Study 20 flashcards on Glomerular Diseases: Classification, Histology & Pathology with OmpathStudy. Quick, focused revision for Kenyan medical and health stu...
Q1. List the 3 broad groups of glomerular disease with examples
Answer: Primary glomerulopathies → postinfectious GN, RPGN, membranous nephropathy, MCD, FSGS, MPGN, IgA nephropathy Systemic diseases → SLE, diabetes, amyloidosis, Goodpasture, vasculitis, HSP Hereditary → Alport syndrome, thin basement membrane nephropathy, Fabry disease
Q2. Define focal, segmental, diffuse, and global in glomerular biopsy reporting
Answer: Diffuse → all glomeruli involved Global → entire individual glomerulus involved Focal → only a fraction of glomeruli involved Segmental → only part of an individual glomerulus affected
Q3. List the 4 basic pathologic responses to glomerular injury with brief descriptions
Answer: Hypercellularity → increased cell number via proliferation, leukocyte infiltration, crescent formation Basement membrane thickening → immune deposits, increased synthesis, or GBM duplication Hyalinosis → leaked plasma proteins accumulate, obliterating capillary lumens Sclerosis → collagenous matrix deposition — irreversible final common pathway
Q4. Explain crescent formation — composition, location, trigger, and progression
Answer: Composed of proliferating parietal epithelial cells + infiltrating leukocytes Form in urinary (Bowman's) space Triggered by GBM breaks → plasma proteins leak → fibrin deposition → thrombin activation Progression: cellular → fibrocellular → fibrous (irreversible) Hallmark of RPGN
Q5. List the clinical syndromes of glomerular disease with their defining features
Answer: Nephritic → haematuria, red cell casts, subnephrotic proteinuria, oliguria, hypertension, azotemia RPGN → nephritic features + rapid renal function loss over days to weeks Nephrotic → proteinuria 3.5g/day, hypoalbuminemia, oedema, hyperlipidaemia, lipiduria CKD → azotemia progressing to uraemia over months to years Isolated urinary abnormalities → asymptomatic haematuria/subnephrotic proteinuria
Q6. List the 3 main immune mechanisms underlying glomerular injury
Answer: Antibody-mediated injury Cell-mediated immune injury Activation of the alternative complement pathway
Q7. What fixed intrinsic antigens are targeted in in situ immune complex formation? Give disease associations
Answer: NC1 domain of type IV collagen → Goodpasture syndrome PLA2R on podocytes → primary membranous nephropathy (~75%) THSD7A → less common membranous nephropathy Mesangial antigens → various mesangial GN
Q8. Compare in situ vs circulating immune complex deposition — mechanism and IF pattern
Answer: In situ → antibodies react with antigens already in glomerulus → Granular IF Circulating → complexes form in blood, trapped in glomerulus → Granular IF Anti-GBM → antibodies against uniformly distributed NC1 collagen → Linear IF
Q9. Explain the pathogenesis of dense deposit disease / C3 glomerulopathy
Answer: Alternative complement pathway activated C3NeF stabilizes C3 convertase → uncontrolled C3 consumption Low C3, normal C1 and C4, low Factor B and properdin Glomerular C3 and properdin deposits but no IgG
Q10. Summarise the high-yield immunofluorescence patterns and their disease associations
Answer: Linear IgG along GBM → anti-GBM antibodies → Goodpasture syndrome Granular subepithelial → in situ immune complexes → membranous nephropathy Granular subendothelial/mesangial → circulating complexes → MPGN, lupus nephritis C3 only, no IgG → alternative complement pathway → dense deposit disease Negative → podocyte injury, no deposits → minimal change disease
Q11. List the features of nephritic syndrome and explain the pathophysiology of each
Answer: Haematuria + red cell casts → inflammatory injury breaks capillary walls Proteinuria (subnephrotic) → capillary wall damage Oliguria + azotemia → reduced GFR from inflammation Hypertension → fluid retention + renin release from ischaemic kidneys Oedema → fluid retention
Q12. Describe the morphology of acute postinfectious GN on LM, IF, and EM
Answer: LM → diffuse endocapillary proliferation, neutrophil + monocyte infiltration, enlarged hypercellular glomeruli IF → granular IgG and C3 in GBM and mesangium — "starry sky" pattern EM → subepithelial electron-dense deposits — "humps" (pathognomonic)
Q13. What are the complement findings in postinfectious GN and what do they indicate?
Answer: Low C3, normal C1 and C4 Indicates alternative complement pathway predominantly activated Elevated ASO titre and anti-DNase B confirm streptococcal trigger
Q14. List the 3 types of Crescentic (RPGN) GN with immunopathogenesis, IF pattern, and disease association
Answer: Type I → anti-GBM antibodies → linear IgG + C3 → Goodpasture syndrome Type II → immune complex deposition → granular IgG/IgM + C3 → SLE, postinfectious GN, IgA nephropathy Type III → pauci-immune ANCA-mediated → negative → microscopic polyangiitis, GPA
Q15. Explain how ANCAs cause glomerular injury in Type III RPGN
Answer: p-ANCA (anti-MPO) → microscopic polyangiitis c-ANCA (anti-PR3) → granulomatosis with polyangiitis ANCAs activate neutrophils → endothelial injury → necrotizing vasculitis → GBM breaks → crescent formation
Q16. List the 4 diagnostic criteria of nephrotic syndrome and explain the pathophysiology linking them
Answer: Proteinuria 3.5g/day → glomerular capillary hyperpermeability Hypoalbuminemia → albumin lost in urine Oedema → low albumin → reduced oncotic pressure → fluid shifts to interstitium Hyperlipidaemia + lipiduria → liver compensates with increased lipoprotein synthesis → excess filtered into urine
Q17. Explain the pathogenesis of primary membranous nephropathy
Answer: Autoantibodies target PLA2R on podocytes Granular subepithelial immune deposits form Complement activation especially C5b-9 (membrane attack complex) Podocyte injury → foot process effacement → proteinuria No inflammatory infiltrate
Q18. Describe the EM stages of membranous nephropathy
Answer: Stage 1 → scattered subepithelial electron-dense deposits Stage 2 → GBM spikes between deposits Stage 3 → deposits surrounded/incorporated into GBM (intramembranous) Stage 4 → electron-lucent areas — resorption of prior deposits
Q19. What is the Rule of Thirds in membranous nephropathy? List adverse prognostic factors
Answer: ⅓ spontaneous complete remission ⅓ stable, persistent proteinuria, little progression ⅓ progressive decline to ESRD Adverse factors: high PLA2R titre, proteinuria 6 months, male sex, advanced age, renal insufficiency at presentation
Q20. Explain the pathogenesis of minimal change disease and its characteristic clinical and morphologic features
Answer: T-cell dysfunction → circulating permeability factor → loss of GBM polyanion (negative charge) Charge-selective barrier lost → albumin leaks LM → completely normal glomeruli IF → negative (no immune deposits) EM → diffuse foot process effacement (diagnostic finding) Clinically: massive selective proteinuria, no haematuria, no hypertension, normal renal function 90% of children respond to steroids