Renal: Pathology - Glomerular disease Flashcards
Describe the 4 stages of renal failure (GFR, other laboratory abnormalities, and symptoms)
- Decreased renal reserve
- eGFR 50% of normal
- Normal serum BUN and Cr
- Asymptomatic
- More susceptible to insult - Renal insufficiency
- eGFR 20-50%
- Elevated serum BUN and Cr
- anaemia, HTN, decreased urine concentrating capacity causes polyuria and nocturia - Chronic renal failure
- eGFR <20-25%
- Elevated serum BUN, Cr and K+
- Metabolic acidosis, uraemia, oedema - End-stage renal failure
- eGFR <5%
- Terminal uraemia
Outline the systemic manifestations of chronic renal failure and uraemia as seen in 7 different organ systems/compartments
- Fluid and electrolytes:
- Dehydration, oedema, hyperkalaemia, metabolic acidosis - Bone
- Hyperphosphataemia, hypocalcaemia, secondary hyperparathyroidism, renal osteodystrophy - Haematologic
- Anaemia, bleeding diathesis - Cardiopulmonary
- HTN, CHF, cardiomyopathy, pulmonary oedema, uraemic pericarditis - Gastrointestinal
- Nausea and vomiting, bleeding, oesophagitis/gastritis/colitis - Neurologic
- Myopathy, peripheral neuropathy, encephalopathy - Dermatologic
- Sallow colour, pruritis, dermatitis
What is the mechanism underlying the bleeding diathesis seen in chronic renal failure patients?
Uraemia impairs platelet aggregation and platelet–vessel wall interaction
How can causes of renal failure be broadly categorised?
Pre-renal: hypoperfusion injury
Intra-renal: glomerular disease, tubular and interstitial disease, congenital anomalies, neoplasm (may also be post-renal)
Post-renal: obstruction
Describe the pathophysiology of pre-renal AKI
Hypovolaemia, hypotension or CCF -> poor renal perfusion -> decreased clearance of renal toxins and ischaemia of tubular cells
Describe the 5 glomerular syndromes
- Nephritic syndrome: haematuria, azotemia, oliguria, mild to mod HTN, proteinuria and oedema (less severe than nephrotic)
- Rapidly progressive (crescenteric) glomerulonephritis: acute nephritis, proteinuria, acute renal failure
- Nephrotic syndrome: >3.5g/day proteinuria, hypoalbuminaemia (<3g/dL), oedema, hyperlipidaemia, lipiduria
- Chronic renal failure: azotemia progressing to uraemia over months to years
- Isolated urinary abnormalities: glomerular haematuria and/or subnephrotic proteinuria
What is primary vs secondary glomerular disease?
Primary: predominant or isolated renal involvement
Secondary: disorders causing glomerular disease which have other systemic manifestations
8 primary glomerulopathies
- Acute proliferative glomerulonephritis (e.g. post-Streptococcal, post-infectious)
- Rapidly progressive (crescenteric) glomerulonephritis
- Membranous glomerulopathy
- Minimal-change disease
- Focal segmental glomerulosclerosis
- Membranoproliferative glomerulonephritis
- IgA nephropathy
- Chronic glomerulonephritis
8 causes of secondary glomerulopathy
- SLE
- Amyloidosis
- Diabetes mellitus
- Microscopic polyangiitis
- Wegener’s granulomatosis
- Goodpasture syndrome
- Henoch-Schonlein purpura
- Infective endocarditis
3 hereditary causes of glomerulopathy
- Alport syndrome
- Thin basement membrane disease
- Fabry disease
Three histologic changes seen in glomerular disease and brief explanation of their aetiology
- Hypercellularity: increased mesangial and endothelial cells, leukocyte infiltration, crescent formation (accumulations of epithelial cells and leukocytes)
- Basement membrane thickening: due to abnormal deposition of proteins or increased synthesis of normal proteins
- Hyalinosis/sclerosis: hyalinosis describes plasma protein accumulation in capillary lumen/wall, sclerosis describes proliferation of ECM
6 immune mechanisms of glomerular injury
- Antibody-mediated
- In-situ immune complex deposition
- Circulating immune complex deposition
- Cytotoxic antibodies
- Cell-mediated immune injury
- Activation of alternative complement pathway
With what mechanism of glomerular injury would you see subendothelial vs GBM vs subepithelial immune complex or antibody deposition?
Subendothelial: circulating immune complexes (Ag-Ab)
GBM: anti-GBM binds along length of GBM
Subepithelial: in Heymann nephritis (rat model resembling membranous nephropathy) with antibodies to epithelial cells of the proximal tubular brush border
How do anti-epithelial cell Abs cause proteinuria?
Cytotoxic and complement-mediated injury causes effacement and detachment of podocyte foot processes which leads to protein leakage
Describe the clinical presentation, pathogenesis and pathological findings seen in post-streptococcal glomerulonephritis
Clinical presentation: nephritic syndrome
Pathogenesis: circulating and planted Ag (immune complex-mediated)
Glomerular pathology: granular IgG and C3 in GBM and mesangium, enlarged hypercellular glomeruli
