Liver diseases

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 skin
on midclavic line below right nipple. Upper and lower
level of scratching sound = distance
- 10-12 cm = normal
> 14 cm = hepatomegaly
< 8 cm = cirrhosis
 Diagnoses
 Hepatomegaly
 Cirrhosis
 Reidel’s lobe (normal variant of prominent
right lobe)
 Primary hepatocellular carcinoma
 Tricuspid regurgitation
 Splenomegaly
 Palpate in right lateral decubital position
 Percuss spleen during inspiration and
expiration
Diagnoses:
Splenomegaly
Splenectomy
 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
 CLASSIFICATION OF
JAUNDICE
Unconjugated Conjugated
Hyperbilirubinemia Hyperbilirubinemia

A. Decreased hepatic uptake A. Impaired hepatocellular

B. Overproduction secretion of bilirubin
C. Impaired bilirubin B. Cholestasis
conjugation (decreased
glucuronyl transferase
activity )
 Unconjugated Hyperbilirubinemia

A. Overproduction

Intravascular hemolysis: Hemolytic anemias

Extravascular hemolysis: Resorption of blood

from large hemorrhagic infarcts (e.g., pulmonary)
large hematomas, gastrointestinal bleeding
 Unconjugated Hyperbilirubinemia

B. Decreased hepatic uptake

 Prolonged severe fasting

 Sepsis
 Unconjugated Hyperbilirubinemia

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)
 Conjugated Hyperbilirubinemia

A.Impaired hepatocellular excretion of

bilirubin

 Dubin-Johnson syndrome

 Rotor syndrome
 Conjugated 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
 Acute liver disease

Acute viral hepatitis

Drug-induced liver disease

Alcoholic liver disease

 Chronic liver disease

Chronic active hepatitis

Cirrhosis of the liver

Liver abcess

Hepatic polichistosis
 Systemic diseases with prominent liver
involvement

Alpha 1-antitripsin deficiensy

Amyloidosis
Hemochromatosis
Sarcoidosis
Wilson`s disease
Liver disease of pregnancy
Acute fatty liver
 Inherited disorders of bilirubin
metabolism

Gilbert`s syndrome

Crigler –Najar syndrome

Rotor syndrome

Dubin-Jonson syndrome
 Acute viral hepatitis
Etiology
Hepatitis A = 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
 
 Clinical 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
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.
Primary care level attitude
•Intravenous fluids hydration, correction of
electrolyte abnormalities
•Provide caloric intake if nausea and vomiting
are present
•Vitamin K should be given if the protime is
elevated
•Address patient to hospital of infectious
diseases
 Agents of Drug-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
Heavy metals Intravenous Sulfonamides Quinidine Propylthiouracil Nitrofurantoin
tetracycline
Methotrexate Valproic acid Sulfa drugs Thiazides Oxyphenisatin
Mushroom toxins
(phalloidin and phallin)
Phosphorus
 Alcoholic 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
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)
Diagnosis
•liver biopsy: large droplet fatty liver,
polymorphonuclear infiltration, alcoholic hyaline
(Mallory bodies), hepatocyte necrosis, sclerosis
of central veins

Therapy
•supportive
•daily diet of 2500-3000 kcal
•supplements B vitamins (especially thiamine)
and folate
•absolute abstinence from alcohol is crucial
•Corticosteroids = controversial therapeutic role
(useful in very severe cases)
 Gallstones
•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 with chronic
hemolysis as well as in Oriental population

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

asymptomatic and should be treated expectantly
Surgical removal of asymptomatic gallstones is
unnecessary except for diabetic patients in whom the
risk of acute cholecystitis with complications is high
 Choledocholithiasis

•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
•CT
 Liver Test Patterns in Hepatobiliary Disorders

Type of Disorder Bilirubin

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

85% due to indirect fractions
No bilirubinuria

Acute hepatocellular necrosis Both fractions may be

(viral and drug hepatitis, elevated
hepatotoxins, acute heart Peak usually follows
failure) aminotransferases
Bilirubinuria

Chronic hepatocellular disorders Both fractions may be

elevated

Bilirubinuria

Alcoholic hepatitis / Both fractions may be

Cirrhosis elevated
Bilirubinuria

Intra- and extra-hepatic Both fractions may be

cholestasis elevated
(obstructive jaudice) Bilirubinuria
 Pancreatic 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)
 Fatty liver
 Accumulation of lipid in hepatocytes
(macro/microvesicular)
 Asymptomatic hepatomegaly discovered on
physical examination
 No association with biochemical tests for
liver disease
 Cirrhosis
 Diffuse disorganisation of hepatic structure
by regenerative nodules/fibrotic tissue
 General signs:
- asymptomatic for years
- weakness, anorexia, weight loss
- malnutrition (fat malabsorbtion, fat-
soluble vitamin deficiency)
 Cirrhosis
Occasional presentation:
- Massive upper GI bleeding from esophageal
varices secondary to portal hypertension
- Hepatocellular failure with ascites or portal
– systemic encephalopathy
 Cirrhosis
Clinic
 Palpable, firm liver with blunt edge
 Cirrhotic nodules occasionally
 Ascites
 Portal hypertension
 Splenomegaly
 Vascular spiders, muscle wasting, gynecomastia,
hair loss, palmar erythema, peripheral neuropathy
 Cirrhosis
Lab
 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
 Cirrhosis
Investigations
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
 Cirrhosis
Complications
Portal hypertension
Hypersplenism
Esophageal varices
Hypoxemia (intrapulmonary shunting0
Hepatic encephalopathy
Hepatocellular carcinoma
 Cirrhosis
Treatment
- Supportive
- withdrawal of toxic agents
- supplemental vitamins
- nutrition
- treatment of complications
- In-hospital – interferon-gamma, corticosteroids,
azathioprine
- Liver transplant
 Hepatic granulomas
Infiltrative liver disorder +/- additional hepatic
inflammation and fibrosis
Etiology
 Infectious: bacterial (TB, brucella, tularemia),
fungi (histoplasmosis, blastomycosis), parasitic
(schistosomiasis, toxoplasmosis, larva migrans),
viral
 Sarcoidosis
 Collagen disease
 Hepatic granulomas
 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
 Hepatic granulomas
Treatment

 Etiologic
 Complete regression of infective or drug
induced granulomas
 Do not give antibiotics blindly
 Sarcoidosis: corticosteroids
 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
 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