Renal Pathology

Question 1

What are the causes of acute kidney injury (or acute tubular necrosis)?
(Prompt: provide examples)

Answer 1

• Ischaemia - shock, circulatory collapse, dehydration, malignant hypertension, vasculitis, hypercoagulable states
• Direct toxic injury - drugs, radiocontrast dyes, myoglobin, Hb, radiation
• Acute tubulointerstitial nephritis - hypersensitivity response to drugs
• Urinary obstruction - tumours, prostatic hypertrophy, calculi, blood clots

Question 2

Describe the clinical course of AKI

Answer 2

Highly variable. Classically 3 stages:
• Initiation phase (up to 36 hrs) - inciting event with slight decline in UO and rise in BUN
• Maintenance phase - oliguria (40 - 400 mL/day), NaCl and H2O overload, hyperK, metabolic acidosis, rising BUN
• Recovery phase - polyuria (up to 3 L/day), H2O, Na and K losses (risk of hypoK), eventually renal tubular function restored and concentrating ability improves

Question 3

What is the prognosis of AKI?

Answer 3

Depends partly on cause.
Good (> 95% survival) in most cases of nephrotoxic AKI
Poor (> 50% mortality) from overwhelming sepsis or other causes of MOF

Question 4

What are the features of nephrotic syndrome vs nephritic syndrome?

Answer 4

Nephrotic sy: excessive glomerular permeability to plasma proteins with proteinuria (> 3.5 g/day). Albuminuria, hypoalbuminaemia, decreased colloid osmotic pressure and systemic oedema. Also, Na and H2O retention, hyperlipidaemia, lipiduria, susceptible to infection and thrombotic complications
Nephritic sy: haematuria, mild to moderate proteinuria, HTN +/- oedema.

Question 5

What are the causes of nephrotic syndrome vs nephritic syndrome?

Answer 5

Nephrotic sy:
• Primary glomerular disease - membranous glomerulopathy, minimal-change disease, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritides
• Systemic diseases - DM, amyloidosis, SLE, drugs (NSAIDs, penicillamine), infections (malaria, syphilis, hep B and C), malignancy (carcinoma, lymphoma).
Nephritic sy:
• Acute proliferative (post streptococcal) glomerulonephritis - immune complex-mediated disorder caused by deposition of Ag-Ab complexes containing proteins derived from certain bacterial infections
• Rapidly progressive (crescentic) glomerulonephritis:
Type I RPGN - anti-GBM disease (Goodpasture sy)
Type II RPGN - immune complex-mediated disease
Type III RPGN - pauci-immune type, circulating ANCA a/w systemic vasculitis

Question 6

Define acute kidney injury

Answer 6

Characterised by renal tubular epithelial cell injury

Question 7

What is the pathogenesis of AKI?

Answer 7

Reversible and irreversible tubular damage leading to diminished renal function. Tubular epithelial cells very sensitive to ischaemia and toxins.
Arteriolar vasoconstriction leads to increased endothelia and decreased NO and prostacyclin
Tubular obstruction by necrotic and apoptotic epithelial cells and proteinaceous material
Back-leak of tubular fluids
Glomerular ultrafiltration directly affected by ischaemia and toxins

Question 8

What factors play a role in urinary stone formation?

Answer 8

Increased concentration of stone constituents
Changes in urinary pH
Decreased urine volume
Bacteria
Loss of inhibitors of crystal formation, e.g. citrate, pyrophosphate or nephrocalcin