Pathology of Glomerular Disease Part II

Question 1

** What is the hallmark of NEPHROTIC syndrome?

Answer 1

proteinuria (> 3.5 g/day) resulting in:

• hypoalbuminemia (pitting edema due to loss of solute)
• hypogammaglobulinemia (increased risk of infection)
• hypercoagulable state (due to loss of antithrombin III)
• hyperlipidemia and hypercholeserolemia (due to liver trying to increase substances in the blood; may result in fatty casts in urine).

Question 2

** What is minimal change disease (MCD)?

picmonic

Answer 2

• most common cause of nephrotic syndrome in CHILDREN.

- Usually idiopathic, but may be associated with HODGKIN’S LYMPHOMA.

Question 3

** What are the key findings of minimal change disease (MCD)?

Answer 3

• normal glomeruli on H&E stain; limpid may be seen in PCT cells.
• EFFACEMENT of FOOT PROCESSES (podocytes) on EM, due to cytokine mediated damage.
• negative immunofluorescence (bc no immune complex deposition).
• selective proteinuria (loss of albumin, but not immunoglobulin).

Question 4

How do you treat MCD?

Answer 4

steroids because the damage is mediated by cytokines from T cells.

Question 5

** What is focal segmental glomerulosclerosis (FSGS)?

picmonic

Answer 5

• most common cause of nephrotic syndrome in HISPANICS and AFRICAN AMERICANS.
• usually idiopathic; may be associated with HIV, HEROIN use, and SICKLE CELL disease.

Question 6

What are the key findings of FSGS?

Answer 6

• focal (some glomeruli) and segmental (involving only part of the glomerulus) sclerosis (more pink) on H&E.
• Effacement of foot processes on EM.
• Negative IF (no immune complex deposits).
• This is what MCD progresses to, if it does NOT respond to steroids. It will then progress to chronic renal failure.

Question 7

** What is membranous nephropathy?

picmonic

Answer 7

• most common cause of nephrotic syndrome in CAUCASIAN ADULTS.
• usually idiopathic; may be associated with HEPATITIS B or C, solid tumors, SLE, or drugs (NSAIDS and penicillamine).

Question 8

** What are the key findings of membranous nephropathy?

Answer 8

• thick glomerular basement membrane on H&E, due to immune complex deposition (granular IF). This is a SUBEPITHELIAL deposition that causes a “SPIKE and DOME” appearance on EM.
• Whenever there is the word membranous, it is due to immune complex deposition.

Question 9

** What is membranoproliferative glomerulonephritis?

picmonic

Answer 9

• thick glomerular basement membrane on H&E, often with “TRAM-TRACK” appearance (due to mesangial cells splitting the immune-deposits as they proliferate).
• due to immune complex deposition (granular IF).

Question 10

** What are the 2 types of membranoproliferative glomerulonephritis?

Answer 10

• Type I= SUBENDOTHELIAL (associated with Hep B & C) and is more associated with tram-track appearance.
• Type II (dense deposit disease)= INTRAMEMBRANOUS (associated with C3 nephritic factor, which is an autoantibody that stabilizes C3 convertase, leading to over activation of complement, inflammation, and low levels of circulating C3).

Question 11

** What happens in diabetes mellitus?

Answer 11

• high serum glucose, which leads to nonenzymatic glycosylation (aka sticking glucose on the basement membrane without an enzyme) of the vascular basement membrane resulting in hyaline arteriolosclerosis (more in EFFERENT arteriole of glomerulus). This leads to high glomerular filtration pressure.

Question 12

** What does the high glomerular filtration pressure result in with DM?
(picmonic)

Answer 12

microalbuminuria and eventually progresses to nephrotic syndrome (sclerosis of the mesangium with formation of Kimmelstiel-Wilson nodules).

Question 13

What will slow the progression of hyperfiltration-induced damage caused by DM?

Answer 13

ACE inhibitors

Question 14

** What is systemic amyloidosis?

picmonic

Answer 14

• kidney is the most commonly involved organ.
• amyloid deposits in the mesangium, resulting in nephrotic syndrome.
• characterized by apple-green birefringence under polarized light after staining with CONGO RED!