Nephrotic Syndrome - Pathoma Flashcards
What is the major hallmark of Nephrotic disorders?
- Proteinuria (>3.5 g/day)
- Hypoalbuminemia → edema
- Hypogammuglobulinemia → more infection
- Hypercoagulable state → lose AT III
- Hyperlipidemia & hypercholesterolemia
- blood thin → liver releases fat to thick up blood
What is the most common cause of nephrotic syndrome in children?
Minimal Change Disease (75%)
What condition can be associated with Minimal Change Disease?
Hodgkin Lymphoma
- MCD → loss of foot processes due to cytokine-induced damage
- HL → increased cytokine production by Reed-Sternberg cells
What are less prominent associations with Minimal Change Disease?
- Atopy
- Recent infection
- Recent immunization
What is the most common cause of Minimal Change Disease?
- Idiopathic
What is the histological hallmark of Minimal Change Disease? Other histological findings?
- Normal glomeruli on H&E stain
- lipid may be seen in proximal tubule cells
- Effacement of foot processes on EM
- No immune complex deposits
- negative IF
The “minimal” in Minimal Change Disease refers to the type of proteinuria present, which is?
Selective proteinuria
- loss of albumin
- no loss of immunoglobulin
What is the effective treatment for Minimal Change Disease?
- Corticosteroids
- excellent repsonse because damage is due to cytokine release from T-cells
What is the most common cause of nephrotic syndrome in Hispanics and African Americans?
Focal Segmented Glomerulosclerosis
What is Focal Segmented Glomerulosclerosis (FSGS) associated with?
- Usually idiopathic
- ASSOCIATED WITH:
- HIV
- Heroin use
- Sickle Cell Disease
What are the histological findings in FSGS?
(Hint: think about the name)
-
Focal & segmental sclerosis on H&E
- only segment of glomeruli involved
- only some glomeruli effected (focal)
- Effacement of foot processes on EM
- No immune complex deposits
- negative IF
What would happen if you treated Minimal Change Disease with Corticosteroids, and it did not improve?
Disease would progress to Focal Segmental Glomerulosclerosis (FSFS)
What is the treatment for FSGS?
- No effective treatment
- Poor response to steroids
- Usually progresses to Chronic Renal Failure
What is the most common cause of nephrotic syndrome in Caucasian adults?
Membranous Nephropathy (30%)
(FYI: Dr. Warren → says FSGS is more common with 35% of adults)
What are the causes/associations of Membranous Nephropathy?
- 85% Idopathic
- May be associated with:
- Hepatitis B
- Hepatitis C
- Solid tumors
- SLE
- Drugs: NSAIDs, penicillamine
What is the most common cause of death in patients with Lupus (SLE)?
Renal failure
- Most common kidney disorder = Nephritic syndrome → Diffuse Proliferative Glomerulophritis
- IF nephrotic syndrome → Membranous Nephropathy
What is the key histological finding in Membranous Nephropathy?
(Hint: the name gives it away)
-
Thick glomerular basement membrane on H&E
- due to immune complex deposition
- granular IF
- Supepithelial deposits with “spike and dome” appearance on EM
- foot processes don’t like to sit on immune complexes → cover deposits with more epithelium (dome) → gap in between foot processes = spike
What are the key histological findings in Membranoproliferative Glomerulonephritis?
-
Thick capillary membranes on H&E
- with “tram-track” appearance
- Due to immune complex deposition
- Granular IF
- Due to immune complex deposition
- with “tram-track” appearance
What does the “membranoproliferative” in Membranoproliferative Glomerulonephritis refer to?
- Cytoplasm of Mesangial cell that holds together capillary loops proliferates
- cytoplasm proliferation separates deposit → creates “tram-track” appearance
What are the two types of Membranoproliferative Glomerulonephritis and how are the divided?
- Type I:
- subendothelial immune complex deposition
- associated with HBV and HCV
- more often associated with formation of “tram-tracks”
- Type II:
- immune complex deposition within basement membrane
- associated with autoantibody C3-nephritic factor
- stabilizes C3 convertase → (can’t be broken down) → overactivation of complement → inflammation
What disease has the potential to cause nephritic syndrome, nephrotic syndrome, or both?
Membranoproliferative Glomerulonephritis
- Type II → overactivation of compliment → inflammation → nephritic syndrome
What is the difference between Membranous Glomerulonephropathy and Membranoproliferative Glomerulonephritis?
- MGN
- immune complex deposition in subepithelial
- under podocytes
- immune complex deposition in subepithelial
- MPGN
- Type I: immune complex deposition in subendothelial
- outside of capillary/under GBM
- Type II: immune complex deposition in basement membrane
- Type I: immune complex deposition in subendothelial
How does diabetes mellitus cause Nephrotic syndrome?
- High serum glucose → leads to Non-Enzymatic Glycosylation of vascular basement membrane
- results in: hyaline arteriolosclerosis
- makes vessel “leaky” → protein escapes
- preferentially effects efferent arteriole
- leads to high glom filtration pressure → results in hyperfiltration → microalbuminuria
- progresses to nephrotic syndrome
- results in: hyaline arteriolosclerosis
How can you improve the high glomerular filtration pressure when hyaline arteriolosclerosis is present in the efferent arteriole?
- Block Ang II with → ACE inhibitors
- Ang II constricts efferent arteriole
What is the histological hallmark of Diabetes mellitus-induced nephrotic syndrome?
- Sclerosis of mesangium
- Formation of Kimmelstiel-Wilson nodules
- pathomnemonic for diabetes!
What is the most commonly involved organ in Systemic Amyloidosis?
Kidney
(obviously)
Where does amyloid deposit in the kidney?
- Amyloid deposits → in the mesangium
- resulting in nephrotic syndrome
What would biopsy of the kidney in Systemic Amyloidosis show?
- Congo red staining → apple-green birefringence under polarized light
What are the 6 nephrotic syndromes? In pairs?
- 1. Minimal Change Disease & 2. FSGS
- 3. Membranous Glomerulonephropathy & 4. Membranoproliferative Glomerulonephritis
- 5. Diabetes mellitus & 6. Amyloidosis
