Firecracker III

Question 1

Pathologic changes in renal interstitium with acute drug-induced interstitial nephritis

Answer 1

acute inflammation of renal interstitium (edema + prominent mononuclear and eosinophilic infiltrate)

Question 2

EM FSGN

Answer 2

diffuse podocyte effacement and focal detachment of visceral epithelial cells

Question 3

strep that causes PSGN

Answer 3

group A β-hemolytic Streptococcus pyogenes

Question 4

large hypercellular glomeruli due to WBC infiltrate and proliferation of mesangial and endothelial cells

Answer 4

PSGN

Question 5

Sub-Endothelial Deposits

Answer 5

DPGN (SLE)

Type 1 membranoproliferative glomerulonephritis

Question 6

Sub-Epithelial Deposits

Answer 6

PSGN (nephritic)
Membranous glomerulonephritis (spike and dome)

Question 7

spike and dome

Answer 7

membranous glomerulonephritis (on silver stain)

Question 8

Drug acts as a hapten by covalently binding to a carrier→ hapten-carrier conjugate serves as an immunogen, triggering a HSR (type I &/or type IV) → injury of tubular cells &/or their BM

Answer 8

Acute drug-induced interstitial nephritis

Question 9

What makes people think that drug-induced interstitial nephritis is a type I hypersensitivity?

Answer 9

Some patients have ↑ serum IgE levels, suggesting Type I hypersensitivity

Question 10

What makes peoples think that drug-induced interstitial nephritis is a type IV hypersensitivity?

Answer 10

Other patients have mononuclear/granulomatous infiltrate on renal biopsy and positive skin tests to drugs, suggesting Type IV hypersensitivity

Question 11

Acute drug-induced interstitial nephritis may be caused by “Please Note All Drugs that Can Possibly Scar Renals”

Answer 11

PCN
NSAIDs
Allopurinol
Diuretics (thiazides, furosemid, acetazolamide)
Cephalosporins
Proton pump inhibitors
Sulfamide antibiotics . Sulfasalazine
Rifampin

Question 12

ICs deposit on the glomerular epi BM → activation of complement cascade → C5b-C9 MAC damages glomerular epithelial & mesangial cells, causing their release of proteases & oxidants which further contribute to glomerular cap wall damage → nephrotic-range proteinuria.

Answer 12

Membranous nephropathy

Question 13

In cases of PSGN (poststreptococcal glomerulonephritis), how long does it usually take for PSGN to develop after a streptococcal infection? Why?

Answer 13

1-4 weeks to make antibodies (↑ anti-DNAse B) and form immune complexes →

Question 14

Drugs that can cause secondary membranous nephropathy

Answer 14

• Penicillamine
• Captopril
• NSAIDs
• Gold

Question 15

Infections that can cause secondary membranous nephropathy

Answer 15

• Hepatitis B
• Hepatitis C
• Syphilis
• Malaria

Question 16

AI diseases that can cause secondary membranous nephropathy

Answer 16

• SLE (systemic lupus erythematosus)
• RA (rheumatoid arthritis)
• SS (sjögren’s syndrome)
• Hashimoto thyroiditis

Question 17

What malignancies can cause secondary membranous nephropathy

Answer 17

• Solid tumors—eg, colon carcinoma, lung carcinoma, melanoma

- Chronic lymphocytic leukemia

Question 18

Membranous nephropathy EM

Answer 18

Subepithelial (subpodocyte) IC deposits

Question 19

Membranous nephropathy LM

Answer 19

Normal-appearing glomeruli (early stages of the disease) or diffuse glomerular capillary wall thickening (later stages of the disease)

Question 20

Membranous nephropathy on silver stain

Answer 20

spike and dome pattern—the spikes are basement membrane material (colored black by the silver stain) and the domes are immune complex deposits (not colored by the silver stain).

Question 21

Intramembranous Deposits (within the GBM):

Answer 21

MPGN type I and II (dense-deposit disease) → EM may show “tram-tracking”, although this is only present in a minority of cases and is not diagnostic of MPGN type II by itself

Question 22

• Fever, rash, joint pain
• Eosinophilia, ↑ serum IgE
• Hematuria, mild proteinuria, pyuria (eosinophiluria)
• 50% of patients develop acute renal failure with azotemia (BUN:Cr ratio≤15) and oliguria

Answer 22

S/sx of acute drug-induced interstitial nephritis ~15 days after first dose of drug

Question 23

The most common nephrotic syndrome in the US

Answer 23

Membranous nephropathy (membranous glomerulopathy):

Question 24

LM PSGN

Answer 24

Large hypercellular glomeruli

Question 25

IF PSGN

Answer 25

Granular/coarse deposits of IgG, IgM, and C3 along the GBM (glomerular basement membrane) and in the mesangium

Question 26

EM PSGN

Answer 26

Large subepithelial (subpodocyte) electron-dense deposits—prominent “bumps and humps”

Question 27

Renal vein thrombosis is classically associated with which nephrotic syndrome subtype?

Answer 27

Membranous nephropathy

Question 28

C3 levels in PSGN

Answer 28

↓ serum C3 level; normal C1 and C4 levels

Question 29

EM shows alternating thickening and thinning of GBM with splitting →“Basket weave appearance”

Answer 29

Alport Syndrome (Hereditary Nephritis)

Question 30

Where do you see deposits in PSGN

Answer 30

sub-epithelial

Question 31

where do you see deposits in membranous glomerulonephritis

Answer 31

sub-epithelial