CHAPTER 18: LIVER AND GALLBLADDER

I. THE LIVER AND BILE DUCTS

Anatomy:

The liver weighs 1400-1600 grams in adults and has a dual blood
supply:

Portal vein: Provides 60-70% of hepatic blood flow.

Hepatic artery: Supplies the remaining 30-40%.

The lobule model divides the liver into hexagonal lobules with
central veins in the center and portal tracts at the periphery.

Acinar model: Based on blood flow, it defines three zones:

Zone 1: Closest to the blood supply.

Zone 3: Farthest from the blood supply.

General Features of Liver Disease:

The liver is vulnerable to various insults, including metabolic, toxic,

microbial, circulatory, and neoplastic.

Hepatocyte injury: Can be reversible or irreversible.

Reversible changes: Steatosis, cholestasis, ballooning.

Irreversible changes: Necrosis, apoptosis.

Scar formation: Primarily involves hepatic stellate cells, which

activate and differentiate into myofibroblasts in response to injury.

Liver failure:

Acute: Sudden and massive hepatic destruction.

Chronic: Years of progressive liver injury.

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Acute-on-chronic: Superimposed acute injury on chronic disease.

Clinical features of liver failure:

Cholestasis: Bilirubin retention, jaundice, increased risk of

infection.

Hepatic encephalopathy: Spectrum of consciousness

disturbances, from subtle behavioral changes to coma.

Coagulopathy: Deficiencies in clotting factors, bleeding tendency.

Portal hypertension: Increased resistance to portal blood flow,

leading to ascites, portosystemic shunts, splenomegaly.

Hepatorenal syndrome: Renal failure in patients with liver failure.

II. INFECTIOUS DISORDERS

Viral Hepatitis:

Hepatitis A Virus (HAV):

Transmission: Fecal-oral route.

Clinical features: Self-limited, acute hepatitis, no chronic infection.

Prevention: Vaccination.

Hepatitis B Virus (HBV):

Transmission: Parenteral, sexual contact, perinatal.

Clinical features: Acute hepatitis, chronic hepatitis, cirrhosis,

carrier state.

Prevention: Vaccination.

Treatment: Interferon, antiviral agents (entecavir, tenofovir).

Hepatitis C Virus (HCV):

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Transmission: Parenteral.

Clinical features: Usually asymptomatic, chronic hepatitis,

cirrhosis, hepatocellular carcinoma.

Treatment: Antiviral agents targeting NS3/4A protease, NS5A

replication complex, NS5B polymerase.

Hepatitis D Virus (HDV):

Transmission: Parenteral, requires co-infection with HBV.

Clinical features: Acute hepatitis, chronic hepatitis, increased risk

of cirrhosis and HCC.

Treatment: Interferon-γ.

Hepatitis E Virus (HEV):

Transmission: Fecal-oral route, zoonotic.

Clinical features: Acute hepatitis, self-limited, severe in

pregnancy.

Clinicopathologic Syndromes:

Acute asymptomatic infection with recovery.

Acute symptomatic infection with recovery.

Acute liver failure.

Chronic hepatitis.

Carrier state.

Bacterial, Fungal, and Parasitic Infections:

Bacterial infections: Can cause abscess formation, ascending

cholangitis.

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Fungal infections: Disseminated fungal infections can involve the
liver, showing epithelioid granulomas.

Parasitic infections: Malaria, schistosomiasis, strongyloidiasis,

cryptosporidiosis, leishmaniasis, echinococcosis, amebiasis, liver
fluke infections.

III. AUTOIMMUNE HEPATITIS

Pathogenesis: Chronic, progressive hepatitis associated with
genetic predisposition, autoantibodies, and response to
immunosuppression.

Clinical features: Variable presentations, from asymptomatic to

acute liver failure, chronic hepatitis, and cirrhosis.

Diagnosis: Based on autoantibodies, elevated serum IgG, exclusion

of other etiologies, and supportive histologic findings.

Treatment: Immunosuppression with prednisone, with or without

azathioprine.

IV. DRUG- AND TOXIN-INDUCED LIVER INJURY

Pathogenesis: Liver injury caused by a wide array of compounds,
including medicines, herbal products, dietary supplements,
poisonous plants, and household/industrial products.

Clinical features: Variable presentations, mimicking other liver

diseases.

Diagnosis: Based on temporal association of drug/toxin exposure

with onset of liver injury, exclusion of other etiologies, and recovery
on withdrawal of the offending agent.

V. FATTY LIVER DISEASE

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Alcoholic Liver Disease:

Pathogenesis: Excessive alcohol consumption leads to steatosis,

alcoholic hepatitis, fibrosis, and cirrhosis.

Risk factors: Gender, ethnic and genetic differences, comorbid

conditions.

Clinical features: Hepatic steatosis, alcoholic hepatitis, alcoholic

cirrhosis.

Treatment: Abstinence from alcohol, adequate diet.

Nonalcoholic Fatty Liver Disease (NAFLD):

Pathogenesis: Presence of hepatic steatosis in individuals without

excessive alcohol consumption, associated with obesity, diabetes
mellitus type 2, and hyperlipidemia.

Clinical features: Asymptomatic, nonspecific symptoms, increased

risk of hepatocellular carcinoma.

Treatment: Weight loss, diet, exercise, pharmacologic approaches

under investigation.

VI. INHERITED LIVER DISEASE

Hemochromatosis:

Pathogenesis: Excessive iron absorption, leading to iron deposition

in various organs, including the liver, pancreas, heart, joints, and
endocrine organs.

Clinical features: Micronodular cirrhosis, diabetes mellitus,

abnormal skin pigmentation, cardiac dysfunction.

Diagnosis: Serum iron measurements, DNA sequencing, liver

biopsy.

Treatment: Regular phlebotomy.

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Wilson Disease:

Pathogenesis: Autosomal recessive disorder caused by mutation of

the ATP7B gene, resulting in impaired copper excretion and
accumulation of copper in various tissues.

Clinical features: Liver disease, neurologic involvement, Kayser-

Fleischer rings.

Diagnosis: Decreased serum ceruloplasmin, increased hepatic

copper content, increased urinary excretion of copper, ATP7B gene
sequencing.

Treatment: Copper chelation therapy (D-penicillamine or trientine),

zinc-based therapy, liver transplantation.

α1-Antitrypsin Deficiency:

Pathogenesis: Autosomal recessive disorder of protein folding,

leading to low levels of circulating α1-antitrypsin and accumulation
of misfolded protein in hepatocytes.

Clinical features: Pulmonary emphysema, liver disease.

Diagnosis: Low serum α1-antitrypsin levels, liver biopsy.

VII. CHOLESTATIC DISEASE

Bile Formation and Secretion: Bile plays a crucial role in
elimination of bilirubin, excess cholesterol, xenobiotics, and trace
metals.

Pathophysiology of Hyperbilirubinemia: Elevated serum

bilirubin levels lead to jaundice.

Types of Hyperbilirubinemia:

Unconjugated: Excess bilirubin production or defective

conjugation.

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Conjugated: Hepatocellular disease, bile duct injury, biliary
obstruction.

Specific Cholestatic Disorders:

Physiologic jaundice of the newborn: Transient, mild

unconjugated hyperbilirubinemia in newborns.

Hereditary hyperbilirubinemia: Genetic mutations leading to

impaired uptake, conjugation, or secretion of bilirubin.

Large bile duct obstruction: Obstruction of large bile ducts,

leading to cholestasis and potentially biliary cirrhosis.

Cholestasis of sepsis: Cholestasis associated with systemic

infection.

Primary Hepatolithiasis: Stones in the intrahepatic bile ducts,

leading to ascending cholangitis and liver damage.

Neonatal Cholestasis: Jaundice beyond 14-21 days after birth,

requiring evaluation for obstructive or nonobstructive biliary disease.

Extrahepatic biliary atresia: Complete or partial obstruction of

the extrahepatic biliary tree.

Nonobstructive neonatal cholestasis: Diverse disorders,

including Alagille syndrome, inborn errors of metabolism, and bile
transport defects.

Autoimmune Cholangiopathies:

Primary Biliary Cholangitis (PBC): Autoimmune disease with

inflammatory destruction of small- and medium-sized intrahepatic
bile ducts.

Primary Sclerosing Cholangitis (PSC): Inflammation and

obliterative fibrosis of extrahepatic and large intrahepatic ducts.

VIII. STRUCTURAL ANOMALIES OF THE BILIARY TREE

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Choledochal Cyst: Congenital dilation of the common bile duct,
predisposing to stone formation, stenosis, pancreatitis, and
obstructive biliary complications.

Fibropolycystic Disease: Heterogeneous group of lesions with

congenital malformation of the biliary tree, including von Meyenburg
complexes, biliary cysts, and congenital hepatic fibrosis.

IX. CIRCULATORY DISORDERS

Impaired Blood Flow Into the Liver:

Hepatic artery compromise: Obstruction of hepatic artery

branches, leading to localized infarct.

Portal vein obstruction and thrombosis: Blockage of portal vein,

leading to abdominal pain and portal hypertension.

Impaired Blood Flow Through the Liver:

Cirrhosis: Most common intrahepatic cause of blood flow

impairment.

Sinusoidal obstruction syndrome: Toxic injury to sinusoidal

endothelium, leading to obstruction of sinusoidal blood flow.

Impaired Blood Flow From the Liver:

Hepatic vein thrombosis (Budd-Chiari syndrome): Obstruction

of major hepatic veins, leading to liver enlargement, pain, and
ascites.

Passive congestion and centrilobular necrosis: Hepatic

manifestations of systemic circulatory compromise.

X. HEPATIC DISEASE ASSOCIATED WITH PREGNANCY

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Viral hepatitis: Most common cause of jaundice in pregnancy.

Preeclampsia and eclampsia: Hypertension, proteinuria,

peripheral edema, coagulation abnormalities, and potentially hepatic
rupture.

Acute fatty liver of pregnancy: Diffuse microvesicular steatosis

in hepatocytes, leading to hepatic failure and death.

Intrahepatic cholestasis of pregnancy: Pruritus, darkening of

urine, jaundice, and elevated bile salt levels.

XI. NODULES AND TUMORS

Non-Neoplastic Mass Lesions:

Focal nodular hyperplasia (FNH): Benign, non-neoplastic lesion,

often with a central stellate scar.

Other non-neoplastic mass lesions: Abscesses, granulomas,

inflammatory pseudotumors, regenerative nodules, nodular
regenerative hyperplasia.

Benign Neoplasms:

Cavernous hemangioma: Most common benign liver tumor,

consisting of dilated vascular channels.

Hepatocellular adenoma: Benign neoplasm, associated with oral

contraceptive and anabolic steroid use, classified into three
subtypes based on driver mutations.

Primary Malignant Neoplasms:

Hepatoblastoma: Most common liver tumor of early childhood,

associated with Wnt pathway activation.

Hepatocellular Carcinoma (HCC): Most common primary hepatic

malignant neoplasm, often occurring in the setting of cirrhosis.

Malignant Biliary Tumors:

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Intrahepatic cholangiocarcinoma: Adenocarcinoma arising from
the intrahepatic biliary tree.

Extrahepatic biliary adenocarcinoma: Adenocarcinoma arising

from the extrahepatic bile ducts.

Other primary hepatic malignant tumors: Combined

hepatocellular-cholangiocarcinoma, angiosarcoma, epithelioid
hemangioendothelioma, primary hepatic lymphoma.

Metastasis: Involvement of the liver by metastatic malignancy is

far more common than primary hepatic neoplasia.

XII. GALLBLADDER
Congenital Anomalies: Gallbladder may be absent, duplicated, or
have aberrant locations.

Cholelithiasis (Gallstones):

Types: Cholesterol stones, pigment stones.

Risk factors: Age, sex, environmental factors, acquired disorders,

hereditary factors.

Pathogenesis: Cholesterol stones form due to supersaturation of

bile with cholesterol, gallbladder hypomotility, accelerated crystal
nucleation, and hypersecretion of mucus. Pigment stones form due
to elevated levels of unconjugated bilirubin in bile.

Clinical features: Asymptomatic, biliary colic, complications

including empyema, perforation, fistula, cholangitis, obstructive
cholestasis, and pancreatitis.

Cholecystitis:

Acute: Inflammation of the gallbladder, usually caused by

obstruction by a stone.

Acute calculous cholecystitis: Most common complication of

gallstones.
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Acute acalculous cholecystitis: Occurs in severely ill patients,
thought to result from ischemia.

Chronic: May be a sequel to repeated acute cholecystitis or develop

in the absence of antecedent attacks.

Gallbladder Carcinoma: Most common malignancy of the

extrahepatic biliary tract, associated with gallstones and chronic
inflammation.

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