Pathophysiology of liver cirrhosis and alcholoic liver disease

Etiological, risk factors, clinical conflications and pathogenesis of liver cirrhosis

1. Pathophysiology Liver Cirrhosis RVS Chaitanya K oppala

2. Functions of liver

3. Causes of liver disease Viral infections: HAV, HBV, HCV, HDV, HEV Alcohol Non alcohol induced liver disease (obesity , DM and other metabolic disorders) Immune disorders: Autoimmune hepatitis (anti kidney, anti smooth muscle antibodies) Primary biliary cirrhosis (Anti mitochondrial and granulomatous destruction of lobular bile duct) Primary sclerosing cholangitis ( biliary strictures, cholestatic and cirrhosis) Vascular abnormalities Metabolic and genetic disorders: Hemochromatosis ( iron salts) Wilson’s disease (copper) Alpha antitrypsin deficiency Glycogen deficiency Drugs

4. CLASSIFICATION OF CIRRHOSIS

5. Clotting abnormalities : pathophysiology

6. PORTAL HYPERTENSION

7. Ascites The aim in treatment is to mobilise the abnormal collection of third space fluid (intra abdominal fluid) Achieved by ↓sodium intake (60-90mEq/day) + delayed reaccumulation of fluids (1-1.5L/day) Aggressive fluid reduction in absence of peripheral edema may leads to intravascular fluid depletion and renal dysfuntion Potassium sparing diuretics, loop diuretics and paracentasis (perforation in a cavity to remove the fluids)/ colloid replacement

8. Hepatic encephalopathy Reversible neuropsychiatric complication that occurs with significant liver function Main cause unknown , but there are three main factors which affect the hepatic encephalopathy Portosystemic shunting (bypass of liver) Metabolic dysfuntion Alteration of Blood brain barrier Agents which causes this conditions ( fails to break down) Ammonia Free fatty acids GABA Glutamate

9. Hepatic encephalopathy

10. Investigations Biochemical test: simple, inexpensive and easy to perform Aminotransferases (aspartate transaminases, alanine transaminase): enzymes present in hepatocytes released in blood only in case of liver damage (acute liver disease) Alkaline phosphatase (present in cananicular and sinusoidal membranes of liver and also in other sites like bones, levels seen in chronic liver disease) Gamma glutamyl transpeptidase (confirms the hepatic origin of elevated levels of alkaline phosphatase enzyme)

11. Laboratory investigation of aetiology Derangement of liver functions should be investigation for Hepatitis A, B and C Auto antibodies or immune globulins to screen for autoimmune disease screening should be done Serum ferratin Ceruloplasmin Alpha1 antitrypsin Lipid profile

12. Imaging techniques Ultrasound techniques for assessment of size, shape and texture , dilatation of biliary duct Patency of portal vein to check for portal hypertension (increased spleen , ascites) For checking Hepatocellular carcinoma, hepatobiliary malignancies CT and MRI scan Live biopsy: Invasive procedure associated with mortality and morbidity Remains the gold standard for diagnosis of liver damages and severity of chronic liver disease Recent advanced technique in liver biopsy is non invasive like FIBROSCAN , effective in patients with HCV In acute live dysfunction the liver biopsy is not necessary

13. SPECIFIC TYPES OF CIRRHOSIS ( Alcoholic Liver Disease) Alcoholic liver disease is the term used to describe the spectrum of liver injury associated with acute and chronic alcoholism . There are three sequential stages in alcoholic liver disease : Alcoholic steatosis (fatty liver). Alcoholic hepatitis. Alcoholic cirrhosis.

14. PATHOGENESIS Ethanol and its metabolites are responsible for ill-effects on the liver in a susceptible chronic alcoholic. Briefly , the biomedical and cellular pathogenesis due to chronic alcohol consumption culminating in morphologic lesions of Alcoholic steatosis (fatty liver), Alcoholic hepatitis and Alcoholic cirrhosis

15. PATHOGENESIS OF ALCOHOLIC LIVER DISEASE

16. ETHANOL METABOLISM

17. PATHOGENESIS OF ALD Direct hepatotoxicity to liver Hepatotoxicity by ethanol metabolites Oxidative stress Immunological mechanism Inflammation Fibro genesis Increase redox ration Retention of liver cell water and proteins Hypoxia Increased liver fat

18. RISK FACTORS Drinking patterns ( daily imbibing of 60-80 gm. of ethanol) Gender ( women more susceptible with less alcohol 20-40g/day) Malnutrition (calorie derived from alcohol displace the nutrients) Infections ( intercurrent bacterial infections are common) Genetic factors (MEOS and alcohol dehydrogenase enzyme with HLA) Hepatitis C infection ( HCV + 20-50g/day)

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