Acute tubular necrosis

Know the mechanism of oliguria in ATN

• See fig. 21-33 in Robbins (p970)

• Tubular damage secondary to toxic/ischemic damage  Activation of vasoconstrictors (angiotensin, thromboxane, catecholamine) & decreased secretion of prostoglandins and kallikreins  Decreased GFR  Decreased tubular fluid  Oliguria

• Tubular casts formed by necrotic debris  obstruction of tubules  increased intratubular pressure  Decreased GFR

• Tubular damage  Back leak of tubular fluid into interstitial tissue  Edema

• Decreased GFR by direct effect of toxins/ischemia

• Ischemia is thought to inhibit production of endothelium-derived relaxation factor (EDRF), and thereby inhibit the effect of vasodilators

• Ischemia stimulates release of endothelin, a potent vasoconstrictor

• Any mixture of the above scenarios

Know the histology of ATN and the characteristic histologic features of ischemic ATN and nephrotoxic ATN

• See figs. 21-34 and 35 in Robbins

• ATN involves necrosis of (proximal) tubular cells, leading to acute renal failure (ARF), and is in fact the most common cause of ARF

• Ischemic ATN

  • Single/Small cluster cell necrosis  Necrosis at multiple points w/ large skip areas

  • Rupture of tubular basement membrane (BM)

  • Lesion is mild and focal – most frequently affects proximal tubules

  • Nonnecrotic tubules are dilated and show loss of brush border

  • Edema of interstitial tissue

  • Accumulation of leukocytes w/in vasa recta

  • TEM - Often fibrin deposition and platelet thrombi in glomerular capillaries

  • SEM – Enlargement of podocytes

  • Signs of epithelial regeneration one week after acute episode - Hyperchromatic nuclei and mitoses

• Nephrotoxic ATN

  • Massive necrosis – often affects proximal and distal tubules

  • BM is intact

Know the causes of nephrotoxic ATN and the characteristics of renal lesions in mercuric chloride, carbon tetrachloride and ethylene glycol

• HgCL₂ - Large eosinophilic inclusions in nucleus during acute phase; stains w/ acid-fast bacillus stain

• CCl₄ - Accumulation of neutral fat

• Ethylene glycol - Calcium oxalate crystals in tubular lumens

Know the different phases of ATN

• Initial phase

  • Can last from 0 (in the case of ischemic insult) to 7 days (in the case of CCl₄)

  • Asymptomatic – normal urine output

  • Elevated BUN and serum creatinine

  • Decreased total solute excretion rate

  • Hypotension / Shock

• Oliguric phase

  • Can last 4 days – 4 weeks

  • Urine output <>

  • If <100>

  • Elevated BUN, serum creatinine, and K

  • Low osmolar urine – FENa >3%

  • May be a slight, nonselective proteinuria due to necrotic debris

• Diuretic phase

  • Gradual increase in urine volume – about 100 cc/day

  • Immature tubule cells aren’t good at reabsorption yet

  • Urine has a low osmolality, but high concentration of Na, K, Cl

  • Proteinuria up to 4 g/day

  • Elevated BUN and serum creatinine

  • Most patients (25%) die during this phase b/c of volume and electrolyte imbalances

• Recovery phase

  • Usually in 17 days – but variable

  • BUN and serum creatinine final return towards normal

  • Complete recovery is influenced by previous renal status, age, and severity of disease (usually proportional to length of oliguric phase)

Know the causes of death in ATN

• Over the years, development of ARF has dramatically declined but ~65% of patients w/ oliguria still die

• Sepsis – uremia and azotemia predispose to infection

• Respiratory failure – due to water retention and edema

• Myocardial failure

• GI bleeding

• Biochemical disorders – wounds, devitalized tissue

• Depends on cause of renal failure, age, injury to other organs, and type of injury (Post traumatic > Post surgical > Medical > Obstetric cases in terms of % mortality)

Know the mechanism of nonoliguric ATN

• Often seen with aminoglycoside toxicity

• Better prognosis than oliguric ATN

• Filtering still occurs in residual nephrons

• Urine output > 400cc/day

Category: Pathology Notes