule at the end Burrows
containing the mite
Etiologic cause of scabies Sarcoptes scabiei
Intense pruritus of the scalp, posterior cervical lymphadenopathy, excoriations and
erythematous papules at the nape of the neck and retriauricular area secondary Pediculosis capitis
impetigo, nits more common in retroarticular area, common in children
Discrete extremely pruritic erythematous papulovesicles accompanied by prickling Miliaria rubra or prickly heat
burning or tingling, frequently on the antecubital, popliteal, trunk and inframammary (“bungang araw”)
areas, common in hot humid climates
Erythematous Non-Scaly Nodules

Acute, round, tender, circumscribed, perifollicular, erythematous lesion that ends in Furuncle
central suppuration
Refers to two or more confluent furuncles Carbuncle
Refers to inflammation of the follicles resulting to erythematous papules that may Folliculitis
eventually develop pustules
Most common implicated causative agent for the diseases above Staphylococcus aureus
Erythematous Non-Scaly Plaques

Dark-red to purple skin discoloration, dusky with borders not clearly delineated, deeper
tissue involvement, pain out of proportion to he physical findings, rapid progression of Necrotizing fasciitis
lesion, may have crepitus
History of wound or blister, erythematous area with non-distinct borders, warm,
edematous, painful, may have fever, central portion of lesion may become fluctuant Cellulitis
and may rupture and discharge purulent material
Most common portal of entry in the leg for cellulitis Tinea pedis
Erythematous plaque, heat, swelling, highly characteristic raised indurated border, Erysipelas
fever, systemic symptoms
Ill-defined hypopigmented macules and/or plaque, with minimal sensory loss to light Tuberculoid leprosy, mild/early
touch and temperature, low AFB bacterial counts on skin biopsy
Macules, papules, plaques and nodules, nerves are enlarged and tender, progressive Borderline to lepromatous
loss of hair, high AFB bacterial counts, leonine facies leprosy
Loss of eyebrows in leprosy Madarosis
High-Yield Concepts on Eczematous Dermatitis

Erythematous greasy yellow brown scaling on scalp, eyebrows, ears and perinasal Seborrheic dermatitis
areas, dandruff, can spread beyond the hairline to the forehead
Most common location of seborrheic dermatitis Scalp presenting as dandruff
In infants yellow brown scaling on the scalp or seborrheic dermatitis of the scalp Cradle cap
Organism implicated in seborrheic dermatitis Pityrosporum ovale
Pruritic erythematous patches and plaques, scaling, lichenification, on the flexural, Atopic dermatitis
antecubital, popliteal areas in adults and in the face and extensors in infants and
348
children
Linear transverse fold below edge of the lower eyelids Dennie-Morgan folds
Discrete coin-shaped erythematous, edematous vesicular and crusted patches on the Nummular eczema
lower extremities and extensor surfaces of the arms
Dermatitis sudden in onset, no previous history or exposure, symptoms of pain and Irritant contact dermatitis
burning usually from acidic or alkali substances
Most common site of involvement of Irritant Contact Dermatitis Hands
Eczematous eruption following exposure to a known or unknown allergen, usually
appearing first at the site of contact, associated with plants, nickel and other Allergic contact dermatitis
compounds, can form patterns on the skin (i.e. lineal lesions with plant exposure)
Most common cause of allergic contact dermatitis Exposure to plants
Papulosquamous Scaly Diseases

Erythematous papule and plaques covered with silvery scales o elbows, knees, scalp, Psoriasis
with nail pits and other nail changes
Pinpoint bleeding spots from exposure of dermal papillae when scales are scraped off Auspitz sign
in psoriasis
Psoriasis involving the folds, recesses, and flexor areas such as axillae, groin, Inverse psoriasis
inframammary folds
Abrupt eruption of psoriasis lesion following acute infection such as streptococcal Guttate psoriasis
pharyngitis
Circular sharply circumscribed slightly erythematous dry scaly hypopigmented patches Tinea
with advancing scaly border and central clearing producing annular outlines
Most common fungal disease Tinea pedis
Causes majority of tinea pedis Trichophyton rubrum
Infection of the nail plate Onychomycosis
Multiple scale hyper- or hypo-pigmented macules over the chest, back, abdomen and Tine versicolor
proximal extremities
Etiologic cause of Tinea versicolor Malassezia furfur
Classical microscopic finding in Tine versicolor of short, thick fungal hyphae and large Spaghetti and meatballs
numbers of variously sized spores
Salmon-colored macules and papules, collarette of scaling, scales tend to fold along
the long axis of stretch follows skin lines (hanging curtain or “christmas tree” sign), Pityriasis rosea
herald patch
Sexually-Transmitted and Vesiculobullous Diseases

Symmetrical, generalized, maculopapular eruptions, polymorphous, usually over the
face, shoulders, flanks and pamls and soles with scaling, with suggestive sexual Secondary syphilis
history, painless genital ulcer
Popular lesions located on folds of moist skin usually around genitals and anus, may
become hypertrophic, forming soft, red, mushroom-like mass, moist weeping gray Condylomata lata
surface
Most frequent manifestation of orolabial herpes Fever, blister or cold sore
Dew drop on rose petal, teardrop on an erythematous base, starting with macules
progressing to vesicles pustules and crusting, examination of lesions show different Varicella
ages of healing usually starting on the trunk, spreading centripetally outward
Most common complication of varicella Secondary bacterial infection
Erythema, papules and plaques initially, mild pain a few days before, subsequently Herpes zoster
developing vesicles and blisters following a dermatomal distribution, painful
Vesicles on the side and tip of nose, indicative of ophthalmic zoster Hutchinson’s sign
Involvement of the facial and auditory nerves by varicella zoster virus Ramsay-Hunt Syndrome
Large tense blisters on flexor surfaces, groin axillae, and trunk, subepidermal blister, Bullous pemphigoid
anti-hemidesmosome antibodies
Papules, vesicles and pustules with honey-colored crusts Impetigo contagiosa
Variant of impetigo, inadequately treated leading to punched out ulcerative lesions Ecthyma
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High-Yield Concepts on Drug-Induced or –Related Reactions
Blisters, epidermal detachment resulting from epidermal necrosis, targer lesions, dusky Steven Johnson’s Syndrome
purpuric macules with mucosal involvement, <10% body surface area involved
>30% involvement of body surface area Toxic Epidermal Necrolysis
(TEN)
10-30% involvement of body surface area SJS-TEN Overlap
Sulfa drugs, anticonvulsants,
Drugs commonly associated with SJS-TEN nevirapine, allopurinol,
lamotrigine, oxicam NSAIDs
Multiple erythematous plaques with target or iris lesion morphology, usually
precipitated by recent new drug ingestion, often triggered by mycoplasma pneumonia Erythema multiforme
and HSV
Manual pressure to the skin may elicit separation of the epidermis (found in Nikolsky’s sign
staphylococcal scalded skin syndrome, SJS, TEN and pemphigus vulgaris)
Most common pattern of drug-induced reaction Morbilliform or maculopapular
Other Important Skin Diseases and Terminologies

Young children with individual lesions of smooth surfaced, firm, dome-shaped, pearly, Molluscum contagiosum
fleshy papules with central umbilication
Numerous small eosinophilic and basophilic inclusion bodies found in histology of Henderson-Paterson bodies
molluscum contagiosum
Brown-black plaques with adherent greasy scales, stuck on appearance Seborrheic keratosis
Sudden appearance of multiple seborrheic keratoses suggestive of visceral and Sign of Leser Trelat
hematologic malignancy
Erythematous macules and papules, macerated skin areas and satellite lesions, white Candida infection
friable patches on mucosal surfaces, immunocompromised states
Increased thicknes of the stratum corneum Hyperkeratosis
Hyperkeratosis with retention of nuclei in stratum corneum Parakeratosis
Epidermal accumulation of edematous fluid in intracellular space Spongiosis
Process referring to loss of cohesion between epidermal cells Acantholysis
Violaceous flat-topped papules and plaques with gray lines (Wickham’s striae) Lichen planus
Condition in dermatological diseases wherein traumatized areas tend to develop new Koebner phenomenon
lesions (found in verruca and psoriasis)
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SECTION 11
NEUROLOGY
High-Yield Physiology Concepts in Neurology
Found in various sites (e.g. ANS and NMJ), decreased in Huntington’s Acetylcholine (Ach)
dementia and Alzheimer’s dementia
Found in the locus ceruleus of the pons, for arousal/wakefulness Norepinephrine (NE)
Found in the substantial nigra, decreased in Parkinson’s Disease, increased in Dopamine
schizophrenia, for fine-tuning of movements
Found in the median raphe of the brainstem, derived from tryptophan, Serotonin
converted to melatonin, involved in mood and sleep
Mnemonic: “Pare, True Love Does Not
Exist To Me”: Phenylalanine
Derivatives of phenylalanine Tyrosine L-Dopa Dopamine
Norepinephrine Epinephrine
(Thyroxine and Melanin from Tyrosine)
Found in the spinal interneurons, main inhibitory neurotransmitter Glycine
Found in the brain, main inhibitory neurotransmitter, from glutamate GABA
Excitatory neurotransmitter in the CNS Glutamate
Output pathway from reward and punishment centers, lesions here will produce Hippocampus
anterograde amnesia
Helps search memory storehouses, lesions here will produce retrograde Thalamus
amnesia
Waves in the EEG of alert, sleeping and relaxed individuals, respectively Beta waves, Alpha waves, Delta waves
High-Yield Physiology Concepts Relating to Cranial Nerves

Cranial nerve for opening of eyelids, contraction of most EOMs, accommodation CN III (Oculomotor nerve)
and pupillary constriction (miosis)
Cranial nerve for special sensation (taste) of the anterior 2/3 of the tongue CN VII (Facial nerve)
Cranial nerve for general sensation (e.g. pain) of the anterior 2/3 of the tongue CN V (Trigeminal nerve)
Cranial nerve for facial msucles CN VII (Facial nerve)
Cranial nerve for facial sensation and muscles of mastication CN V (Trigeminal nerve)
High-Yield Physiology Concepts Relating to the Autonomous Nervous System

Mydriasis, sweating, increased HR, bronchodilation, GU and GI contraction, uterine
Sympathetic effects relaxation and contraction, vasodilation of the skeletal muscles, vasoconstriction of
the skin and GI tract, ejaculation
Mnemonic: “PLASMA”
Parasympathetic Nervous System Parasympathetic, Long Pre-Ganglionic Tract, Ach used (pre-synaptic), Short Post-
Ganglionic Tract, Muscarinic Receptors, Ach used (post-synaptic)
Alpha-1 (for smooth muscle contraction in sphincters, radial muscles of the iris,
vasoconstriction)
Adrenergic Receptors Alpha-2 (in pre-synaptic terminals),
Beta-1 (heart and kidney),
Beta-2 (for smooth muscle relaxation in bronchiolar muscles, uterus, vasodilation)
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DISEASES OF THE NERVOUS SYSTEM
High-Yield Concepts Related to Headaches
Highly characteristic of posterior fossa brain tumors Vomiting that precedes headache
Dominant symptom in temporal (giant cell) arteritis Headache
Most common primary hadache syndromes Migraine, tension-type headache and cluster headache
Key pathway for pain in migraine Trigeminovascular input from the meningeal vessels
Most disabling headache Migraine
Mainstays of pharmacologic therapy in migraine Judicious use of one or more drugs that are effective in
migraine
Most important factor in selection of the optimal regimen for Severity of the attack
a migraine patient
Most effective drug classes in the treatment of migraine Anti-inflammatory agents 5-HT1B/1D receptor agonists
(triptans), and dopamine receptor antagonists
Most efficacious of the triptans Rizatriptan and eletriptan
Core feature of cluster headache Periodicity
Most satisfactory treatment in cluster headache Administration of drugs to prevent cluster attacks until the
bout is over
Most serious cause of secondary headache Subarachnoid hemorrhage
Classic headache associated with brain tumor Most evident in the morning and improves during the day
High-Yield Concepts Related to CNS Tumors

Preferred diagnostic test for any patient suspected of
having a brain tumor, and should be performed with Cranial MRI
gadolinium contrast administration
The only test necessary to diagnose a brain tumor Neuroimaging
Glucocorticoid of choice for brain tumors because of ts Dexamethasone
relatively low mineralocorticoid activity
Exposure to ionizing radiation: meningiomas, gliomas,
The only established risk factors for primary brain tumors schwannomas
Immunosuppression: primary CNS lymphoma
Most common primary brain tumor of childhood Grade I astrocytomas: pilocytic astrocytomas (WHO grade
I)
Most common primary brain tumor overall Meningiomas
Frequently plays an important role in the pathogenesis of Epstein-Barr Virus (EBV)
HIV-related primary CNS lymphoma
Most common malignant brain tumor of childhood Medulloblastomas
Most common malignant brain tumor overall Grade IV astrocytoma (Glioblastoma)
Meningiomas are most commonly located over the Cerebral convexities
Main differential diagnosis of meningioma Dural metastasis
Most common schwannomas Vestibular schwannomas or acoustic neuromas
Most common site of brain metastases Gray matter-white matter junction
85% of all brain metastases are Suprenetorial
Most common sources of brain metastases Lung and breast cancer
Malignancy with greatest propensity for brain metastasis, Melanoma
found in 80% of patients at autopsy
Malignancies with propensity to metastasize to the dura Prostate and breast cancer
and can mimic meningioma
Arises in prostate and breast cancer, which have strong Spinal cord compression
propensity to metastasize to axial skeleton
Brain metastases are best visualized on ___ where they MRI
appear as well-circumscribed lesions
Cancers with greatest propensity to bleed Melanoma, thyroid, kidney cancer
Most common cause of a hemorrhagic metastasis Lung cancer
Most common among hematologic malignancies to Acute leukemia
metastasize to the subarachnoid space
Solid tumors that most frequently cause leptomeningeal Breast and lung carcinomas and melanoma
metastases
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Definitive method and often considered the gold standard Demonstration of tumor cells in CSF
to diagmose leptomeningeal metastases
CSF cytologic examination is most useful in Hematologic malignancies
Part of the spine affected most commonly in epidural Thoracic spine, followed by the lumbar and then cervical
metastases spine
Presenting symptom of epidural metastasis in virtually all Back pain
patients
Best test for epidural metastasis MRI of the complete spine
Surgical procedure of choice for epidural metastasis Complete removal of the mass, typically anterior to the
spinal canal
Standard treatment for brain metastases Whole-Brain Radiotherapy (WBRT)
Most serious toxicity from radiotherapy as they are often Late delayed toxicity
irreversible
Complication seen most commonly after WBRT Leukoencephalopathy
Second only to myelosuppression as dose-limiting toxicity Neurotoxicity
of chemotherapeutic agents
High-Yield Concepts in CNS Infections

Identify whether an infection predominantly involves the
subarachnoid space (meningitis) or whether there is
First task in the approach to CNS infection evidence of either generalized or focal involvement of brain
tissue in the cerebral hemispheres, cerebellum or
brainstem
Encephalitis Brain tissue is directly injured by a viral infection
Classic clinical triad of meningitis Fever, headaches and nucal rigidity
Classic clinical triad of brain abscess Headache, fever, focal neurologic deficit (present in <50%)
Cerebritis Non-encapsulated brain abscess
Pathognomonic sign of meningeal irritation and is present Nuchal rigidity (“stiff neck”)
when neck resists passive flexion
Most common form of suppurative CNS infection Bacterial meningitis
Most common cause of meningitis in adults >20 years S. pneumoniae
Important clue to diagnosis of meningococcal infection Petechial or purpuric skin lesions
Most disastrous complication of increased ICP Cerebral herniation
Most common etiologic organisms of community-acquired S. pneumoniae and N. meningitides
bacterial meningitis
Most important agents in acute viral meningitis Enteroviruses, HSV type 2, HIV, arboviruses
Most common symptom of brain abscess Headache
Optimal therapy for brain abscess Combination of high dose parenteral antibiotics and
neurosurgical drainage
High-Yield Concepts Related to Seizures

Paroxysmal event due to abnormal excessive or Seizure
synchronous neuronal activity in the brain
Condition where a person has recurrent seizures die to
underlying causes not associated with structural brain Epilepsy
damage
1. Multiple seizure types (usually generalized tonic-clonic,
atonic and atypical absence seizures)
Triad of Lennox-Gastaut Syndrome 2. EEG showing slow (<3 Hz) spike-and-wave discharges
and a variety of other abnormalities
3. Impaired cognitive function in most but not all cases
Highest incidence of seizures Early childhood and late adulthood
First clue of typical absence seizures Daydreaming and a decline in school performance
recognized by the teacher
Generalized, symmetric, 3-Hz spike-and-wave discharge
Electrophysiologic hallmark of typical absence seizures that beings and ends abruptly, superimposed on a normal
EEG background
Main seizure type in 10% of all persons with epilepsy Generalized tonic-clonic seizures
353
Most common seizure type resulting from metabolic Generalized tonic-clonic seizures
derangements
Pathologic myoclonus is most commonly see in association Metabolic disorders
with Degenerative CNS diseases
Anoxic brain injury
Most common syndrome associated with focal seizures Mesial Temporal Lobe Epilepsy Syndrome
with dyscognitive features
Most common seizures arising in late infancy and early Febrile seizures
childhood
First goal in the approack to seizure Determine if event was truly a seizure
Best initial choice for the treatment of primary generalized Valproic acid
tonic-clonic seizures Lamotrigine
Drug of choice in patients wiith generalized epilepsy Valproic acid
syndromes having mixed seizure types
Key determinants in initiation and monitoring of therapy Clinical meaures of seizure frequency and presence of side
effects, not the laboratory values
Most recurrences of seizures occur in the First 3 months after discontinuing therapy
Most common surgical procedure for patients with temporal Resection of the anteromedial temporal lobe (temporal
lobe epilepsy lobectomy) or a more limited removal of the underlying
hippocampus and amygdala (amygdalohippocampectomy)
High-Yield Concepts Related to Cerebrovascular Diseases

Requires that all neurologic signs and symptoms resolve within 24 hours (most
last <1 hr) regardless of whether there is an imaging evidence of new Transient Ischemic Response (TIA)
permanent brain injury
Occurred if the neurlogic signs last for more than 24 hours Stroke
Tissue surrounding the core region of infarction is ischemic but reversibly Ischemic Penumbra
dysfunctional
Refers to infarction following atherothrombotic or liphyalinotic occlusion of a Lacunar Infarction
small artert (30-300 um)
Decrease in cerebral blood flow to zero causes death of brain tissue within 4-10 minutes
Most common cause of cerebral embolism overall Nonrheumatic atrial fibrillation
Most common source of artery to artery embolism Carotid bifurcation atherosclerosis
Atherosclerosis within the carotid artery occurs most frequently within Common carotid bifurcation and
proximal internal carotid artery
Herald a small-vessel infarct Transient symptoms (small vessel TIA)
Most significant risk factor of stroke and TIA Hypertension
Only antiplatelet agent that has proven effective for the acute treatment of Aspirin
ischemic stroke
Principal side effect of dipyrimadole Headache
Within 2 weeks of symptom onset
Endarterectomy for carotid atherosclerosis is most benefical when performed (benefit is more pronounced in men
>75 years)
Sudden onset of bilateral signs,
Hallmark on top of the basilar artery occlusion including ptosis, papillary asymmetryor
lack of reaction to light and
somnolence
Imaging modality of choice in patients with acute stroke to rule out bleed Plain cranial CT
Gold standard for identifiying and quantifying atherosclerotic stenosis of arteries Conventional x-ray cerebral
angiography
Bleeding into subdural and epidural spaces is principally produced by Trauma
Most common sites of hypertensive intraparenchymal hemorrhage Basal ganglia (especially putamen),
thalamus, cerebellum, pons
Most common site of hypertensive hemorrhage Putamen (Sentinel) sign: contralateral
hemiparesis
Most common cause of lobar hemorrhage in the elderly Cerebral amyloid angiopathy
Most common metastatic tumors associated with intracerebral hemorrhage Choriocarcinoma
Malignant melanoma
354
Renal cell carcinonma
Bronchogenic carcinoma
Most cerebellar hematomas of this diameter will require surgical evacuation >3 cm in diameter
High-Yield Concepts Related to Nerve Disorders

Most common cause of peripheral neuropathy in developed countries DM
Most common diabetic mononeuropathies Median neuropathy at the wrist and
ulnar neuropathy at the elbow
Seventh nerve palsy, followed by third
Most common cranial mononeuropathies in DM nerve, sixth nerve and, less frequently,
fourth nerve palsies
Most common cranial nerve involved in scleroderma Trigeminal nerve
Most common cranial nerve involved in sarcoidosis Seventh nerve
Most common mononeuropathoes in uremia Carpal tunnel syndrome
Most common form of peripheral neuropathy associated with HIV infection & Distal symmetric polyneuropathy
usually seen in patients with AIDS
Most common associated malignancy with neuropathies Lung cancer
Most common causes of acute generalized weakness leading to admission to GBS and MG
ICU
Manifests as a rapidly evolving arefexlic motor paralysis with or without sensory
disturbance, associated with Campylobacter jejuni found in undercooked Guillain Barre Syndorme (GBS)
chicken
Neuromuscular disorder characterized by weakness and fatigability of skeletal Myasthenia Gravis (MG)
muscles
High-Yield Concepts Related to Movement Disorders

Most common form of Parkinson Parkinson’s Disease (PD)
Most common cause of Familial PD Mutations of the LRRK2 gene
Most common cause of secondary Parkinsonism Dopamine blocking agents
Most significant pathogenic mechanism in Parkinsonism Protein misfolding & accumulation and
mitochondrial dysfunction
Mainstay of therapy for PD Levodopa-carbidopa
Major clinical effect of central-acting anticholinergic drugs Tremors
Most widely used antidyskinesia agent in patients with advanced PD and the
only oral agent that has beeb demonstrated in controlled studies to reduce Amantadine
dyskinesia
Most common cause of nursing home placement in PD patients Dementia
Most common movement disorder Essential tremor
Major differentials for tremors Dystonic tremor or PD
Standard drug therapies for essential tremors β-blockers or primidone
Most common forms of dystonia Focal dystonia
Most commonly seen with neuroleptic drugs or after chronic levodopa treatment Drug-induced dystonia
in PD patients
Most common systemic disorder that causes chorea SLE
Most common acute hyperkinetic drug reaction Dystonia
Most common subacute drug reaction Akathisia
Gold standard for diagnosis of Wilson’s disease Liver biopsy
Most common psychogenic movement disorder Tremor affecting the upper limbs
355
NERVOUS SYSTEM PHARMACOLOGY
Sedative Hypnotics
Midazolam Used in acute anxiety attacks, anesthesia induction, preoperative sedation
Diazepam Used in seizure disorders (status epilepticus), alcohol withdrawal, tranquilizer
Flunitrazepam Date-rape drug
Flumazenil Antidote to benzodiazepine overdose
Thiopental Used in anesthesia induction, Lethal injection, Truth serum
Phenobarbital Used in seizure disorders in children, can precipitate porphyria, potent inducer of CYP450
GABA receptor effects

FREnzodiazepines: FREquency
BarbiDURATes: DURATion
zzZZzzZZzzZZzz (sleep)
Zolpidem, Zaleplon = Zleep disorders
Buspirone for Busy People

(Always Anxious)
BuSPirone like your BenzodiazeSePine
Sedative-hypnotic poisoning
Hot Hot Hot DeCiSioN!
Hypothermia
Hypotension
Hypoactive BS
Disinhibition
Coma
Nystagmus
Alcohols
Ethanol Most frequently abused drug, causes Wernicke-Korsakoff syndrome in overdose and delirium
tremens in withdrawal
Thiamine Used for prevention of Wernicke-Korsakoff syndrome
Diazepam Used for treatment of alcohol withdrawal
Methanol Wood alcohol, causes visual dysfunction due to formaldehde accumulation
Ethylene glycol Found in antifreeze, causes nephrotoxicity due to oxalic acid accumulation
Fomepizole Alcohol dehydrogenase inhibitor
Disulfiram Aldehyde dehydrogenase inhibitor
Drugs Causing Disulfiram-like Reactions

Clara took the Pre-Medical Test in the PM
Chlorpropamide
CefoPerazone
CefaMandole
CefoTetan
Procarbazine
Metronidazole
Anti-Seizure Medications
SEIZURE TYPE DRUGS OF CHOICE ALTERNATIVE DRUGS
Valproic Acid Phenobarbital, Lamotrigine,
Generalized Tonic-Clonic Seizures Phenytoin Topiramate
Carbamazepine
Carbamazepine Felbamate, Phenobarbital,
Partial Seizures Lamotrigine Topiramate, Valproic Acid
Phenytoin
Absence Seizures Ethosuximide Lamotrigine, Levetiracetam,
Valproic Acid Zonisamide, Clonazepam
356
Myoclonic and Atypical Absence Valproic Acid Clonazepam, Levetiracetam,
Syndromes Topiramate, Zonisamide, Felbamate
Lorazepam
Status Epilepticus Diazepam
Phenytoin
Phenobarbital
357

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CHAPTER 1

II. HISTORY AND PHYSICAL EXAMINATION

III. WRITING THE ORDERS

The orders for the patient usually contain the following:

Dx: Chest X-Ray (PA and lateral views)

Monitor VS q4 with temp and O2 sat

IV. PRESENTING THE CASE

E. Case summary – two or three sentences

H. Entertain clarifications or questions from the audience

II. THE P-QRST WAVES, SEGMENTS AND THE CARDIAC CYCLE

Step 1: Determine rate

STEP 1: DETERMINE HEART RATE

Heart Rate = # of QRS complexes within 30 large boxes x 10

STEP 1: DETERMINE RHYTHM

Sinus Tachycardia and Bradycardia

Wave/Interval Description Normal Values

Corrected QT-interval (QTc) using the Bazett’s formula

STEP 4: DETERMINE AXIS

INTERPRETATION LEAD I LEAD aVF

STEP 5: LOOK FOR CHAMBER ENLARGEMENTS

SOKOLOW-LYON CRITERIA CORNELL CRITERIA

[S in V1] + [R in V5 or v6] > 35 mm (>35 small boxes) S in V3 + R in aVL:

C. Right Ventricular Hypertrophy (RVH)

Pacemaker: AV junction with a ventricular rate of 40 to 60 bpm

Pacemaker: Hiis-Purkinje system (HPS) with a ventricular rate between 15 to 40 bpm

Temporary cessation of sinus node activity

B. Sinus Exit Block

Failure of impulse transmission

ATRIOVENTRICULAR (AV) BLOCKS

B. Second Degree AV Block, Mobitz Type I (Wenckebach)

D. High Grade AV Block

2 out of every 3 or more

E. Third Degree (Complete) AV Block

P and QRS waves occur

B. Atrial Fibrillation (AF)

Rate: Fast; Irregular

SUPRAVENTRICULAR TACHYCARDIA (SVT)

Arrhythmia has such a

Atrioventricular Nodal Reentrant Tachycardia (AVNRT)

Most common form of

Trigeminy: PVC occurs after every 2 sinus beats

B. Ventricular Tachycardia (VT)

a. Sustained: ventricular tachycardia that lasts for more than 30 seconds

B. Atrial Paced Rhythm

C. Dual Pacemaker (Atrial and Ventricular)

Findings suggestive of ischemia(should be in 2 or The Contiguous Leads

Significant ST elevation:manifestation of myocardial necrosis; the earliest sign of acute infarction

Indicate myocardial necrosis

C. Classification as to Timing of Myocardial Infarction

CLASSIFICATION TIMING ECG FINDINGS

D. Posterior LV wall involvement

Beat to beat variation in the QRS amplitude

BUNDLE BRANCH BLOCKS

QRS duration >0.12 sec (complete LBBB)

B. Right Bundle Branch Block (RBBB)

QRS duration >0.12 sec (complete RBBB)

WOLFF PARKINSON WHITE (WPW) PATTERN

Pre-excitation pattern: atrial impulse activates the

ARRHYTHMOGENIC RV DYSPLASIA (ARVD)