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PA27.1-7 | Renal Pathology I: Glomerular Disease & Renal Failure — Graded Quiz
Graded
12 questions · Untimed · 2 attempts
Click any question card to reveal the correct answer.
A 5-year-old boy presents with periorbital oedema, massive proteinuria (6 g/day), hypoalbuminaemia, and hyperlipidaemia. Urinalysis shows no haematuria and no casts. Renal biopsy is processed for light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM). LM shows normal glomeruli, IF is negative for immunoglobulins and complement, and EM shows diffuse effacement of podocyte foot processes. He is started on high-dose corticosteroids and achieves complete remission within 4 weeks. Which of the following pathophysiological explanations best accounts for the massive proteinuria in the absence of structural glomerular damage on LM?
A
Loss of the glomerular basement membrane charge barrier caused by IgG deposition along the capillary wall, allowing albumin to cross freely
B
A circulating permeability factor (possibly soluble urokinase receptor) disrupts the podocyte slit diaphragm and foot process structure, abolishing size and charge selectivity of the filtration barrier
✓
C
Complement-mediated lysis of the glomerular endothelium creates fenestrae through which albumin escapes into Bowman's space
D
T-cell-mediated cytotoxicity directed against the GBM destroys collagen IV fibres, creating structural pores that allow protein leakage
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A 52-year-old man with HIV infection presents with nephrotic-range proteinuria (8 g/day), serum albumin 2.1 g/dL, and rapid progression to dialysis-dependent renal failure over 8 weeks. Renal biopsy shows focal and segmental sclerosis with collapse of glomerular capillary tufts and overlying podocyte hyperplasia, creating an 'endocapillary hypercellularity' appearance. A pathologist notes this is distinct from the classical FSGS pattern. Which subtype of FSGS does this represent, and what is the key pathogenetic mechanism in HIV-associated disease?
A
Tip variant FSGS — injury restricted to the periurinary (tubular) pole of the glomerulus — caused by high glomerular capillary pressure in HIV nephropathy
B
Collapsing FSGS — diffuse glomerular capillary collapse with podocyte hypertrophy and hyperplasia — caused by direct HIV viral protein (Vpr, Nef) entry into podocytes and tubular epithelial cells, inducing dysregulated proliferation and apoptosis
✓
C
Perihilar FSGS — sclerosis at the vascular pole — caused by hyperfiltration injury in the setting of immune-complex deposition from HIV antigenemia
D
Cellular variant FSGS — endocapillary hypercellularity with foam cells — caused by amyloid protein deposition from chronic HIV-related inflammation
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A 38-year-old woman presents with haemoptysis and rapidly progressive glomerulonephritis (RPGN) with oliguria over 3 weeks. Serum creatinine has risen from 0.9 to 6.2 mg/dL. Urinalysis shows 4+ protein, RBC casts, and dysmorphic RBCs. Chest CT shows bilateral alveolar haemorrhage. Serum anti-GBM antibody is strongly positive. Renal biopsy shows crescentic GN with linear IgG deposits along the GBM on immunofluorescence. Which cell type forms the crescent, and which mechanism is responsible for the rapid deterioration of renal function?
A
Crescent formed by proliferating mesangial cells; rapid deterioration from immune-complex-mediated complement activation in the mesangium
B
Crescent formed by parietal epithelial cells (Bowman's capsule lining) and infiltrating macrophages; rapid deterioration from obliteration of Bowman's space compressing and destroying the glomerular tuft
✓
C
Crescent formed by endothelial cell proliferation; rapid deterioration from thrombosis of glomerular capillaries by anti-GBM antibodies
D
Crescent formed by podocytes; rapid deterioration from loss of the slit diaphragm causing massive unselective proteinuria and nephrotic collapse
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A 14-year-old boy presents with cola-coloured urine 48 hours after a sore throat. His blood pressure is 148/94 mmHg. Urinalysis shows microscopic haematuria, 2+ protein, and RBC casts. Serum C3 is markedly reduced, C4 is normal, and ASO titre is elevated. Renal biopsy shows diffuse endocapillary hypercellularity with neutrophil infiltration and 'lumpy-bumpy' granular IgG and C3 deposits on immunofluorescence. Electron microscopy reveals large subepithelial electron-dense deposits ('humps'). Which immunological mechanism best explains why C3 is low but C4 is normal in this patient?
A
Streptococcal antigens activate the classical complement pathway via Fab-mediated IgG binding, consuming C3 and C4 equally
B
Streptococcal proteins (streptokinase, zymogen) directly activate the alternative complement pathway at C3, consuming C3 without depleting C4 which is proximal only to the classical pathway
✓
C
Immune complexes deposit preferentially in subepithelial locations, activating only the terminal complement pathway (C5–C9) without involving C3 or C4
D
Streptococcal M-protein acts as a superantigen that non-specifically polyclonally activates B cells, saturating C3 by depositing excessive IgG immune complexes while sparing C4
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A 44-year-old woman with a 15-year history of systemic lupus erythematosus presents with nephrotic-range proteinuria (5 g/day), haematuria, RBC casts, and a serum creatinine of 2.8 mg/dL. Anti-dsDNA titre is markedly elevated. Renal biopsy shows diffuse global endocapillary proliferation affecting > 50% of glomeruli with 'wire loop' lesions and subendothelial deposits. Immunofluorescence shows 'full house' staining (IgG, IgA, IgM, C3, C1q). This biopsy pattern corresponds to which class of lupus nephritis, and what is the clinical significance of classifying it correctly?
A
Class II (mesangial proliferative) lupus nephritis — mild and managed with hydroxychloroquine alone; classification ensures appropriate risk stratification
B
Class IV (diffuse proliferative) lupus nephritis — the most severe form with highest risk of ESRD; classification mandates aggressive immunosuppression (cyclophosphamide or mycophenolate + high-dose corticosteroids)
✓
C
Class V (membranous) lupus nephritis — immune-complex subepithelial deposits producing pure nephrotic syndrome; classification directs RAAS blockade rather than cytotoxic agents
D
Class III (focal proliferative) lupus nephritis — segmental endocapillary proliferation in < 50% of glomeruli; classification indicates moderate immunosuppression
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A 62-year-old man with 25-year history of type 2 diabetes and hypertension presents with 4.5 g/day proteinuria, creatinine 2.6 mg/dL, and eGFR 28 mL/min/1.73m². He has bilateral background and proliferative diabetic retinopathy. Renal biopsy shows diffuse glomerulosclerosis with GBM thickening, diffuse mesangial matrix expansion, and a discrete PAS-positive nodule in the mesangium of several glomeruli. The nodules are acellular and displace the surrounding capillaries to the periphery. No amyloid deposits are identified on Congo Red stain. What is this nodular lesion, and what is its pathogenetic basis?
A
Kimmelstiel-Wilson nodule — acellular mesangial nodule of homogeneous matrix material caused by hyperglycaemia-driven advanced glycation end-product (AGE) accumulation and PKC activation expanding the mesangial matrix
B
Amyloid nodule — Congo Red-positive fibrillar deposit in the mesangium representing AL or AA amyloid that mimics diabetic nodular glomerulosclerosis
C
Light chain cast — linear deposits of filtered monoclonal immunoglobulin light chains precipitating in the mesangium and forming acellular nodules in myeloma kidney
D
Mesangial IgA deposit — granular IgA immune-complex nodule in the mesangium representing IgA nephropathy superimposed on diabetic nephropathy
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A 68-year-old woman with CKD Stage G4 (eGFR 18 mL/min/1.73m²) secondary to diabetic nephropathy is admitted with confusion, asterixis, and Kussmaul breathing. Serum investigations show: creatinine 9.4 mg/dL, urea 142 mg/dL, bicarbonate 9 mEq/L, pH 7.18, potassium 6.8 mEq/L, haemoglobin 7.2 g/dL, PTH 380 pg/mL (elevated). Phosphate 7.2 mg/dL. A 12-lead ECG shows peaked T waves and a widened QRS complex. Which single complication explains the immediate threat to life in this patient, and through which pathological mechanism does advanced uraemia produce this complication?
A
Uraemic encephalopathy from retention of urea and organic acids disrupting the blood-brain barrier, causing immediate cerebral herniation
B
Hyperkalaemia — GFR < 10 mL/min eliminates the kidney's ability to excrete potassium; metabolic acidosis drives H+/K+ exchange causing cellular K+ shift to plasma; peaked T waves and widened QRS herald ventricular fibrillation
✓
C
Severe metabolic acidosis causing myocardial depression and peripheral vasodilation, leading to distributive shock as the immediate cause of death
D
Renal osteodystrophy from secondary hyperparathyroidism causing spontaneous vertebral fractures that compress the spinal cord, explaining the neurological findings
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A 74-year-old man with known ADPKD (autosomal dominant polycystic kidney disease) presents for routine follow-up. Renal ultrasound shows massively enlarged kidneys bilaterally (combined renal length 35 cm) with innumerable cysts of varying sizes. He is found to have a blood pressure of 178/104 mmHg. He has a family history of subarachnoid haemorrhage in his father at age 52. Which extrarenal complication is most specifically associated with ADPKD and explains the family history of subarachnoid haemorrhage?
A
Hepatic fibrosis and portal hypertension from biliary hamartomas developing in the liver parenchyma, causing variceal haemorrhage mistaken for subarachnoid blood
B
Intracranial berry (saccular) aneurysms — occurring in 10-15% of ADPKD patients — at the circle of Willis; rupture causes subarachnoid haemorrhage, explaining the familial clustering
✓
C
Aortic dissection type A from medial degeneration in ADPKD, causing haematoma extending into the cerebral arteries and causing haemorrhage
D
Mitral valve prolapse in ADPKD causing cardioembolism, with emboli lodging in cerebral vessels and producing haemorrhagic transformation of ischaemic infarcts
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A 35-year-old woman with known SLE and Class IV lupus nephritis (previously confirmed on biopsy 3 years ago, treated with mycophenolate) presents with worsening renal function. Repeat biopsy now shows segmental collapse of glomerular capillary loops, tubular microcysts, and ischaemic-appearing glomeruli with wrinkling of the GBM. There is no endocapillary proliferation and no active crescents. IF shows reduced IgG and C3 compared to prior biopsy. Which complication of SLE should be prioritised in the differential diagnosis of this biopsy pattern?
A
Transition to Class V membranous lupus nephritis from epitope spreading of the anti-dsDNA immune response to subepithelial GBM targets
B
Lupus-associated antiphospholipid syndrome (APS) causing renal thrombotic microangiopathy — thrombotic occlusion of glomerular capillaries and arterioles with ischaemic glomerular collapse and tubular injury
✓
C
Cyclophosphamide-induced nephrotoxicity causing tubular microcysts and ischaemic glomeruli as a drug adverse effect
D
Renal amyloidosis developing as a complication of chronic SLE inflammation, with AA amyloid deposits causing glomerular collapse
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A 22-year-old male medical student is asked to review a renal biopsy from a patient with nephrotic syndrome. Light microscopy shows that some glomeruli appear normal while others show segmental areas of sclerosis with hyalinosis (PAS-positive, amorphous material). Immunofluorescence shows non-specific IgM and C3 entrapment in the sclerotic segments. Electron microscopy shows diffuse foot process effacement in both affected and unaffected glomeruli. The patient's serum albumin is 1.8 g/dL and he has been steroid-resistant for 12 weeks. How does the electron microscopy finding of diffuse foot process effacement in non-sclerotic glomeruli inform the pathogenesis of this condition?
A
It confirms that podocyte injury is global and precedes segmental sclerosis — the sclerotic lesions represent sites of injury progression where injured podocytes have detached, allowing GBM collapse and secondary sclerosis
✓
B
It indicates that the entire glomerular population will eventually undergo sclerosis simultaneously within weeks, predicting a rapidly progressive course requiring dialysis initiation immediately
C
It proves that the non-sclerotic glomeruli have IgM deposits that are too small for immunofluorescence detection, causing proteinuria from IgM-mediated podocyte toxicity
D
It suggests that diffuse foot process effacement is the primary cause of haematuria, which distinguishes FSGS from MCD where effacement causes only proteinuria
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A 60-year-old man with no known kidney disease presents to the emergency department with 3 hours of oliguria and confusion after a septic shock episode requiring vasopressors for 8 hours in the ICU. Urine output was 15 mL/hour over the last 4 hours. Urine microscopy shows coarsely granular 'muddy brown' casts and tubular epithelial cells. Serum creatinine has risen from 0.9 to 3.8 mg/dL in 12 hours. Which pathological sequence at the level of the tubular epithelium best explains the mechanism of 'muddy brown' cast formation?
A
Glomerular endothelial injury releases RBCs into the tubular lumen; these haemolyse and precipitate with Tamm-Horsfall protein forming pigmented granular casts
B
Ischaemia causes PCT epithelial cell necrosis and detachment from the basement membrane; sloughed epithelial cells and their debris aggregate with Tamm-Horsfall protein in the tubular lumen, forming coarsely granular 'muddy brown' casts
✓
C
Contrast media nephrotoxicity induces tubular microvacuolisation; lipid-laden tubular cells detach and aggregate with albumin to form granular casts
D
Bence-Jones protein from myeloma light chains precipitates in the distal tubule, forming large laminated casts that obstruct and distend the tubular lumen producing the granular appearance
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A 55-year-old woman with CKD Stage G5 secondary to chronic GN undergoes renal biopsy before initiating dialysis. The biopsy shows globally sclerosed glomeruli with complete hyalinisation, periglomerular fibrosis, tubular atrophy with thickened tubular basement membranes, and dense interstitial fibrosis with a lymphocytic infiltrate. Only 12% of glomeruli appear viable. She asks her nephrologist why both kidneys are shrunken and scarred despite her original disease starting only in the glomeruli. Which mechanism best explains how glomerular injury propagated irreversibly to affect the entire nephron unit?
A
Haematuria from glomerular injury caused iron deposition in tubular cells, resulting in oxidative tubular injury and secondary tubular atrophy independent of nephron loss
B
Progressive glomerular sclerosis eliminates peritubular capillary perfusion; downstream tubules undergo ischaemia-driven atrophy; surviving nephrons develop hyperfiltration injury and subsequent sclerosis, creating a self-perpetuating cycle of nephron loss and fibrosis
✓
C
Proteinuria in the tubular lumen directly stimulates tubular NF-κB inflammatory pathway activation, causing tubulo-interstitial nephritis that then independently progresses to fibrosis of the entire kidney without further glomerular injury
D
Uraemic toxins retained in CKD inhibit erythropoietin production, causing renal anaemia; the resulting hypoxia uniformly damages all compartments of the nephron simultaneously
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