Cirrhosis of liver

LIVER CIRRHOSIS

1. Cirrhosis of Liver

2. Objectives Define cirrhosis, list its causes, and understand its pathogens & complications Classify portal hypertension, know its causes and the pathogenesis of its complications Enlist causes and identify morphology of cholecystitis Enlist causes and describe pathogenesis of Pancreatitis

3. Cirrhosis A diffuse process characterized by fibrosis and conversion of liver architecture into abnormal nodules (End-stage of chronic liver disease) Three main characteristics are: Bridging fibrous septae P-P, P-C, C-C Parenchymal nodules Proliferating hepatocytes encircled by fibrosis, with diameters varying from very small (<3 mm, micronodules ) to large (several centimeters, macronodules ) Disruption of lobular architecture of entire liver

4. Cirrhosis of Liver ETIOLOGY Alcoholic liver disease 60% to 70% Viral hepatitis (HBV ,HCV) 10% NASH Biliary diseases 5% to 10% Primary hemochromatosis 5% Cryptogenic cirrhosis 10% to 15% Cardiac cirrhosis in the setting of cardiac disease

5. Pathogenesis of Liver cirrhosis Fibrosis: Stellate (Ito) cell in space of Disse transformed by inflammatory mediator to myofibroblasts -collagen producing cells Parenchymal injury & consequent fibrosis : a diffuse process Nodularity: reflects balance between regenerative activity and constrictive scarring Vascular architecture: reorganized with formation of abnormal interconnections between vascular inflow and hepatic vein outflow channels resulting in portal vein and arterial blood partially by passes functional hepatocyte mass

6. Cirrhosis Macro/Micro Nodules

7. Massom Trichrome Stain for Fibrosis

8. Complications of Cirrhosis Progressive Liver failure Portal Hypertension Development of Hepatocellular Carcinoma 1/9/19

9. Portal Hypertension in Cirrhosis Pathogenesis Results from increased resistance to portal flow; at the level of the sinusoids and compression of central veins by perivenular fibrosis and expanded parenchymal nodules Anastomoses between arterial and portal systems; in the fibrous bands also contribute to portal hypertension by imposing arterial pressure on the normally low-pressure portal venous system An increase in portal venous blood flow; caused by arterial vasodilation in the splanchnic circulation, resulting primarily from increased production of nitric oxide (NO) in the vascular bed by bacterial DNA

10. Complications of Portal hypertension Development of Portosystemic Shunt : Principal sites are; Veins around and within the rectum (hemorrhoids) C ardioesophageal junction ( esophagogastric varices) R etroperitoneum , and the falciform ligament of the liver (involving periumbilical and abdominal wall collaterals- caput medusae ) Splenomegaly; Long-standing congestion may cause congestive splenomegaly (1000 g or less) Massive splenomegaly may secondarily induce a variety of hematologic abnormalities attributable to hypersplenism

11. Acute Cholecystitis Incidence: 4F’s(female, forty, fertile, fatty) C/F: Acute right upper quadrant pain, tenderness and fever Etiology: Usually related to obstruction by gallstones, 90% of the cases are precipitated by obstruction of neck or cystic duct few are caused by torsion of neck Morphology: Edema of gall bladder wall with hemorrhage and neutrophils infiltrate 1/9/19

12. Chronic Cholecystitis Incidence: peaks in 40's and 50's, predominantly female C/F: usually recurrent right upper quadrant pain Etiology: main cause gallstones Morphology: chronic inflammatory cells infiltrate in the wall Rokitansky's-Aschoff sinuses present Complications: Gangrene, perforation, empyma , fistula formation and risk of malignancy 1/9/19

13. Acute Pancreatitis Etiologic Factors includes: Metabolic; Alcoholism, hyperlipoproteinemia , hypercalcemia, drugs (e.g., azathioprine) Genetic; Mutations in the cationic trypsinogen (PRSS1) and trypsin inhibitor (SPINK1) genes Mechanical; Gallstones, trauma Vascular; Shock, Atheroembolism Infectious; Mumps, Coxsackievirus Pathogenesis: Autodigestion of the pancreatic tissue by inappropriately activated pancreatic enzymes 1/9/19

14. Acute Pancreatitis Gross; tan-yellow flecks of soft material within and on the surface of pancreas due to fat necrosis Microscopy; necrosis of pancreatic parenchyma, acute inflammation, fat necrosis and destruction of blood vessels leading to hemorrhage ( autodigestion ) Acute pancreatitis; a medical emergency , present with sudden onset of an “acute abdominal pain, abdominal guarding, and absence of bowel sounds 1/9/19

15. Chronic Pancreatitis Irreversible parenchymal damage resulting from long-standing inflammation, fibrosis with destruction of the exocrine and in its late stages, the endocrine parenchyma Microscopy; chronic inflammatory cells in a fibrous stroma with a few islets of Langerhans 1/9/19

16. References Robbins Basic Pathology, 10 th Edition Kumar, Abbas, Aster www.studentconsult.com www.web p athology.com