Alcoholic Liver Disease - B. Pharma 2nd Semester Pathophysiology notes pdf

Alcoholic Liver Disease

Content

•       Alcoholic Liver Disease

•       Symptoms

•       Pathogenesis

•       Laboratory Diagnosis

Objectives

At the end of this session, student will be able to –

•       Explain the Pathogenesis of Alcoholic Liver Disease

•       Describe the Symptoms of Alcoholic Liver Disease

•       Explain various laboratory diagnosis test for Alcoholic liver Disease

Alcoholic Liver Disease

Alcoholic liver disease is the term used to describe the spectrum of liver injury associated with acute and chronic alcoholism

Signs and Symptoms

•       Progresses in the liver as inflammation (hepatitis) and leads to fatty liver and cirrhosis

Risk factors

•       Occurs after many years of excessive drinking

•       Acute alcoholic hepatitis – Binge drinking

•       Severe drinking – Life threatening

•       Genetic factors - Women have increased susceptibility to develop advanced alcoholic liver disease with much lesser alcohol intake

•       Malnutrition

•       Toxicity of ethanol in liver

•       Infection – Hepatitis C infection

Distinctive forms of Alcoholic Liver Disease

Hepatic Steatosis (Fatty liver)

•          Moderate consumption - Deposition of small lipid droplets in hepatocytes

•          Excessive consumption – accumulation of lipids in macrovascular  droplets

•          Nucleus gets displaced, Enlarged liver

Alcoholic hepatitis

•          Necrosis of liver cells in centrilobular region

•          Neutrophillic reaction

•          Fibrosis

Alcoholic Cirrhosis

•          Irreversible - Final stage

•          Liver turns brown, shrunken and non-fatty appearance

•          Resembles post necrotic cirrhosis 

Pathogenesis of Alcoholic Liver Disease

Ethanol Metabolism

ADH = Alcohol Dehydrogenase; ALDH or ACDH = Hepatic Acetaldehyde Dehydrogenase; NAD = Nicotinamide Adenine Dinucleotide; NADH = Reduced NAD

•       Direct hepatotoxicity by ethanol to microtubules, mitochondria, membrane hepatocytes

•       Hepatotoxicity by ethanol metabolites

–      Production of protein-aldehyde adducts

–      Formation of malo-di-aldehyde-acetaldehyde (MAA)

•       Oxidative Stress -  oxidation of ethanol by cytochrome 450 oxidase, generation of free radicals and oxidative damage

•       Immunological attacks on hepatocytes

•       Fibrogenesis

–      Damaged hepatocytes,

–      Malon-di-aldehyde-acetaldehyde adducts,

–      Activated kupffer cells, and

–      Direct stimulation by acetaldehyde

Laboratory Diagnosis For Alcoholic Liver Disease

•       Elevated transaminases: increase in SGOT (AST) is more than that of SGPT (ALT)

•       Rise in serum γ-glutamyl transpeptidase (γ-GT)

•       Elevation in Serum alkaline phosphatase

•       Hyperbilirubinaemia

•       Hypoproteinaemia with reversal of albumin-globulin ratio

•       Prolonged prothrombin time and partial thromboplastin time

•       Anemia and Neutrophilic leucocytosis

Summary

•       Alcohol liver disease is damage to liver and its function due to alcohol abuse

•       Progresses in the liver as inflammation (hepatitis) and leads to fatty liver and cirrhosis

•       Major forms include hepatic steatosis, hepatitis, cirrhosis

•       Alcohol is a caloric food source which displaces nutrients

•       Causes the activation of Kupffer cells and release of proinflammatory mediators