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Liver diseasesLiver diseases

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Hepatomegaly

Hepatomegaly

Clinic: measure size of liver 

Palpate lower edge of liver 

Percuss upper edge of liver 

Liver scratch test

- patient supine, auscult over epigastrum, scratch skinon midclavic line below right nipple. Upper and lower level of scratching sound = distance

- 10-12 cm = normal

> 14 cm = hepatomegaly

< 8 cm = cirrhosis

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Diagnoses

Diagnoses

Hepatomegaly

Cirrhosis Reidel¶s lobe (normal variant of prominent

right lobe)

Primary hepatocellular carcinoma

Tricuspid regurgitation

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Splenomegaly

Splenomegaly

Palpate in right lateral decubital position

Percuss spleen during inspiration and

expiration

Diagnoses:

Splenomegaly

Splenectomy

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 Ascites

 Ascites

Percuss abdomen for shifting dullness

Percuss abdomen for fluid waves

Auscult abdomen while percussing flank 

(puddle sign)

Visually inspect venous pattern of skin over 

abdomen

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CLASSIFICATION OFCLASSIFICATION OF

JAUNDICEJAUNDICE

Unconjugated

Hyperbilirubinemia

A. Decreased hepatic uptake

B. Overproduction

C. Impaired bilirubinconjugation (decreased

glucuronyl transferase

activity )

Conjugated

Hyperbilirubinemia

A. Impaired hepatocellular 

secretion of bilirubin

B. Cholestasis

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 A. Overproduction

Intravascular hemolysis: Hemolytic anemias

Extravascular hemolysis: Resorption of blood

from large hemorrhagic infarcts (e.g., pulmonary)

large hematomas, gastrointestinal bleeding

Unconjugated HyperbilirubinemiaUnconjugated Hyperbilirubinemia

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B. Decreased hepatic uptake

Prolonged severe fasting

Sepsis

U nconjugated HyperbilirubinemiaU nconjugated Hyperbilirubinemia

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C . Impaired bilirubin conjugation (decreased 

glucuronyl transferase activity)

Gilbert's syndrome

Crigler-Najjar syndrome

Jaundice in newborns

Diffuse advanced hepatocellular disease

(e.g., hepatitis, cirrhosis)

U nconjugated HyperbilirubinemiaU nconjugated Hyperbilirubinemia

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C onjugated HyperbilirubinemiaC onjugated Hyperbilirubinemia

B. Cholestasis

Intrahepatic Drug-induced (e.g., methyltestosterone, estrogens, oral contraceptives)

Recurrent jaundice of pregnancy

Recurrent familial jaundice

Early primary biliary cirrhosis

Viral hepatitis

Alcoholic hepatitis

Extrahepatic Obstruction of major excretory bile ducts: gallstones

Carcinomas of common bile duct, ampulla of Vater, head of pancreas

Inflammatory strictures of bile ducts

Atresia of bile ducts

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Acute liver diseaseAcute liver disease

Acute viral hepatitis

Drug-induced liver disease

Alcoholic liver disease

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Chronic liver diseaseChronic liver diseaseChronic active hepatitis

Cirrhosis of the liver

Liver abcess

Hepatic polichistosis

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Systemic diseases with prominent liver Systemic diseases with prominent liver 

involvementinvolvement

Alpha 1-antitripsin deficiensy

Amyloidosis

HemochromatosisSarcoidosis

Wilson`s disease

Liver disease of pregnancy

Acute fatty liver

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Inherited disorders of bilirubinInherited disorders of bilirubin

metabolismmetabolism

Gilbert`s syndrome

Crigler ±Najar syndrome

Rotor syndrome

Dubin-Jonson syndrome

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Acute viral hepatitisAcute viral hepatitis

EtiologyHepatitisA= RNA virus transmitted by fecal- oral route

anicteric in 50% of cases.

Hepatitis B = DNA virus transmitted parenterally

Individuals at high risk: - intravenous drug abusers

- exposure to blood and blood products (eg., patients and health

professionals in dialysis units)

Non-A, non-B hepatitis= more than one virus

transmitted by blood transfusions

Delta agent = small, defective RNA, infectious only in presence of hepatitis

B infection (relies on hepatitis B proteins for replication)

Other viruses: Epstein-Barr virus, cytomegalovirus, herpes simplex virus,

yellow fever, rubella

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C linical features of viral hepatitis include

(1) Malaise, anorexia, fatigue(2) Arthritis and urticaria, common in hepatitis

B (circulating immune complexes)

(3) Influenza-Iike syndrome, common in

hepatitis A

(4) Jaundice (with dark urine or light stools), in

50% of cases

(5) Hepatic enlargement or tenderness

(6) Splenomegaly, in 20% of patients

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Diagnosis of acute viral hepatitis

based on clinical features + laboratory

findings = elevated levels of transaminases,

serum bilirubin, serum alkaline phosphatase

the rise in bilirubin exceeds the increase in

alkaline phosphatase.

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P rimary care level attitude

Intravenous fluids hydration, correction of 

electrolyte abnormalities

Provide caloric intake if nausea and vomitingare present

Vitamin K should be given if the protime is

elevated

Address patient to hospital of infectiousdiseases

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 Agents of Drug  Agents of Drug--Induced Liver Disease Induced Liver Disease

  Drugs Causing Drugs Causing Viral Granulomatous Inflammatory Chronic Active

  Direct Toxicity Altered Metabolism Hepatitis-Iike Hepatitis Cholestasis Hepatitis

Acetaminophen Androgens Halothane Allopurinol Chlorpromazine Acetaminophen

Aspirin Corticosteroids (?) Isoniazid Hydralazine Chlorpropamide Aspirin

Alcohol Estrogens Oxacillin Phenylbutaz. Erythromycin Isoniazid

Carbon tetrachloride Ethanol Phenytoin Phenytoin Estolate Methyldopa

Heavymetals Intravenous Sulfonamides Quinidine Propylthiouracil Nitrofurantoin

tetracycline

Methotrexate Valproic acid Sulfa drugs Thiazides Oxyphenisatin

Mushroom toxins

(phalloidin and phallin)

Phosphorus

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Alcoholic hepatitisAlcoholic hepatitis

acute syndrome due to heavy alcohol

consumption (ingestion > 100 g alcohol daily  for 

more than 1 year) 8 oz whiskey, 30 oz wine, eight

12-oz cans beer 

decreased vitamin and protein intake

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Clinical features

Fever, jaundice, hepatomegaly, liver tenderness

Ascites, encephalopathy, variceal bleeding

occasionally

Laboratory

Leukocytosis

Elevated GOT elevated serum bilirubin

decreased serum albumin

modest increase in serum alkaline phosphatase

Cholestatic phase

marked elevations of alkaline phosphatase and

direct bilirubin

GPT always < GOT

Alcohol-induced thrombocytopenia (10% of patients)

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Diagnosis liver biopsy: large droplet fatty liver,

polymorphonuclear infiltration, alcoholic hyaline

(Mallory bodies), hepatocyte necrosis, sclerosis

of central veins

Therapysupportive

daily diet of 2500-3000 kcal

supplements B vitamins (especially thiamine)

and folate

absolute abstinence from alcohol is crucialCorticosteroids = controversial therapeutic role

(useful in very severe cases)

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GallstonesGallstones

extremely common, occur in 20% of the population in Western populations composed primarily of 

cholesterol

pigment gallstones, composed primarily of  

calcium bilirubinate, are found in patients withchronic hemolysis as well as in Oriental population

one-third to one-half of patients with gallstones are

asymptomatic and should be treated expectantlySurgical removal of asymptomatic gallstones is

unnecessary except for diabetic patients in whom the

risk of acute cholecystitis with complications is high

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CholedocholithiasisCholedocholithiasis

gallstone passed into the common bile duct from gallbladder 

retained gallstone missed during cholangiography or common

duct exploration.

formed de novo in the common duct (stasis from ductal

obstruction)

Symptoms intermittent colicky pain in right upper quadrant

fever, chills, jaundice

sepsis from ascending cholangitis, closed space infection

Lab elevated serum levels of alkaline phosphatase and

transaminases

Dg

Endoscopic retrograde cholangiopancreatography

Percutaneous transhepatic cholangiography

Ultrasound

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Liver Test Patterns in Hepatobiliary DisordersLiver Test Patterns in Hepatobiliary Disorders

Type of Disorder Bilirubin

Hemolysis/Gilbert's syndrome Normal to 5 mg/dl

85% due to indirect fractions

No bilir ubinuria

 Acute hepatocellular necrosis Both fractions may be

(viral and dr ug hepatitis, elevated

hepatotoxins, acute heart Peak usually follows

failure) aminotransferasesBilir ubinuria

Chronic hepatocellular disorders Both fractions may be

elevated

Bilir ubinuria

 Alcoholic hepatitis / Both fractions may be

Cirrhosis elevatedBilir ubinuria

Intra- and extra-hepatic Both fractions may be

cholestasis elevated

(obstr uctive jaudice) Bilir ubinuria

Infiltrative diseases (tumor, Usually normal

granulomata); partial bile duct

obstr uction

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Pancreatic carcinomaPancreatic carcinoma

Weight loss, anorexia and chronic persistent pain in

the epigastrium ,radiating to the back 

Obstructive jaundice with painless palpable

dilatation of the gallblader (Courvoisier`s sign)

Migratory thrombophebitis (Trousseau syndrome)

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Fatty liver 

Fatty liver 

Accumulation of lipid in hepatocytes

(macro/microvesicular)

Asymptomatic hepatomegaly discovered on

 physical examination

 No association with biochemical tests for 

liver disease

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CirrhosisCirrhosis Diffuse disorganisation of hepatic structure

 by regenerative nodules/fibrotic tissue

General signs:- asymptomatic for years

- weakness, anorexia, weight loss

- malnutrition (fat malabsorbtion, fat-solublevitamin deficiency)

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CirrhosisCirrhosisOccasional presentation:

- Massive upper GI bleeding from esophageal

varices secondary to portal hypertension

- Hepatocellular failure with ascites or portal

 ± systemic encephalopathy

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CirrhosisCirrhosisLab

Decreased serum albumin impaired

Prolonged prothrombin time liver function

Increased serum gamma globulin

AST/ALT elevated

Alkaline P normal/increased

Bilirubin normal/elevated

  Normocytic normochromic anemia hypersplenism

Thrombocytopenia/leukopenia

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CirrhosisCirrhosisInvestigations

US

- Confirm hepatomegaly/splenomegaly

- Enlargement/venous obstruction of portal/splenic veins

- Estimate portal vein flow

Isotopic scintiscan

- irregular pattern of liver uptake, increased uptake in spleen

and bone marrow

Biopsy

- etiology

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CirrhosisCirrhosisComplications

Portal hypertension

Hypersplenism

Esophageal varices

H

ypoxemia (intrapulmonary shunting0Hepatic encephalopathy

Hepatocellular carcinoma

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CirrhosisCirrhosisTreatment

- Supportive

- withdrawal of toxic agents- supplemental vitamins

- nutrition

- treatment of complications

- In-hospital ± interferon-gamma, corticosteroids,azathioprine

- Liver transplant

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Hepatic gran

ulomas

Hepatic gran

ulomas

Infiltrative liver disorder +/- additional hepaticinflammation and fibrosis

Etiology Infectious: bacterial (TB, brucella, tularemia),

fungi (histoplasmosis, blastomycosis), parasitic(schistosomiasis, toxoplasmosis, larva migrans),

viral Sarcoidosis

Collagen disease

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Hepatic gran

ulomas

Hepatic gran

ulomas

Clinic

- evolution subclinical

- FUO (fever of unknown origin)!

- liver fct tests normal, except disproportionate

elevation of alk P

Dg

- liver biopsy ( especially important in FUO)

- cultures, skin tests, x-ray

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Hepatic gran

ulomas

Hepatic gran

ulomas

Treatment

Etiologic

Complete regression of infective or drug

induced granulomas

Do not give antibiotics blindly

Sarcoidosis: corticosteroids

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Neoplasms of the liver Neoplasms of the liver  Hepatocellular carcinoma

Metastatic disease ± most common

Symptoms

- weight loss

- abdominal pain

- right upper quadrant mass- unexplained deteriorationof previously stable

 patient with cirrhosis

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Neoplasms of the liver Neoplasms of the liver Dg: 3 key elements

Hepatic friction rub or bruit

Painful growing hepatomegaly in pts with

cirrhosis

Elevation of alfa-fetoprotein in serum >

400microg/l