Liver cirrhosis for students n

Histopathology of Liver Cirrhosis

1. Liver Cirrhosis Lecture 19 Dr Mohammad Manzoor Mashwani BKMC Mardan

2. Yellowish brown color Tawny

3. Introduction The term cirrhosis was first used by Rene Laennec (1781-1826) to describe the abnormal liver color of individuals with alcohol induced liver disease. Derived from Greek word Kirrhos means Yellowish brown color. Cirrhosis is among the top 10 causes of death in the Western world.

4. Definition Cirrhosis is defined as a diffuse process c haracterised by fibrosis & the conversion of normal liver architecture into structurally abnormal nodules.

5. Common Causes Chronic alcoholism & NASH Chronic hepatitis B& C Biliary disease Hemochromatosis (Iron oveload ) Cryptogenic 10% Wilson's disease, Alpha-1 anti-trypsin deficiency.

6. Causes of Liver Cirrhosis Obesity Autoimmune hepatitis Diseases that damage or destroy bile ducts. Inherited diseases Drugs & toxins

7. Types of Cirrhosis 1. Alcoholic Cirrhosis (Laennec) 2. Post necrotic Cirrhosis (macronodular) 3. Billiary Cirrhosis 4. Cardiac Cirrhosis

8. Pathogenesis Hepatocellular death Regeneration Progressive fibrosis Vascular reorganization Three processes are central to the pathogenesis of cirrhosis: death of hepatocytes, extracellular matrix deposition, a nd vascular reorganization .

9. Morphology Its three main morphologic characteristics are: 1.Bridging fibrous septa (delicate fibrous bands/broad scars) 2. Parenchymal nodules- micro (<3mm) & macro (>1cm) 3. Disruption of the architecture of the entire liver. 4. It occurs following hepatocellular necrosis of varying etiology so that there are alternate areas of necrosis and regenerative nodules. However, regenerative nodules are not essential for diagnosis of cirrhosis since biliary cirrhosis and cirrhosis in haemochromatosis have little regeneration.

10. Clinical manifestations Early manifestations No symptoms GI disturbances : anorexia, dyspepsia, flatulence, weakness, fatigue, nausea, vomiting, weight loss, abdominal pain, bloating, diarrhea, constipation Abdominal pain, dull and heavy feeling Fever, lassitude, weight loss, enlargement of liver and spleen.

11. Clinical manifestations Cont… Later manifestations: Results from liver failure and portal hypertension Jaundice Peripheral edema Ascites Others: Skin lesion, hematological disorders, endocrine disturbances, and peripheral neuropathy Advanced stage : small and nodular liver

12. Clinical Manifestations

13. Complications The ultimate mechanism of deaths in most cirrhotic patients is (1) progressive liver failure , (2) a complication related to portal hypertension , or (3) the development of hepatocellular carcinoma . Ascites Esophageal variceal bleeding Hepatic encephalopathy Hepatorenal syndrome Spontaneous bacterial peritonitis Portal hypertensive gastropathy Infection Liver failure Hepatocellular carcinoma

14. Annual Exame 2013 A biopsy report of a 55 years old lady, admitted to hospital for complaints of abdominal distension and palor , reveals loss of normal lobular architecture with replacement of liver parenchyma by haphazardly regenerating nodules surrounded by coarse fibrous septa a. Name the disease, the lady is most probably suffering from. 2 b. Enlist only o5 important causes of this disease 2.5 c. Enumerate only five complications of this disease 2.5 d. What is the most important complications of ascites in this disease 1 e. Name only four poor prognostic signs of this disease 2

15. Answer a. Liver Cirrhosis b. Chronic alcoholism & NASH, Chronic hepatitis B& C, Biliary disease ,Hemochromatosis, Cryptogenic 10% , Wilson's disease, , Alpha-1 anti-trypsin deficiency. c. Ascites, Esophageal variceal bleeding, Hepatic encephalopathy, Hepatorenal syndrome, Spontaneous bacterial peritonitis, Portal hypertensive gastropathy, Infection, Hepatic failure, Hepatocellular carcinoma d, Pleural effusion, dyspnea, Infections (spontaneous bacterial peritonitis (SBP)), Hepatorenal syndrome. e. Serum albumin ( Hypoalbuminemia ), Serum bilirubin ( Hyperbilirubinemia ), INR ( increased International Normalized Ratio ), Ascites, Encephalopathy.

16. International normalized ratio (INR) The prothrombin time ( PT ) and its derived measures of prothrombin ratio ( PR ) and international normalized ratio ( INR ) are measures of the extrinsic pathway of coagulation . This test is also called "ProTime INR" and "PT/INR". They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status. PT measures factors I (fibrinogen) , II (prothrombin) , V , VII , and X . It is used in conjunction with the activated partial thromboplastin time ( aPTT ) which measures the intrinsic pathway . International normalized ratio: A system established by the World Health Organization (WHO) and the International Committee on Thrombosis and Hemostasis for reporting the results of blood coagulation (clotting) tests. Abbreviated INR. Under the INR system, all results are standardized. For example, a person taking the anticoagulant warfarin (brand name: Coumadin) would regularly have blood tested to measure the INR. The INR permits patients on anticoagulants to travel and obtain comparable test results wherever they are.

17. A known patient of chronic Hepatitis B presents with ascites, weight loss, and splenomegaly. Biopsy was performed. External surface is irregular and it is firm in consistency. It showed loss of normal tissue architecture and fibrosis. TASK What is your diagnosis? Name different etiological factors leading to this condition. What is the most common cause of fatty liver? What are various types of this disease entity?