Acute tubular necrosis (ATN)

1. Definition

• Clinicopathological entity:
  • Morphologically: damaged tubular epithelial cells.
  • Clinically: acute suppression of renal function.
• Most common cause of acute renal failure.
• Urine output < 400 mL/day within 24 h → oliguria.

2. Three Types of ATN

A) Ischemic ATN

• Shock → redistribution of circulation → ↓ renal blood flow → ↓ O₂ + substrate delivery → ischemia of tubules.
• Causes: severe hypovolemia, sepsis, hemorrhage, burns, dehydration, CHF.

B) Pigment-Induced ATN

• Pigment precipitation in tubular lumen → cast formation → obstructs flow → ↑ intratubular pressure → leakage of H₂O + plasma into interstitium → ↑ external pressure → tubular collapse.
• Two main pigments:
  • Hemoglobin — severe intravascular hemolysis (transfusion reaction, malaria).
  • Myoglobin — crush syndrome / rhabdomyolysis (muscle breakdown).

C) Nephrotoxic ATN

• Caused by:
  • Heavy metals — mercury, lead, arsenic
  • Drugs — aminoglycosides, amphotericin, cisplatin, contrast media
  • Organic solvents — carbon tetrachloride, ethylene glycol

3. Pathogenesis

• ATN is reversible if cause removed in time.
• Shock (dehydration, renal artery stenosis, CHF) → ↓ blood flow → RAAS up-regulated → pre-capillary contraction → ↓ glomerular plasma flow + ↓ O₂ to tubules.
• Shedding of tubular cells + pigments → cast formation → blocks urine flow → ↑ intratubular pressure → fluid leak into interstitium (edema) → ↓ GFR → tubular collapse.

4. Morphology

Ischemic + Pigment-Induced ATN

• Segmental necrosis at:
  • Straight portion of proximal tubule (PST/S3)
  • Thick ascending limb (TAL) of loop of Henle
• Distribution → “skip lesions” along tubule.
• Basement membrane fragmentation → worse prognosis (≈ 50 % lethality).
• Tubular casts (“muddy brown” granular casts) in distal tubules.

Nephrotoxic ATN

• Necrosis predominantly in proximal convoluted tubule (PCT) — site of drug/toxin reabsorption.
• Basement membrane preserved → better prognosis (allows regeneration).

5. Comparison Table

Feature	Ischemic + pigment	Nephrotoxic
Cause	Shock, hemolysis, rhabdo	Drugs, heavy metals, solvents
Site	Straight PT (S3) + TAL — skip lesions	Proximal convoluted tubule
Basement membrane	Fragmented	Preserved
Prognosis	Worse (50 % lethality)	Better (regeneration possible)

6. Clinical Course — Three Stages

A) Initiation (~36 h)

• Rapid drop in urine output → oliguria.
• ↑ Serum creatinine + BUN.

B) Maintenance (3–6 days)

• Urine output continues to drop → oliguria/anuria.
• Uremia + hypervolemia signs and symptoms.
• Hyperkalemia, metabolic acidosis, fluid overload → life-threatening.

C) Recovery

• ↑ Urine output → polyuria (~3000 mL/day) → hypovolemia.
• Severe electrolyte imbalances (K⁺, Na⁺, PO₄³⁻ losses).
• ↑ Vulnerability to infection (#1 cause of death).
• Complete recovery within months typically (especially nephrotoxic).

💡 High-yield: ATN = #1 cause of acute renal failure with oliguria. 3 types: ischemic (shock), pigment-induced (Hb / myoglobin from rhabdomyolysis), nephrotoxic (drugs, heavy metals). Sites: ischemic = straight PT + TAL with BM fragmentation (worse prognosis); nephrotoxic = PCT with preserved BM (better prognosis). 3 stages: initiation → maintenance (oliguria + uremia + hyperkalemia) → recovery (polyuria + hypovolemia + infection risk). Reversible condition.