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Hepatic Cirrhosis

Yu Baoping

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Introduction

CIRRHOSIS Term was 1st coined by Laennec in 1826

Many definitions but common theme is injury, repair,regeneration and scarring

NOT a localized process; involves entire liver

Primary histologic features:

1. Marked fibrosis

2. Destruction of vascular & biliary elements

3. Regeneration4. Nodule formation

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Definition

Cirrhosis is a pathological diagnosis. It is

characterized by widespread fibrosis with

nodular regeneration. Its presence implies

previous or continuing hepatic cell damage

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Aet io logyandPathogenesis

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Etiologic classification of cirrhosis

Alcohol (>70%)

Chronic infections

hepatitis C, B, B+D

brucellosis, syphilis

Chr. biliary

obstruction

PBC, PSC, stricture,

stones, cystic fibrosis,cong.b. atresia, ~cysts

Autoimmune

Cardiovascular

heart failure, pericarditis,

Budd-Chiary-sy

Metabolic/genetic errors

Fe, Cu, 1-AT, lipids,

Drugs and chemicals

NASH

Cryptogenic Combined

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Pathogenesis:

Diffuse liver injury leading to necrosis. (Alcohol, virus, drugs, toxins, genetic etc.)

Chronic inflammation & healing (hepatitis).

Bridging fibrosis loss of architecture.

Regeneration nodules. Obstruction to blood flow & shunts.

Portal hypertension spleen, varices

Liver failure Debilitation, Jaundice, Ascitis, edema,

bleeding, jaundice. Hormone imbalance spider nevi, testes atrophy etc..

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Pathologyand Pathophysiology

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Pathologyliver

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Classification of Cirrhosis

WHO divided cirrhosis into 3 categories

based on morphological characteristics of the

hepatic nodules

1. Micronodular

2. Macronodular

3. Mixed

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Micronodular Cirrhosis

Nodules are

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Micronodular cirrhosis

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Macronodular & Mixed Cirrhosis

Nodules are >3 mm in diameter and vary considerably

in size

Usually contain portal tracts and efferent veins

Liver is usually normal or reduced in size Mixed pattern if both type of nodules are present in

equal proportions

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Macronodular cirrhosis

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Cirrhosis

Fibrosis

Regenerating Nodule

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Pathologyothers

gastrointestinal tract

varicose veinshemorrhagecongestion

Kidney

glomerulonephritis

Endocrinemuscular atrophydegenerationtestis

ovary thyroidadrenal cortex

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Cirrhosis: Pathophysiology

Primary event is injury to hepatocellularelements

Triggering inflammatory response with cytokine

release-toxic substances Destruction of hepatocytes, bile duct cells,

vascular endothelial cells

Repair thru cellular proliferation and

regeneration Formation of fibrous scar

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Stellate cell is activated in response to injuryand lead to expression of fibril-forming collagen

Above process is also influenced by Kupffer

cells which activate stellate cells by elicitingproduction of cytokines

Sinusoidal fenestrations are obliteratedbecause of collagen

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Prevents normal flow of nutrients tohepatocytes and increases vascular resistance

Initially, fibrosis may be reversible if inciting

events are removed With sustained injury, process of fibrosis

becomes irreversible and leads to cirrhosis

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Pathophysiology

Protal hypertension

Ascites

endocrine

respiratory system hepatic hydrothorax

hepatopulmonary syndrome

the urinary system : hepatorenal syndrom, HRS

hematological system

nervous system : HE

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Portal Hypertension (PH)

Portal vein pressure above the normal range of5 to 8 mm Hg

Portal vein - Hepatic vein pressure gradientgreater than 5 mm Hg (>12 clinically significant)

Represents an increase of the hydrostaticpressure within the portal vein or its tributaries

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Pathophysiology of PH

Cirrhosis results in scarring (perisinusoidal deposition ofcollagen)

Scarring narrows and compresses hepatic sinusoids(fibrosis)

Portal vein thrombosis, or hepatic venous obstructionalso cause PH by increasing the resistance to portalblood flow

Progressive increase in resistance to portal venous

blood flow results in PH

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Pathophysiology of PH

As pressure increases, blood flow decreases and thepressure in the portal system is transmitted to itsbranches

Results in dilation of venous tributaries

Increased blood flow through collaterals andsubsequently increased venous return cause anincrease in cardiac output and total blood volume and adecrease in systemic vascular resistance

With progression of disease, blood pressure usuallyfalls

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Portal Vein Collaterals

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

Inferior mesenteric vein -> rectal branches which, when

distended, form hemorrhoids

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

Retroperitoneal collaterals ->gastrointestinal veins

through the bare areas of the liver

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Ascites

Sodium and water retention occur due to renin-angiotensin release secondary to arterial vasodilatation,caused by vasoactive substances such as nitric oxide

Portal hypertension per se causes fluid to accumulatein the peritoneal cavity due to increased hydrostatic

pressure, hence further reduces intravascular volumeand stimulates sodium and water retention viaaldosterone.

Low albumin in plasma

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Clin ical p resen tat ion

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Clinical presentation

There may be no abnormal clinical

or biochemical features of liver

disease in initial timesFeatures of hepatocellular failure,

portal hypertension, or both may

appear in advanced times.

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Cirrhosis

ClinicalFeatures

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Symptoms of advanced cirrhosis

Fatique, weakness Nausea, vomiting and

loss of appetite

Weight loss, musclewasting

Jaundice, dark urine

Spider naevi, caputMedusae

Bloody, black stools

or unusually light-colored stools

Vomiting of blood

Abdominal swelling Swollen feet or legs

Liver palms

Gynecomastia

Loss of sex drive Menstrual changes in

women

Generalized itching

Sleep disturbances,confusion,desorientation,tremor, asterixis

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Clinical Features

Hepatocellular failure.

Malnutrition, low albumin & clotting factors,

bleeding.

Hepatic encephalopathy.

Portal hypertension.

Ascites, Porta systemic shunts, varices,

splenomegaly.

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Gynecomastia

Ascites

Caput Medusae

Umbilical hernia

Visible signs

of advanced livercirrhosis

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Complications

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Complications

Upper gastrointestinal hemorrhage

Hepatic encephalopathy

Infection Hepatorenal syndrome

Hepatopulmonary Syndrome

Primary carcinoma of the liver Disturbance of electrolyte and acid-base

balance

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Laboratory tes ts

and inves t igat ions

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laboratory tests and investigations

Blood-RTanaemiahypersplenia:WBC Plt

Urine-RTurine bilirubin

urobilinogen

sometimesalbumenhaematuria

Stool-RTmelena

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liver function tests

Compensation normal or abnormal slightly Decompensation

transaminase ALT AST

cholesterol

albumin and globulin

prothrombin time

bilirubin

PP, and so onQuantitation- liver function testsIGG

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Biochemistry can be surprisingly normal but someabnormality will often be present with slightly

raised transaminases and alkaline phosphatases.

In severe cases, all live enzymes will be abnormal.

Low sodium and albumin are also seen.

Coagulopathy is a very sensitive indicator of liver

dysfunction and is reflected in the prolonged

prothrombin time.

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immunologic function test

AFP

virus hepatitis markers

antinuclear antibody, ANA non-specificity

antismooth muscle antibody autoantibody

anti-mitochondrial antibody

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Imaging examinationBarium meal

CT or MRI

Ultrasound demonstrates fatty change, size, andfibrosis as well as hepatocellular carcinoma

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MRI Cirrhosis


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Special test

Endoscope

Biopsy

Laparoscope

Hydroperitoneum test Measure the Pressure of Portal Vein

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Diagnosis and

dif ferent ial

d iagnosis

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Diagnosis of liver cirrhosis

The gold standard: liver biopsy histology

Diffuse, chronic liver disease

(hystory, physical, laboratory and US

findings)

with evidences of portal hypertension

(oesophageal varices on gastroscopy;

dilated portal vein and its branches by US)

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Child-Pughs classification

Categories

Classification Points

1 2 3

Encephalopathy None Grade I & II Grade III & IV

Ascites Absent Slight-moderate Tense

Bilirubin (mg/dl) 3 (>10)

Albumin (g/dl) >3.5 2.8-3.5 6

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

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Differentialdiagnosis

Liver diseases

chronic hepatitisprimary carcinoma of the liverschistosomiasisclonorchiasis sinensishepatichydatidosishemopathy

Ascites and abdomen enlargedtuberculous peritonitisconstrictive pericardiumchronic glomerulonephritisovarian cysts

Complications

Upper gastrointestinal hemorrhageInfectionHepatic encephalopathyHepatorenal syndromeHepatopulmonary Syndrome Primary carcinoma ofthe liver

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Treatment

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Treatment of liver cirrhosis

Removal of the etiological factors

can stop or delay further progression

may lead to regression

may reduce complications

Prevention and treatment and of

complications

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Cirrhotic ascites

Rest

Diet

Treatment:

bed rest, salt restriction,

Water immersion diuretics: spironolactone, furosemide; under

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

Refractory ascites:

large-volume paracentesis

TIPS

peritoneovenous shunting

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Complications

Spontaneos bacterial peritonitis (SBP): fever, sepsis,

hypotension, fast deteoriation of liver function, azotaemia,encephalopathy, death

Dg.:PMN count in the ascites > 250/l; culture

Th.: antibiotics;paracentesis

Hepatorenal syndrome: renal failure with severe liverdisease without an intrinsic abnormality of the kidney

Cause: reduction in RBF, GFR (vasoconstrictors!)

Dg.: urine Na < 10 mM, oliguria without volume depletion

Th.: prevention of hypovolemia, hypotensionterlipressin;TIPS

Prognosis: lethal if the liver disease is untreatable

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Bleeding oesophageal and

gastric varices

Features:hematemesis, melena, shock

Dg. and treatment:stabilizing BP, replacing

fluid and blood, somatostatin

endoscopic sclerotherapy or ligation

or balloon tamponade;

eradication of varices; TIPS, P-C shunting

Prevention: propranolol

Liver transplantation

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Prognosis

Liver transplantation

Prognosis

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" With ordinary talent and

extraordinary perseverance, all

things are attainable."- Thomas E. Buxton

" Achievement is connected

with action..!

- Conrad Hilton

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