Study 20 flashcards on FSGS & HIV Nephropathy: Causes, Symptoms, Diagnosis & Prognosis with OmpathStudy. Quick, focused revision for Kenyan medical and healt...
Q1. List the settings in which FSGS occurs
Answer: Primary (idiopathic) → most common, no known cause Secondary — associated conditions → HIV, heroin, sickle cell, obesity Secondary — scarring → from prior IgA nephropathy or focal GN Adaptive → kidney loses nephrons (e.g. one kidney missing) → remaining filters overworked → scar Inherited → faulty podocyte genes: podocin, α-actinin 4, TRPC6
Q2. Explain the pathogenesis of FSGS in simple steps
Answer: FSGS is a podocyte disease — the gatekeepers of the kidney filter get damaged Damaged podocytes → drop off → bare patch of filter membrane exposed Blood flows through bare GBM unfiltered → capillary loops collapse Collapsed loops stick to Bowman's capsule → segmental scar forms More podocytes lost → more scars → eventually kidney fails
Q3. Describe FSGS on LM, IF, and EM
Answer: LM → some glomeruli scarred (focal), only part of each affected (segmental); hyalinosis, foam cells, lipid droplets IF → IgM and C3 in scarred areas — nonspecific, just trapped proteins EM → foot processes fused/effaced in ALL glomeruli (even non-scarred ones) — shows podocyte injury is widespread
Q4. What is collapsing glomerulopathy? Features and associations?
Answer: Worst variant of FSGS — the entire glomerular tuft collapses, not just a segment Visceral epithelial cells (podocytes) proliferate and enlarge — characteristic feature Tubules form microcysts filled with protein + surrounding inflammation Associated with: HIV , pamidronate (drug), idiopathic Poor prognosis
Q5. What are the prognostic factors in FSGS?
Answer: ~20% → rapid course → renal failure within 2 years Worse prognosis if: heavy proteinuria, renal insufficiency at diagnosis, collapsing variant Tip variant → best prognosis Children do better than adults 25–50% recurrence after kidney transplant — because circulating permeability factors persist
Q6. What are the 3 distinguishing morphologic features of HIV-associated nephropathy?
Answer: Collapsing FSGS → entire glomerular tuft collapses — most common pattern in HIV Cystic tubular dilation → kidney tubules balloon up, filled with protein + surrounded by inflammation and fibrosis — striking, not seen in regular FSGS Tubuloreticular inclusions → abnormal structures inside endothelial cells on EM, caused by interferon-α released during HIV infection → also seen in SLE, NOT in idiopathic FSGS → diagnostic clue
Q7. Compare MPGN Type I vs Dense Deposit Disease
Answer: MPGN Type I → immune complexes (IgG + complement) deposited under endothelium → low C3, low C1q, low C4 → IF: IgG, C3, C1q, C4 granular subendothelial Dense Deposit Disease → alternative complement pathway goes out of control (C3NeF) → low C3, normal C1 and C4 → IF: C3 only, no IgG Both → "tram-track" GBM on LM + nephritic/nephrotic overlap
Q8. What is the pathognomonic EM finding in dense deposit disease? What is it associated with clinically?
Answer: EM → dense, ribbon-like deposits sitting inside the GBM itself (lamina densa) — looks almost black on EM Partial lipodystrophy → C3NeF also activates complement in fat cells → patient loses fat from upper body (face, arms) Drusen → same deposits form in the retina → visual disturbance Poor prognosis → most reach ESRD within 10 years; high recurrence after transplant
Q9. What is the tram-track appearance in MPGN? What causes it?
Answer: GBM looks like two parallel lines (double contour) on silver stain Caused by mesangial cells creeping between the endothelium and GBM — splitting the membrane On EM → subendothelial electron-dense deposits push the membrane apart Think: the GBM gets sandwiched and duplicated
Q10. How do you distinguish fibrillary GN from amyloid?
Answer: Both have fibrils deposited in the glomerulus Amyloid → Congo red positive (apple-green birefringence), thin fibrils (~10 nm) Fibrillary GN → Congo red negative , larger fibrils (~20 nm) Special marker: DNAJB9 found in deposits → highly specific for fibrillary GN IF → polyclonal IgG (mainly IgG4), C3, kappa and lambda light chains
Q11. Explain the pathogenesis of IgA nephropathy
Answer: Patient produces abnormal IgA1 — missing sugar molecules (galactose-deficient) Body recognises it as foreign → makes antibodies against it → immune complexes form Complexes deposit in mesangium → complement activation → mesangial cells proliferate → injury Triggered by throat or gut infections → haematuria appears at same time as infection (synpharyngitic) — NOT weeks later like postinfectious GN
Q12. Describe IgA nephropathy morphology and poor prognostic factors
Answer: LM → mesangial widening and proliferation IF → IgA dominant in mesangium ± IgG, IgM, C3 — pathognomonic EM → mesangial electron-dense deposits Poor prognosis: heavy proteinuria, hypertension, renal insufficiency at presentation, crescents on biopsy 20–30% reach ESRD over 20 years
Q13. Describe the genetics, pathogenesis, and clinical triad of Alport syndrome
Answer: X-linked (~80%) → COL4A5 gene mutation Autosomal recessive/dominant → COL4A3 or COL4A4 mutations Faulty type IV collagen → weak GBM → progressive glomerular damage Clinical triad: Haematuria (persistent microscopic + episodic macroscopic) Sensorineural deafness (cochlear BM affected) Eye problems → anterior lenticonus, macular flecks ESRD by 3rd–4th decade in X-linked males After transplant → risk of anti-GBM nephritis (new kidney has normal collagen → immune system attacks it)
Q14. What are the diagnostic findings in Alport syndrome on EM and IF?
Answer: EM → GBM looks like a basket-weave — irregular thickening, thinning, and splitting of lamina densa — diagnostic IF → absent staining for α3, α4, α5 chains of type IV collagen — confirms diagnosis
Q15. Distinguish thin basement membrane nephropathy from Alport syndrome and IgA nephropathy
Answer: TBMN → just microscopic haematuria, no proteinuria, normal renal function, benign — found incidentally EM → GBM uniformly thin (<150–200 nm; normal = 300–400 nm) IF → completely normal Genetics → heterozygous COL4A3/COL4A4 (homozygous = Alport) No deafness, no eye problems, no progression to ESRD
Q16. List the ISN/RPS classification of lupus nephritis with key features
Answer: Class I → normal on LM; mesangial deposits on IF/EM only Class II → mesangial proliferation; mild haematuria/proteinuria Class III → focal; <50% glomeruli affected Class IV → diffuse; 50% glomeruli; most severe; can cause RPGN Class V → membranous pattern; nephrotic syndrome Class VI → 90% sclerosed; end-stage, irreversible
Q17. What is "full house" IF and wire loop lesions? What disease?
Answer: Full house → IgG + IgA + IgM + C3 + C1q ALL positive on IF → classic lupus nephritis pattern — no other disease gives all five Wire loop lesions → capillary walls look thick and rigid on LM → caused by massive subendothelial immune complex deposits → seen in Class IV lupus nephritis
Q18. Describe the pathogenesis and pathognomonic lesion of diabetic nephropathy
Answer: High blood sugar → glycation of GBM proteins → GBM thickens and weakens Glomerular hyperfiltration → physical stress → sclerosis RAAS activation + TGF-β → mesangial matrix expands Pathognomonic lesion → Kimmelstiel-Wilson nodule → oval ball of matrix sitting in the glomerulus periphery Also pathognomonic → hyalinosis of efferent arteriole (unique to diabetes)
Q19. List the Mogensen stages of diabetic nephropathy. What is the earliest clinical marker?
Answer: Stage I → hyperfiltration, GFR increased Stage II → silent, albumin normal Stage III → microalbuminuria (30–300 mg/day) → earliest detectable marker — not on dipstick Stage IV → macroproteinuria ( 300 mg/day), GFR falling Stage V → ESRD
Q20. List the tetrad of Henoch-Schönlein Purpura and its relationship to IgA nephropathy
Answer: Purpura → raised, non-blanching rash on buttocks, legs, arms — not from low platelets Arthralgia → joint pain, large joints, non-destructive Abdominal pain → colicky; risk of intussusception in children Renal disease → haematuria, proteinuria; adults can get RPGN Relationship to IgA nephropathy → same disease, same mechanism (Gd-IgA1 deposits in mesangium) — HSP just also has systemic vasculitis on top