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

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