Diseases of the Liver & Biliary Tract

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Diseases of the Liver Biliary Tract
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• The circulation of blood through the intestines
  liver is unique in human anatomy blood from one
  capillary system, the intestinal, flows into
  another capillary system, the hepatic, before
  returning to the heart

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Enterohepatic Circulation
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Major Determinants of Disease

• The metabolic consequences of liver disease are
  serious include
• toxic accumulations of
• metabolic waste (especially ammonia bilirubin)
• drugs toxins
• endogenous hormones (especially estrogen)
• bleeding, associated with a deficiency of
  coagulation factors
• edema, associated with a deficiency of albumin
• failure to absorb intestinal fat because of a
  deficiency of bile acids
• Viral hepatitis is a common contagious disease
• Cirrhosis is the final endpoint for many liver
  diseases
• Portal HTN is the most important consequence of
  cirrhosis can be associated with liver failure
  severe hemorrhage
• Stones often form in the gallbladder may pass
  into obstruct the bile duct

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Response to Injury

• Responds well as it has a functional reserve that
  must suffer a large loss before become
  symptomatic
• Liver function tests (LFTs)
• enzymes
• Lactic dehydrogenase (LDH)
• Aspartate aminotransferase (AST)
• Alanine aminotransferase (ALT)
• Alkaline phosphatase (ALKP)
• bilirubin
• albumin
• PT PTT
• viral antigens antibodies
• autoimmune antibodies

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Anatomic Patterns of Injury

• Inflammation
• hepatitis
• Degeneration
• hydropic
• fatty
• Necrosis
• infarct
• Councilman bodies
• Fibrosis
• cirrhosis

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Functional Patterns of Liver Injury

• Direct metabolic consequences
• jaundice
• cholestasis
• accumulation of bile acids cholesterol in blood
  due to obstruction
• hepatic failure

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Jaundice

• Bilirubin gt 2mg/dl

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Cholestasis

• Usually accompanied by jaundice pruritis
• Due to
• primary liver disease
• drug interference with bile secretion
• pregnancy
• Elevated blood cholesterol
• Xanthomas
• Increased ALKP

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Hepatic Failure

• Die within a few weeks or months
• May be sudden injury or chronic injury
• Loss of 90 of function
• Clinically
• jaundice
• ascites
• fetor hepaticus
• hypoalbuminemia
• hypoglycemia
• palmar erythema
• spider angiomata
• testicular atrophy
• balding
• gynecomastia
• bleeding disorders
• hepatorenal syndrome
• hepatic encephalopathy

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Cirrhosis

• Final, common end-stage for a variety of chronic
  liver diseases

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• Patterned fibrosis characterized by
  interconnecting bands of scar tissue
• divides liver into small nodules separated by
  dense fibrous tissue
• Progressive
• Irreversible
• Incurable

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Anatomic Types of Cirrhosis

• Portal
• caused by diffuse liver cell injury
• repeated episodes of necrosis followed by
  regeneration growth of fibrous tissue from
  portal triad area
• most common type
• usually due to alcoholic liver disease or chronic
  viral hepatits
• Biliary
• caused by chronic disease of the biliary tree
• chronic inflammation of bile ducts due to
• autoimmune disease
• obstruction by gallstones
• sclerosing cholangitis

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• Causes portal hypertension

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Viral Hepatitis

• Several viruses involved
• HAV
• HBV
• HCV
• HDV
• HEV

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• Hepatitis A is a mild, epidemic disease spread by
  contaminated food H2O
• does not cause chronic hepatitis or cirrhosis
• Hepatitis B C are spread from individual to
  individual by needles or sexual contact
• can cause chronic hepatitis or cirrhosis

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Clinical Syndromes of Viral Hepatitis

• Asymptomatic hepatitis
• no lasting liver injury
• Carrier state
• harbors virus but is asymptomatic
• can transmit to others
• mostly HCV
• Acute viral hepatitis
• 4 clinical phases
• Chronic viral hepatitis
• Fulminant hepatic failure
• Hepatocellular carcinoma
• increased risk with HBV HCV

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Acute Viral Hepatitis

• Incubation
• a few weeks
• Symptomatic prejaundice phase
• malaise
• fatigue
• nausea/vomiting
• anorexia
• RUQ pain
• fever
• headache

• Symptomatic jaundice phase
• jaundice appears other symptoms fade
• increase in conjugated bilirubin
• pale stools
• Convalescence
• jaundice fades
• infectivity disappears
• Abs in blood

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Chronic Viral Hepatitis

• Liver biopsy 6 months or more of clinical or
  lab evidence
• About 10 of HBV patients 50 of HCV patients
• Lab tests reveal extent of disease as there are
  few signs/symptoms
• prolonged PT PTT
• increased enzymes
• increased bilirubin
• Present with
• hepatomegaly
• splenomegaly
• palmar erythema
• spider angiomas

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Fulminant Hepatic Failure

• Acute liver disease that progresses to hepatic
  failure or encephalopathy in just a few weeks
• More than ½ of the cases are fulminant hepatitis
  usually involving HAV or HBV
• Other causes include drugs, heat stroke

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Hepatitis A

• HAV
• Epidemic hepatitis
• Primarily fecal-oral transmission
• Benign self-limiting
• Incubation is about 2-6 weeks
• Most common type in the world
• infection more common than the disease
• more common in developing nations
• about 10,000 new cases/yr in US
• Fatalities rare
• No carrier state
• Vaccine

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Hepatitis B

• HBV
• Infects hundreds of millions worldwide
• Incubation varies from a few weeks to 6 months

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Acute Infection

• Detected by presence of hepatitis B surface
  antigen (HBsAg)
• Viremia may last for many weeks
• 1st antibody to appear is hepatitis B core
  antigen antibody (anti-HBc)
• Beginning of recovery marked by appearance of
  hepatitis B surface antigen antibodies (anti-HBs)
• confers immunity

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• Spread by
• sexual contact
• blood transfusion
• renal dialysis
• needlestick
• IV drug users
• fetus in utero or during vaginal delivery
• 1/3 of cases, not known

• Transmitted in
• blood
• saliva
• semen
• almost any bodily fluid

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Hepatitis C

• Major cause of chronic liver disease
• Incubation varies from a few weeks to 6 months
• About 40,000 new cases/yr

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• About 2 have antibodies indicating previous
  infection
• About 50 of these have detectable virus in blood
• indicates a chronic carrier state

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• Transmission
• over 12/ of new infections due to IV drug abuse
• about 15 through sexual contact, infected health
  care workers, neonates
• in about 1/3 of cases, not known
• Mutating RNA virus with dozens of subtypes has
  made developing a vaccine difficult

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• Hepatitis D
• HDV
• delta virus
• co-exist with HBV
• co-infect
• infect a carrier of HBV
• mostly in
• IV drug abusers
• hemophiliacs

• Hepatitis E
• rare in US but most common form of epidemic
  hepatitis in India
• transmitted like HAV
• mild self-limiting

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Anatomic Pathology of Hepatitis

• Carrier state
• liver biopsy normal usually
• in HCV, may have evidence of low-grade
  inflammation
• in HBV, may have ground glass appearance due to
  virus particles
• Acute hepatitis
• hydropic degeneration
• chronic inflammation
• necrosis of individual cells

• Fulminant hepatitis or hepatic failure
• extensive necrosis
• Chronic hepatitis
• see those changes seen in acute but more severe
  damage
• disorganized
• more intense inflammatory reaction
• more extensive necrosis
• scar tissue

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Autoimmune Hepatitis

• About 20 of cases of chronic hepatitis
• Not associated with viral infection
• Mostly in young women
• High titers of autoantibodies
• antinuclear
• anti-smooth muscle
• anti-mitochondrial
• In about ½ of the cases, they have an autoimmune
  disease

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Liver Abscess

• Focal collection of necrotic tissue, inflammatory
  debris, fluid
• Rare in industrialized nations
• usually due to bacteria or fungi
• Most caused by E. histolytica

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Toxic Liver Injury

• Symptoms from imperceptible to fatal onset from
  instantaneous to weeks after exposure
• Mild injury
• asymptomatic
• modest elevation of enzymes
• Severe injury
• hepatic failure
• hepatic coma
• death
• Dose related reactions
• damage certain if enough chemicals present
• uncommon
• suicidal doses of acetaminophen
• Unpredictable toxic injury
• damage out of proportion to the dose
• cannot metabolize a chemical as well as others
• may initiate autoimmune hepatitis
• drugs involved include
• sulfonamides
• isoniazid

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Alcoholic Liver Disease

• Alcoholism is the leading cause of liver disease
  in industrialized nations
• About 20 million Americans abuse alcohol
• About 25 of hospitalized patients have some
  alcohol-related problem
• Amount necessary to produce cirrhosis is about
  200gms/day for 10-16 years
• Sequence of damage
• fatty liver
• alcoholic hepatitis
• cirrhosis

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Fatty Liver

• 1st sign of alcohol injury
• aka steatosis
• Can be 2-3X its size, yellow, greasy
• Usually asymptomatic
• May have elevated enzymes
• Histologically, see Councilman bodies, Mallory
  bodies

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Alcoholic Hepatitis

• Subacute or chronic form of alcohol liver injury
• Characterized by inflammation, necrosis, early
  fibrosis
• Can progress to cirrhosis
• Clinically
• malaise
• anorexia
• RUQ pain
• jaundice
• elevated enzymes
• leukocytosis
• Each bout has 10-20 chance of death from
• liver disease
• intestinal hemorrhage
• pancreatitis
• Severe damage if
• abnormal clotting tests
• low albumin
• signs of hepatic failure
• May not be reversible

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Alcoholic Cirrhosis

• Final irreversible stage of alcoholic liver
  disease
• Only about 15 of alcoholics develop
• One of the leading causes of liver
  transplantation in US

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Hemochromatosis

• Toxic accumulation of iron in cells, especially
  liver, heart, pancreas
• Primary
• inherited autosomal recessive disorder
• abnormally high absorption of Fe from intestine
• one of the most common inborn errors of
  metabolism in US
• Secondary
• acquired
• usually due to repeated transfusions given for
  sickle cell, thalassemia, aplastic anemia
• chelate it to an excretable form

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• Takes years to accumulate enough Fe to cause
  damage

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• Cirrhosis if untreated
• Diagnosis depends on
• clinical features
• increased blood levels of Fe, ferritin,
  transferrin
• confirmed by liver biopsy
• Primary
• regular phlebotomy
• Secondary
• chelation of Fe

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Wilson Disease

• Autosomal recessive disorder
• Toxic accumulation of copper mainly in brain
  liver
• Copper absorbed in GI tract excreted in bile
• albumin transports to liver
• bound to ceruloplasmin then secreted
• if biliary excretion decreases, accumulates in
  liver brain
• Manifests as behavioral oddities, psychosis,
  tremors, abnormal gait
• Diagnosis confirmed by liver biopsy
• Early diagnosis critical
• Chelation therapy

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Hereditary Alpha-1-Antitrypsin Deficiency

• Protein made by liver
• Accumulate excessive amounts of defective AAT in
  liver
• Only 10 of patients develop clinically
  significant liver disease

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Primary Biliary Cirrhosis

• Autoimmune disease
• Usually have another autoimmune disease
• Evolves from inflammatory destruction of
  intrahepatic bile ducts
• Early on see accumulation of lymphocytes around
  bile ducts
• Death due to hepatic failure portal HTN

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Primary Sclerosing Cholangitis

• Chronic liver disease
• 2/3 of patients have ulcerative colitis
• Inflammation fibrosis of intrahepatic
  extrahepatic bile ducts
• Typical patient is male under 40 with
  long-standing ulcerative colitis

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Circulatory Disorders

• Portal vein obstruction as it flows into the
  liver
• changes similar to portal HTN caused by cirrhosis
• usually due to thrombosis
• As it flows through the liver
• most common cause is chronic passive congestion
  usually with R heart failure
• Obstruction in the hepatic vein as it flows out
  of the liver
• hepatic vein thrombosis
• Infarcts uncommon

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Metastatic Carcinoma

• Most common neoplasm in the liver
• Usually from colon, lung, breast

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Hepatocellular Carcinoma

• Usually related to HBV HCV
• Hematogenous metastases are common
• High levels of alpha fetoprotein
• Prognosis is grim

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Cholelithiasis

• Gallstones in the gallbladder or biliary tree
• Form in gallbladder
• Usually have multiple stones
• About 1 million new cases/yr in US
• 50 require surgery

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• Cholesterol gallstones
• 80 of cases
• Bile saturated with cholesterol
• Conditions associated with their development
• age gender
• weight
• ethnic, hereditary, geographic factors
• drugs
• acquired conditions

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• Pigment gallstones
• 20 of cases
• Form in gallbladder in biliary tree
• Composed of bilirubin bile substances other
  than cholesterol

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• Usually no symptoms until they begin to move
  mid-size stones are the worst
• Painful cramps in RUQ
• Nausea/vomiting
• Complications include
• cholecystitis
• pancreatitis
• perforation
• empyema of gallbladder

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Acute Cholecystitis

• Most common major complication of gallstones
• 90 associated with obstruction of the neck
• Gallbladder is enlarged, tense, inflamed
• Persistent rather mild RUQ pain to very severe
  pain

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Chronic Cholecystitis

• Do not have to have a history of acute attacks
• Almost always associated with gallstones although
  obstruction not necessary
• Mild to moderate RUQ pain
• Nausea/vomiting
• Intolerance of fatty foods

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Obstruction of the Extrahepatic Bile Ducts