Cirrhosis of liver.2003 all
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CIRRHOSIS OF LIVERCIRRHOSIS OF LIVER
Dr. Mizanur Rahman Chowdhury
EpidemiologyEpidemiology
40% cases asymptomatic
It is the 12th leading cause of death in
United States.
Approximately 30,000 to 50,000 deaths
per year
Additional 10,000 deaths due to liver
cancer secondary to cirrhosis
CirrhosisCirrhosis
Definition: It is the end stage of liver disease characterized by
Bridging fibrous septa in the form of delicate bands or broad scar linking portal tracts with one another and portal tracts with terminal hepatic vein
Parenchymal nodules containing hepatocytes encircled by fibrosis
Disruption of architecture entire of liver
Normal LiverNormal Liver
Normal Liver HistologyNormal Liver Histology
CV
PT
Histological classificationHistological classification
Micronodular Cirrhosis :Thick regular septa and regenerating small nodules varying little in size and involvement of every lobule, mainly seen in alcoholic cirrhosis.
Size of the nodule is less than 1cm
Histological classificationHistological classification
Micronodular Cirrhosis
Micronodular cirrhosis:Micronodular cirrhosis:
Histological classificationHistological classification
Macronodular Cirrhosis :Septa and nodules of variable size and normal lobules in larger nodules, mainly seen in post necrotic cirrhosis.
Size of the nodule is more than 1cm
Histological classificationHistological classification
Macronodular Cirrhosis
Histological classificationHistological classification
Macronodular Cirrhosis
Aetiological classification Aetiological classification
Viral: Chronic Hepatitis B, Hepatitis C infection.
Alcohol
Non alcoholic fatty liver
Metabolic disorder: Haemochromatosis, Wilson’s disease,Alpha-1 antripsin deficiency.
Autoimmune Hepatitis
Primary biliary cirrhosis
Aetiological classification Aetiological classification
Prolong cholestasis
Hepatic venous outflow obstruction: Constrictive pericarditis, Veno occlusive disease, Budd chairi syndrome.
Drugs: Methotraxate, Amioderone.
Cryptogenic: Unknown origin.
Etiology of CirrhosisEtiology of Cirrhosis
Alcoholic liver disease 60-70%
Viral hepatitis 10%
Biliary disease 5-10%
Primary hemochromatosis 5%
Cryptogenic cirrhosis 10-15%
Wilson’s, 1AT def rare
Pathogenesis of cirrhosisPathogenesis of cirrhosis
Hepatocellular death
Regeneration
Progressive fibrosis
Normal liver consists of I, III , IV Collagen in portal tracts and around central veins. A delicate reticulin network of IV collagen in the space of disse “( b/w sinusoidal endothelial cell and hepatocyte.) In cirrhosis there is deposition of type I, III and other components of ECM are deposited in all portion of lobule .
Pathogenesis of cirrhosisPathogenesis of cirrhosis
The induction of fibrosis occurs with activation of hepatic stellate cells, resulting in formation of increased amounts of collagen & other components of extracellular matrix.
Stimuli : o1.Chr.inflammation – cytokines like TNF, Lymphotoxin, IL-1
o 2.Cytokine production by injured Kupffer cells, endothelial cells, hepatocytes, bile duct epithelial cells
Pathogenesis of cirrhosisPathogenesis of cirrhosis
o 3.Disruption of ECM
o 4.Direct stimulation of stellate cells by toxins
On the other hand portal hypertension developed in following way
Pathogenesis of cirrhosisPathogenesis of cirrhosis
Necrosis of hepatic parenchyma due to some injury Collapse of hepatic lobule
Formation of diffuse fibrous septa
Nodular regrowth of liver cells
Altered hepatic vasculature
Portal blood flow is impaired
Development of portal hypertension
Cirrhosis of liver
CirrhosisCirrhosis
Fibrosis
Regenerating Nodule
Liver Biopsy – CirrhosisLiver Biopsy – Cirrhosis
Liver Biopsy – Cirrhosis:Liver Biopsy – Cirrhosis:
Alcoholic cirrhosisAlcoholic cirrhosis
Ethyal alcohol is a common cause of acute/chronic liver disease.
Paterns of alcoholic liver disease:1. Fatty change2. Acute Hepatitis3. Chronic hepatitis with fibrosis4. Cirrhosis, Chronic liver failure
All are reversible except cirrhosis stage
Pathogenesis of Alcoholic cirrhosisPathogenesis of Alcoholic cirrhosis
Acetaldehyde – metabolite – hepatotoxic
Diversion of metabolism – fat storage
Oxidation of ethanol NAD to NADH. NAD is required for the oxidation of fat..
Increased peripheral release of fatty acids
Inflammation, Portal bridging fibrosis
Stimulates collagen synthesis – fibrosis
Micronodular cirrhosis
Alcoholic Liver DamageAlcoholic Liver Damage
Alcoholic Fatty LiverAlcoholic Fatty Liver
Alcoholic Fatty LiverAlcoholic Fatty Liver
Alcoholic Fatty LiverAlcoholic Fatty Liver
Clinical Feature of cirrhosisClinical Feature of cirrhosis
Symptoms: Non specific symptoms: weakness, fatigue, anorexia JaundiceAbdominal distensionSwelling if legsLoss of libido in males and amenorrhoea
in females.Low grade feverLess commonly symptoms of complication
such as epistaxis, heamatemesis, melaena, menorrhagia.
Clinical Feature of cirrhosisClinical Feature of cirrhosis
Clinical Feature of cirrhosisClinical Feature of cirrhosis
Signs:
Jaundice
Fetor hepaticus
Pedal oedema
Generalized wasting
Hands: Leuconychia, clubbing, Jaundice, Flapping tremor, palmar erythema, dupuytren’s contructure
Clinical Feature of cirrhosisClinical Feature of cirrhosis
Parotid enlargement in alcoholic cirrhosis
Loss of secondary sexual hair, axillary and pubic
Gynaecomastia in males and breast atrophy in females.
Testicular atrophy in males.skin: spider naevi in the upper limbs and chest, generalized pigmentation, purpura, bruising
Clinical Feature of cirrhosisClinical Feature of cirrhosis
Abdomen :
Dilated abdominal vessels, caput medusa
Ascitis
Splenomegaly
Hepatomegaly
Haemorrhoid
Palmar erythemaPalmar erythema
Clinical Feature of cirrhosisClinical Feature of cirrhosis
Ascitis in CirrhosisAscitis in Cirrhosis
Porta-systemic anastomosis: Porta-systemic anastomosis: Prominent abdominal veins.Prominent abdominal veins.
Gynaecomastia in cirrhosisGynaecomastia in cirrhosis
Splenomegaly in cirrhosisSplenomegaly in cirrhosis
Submucosal veins in the esophagus become dilated. These Submucosal veins in the esophagus become dilated. These are known as esophageal varices. Varices are seen here in are known as esophageal varices. Varices are seen here in the lower esophagus as linear blue dilated veins. There is the lower esophagus as linear blue dilated veins. There is hemorrhage around one of them. Such varices are easily hemorrhage around one of them. Such varices are easily eroded, leading to massive gastrointestinal hemorrhageeroded, leading to massive gastrointestinal hemorrhage
Lab investigationsLab investigations
Liver function: serum albumin and prothrombin are the best indicator of liver functions. o Albumin is less than 28 g/loProthrombin time increase according to the
severity of the diseaseoSerum bilirubin is elevated
Liver biochemistry: this can be normal depending on the severity of the cirrhosisoALP is elevatedoALT is elevated
Lab investigationsLab investigations
Serum electrolytes: A low sodium indicate severe disease due to defect in the free water clearance or excess diuretic therapy.
Serum Creatinine: An elevation concentration of more than 130micromol/l indicate worse prognosis
In addition Alpha feto protein more than 200ng/ml strongly suggest that hepato cellular carcinoma
Lab investigationsLab investigations
Other test to identify the cause
Viral marker : HBsAg,Anti HCV
Alpha-1 antitripsin
Serum copper, Caeruloplasmin
Serum immunoglobulin
Auto antibody
Iron indices,ferritin
ImagingImaging
Ultrasonogram examinition:◦Liver may show coarse ecotexture◦Dilated portal veins◦Splenomegaly◦Ascitis
CT scan may show hepatosplenomegaly and dilated collaterals are seen in chronic liver disease
Upper GI endoscopy: Oesophageal varices may seen
LIVER BIOPSY IS CONFIRMATORY
Prognosis of CirrhosisPrognosis of Cirrhosis
Poor prognostic indicator of cirrhosis: Blood tests
low Serum albumin is( <28 g/l)Low Sodium is (<125mmol/l)Prolong prothrombin time(> 6sec)Serum Creatinine is (> 130micromol/l)
ClinicalPersistent jaundiceAscitisFailure of response to therapyHemorrhage from the varices,particolarly with
poor liver function
Prognosis of CirrhosisPrognosis of Cirrhosis
Neuropsychiatric complications developing with progressive liver failure
Persistent hypertension
Small liver
Aetiology eg.alcoholic cirrhosis if the patient continue to drink alcohol
Prognosis of CirrhosisPrognosis of Cirrhosis
Prognosis can be assessed by using CHILD-PUGH CLASSIFICATION
Prameter
Ascitis None Mild Moderate/ Severe
Enchaphalopathy
None Mild Marked
Bilirubin <2mg/dl 2-3mg/dl >3mg/dl
Albumin >3.5g/dl 2.8-3.5g/dl <2.8g/dl
Prothrombin time
<4 4-6 >6
Prognosis of CirrhosisPrognosis of Cirrhosis
Score5-6 grade A (well-compensated disease)
Score 7-9 grade B (Significant functional compromise)
Score 10-15 grade C (Decompensated disease)
Complication of cirrhosisComplication of cirrhosis
1. Ascitis2. Spontaneous bacterial
peritonitis3. Heamatemesis4. Enchaphalopathy5. Hepatocellular carcinoma6. Hepato renal syndrome 7. Increased susceptibility of
infection
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