Acute Renal failure

- Regardless of their origin, all forms of acute renal failure, if untreated, result in
acute tubular necrosis, with sloughing of cells that make up the renal tubule.
- Reversibility: Depending on the timing of intervention between onset of initial
injury & eventual acute tubular necrosis, ARF may be irreversible or reversible,
with either prevention of or recovery from acute tubular necrosis.
- Theories of ARF is either a tubular or vascular basis :

- Tubular theory (tubular occlusion): occlusion of the tubular lumen with cellular debris forms a cast that increases
intratubular pressure sufficiently to offset Renal Perfusion Pressure and decrease or abolish Net Filtration Pressure.
- Vascular theories (Vascular hypoperfusion):
hypoperfusion) decreased Renal Perfusion Pressure ressure from the combination of:
of
afferent arteriolar vasoconstriction AND efferent arteriolar vasodilation
reduces Glomerular Perfusion Pressure
ressure and therefore, Glomerular Filtration Rate.
--------------------------------------------------------------------------
- Studies suggest that one consequence of hypoxia is disordered adhesion of renal tubular epithelial cells resulting
both in their : exfoliation and subsequent adhesion to other cells of the tubule, thereby contributing to tubular obstruction.
obstruction
- Renal damage (whether
whether caused by tubular occlusion
occl or vascular hypoperfusion) is potentiated by the hypoxic state of the
renal medulla, which increases the risk of ischemia (Table 16-6).

Table 16-6.
6. Agents and events that ameliorate or exacerbate hypoxia in the renal medulla

Ameliorating effect Exacerbating effect

Decreased tubular transport Polyene antibiotics (eg, amphotericin B)
Decreased glomerular filtration rate Renal hypertrophy
Prostaglandin E2 inflammatory drugs
Nonsteroidal anti-inflammatory
Adenosine Angiotensin II
Bradykinin Calcium
Nitric oxide Myoglobin
Radiographic contrast agents
- Acute Tubular Necrosis Caused by Severe Renal Ischemia. (circulatory shock is commonest causes of pre-renal failure above)
• If the ischemia is :
1- Severe enough to seriously impair the delivery of nutrients and oxygen to the renal tubular epithelial cells.
2- Insult is prolonged,
damage or eventual destruction of the epithelial cells can occur when this happens, tubular cells “slough off”
and plug many of the nephrons so that there is no urine output from the blocked nephrons;
N.B. the affected nephrons often fail to excrete urine even when renal blood flow is restored to normal, as long as the tubules remain plugged.

- Research has implicated cytokines & endogenous peptides such as endothelins and the regulation of their production as
possible explanations for : why, subjected to the same toxic insult, some patients develop acute renal failure and others do
not and why some with acute renal failure recover and others do not ?

It appears that these products together with activation of complement & neutrophils increase vasoconstriction in the
already ischemic renal medulla and in that way exacerbate the degree of hypoxic injury that occurs in acute renal failure.

Clinical Manifestations :
Retention in :
a- Blood and extracellular fluid of water water & salt overload leading to :
- Hypertension
- HF due to volume overload : dyspnea, orthopnea, crackles, prominent 3rd heart sound (S3) & peripheral edema.
- In the most severe cases of acute renal failure, complete anuria occurs The pa8ent will die in 8 to 14
days unless kidney function is restored or unless an artificial kidney is used

b- Waste products of metabolism Uremia :

- Altered mental status reflects the toxic effect of uremia on the brain
- Check other symptoms of uremia in last page.

c- Electrolytes hyperkalemia :
- More serious threat to patients with ARF / more than about 8 mEq/L (only twice normal) can be fatal.

d- Hydrogen ions Metabolic acidosis :

- Because the kidneys are also unable to excrete sufficient hydrogen ions, patients with ARF develop
metabolic acidosis,
- Acidosis itself:
• can be lethal ( if < 6.8 )
• can aggravate the hyperkalemia, by :
1- Loss of K from cells in exchange with H ions.
2- Acidosis reduce the activity of the sodium-potassium adenosine triphosphatase (ATPase) pump (Mechanism
of K secretion & Na reabsorption by the principal cells of the late distal and collecting tubules) This in
turn decreases cellular uptake of potassium & raises extracellular potassium concentration.

The clinical manifestations of acute renal failure depend not only on the cause BUT also on the stage in the natural
history of the disease at which the patient comes to medical attention :

Prerenal azotemia Acute tubular necrosis

- Patients with renal hypoperfusion (prerenal causes) decreased GFR first develop prerenal azotemia (elevated
BUN without tubular necrosis) :
• With appropriate treatment, renal perfusion can typically be improved :
- Prerenal azotemia can be reversed, and the development of acute tubular necrosis can be prevented.
• Without treatment, prerenal azotemia may progress to acute tubular necrosis.
- Recovery from acute tubular necrosis, if it occurs, will then follow a more protracted course, often
requiring supportive dialysis before adequate renal function is regained.

A variety of clinical tests can help determine whether a patient with signs of acute renal failure is :
- in the early phase of prerenal azotemia or
- has progressed to full-blown acute tubular necrosis
 1- Ra3o of BUN to serum crea3nine : ( Normally 10-1510 :1)
- The earliest manifestation of prerenal azotemia is an - If the patient proceeds to acute tubular necrosis:
elevated ratio of BUN to serum creatinine. • Ratio
atio may return to normal
• Ra8o may rise to 20-30:1 • but with a progressively elevated serum creatinine.
creat
• with a normal or near-normal
normal serum creatinine.
A fluctuating but not inexorably rising serum creatinine
suggests prerenal azotemia

2- Urine analysis :

A- There are no typical abnormal findings. A- Abnormal findings revealed :

- granular casts
- tubular epithelial cells
- epithelial cell casts

Casts are formed when debris in the renal tubules (protein,

red cells, or epithelial cells) takes on the cylindric, smooth-
smooth
bordered shape of the tubule.

B- Because
ecause hypovolemia is a stimulus to ADH release B- However, with progression to acute tubular necrosis,
the urine is maximally concentrated (up to 1500 the ability to generate a concentrated urine is largely lost.
mOsm/L) in prerenal azotemia. Thus, a urine osmolality of less than 350 mOsm/L is a
typical finding in acute tubular necrosis.

3- Fractional excretion of Na+ :

- is an important indicator in oliguric acute renal failure to

In simple prerenal azotemia : With progression to acute tubular necrosis :

more than 99% of filtered Na+ is reabsorbed. this ability of the kidney to retain sodium avidly is
generally lost.
This value allows accurate identification of Na+ retention
states (such as prerenal azotemia) even when there is
water retention as a result of vasopressin release.

Table 16-7. Causes of acute renal failure in which FENa+ may be below 1%
Prerenal disease
Acute tubular necrosis
- 10% of nonoliguric cases
- Superimposed upon chronic prerenal state
Hepatic cirrhosis
Heart failure
Severe burns
- Myoglobinuria or hemoglobinuria
- Radiocontrast media
Sepsis
- Acute glomerulonephritis or vasculitis
- Acute obstructive uropathy
- Acute interstitial nephritis
 Chronic Renal failure

Etiology :
• The most common causes of chronic renal failure are:
1- Diabetes mellitus
2- Hypertension
3- Glomerulonephritis

Pathogenesis of Development of Chronic Renal Failure :

The pathogenesis of acute renal disease is very different from that of chronic renal disease.
- Acute injury to the kidney results in death and sloughing of tubular epithelial cells, often followed by their regeneration
with reestablishment of normal architecture.
- Chronic injury to the kidney results in irreversible loss of nephrons :
• As a result of Irreversible loss of nephrons a greater functional burden is borne by fewer nephrons,
nephrons manifested as:
1- Increase in Glomerular Filtration
iltration Pressure and
2- Hyperfiltration (which can be thought of as a form of "hypertension" at the level of the individual nephron)

• This compensatory hyperfiltration predisposes to:

to
- Increased pressure and stretch of the remaining nephrons especially the glomeruli, which occurs as a result of
functional vasodilation or increased blood pressure;
arterioles and glomeruli lead to fibrosis and scarring
- Chronic increase in pressure and stretch of the small arterioles
(glomerular sclerosis) rate of nephron destruction and loss increases further adaptive changes in the
remaining nephrons slowly progressing vicious circle that eventually terminates in end-stage renal disease

Complex
omplex of symptoms and signs that occurs when residual renal function is inadequate (less than 20-25
20 %)
further loss of nephrons to the point where the person must be placed on dialysis treatment or transplanted with a
functional kidney to survive. This condition is referred to as end-stage renal disease.
• When GFR is further reduced, leaving only about 20% of initial renal capacity :
- some degree of azotemia (elevation of blood levels of products normally excreted by the kidneys) is observed.
- Nevertheless, patients may be largely asymptomatic because a new steady state is achieved in which blood
levels of these products are not high enough to cause overt toxicity.
Precipitating factors : because patients with this level of GFR have little functional reserve, they easily become uremic with :
1- Any
ny added stress (eg, infection, obstruction, dehydration, or nephrotoxic drugs) or
2- with any catabolic state associated
ociated with increased turnover of nitrogen-containing
taining p
products with reduction in GFR.
The pathogenesis of chronic renal failure derives in part from a combination of the toxic effects of
1- Retained products normally excreted by the kidneys (eg, nitrogen-containing products of protein metabolism)
2- Normal products such as hormones now present in increased amounts,
3- Loss of normal products of the kidney (eg, loss of erythropoietin).
4- Excretory failure results also in 1- fluid shifts, with increased intracellular Na+ and water 2- decreased intracellular K+.

Clinical Manifestations
Na+ balance & volume status :
A) Loss of the renal route of salt & water excretion Na+ & water excess .
+
- Continued excessive Na ingestion contributes to :
1- Congestive heart failure
2- Hypertension
3- Ascites
4- Peripheral edema
5- Weight gain.
- Excessive water ingestion contributes to: hyponatremia.

Recommendation for the patient with chronic renal failure:

• Avoid excess salt intake
• Restrict fluid intake so that it equals urine output plus 500 mL (insensible losses).
• Further adjustments in volume is either by 1- use of diuretics (in a patient who still makes urine) or 2- dialysis.

B) Loss of renal salt & water conservation mechanisms they are more sensitive than normal to sudden
extrarenal Na+ and water losses (eg, vomiting, diarrhea, and increased sweating with fever).
- Under these circumstances, they more easily develop ECF depletion further deterioration of renal function (which
may not be reversible) vascular collapse & shock.
- Symptoms suggestive of progression of volume depletion :
1- dry mucous membranes,
2- dizziness,
3- syncope,
4- tachycardia
5- decreased jugular venous filling,
6- suggest progression of volume depletion.

K+ Balance : depending on GFR :

- GFR Below 5 ml/min Hyperkalemia especially pa8ents whose GFR has fallen below 5 mL/min.
• Chronic renal failure patients are at greater risk of hyperkalemia in the face of sudden loads of K from either:
+

1- endogenous sources (eg, hemolysis, infection, trauma) or

+ +
2- exogenous sources (eg, stored blood, K -rich foods, or K -containing medications).

- GFR is between 50 - 5 mL/min compensated by increased aldosterone-mediated K+ transport in the distal tubule.
- Treatment with:
1- K+-sparing diuretics may impair aldosterone-mediated K+ transport can therefore, precipitate dangerous
2- ACE inhibitors hyperkalemia in a patient with chronic renal failure.
3- Alpha-blockers

Patients with diabetes mellitus (the leading cause of chronic renal failure) may have a syndrome of
hyporeninemic hypoaldosteronism (syndrome termed type 4 renal tubular acidosis) is a condition in which lack
of renin production by the kidney diminishes the levels of angiotensin II therefore, impairs aldosterone
secretion patients are unable to compensate for falling GFR by enhancing their aldosterone-mediated K+
transport manifested as extreme hyperkalemia even before GFR has fallen below 5 mL/min.
METABOLIC ACIDOSIS :
- Causes:
iminished capacity to excrete acid
1- Diminished
2- Diminished capacity to generate buffers
- In most cases when the GFR is above 20 mL/min only moderate acidosis develops
ops before reestablishment of a
new steady state of buffer production and consumption.
- Treatment:
The fall in blood can be corrected with 20-30
20 mmol (2-3
3 g) of sodium bicarbonate by mouth daily.

MINERAL AND BONE

1- Decreased renal biosynthetic function :

- Vitamin D must be converted by a two-stage
two process ( first in the liver / second in the kidneys, into 1,25
dihydroxycholecalciferol ) before it is able to promote calcium absorption from the intestine.
- Chronic renal failure reduces the blood concentration of active vitamin D decreases intestinal absorption of
calcium decreases availability of calcium to the bones.

2- Decrease renal excretory function (as a result of decreased GFR ) :

a- Rise in serum phosphate concentration :
- This rise in serum phosphate causes increased binding of phosphate with calcium in the plasma thus
decreasing the plasma serum ionized calcium concentration in turn stimulates PTH secretion (2ry
hyperparathyroidism) stimulate ostoclast activity leading to :
1- Remodeling & redistribution of bone ( Osteosclerosis ).
2- Osteitis cystic fibrosa.
a- Metabolic acidosis :
- Causes dissolution of bone buffers ( Ca gluconate ).

b- Retention of Toxic metabolites ( as Aluminum toxicity ) : leading to :

1- Protein calorie malnutrition.
2- Decreased responsiveness of bone to 1.25 (OH)2D3.
Cardiovascular and Pulmonary abnormalities :
1- Volume & salt overload , result in :
a- Congestive heart failure
b- pulmonary edema
c- Hypertension
2- Increased permeability of the alveolar capillary membrane (poorly understood syndrome) result in :
a- pulmonary edema , even with normal or only slightly elevated pulmonary capillary wedge pressures.
3- Hyporeninemic hypoaldosteronism (type 4 renal tubular acidosis) :
a- Failing kidney to overproduce renin elevate systemic blood pressure.
4- Uremic toxins :
a- result in irritation & inflammation of the pericardium (Pericarditis).
5- Cardiovascular risk factors in these patients include: (leading cause of mortality)
a- Hypertension,
b- Hyperlipidemia
c- glucose intolerance
d- chronic elevated cardiac output
e- valvular & myocardial calcification as a consequence of elevated Ca2+— PO4
It results in :
1- myocardial infarction, 2- Stroke 3- Peripheral vascular disease.

Hematological Abnormalities :
A- Abnormalities in red blood cell count:
• Cause of abnormality :
1- Lack of production of erythropoietin loss of its stimulatory effect on erythropoiesis
Patient shows a dramatic improvement in hematocrit when treated with erythropoietin (epoetin alfa).
2- Additional causes of anemia :
- Uremic toxins bone marrow suppression
- Elevated blood PTH bone marrow fibrosis
- Toxic effects of aluminum (from either 1- decrease renal excretion or 2- dialysis solutions)
- Hemolysis and GI blood loss related to dialysis (while the patient is anticoagulated with heparin).
• Manifested by :
- Normochromic, normocytic anemia ( Symptoms of anemia ).
- Hematocrits typically in the range of 20-25%, is a consistent feature

B- White blood cell function: (immunosuppressive)

• Cause of abnormality :
- Leukocyte suppression by uremic toxins.
The suppression seems to be greater for lymphoid cells than neutrophils and seems also to affect :
a- chemotaxis,
Other causes of immunosupression :
b- acute inflammatory response,
1- Acidosis,
c- delayed hypersensitivity more than other leukocyte functions. 2- hyperglycemia,
• Manifested by : 3- malnutrition,
- Uremia is associated with increased susceptibility to infections 4- hyperosmolality

C- Clotting parameters.
• Laboratory abnormalities : (none of which are reversible even in well-dialyzed patients)
- Prolonged bleeding time,
- Decreased platelet factor III, abnormal platelet aggregation and adhesiveness,
- impaired prothrombin consumption.

• Manifested by : Patients with chronic renal failure display abnormal hemostasis manifested as
- Increased bruising,
- increased blood loss at surgery
- increased incidence of spontaneous GI and cerebrovascular hemorrhage (including both hemorrhagic
strokes and subdural hematomas).
Neuromascular abnormalities :
1- CNS symptoms and signs may range from :
- Mild sleep disorders and impairment of mental concentration, loss of memory, errors in judgment, and
neuromuscular irritability (manifested as hiccups, cramps, fasciculations, and twitching) to
- Asterixis (due to altered nerve conduction in metabolic encephalopathy from a wide variety of causes),
myoclonus, stupor, seizures, and coma in end-stage uremia.
2- Peripheral neuropathy (sensory greater than motor, lower extremities greater than upper), typified by :
- Restless legs syndrome (poorly localized sense of discomfort and involuntary movements of the lower extremities),
is a common finding in chronic renal failure and an important indication for starting dialysis.
3- Complication of Dialysis :
- Patients receiving hemodialysis can develop aluminum toxicity, characterized by :
1- speech dyspraxia (inability to repeat words) 2- myoclonus,
3- dementia, 4- seizures.
- Aggressive acute dialysis rapid pH or osmolality change in ECF, resulting in cerebral edema , manifested by :
1- nausea, vomiting,
2- drowsiness, headache, and seizures.

GIT abnormalities :
1- Peptic ulcer disease :
- Up to 25% of pa8ents with uremia have peptic ulcer disease, perhaps as a consequence of 2ry hyperparathyroidism.
2- Uremic gastroenteritis : characterized by :
- Mucosal ulcerations with blood loss
- Distinctive form of bad breath (uremic fetor) resulting from : degradation of urea to ammonia by enzymes in saliva.
3- Nonspecific GI findings in uremic patients include :
- Anorexia, hiccups, nausea, vomiting, and diverticulosis.
- Although their precise pathogenesis is unclear, many of these findings improve with dialysis.

Endocrinal & metabolic abnormalities :

1- Women with uremia have low estrogen levels, which explains :
- high incidence of amenorrhea and
- rarely are able to carry a pregnancy to term.
2- Men with uremia have low testosterone levels, which explains:
- impotence
- oligospermia
- germinal cell dysplasia
3- Chronic renal failure eliminates the kidney as a site of insulin degradation thereby increasing the half-life of
insulin.

Dermatological abnormalities :
1- Pallor because of anemia
2- Gray discoloration resulting from transfusion-mediated hemochromatosis .
3- Ecchymoses & hematomas as a result of clotting abnormalities.
4- Pruritus & Excoriations as a result of Ca2+ deposits from 2ry hyperparathyroidism.
5- Extremely high concentration of urea evaporation of sweat leaves a residue of urea termed uremic frost.
 Clinical abnormalities in uremia (I) denotes an abnormality that usually improves with
Fluid and electrolyte
Volume expansion and contraction (I) an optimal program of dialysis and related therapy.
Hypernatremia and hyponatremia (I)
Hyperkalemia and hypokalemia (I)
Metabolic acidosis (I)
Hypocalcemia (I) (P) denotes an abnormality that tends to persist or
Bone and mineral
Renal osteodystrophy (I or P) even progress, despite an optimal program.
Osteomalacia (D)
Metabolic
Carbohydrate intolerance (I)
Hypothermia (I)
Hypertriglyceridemia (P)
Protein-calorie malnutrition (I or P)
Impaired growth and development (P)
Infertility and sexual dysfunction (P)
Amenorrhea (P)
Dialysis (amyloid, -microglobulin) arthropathy
Neuromuscular
Fatigue (I)
Sleep disorders (P)
Impaired mentation (I)
Lethargy (I)
Asterixis (I)
Muscular irritability (I)
Peripheral neuropathy (I or P)
Restless legs syndrome (I or P)
Paralysis (I or P)
Myoclonus (I)
Seizures (I or P)
Coma (I)
Muscle cramps (D)
Dialysis disequilibrium syndrome (D)
Dialysis dementia (D)
Myopathy (P or D)
Cardiovascular
Arterial hypertension (I or P)
Congestive heart failure or pulmonary edema (I)
Pericarditis (I)
Cardiomyopathy (I or P)
Uremic lung (I)
Accelerated atherosclerosis (P or D)
Hypotension and arrhythmias (D)
Skin
Skin pallor (I or P)
Hyperpigmentation (I, P, or D)
Pruritus (P)
Ecchymoses (I or P)
Uremic frost (I)
Gastrointestinal
Anorexia (I)
Nausea and vomiting (I)
Uremic fetor (I)
Gastroenteritis (I)
Peptic ulcer (I or P)
Gastrointestinal bleeding (I, P, or D)
Hepatitis (D)
Refractory ascites on hemodialysis (D)
Peritonitis (D)
Hematologic
Normocytic, normochromic anemia (P)
Microcytic (aluminum-induced) anemia (D)
Lymphocytopenia (P)
Bleeding diathesis (I or D)
Increased susceptibility to infection (I or P)
Splenomegaly and hypersplenism (P)
Leukopenia (D)
Hypocomplementemia (D)
 Acute Kidney Injury
Management Investigations are aimed at :
1- Determination of the volume status : 1- Defining whether the patient has acute or chronic uraemia.
2- Defining whether uraemia results from prerenal, renal or postrenal factors,
A) If Hypovolaemia and Hypotension : Once initial resuscitation has been performed : 3- Establishing the cause.
fluid intake should be : Urine
1- Should be corrected by replacement of IV fluid or blood
1- matched to urine output plus
Criteria for Urine specific Urine sodium
- Types of fluid : Balanced salt solutions, such as : distinction between : osmolality FENa BUN : Cr. ratio
2- 500 mL to cover insensible losses gravity (mmol/L)
1- Isotonic (0.9%) saline (mOsm/kg)
2- Ringer’s lactate preferable when large volumes of fluid resuscitation are required, in order to avoid hyperchloraemic acidosis Pre-Renal > 1.020 > 500 < 20 < 1% 30 : 1
- Monitoring : Renal < 1.010 < 350 > 40 > 1% 15 : 1
Prerenal & renal uraemia may coexist, excessive fluid may lead to volume overload with pulmonary oedema Monitoring of (CVP) .
2- Critically ill patients may require Inotropic drugs to restore effective blood pressure.(clinical trials do not support a specific role for low-dose
low dopamine) 17.16 Investigation of patients with established acute kidney injury
B) If Hypervolemia : (Signs: Peripheral oedema, Basal
asal crackles, Elevation of jugular venous pressure) : Urea and Compare to previous results. Chronically abnormal in CKD
1- Diuretic therapy , after the adequate circulating blood volume : Mannitol (0.5 g/kg) & furosemide (2–4
4 mg/kg) IV single dose creatinine
2- Severe fluid overload in the presence of marked oliguria or anuria is indication for dialysis. Electrolytes If potassium > 6 mmol/L, treat urgently
2- Correction of serum electrolytes : Calcium and Low calcium and high phosphate may indicate CKD
ECG changes s : Calcium low in rhabdomyolysis: measure creatine kinase
Hyperkalemia The earliest ECG change hyperkalemia is the appearance of peaked T waves followed by widening of QRS
phosphate
Hypercalcaemia in myeloma
• Skeletal muscle : intervals ST segment depression ventricular arrhythmias cardiac arrest. Albumin Low albumin in nephrotic syndrome (see urinalysis below)
weakness, flaccid Indications : Low albumin in sepsis: take blood cultures
paralysis, areflexia. Procedures should be initiated when the serum potassium value rises above 6.0 mEq/L . Full blood count Anaemia may indicate CKD or myeloma
• Smooth muscle : Treatment :
Clotting screen Anaemia and fragmented RBC on blood film with raised LDH in thrombotic microangiopathy
Intestinal colic, nausea, A) Stabilize cell membrane potential : Low platelets and abnormal coagulation in DIC, including in sepsis: take
take blood cultures
vomiting. - IV calcium gluconate (10 mL of 10% solution) C-reactive protein ESR is misleading in renal failure
• Cardiac muscle : B) Shift K into cells : High CRP may indicate sepsis or inflammatory disease
-ECG changes : " see " - Inhaled β2-adrenoceptor
adrenoceptor agonist (e.g. salbutamol) Urinalysis Less reliable in an oliguric catheterised patient
-Arrhythmias /cardiac arrest. - IV glucose (50 mL of 50% solu9on) and insulin (5 U Actrapid®) Seek earlier results if possible
- IV sodium bicarbonate if acidosis present. Marked haematuria suggests glomerulonephritis, tumour of renal tract or bleeding disorder
C) Remove K from body Heavy proteinuria suggests glomerular disease: measure PCR or ACR
- IV furosemide and normal saline Casts or dysmorphic red cells suggest glomerulonephritis
Urine microscopy
- Ion-exchange
exchange resin (e.g. Resonium®) orally or rectally Leucocytes suggest infection/interstitial nephritis
- Dialysis Crystals may be observed in drug-induced
drug or uric acid nephropathy
- Dilutional disturbance corrected by fluid restriction rather than NaCl administration.
Hyponatremia - Administration of hypertonic (3%) saline should be limited to patients with :
Renal ultrasound Hydronephrosis enlarged bladder in urinary tract obstruction: consider
ider PSA and further imaging.
Small kidneys suggest CKD
1- Symptomatic
ymptomatic hyponatremia (seizures, lethargy) or Asymmetric kidneys suggest renovascular or developmental disease: consider renal artery imaging
2- Serum sodium level <120 mEq/L. Culture blood, urine, sputum, wounds as appropriate
Cultures
Hypocalcemia & - lowering the serum phosphorus by : Treat all infections
1- Dietary
ietary phosphorus restriction and Pulmonary oedema in fluid overload
Hyperphosphatemia Chest X-ray
2- Administration
dministration of phosphate binders (calcium acetate and calcium carbonate). Globular heart in pericardial (uraemic) effusion: perform echocardiogram
echocardio
Symptomatic hypocalcemia (tetany) can be treated with IV calcium; it must be given cautiously. HIV and hepatitis serology is urgent if dialysis is needed
Serology
Restoration of blood volume will correct acidosis by restoring kidney function
ECG If patient is > 40 yrs or has electrolyte abnormali9es or risk of cardiac disease
- Indications of treatment : 1- If acidosis is severe (arterial pH <7.15; serum bicarbonate <8 mEq/L)
Metabolic acidosis
2- contributes to hyperkalemia.
Rarely requires TTT - Treatment:
1- NaHCO3 IV,, to raise arterial pH to 7.20 (which approximates a serum HCO3 level of 12 mEq/L).
emainder of the correction by oral after normalization of the serum Ca & phosphorus levels.
2- Remainder
Renal AKI
3- ARF patients are predisposed to gastrointestinal bleeding : Factors that can help differentiate the various causes of
• Causes: Because
ecause of uremic platelet dysfunction, increased stress, and heparin exposure if on hemodialysis renal and post-renal AKI are summarised in :
• Treatment: Oral or IV H2 blockers as: ranitidine.
4- Hypertension :
• Cause : 1- may result from hyperreninemia associated with the primary disease process and/or
2- expansion of the extracellular fluid volume and is most common in ARF patients .
• Treatment: Salt & water restriction + Diuretic administration:
1- Severe symptomatic hypertension continuous infusions of sodium nitroprusside .
2- Longer acting agents such as for maintaining control of BP.
5- Anemia :
• The anemia of ARF is generally mild (Hb 9–1010 g/dL) and primarily results from volume expansion (hemodilution).
• Slow (4–66 hr) transfusion with packed red blood cells (10 mL/kg) diminishes the risk of hypervolemia.
• The use of fresh, washed red blood cells minimizes the risk of hyperkalemia.
6- Infection :
• Patients
nts with AKI are at substantial risk of intercurrent infection because humoral and cellular immune mechanisms are depressed.
• Clinical examination + microbiological investigation, is required to diagnose infection treated promptly .
7- Neurological symptoms: include: headache, seizures, lethargy, and confusion.
• Causes: hyponatremia, hypocalcemia, hypertension, cerebral hemorrhage, cerebral vasculitis, and uremic state.
• Treatment: Diazepam is the most effective agent in controlling seizures
8- Nutritional : - Na, K,, phosphorus should be restricted. /Protein intake should be restricted moderately while
- Maximizing
aximizing caloric intake to minimize the accumulation of nitrogenous wastes
9- Renal Replacement Therapy : 2 main options for RRT in AKI are : 1- haemodialysis 2- high-volume volume haemofiltration,, indications:
Clinical Laboratory
• Acute Pulmonary edema. B. Laboratory :
• Pericarditis. • Urea : > 200 mg/dl ( N : 20 - 40 mg/dl )
• Persistent diarrhea. • Crea9nine : > 8 mg/dl , > 7 in DM ( N : 0.7 - 1.2 mg/dl )
• Preoperative. • K : > 7 mEq/L . ( N : 3.5 - 5.5 mEq/L )
• Coma. • HCO3 : < 14 mEq/L .
• Convulsion • PH : < 7.2
• Deterioration of general health. • Hypercatabolic RF : - Creatinine by > 1mg/d.
- K by > o.8 mEq/d.
 Chronic renal failure
The aims of management in CKD are to : Blood : Suggested investigations in chronic kidney disease
1- Prevent or slow further renal damage Urea and To assess stability/progression: compare to
2- Limit
imit adverse physiological effects of renal impairment on skeleton & haematopoiesis 1- Anemia : creatinine previous results
3- Treat risk factors for cardiovascular disease; • Anaemia is common in patients with
h a GFR below 30 mL/min/1.73 m2. Urinalysis and Haematuria and proteinuria
uria may indicate cause.
quantification Proteinuria indicates risk of progressive CKD
• Regimens : of proteinuria requiring preventive ACE E inhibitor
inhibito or ARB therapy
1- Diet & lifestyle Modifications : 1- Recombinant human erythropoietin ( Eprex ) : 4000 u 2 9mes / week.
2- Packed RBCs.
Electrolytes
Calcium, phosphate,
To identify hyperkalaemia and acidosis

Diet : parathyroid hormone Assessment of renal osteodystrophy

• Target :
1- Preventing excessive
xcessive consumption of protein. and 25(OH)D
The target haemoglobin is usually between 100 and 120 g/L (10–20
(10 g/dL). Albumin Low albumin: consider malnutrit
alnutrition, inflammation
2- Ensuring
uring adequate calorific intake.
FBC (± Fe, ferritin, If anaemic, exclude common non-renal
non
3- Limiting potassium & phosphate intake.
4- Limiting excessive water intake to avoid body water retention. Renal bone disease folate, B12) explanations then manage as renal anaemia
Lipids, glucose ± Cardiovascular risk high in CKD: treat risk factors
Life style : 1- Treatment should be initiated with active vitamin D metabolites , either : HbA1c aggressively
1- Stop smoking: this a) slows decline in renal function b)reducing cardiovascular risk. • 1-α-hydroxyvitamin D or Only if there are urinary symptoms (to exclude
• 1,25- dihydroxyvitamin D obstruction) or progressive CKD.
2- Exercise and weight loss may also reduce proteinuria and have beneficial effects on Renal ultrasound Small kidneys suggest chronicity.
cardiovascular risk profile. - Indications : patients who are found to have : Asymmetric renal size suggests renovascular or
• Hypocalcaemia or developmental disease
2- Medications : • Serum
erum PTH levels more than twice the upper limit of normal. Hepatitis and HIV If dialysis or transplant is planned. Hepatitis B
serology vaccination recommended if seronegative
Cardiovascular : - The dose should be adjusted to try to reduce PTH levels to between 2 and 4 9mes the ECG If patient is > 40 yrs or hyperkala
yperkalaemic, or there are
risk factors for cardiac disease
upper limit of normal to avoid over-suppression
suppression of bone turnover.
1- Anti-hypertensives :
Investigations
1- Slows the rate at which renal function declines in CKD • The recommended investigations in patients with CKD are shown in
2- Lowering the risk of hypertensive heart failure, stroke and peripheral vascular disease, 2- Hyperphosphataemia :
• Their main aims are:
3- Reducing proteinuria 1) Dietary
ietary restriction of foods with high phosphate content (milk, cheese, eggs ) 1- to identify the underlying cause where possible, since this may
2) Phosphate-binding drugs : influence the treatment.
• Targets: • Calcium carbonate / Aluminium hydroxide / Lanthanum carbonate / 2- to identify reversible factors that may worsen
orsen renal
ren function, such as
- 130/80 mmHg for uncomplicated CKD, Polymer-based
based phosphate binders such as sevelamer hypertension, UTI, nephrotoxic drugs, and d salt and
an water depletion.
- 125/75 mmHg for CKD complicated by significant proteinuria of more than 1 g/day. 3- to screen for complications of CKD.
• Aim: 4- to screen for cardiovascular risk factors.
• Regimen : - maintain serum phosphate values at 5.6 mg/dL or below .
- ACEIs, methyl dopa , β blocker , Caa channel blocker or Diuretic. Referral to a nephrologist :
Criteria for referral of chronic kidney disease patients to a nephrologist :
3- Hyperparathyroidism : • Age < 40 years
2- Lipid-lowering
lowering therapy (Statins) : 1) ttt of renal osteodystrophy • Stage 4 CKD or worse (eGFR < 30 mL/min/1.73 m2)
• Hypercholesterolaemia is almost universal in patients with significant proteinuria
proteinuria,, and 2) Parathyroidectomy may required for the treatment of 3ry hyperparathyroidism. • Rapid deterioration in renal function1
increased triglyceride levels are also common in patients with CKD. 3) Calcimimetic agents, such as cinacalcet : • Significant proteinuria (PCR > 100 mg/mmol or ACR > 70 mg/mmol)
• Significant haematuria:
- which bind to the calcium-sensing
sensing receptor and reduce PTH secretion.
• Effect : - After exclusion of urinary tract infection and urological abnormalities
- They have a place if parathyroidectomy is unsuccessful or not possible. such as stones and tumours.
1- Lipid lowering shown to reduce vascular events in non
non-dialysis CKD patients.
2- Control of dyslipidaemia with statins may slow rate of progression of renal disease.
Maintaining fluid and electrolyte balance :
3- Reduction of proteinuria : 1- Patients with evidence of fluid retention :
• There is a clear relationship between the degree of proteinuria and the rate of
1) Dietary
ietary sodium intake limited to about 100 mmol/day.
mmol/day
progression of renal disease,, and strong evidence that :
2) Loop
oop diuretics may also be required to treat fluid overload.
reducing proteinuria reduces the risk of progression.
1- Angiotensin-converting
converting enzyme (ACE) inhibitors and 2- If hyperkalaemia occurs :
2- angiotensin II receptor blockers (ARBs) 1) Drug
rug therapy should be reviewed, to reduce or stop potassium-sparing
potassium diuretics,
ACE inhibitors and ARBs.
• Effect:
1- Reduce
educe proteinuria and retard the progression of CKD due to the reduction 2) Correction of acidosis may be helpful,
in blood pressure. 3) Limi9ng
imi9ng potassium intake to about 70 mmol/day may be necessary in late CKD.
2- Reduce the risk of cardiovascular events .
binding resins, such as calcium resonium, may be useful in the
4) Potassium-binding
• Treatment with ACE inhibitors and ARBs accompanied by an immediate reduction in short term but should not be used chronically.
GFR when treatment is initiated, due to a reduction in glomerular perfusion pressure.
3- Bicarbonate :
• Treatment can be continued so long as reduction in GFR is < 20% and is not progressive.
progressive • Should
hould be maintained above 22 mmol/L
• Accordingly ACE inhibitors and/or ARBs should be prescribed to all patients with • by giving NaHCO3 supplements (star9ng dose of 1 g 3 9mes daily, increasing as required).
diabetic nephropathy and those with proteinuria, irrespective of whether or not
• If the increased sodium intake induces hypertension or oedema :
hypertension is present (providing
providing that hyperkalaemia does not occur
occur).
calcium carbonate (up to 3 g daily) may be used as an alterna9ve, since this has
the advantage of also binding dietary phosphate.
phosphat
Urea and To assess stability/progression: compare to previous results
creatinine
Urinalysis and Haematuria and proteinuria may indicate cause. Proteinuria indicates risk of progressive CKD requiring
quantification preventive ACE inhibitor or ARB therapy
of proteinuria
Electrolytes To identify hyperkalaemia and acidosis
Calcium, phosphate, Assessment of renal osteodystrophy
parathyroid hormone and
25(OH)D
Albumin Low albumin: consider malnutrition, inflammation
±
Full blood count ( Fe, If anaemic, exclude common non-renal explanations then manage as renal anaemia
ferritin, folate, B12)
Lipids, glucose ± HbA1c Cardiovascular risk high in CKD: treat risk factors aggressively
Renal ultrasound Only if there are urinary symptoms (to exclude obstruction) or progressive CKD. Small kidneys suggest
chronicity. Asymmetric renal size suggests renovascular or developmental disease
Hepatitis and HIV If dialysis or transplant is planned. Hepatitis B vaccination recommended if seronegative
serology
ECG If patient is > 40 yrs or hyperkalaemic, or there are risk factors for cardiac disease
Other tests Consider relevant tests from Boxes 17.16 and 17.17 (p. 480), especially if the cause of CKD is unknown
 Approach to the Patient: Glomerular Disease
Patients with glomerular diseases have clinical
linical and laboratory features of glomerular injury :
• Leakage of cells & macromolecules across the glomerular filtration barrier :
1) Proteinuria: characteristic of diseases that: 1. affect the podocyte 2. scarring & deposition of foreign material / 2) Haematuria: characteristic of diseases of : 1. Inflammatory process 2. destructive processes.
• Impaired renal function and reduced GFR
• Hypertension
Hematuria Protienuria
Normally : • Identifing the type of protein in the urine :
• Less
ess than 150 mg of protein is excreted in the urine /day. 1- Low-molecular
molecular-weight proteins :
• A proportion of this is Tamm–Horsfall protein, secreted - Amount : Appear in urine in quantities > 150 mg/day.
by the renal tubules. - Assessed
ssessed by:
by measurement of specific low molecular-
Pathological Proteinuria : weight proteins, such as β2-microglobulin.
• The presence of larger amounts of protein is usually - Large amounts of small proteins in the urine suggest
indicative of significant renal disease (Box
( 17.13). renal tubular damage (tubular proteinuria).
"This rarely exceeds 1.5–2 g/24 hours"
Approach
2- High-molecular
molecular-weight proteins :
A) Clinical assessment :
- When more than 2 g protein per day is being
• Proteinuria is usually
usuall asymptomatic. Fig. 17.21 Spectrum of glomerular diseases.
excreted, glomerular disease is likely this is
• Sustained proteinuria: • At one extreme :
an indication for renal biopsy.
- >1–2 g/24 h is associated with glomerular disease. - specific injury to podocytes or structural alteration of the glomerulus affecting podocyte function
- The diseases that cause nephrotic syndrome all
- Patient will become edematous. (for example, by scarring or deposition of excess matrix or other material) causes proteinuria and
affect the glomerulus (see Fig. 17.21, ).
- Large amounts of protein make urine froth. nephrotic syndrome .
• Transient (Benign) proteinuria can occur : 3- Free immunoglobulin light chains (25 kDa) : - The histology to the left shows diabetic nephropathy.
Normally : Healthy individuals may have : - After vigorous exercise, - During fever, - filtered freely at glomerulus and can be identified as • At the other end of the spectrum :
RBCs in the urine (up to 12 500 cells/mL) - In heart failure - urinary tract infection. - Inflammation
nflammation leads to cell damage & proliferation, breaks form in the e GBM and
a blood leaks into urine.
‘Bence Jones protein’ in fresh urine samples.
Pathological hematuria : Patients should be assessed for the presence of these - Bence Jones protein is poorly identified by dipstick - In its extreme form, with acute Na retention & HTN,, such disease is labelled nephritic syndrome.
1- Macroscopic haematuria or conditions and treated then urine testing repeated tests by: specific immunodetection methods. - The
he histolo
histology to the right shows a glomerulus with many extra nucleii from proliferating
p intrinsic
2- Microscopic haematuria on dipstick testing : • Orthostatic
O proteinuria : May arise in absence of renal disease - This may occur
occu in : cells, and influx of inflammatory cells shows crescent formation (arrows)
ows) in response
r to severe post-
(15 000–20 000 cells/mL or more) - This occurs only during the day, in association with an a- AL amyloidosis infectious glomerulonephritis.
is indicative of bleeding from the urinary tract (causes
causes above
above) upright posture, and the first morning sample is –ve . b- B-cell disorders, (FSGS = focal and segmental glomerulosclerosis; MCGN = mesangiocapillar
iocapillary glomerulonephritis)
Approach - Typically, < 1 g protein per day is excreted. c- important marker for myeloma .
1- Confirming presence of RBCS in urine by microscopymicroscopy: - Benign disorder does not require treatment. Glomerulopathy (GN) is a general term for a group of disorders in which:
a- Since
ince dipstick tests can also be positive in presence of • Microalbuminuria : in diabetic Nephropathy There is primarily an immunologically mediated injury to glomeruli, although h renal interstitial
i damage is a
free haemoglobin or myoglobin. - It's defined as 30–299 mg/d in a 24-h collection or regular accompaniment.
b- Other causes of red or dark urine may sometimes be 30–299 ug/mg creaCnine in a spot collecCon (preferred) • The kidneys are involved symmetrically.
confused with haematuria but produce negative - Although the appearance of microalbuminuria in type • Secondary
econdary mechanisms of glomerular injury come into play following an initial immune insult such as
dipstick tests and microscopy (Box 17.10). 1 DM is important risk factor for progression to fibrin deposition, platelet aggregation, neutrophil infiltration and free radical-induced
radical damage.
2- Exclude the following: positive tests may also occur during:: macroalbuminuria (>300 mg/d or > 300 ug/mg creatinine), • Renal lesions may be part of a generalized disease (e.g. systemic lupus erythematosus, SLE).
a- Menstruation. - Persistent microalbuminuria is associated with an
risk of atherosclerosis & cardiovascular mortality Pathogenesis :
b- Infection
• GN is considered to be immunologically mediated disorder with involvement of :
c- Strenuous exercise. • Isolated proteinuria : sustained over multiple clinic visits
- cellular immunity (T lymphocytes, macrophages/dendritic cells),
is found in :
3- Imaging of renal tract : - humoral immunity (antibodies, immune complexes, complement), and
1-- Diabetic nephropathy 2- nil lesion 3- FSGS.
A) Anatomical lesions present: - other inflammatory mediators (including cytokines,
cytokines, chemokines and the coagulation cascade).
4-- mesangioproliferative glomerulonephritis,
• Investigations of hematuria, should be directed first • The immune response can be directed against known target antigens :
N.B.
N.B.1
at the exclusion of an anatomical bleeding lesion. - Particularly
articularly when GN complicates 1- infecCons 2- neoplasia 3- drugs.
• In most adults with glomerular disease :
• Examples of Visible haematuria : Proteinuria is nonselective, containing albumin and a mixture of
- More frequently the underlying antigenic target is unknown.
1. Tumour, (any part of the urogenital tract ). other serum proteins, • Primary GN may occur in genetically susceptible individuals following an environmental insult.
2. Urine infection • In
n children with nil lesion from minimal change disease : 1- Genetic
enetic susceptibility : is determined by major (HLA) genes (e.g. HLA-A1,
A1, B8, DR2, DR3).
3. Stones. Proteinuria
roteinuria is selective & composed largely of albumin. 2- Environmental
nvironmental factors :drugs ( hydralazine), chemicals ( gold, silica, hydrocarbons)
hydroca or infectins .
Investigation of haematuria N.B.
N.B.2 • The physical evidence of immune reactions is indicated by :
B) Anatomical lesions absent:
Some patients with inflammatory glomerular disease, such as acute - the presence of circulating autoantibodies and/or
• If haematuria occurs with proteinuria and other poststreptococcal glomerulonephritis or MPGN,
MPGN have pyuria - abnormalities in serum complement and
clinical features of kidney disease (see Box 17.11), characterized by presence of considerable numbers of leukocytes.
- glomerular deposition of antibodies, immune complexes, complement
complement and fibrin.
inflammatory renal disease should be ( has to be distinguished from urine infected with bacteria)
bacteria
considered and a renal biopsy may be indicated.
B) Investigations : Pathological terms in glomerular disease :The most commonly used terms are:
• If:
• Focal: some but not all the glomeruli contain the lesion.
- features of significant kidney disease, and
Urine Assays for Albuminuria/Proteinuria • Diffuse (global): most of the glomeruli (> 75%) contain the lesion.
- malignancy & renal stones excluded,
• Segmental: only a part of the glomerulus is affected (most focal lesions are also segmental,
s e.g. focal
manage by observation with periodic review. 24-Hour Albumin/Creatinine Dipstick 24-Hour
Albumin Ratio (mg/g) Proteinuria Urine segmental glomerulosclerosis).
(mg/24 h) Protein
(mg/24 h) • Proliferative: an increase in cell numbers due to hyperplasia of one or more
ore of the
th resident glomerular
cells with or without inflammation.
Normal 8–10 <30 – <150 • Membrane alterations:
al capillary wall thickening due to deposition of immune
mune deposits
de or alterations in
Microalbuminuria 30–300
basement membrane.
30–300 –/Trace/1+ –
• Crescent formation: epithelial cell proliferation with mononuclear cell infiltration
filtration in Bowman’s space.
Proteinuria >;300 >;300 Trace–3+ >;150

• First, amount of protein quantified to guide further Classification of glomerulopathies : Glomerular diseases to 4 major glomerular syndromes:
investigations (see
( ). 1- Nephrotic syndrome :
- Since quanCficaCon by 24-hour urine collection is - massive proteinuria (> 3.5 g/day), hypoalbuminaemia, oedema, hyperlipidaemia.
often inaccurate, protein : creatinine ratio (PCR) in 2- Acute glomerulonephritis (acute nephritic syndrome) –:
a spot sample of urine is preferred. - abrupt onset of glomerular haematuria (RBC casts or dysmorphic RBC), non--nephrotic range
- Changes in PCR also give valuable information about proteinuria, oedema, hypertension and transient renal impairment.
the progression of renal disease in CKD. 3- Rapidly progressive glomerulonephritis :
- features of acute nephritis, focal necrosis with or without crescents and rapidly progressive renal
- 24-hour albumin excretion or albumin : creatinine
failure over weeks.
ratio (ACR), requires a more expensive immunoassay
and is usually reserved for detection of the early 4- Asymptomatic haematuria, proteinuria or both.
stages of diabetic nephropathy. Certain types of GN, that a part of a systemic disease, can present as more
ore than one syndrome, e.g.
1- lupus nephriCs 2-
2 cryoglobulinaemia 3- Henoch–Schonlein purpura,
BUTmore typically they are associated with the nephrotic syndrome.
syndrome
 Differential Diagnosis of Glomerular Diseases
Glomerulonephritis can be classified as: Nephrotic or Nephritic (mild or moderate-to-severe)

Nephrotic Syndrome
Proteinuria >3.5 g/day, Hypoalbuminemia, edema, hyperlipidemia + bland urinary sediment (few cells or casts)
 Most common cause of nephrotic syndrome in children (Children age <10)
 Idiopathic  T -cell injury to podocytes  increased permeability to albumin.
 Associations  Hodgkin's lymphoma / NSAID
Minimal change  Children age <10 with isolated nephrotic syndrome do not require biopsy for
disease diagnosis as MCD is highly likely  next step: prednisone.
 LM: Normal finding (MCQ).
 EM: foot processes fusion of podocytes
 Immunofluoresence: negative.
 Most common cause of nephrotic syndrome in adults.
 African American
 Associations  HIV / Heroin use / Obesity (HHO)
 LM: focal and segmental glomerulosclerosis.
Focal segmental  EM: foot processes fusion of podocytes.
glomerulosclerosis
 Other forms of HIV-related glomerulopathies that can present with nephrotic-range
proteinuria (less common than FSGN) :
1. Membranous glomerulonephritis  if they also have hepatitis-B infection.
2. Membranoproliferative glomerulonephritis  see below.
3. Diffuse proliferative glomerulonephritis In lupus nephritis type IV
 It is a common cause of nephrotic syndrome in adults + adolescents (14 yrs)
especially if associated with HBV infection "hepatitis B virus-associated
membranous nephropathy (HBVMN)"
Membranous  Associations  Adenocarcinoma (lung & breast) /Hepatitis B/ SLE/ NSAID (ABSD)
nephropathy 1. HBVMN : serum C3 is low.
2. Lupus nephritis: antinuclear antibody is elevated
 LM: Thickened GBM and subepithelial "spikes".
 EM: Subepithelial deposits.
 Immunofluoresence: Granular IgG, C3.
 Membranoproliferative glomerulonephritis can be Nephrotic or Nephritic.
 Associations Hepatitis B (less common than membranous nephropathy)
Hepatitis C  mixed cryoglobulinemia (test for viral markers) :
 The immune complexes are lgM antibodies (similar to RF) that form
complexes with lgG anti-hepatitis C virus antibodies  Immune
complex deposition in small blood vessels (vasculitis).
o Skin (eg, palpable purpura doesn't blanch with pressure)
o Kidney (eg, MPGN)
Membranoproliferative o Nervous system (eg, motor sensory axonopathy),
glomerulonephritis o Musculoskeletal system (eg, arthralgias).
 Serologically (serum cryoglobulins + low complement levels +
increased RF + increased liver enzymes ) + Biopsy.
D.D. of Low complement levels with glomerulonephritis
Occurs 10-21 days after a streptococcal or
Postinfectious GN
staphylococcal infection.
Lupus nephritis Positive antinuclear antibody.
Mixed cryoglobulinemia Positive HCV + increased RF
with hepatitis C

 LM: Mesangial hypercellularity

 EM: Type I: Mesangial and subendothelial deposits.
Type II: Dense deposits Disease (DDD) in GBM
 Immunofluoresence: Granular IgG, C3 (in type I)
  Patient with diabetes for long time ( > 10 years) + poor glycemic control.
Diabetic Nephropathy  Diabetic nephropathy is characterized by proteinuria & progressive decline in GFR.
 Glomerular hyperfiltration (MCQ) is the earliest renal abnormality seen.
Diabetes mellitus is the
leading cause of end-  Histology :
stage renal disease in  First change that quantitated: Thickening of the glomerular basement membrane.
United States  Pathognomonic hallmark: nodular glomerulosclerosis (Kimmelstiei-Wilson nodules).
 The most common histologic lesion is diffuse glomerulosclerosis
 Amyloidosis is a group of dieases in which amyloid fibrils, builds up in tissue.
 Deposits consist of light chains (AL amyloidosis) or abnormal proteins (AA amyloidosis).
Amyloidosis AL amyloidosis AA amyloidosis
(Inflammatory amyloidosis)
 Rheumatoid arthritis is Associated  Multiple myeloma Chronic inflammatory conditions:
the most common condition  Waldenstrom  Rheumatoid arthritis
cause of AA Macroglobulinemia  Inflammatory bowel disease
amyloidosis in the Composition  Light chains (usually Abnormally folded proteins:
United States. of amyloid lambda). beta-2 microglobulin, apolipoprotein
or transthyretin
 History:
 Patient with Rheumatoid arthritis, presented with nephrotic manifestations +
 Hepatomegaly. + U/S : bilateral kidneys enlargement.
 Renal biopsy:
 Amyloid deposits are seen in GBM, blood vessels, and interstitium of the kidneys.
 Immunofluoresence: Deposits that stain with Congo red and demonstrate a
characteristic apple-green birefringence under polarized light.
 EM: randomly arranged thin fibrils.

Nephritic Syndrome
RBCs (dysmorphic), WBCs, casts (red blood cell and/or white blood cell), and variable degrees of proteinuria

 lgA nephropathy can present with nephrotic syndrome (<10%), but more commonly
(40%) presents with hematuria following an URT infection.
 Associations  Upper respiratory tract infection (within 5 days)
lgA nephropathy  Symptoms :
(Berger's disease)  More common in young adult men (age 20-30)
 Presents as: episodes of gross hematuria
 Diagnosis :
 Serum complements: Normal
 Kidney biopsy: Mesangial IgA deposits seen in
 Acute post-streptococcal glomerulonephritis after throat or skin infections with B-
hemolytic streptococcal infection.
 Associations  Upper respiratory tract infection (10-21 days postpharyngitic)
 Symptoms :
Poststreptococcal  More common in children (age 6-1 0), but can occur in adults.
Glomerulonephritis  Presents as: gross hematuria.
 Diagnosis :
 Serum complements: Low
 Kidney biopsy: subepithelial humps consisting ofC3 complement.
 Elevated anti-streptolysin O &/or anti-DNAse B
 Immune complexes composed of dsDNA (and) anti-dsDNA antibodies deposit in :
1) Mesangium and/or subendothelial space  inflammatory reaction with activation
of complement system, lowering C3 & C4 (Diffuse membranoproliferative GN).
2) Subepithelial space  presenting with nephrotic syndrome without normal
Lupus nephritis complement levels (membranous GN)
 Laboratory :
 Anemia, leukopenia, thrombocytopenia
 Positive ANA, anti-dsDNA, anti-Sm
 Low complement levels, increased immune complexes
 Pathogenesis of Glomerular Diseases
- Immune mechanisms underlie most types of primary glomerular diseases and many of the secondary glomerular
diseases.

- GN can be induced by antibodies, and glomerular deposits of immunoglobulins(often

often various
va components of complement
are found frequently in patients with glomerulonephritis).
glomerulonephritis

- Cell-mediated
mediated immune mechanisms may also play a role in certain glomerular diseases

- There are Two forms of antibody-associated:

associated:

(1) injury resulting from deposition of soluble circulating antigen-antibody

antigen antibody complexes in the glomerulus,

(2) injury by antibodies reacting in situ within the glomerulus, either with insoluble fixed (intrinsic) glomerular
antigens or with moleculess planted within the glomerulus. In addition, antibodies
ntibodies directed against glomerular
cell components may cause glomerular injury.

- Other Mechanisms of Glomerular Injury

1- Podocyte Injury
This can be induced by antibodies to visceral epithelial
epit cell antigens; by certain cytokines; or by still poorly
characterized factors, as in some cases of focal and segmental glomerulosclerosis (see below).

2- Nephron Loss :

Once any renal disease destroys sufficient func+oning nephrons to reduce the GFR to 30% to 50% of normal, will
lead to progression to end-stage
stage renal failure.

Such individuals develop proteinuria, and their kidneys show widespread glomerulosclerosis.(Such progressive sclerosis is
initiated by the adaptive changes that occur in the remaining glomeruli not destroyed )

These remaining glomeruli undergo hypertrophy to maintain renal function. This is associated with hemodynamic
changes, including :

1- increases in single-nephron
nephron GFR,
2- increase blood flow,
3- increasetranscapillary
transcapillary pressure (capillary hypertension).

leading to :

1- further endothelial and epithelial cell injury,

2- increased glomerular permeability to proteins, and accumulation of proteins and lipids in the mesangial
matrix.
3- This is followed by capillary collapse and obliteration, hyaline entrapment, increased deposition of mesangial
matrix, and ultimately by segmental or global sclerosis of glomeruli.

The last results in further reductions in nephron mass and a vicious cycle of continuing glomerulosclerosis.
 The Nephritic Syndrome

- Definition :
The nephritic syndrome is a clinical complex, usually of acute onset, characterized by :

(1) hematuria with dysmorphic red cells and red blood cell casts in the urine,

(2) some degree of oliguria and azotemia,

(3) hypertension.

(4) some
ome proteinuria and even edema,…… usually not as severe as in the nephrotic syndrome.

- Causes :
- The lesions that cause the nephritic
phritic syndrome have proliferation of the cells within the glomeruli, accompanied
by a leukocytic infiltrate.

- This inflammatory reaction injures the capillary walls, permitting escape of red cells into the urine, and induces
hemodynamic changes thatlead to a reduction in the GFR leading toOliguria, fluid retention .

- Hypertension is probably a result of both:

both

1- the fluid retention and

2- some augmented renin release from the ischemic kidneys.

• The acute nephritic syndrome may be produced:

1- By systemic disorders ( e.g. SLE ).

)
2- As a result of primary glomerular disease ( e.g. acutepostinfectious GN ).
 Acute Postinfectious (Poststreptococcal) Glomerulonephritis
It's caused by glomerular deposition of immune complexes resulting in:
in

1- diffuse proliferation and swelling of resident glomerular cells

2- frequent infiltration of leukocytes, especially neutrophils.

- The antigen may be: exogenous or endogenous,,,,,

endogenous ( exogenous pattern is seen in poststreptococcal GN).
GN

- Infections by :* Bacteria: Streptococci

treptococci, pneumococcal, staphylococcal infections

* viral diseases:
diseases mumps, measles, chickenpox, and hepatitis B and C.

- The classic case of poststreptococcal GN develops in a child 1 to 4 weeks a;er the individual recovers from a group
A streptococcal infection. ( In most cases the initial infection is localized to the pharynx or skin )

N.B. Only certain "nephritogenic" strains of β-hemolytic

β streptococci are
re capable of evoking glomerular disease.

- Pathogenesis: ___________________________________________________
- Immune
mmune complex deposition is involved in the pathogenesis of acute poststreptococcal GN.

( The relevant antigens are probably streptococcal proteins

pro )

- It is not clear if immune complexes are formed mainly in the circulation or in situ (the latter by binding of
antibodies to bacterial antigens "planted" in the GBM)

- C3 deposition on the GBM occurs before IgG; hence, the primary injury might
ht be by complement activation
and then eventually immune complexes are formed.

- Clinical course :______________________________________________________

______________________________________________________
- The onset is abrupt, accompanied by: malaise,
malaise a slight fever, nausea, and nephritic syndrome.
syndrome

- In the usual
ual case, oliguria, azotemia, and hypertension are only mild to moderate.

- There is gross hematuria,, the urine appearing smoky brown rather than bright red.

- Some proteinuria ,it

it may be severe enough to produce the nephrotic syndrome.

• Serum complement levels are low during the active phase of the disease,
• serum anti-streptolysin
streptolysin O antibody titers are elevated in poststreptococcal cases.

- Prognosis: ______________________________________________________________
1- children :

- Most children undergoes recovery .

- Some children suffers from development of rapidly progressive GN or chronic renal disease .

2- Adults :

15% to 50% of pa+ents develop end stage renal disease .

 Rapidly Progressive (Crescentic) Glomerulonephritis
(RPGN is a clinical syndrome and not a specific etiologic form of GN)

- Definition :
- it is clinical syndrome characterized by rapid and progressive loss of renal function , often associated
with:

1- severe oliguria
2- and (if untreated) death from renal failure.

- Histologically characterized by the presence of crescents in most of glomeruli , produced:

1- in part by proliferation of the parietal epithelial cells of Bowman's capsule in response to injury &
2- in part by infiltration of monocytes and macrophages

- Pathogenesis :
It may be caused by :

1- diseases restricted to the kidney &

2- others systemic

- in most cases the glomerular injury is immunologically mediated.

- Thus, CrGN is classified into three groups on the basis of immunologic findings. In each group, the disease
may be :

- associated with a known disorder or idiopathic.

MORHPOLOGY
Gross picture Microscopic picture E.M

1- The kidneys are enlarged 1- The glomeruli may show focal necrosis, 1- In all cases:
and pale. thrombosis, diffuse or focal endothelial Distinct rupture in the GBM.
proliferations and mesangial proliferations.
2- Cortical surfaces show 2- in some cases:
petechial haemorrahges. 2- Presence of Crescnts formed by proliferation of Subepithelial deposits.
parietal cells and by margination of monocytes into
Bpwman's space.

3- Crescents
Crescen eventually obliterate Bowman's
capsule and compress the glomeruli.

4- Fibrin strands are prominent between cellular

layers in the crescents which may undergo scarring.
 Acute Tubular Necrosis (ATN)

- Definition :
- ATN is a clinicopathologic condition characterized :

- morphologicallybyby damaged tubular epithelial cells.

- by acute suppression of renal function.
clinicallyby
- manifestationsare oliguria, uremia, and signs of fluid overload

• It is the most common cause of acute renal failure.

• In acute renal failure, urine flow falls within 24 hours to less than 400 mL per day (oliguria).

ATN is a reversible renallesion that arises in a variety of clinical settings which ranging from

severe trauma to acute pancreatitis to septicemia,,, have in common a period of inadequate blood
flow to the peripheral organs, often in the setting of marked hypotension and shock..

- Patterns of ATN :

1- First pattern, called ischemic ATN ,

- in which ATN associated with shock.
shock

Mismatched blood transfusions , myoglobinuria, also produce a picture

N.B.Mismatched icture resembling ischemic
ATN.

ATN is caused by
2- A second pattern, called nephrotoxic ATN,
a- a variety of poisons, including heavy metals (e.g., mercury); organic solvents (e.g., carbon
tetrachloride).
b- drugs such as gentamicin
entamicin and other antibiotics.
c- radiographic contrast agents. Because of the many precipitating factors,
factor ATN occurs quite
frequently.

- Pathogenesis :
The main events in both ischemic
ic and nephrotoxic ATN are :

1- tubular injury &

persistent and severe disturbances in blood flow resulting in diminished oxygen and substrate
2-persistent subst delivery
…..to tubular cells.
- Ischemia causes structural alterations
lterations in epithelial cells :

1- Loss of cell polarity.

This leads to redistribution of membrane proteins (e.g., Na+, [Kgr ]+-ATPase)
ATPase) from the basolateral to the
luminal
minal surface of tubular cells resulting in decreased sodium reabsorption by proximal tubules and
hence increased sodium delivery to distal
dist tubules. The latter, through Tubuloglomerular
ubuloglomerular feedback
system, contributes to vasoconstriction reduced GFR Oliguria.

2- Alteration
lteration of integrins that anchor tubular cells to their underlying basement membranes results in
damage and shedding of tubular cells into the urine, In which the resultant tubular debris can block urine
outflow and eventually increase intratubular pressure, thereby decreasing GFR.
Additionally, fluid from the damaged tubules could leak into the interstitium, resulting in increased
interstitial pressure and collapse of the tubules.

3- Ischemic tubular cells also express chemokines, cytokines, and adhesion molecules such as P-selectin
P
that recruit and immobilize leukocytes that can participate in tissue injury.

- Ischemia causes severe hemodynamic alterations

alterations that cause reduced GFR :

1- intrarenalvasoconstriction, which results in both :

a- reduced glomerular plasma flow
b- and reduced oxygen delivery to the functionally important tubules in the outer medulla.
medulla

2- Vasoconstrictor pathways have been implicated (e.g., renin-angiotensin,

renin angiotensin, thromboxane A2, sympathe:c
nerve activity),

3- Vasoconstriction
asoconstriction is mediated by sublethal endothelial injury leading to :
a- increased release of the vasoconstrictor endothelin
b- decreased production of vasodilatorynitric
vasodilatory oxide and prostaglandins.

Finally, there is also some evidence of a direct effect of ischemia or toxins on the glomerulus, causing a reduced effective
N.B.Finally,
glomerular filtration surface.
- Morphology :
1- Ischemic ATN :
It is characterized by necrosis of short segments of the tubules.

- Most of the lesions are seen in the straight portions of the proximal tubule and the ascending thick limbs.

- Widespread necrosis of tubular cells is uncommonly seen in renal biopsy samples. Instead, there is often a variety
of tubular injuries, including:

a- Attenuation of proximal tubular brush borders.

b- Sloughing of brush borders.
c- Vacuolization of cells.
d- Detachment of tubular cells from their underlying basement membranes with sloughing of cells
into the urine.

- Presence of proteinaceous casts in the distal tubules and collecting ducts. They consist of

1- Tamm-Horsfall protein (secreted normally by tubular epithelium).

2- Along with hemoglobin and other plasma proteins.
3- When crush injuries have produced ATN, the casts are composed of myoglobin.

- The interstitium:usually shows generalized edema along with a mild inflammatory infiltrate consisting of
……………………………..polymorphonuclear leukocytes, lymphocytes, and plasma cells.

2- Toxic ATN :
is basically similar, with some differences:

Necrosis is most prominent in the proximal tubule, and the tubular basement membranes are generally spared.

- Clinical course :
The clinical course of ATN can be divided into initiation, maintenance, and recovery stages.

The initiation The maintenance The recovery

Las:ng about 36 hours from the second to the sixth day Over course of few days
Dominated by: - Dominated by the signs and symptoms The recovery is indicated by a steady
The inciting medical, surgical, or of uremia and fluid overload. increase in urine volume, reaching as
obstetric event in the ischemic form of much as about 3 L/day over the course
ATN. of a few days.
25% of deaths from ATN occur during
- Patients may die during this phase this phase due to :
‫ـــــــــــــــــــــــــــــــــــــــــ‬ in absence of careful supportive 1- Serious electrolyte imbalances may
treatment or dialysis. occur during this phase.
2- increased vulnerability to infection
The only indication of renal involvement - Urine output falls between 50 and 400
is : mL/day(oliguria)& sometimes to only a
1- a slight decline in urine output few milliliters per day, but complete N.B.subtle functional impairment of the
2- with a rise in serum creatinine, anuria is rare. ………kidneys, particularly of the tubules,
- Oliguria may last only a few days or ………may persist for months
may persist as long as 3 weeks
(Type ICrGN) Anti-Glomerular
ular Basement Membrane Antibody12% of cases
- It's characterized by linear deposits of IgG and, in many cases, C3 on the GBM
- Goodpasture syndrome
anti-GBM
GBM antibodies bind to pulmonary alveolar capillary basement membranes to produce the clinical picture of : - pulmonary hemorrhages.
- associated with renal failure.
In idiopathic cases, renal involvement occurs in the absence of pulmonary disease.
-In
- Anti-GBM antibodies are present in the serum and are helpful in diagnosis.
- These
hese individuals benefit from plasmapheresis, which removes pathogenic antibodies from the circulation
circulation.
(Type II CrGN )immune complex-mediated mediated disorders44% of cases
- This can be a complication of any of the immune complex nephritides, including
including:
1- poststreptococcal GN,
2- SLE,
3- IgA nephropathy

- immunofluorescence studies reveal the characteristic granular ("lumpy bumpy") pattern of staining of the GBM and/or mesangium .
- These individuals cannot usually be helped by plasmapheresis.
(Type I CrGN) Pauci-Immune 44 % of cases
- It's defined by the lack of anti-GBM
GBM antibodies immune complex deposition detectable by immunofluorescence and electron microscopy.

- Most of these individuals have antineutrophil cytoplasmic antibodies in the serum, which have a role in some vasculitides.

- In some cases ,pauci-immune

immune CrGN is a component of a systemic vasculitis
vasculitissuch as microscopic polyangiitis or Wegener granulomatosis.

- In Other cases , immune CrGN is limited to the kidney and is thus called idiopathic.

- Clinical Course :
The onset :is
is much like that of the nephritic syndrome except that the oliguria and azotemia are more pronounced.
Proteinuria may approach rangess of nephrotic syndrome
syndrome.
Some of these persons become :anuric
anuric and require long
long-term dialysis or transplantation.

- The prognosis:(depends on the number of crescents )

Those
hose with crescents in less than 80% of the glomeruli have a be5er prognosis than those with higher percentages of crescents.
crescents

N.B. Plasma exchange benefits some individuals, particularly those with anti
anti-GBM
GBM antibody GN and Goodpasture syndrome.
Nephrotic syndrome
1- Glomerular capillaries are lined by endothelial cells , that contains "fenestrations"
2- Glomerular
lomerular basement membrane (GBM) forms a continuous layer between :
- Endothelial
ndothelial and mesangial cells on one side and
- Epithelial cells on the other.
The membrane has 3 layers:
(1) Central lamina densa
(2) Lamina
amina rara interna, which lies between the lamina d
densa
ensa and the endothelial cells
(3) Lamina
amina rara externa, which lies between the lamina densa and the epithelial cells.
3- Visceral epithelial cells (Podocytes) cover the capillary and project cytoplasmic “foot
processes,” which attach
ach to the lamina rara externa etween the foot processes "filtration slits"
between
• Mesangium (mesangial cells and matrix) lies between the glomerular capillaries on the endothelial cell
side of the GBM and forms the medial part of the capillary wall.
- The mesangium may serve as a supporting structure for the glomerular capillaries and probably has a role in :
1- Regulation
egulation of glomerular blood flow and fi
filtration and
2- Removal
emoval of macromolecules (such as immune complexes) from the glomerulus, either through a- intracellular phagocytosis or b- by transport through intercellular channels to the juxtaglomerular region.
• Bowman's capsule,, which surrounds the glomerulus, is composed of
(1) a basement membrane, which is con-nuous with the basement membranes of the glomerular capill
capillaries
aries and the proximal tubules
(2) the parietal epithelial cells, which are con-nuous with the visceral epit
epithelial cells.

• The endothelial cell, basement membrane, and epithelial cell of the glomerular capillary wall possess strong negative ionic charges
charges.
These charges are a consequence of two negatively charged moieties: 1- Proteoglycans (heparan sulfate) 2- Glycoproteins containing sialic acid.
• Proteins in the blood carry a net negative charge Consequently, they are repelled by the negatively charged sites iin the glomerular capillary wall thus restricting filtration.

Types of Nephrotic syndrome : Summary of Primary Renal Diseases That Present as Idiopathic Nephrotic Syndrome
1- Primary Idiopathic nephro'c syndrome (90%) : MINIMAL CHANGE FOCAL SEGMENTAL MEMBRANOUS MEMBRANOPROLIFERATIVE
- Minimal change nephrotic syndrome (MCNS) is the most common NEPHROTIC SYNDROME GLOMERULOSCLEROSIS NEPHROPATHY GLOMERULONEPHRITIS
histologic form
Type I Type II
- More than 80% of children under 7 years of age with nephro-c
[*]
syndrome have MCNS. FREQUENCY
2- Secondry nephro'c syndrome (10%) : Children 75% 10% <5% 10% 10%
- may be seen with systemic lupus erythematosus, Schönlein
Schönlein-Henoch
purpura, infections (hepatitis B, hepatitis C, malaria), Wegener and other Adults 15% 15% 50% 10% 10%
vasculitides, allergic reactions, diabetes, amyloidosis, malignancies,
congestive heart failure, constrictive pericar
pericarditis, renal vein thrombosis. Clinical Manifestations

3- Congenital Nephrotic syndrome : Age (yr) 2–6, some adults 2–10, some adults 40–50 5–15 5–15
- The Finnish type is an autosomal recessive disorder most common
Sex 2 : 1 male 1.3 : 1 male 2 : 1 male Male-female Male
Male-female
- presents during the first 2 months of life.
- Prenatal onset is supported by of maternal alpha-fetoprotein. Nephrotic syndrome 100% 90% 80% 60% 60%
Pathogenesis : Asymptomatic 0 10% 20% 40% 40%
- The underlying abnormality in nephrotic syndrome is an increase in proteinuria
wall, which leads to massive
permeability of the glomerular capillary wall
proteinuria and hypoalbuminemia. Hematuria 10–20% 60–80% 60% 80% 80%
- The cause of the increased permeability
ability is not well understood, THYOERIS : Hypertension 10% 20% early Infrequent 35% 35%
A. In minimal change disease :
1- It is possible that T-cell
cell dysfunction leads to alteration of cytokines, Rate of progression to Does not progress 10 yr 50% in 10–20
10 yr 10–20 yr 5–15
15 yr
which causes loss of negatively charged glycoproteins within the renal failure
glomerular capillary wall. Associated conditions Allergy? Hodgkin None Renal vein thrombosis, None Partial
2- Certain HLA types (HLA-DR7,DR7, HLA
HLA-B8, and HLA-B12) are associated disease, usually none cancer, SLE, hepatitis B lipodystrophy
with an increased incidence of NS.
B. In focal segmental glomerulosclerosis : Manifestations of Manifestations of nephrotic Manifestations of
nephrotic syndrome syndrome nephrotic
1- A plasma factor (produced by lymphocytes) may be responsible for
Laboratory Findings
the increase in capillary wall permeability. ↑ BUN in 15–30% ↑ BUN in 20–40% syndrome Low C1, C4, C3–C9 Normal C1, C4, low
2- Mutations in podocyte proteins (podocin, α-ac'nin 4).
C3–C9
C9
Pathophysiology:
[†] [†]
1- Proteinuria : Immunogenetics HLA-B8, B12 (3.5) Mutations in podocin, α- HLA-DRw3
DRw3 (12–32)
(12 Not established C3 nephri-c factor
actinin-4, other genes Not established
• In patients with NS, the structural changes:
(1) damage to the endothelial surface, causing loss of the -ve charge. Renal Pathology
(2) damage to the GBM
(3) effacement of the foot processes. Light microscopy Normal Focal sclerotic lesions Thickened GBM, spikes Thickened GBM, Lobulation
Leading to increased glomerular capillary wall permeability large amounts proliferation
of protein (primarily albumin) cross the barrier and are excreted
Immunofluorescence Negative IgM, C3 in lesions Fine granular IgG, C3 Granular IgG, C3 C3 only
Types of proteinuria
(Highly) selective proteinuria Non- selective proteinuria: Electron microscopy Foot process fusion Foot process fusion Subepithelial deposits Mesangial and Dense deposits
the damage of glomeruli is mild and the injuries of the glomeruli are severe, both: subendothelial
permeability of GBM would be selectively • Small (albumin, transferrin) & deposits
altered increasing capillary transport of • Large proteins (α2- macroglobulin)
anionically charged particles(albumin et al) can pass through the GBM Response to Steroids 90% 15–20% May be slow progression Not established Not established
2- Hypoproteinemia :
• Increased urinary loss of proteins is the main cause Clinical manifestations : Complications :
• Other factors: • Age: 75% of pa-ents <6y at onset with peak age of onset between 22-3y. 1- Infections
- The capacity to increase hepatic synthesis appears insufficient to • Sex: male: female = 2:1-3:2 • Causes:
compensate for the large urinary losses. - decreased immunity ( urinary loss of Ig and C )
• Manifestations :
- Increased protein catabolism. - edema fluid acting as a culture medium
1- Eedema the major clinical manifestation.
- immunosuppressive therapy
A- Edema : 2- Lethargy, poor appetite, weakness, pallor, diarrhea and occasional
- protein deficiency
• Hypoalbuminemia,
ypoalbuminemia, which causes a decrease in the plasma oncotic abdominal pain.
• The common infectious complications:
pressure and transudation of fluid from the intravascular compartment 3- Hematuria & hypertension are unusual but in a minority of patients.
bacterial sepsis, cellulitis, pneumonia, urinary tract infections and
to the interstitial space.
Edema (soft and pitting in nature) : primary peritonitis.
• Edema is enhanced by: (which causes massive generalized edema) - A presenting symptom in 95% of children with NS
The reduction of intravascular volume which causes:
2- Hypovolemia
- Usually begins insidiously with unexpected weight gain and early • Causes:
1- Decreases Renal Perfusion P
Pressure, activating renin-angiotensin- morning periorbital swelling dependent areas (lower extremities, - Hypoalbuminemia the plasma oncotic pressure decreases
aldosterone system stimulates tubular reabsorption of Na . genitals and feet). loss of plasma water into the interstitial space and causing a
2- The reduction in intravascular volume stimulates release of ADH - It can develop into
to generalized and marked edema. decrease in circulating blood volume.
enhances the reabsorption of water in the collecting duct. • "anasarca" : inability to open the eyes
eyes. - Diuresis
• Recent opinions: • ascites and pleural effusion respiratory distress , swelling in
• Symptoms & signs: restlessness, cold hands and feet, delayed capillary
primary renal disturbance (reduced GFR) primary renal retention of the abdomen, scrotal or labial areas prevents walking.
filling, oliguria, tachycardia and Hypotension.
sodium and water • decreased urine output.
- suppression of the renin- angiotensin
angiotensin-aldosterone system
• Classifications : 3- Electrolyte disturbances
- Expansion of plasma increased capillary hydrostatic pressure
Hypoonatremia, Hypokalemia, Hypocalcemia
ypocalcemia
extravasation of fluid into the interstitial space edema A-- Clinical classification : • Causes:
B- Other effects : 1 Simple nephrosis : Only has the 4 major features of NS:
1- - Limitations of diet
• Like albumin, the concertration of other plasma proteins are decreased: • massive proteinuria, - Poor intake
- IgG and some components of complemen
complement decreased immunity • hypoalbuminemia, - GI loss (vomiting and diarrhea)
- Some anti-coagulant factors hypercoagulability state • marked edema, - Diuresis
- Vitamin D combining protein hypocalcemia • hypercholesterolemia.
- Transferrin anemia 2-
2 Nephritic nephrosis hypertension, C3 ↓
hematuria, azotemia, hypertension 4- Hypercoagulability states and thrombosis
3- Hyperlipidemia : Besides the 4 major features of NS, also has one or more of the • Causes:
following features: - Urinary loss of anti-coagulant
anti proteins
• Serum lipid levels(cholesterol,
(cholesterol, triglycerides) are elevated for two reasons:
1- Hypoalbuminemia stimulates generalized hepatic protein synthesis, • Hematuria: Increased RBCs (>10/HP) in urine are detected for several - Hemoconcentration and hypovolemia
-mes (at least in 3 centrifuged urine specimens within 2 weeks) - Hyperlipidemia (increased viscosity) and increased platelet
including synthesis of lipoproteins.
2- Increased urinary losses of enzyme "lipoprotein lipase" reduced • Repeated hypertension: BP>130/90mmHg in shchool
shchool-aged patients, & aggregation
>120/80 in preshchool-aged
aged patients (not caused by corticosteroids) - Elevated coagulation factors
plasma levels of this enzyme Lipid catabolism is diminished.
• Persistent azotemia: BUN>10.7mmol/L (not caused by hypovolemia) • Renal vein thrombosis is more common
• Two pathologic patterns: • Pulmonary or cerebral embolism life-threatening
• Repeated or prolonged low serum levels of total complement(CH50)or C3
1- hypercholesterolemia alone and • Avoidance of bed rest, volume depletion, diuretics and deep venous or
2- combined hypercholesterolemia & hypertriglyceridemia . B- Responsive to steroid therapy (prednisone 1.5~2mg/
1.5~2mg/kg/d) : arterial punctures to prevent embolism.
• It plays a role in: 1 Complete response: urinary protein negative
1- egative 5- Acute renal
re failure
1- Hypercoagulable state. 2 No response: + + + ~ + + + +
2- • Is more
ore often
ofte precipitated by hypovolemia
2- Progression of glomeruloscler
rulosclerosis. 3 Partial response: + ~ + +
3- • Reduction
uction in the glomerular filtration rate has also been hypothesized
hy
Laboratory findings : B) Short term prednisone therapy :
1. Urinalysis : • Prednisone dosage at:
1-- 2mg/kg/d (maximum 60 mg/day) once daily, for 4 weeks
a- Proteinuria:
Regardless of the responses, entered the next phase.
- Protein: qualitatively +++~++++
2-- 1.5mg/kg, qod for another 4 weeks, then stopped.
quan-ta-vely >0.1g/kg.d.
• The total therapy course is 8~12 weeks.
- The ratio of urinary protein to urinary crea-nine: >2
• May be associated with a higher rate of early recurrence or relapse.
b- Hematuria :
- RBC may be increased in nephritic
nephritic-nephrotic
nephrotic syndrome NS types classified by response to steroid therapy
- Occasionally appears in simple nephrosis
1- Steroid
teroid sensitive NS:
2. Blood: Complete remission is achieved within the first 8 w of the ini-al steroid therapy.
• Hypoalbuminemia: albumin < 10g~20g/L 2- Partialy steroid sensitive NS:
• Hyperlipidemia: cholesterol > 5.7mmol/L AZer 8w of the ini-al steroid therapy, edema subsides, but urinary protein is
• ESR > 100mm/h
still +~++.
3- Steroid resistant NS:
• Renal
enal func'ons and serum complement 3 may be reduced In nephritic-
Failure to achieve remission (urinary protein ≥ +++) in spite of 8 weeks of
nephrotic syndrome, standard prednisone therapy.
• Serum electrolyte determination: to evaluate hyponatremia, hypokalemia,
• Steroid dependent NS: Pa-ents who has 2~3 consecu-ve relapses occurring during
hypocalcemia
the period of steroid taper or within 14 days of its cessa-on is d
defined
efined as…
Criteria of diagnosis : • Relapse or recurrence: Patients who has urinary protein≥++
protein ++ aZer 4w of steroid
1- Massive proteinuria: Urinalysis reveals 3+ or 4+. Protein excre-on exceeds cessation or during maintenance
100mg/kg.d. • Frequent relapses or recurrences: Pa-ents who has 2 or more relapses or
erum albumin level is less than 30g/L (usually 10g~20g/L)
2- Hypoalbuminemia: Serum recurrences within 6 months, or ≥3
3 within 12 months is said to have …
3- Hypercholesterolemia: the serum concentra-on of cholesterol is > 5.7mmol/L
4- Edema with various degrees Adverse effects of long term corticosteroid treatment
• Cushingoid features (obesity, round face, striae)
• The first two items are the most necessary for diagnosis
• Increased susceptibility to infections
• The diagnosis of different clinical types of NS
• Hypertension
• Osteoporosis
Differential Diagnosis : • Hypokalemia
Primary NS should be differentiated from : • retarded growth
1- Secondary NS or • Cataracts
2- GN with nephrotic picture, such as HSP nephritis, SLE nephritis, APSGN. • Peptic ulcer disease
Treatment : • Diabetes mellitus
A- General measures
1- Activity :
• Do not restrict activity unless the patient is severely edematous or with severe
2- Cytotoxic agent therapy :
• Cyclophosphamide, cyclosporine, chlorambucil, nitrogen mustard…
hypertention or infections.
• To prevent thrombosis, patients restricted to bed rest should change position • Indication:
frequently. - Intractable NS (steroid resistance, frequent relapses or recurrences)
- Steroid dependent NS with signs of steroid toxicity.
2- Diet :
• The adverse effects: sexual gland damage; bone marrow depression; hemorrhagic
• The diet should provide adequate energy (calorie) intake and adequate protein
(1-2 g/kg/d). cystitis; nausea, vomitting, gastritis; alopecia; liver damage.
• Sodium restriction (Low sodium or no sodium diet) is indicated for patients with
edema or hypertension, but should be adjusted according to the serum levels of 3- Pulse therapy :
sodium. Long-term
term sodium restriction is not recommended.
recommend
• Fluid restriction is required when the edema is severe with oliguria. 1- Methylprednisolone:
• Replacement of vitamins and minerals. - 15~30 mg/kg.d (<1.0g/d)
1.0g/d) add 10% glucose 100~250 ml in drip, for 3 days.
Repeated same as above every 1~2 weeks if necessary.
3- Diuretic therapy :
• Diuretic is indicated when edema is severe, esp. with ascites 2- CTX:
• It can be used for symptomatic relief until steroid diuresis occurs
- 0.5~0.75g/m2 in drip, once monthly, for 6 months if necessary.
- Hydrochlorothiazide(HCT): 2 2-4mg/kg.d
- Antisterone: may be added if HCT is not effective.
- Salt-poor
poor albumin at 0.5~1g/kg iv, over 1 hr (when serum albumin<20g/L), Prognosis :
followed by iv injec-on furosemide 11-2mg/kg.dose
2mg/kg.dose . Mul-ple use is not • Varies depending on the histological type
recommended. • >90%
90% of MCNS respond to cor-costeroid therapy
- A renal blood vessel dilator should be given (dopamine 2~4 μg/kg.min) in - Only 30% of children never have a relapse aZer the ini-al remission
patients with refractory edema, combined with furosemide. - approximately 50% have 1-2 2 relapses within 5 years
• Hypovolemic shock or postural hypotension should be monitored during - 20% con-nue to relapse 10 years aZer diagnosis\
diagnosis
diuresis. - Approximately 3% of pa-ents who initially
initially responded to steroids become
4- Treatment of complications steroid resistant.
• Anti-infection: antibiotics
ntibiotics that cover both gram
gram-positive
positive and negative organisms - Only approximately 20% of pa-ents with FSGS undergo remission of
should be given; But continuous prophylactic antibiotics are not recommended. proteinuria
• Anti-coagulation
coagulation therapy: heparin, persantin,
antin, exercise of extremities, - Approximately 50% of pa-ents with MsPGN undergo complete remission of
• Therapy for electrolyte disturbance.
proteinuria during steroid therapy
- MPGN has the mostt worse prognosis. no difference was evident in the
B- Specific therapy : outcome between treated and untreated patients;
1- Glucocorticoid therapy
2- Cytotoxic agent therapy
3- Pulse therapy Indications of renal biopsy
• Unsuccessful therapeutic trial of steroids :
1- Glucocorticoid therapy - Steroid resistance

- At initial diagnosis, Prednisone or Prednisolone oral therapy is the first line: - Frequent relapses or steroid dependency

- Before starting steroid therapy, a tuberculin skin test should be done. • A child >10y at onset
long term prednisone therapy
A) Medium-long • Coexistence of significant hematuria, hypertension, azotemia and depressed serum
• Commonly used in China, including 3 phases: C3 at onset.
1- 2mg/kg/d (maximum 60 mg/day) once daily, un-l the proteinuria has • Secondary causes of nephrotic syndrome.
dissappeared for 6 weeks
- Remission can be achieved during this phase in most children with PNS, then
entered the next phase
- If remission isn’t achieved, con nue the ini al dosage, but not over 8 weeks
before entered the next phase.
2- 1.5- 2mg/kg, qod (single dose, every other morning, alternate-day
alternate therapy) Sources : 1- Nelson
for another 4 weeks.
3- Reduced by 2.5~5 mg q2 q2-4w un-l stopped.
2- Lang pathophysiology
• Medium term therapy: tota
total course is 6m 3- Dr/ Sherein Shalaby
alaby lecture
• Long term therapy: total co
course is 9~12m
 Hypernatremia Hyponatremia
A) Net water loss B) Hypertonic sodium gain 1- Euvolemic ( Urine Na > 20  patient not Hypovolemic )
Hypotonic fluid Pure water Primary hyperaldosteronism Cushing syndrome Urine Osmolality < 100 Psychogenic polydepsia
 Central DI: -  aldosterone secretion from adrenal gland. -  cortisol level : Urine Osmolality > 100 the urine is inappropriately concentrated :
a- Renal losses : - Low ADH secretion. - Causes: A) Iatrogenic : exogenous steroids (most common)
 Loop diuretics SIADH Adrenal insufficiency Hypothyroidism
- Idiopathic 50% / head * functioning adenoma "Conn Syndrome" B) Non-iatrogenic: Diagnostic test:  Urine osmolality > 100 /  urine Na > 40 -I feel Tired (Weakness, fatigue) -I feel Tired (Weakness, fatigue)
 Osmotic dieresis * Bilaternal Adrenal Hyperplasia * ACTH independent  from adrenal gland (1ry)
trauma/ destructive disea.  Plasma osmolality < 280 -because I'm "anorexic, vomiting , lost weight" & hypotensive - I'm " Constipated , gain weight " / braycardiac
 Postobstructive - C/P * ACTH dependent 2ry :
 Nephrogenic DI: The most accurate test is a high ADH level. - Hyperpigmentation - cold intolerance / dry , cold , puffy skin.
dieresis - Unresponsiveness of renal *  Na & Water  Hypertension -- ACTH From pituitary: "Cushing's disease" Causes Types Causes of 1ry hypothyroidism
 Intrinsic renal * K & H ions  Hypokalemia & M.Alkalosis -- Etopic ACTH production : SSC of lung
tubules to ADH. CNS Sub Arachnoid Hemorrhage "SAH" : 1ry 2ry 1- Hashimoto’s thyroiditis :
disease + 1) Polydipsia, nocturnal polyuria (due to hypokalemia) - C/P st nd
-Head trauma (SAH) - Causes: 1 trauma / 2 berry aneurysm - Hashitoxicosis  followed by hypothyroidism
- Acquired : Mostly by :  ACTH by the
2) Absence of peripheral edema -Changes in appearance: central obesity, hirsutism,moon - Sudden severe headache (worst in my life)
Chronic Lithium use (most)/ - Diagnosis: -Tumor Autoimmune destruction pituitary, by: - Lab: +ve Anti-TPO antibodies / antimicrosomal antibodies
b- Non-renal losses: facies, “buffalo hump,” purple striae on abdomen, acne/ + signs of meningeal irritation + Fluctuating LOC (Addison's disease) - Biopsy: lymphocytic infiltration.
Hypercalcemia/UTI (pyelo) - do CT scan before LP ( ICP, RBCs, xanthochromia) MRI +ve  tumor
 Vomiting * Screening: - Diabetes ,Hypertension Others:
- Congenital Once confirmed  Four-vessel angiography MRI –ve  Long-term 2- hypothyroid phase of thyroiditis :
 NG suctioning Plasma: aldosterone / rennin/A:R ratio>30 - Hypogonadism, Masculinization in females, proximal -TB  CT shows: calcification
Diagnosis: Plumonary Sarcoidosis : Non-caseating granulomas Steroids use - Subacute & radiation-induced forms  tender thyroid
 Enterocutaneous * Confirmation: with either: muscle wasting and weakness, Psychiatric disturbances -Metastasis
- Urine:  SG/Osmolality. - Diagnosis:  Fever, malaise , -Hemorr.  acute + blood in CT - Diganosis: ↓ uptake on RAIU during thyrotoxic phase
fistula 1) Saline infusion test: C/P : GRUELING Investigations
- P.osmolality: weight loss -Adrenoluckodystrophy 
 Burns - Infusion of saline will decrease aldosterone - Screening: Granulomas CXR: Bilateral hilar 3- Iatrogenic factors :
Normal: 250 to 290 mOsm/kg  cough, dyspnea, aRthritis lymphadenopathy alone VLCFA + enlarged glands in CT
 Excessive sweating levels in normal patients 1) low-dose dexamethasone suppression test a- Radioactive thyroid ablation or excision
DI: 280 to 310 mOsm/kg  Polyarthritis Uveitis Hyponatremia + eosinophilia + Hypercalcemia (1/3)
2) Oral Sodium Loading * If the serum cortisol is <5  No Cushing. TTT: Biopsy: noncaseating
b- Infiltrative disease
- A water deprivation test : Erythema nodosum No aldosterone : ACTH independent
* Diagnose cause: * If the serum cortisol is >5  Cusing syndrome Systemic Steroids Lymphadenopathy granulomas c- Drugs: Lithium / Amiodarone
• Withhold fluids, and measure  Hyperkalemia  Normal
urine osmolality every hour 1) Adrenal venous sampling 2) 24-hour urinary free cortisol level Brain : cranial nerve Interstitial fibrosis
PFTs:  lung volumes TTT TTT β-blockers for hyperthyroidism/levothyroxine for hypothyroidism.
• When urine osmolality is stable  aldosterone level on one side indicates an adenoma. - ACTH level: defects (Facial palsy) Negative TB test
(restrictive pattern) Glucocorticoid+mineralocorticoid Glucocorticoid NSAIDs or oral steroids in severe cases for : Subacute thyroiditis.
(<30 mOsm/kg hourly increase for 3  aldosterone on both sides indicate bilateral hyperplasia. Heart : arrhythmias/ Gammaglobulinemia
* If low 1ry Cushing(adenoma/or hyperplasia)
hours), inject 2 g desmopressin S.C. 2) Imaging tests * If high 2ry (pituitary /or ectopic production):
restrictive 3↑: serum ACE levels / Hypercalcemia, ALP (liver). In adrenal crisis : 4 S Myxedema coma : severe hypothyroidism with: (Mortality 60%.)
Measure urine osmolality 1 h later : cardiomypathy 1  lymphopenia. Salt: 0.9% saline Steroids: IV hydrocortisone 100 mg q 8 hours ↓ mental status + hypothermia + other parasympathetics
urine osmo response to ADH
- Treatment: to differentiate between pituitary & ectopic ACTH: Support Search for the underlying illness
Paraneoplastic Small cell lung cancer (SCLC) TTT 1- IV levothyroxine
1. For adenoma— adrenalectomy. a) High dose dexa suppression test :
Normal + - syndrome Cigarette exposure + Central location. 2- IV hydrocortisone (if adrenal insufficiency has not been excluded)
2. For bilateral hyperplasia In Pituitary decrease in cortisol > 50%
C-DI - + In ectopic  No suppression occur. Diagnosis : 1- Synthetic ACTH stimulation test: Diagnosis :
a. Spironolactone  action of aldosterone. Drugs
SSRis, tricyclic antidepressants/
N-DI - - b) CRH stimulation test. vincristine, cyclophosphamide/ sulfonylureas Cosyntropin  plasma cortisol level < 20 ug/dl 1ry :  TSH /  T4 & T3 (T3 to lesser extent)
b. Surgery is not indicated. 2ry & 3ry : Normal or  TSH /  T4 & T3
2- Insulin tolerance test.
2- Hypovolemic
Urine Na < 20 1- Vomiting 2- Diarrhea 3- Nasogastric tube 4- Sequestration of fluid in burns , ilues , Traumatized muscle , pancreatitis
1- Diuretics 2- Mineralcorticoid deficiency
Urine Na > 20 : Loop Water loss Metabolic alkalosis  Ca2 K, sulfa allergy Ototoxicity 1- Na+ loss with Hyponatremia, hypovolemia, hypotension
Thiazide Water loss, Metabolic alkalosis Na  Ca2 K, glucose /Uric acid sulfa allergy Pancreatitis 2- Impaired secretion of both K+ and H+ in the renal tubules  Hyperkalemia & metabolic acidosis

3- Hypervolemic
Urine Na > 20 : 1- Acute & chronic renal failure
ARF Causes Urine osmolality Urine Na FENa FEUREA BUN/creatinine 
Hyaline casts - Normal, BUT  amount suggests dehydration – Prerenal Indications for urgent dialysis— AEIOU
Hypoperfusion in : heart failure / liver failure / sepsis / burns / bilateral renal artery stenosis 
Red cell casts, dysmorphic red cells – Glomerulonephritis – Intrinsic Acidosis
Pre-renal >500 : dehydration release ADH leading <20 <1 % <= 35 % >20 : 1
to increases water absorption

Granular casts “muddy-brown cast” , tubular cells– Acute Tubular Necrosis – Intrinsic Electrolyte abnormalities (hyperkalemia)
Acute tubular necrosis (ATN) "most common" / Allergic interstitial nephritis (AIN); 
White cells, eosinophils – Acute (Allergic) interstitial nephritis – Intrinsic Overload (fluid).
Renal <300 : Similar in osmolality to blood (300 >20 >1 % > 50 % < 20 : 1 (about 10:1) Uremic symptoms (pericarditis, encephalopathy, bleeding, nausea, pruritus, myoclonus).
Glomerulonephritis; / Nephrotoxin exposure (including myoglobin from rhabdomyolysis); mOsm/L). This is called isosthenuria
(Wright & Hansel stains detect eosinophils in urine) / NO eosinophils in NSAID
Obstruction 2ry to : benign prostatic hypertrophy (BPH) / bladder & pelvic tumors / calculi  White cells, white cell casts – Pyelonephritis – Postrenal (WBC with -ve culture: TB)
Post-renal <350 >40 >4 % 20 : 1
Urine Na < 20 : Causes of generalized edema :
Nephrotic syndrome Cirrhosis Congestive heart failure
Criteria of diagnosis (4) : 1- Proteinuria (≥ 3.5 g/day) 2- Hypoalbuminemia (< 3 g/dL) 3- Hyperlipidemia (>250 mg/dl) 4- Generalized edema Abnormal LFTs: ↓ albumin, ↑ PT/PTT, ↑ bilirubin. / Anemia or thrombocytopenia (2ry to hypersplenism).
- Most common cause in children Tendency toward : LM: Normal TTT: 1- Chronic hepatitis: HCV / HBV  Search for serological markers. Systolic Dysfunction Diastolic Dysfunction
Minimal change Disease - 1ry idiopathic - Infection EM: fusion of epithelial foot processes Steroids HBV : HBsAg  found on the surface of HBV; continued presence indicates carrier state.
- 2ry causes : NSAIDs - Thrombotic events Excellent prognosis
Impaired contractility  decrease in EF Impaired ventricular filling during diastole
HBsAb  provides immunity to HBV. (either:  relaxation or  stiffness or both)
Focal segmental - Idiopathic - IV drug use Young black male with uncontrolled LM: sclerosis in capillary tufts - Prednisone HBcAg  associated with core of HBV.
- HIV infection - Obesity hypertension + microscopic hematuria - Cytotoxic therapy HBcAb  during window period. IgM HBcAb is an indicator of recent disease.
glomerulosclerosis 1- HTN , resulting in cardiomyopathy 1- HTN: Most common cause.
HBeAg  antigenic determinant in the HBV core. An important indicator of transmissibility. (BEware!) 2- Post-MI (IHD) 2- Valvular: AS , MS , AR
2ry causes : - Mostly in Caucasian adults "Spike & dome appearance" - Prednisone
Membranous nepthropathy HBeAb  indicates low transmissibility
- Solid tumor malignancies. - Associated with : Due to granular deposits of : - Cytotoxic therapy 3- Valvular heart disease 3- Restrictive cardiomyopathy
- Immune complex disease HBV / syphilis / malaria / gold IgG & C3 at the basement membrane 2- Biliary tract diseases : 4- Myocarditis (postviral) (e.g.,amyloidosis, sarcoidosis, hemochromatosis)
- Type I is associated with : - “Tram-track,” double-layered basement membrane. - Prednisone a- 1ry biliary cirrhosis : the most accurate test is "liver biopsy" / TTT: ursodeoxycholic acid
Membranoproliferative Can also be nephritic syndrome. - Middle aged Femal > male with RA, Sjögren syndrome, Scleroderma + progressive jaundice, pruritus, fatigue
Symptoms: Symptoms & signs :
HCV / cryoglobulinemia / lupus / - Type I : subendothelial deposits + mesangial deposits; - Cytotoxic therapy
subacute bacterial endocarditis. - Type II : - Lab: ↑ ALP+GGTP, Normal bilirubin BUT elevated in advaced , most specific: +ve antimitochondrial antibody. Dyspnea, orthopnea, Paroxysmal nocturnal Peripheral pitting edema,JVD, Ascites, Nocturia,
nephropathy Slow progression to renal failure.
Two forms: Long-standing, poorly controlled DM - Thickened GBM - Control of diabetes b- 1ry sclerosing cholangitis: the most accurate test is "ERCP"/ TTT:cholestyramine or ursodeoxycholic acid
dyspnea, Nocturnal cough (nonproductive) Hepatomegaly/hepatojugular reflux,
1- Diffuse hyalinization with evidence of retinopathy or -  mesangial matrix - ACEIs for type1DM - Yong male > female with IBD (ulcerative colitis) + progressive jaundice, pruritus, fatigue Signs: Right ventricular heave.
Diabetic nephropathy
2- Nodular glomerulosclerosis neuropathy. - ARBS for type2DM - Lab: ↑ ALP+GGTP+bilirubin / ERCP : multiple bile duct strictures / Liver biopsy:periductal sclerosis (“onion skinning”). Displaced PMI, Pathologic S3, S4 gallop , left-sided heart failure will always lead to
(Kimmelstiel-Wilson lesions) 3- Budd-Chiari syndrome : Crackles/rales at lung bases,  intensity P2 right-sided heart failure and vice versa
1ry : plasma cell dyscrasia May Associations with : - Fat pad biopsy / Seen with Congo red stain - Prednisone - Hypercoagulability  hepatic vein thrombosis  acute onset of abdominal pain, jaundice  cirrhosis (Dx:RUQ US) indicates pulmonary HTN (heard over left
Renal amyloidosis
2ry: infectious / inflammatory 1- Multiple myeloma 2- RA - Apple-green birefringence by polarized light - Melphalan 3- Wilson’s Disease : autosomal-recessive defect on Chr. 13. / Age < 30 years of age : ABCD- Asterixis / Basal upper sternal border).
I • No renal involvement visible by histopathology ganglia deterioration Ceruloplasmin  , Copper  Cirrhosis , Carcinoma , Choreiform movements / Dementia - Diuretics -Digitalis Patients are treated symptomatically:
II • Mesangial disease with focal segmental glomerular pattern • Tx not typically required for kidney involvement Drugs that lower mortality : (NO medications have proven mortality benefit)
4- Alcohol Liver cirrhosis :
Lupus nephritis III • Focal proliferative disease • Tx = aggressive prednisone ± cyclophosphamide 1- ACEIs / ARBs 2- Spironolactone 1- ACEIs / ARBs 2- B-Blockers. 3- Diuretics
5- Alpha 1-Antitrypsin Deficiency 3- B-Blockers 4-Hydralazine, plus nitrate
IV • Diffuse proliferative disease, (Classic LM:- wire-loop abnormality ) • Tx = prednisone + cyclophosphamide, transplant may be required Digoxin & spironolactone should NOT be used!
6- Hemochromatosis
V • Membranous disease, indistinguishable from other 1 ry MGNs • Tx = consider prednisone, may not be required
 Bacteria causing Urinary Tract Infection
Organism Morphology Culture characters Biochemical Diagnosis : Pathogenesis
activates
- They ferment: - The specimen is: Urine, stool, pus ..etc ( Extra-intestinal disease )
- Gram -Vebacilli - Facultative anaerobes. - Glucose 1- Urinary tract infection :
- Maltose - They are cultured on - causes 90% of community acquired UTI.
- Motile . - Grow on:Simple media. - Mannite macConkeymedium:resulting in(look - Certain strains called " uropathogenic Coli
previous) , and further identified by their " colonize the vagina and periurethral
- Sucrose region from where the ascend to the
- On macConkey
macConkeyagar: morphology and biochemical reactions.
- Some strains are - Salicin bladder or kidney causing cystitis or
capsulated. they produce pink With production of
Escherichia colonies due to lactose acid and gas.
In case of diarrhea : pyelonephritis.
* These strains posses :
fermentation. Isolated E.Coli should be futher tested
Coli serologically and virulence proved :
1- Pilli with adhesive proteins to
bind to specific receptors on UT
- has fimbriae or pili +ve to :
- On blood agar
agar: epithelium .
- E. coli is part of the that are frequently 1- Serotyping
they produce - Indole 2- K antigens
normal flora of the colon important for by slide agglutination for EPEC 3- Exotoxins ( haemolysins)
adherence to host Haemolysis. - M.R.
in humans & animals. and EHEC strains. - E.Coli causes hospital UT infection which
mucosal surfaces. - Citrate is associated with urinary catheterization&
- can be pathogenic both 2- When HEHC infection is drug resistant strains
within and outside of the -ve to :
suspected,
GI tract - Oxidase. 2- Neonatal meningitis :
a- rapid diagnostic methods are
- Urease used to detect the verotoxin by E.Coli causes 40% of neonatal meningiBs
- H2S. ELISA,
Strains usually posses K1 anBgen.
- P.V. b- or to detect the organism by
3- Pneumonia, Sepsis ,becteraemia,
immunofluorescence in stools.
- Can generate energy by endotoxic shock .
reducing nitrates to 3- Vivo assays, tissue cultures ,
nitrites. immunoassay, DNA probes, PCR (intestinal disease )
maybe used for detection of Look micro book P. 40-41
toxin
n production or its gene.
- They ferment:
- Gram -ve Bacilli - On macConkey
macConkeyagar: - Glucose - They are cultured on macConkey * K. pneumoniae causes :
they produce pink - Maltose medium: resulting in(look previous) , and
- non-motile. colonies due to lactose - Mannite further identified by their morphology and - lobar pneumonia
fermentation. - Sucrose biochemical reactions.
- urinary tract infections
Klebsiella - capsulated.
- The colonies are
- Salicin
With production of acid - in smears from tissues stained by gram :
- bacteremia,
and gas. capsulated organisms can be seen - neonatal meningitis.
mucoid due to the
production of abundant -ve to : +ve to:
extracellular slime. - It's highly pathogenic to the mice * It's common cause of hospital
indole V.P and cause their death within 24-48
48 hours acquired infections.
M.R. Citrate when injected intra-peritoneally.
 - Normally inhabitants of the intestine
- Gram -ve Bacilli - Facultative anaerobes. +ve to : By: of man, and thy cause infections only
when they leave the intestine.
Proteus - Highly motile.
- On MacConkey agar:
they produce pale non
non-
- phenylalaninedeaminase.
- urease,(which catalyzes the - They cause:
1- Colony morphology.
lactose fermenting ………………….hydrolysis of urea to 1-UTI ,commonly by Pr.mirabilis.
- Very colonies. ………………….ammonia) 2- Biochemical reactions. 2- wound infections, otits media,
* Species are found in:
pleomorphic. Which differentiate them pneumonia, bacteraemia.
- soil
- On nutrient agar: from salmonella &shigella .
- water * Infections maybe hospital or
Due to their
heir highly community acquired.
* The genus includes motility, they give - H2S
two important species: colonies which swarm in Which blackens the butt of N.B. Proteus infections resistant to
successive waves over trple sugar iron (TSI) agar. antibiotics so, antibiotic test should be
1- Pr.vulgaris the surface on nutrient done before the treatment.
2- Pr.mirabilis agar.

- P. aeruginosa disease begins with

- Gram -ve Bacilli - Aerobe. - Ps. Aeruginosa is 1-P. aeruginosa can be isolated in: attachment to and colonization of host
tissue. Via virulence factors:

- Motile.
- On MacConkey agar
agar: Oxidase +ve - (blood agar) 1- Pili on the bacteria mediate adherence
they produce pale non
non- - (MacConkey agar) 2-glycocalyx capsule reduces the
Pseudomonas lactose fermenting Identification is based on the results of
effectiveness of normal clearance
- encapsulated . colonies. mechanisms, with resulting adherence of
- Acid is produced from biochemical and other diagnostic tests the organism to mucous membranes
- On Blood agar: glucose by oxidation allows to life in a biofilm away from
* Species are found in - ( Nutrient agar ) antibiotics and phagocytosis.
Haemolyze the blood. only.
- soil - P. aeruginosa produces:
- sewage 1- endotoxin and enzymes (elastase&
- On nutrient agar: - Doesn't ferment any
- and water protease) that facilitate invasion.
- some are commensals Grow on nutrient agar sugar.
2-Pus from the lesion maybe greenish 2- Exotoxin which cases tissue
in the intestine. leading to greenish
blue. necrosis.
colouration of the
medium due to its
* It causes :
1-urinary tract infection, (particularly in
* The commonest diffusible exopigment
hospitalized patients who have been subjected
human pathogen of this which consists of : 3- Smears stained by gram show gram to catheterization, instrumentation, surgery, or
group is : - pyocyanin (blue) -vebacilli among pus cells. renal transplantation)
- pyoverdin 2- wound infection, otitis externa,
(yellow- green fluorescent) corneal ulcers in lens users,pneumonia
Ps.aeruginosa
, sepsis with ecthyma in skin.
- Culturess have a sweet 3-Osteomylitis and endocarditis in IV
grap-like odour. drug users.
Causes 10% to 20% of hospital infections (p.52)
 The
he parasitic stages detected in urine analysis:
– Schistosoma haematobium eggs.

– Schistosoma mansoni eggs( 5%).

– Hydatid sand.

– Enterobiusvermicularis eggs in females.

– Enterobiusvermicularis Adult.
Enterobiusvermicularis.

– Wuchereriabancrofti microfilaria (chylurea).

– Trichomonasvaginalis
Trichomonasvaginalis.

– Leishmaniadonovani.

- Fannia larva (urinary myiasis).

- adult.
Sarcoptesscabieiadult.

- Phthirus pubis.

*The appearance of urine may be altered in many parasitic infections:

a- Urinary schistosomiasis:

red, cloudy.

b- Black water fever -in P. falciparum-

falciparum (intravascular haemolysis):

brown, cloudy.

Frequent occurrence of rapid intravascular haemolysis, due to auto-haemolysis,

auto haemolysis, where haemoglobin will pass in
urine (haemoglobinuria).

c- Bancroftianfilariasis:

milky-white.
 1- Schistosoma :
Schistosomahematobiumegg Schistosomamansoni egg

• Shape: oval. • Shape: oval.

• Size: 140 x 60 um • Size: 150x 65 um
• Shell: thin with terminal spine • Shell: thin with lateral spine
• Colour: transparent • Colour: transparent
• Contents: mature miracidium. • Contents: mature miracidium.

- W.H.O. (1991) CLASSIFICATION OF SCHISTOSOMIASIS

• S. haematobium:

- light infec#on (< 50 eggs /10 ml)

-------------- frequenthaematuria.

- Heavy infec#on (> 50 eggs /10 ml)

-------------- constanthaematuria.

- Diagnosis of urinary schistosomiasis

1- Sedimentation method;

2- Centrifugation method;

3- Nucleoporefiltrration method.

Ova in urine (terminal urine- mid morning).

- Evaluation of intensity of infection in Urinary schistosomiasis

• Nucleporefiltrra#on method (Feldmeier, 1993):

• Examine 10 ml of urine collected between 11:00 and 14:00 at the peak of the diurnal egg count cycle.

• Detection will be enhanced by centrifugation and examination of the sediment.

• Qualification is possible by using filtration through a Nucleopore membrane of a standard volume of

urine, followed by egg counts on the membrane.
2- Hydatidsand :
- Scolices and broad capsules are separated from germinal layer & floating in hydatid fluid.

- rupture of hydatid cyst in kidney or bladder.

3- Enterobiusvermicularis :
Enterobiusvermicularis adult Enterobiusvermicularis egg (in females).

- Spindle-shaped • Shape: planoconvex.

- Male, 5mm, curved post. end/ Female, • Size: 50x 20 um.
10mm, sharply pointed tail. • Shell: double layer.
- Double -bulbedoesophagus • Colour: transparent
• Contents: mature larva.

• Migration of female Enterobious during night from anus …..

• So, Swabbing of anal or perianal area by :

1- N.I.H. swab (National Institute of Health).

2- Scotch adhesive tape swab.

3- Urine analysis is essential .

4- Tricomonasvaginalistrophozoit
• Shape: pear-shaped
• Size: 15 x 8 um
• Cytosome: present.
• Flagella: four;
• Nucleus: single, anterior.
• Axostyle: very slender axostyle.
• Parabasal body:present,thick.
5- Wuchereriabancrofti :
• Adult worms live in the lymph vessels and lymph nodes of the, trunk, retroperitoneal tissues
and limbs.

• Microfilariae ( embryos laid by female ) reach the circulation via the lymphatics.

• Clinical Picture :

Lymphatic obstruction :

- blockage of the lumen by worms

- proliferation of endothelial lining.

- fibrosis& stenosis of lymph vessels.

- fibrosis of lymph nodes draining the area.

- Distension and varicosity of lymphaticsdistal to the obstruction site.

- Rupture of distended lymphatics in different body sacs and urinary tract (chyluria)

- Persistent lymphatic edema.

• Diagnosis :
- Detection of microfilariae in chylous fluid or chylous urine.

- ( A ) Milky urine passed by a patient with chyluria

compared

( B ) with normal-coloured urine

• Wuchereriabancrofti microfilaria :
- Size: 250x 8 um

- Blunt rounded anterior end & tapering tail

- Sheath: Loose sheath

- Body with graceful curves.

- Central column of cells with deeply stained nuclei.

- Tail free of nuclei

 6- Leishmaniadonovani :

- Amistigote:
- Small oval intracellular, 2x3 u
- Contains a nucleus and a rod-shaped
kinetoplast( formed of parabasal body,
blepharoplasty and an axoneme which
is a short intracellular flagellum).

InKala azar, ulceration of urinary tract, with passage of Leishmania bodies in urine.

7-Sarcoptesscabiei (itch mite):

- It's small oval or globular formed of one piece.

- A capitulum is projecting anteriorly.
- 4 pairs of legs.

- Mites live in tunnels in the corneal layer of the skin.

8- Pediculosis (Lice) :
- Small sized insect ( 2- 4 mm ) dorsoventrally compressed.
- The body is divided into conical head, thorax and abdomen.
- The thorax is wingless and carries 3 pairs of legs adapted
for clinging.
- The abodomen consists of 8 segments. It is notched in
female while in male, there is a protruded spine-like
aedeagus.

• The three lice species that infest humans are:

1- Pediculushumanuscapitis( head louse)
2 - Pediculushumanuscorporis( body louse)
3- Phthiruspubis (crab or pubic louse ),,It's similar to pediculus but the thorax and …..
abdomen are compressed together.

( All three insects are obligate human parasites )

 9- Fannia larva (urinary Myiasis ) :
- Definition:
It's the invasion of tissues of animals or humans by the larval stages of dipterous flies.

- Transmission :
occurs through accidental deposite of eggs on genitourinary openings,

- Fannia larva may enter through the urinary or genital orifices during defaecation or
during sleep, with clinical picture of inflammation of urinary tract, pain during urination.
- The adult flies are not parasitic, but when they lay their eggs in open wounds and these
hatch into their larval stage (also known as magots or grubs), the larva feed on live and/ or
necrotic tissue, causing myiasis to develop.

The causative flies are:-

1- Muscadomestica (House fly).
2- Calliphora spp.
3- Sarcophaga spp.
4- Fanniaspp. (latrine flies).
5- Eristalistenax (Rat –tailed
tailed maggots).
maggots)

- Urine analysis is performed to detect abnormal constituents

that indicate a pathological state.

* General characteristics of urine:

• 1. Volume: normally 1.5 – 2 L / Day.
• 2. Color:: urochrome (amber yellow).
• 3. Transparency: Clear transparent.
• 4. Odor:: faint aromatic odor due to the presence of volatile organic acid.
• 5. PH : slightly acidic 5.5 – 6.5.
• Normal freshly passed urine;
- Clear,
- Pale to dark yellow in color.

* Urine Examinations :
• Include:
– Collection.
– Physical & chemical examination.
examination
– Microscopic examination.
examination
 Urinary Tract Antiseptics/Antimicrobials

• Urinary tract infections (most commonly uncomplicated acute cystitis and pyelonephritis)

- Escherichia coliis
is the most common pathogen, causing about 80 percent of uncomplicated upper
and lower UTIs.

- Staphylococcus saprophyticus is the second most common bacterial pathogen causing UTIs,

- Klebsiellapneumoniaeand Proteus mirabilisother

mirabilis common causes .

Urinary tract antiseptics, including methenamine, nitrofurantoin,

nitrofurantoin, and the quinolone nalidixic acid.

N.B.These
These drugs do not achieve antibacterial levels in the circulation, but because they are
concentrated in the urine,microorganisms
microorganisms at that site can be effectively eradicated.

Mechanism of action Anti-bacterial

bacterial spectrum Side effects

To act, methenaminemust
methenamine - Used for - GIT distress
decompose at an acidic pH of 1- chronic suppressive
5.5 or less in the urine, thus therapy. - albuminuria
producing formaldehyde, which 2- lower UTIs but is not
Methenamine is toxic to most bacteria. - hematuria
effective in upper UTIs.
[Note: Methenamineis
Methenamine frequently - rashes
Urea-splitting bacteria
formulated with a weak acid, such
as mandelic acid or hippuric acid.]\ that alkalinize the urine,
such as Proteus species,
The drug is eliminated unchanged in are usually resistant to
the urine, in which these drugs are the action of
bactericidal for some gram –ve methenamine.
bacteria.

- Sensitive bacteria reduce the - gram +ve - GIT disturbances,

drug to an active agent that
Nitrofurantoin inhibits various enzymes and - acute pneumonitis,
- gram –ve bacteria
damages DNA
is less commonly employed
for treating UTIs because of
- neurologic problems.
its narrow antimicrobial - Antibiotic activity is greater in BUT
spectrum and its toxicity. acidic urine proteus are resistance.

- The drug is bacteriostatic and

bactericidal

dihydrofolatereductase inhibitors
Folate is important to DNA and RNA synthesis , so in absence of flate, cells can't growth or divide.

- Potent inhibitor of bacterial dihydrofolatereductase

Trimethoprim produce the effects of folic acid
The active form of folate is the tetrahydro-derivative deficiency.6 including :
- often compounded that is formed through reduction of dihydrofolic acid by
with: dihydrofolatereductase. - megaloblastic anemia,
sulfamethoxazole This enzymatic reaction is inhibited by trimethoprim,
leading to a decreased availability of the tetrahydrofolate - leukopenia,
producing the coenzymes required for purine, pyrimidine, and amino
combination called acid synthesis. - granulocytopenia, especially in
pregnant patients and those having very
cotrimoxazole. poor diets.
 - Shows greater antimicrobial activity than
equivalent quantities of either drug used alone.

N.B. The combination was selected because of the 1- Dermatologic:

similarity in the half-lives
half of the two drugs. Reactions involving the skin
ski
Cotrimoxazole
Mechanism of action 2- Gastrointestinal:
The combination of
trimethoprimwith
- Nausea,
sulfamethoxazole Antimicrobial activity of cotrimoxazoleresults from
- vomiting,
its inhibition of two sequential steps in the synthesis - glossitis
of tetrahydrofolic acid:

1- Sulfamethoxazole 3- Hematologic:
(from sulfonamides family ),
)
- Megaloblastic anemia
In many microorganisms, dihydrofolic acid is - Leukopenia
synthesized (PABA), - thrombocytopenia may occur.

Because of its structural similarity to PABA, the

sulfonamides compete with this substrate for the
bacterial enzyme, dihydropteroatesynthetase.

They thus inhibit the synthesis of bacterial

dihydrofolic acid

2- trimethoprim
prevents reduction of dihydrofolate to
tetrahydrofolate
 Kidney Function Tests
• Causes of kidney functional disorders:
- Pre-renale.g. decreased intravascular volum
- Renale.g. acute tubular necrosis
- Postrenale.g.ureteral obstruction

• Purposes:

Detect renal damage.

Determine the degree of functional damage.

Determine the principle site of disturbance in the nephron.

Classification of KFTs
Glomerular function tests Tubular function tests
1) Urine examination. 5) Urine concentration test.
2) Estimation of blood urea & serum creatinine. 6) Urine dilution test.
3) Urea clearance test. 7) Plasma electrolyte determination.
4) Creatinine clearance test.

1- Blood urea and serum creatinine:

- Normal values :

• Blood urea= 20-40 mg %

• Serum creatinine= 0.4-1.4 mg %

- The value depends on the balance between production and excretion.

a- Blood urea :
- Bloosurea can be affected by certain factors :

1) Low protein diet.

Blood urea
2) Dialysis.

b- Serum creatinine :
• Creatinine is the end product of creatine catabolism .
• 98% of the body crea2ne is present in the muscles where it functions as store of high energy in the form
of creatine phosphate.
• About 1-2 % of total muscle crea2ne or crea2nephosphate pool is converted daily to crea2nine through
the spontaneous, non enzymatic loss of water.
• Creatinine level is more in males than in females as the greater muscle bulk.
 - Plasma creatinine is an endogenous substance not affected by diet.

- Thus, Creatinine is preferable to Urea estimation as an index of renal function.

2) Urea and Creatinine Clearance:

Clearance :

It is the amount of blood which could be completely cleared of a substance/ minute.

Clearance (C) [ml/min] = [ U x V ] / P

U = The concentration of the substance in urine (mg/dl).

V = Urine volume per minute ( ml/min).

P = Plasma concentration of the substance (mg/dl).

- The Principle of Clearance

Some substances when filtered & enter the tubules are not reabsorbed or secreted.
Thus, excreted= GFR

Some substances are filtered, enter tubules, and more of the substance is secreted into the tubules.

Thus, Clearance>GFR

Some substances are filtered, enter tubules, but are completely reabsorbed

So, they did not reach the final urine

a- creatinineclearance :

Creatinine clearance is more preferable than that of inulin because:

1) Crea/nine is already present in body fluids

(Thus, it can be performed over long periods without the necessity of I.V. administration as in inulin).

2) Crea/nine plasma concentra/on is steady throughout the 24 hours

(Thus, only one sample of blood is needed for a 24 hour collec2on of urine).

This is the practical and best method of obtaining a fairly accurate estimate of the GFR.
The inulin clearance = GFR.
The creatinine clearance is slightly > GFR (as some creatinine is actively secreted by the tubules).
 b- Urea clearance :

This is inferior to creatinine clearance as 40% of the filtered urea is reabsorbed in PCT

Thus, Urea clearance < GFR

2- Tubular function tests :

The functions of the tubules are to :

1) Reabsorb
eabsorb some substances from the tubular fluid.

2) Secrete some substances into the tubular lumen.

1) Urine concentration test = Water deprivation test.

This is a test for renal concentration ability.

The ability to form concentrated urine in response to water deprivation depends on:

- Normal ADH releasing mechanism

- Normal tubular response to the released ADH

• Principle :

Restriction of water intake for a period of hours Maximum stimulation of ADH secretion via
osmoreceptors of hypothalamus Action of ADH on distal tubules and collecting ducts
Water reabsorption & passage of concentrated urine.

2) Urine dilution test = Water load test.

the opposite
 URINE ANALYSIS
1- Physical examination.

2- Chemical examination.

3- Microscopical examination

- Urine sample should be:

1- Early morning.

2- Midstream.

3- Fresh.

4- Non-centrifuged.

5- Collected in dry, clean, sterile container which is free if detergents.

1)) PHYSICAL EXAMINATION:-

EXAMINATION:
1) Volume:
Normally: 750 - 2000 ml / 24 hr.

< 500 ml Oliguria

> 2000mlPolyuria:

1. Diure'cs

2. D.M.

3. ADH deficiency

N.B: Increased frequency of micturition doesn’t mean polyuria e.g. cystitis

2) Color:
Normally: Amber Yellow “ urochromepiment ”

Abnormalities:

brown
1- Red-brown Hb and its derivatives in crush syndrome.

2- Green-yellow Bile pigments (Jaundice).

3- Black Parenteral iron therapy.

3) Smell (Odour):
Normally aromatic ( Urea Ammonia )

Offensive odourGram –ve infection of urine.

Acetone odourKetonuria.

4) Aspect:
Normal urine is clear

Turbid urine may be due to:

1- Pus (WBCs).

2- Crystals

3- RBCs (hematuria)

5) Reac2on (PH):
Normal urine is acidic ( PH = 5 – 6 ).

Alkaline urine may be due to:

1- Eating fruits and vegetables.

2- Some drugs.

3- Bacterial infection.

6) Specific gravity (Sp. Gr.):

It is an indication about soluble solutes in urine.

Sp. Gr. = Mw of Urine / Mw of water (1000).

Normally: 1015 – 1025.

Factors affecting:

1- volume of urine.

2- Concentration of solutes in urine.

- Oliguria Concentate the solutes IncraseSp.Gr.

- Polyuria Dilute the solutes decrease Sp.Gr.

- D.M. Polyuria+GlucosuriaIncraseSp.Gr.

N.B:Fixed Sp.Gr. Means:

Sp. Gr. Of urine = Sp. Gr. Of plasma = 1010 ( Acute tubular necrosis) Bad prognosis.
 2) CHEMICAL EXAMINATION:-
Normal constituents of urine:
1- Organic: 2-Inorganic:

- Urea - Chloride

- Creatinine - Phosphate

-Uric acid - Sulphate

Abnormal constituents of urine:

1) Protein:
- Normal urine contains is: 40 - 150 mg of protein / day.

- The glomerular basement membrane prevent proteinuria by:

1- Size of its pores.

2- Its negative charge.

- Altera'on of 1 or 2 (e.g. acute nephri's or nephro'c syndrome) proteinuria.

- It is detected by: heat coagulation test or urine strips.

2) Glucose:
Renal threshold for glucose = 180 mg %

It can be detected by: Bendict test or Urine strips.

as it is reducing sugar.

Other reducing sugars in urine:

1- Fructose.

2- Glucuronates.

3- Galactose.

4- Lactose.

5- Pentose.

6- Homogentisic acid.
 3) Ketons:
They are:

1- Acetoacetic acid.

2- β-hydroxybutyric acid.

3- Acetone.

Renal threshold for ketonsis:70 mg %.

Normal urine contains: 3 -15 mg / day.

It is present in urine in detectable or high level in case of:

1- D.M.

2- Starvation.

It is detected by: Rothera’s test or urine strips.

4) Bilirubin:
It appears in urine in cases of:regurgitation jaundice.

It is detected by:Fouchet’s test or urine strips.

_______________________________________________________________________________________________
 Tubular transport maximum of glucose

- Normally, measurable glucose does not appear in the urine because essentially all the filtered glucose is
reabsorbed in the proximal tubule.
- However, when the filtered load exceeds the capability of the tubules to reabsorb glucose, urinary excretion
of glucose does occur.
- In the adult human, the transport maximum for glucose averages about 375 mg/min, while the filtered load
of glucose is onlyy about 125 mg/min (GFR \ plasma glucose = 125 ml/min \ 1 mg/ml).With large increases in
GFR and/or plasma glucose concentra(on that increase the filtered load of glucose above 375 mg/min, the
excess glucose filtered is not reabsorbed and passes into the urine.

- Figure 27–4,,shows
shows the relation between :
1- Plasma
lasma concentration of glucose,
2- Filtered load of glucose,
3- Tubular
ubular transport maximum for glucose,
4- Rate
ate of glucose loss in the urine.

- when the plasma glucose concentra(on is 100 mg/100 mL and the filtered load is at its normal
level, 125 mg/min, there is no loss of glucose in the urine.

- When the plasma concentra(on of glucose rises above about 200 mg/100 ml, increasing the
filtered load to about 250 mg/min, a small amount of glucose begins to appear
app in the urine. This
point is termed the threshold for glucose.

- N.B.Note that the appearance of glucose in the urine (at the threshold) occurs before the transport
maximum is reached.
One reason for the difference between threshold and transport maximum
maximum is that not all nephrons have the
same transport maximum for glucose, and some of the nephrons excrete glucosebefore others have reached
their transport maximum.

- The overall transport maximum for the kidneys, whichis normally about 375 mg/min, is reached
when allnephrons have reached their maximal capacity to reabsorbglucose.

- The plasma glucose of a healthy person almost never becomes high enough to cause excretion of
glucose in the urine, even after eating a meal. However, in uncontrolled diabetes mellitus, plasma
glucose may rise to high levels, causing the filtered load of glucose to exceed the transport
maximum and resulting in urinary glucose excretion.
 Cholelithiasis (Gallstones)
Types :
1- Cholesterol stones: contains ( crystalline cholesterol monohydrate ) 80%
2- Pigment stones: composed of ( Bilirubin calcium salts ) 20%

Pathogenesis :
Bile is the only significant pathway for elimination of excess cholesterol from the body, either as free
cholesterol or as bile salts.

Cholesterol is water insoluble and is rendered water soluble by aggregation with bile salts and lecithins
secreted into bile.

When cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation), cholesterol can
no longer remain dispersed and nucleates into solid cholesterol monohydrate crystals.

- Cholesterol gallstone :

formation involves four simultaneously occurring conditions:

1-Supersaturation
Supersaturation of the bile with cholesterol

2- Establishment of nucleation sites by microprecipitatesof calcium salts.

salts

3-Hypomobility
Hypomobility of the gallbladder (stasis), which promotes nucleation.
nucleation

4-Mucus hypersecretion to trap the crystals, enhancing their aggregation into stones.

- Pigment gallstones :

The
he presence of unconjugated bilirubin in the biliary tree increases the likelihood of pigment stone
formation, as occurs in hemolytic anemias and infections
infecti of the biliary tract.

The precipitates are primarily insoluble calcium bilirubinate salts.

Morphology :
Cholesterol Stones Pigment Stones
Arise in gall bladder Arise anywhere in biliary tree.
Consist of 50% - 100% cholesterol Black pigment stone Brown pigment stone
Colour: - Pale yellow Found in sterile gallbladder Found in infected
- Increasing proportions of intrahepatic or
cacarbonate ,phosphates& extrahepatic ducts
bilirubin impart gray white/black
discoloration. small
Shape Ovoid Present in large quantities Present single or few in
number
Consistency firm Crumble easily Soft with a greasy,
Surface faceted soaplike consistency.
Number Single or several
Other - Most are radiolucent
- 20% have sufficient ca carbonate
to render them
hem to radiopaque. radiopaque radiolucent