Liver failure

1. Patterns of Hepatic Injury (overview)

• Degeneration / accumulation: cell swelling; steatosis — microvesicular (alcoholic liver disease, Reye) vs macrovesicular (obese/diabetic, displaces nucleus).
• Necrosis / apoptosis: apoptotic hepatocytes shrunken, pyknotic, eosinophilic; ischemia & many drugs/toxins → centrilobular necrosis.
• Regeneration: hepatocyte replication after loss — mitotic figures.
• Inflammation: influx of acute/chronic inflammatory cells → hepatitis.
• Fibrosis: collagen deposition (central vein / sinusoids) → bridging fibrosis.
• Cirrhosis: parenchymal nodules + scar; normal architecture lost; ↑ malignancy risk.

2. Definition

• Liver failure = clinical syndrome of total loss of liver function from injury / disease.
• Develops insidiously or via repetitive waves of damage; 80–90 % of hepatic function must be lost before failure ensues.
• Definitive treatment = liver transplantation.

3. Etiologic Categories

A) Acute (fulminant) liver failure

• Hepatic insufficiency → encephalopathy within 2–3 weeks.
• >90 % of functional capacity lost; massive hepatic necrosis.
• Gross: atrophica hepatica flava — yellow, shrunken liver (yellow = extensive necrosis).
• Causes:
  • Viral: fulminant HAV / HBV / HCV / HDV
  • Toxic: drugs (acetaminophen), Amanita mushrooms
  • Idiopathic

B) Chronic liver disease (most common route to failure)

• End-point of chronic damage → cirrhosis (regenerative nodules + fibrous bands + vascular shunting).
• Leading causes: chronic HBV / HCV, NAFLD, alcoholic liver disease.
• Not all cirrhosis → failure; not all end-stage chronic disease is cirrhotic.

C) Hepatic dysfunction without overt necrosis

• Hepatocytes viable but unable to perform normal metabolic function.

4. Clinical Consequences (life-threatening complications)

A) Hepatic encephalopathy

• CNS dysfunction from toxin (ammonia) accumulation → reflex abnormalities → deep coma → death.
• Hallmark sign: asterixis (non-rhythmic flapping tremor of hands/head).
• Acute: ↑ blood ammonia → impaired neuronal function + cerebral edema.
• Chronic: altered cerebral amino acid metabolism → deranged neurotransmission.

B) Hepatorenal syndrome

• Renal failure secondary to hepatic dysfunction; reversible.
• Mechanism: splanchnic vasodilation + systemic vasoconstriction “sucks” blood from the kidney.
• Sx: oliguria, azotemia (↑ BUN/Cr).
• Urine: hyperosmolar, low Na⁺, no proteins / no abnormal sediment — distinguishes from ATN.

C) Hemorrhagic diathesis (coagulopathy)

• ↓ hepatic synthesis of clotting factors → bleeding tendency (often massive GI hemorrhage).
• Thrombocytopenia (obligatory):
  • ↓ thrombopoietin (made by liver)
  • Splenomegaly → hypersplenism (platelet sequestration)
• Thrombocytopenia + factor deficiency → hemorrhagic diathesis.

💡 High-yield: Liver failure needs ≥80–90 % function lost; only cure = transplant. Acute / fulminant: yellow atrophy (atrophica flava), drugs/Amanita/viral, encephalopathy in <3 wk. Chronic: cirrhosis from HBV / HCV / NAFLD / alcohol. Triad of complications: encephalopathy (asterixis, NH₃, cerebral edema) + hepatorenal (low urine Na⁺, ≠ ATN) + coagulopathy (factor ↓ + thrombocytopenia from hypersplenism).