Hepatic Failure

Liver

Liver Normal Pathology General Features

Infectious Diseases

Autoimmune Hepatitis

Drugs & Toxins

Alcoholic Liver Disease

Metabolic Liver Disease

Intra Hepatic Biliary Diseases

Circulatory Disorders

Hepatic disease- Pregnancy

BM Transplantation – Hepatic Disease

Tumors

Normal Liver

• Patterns of Hepatic Injury • Hepatic injury • Inflammation =hepatitis • Hep. C = MCC of chronic hepatitis • Degeneration – – ballooning =swelling and edema of hepatocytes – 1. Necrosis - coagulative necrosis (ischemia), less common ( liver has dual blood supply) – 2. Apoptosis =councilman body ( apoptotic bodies in the liver caused by viral hepatitis)

• Regeneration – possible in all but not in fulminant diseases • Fibrosis= seen in cirrhosis • Hepatic failure = fulminate damage = 80 to 90% of liver is damaged

Patterns of Hepatic Injury Normal Liver

Inflammation (Hepatitis)

Apoptotic Body What is the name for it?

Fibrosis (Cirrhosis)

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General Features of Hepatic Disease 1. Hepatic Failure = Severe liver disease MCC of fulminate (acute) hepatic failure= Paracetamol Other causes– Drugs (Halothane, Tetracyclines, mushroom poisoning) – acute fatty liver of pregnancy > 80 to 90% of hepatic function is lost regeneration is rare (Hepatic transplantation - only treatment) Mortality - 70 to 95% Patient dies in 2 to 3 weeks Clinical features  jaundice, hypoalbuminemia, hyperammonemia  Fetor hepaticus (a peculiar body odor related to mercaptan formation)  Hyperestrogenemia a) palmar erythema b) spider angiomas of the skin (one or two are normal esp. in pregnancy) c) hypogonadism d) Gynecomastia Complications a) Coagulopathy ( ↓ hepatic synthesis of clotting factors) b) Multi- organ failure c) Hepatic encephalopathy ( ↑Ammonia) d) Hepatorenal syndrome

palmar erythema

Spider angiomas

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General Features of Hepatic Disease 2. Hepatic Encephalopathy = disorder of CNS &

neuromuscular transmission Disturbances of consciousness & sleep, (behavioral abnormalities, confusion, stupor, coma, death) EEG changes, limb rigidity and Hyperreflexia, Seizures & Asterixis (a flapping tremor of outstretched hands) Pathogenesis= Severe loss of Hepatocellular function & Exposure of the brain to excess ammonia levels

3. Hepatorenal Syndrome= Renal insufficiency (↑Urea and creatinine) secondary to severe liver disease decreased renal perfusion pressure→ renal vasoconstriction oliguria with a hyperosmolar urine without Proteinuria surprisingly low urinary sodium (though kidney can still concentrate Urine) kidney function promptly improves if hepatic failure is reversed

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General Features of Hepatic Disease 4. Cirrhosis =Among the top ten leading causes of death Three characteristics – 1) Fibrosis - delicate bands or broad septa from portal triad to central vein or c vein to c vein. Most imp • Fibrosis - irreversible and result in Portal HTN • In Cirrhosis =Types I and II collagens are deposited every where (normally types I and III) • Stellate cell (Ito cell) =Major source of excess collagen – 2) nodules - regeneration of hepatocytes – 3) Loss of architecture of the entire liver Major causes= MCC is alcohol - (60-70%) called ASH – cryptogenic cirrhosis (10-15%) called NASH – viral hepatitis B an C (10%)

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General Features of Hepatic Disease 4. Cirrhosis Clinically Silent but ultimately leads to • Anorexia, weight loss, Weakness, osteoporosis, debilitation • Jaundice may or may not be seen Causes of death : complications of portal hypertension (MC is Bleeding from Esophageal Varices) 5. Portal HTN= 12 mm Hg or greater Causes: – Pre hepatic = obstructive thrombosis & narrowing of the portal vein – Intra hepatic = Cirrhosis, Schistosomiasis, – Post hepatic = severe Right-sided heart failure, constrictive Pericarditis (MCC- TB), or hepatic veins outflow obstruction (Budd-Chiari syndrome)

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General Features of Hepatic Disease

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5. Portal HTN= 12 mm Hg or greater Clinically 1. Ascites (↑peritoneal fluid) 2. Varicosities 3. Congestive splenomegaly 4. Hepatic encephalopathy 6. Cholestasis = retention of bilirubin , bile salts & cholesterol 7. Jaundice =Bilirubin production > hepatic clearance • Total bilirubin = conjugated + Unconjugated. • Conjugated bilirubin is more soluble Result from Hepatocellular dysfunction (Intrahepatic) or Biliary obstruction (Extahepatic) Symptoms ; jaundice- (↑Bilirubin), pruritus - retention of bile acids, Xanthomas (skin accumulations of cholesterol), Lab data; ↑Bilirubin ,↑ serum alkaline phosphatase

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Portal HTN

Portal HTN

Splenomegaly

Esophageal Varices

Caput Medusa

Cirrhosis

Cholestasis

• Hepatocytes - enlarged with dilated canalicular spaces • Apoptotic cells • Kupffer cells contain regurgitated bile pigments.

Cholestasis - prolonged

• Bile duct proliferation (more than 2 = abnormal)

Cholestasis - Types

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Intrahepatic Hepatocellular dysfunction or intrahepatic bile duct disease congenital Transplantation is only the treatment if uncorrected- becomes cirrhotic

Extrahepatic • resulting from obstruction • Acquired • amenable to surgical correction • if uncorrected- becomes cirrhotic

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General Features of Hepatic Disease 7. Jaundice

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Causes 1. Bilirubin overproduction – hemolytic anemias, Resorption of major hemorrhages, ineffective Erythropoiesis in the bone marrow 2. hepatic uptake of bilirubin = drugs – rifampin 3. Impaired hepatic conjugation of bilirubin – Unconjugated  physiological jaundice of newborns (neonatal jaundice)  Genetic diseases  Gilbert syndrome – MCC , but detected incidentally – mutations of the UGT gene – No clinical consequences – fluctuating jaundice – detected during Intercurrent illness or fasting,  Crigler-Najjar syndrome type I - AR, total absence UGT, fatal  Crigler-Najjar syndrome type II - AD, less UGT levels, nonfatal

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General Features of Hepatic Disease 7. Jaundice Causes 4. Conjugated hyperbilirubinemia =associated with cholestasis – Dubin-Johnson syndrome – AR ,defective canalicular secretion of bilirubin

• liver is brown, with accumulation of pigment granules in hepatocytes (polymers of epinephrine metabolites), • jaundiced with life expectancy –

Rotor syndrome – AR, jaundiced with life expectancy

Pigmented Liver seen in ?

• Liver is brown • Due accumulation polymers of epinephrine metabolites