Acute tubular necrosis

on 9.1.09 with 0 comments

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



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