Download ppt - Hepatic Cirrhosis （肝硬化） Yu Baoping. Introduction CIRRHOSIS Term was 1st coined by Laennec in 1826 Many definitions but common theme is injury, repair,

Hepatic CirrhosisHepatic Cirrhosis

（肝硬化）（肝硬化）

Yu BaopingYu Baoping

IntroductionIntroduction

CIRRHOSISCIRRHOSIS Term was 1st coined by Laennec in 1826Term was 1st coined by Laennec in 1826 Many definitions but common theme is injury, repair, reMany definitions but common theme is injury, repair, re

generation and scarringgeneration and scarring NOT a localized process; involves entire liverNOT a localized process; involves entire liver Primary histologic features:Primary histologic features:

1.1. Marked fibrosisMarked fibrosis2.2. Destruction of vascular & biliary elementsDestruction of vascular & biliary elements3.3. RegenerationRegeneration4.4. Nodule formationNodule formation

DefinitionDefinition

Cirrhosis is a pathological diagnosis. It is Cirrhosis is a pathological diagnosis. It is characterized by widespread fibrosis with characterized by widespread fibrosis with nodular regeneration. Its presence implies nodular regeneration. Its presence implies previous or continuing hepatic cell damageprevious or continuing hepatic cell damage

Aetiology Aetiology andand Pathogenesis Pathogenesis

Etiologic classification of cirrhosisEtiologic classification of cirrhosis

AlcoholAlcohol ( (>70%)>70%) Chronic infectionsChronic infections

hepatitis Chepatitis C, B, B, B, B++DD

brucellosis, syphilisbrucellosis, syphilis Chr. biliary obstructionChr. biliary obstruction

PBC, PSC, stricture,PBC, PSC, stricture,

sstonestones,, cystic fibrosis, cystic fibrosis, cong. cong.b. atresia,b. atresia, ~~cystscysts

AutoimmuneAutoimmune

CardiovascularCardiovascular

heart failure, pericarditis,heart failure, pericarditis,

Budd-Chiary-syBudd-Chiary-sy Metabolic/genetic errorsMetabolic/genetic errors

Fe, Cu, αFe, Cu, α11-AT, lipids, -AT, lipids, Drugs and chemicalsDrugs and chemicals NASHNASH CryptogenicCryptogenic CombinedCombined

Pathogenesis:Pathogenesis: Diffuse liver injury leading to necrosis.Diffuse liver injury leading to necrosis.

(Alcohol, virus, drugs, toxins, genetic etc.)(Alcohol, virus, drugs, toxins, genetic etc.) Chronic inflammation & healing Chronic inflammation & healing (hepatitis).(hepatitis). Bridging fibrosis – loss of architecture.Bridging fibrosis – loss of architecture. Regeneration Regeneration nodules. nodules. Obstruction to blood flow & shunts.Obstruction to blood flow & shunts. Portal hypertension Portal hypertension spleen, varices spleen, varices Liver failure – Debilitation, Jaundice, Ascitis, edema, bleediLiver failure – Debilitation, Jaundice, Ascitis, edema, bleedi

ng, jaundice.ng, jaundice. Hormone imbalance – spider nevi, testes atrophy etc..Hormone imbalance – spider nevi, testes atrophy etc..

Pathology Pathology and and PathophysiologyPathophysiology

Pathology Pathology （（ liverliver ））

Classification of CirrhosisClassification of Cirrhosis

WHO divided cirrhosis into 3 categories baseWHO divided cirrhosis into 3 categories based on morphological characteristics of the hepad on morphological characteristics of the hepatic nodulestic nodules

1.1. MicronodularMicronodular

2.2. MacronodularMacronodular

3.3. MixedMixed

Micronodular CirrhosisMicronodular Cirrhosis

Nodules are <3 mm in diameterNodules are <3 mm in diameter Relatively uniform in sizeRelatively uniform in size Distributed throughout the liverDistributed throughout the liver Rarely contain portal tracts or efferent veinsRarely contain portal tracts or efferent veins Liver is of uniform size or mildly enlargedLiver is of uniform size or mildly enlarged Reflect relatively early diseaseReflect relatively early disease

Micronodular cirrhosis

Macronodular & Mixed CirrhosisMacronodular & Mixed Cirrhosis

Nodules are >3 mm in diameter and vary considerably Nodules are >3 mm in diameter and vary considerably in sizein size

Usually contain portal tracts and efferent veinsUsually contain portal tracts and efferent veins Liver is usually normal or reduced in sizeLiver is usually normal or reduced in size Mixed pattern if both type of nodules are present in Mixed pattern if both type of nodules are present in

equal proportionsequal proportions

Macronodular cirrhosis

CirrhosisCirrhosis

Fibrosis

Regenerating Nodule

Pathology Pathology （（ splenomegalysplenomegaly

））

Pathology Pathology （（ others ）） gastrointestinal tract

varicose veins ，， hemorrhage ， congestion

Kidney

glomerulonephritis

Endocrine muscular atrophy ， degeneration （ testis ， ovary ， thyroid ， adrenal cortex ）

Cirrhosis: PathophysiologyCirrhosis: Pathophysiology

Primary event is injury to hepatocellular elemenPrimary event is injury to hepatocellular elementsts

Triggering inflammatory response with cytokine Triggering inflammatory response with cytokine release-toxic substancesrelease-toxic substances

Destruction of hepatocytes, bile duct cells, vascDestruction of hepatocytes, bile duct cells, vascular endothelial cellsular endothelial cells

Repair thru cellular proliferation and regeneratioRepair thru cellular proliferation and regenerationn

Formation of fibrous scarFormation of fibrous scar


Stellate cell is activated in response to injury anStellate cell is activated in response to injury and lead to expression of fibril-forming collagend lead to expression of fibril-forming collagen

Above process is also influenced by Kupffer cellAbove process is also influenced by Kupffer cells which activate stellate cells by eliciting producs which activate stellate cells by eliciting production of cytokinestion of cytokines

Sinusoidal fenestrations are obliterated becausSinusoidal fenestrations are obliterated because of collagene of collagen


Prevents normal flow of nutrients to hepatocytePrevents normal flow of nutrients to hepatocytes and increases vascular resistances and increases vascular resistance

Initially, fibrosis may be reversible if inciting eveInitially, fibrosis may be reversible if inciting events are removednts are removed

With sustained injury, process of fibrosis becomWith sustained injury, process of fibrosis becomes irreversible and leads to cirrhosis es irreversible and leads to cirrhosis

PathophysiologyPathophysiologyProtal hypertensionProtal hypertension

AscitesAscites

endocrineendocrine

respiratory systemrespiratory system hepatic hydrothoraxhepatic hydrothorax

hepatopulmonary syndromehepatopulmonary syndrome

the urinary system : hepatorenal syndrom, HRSthe urinary system : hepatorenal syndrom, HRS

hematological systemhematological system

nervous system : HEnervous system : HE

Portal Hypertension (PH)Portal Hypertension (PH)

Portal vein pressure above the normal range of Portal vein pressure above the normal range of 5 to 8 mm Hg5 to 8 mm Hg

Portal vein - Hepatic vein pressure gradient grePortal vein - Hepatic vein pressure gradient greater than 5 mm Hg (>12 clinically significant)ater than 5 mm Hg (>12 clinically significant)

Represents an increase of the hydrostatic pressRepresents an increase of the hydrostatic pressure within the portal vein or its tributariesure within the portal vein or its tributaries

Pathophysiology of PHPathophysiology of PH

Cirrhosis results in scarring (perisinusoidal deposition of Cirrhosis results in scarring (perisinusoidal deposition of collagen)collagen)

Scarring narrows and compresses hepatic sinusoids Scarring narrows and compresses hepatic sinusoids (fibrosis)(fibrosis)

Portal vein thrombosis, or hepatic venous obstruction Portal vein thrombosis, or hepatic venous obstruction also cause PH by increasing the resistance to portal also cause PH by increasing the resistance to portal blood flowblood flow

Progressive increase in resistance to portal venous Progressive increase in resistance to portal venous blood flow results in PHblood flow results in PH

Pathophysiology of PHPathophysiology of PH

As pressure increases, blood flow decreases and the As pressure increases, blood flow decreases and the pressure in the portal system is transmitted to its pressure in the portal system is transmitted to its branchesbranches

Results in dilation of venous tributariesResults in dilation of venous tributaries Increased blood flow through collaterals and Increased blood flow through collaterals and

subsequently increased venous return cause an subsequently increased venous return cause an increase in cardiac output and total blood volume and a increase in cardiac output and total blood volume and a decrease in systemic vascular resistancedecrease in systemic vascular resistance

With progression of disease, blood pressure usually With progression of disease, blood pressure usually fallsfalls

Portal Vein CollateralsPortal Vein Collaterals

Coronary vein and short gastric veins -> veins of the Coronary vein and short gastric veins -> veins of the lesser curve of the stomach and the esophagus, lesser curve of the stomach and the esophagus, leading to the formation of varicesleading to the formation of varices

Inferior mesenteric vein -> rectal branches which, when Inferior mesenteric vein -> rectal branches which, when distended, form hemorrhoidsdistended, form hemorrhoids

Umbilical vein ->epigastric venous system around the Umbilical vein ->epigastric venous system around the umbilicus (caput medusae)umbilicus (caput medusae)

Retroperitoneal collaterals ->gastrointestinal veins Retroperitoneal collaterals ->gastrointestinal veins through the bare areas of the liverthrough the bare areas of the liver

AscitesAscites Sodium and water retention occur due to renin-angioteSodium and water retention occur due to renin-angiote

nsin release secondary to arterial vasodilatation, causensin release secondary to arterial vasodilatation, caused by vasoactive substances such as nitric oxided by vasoactive substances such as nitric oxide

Portal hypertension per se causes fluid to accumulate iPortal hypertension per se causes fluid to accumulate in the peritoneal cavity due to increased hydrostatic pren the peritoneal cavity due to increased hydrostatic pressure, hence further reduces intravascular volume and ssure, hence further reduces intravascular volume and stimulates sodium and water retention via aldosterone.stimulates sodium and water retention via aldosterone.

Low albumin in plasmaLow albumin in plasma

Clinical presentationClinical presentation

Clinical presentationClinical presentation

There may be no abnormal clinical oThere may be no abnormal clinical or biochemical features of liver diseasr biochemical features of liver disease in initial timese in initial times

Features of hepatocellular failure, poFeatures of hepatocellular failure, portal hypertension, or both may appertal hypertension, or both may appear in advanced times.ar in advanced times.

CirrhosisCirrhosisClinical Clinical

FeaturesFeatures

Symptoms of advanced cirrhosisSymptoms of advanced cirrhosis Fatique, weaknessFatique, weakness Nausea, vomiting and Nausea, vomiting and

loss of appetiteloss of appetite Weight loss, muscle Weight loss, muscle

wastingwasting Jaundice, dark urineJaundice, dark urine Spider naevi, caput Spider naevi, caput

MedusaeMedusae Bloody, black stools Bloody, black stools

or unusually light-or unusually light-colored stoolscolored stools

Vomiting of bloodVomiting of blood

Abdominal swellingAbdominal swelling Swollen feet or legs Swollen feet or legs Liver Liver palmspalms GynecomastiaGynecomastia Loss of sex driveLoss of sex drive Menstrual changes in Menstrual changes in

women women Generalized itchingGeneralized itching Sleep disturbances, Sleep disturbances,

confusion,desorientatconfusion,desorientation,ion,tremor, asterixistremor, asterixis

Clinical FeaturesClinical Features

Hepatocellular failure.Hepatocellular failure. Malnutrition, low albumin & clotting factors, Malnutrition, low albumin & clotting factors,

bleeding.bleeding. Hepatic encephalopathy.Hepatic encephalopathy.

Portal hypertension.Portal hypertension. Ascites, Porta systemic shunts, varices, Ascites, Porta systemic shunts, varices,

splenomegaly.splenomegaly.

Gynecomastia

Ascites

Caput Medusae

Umbilical hernia

Visible signs of advanced liver

cirrhosis

ComplicationsComplications

ComplicationsComplications

Upper gastrointestinal hemorrhageUpper gastrointestinal hemorrhage Hepatic encephalopathyHepatic encephalopathy InfectionInfection Hepatorenal syndromeHepatorenal syndrome Hepatopulmonary SyndromeHepatopulmonary Syndrome Primary carcinoma of the liverPrimary carcinoma of the liver Disturbance of Disturbance of electrolyteelectrolyte and acid-base and acid-base

balancebalance

Laboratory tests Laboratory tests and investigations and investigations

laboratory tests and investigations

Blood-RTBlood-RT anaemiaanaemia ；； hyperspleniahypersplenia:WBC :WBC ，， PltPlt Urine-RTUrine-RT

urine bilirubinurine bilirubin ，， urobilinogenurobilinogen ；； sometimsometimes es albumenalbumen ，， haematuriahaematuria

Stool-RTStool-RT melenamelena


liver function tests Compensation normal or abnormal slightly Decompensation transaminase transaminase ：： ALT AST ALT AST cholesterolcholesterol albumin and globulinalbumin and globulin prothrombin timeprothrombin time bilirubinbilirubin P P, and so onⅢP P, and so onⅢQuantitation- liver function tests IGG


Biochemistry can be surprisingly normal but some Biochemistry can be surprisingly normal but some abnormality will often be present with slightly raisabnormality will often be present with slightly raised transaminases and alkaline phosphatases. In seed transaminases and alkaline phosphatases. In severe cases, all live enzymes will be abnormal. Low vere cases, all live enzymes will be abnormal. Low sodium and albumin are also seen. sodium and albumin are also seen.

Coagulopathy is a very sensitive indicator of liver Coagulopathy is a very sensitive indicator of liver dysfunction and is reflected in the prolonged prothdysfunction and is reflected in the prolonged prothrombin time.rombin time.


immunologic function test

AFP

virus hepatitis markers

antinuclear antibody, ANA non-specificity

antismooth muscle antibody autoantibody

anti-mitochondrial antibody


Imaging examinationImaging examination Barium mealBarium meal

CT or MRICT or MRI

Ultrasound Ultrasound demonstrates fatty change, size, and demonstrates fatty change, size, and

fibrosis as well as hepatocellular carcinomafibrosis as well as hepatocellular carcinoma



MRI CirrhosisMRI Cirrhosis



Special testSpecial test Endoscope Biopsy Laparoscope Hydroperitoneum test Measure the Pressure of Portal Vein

Diagnosis and Diagnosis and differential differential

diagnosisdiagnosis

Diagnosis of liver cirrhosisDiagnosis of liver cirrhosis

The gold standard: liver biopsy histologyThe gold standard: liver biopsy histology

Diffuse, chronic liver diseaseDiffuse, chronic liver disease

(hystory, physical, laboratory and US finding(hystory, physical, laboratory and US finding

s) s)

with evidences of portal hypertensionwith evidences of portal hypertension

(oesophageal varices on gastroscopy; dilate(oesophageal varices on gastroscopy; dilate

d portal vein and its branches by US)d portal vein and its branches by US)

Child-Pugh’s classificationChild-Pugh’s classification

CategoriesCategoriesClassification PointsClassification Points

11 22 33

EncephalopathyEncephalopathy NoneNone Grade I & IIGrade I & II Grade III & IVGrade III & IV

AscitesAscites AbsentAbsent Slight-moderateSlight-moderate TenseTense

Bilirubin (mg/dl)Bilirubin (mg/dl) <2 (4)<2 (4) 2-3 (4-10)2-3 (4-10) >3 (>10)>3 (>10)

Albumin (g/dl)Albumin (g/dl) >3.5>3.5 2.8-3.52.8-3.5 <2.8<2.8

Prothrombin TimeProthrombin Time 1-41-4 4-64-6 >6>6

Grade A: 5-6 Grade B: 7-9 Grade C: 10-15

Differential diagnosis

Liver diseasesLiver diseases chronic hepatitischronic hepatitis ；； primary carcinoma of the liverprimary carcinoma of the liver ；； scsc

histosomiasishistosomiasis ；； clonorchiasis sinensisclonorchiasis sinensis ；； hepatic hydatihepatic hydatidosisdosis ；； hemopathyhemopathy

Ascites and abdomen enlargedAscites and abdomen enlarged tuberculous peritonitistuberculous peritonitis ；； constrictive pericardiumconstrictive pericardium ；； cc

hronic glomerulonephritishronic glomerulonephritis ；； ovarian cystsovarian cysts ComplicationsComplications Upper gastrointestinal hemorrhageUpper gastrointestinal hemorrhage ；； InfectionInfection ；； HepHep

atic encephalopathyatic encephalopathy ；； Hepatorenal syndromeHepatorenal syndrome ；； HepatHepatopulmonary Syndromeopulmonary Syndrome ；； Primary carcinoma of the Primary carcinoma of the liverliver

TTreatmentreatment

Treatment of liver cirrhosisTreatment of liver cirrhosis

Removal of the etiological factorsRemoval of the etiological factors

can stop or delay further progressioncan stop or delay further progression

may lead to regressionmay lead to regression

may reduce complicationsmay reduce complications

Prevention and treatment and of coPrevention and treatment and of co

mplicationsmplications

Cirrhotic ascites Cirrhotic ascites RestRest Diet TreatmentTreatment::

bed rest, salt restriction, bed rest, salt restriction, Water immersion Water immersion diuretics:diuretics: spironolactone, furosemide; under spironolactone, furosemide; under

regular check-up (body wt, electrolyites, renal function)regular check-up (body wt, electrolyites, renal function)

Refractory ascites:Refractory ascites: large-volume paracentesislarge-volume paracentesis

TIPSTIPS peritoneovenous shuntingperitoneovenous shunting

ComplicationsComplications Spontaneos bacterial peritonitis (SBP): Spontaneos bacterial peritonitis (SBP): fever, sepsis, hyfever, sepsis, hy

potension, fast deteoriation of liver function, azotaemia, enpotension, fast deteoriation of liver function, azotaemia, encephalopathy, deathcephalopathy, deathDg.:Dg.: PMN count in the ascites > 250/μl; culture PMN count in the ascites > 250/μl; culture

Th.:Th.: antibiotics; antibiotics; paracentesisparacentesis Hepatorenal syndrome: Hepatorenal syndrome: renal failure with severe liver diserenal failure with severe liver dise

ase without an intrinsic abnormality of the kidneyase without an intrinsic abnormality of the kidneyCause: reduction in RBF, GFR (vasoconstrictors!)Cause: reduction in RBF, GFR (vasoconstrictors!)Dg.:Dg.: urine Na < urine Na < 10 mM, oliguria without volume depletion 10 mM, oliguria without volume depletion Th.:Th.: prevention of hypovolemia, hypotension prevention of hypovolemia, hypotensionterlipressin;terlipressin; TIPSTIPS

Prognosis:Prognosis: lethal if the liver disease is untreatable lethal if the liver disease is untreatable

Bleeding oesophageal and gasBleeding oesophageal and gastric varicestric varices

Features:Features: hematemesis, melena, shockhematemesis, melena, shock

Dg. and treatment:Dg. and treatment: stabilizing BP, replacing fstabilizing BP, replacing f

luid and blood, somatostatinluid and blood, somatostatin

endoscopic sclerotherapyendoscopic sclerotherapy or ligation or ligation

or balloon tamponade; or balloon tamponade;

eradication of varices; TIPS, P-C shuntingeradication of varices; TIPS, P-C shunting

Prevention:Prevention: propranolol propranolol

Liver transplantationLiver transplantation

PrognosisPrognosis

Liver transplantationLiver transplantation PrognosisPrognosis

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