What are 6 common causes of nephrotic syndrome?
1. minimal change disease
2. focal segmental glomerulosclerosis
3. membranous nephropathy
4. membranoproliferative glomerulonephritis
5. diabetes mellitus
6. systemic amyloidosis
What is the most common cause of nephrotic syndrome in:
b. Hispanics and African Americans
c. Caucasion adults
a. minimal change disease
b. focal segmental glomerulosclerosis
c. membranous nephropathy
What is the cause of minimal change disease?
Usually idiopathic, but may be associated with Hodgkin lymphoma
What is the cause of focal segmental glomerulosclerosis?
Usually idiopathic, but may be associated with:
sickle cell disease
How do minimal change disease and focal segmental glomerulosclerosis differ with regard to treatment?
Minimal change disease shows an excellent response to steroids, while focal segmental glomerulosclerosis shows poor response to steroids (and can progress to chronic renal failure).
Why does minimal change disease show an excellent response to steroids?
The damage in minimal change disease is mediated by cytokines from T cells--steroids stop the production of cytokines.
Normal glomeruli are observed on H&E stain, effacement of foot processes is seen on electron microscopy, and the immunofluorescence is negative (no immune deposits). What is the likely diagnosis?
minimal change disease
these are the classical histopathologic findings
What are the classic histopathologic findings with minimal change disease?
1. normal glomeruli on H&E stain
2. effacement of foot process on EM
3. Negative IF, no immune deposits
Minimal change disease is a cause of nephrotic syndrome. What type of protein loss is observed in this disease?
Selective protein loss: loss of albumin, but not immunoglobulin.
Histopathology for a patient shows focal and segmental sclerosis of the glomeruli on H&E stain, effacement of foot processes on EM, and a negative IF (no immune complex deposits). With what risk factos is this disease associated?
This is focal segmental glomerulonephritis.
This disease is usually idiopathic, but it is associated with HIV infection, heroin use, and sickle cell disease.
Which two causes of nephrotic syndrome are associated with immune complex deposition?
1. membranous nephropathy
2. membranoproliferative glomerulonephritis
What is the cause of membranous nephropathy?
Usually idiopathic, but may be associated with:
Hep B or C
Drugs (NSAIDS, penicillamine)
What is the most common cause of death in SLE patients?
What is the most common disorder SLE patients get within the kidney?
Diffuse nephritic glomerulonephritis, a nephritic syndrome
A patient shows a thick glomerular basement membrane on H&E, has a positive IF (positive for immune complex deposition), and has a "spike and dome" appearance on EM. What is the likely diagnosis?
What is the functional unit of the glomerulus? What holds these units together?
The functional unit of the glomerulus is lobules, which are held together by mesangial cells.
What is anuria?
A lack of urine production, defined in practice as the passage of <100mL of urine/day
A 19 yo woman is brought to the ED b/c of a crush injury that occurred when a bookshelf fell on her abdomen and legs. Physical exam shows mutliple bruises on the lower abdomen and thighs. 2 days later, she develops generalized edema. Lab studies show a rise in creatinine from 1-4 mg/dL. She is aggressively hydrated, but remains oliguric. Why has her creatinine increased from 1-4 mg/dL?
This woman has suffered a crush injury, which can result in two prominent sequelae:
(2) acute renal failure secondary to myoglobinuria.
The increased creatinine is a sign that she is experiencing renal failure secondary to myoglobinuria from the crush injury.
What is the mechanism of action of furosemide?
Furosemide is a loop diuretic that inhibits the Na/K/2Cl "mega transporter" in the thick ascending loop of henle.
Due to this mechanism, furosemide can induce massive diuresis.
It is not a K+-sparing diuretic
A 19 yo woman is brought to eh ED b/c of a crush injury that occurred when a bookshelf fell on her abdomen and legs. Physical exam shows mutliple bruises on the lower abdomen and thighs. 2 days later, she develops generalized edema. Lab studies show a rise in creatinine from 1-4 mg/dL. She is aggressively hydrated, but remains oliguric. Which of the following drugs is most likely contraindicated in this patient?
This woman has a cruch injury, and may develop hyperkalemia as the injured cells release K+ into the blood. Spirololactone is an aldosterone receptor inhibitor and therefore a K+-sparing diuretic. This will exaccerabte the hyperkalemia. Hyperkalemia can lead to arrythmia, which can be fatal
What is the mechanism of actino of hydrochlorothiazide?
Hydrochlorothiazide inhibits resorption of NaCl in the early distal convoluted tubule.
What is the pharmacological mechanism of action of mannitol in the kidney?
Mannitol is an osmotic diuetic.
It is contraindicated in anuria.
What is the mechanism of action of acetazolamide?
Stimulated diuresis by inhibiting carbonic anhydrase in the proximal convoluted tubule and preventing the reabsorption of bicarbonate.
Due to its mechanism, this drug has the potential to cause metabolic acidosis.
A 66 yo man is brought to the ED b/c of nausea, vomiting, and malaise. His records show he had an MI 4 weeks ago and recently completed treatment for a lower respiratory tract infection. Labs show a serum creatinine of 4.8 mg/dL. What is the cause of this man's nausea, vomiting, and malaise?
Azotemia (increase in notrogenous waste products in the blood)
*The initial symptoms in acute renal failure are commonly due to the presence of azotemia.
What is acute renal failure?
ARF is defined as a sudden decrease in renal function, resulting in an inability to maintain fluid and electrolyte balance and excrete nitrogenous wastes.
What is the most common cause of acute renal failure?
Prerenal azotemia, which is due to renal hypoperfusion (decreased blood flow to the kidneys)
What are 3 causes of decreased renal perfusion?
1. change in vascular resistance
2. decrease in intravascular volume (hypovolemia)
3. decreased cardiac output (e.g., cardiac failure, CHF)
Prerenal azotemia, which occurs due to hypoperfusion of the kidney, can be due to changes in vascular resistance. Name four causes of a change in vascular resistance that lead to renal hypoperfusion.
4. ACE inhibitors
How do ACE inhibitors lead to renal hypoperfusion?
Angiotensin II (the product of ACE), leads to efferent renal arteriolar constriction out of proportion to its effect on the afferent arteriole. This leads to increased glomerular hydrostatic pressure, and increased GFR.
ACE inhibitors, therefore, disproportionately prevent the efferent renal arteriole from contricting as compared to the afferent. This leads to a decreased in the GFR and renal hypoperfusion.
What is the normal range for serum creatinine?
What is the typical presentation of acute interstitial nephritis?
Oliguria, fever, and rash that starts days to weeks aftger starting the offending drug.
Eosinophils are seen in the urine.
How do you treat acute interstitial nephritis?
Treatment consists primarily of
removing the inciting drug
corticosteroids (e.g., prednisone)
What drugs are known to cause acute interstitial nephritis?
Antibiotics (penicillins, cephalosporins, sulfonamides)
diuretics (furosemide, thiazides)
proton pump inhibitors
A 72 yo woman is brought to the ED b/c of periorbital edema, a maculopapular rash on her chest, and a fever (101). She has a hx of HTN, DM, and osteoarthritis. Labs show increased BUN and Cr. Urinalysis shows mild proteinuria and eosinophils. What is the likely diagnosis?
Acute Interstitial Nephritis.
classically presents with oliguria (increased BUN and Cr; edema), rash, and fever days to weeks after the inciting drug; eosinophils are seen in the urine.
What is the normal range for serum K+, Na, Cl, and HCO3?
K+: 3.5-5 mEq/L
Na: 137-145 mEq/L
Cl: 98-110 mEq/L
HCO3: 22-26 mEq/L
A 68 yo woman comes to the physician for a routine exam. She says that she occasionally has swelling of her ankles and cramping in her lower legs. Treatment with a diuretic is begun. What class of diuretic should be used in her case?
A K+-sparing diuretic; her K is low (normal is 3.5-5 mEq/L)
Potassium-sparing diuretics act on the principle cells of the cortical collecting duct, by either inhibiting the aldosterone receptor (spironolactone), or by inhibiting the Na+ channel on the lumenal membrane (amiloride, triemterene)
What is the mechanism of action of spironolactone?
This acts by cometitively inhibiting the aldosterone receptor in the cortical collecting duct.
What is the medial umbilical ligament?
The adult derivative of the distal portion of the umbilical artery
What is the medial umbilical fold?
The fold of the parietal peritonem that covers the medial umbilical ligament, which is the adult derivative of the umbilical artery.
What is the median umbilical ligament?
The urachus, which is the adult derviative of the allantoic duct. This passes from the upper end of the bladder to the umbilicus.
What is the median umbilical fold?
The fold of the peritoneum that covers the median umbilical ligament, the adult derivative of the urachus.
A 1 week old newborn is brought into the ED b/c of fluid draining from his umbilicus. Phys exam shows no abnormalities except clear fluid that is pooled around the umbilical stump. Labs of the fluid show a pH of 6.0, specific gravity of 1.020, 1-2 epithelial cells/hpf, and no leukocytes, RBCs, or hemoglobin. What is the fluid that is pooling around the umbilical stump? What patent embryonic structure is this fluid passing through?
The fluid is urine.
It's passing through the median umbilical ligament, the adult derivative of the urachus. Failure of the urachus to close --> leaking of urine through the neonate's umbilicus.
A newborn has difficulty breathing. Phys. exam shows flattened facial features, low-set ears, and deformities of the feet. A chest X-ray shows pulmonary hypoplasia. The pregnancy was complicated by severe oligohydramnios. What is the patient's condition? What is this condition a result of?
This patient has bilateral renal agenesis --> oligohydramnios --> Potter's sequence.
Renal agenesis is due to malformation of what embryonic structure?
The ureteric buds.
The ureteric buds form the ureters, renal pelvis, calyces, and collecting tubules. The collecting tubules induce the formation of metanephric vesicles, which differentiate into the tubular components of the nephron.
What is renal agenesis?
Absent kidney formation, which may be unilateral or bilateral.
What is the result of bilateral renal agenesis?
This leads to oligohydramnios, which leads to:
developmental defects of the extremities
This is known as Potter's sequence and is incompatible with life.