PARENCHYMAL LIVER DISEASEPARENCHYMAL LIVER DISEASE Parenchymal liver disease may be classified as acute Parenchymal liver disease may be classified as acute

(<6month) or chronic (>6month) or on a histological basis.(<6month) or chronic (>6month) or on a histological basis. Broadly however parenchymal liver disease can be classified Broadly however parenchymal liver disease can be classified

into fatty liver, hepatitis, and cirrhosis.into fatty liver, hepatitis, and cirrhosis.

Chronic Hepatitis Chronic Hepatitis Symptomatic, biochemical or aetiological evidence of Symptomatic, biochemical or aetiological evidence of

continuing or relapsing hepatic disease for more than 6 months continuing or relapsing hepatic disease for more than 6 months without steady improvement is called chronic hepatitis. without steady improvement is called chronic hepatitis.

CIRRHOSIS OF LIVERCIRRHOSIS OF LIVER

DefinitionDefinition:-:- Cirrhosis is defined as diffused process characterized by Cirrhosis is defined as diffused process characterized by

fibrosis and conversion of normal liver architecture into fibrosis and conversion of normal liver architecture into structurally abnormal nodule.structurally abnormal nodule.

Cirrhosis is gradually progressive widespread death of liver Cirrhosis is gradually progressive widespread death of liver cells assocoiated with inflammation and fibrosis leading to cells assocoiated with inflammation and fibrosis leading to loss of normal lobular liver architecture. loss of normal lobular liver architecture.

Anatomical(Histological)ClassificationAnatomical(Histological)Classification

1.Micronodular cirrhosis1.Micronodular cirrhosis:-:- < 3mm in size. (Alcoholic)< 3mm in size. (Alcoholic) Characterized by regular connective tissue septa, Characterized by regular connective tissue septa,

regenerative nodules, and involvement of every lobule.regenerative nodules, and involvement of every lobule.

2.Macronodular cirrhosis2.Macronodular cirrhosis:-:- >3mm in size ( Viral Hepatitis) >3mm in size ( Viral Hepatitis) Connective tissue vary in thickness and nodulesConnective tissue vary in thickness and nodules Show marked difference in size.Show marked difference in size.

3.Intermediate mixed forms.3.Intermediate mixed forms. (Alcoholic cirrhosis with time)(Alcoholic cirrhosis with time)

Cirrhosis is defined by its pathological features on microscopy:Cirrhosis is defined by its pathological features on microscopy:

(1) the presence of regenerating nodules of hepatocytes and(1) the presence of regenerating nodules of hepatocytes and

(2) the presence of fibrosis, or the deposition of connective tissue between (2) the presence of fibrosis, or the deposition of connective tissue between these nodules.these nodules.

Necrosis of hepatocytesNecrosis of hepatocytes IrreversibleIrreversible Progressive disorder Progressive disorder Entire Liver is involvedEntire Liver is involved

CAUSESCAUSES

CommonCommon AlcoholAlcohol Hepatitis BHepatitis B+/-+/-DD Hepatitis CHepatitis C

OthersOthers

Biliary ObstructionBiliary Obstruction Primary Biliary cirrhosisPrimary Biliary cirrhosis Secondary Biliary cirrhoses (stones, stricture)Secondary Biliary cirrhoses (stones, stricture)

Metabolic Metabolic HaemochromatosisHaemochromatosis Wilson’s diseaseWilson’s disease a1-antitrysin deficiencya1-antitrysin deficiency Cystic fibrosisCystic fibrosis

Hepatic congestionHepatic congestion Cardiac failure Cardiac failure Budd-chiari syndromeBudd-chiari syndrome

Idiopathic Idiopathic

Alcoholic Liver DiseaseAlcoholic Liver Disease

ALD comprises of 3 distinct forms of Liver diseasesALD comprises of 3 distinct forms of Liver diseases Hepatic steatosis/ fatty Liver Hepatic steatosis/ fatty Liver Alcoholic hepatitis Alcoholic hepatitis Cirrhosis Cirrhosis

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HaemochromatosisHaemochromatosis Is defined as the excessive accumulation of body iron, most Is defined as the excessive accumulation of body iron, most

of which deposited in the parenchymal cell of various organ of which deposited in the parenchymal cell of various organ particularly liver & pancreas particularly liver & pancreas

Types Types Hereditary/primary/idiopathic Hereditary/primary/idiopathic Secondary – occuring as a secondary complications to a Secondary – occuring as a secondary complications to a

variety of diseases variety of diseases

Dr S ChakradharDr S Chakradhar 88

Wilson’s Disease Wilson’s Disease Is an autosomal recessive disorder of copper metabolism & Is an autosomal recessive disorder of copper metabolism &

is marked by accumulation of toxic levels of copper in many is marked by accumulation of toxic levels of copper in many tissues in many tissues & organs principally the liver, brain tissues in many tissues & organs principally the liver, brain & eye & eye

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Biliary cirrhosis Biliary cirrhosis

Primary intrahepatic biliary cirrhosis Primary intrahepatic biliary cirrhosis An autoimmune disease marked by the slow progressive An autoimmune disease marked by the slow progressive

destruction of the small intrahepatic bile ducts.destruction of the small intrahepatic bile ducts. Bile builds up in the liver and over time damages the tissue. Bile builds up in the liver and over time damages the tissue. This can lead to scarring, fibrosis and cirrhosisThis can lead to scarring, fibrosis and cirrhosis

Secondary biliary cirrhosis Secondary biliary cirrhosis Results from obstruction to the major extra hepatic duct Results from obstruction to the major extra hepatic duct

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Alpha1 antitrypsin deficiencyAlpha1 antitrypsin deficiency

Is an autosomal recessicve disorder marked by abnormally low Is an autosomal recessicve disorder marked by abnormally low levels of of levels of of αα1-antitrypsin in serum 1-antitrypsin in serum

Predominantly synthesized in Hepatocytes & to less extent in Predominantly synthesized in Hepatocytes & to less extent in macrophage macrophage

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PATHOGENESISPATHOGENESIS Following liver injury cytokines produced by kupffer cells Following liver injury cytokines produced by kupffer cells

and hepatocytes activate the stellate cells.and hepatocytes activate the stellate cells. Following activation the stellate cells becomes transformed Following activation the stellate cells becomes transformed

into multifunctional cells, capable of collagen production, into multifunctional cells, capable of collagen production, contraction and cytokine synthesis.contraction and cytokine synthesis.

The net outcome is The net outcome is A fibrotic, nodular liver in which delivery of blood to A fibrotic, nodular liver in which delivery of blood to

hepatocytes is severely compromised, as is the ability of hepatocytes is severely compromised, as is the ability of hepatocytes to secrete substances into plasma. hepatocytes to secrete substances into plasma.

Disruption of the interface between the parenchyma and Disruption of the interface between the parenchyma and portal tracts obliterates biliary channels as well. portal tracts obliterates biliary channels as well.

Thus, the cirrhotic patient may develop jaundice and even Thus, the cirrhotic patient may develop jaundice and even hepatic failure, despite having a liver of normal mass.hepatic failure, despite having a liver of normal mass.

Dr S ChakradharDr S Chakradhar 1414

CLINICAL FEATURESCLINICAL FEATURES

Frequent complains include:-Frequent complains include:- weakness, fatigue, muscle cramps, weight loss, weakness, fatigue, muscle cramps, weight loss, And non specific digestive symptoms - anorexia, vomiting, And non specific digestive symptoms - anorexia, vomiting,

upper abdominal discomfort.upper abdominal discomfort. Hepatomegaly (decrease as the disease progress) – Non Hepatomegaly (decrease as the disease progress) – Non

tender, hard, irregulartender, hard, irregular Jaundice Jaundice AscitesAscites

Circulatory changesCirculatory changes spider telangiectasia, palmar erythema, cyanosis,spider telangiectasia, palmar erythema, cyanosis,

Endocrine changesEndocrine changes Loss of libido, hair lossLoss of libido, hair loss Men: gynaecomastia, testicular atrophy, impotenceMen: gynaecomastia, testicular atrophy, impotence

Women:Women: Breast atrophy,Breast atrophy, irregular menses,irregular menses, amenorrhoeaamenorrhoea

Haemorrhagic tendency Haemorrhagic tendency Bruises, purpura, epistaxis, menorrhagiaBruises, purpura, epistaxis, menorrhagia

Portal hypertensionPortal hypertension Splenomegaly, collateral vessels, variceal bleeding,Splenomegaly, collateral vessels, variceal bleeding, Fetor hepaticusFetor hepaticus Hepatic encephalopathyHepatic encephalopathy

Other featuresOther features Pigmentation, digital clubbing, low-grade feverPigmentation, digital clubbing, low-grade fever

COMPLICATIONCOMPLICATION Hepatic encephalopathyHepatic encephalopathy Portal hypertensionPortal hypertension AscitesAscites Renal failureRenal failure Hepatocellular carcinomaHepatocellular carcinoma

InvestigationsInvestigations TC, DC, ESR, HbTC, DC, ESR, Hb Liver function test (LFT) Liver function test (LFT)

Serum bilirubin - increasedSerum bilirubin - increased Plasma Aminotransferase (ALT, AST) – low in established Plasma Aminotransferase (ALT, AST) – low in established

case case Prothrombin time - prolongedProthrombin time - prolonged Plasma alkaline phosphatase – increased in biliary cirrhosis Plasma alkaline phosphatase – increased in biliary cirrhosis Plasma albumin – Decreased Plasma albumin – Decreased

Liver Biopsy – Diagnostic Liver Biopsy – Diagnostic USG of hepatobilliary system / CTUSG of hepatobilliary system / CT Viral markers – Hbs Ag, antibody against HCV Viral markers – Hbs Ag, antibody against HCV

MANAGEMENTMANAGEMENT

Main objective of treatment Main objective of treatment Treatment of any known (treatable) cause Treatment of any known (treatable) cause Prevention & correction of malnutrition Prevention & correction of malnutrition Management of chronic cholestasis Management of chronic cholestasis Treatment of complications Treatment of complications

No treatment can reverse cirrhosis or even ensure that no further No treatment can reverse cirrhosis or even ensure that no further progression occurs. Rx is symptomatic and supportive. progression occurs. Rx is symptomatic and supportive.

Withdrawal or treatment of aetiological factors e.g. Alcohol Withdrawal or treatment of aetiological factors e.g. Alcohol consumption, drugs, Haemochromatosis.consumption, drugs, Haemochromatosis.

No strenuous activity to reduce metabolism No strenuous activity to reduce metabolism Nutrition Nutrition

High energy protein (in absence of encephalopathy) & CHO rich diet High energy protein (in absence of encephalopathy) & CHO rich diet Fat restriction (if Cholestasis) Fat restriction (if Cholestasis) Alcohol must be forbidden Alcohol must be forbidden Vitamin B-complex. Vitamin B-complex.

  Treatment of complications Treatment of complications Ascites – low salt diet , Diuretics Ascites – low salt diet , Diuretics

  Liver Transplant Liver Transplant 6 monthly USG and AFP to detect the development of hepatocellular 6 monthly USG and AFP to detect the development of hepatocellular

carcinomacarcinoma

Patterns of Hepatic InjuryPatterns of Hepatic InjuryNormal Liver Apoptotic Body

What is the name for it?

Inflammation (Hepatitis) Fibrosis (Cirrhosis)

Portal HTNPortal HTN

Cirrhosis

Esophageal Varices

Caput Medusa

Splenomegaly