Systemic Pathology: Cirrhosis and Liver Pathology

Introduction

Lecturer: Dr. Priyanka Sachdeva
Topic: Cirrhosis of the Liver (Hepatobiliary System)
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Overview of Cirrhosis

Irreversible and end-stage disease of the liver
Entire liver is involved (diffuse disease)
Characterized by the conversion of normal liver lobules to multiple nodules
Normal architecture converts to nodular architecture via fibrosis

Normal Liver Architecture

Liver lobules: Hexagonal structures with central veins and portal triads (hepatic artery, portal vein, bile duct)
Hepatic injury leads to the conversion of lobular to nodular model
Ito cells in the liver store fat and Vitamin A, and become myofibroblasts forming collagen during hepatic injury

Pathogenesis of Cirrhosis

Hepatic Injury from various causes (alcohol, virus, excess iron, copper, etc.)
Hepatocytes are injured mainly by accumulating toxic substances
Ito cells convert to myofibroblasts and produce collagen fibers
Result: Diffuse liver fibrosis and nodular regeneration of surviving hepatocytes
Final stage: irreversible nodular liver architecture (only treatment is liver transplant)

Classification of Cirrhosis

Morphological Classification

Micronodular: Nodules < 3 mm (e.g., alcohol, Wilson’s disease, viral hepatitis B and C)
Macronodular: Nodules > 3 mm (e.g., hemochromatosis)

Etiological Classification

Alcoholic Cirrhosis: Due to chronic alcohol intake
Post-Neoteric: Due to viral infections (especially hepatitis B and C)
Biliary Cirrhosis: Due to obstruction in bile ducts
Hemochromatosis Cirrhosis: Excess iron deposition
Wilson’s Disease: Excess copper accumulation
Cardiac Cirrhosis: Secondary to right heart failure

Detailed Pathology of Some Types of Cirrhosis

Alcoholic Cirrhosis

Stages: Fatty liver, alcoholic hepatitis, cirrhosis
Histology: Micro and macro vesicular steatosis, balloon degeneration, Mallory bodies, neutrophilic infiltration, and fibrosis (chicken wire fence appearance in second stage involving fibrosis)

Wilson’s Disease

Genetic Defect: ATP7B gene on chromosome 13
Pathogenesis: Failure to convert free copper to ceruloplasmin; free copper accumulates in the liver, eyes (Kayser-Fleischer ring), and brain (basal ganglia)
Diagnosis: Measure liver copper (>200 mg/g), serum ceruloplasmin (low), urinary copper (high), genetic testing
Clinical Features: Liver cirrhosis, neurologic symptoms, Kayser-Fleischer ring in the cornea, sunflower cataracts
Treatment: Chelating agents (e.g. penicillamine)

Hemochromatosis

Genetic Defect: HFE gene mutation (most common)
Pathogenesis: Excess iron absorption and accumulation, inadequate hepcidin regulation, iron deposits in liver (causing cirrhosis), skin, pancreas (causing diabetes), joints, heart, and pituitary gland
Diagnosis: Liver biopsy showing iron (stains like Prussian blue), genetic testing, serum ferritin levels, transferrin saturation
Clinical Features: Liver cirrhosis, diabetes mellitus (bronze diabetes), skin pigmentation, joint pain, and hypogonadism
Treatment: Phlebotomy, chelation therapy

Summary and Conclusion

Cirrhosis is a complex and irreversible liver disease with various etiologies
Key to management involves understanding histological changes, clinical features, and appropriate treatment modalities
Continuous learning and comprehension of pathology aids in better diagnosis and treatment of liver diseases

Important Resources

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Engage in continuous studies and refer to provided materials for in-depth understanding

Preparation: Further understanding specific cirrhosis pathology and clinical implications. Practice with diagrams and histological slides to ensure clear identification of stages and types.