Liver Failure

LIVER FAILURE

1. Tutorial Pathophysiology of Liver Failure 1/9/19

2. Learning Objectives By the end of this tutorial you should be able to: List the major causes of Acute Liver Failure List the major causes of Chronic Liver Failure Describe the types of Liver Failure Describe pathophysiology of sign and symptoms of Liver Failure Identify Hepatic Encephalopathy Identify Hepatorenal Syndrome Identify Hepatopulmonary Syndrome

3. 3 Liver Failure (LF) or Hepatic Failure (HF) About 80 to 90% loss of hepatic functional capacity results in LF Types: Acute liver failure associated with encephalopathy within 6 months after the initial diagnosis Fulminant liver failure when encephalopathy develops within 2 weeks of the onset of jaundice Sub-fulminant liver failure when encephalopathy develops within 3 months of onset of jaundice Chronic liver failure , end result of chronic hepatitis or chronic liver disease, leads to cirrhosis Hepatic dysfunction without apparent liver necrosis

4. LIVER FAILURE Acute liver failure, due to massive liver necrosis caused by Drug or toxin induced; direct toxic damage to hepatocytes or combination of toxicity and inflammation with immune-mediated hepatocyte destruction e.g acetaminophen, halothane, rifampin , isoniazid, antidepressant monoamine oxidase inhibitors, CCL4 , and mushroom poisoning ( Amanita phalloides ) Viral Hepatitis; A, B & E infection accounts for 4-8% but not with HCV infection Chronic liver disease Most common route to LF; chronic hepatitis ending in cirrhosis Hepatic dysfunction without necrosis Hepatocytes may be viable but unable to perform normal function , seen in Reye syndrome , tetracycline toxicity, and acute fatty liver of pregnancy

5. Pathologic Basis of Clinical Manifestation of LF Hypoalbuminemia; Peripheral edema and ascites Hyperammonemia ; Cerebral dysfunction (encephalopathy) Mercaptans formation; action of GIT bacteria on methionine, causes Fetor hepaticus (body odor "sweet and sour“) Impaired estrogen metabolism; Hyperestrogenemia , leads to hypogonadism and gynecomastia in male Reflection of local vasodilation -palmar erythema and spider angioma (a central, pulsating, dilated arteriole from which small vessels radiate) Impaired hepatic synthesis of clotting factors II, VII, IX & X; Bleeding tendency in GIT Intestinal absorption of blood, metabolic load on liver, worsens extent of LF Highly susceptible to failure of multiple organ system; respiratory failure with pneumonia and sepsis combine with renal failure

6. Hepatic encephalopathy Disorder of neurotransmission in CNS and neuromuscular system associated with elevated blood ammonia levels Disturb consciousness, confusion, deep coma and death Flapping tremors Encephalopathy reversible if acute onset, in the chronic setting neuronal dysfunction

7. Hepatorenal syndrome Renal failure in severe CLD due to decrease glomerular filtration because of ; Sodium and water retention Due to decreased renal perfusion pressure secondary to systemic vasodilation Activation of renal SNS with vasoconstriction of afferent renal arteriole Increased synthesis of renal vasoactive mediators

8. Portopulmonary Hypertension or Hepatopulmonary Syndrome Abnormal intrapulmonary vascular dilatation in combination with increased pulmonary blood flow results in shunting of blood which leads to; Ventilation-perfusion mismatch Reduced oxygen diffusion S evere arterial hypoxemia D yspnea C yanosis

9. Ascites The pathogenesis of ascites involves following mechanisms: Increased movement of intravascular fluid into the extravascular space of Disse , caused by sinusoidal hypertension and hypoalbuminemia Renal retention of sodium and water due to secondary hyperaldosteronism