Paper I
Question
A 72year old gentleman with long standing Diabetes mellitus presented with frequent urination and dysuria since a week, followed by fever of 101.8o F. On examination, his face appeared flushed, heart rate was 102/min and BP was 88/60mm Hg. CBC showed neutrophilicleukocytosis. He was started on antibiotics, but his urine output decreased to 50ml/24h by 2nd day.
- (a) What is your provisional diagnosis and cause of death 3 mark(s)
- (b) Explain the pathogenesis of this condition 6 mark(s)
- (c) Add a note in the gross and microscopic changes in the kidney in this condition 6 mark(s)
Answer
(a) Provisional diagnosis and cause of death
- Provisional diagnosis: Acute pyelonephritis (ascending urinary tract infection) in a diabetic patient, progressing to urosepsis/septic shock with acute kidney injury
- Cause of death: Septic shock leading to acute tubular necrosis and multi-organ failure — the clinical progression (fever, tachycardia, hypotension, flushed warm extremities suggesting the vasodilated phase of septic/distributive shock, neutrophilic leucocytosis, followed by oliguria/anuria) is characteristic of severe sepsis progressing to septic shock and renal failure
(b) Pathogenesis
- Diabetes mellitus predisposes to urinary tract infection through multiple mechanisms: glucosuria providing a favourable growth medium for bacteria, impaired neutrophil function, diabetic autonomic neuropathy causing incomplete bladder emptying (urinary stasis), and microvascular disease impairing local host defences
- Bacteria (commonly E. coli) ascend from the lower urinary tract to the renal pelvis and, via the collecting ducts, into the renal parenchyma, causing acute suppurative (pyogenic) inflammation — acute pyelonephritis
- In diabetics, this can progress to necrotizing papillitis (renal papillary necrosis) due to the combination of infection and underlying microvascular ischaemia of the papillae
- Bacterial products (endotoxin from Gram-negative organisms) enter the systemic circulation, triggering a massive cytokine-mediated inflammatory response (TNF-α, IL-1, IL-6), causing widespread vasodilatation, hypotension, and increased vascular permeability — the picture of septic (distributive) shock
- Progressive renal hypoperfusion (from both the septic shock and direct infective damage) leads to acute tubular necrosis, manifesting as the observed oliguria, and if uncorrected progresses to irreversible multi-organ failure and death
(c) Gross and microscopic changes in the kidney
Gross appearance
- Kidney may be enlarged, with a swollen, hyperaemic surface
- Multiple small, yellowish-white raised abscesses may be visible on the cortical surface (in acute pyogenic pyelonephritis)
- In necrotizing papillitis: grey-white to yellow necrosis of the renal papillae, which may slough into the renal pelvis
- Later, if superimposed ATN develops: pale, swollen cortex with a congested medulla
Microscopic appearance
- Acute pyelonephritis: Patchy interstitial suppurative inflammation with neutrophilic infiltration, involving the tubules and interstitium in a patchy distribution; tubules may contain neutrophilic casts; glomeruli are typically relatively spared until late stages
- Necrotizing papillitis: Coagulative necrosis of the renal papillae, with an adjacent zone of neutrophilic infiltration and preserved outline of tubules (“tubular ghosts”)
- Acute tubular necrosis (superimposed, from shock/sepsis): Patchy necrosis of tubular epithelial cells (especially proximal tubules), loss of brush border, tubular epithelial cell flattening, intraluminal casts, and denuded basement membrane in severely affected segments