liver cirrhosis lecture

Cirrhosis of the liver

Definition Cirrhosis is a common chronic, progressive and diffusive liver disease, caused by one or several agents act repeatedly and persistently.

Histologically, cirrhosis is an irreversible alteration of the liver architecture, consisting of hepatic fibrosis and areas of nodular regeneration

Epidemiology

Worldwide major heath problem Over 500,000 deaths per year Over 20% were latent 2 ~ 10% in postmortem examination Common and death leading disease in China

Etiology and pathogenesisViral hepatitisParasites (schistosomiasis)Alcoholic liver diseaseCholestasis

Hepatic-Venous outflow obstructionToxicant and drugsMetabolic abnormalityMalnutritionCryptogenic cirrhosis

Viral hepatitis

HBV

HCV

HBV + HDV

HAV

HEV

Viral hepatitis (HBV)

Global prevalence: >300 million carriers 5% world populationVaries widely High prevalence: 8% ~ 15% Far East (southeast Asia China Philippines Indonesia) Middle East Africa parts of South America Intermediate prevalence: 2% ~ 7% Japan parts of south America parts of central Asia eastern and southern Europe Low prevalence:

Viral hepatitis

Elimination of viral infected hepatocytes is dependent on recognition of viral determinants in association with HLA proteins on the infected hepatocytes by cytotoxic T cells.

HLA protein display is modulated by exposure to interferon and cytotoxic T cell, NK lytic processes.

During chronic HBV infection, infected liver cells failed to induce IFN. Therefore, viral protein synthesis is not decreased, HLA protein display is not enhanced.

Parasites (Schistosomiasis) Ova deposited in the portal zones Exciting a fibrous tissue reaction

Co-existence of malaria and cirrhosis reflects malnutrition, viral hepatitis and toxic factors

Alcoholic liver disease 1/3 cause of cirrhosis in Western country Most important factor: threshold dose: 600 Kg (men) 150~300 Kg (women) average daily consumption of alcohol > 40 ~ 80 g/D, over 10 ~ 15 years Liver: primary site of ethanol metabolism Ethanol can be oxidized by three enzymes systems ADH CYP2E1 catalase

Alcoholic liver diseaseMechanism Direct effect by ethanol, or its first metabolite (acetaldehyde redox shift oxidant stress) Cell-mediated immune

Three histopathologic lesion: fatty liver, alcoholic hepatitis, cirrhosis

Biliary cirrhosis Primary Biliary Cirrhosis: Progressive destruction of small and intrahepatic bile ducts Prevalence: 40~150 cases/million Women >90 of cases 50y Abnormal immunoregulation Associated with HLA phenotyeps

Biliary cirrhosis

Secondary biliary cirrhosis:

Obstruction of the biliary tree, further divided into two groups intra-hepatic and extra-hepatic obstruction

Hepatic-Venous outflow obstruction Veno-occlusive disease Budd-chiari syndrome Constrictive pericarditis Chronic congestive heart failure

Toxicant and drugs Tetrachloride carbon - methyldopa Tetracycline Phosphorus Arsenic

Metabolic abnormality Iron storage disease (Hemochromatosis)

Copper storage disease (Wilsons disease)

Malnutrition Chronic inflammatory bowel disease

Prolonged lack of dietary proteins and vitamins

Cryptogenic cirrhosis Etiology is unknown

Viral infection are suscepted in some cases

PathophysiologyAlcoholic cirrhosis accumulation of fat and scar formation in the liver cellsPostnecrotic cirrhosis broad bands of scar tissue resulted from viral, toxic, or autoimmune hepatitisBiliary cirrhosis diffuse fibrosis with jaundice from chronic biliary obstructionCardiac cirrhosis from long-standing right sided heart failure

Pathology and classificationHistopathological diagnosis:

Excessive fibrous tissue

Regenerating nodules Complete distortion of the normal relationship of hepatic venous outflow radicles and portal veins.

Anatomical types of regenerating nodules

Micronodular

Macronodular

Mixed cirrhosis

Macronodular cirrhosis Features: Septa Nodules of variable size (>3mm, even 1~ 3 cm) Normal lobules in the large nodules

Two subtypes: postnecrotic posthepatitic

Macronodular cirrhosisPostnecrotic type: Coarsely scarred liver Large nodules surrounded by broad fibrous septa Clumping togathered numerous portal trials

Toxic cirrhosis Cryptogenic cirrhosis Multilobular cirrhosis

Macronodular cirrhosisPosthepatitic type: Macronodules separated by slender fibrous strands Connect individual portal areas to each other

Viral hepatitis Wilsons disease

Mixed cirrhosisFeatures:

Presenting both micro- and macronodules From micronodules to macronodules

Alcoholism Antitrypsin deficiency

Some aspects of pathology The most useful morphologic classification: gross appearance of the liver The morphologic diagnosis of cirrhosis is more reliable than the histopathological diagnosis Schistosomiasis: incomplete septal cirrhosis coarse portal fibrosis Initially enlarged/subsequcetly shrinks

Clinical manifestation Onset: Cryptical and slowly progressive Majority: 3~5 years or 10 years Minority: 3~6 months

Stages: Compensated Decompensated

Compensated stage Fatigue Loss of appetite Anorexia Abdominal discomfort Abdominal pain

Hepatomegaly (slightly or moderately) Splenomegaly

Decompensated stage

Deterioration of liver function

Feature of portal hypertention

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Deterioration of liver function General deterioration Deterioration of heath, anorexia, weight loss, weakness, fatigue, Flatulent dyspepsia, abdominal distress, swelling of legs or abdomen, mild fever, loss of libido and hemorrhage.

Findings of physical examination Jaundice Dermatological and sexual signs Liver (enlarge or shrunken)

Jaundice

It always implies liver cell destruction exceeds the capacity for regeneration

Dermatologic and sexual signs

Skin pigmentation Clubbing fingers Spider angioma Liver palms (palmar erythema) Purpura Spontaneous bruising / epistaxes

Dermatologic and sexual signs Feminization and hypogonadism Gynecomastiatesticular atrophysparse body hairchanges in hair distributionmenstrual irregularities Mechanism: serum testosterone estrogens

Liver Early stage Enlarged and palpable firm regular edge a fine to coarsely nodular surface Later stage Shrunk and impalpable

Features of portal hypertension

Portal-systemic collaterals

Ascites

Splenomegaly

Anatomy and physiology of portal venous system Begins in the capillaries of the intestines Terminates in the hepatic sinusoids Formed by the confluence of the superior and inferior mesenteric veins and splenic vein Liver receives 1500ml/min, 2/3 from portal vein Hepatic artery provides 50% oxygen The pressure within the sinusoids is low Lack of valves ***: Between the splanchnic venules and the heart

Portal-systemic collaterals Esophageal and gastric varices

Dilation of the remnant of the umbilical vein Dilation of abdominal veins

Hemorrhoidial venous collaterals

Splenomegaly Slightly or moderatory enlarged

Hypersplenism Leukopenia Thrombocytopenia Anemia

Ascites Prominent feature of portal-hypertension 70% of patients are positive An early sign in presinusoidal portal hypertension relative late in intrahepatic portal hypertension

Massive ascites: abdominal herniae (

Complications

Upper gastrointestinal bleeding Hepatic encephalopathy Infection Hepatorenal syndrome Primary liver cancer Imbalance of electrolytes and acid-alkaline

Upper gastrointestinal bleeding Major complication Incredible high mortality Source of bleeding: esophageal varices 60%~80% gastric varices 7% congestive gastropathy 5%~20% (paptic ulcer, acute erosive gastritis etc)

Hepatic encephalopathy

The most severe and deadly complications

Infection Increased risk for bacterial infection

pneumoniabiliary infectionE.coli infection and spontaneous bacterial peritonitis (SBP)

SBP Pathogen of SBP: grams negative bacteria Features of SBP: fever, abdominal pain or tenderness decreased bowel soundsSuspected patients: sudden onset of HE or hypotension Diagnosis: elevated ascites fluid white blood cells positive ascitic fluid culture

Hepatorenal syndrome Decreased renal function due to severe liver disease Histologically normal kidney Involved factors Sympathetic nervous system Renin-angiotensin-aldosterone Prostaglandins Endoto