hepatocytes
b. Apoptosis of hepatocytes (Councilman's bodies) 2. Microscopic findings in chronic viral hepatitis
a. Inflammation disrupts the normal demarcation between the portal triad and hepatocytes located around the portal triad (piecemeal necrosis).
Most common cause of massive hepatic necrosis:
viral hepatitis
224 Pathology
Senescent RBC Globin chain splits off Macrophage - Heme
Iron
Unbound unconjugated bilirubin (lipid soluble) Blood -[
Unconjugated bilirubin (bilirubin + albumin) UGT
Liver -
Conjugated bilirubin (water soluble) Secreted into bile
Bowel -
Urobilinogen 80% Urobilin (color of stool) 20%
Enterohepatic circulation
Liver (90%) Kidneys (10%) —)-Urobilin (color of urine) Figure 18-1 Bilirubin metabolism. RBC, red blood cell; UGT, uridine glucuronosyltransferase
b. Fibrosis connects a portal triad to another portal triad or the portal triad to the central vein.
B. Phases of acute viral hepatitis
1. Prodrome: fever, hepatomegaly; steadily increasing serum transaminases, which peak just before jaundice occurs; atypical lymphocytosis
2. Icteric: severity of jaundice varies depending on the type of hepatitis; bilirubinuria, increased urine urobilinogen
3. Recovery: jaundice resolves.
C. Transmission and clinical features (Table 18-3); acute hep- atitis becomes chronic when symptoms last more than 6 months.
D. Serology
1. Hepatitis A virus (HAV)
a. IgM anti-HAV indicates active infection.
b. IgG anti-HAV indicates recovery from infection or vaccination (protective antibody).
2. Hepatitis B virus (HBV) (Figure 18-2; Table 18-4) a. Hepatitis B surface antigen (HBsAg)
(1) Appears within 2-8 weeks; first marker of infection
(2) Persists up to 4 months in acute HBV and more than 6 months in chronic HBV b. Hepatitis B e antigen (HBeAg) and HBV DNA
(1) Infective particles; appear after HBsAg and disappear before HBsAg
Most common type of hepatitis associ- ated with accidental needlestick and in- travenous drug use:
HBV
Chapter 18 Hepatobiliary and Pancreatic Disorders 225
TABLE 18-2 Causes of Jaundice
Type of Urine Urine
Hyperbilirubinemia Bilirubin Urobilinogen Examples of Disorders Unconjugated
Conjugated bilirubin
< 20%
Increased produc- Absent 1. Extravascular hemolytic anemias:
tion of unconju- congenital spherocytosis, Rh and
gated bilirubin ABO hemolytic disease of newborn
Destruction of RBCs in bone marrow:
severe j3-thalassemia, deficiencies of vitamin B 12 and folate
Decreased conjuga- Absent Normal Gilbert syndrome: genetic defect in tion of unconju- uptake of bilirubin; jaundice occurs
gated bilirubin with fasting
Crigler-Najjar syndrome: genetic disorder caused by decrease in conjugating enzymes
Physiologic jaundice of newborn:
begins on day 3 of life (caused by destruction of fetal RBCs) Mixed
Conjugated bilirubin T T Viral hepatitis: also a defect in uptake
20-50% of bilirubin
Obstructive
Conjugated bilirubin T
> 50%
Absent Decreased intrahepatic bile flow Drug-induced (e.g., oral contra-
ceptives)
Primary biliary cirrhosis
Dubin-Johnson syndrome: genetic defect in secretion into intrahe- patic bile ducts; black pigment in hepatocytes
Rotor's syndrome: similar to Dubin-Johnson syndrome but without black pigment in hepatocytes
Decreased extrahepatic bile flow Gallstone in common bile duct Carcinoma of head of pancreas RBCs, red blood cells.
(2) Presence for more than 6 months in conjunc- tion with HBsAg indicates an infective chronic carrier.
c. IgM anti-HBV core antibody (IgM anti-HBc) (1) Nonprotective antibody; remains positive in
acute and chronic infections.
(2) Persists during the "window phase," or "se- rologic gap," when HBsAg, HBV DNA, and HBeAg are absent
(3) Converts to IgG anti-HBc when there is no viral replication
...anti-HBcIgG
•..
anti-HBs HBsAg...
226 Pathology
TABLE 18-3 Viral Hepatitis: Transmission and Clinical Findings Virus Transmission Clinical Findings
Hepatitis A Fecal-oral
Hepatitis B Parenteral, sexual, vertical
No carrier state; does not lead to chronic hepatitis
Occurs in day care centers, prisons, travelers to developing countries, and male homo- sexuals
Carrier state; becomes chronic in 10% of immunocompetent patients
Serum sickness prodrome (5-10%): vasculitis (polyarteritis nodosa), polyarthritis, glomerulonephritis (membranous) Increased incidence of hepatocellular
carcinoma
Hepatitis C Parenteral, sexual Carrier state; becomes chronic in > 70% of cases
Associated with posttransfusion hepatitis, type I membranoproliferative glomerulo- nephritis, alcohol excess
Hepatitis D Parenteral, sexual Carrier state; chronic state less likely with coinfection than superinfection; requires hepatitis B surface antigen to replicate Hepatitis E Fecal-oral (waterborne) No carrier state or chronic hepatitis; fulmi-
nant hepatitis may develop in pregnant women
Occurs in developing countries Hepatitis G Parenteral Carrier state
No chronic hepatitis
12 24
/
Serologic gap Jaundice
Symptoms
HBeAg
HBV DNA anti-HBe
,••
3 4 5 6 112 214
Months after exposure
Figure 18-2 Serologic markers in hepatitis B Anti-HBc, anti-HBV core antigen; anti-HBe, anti-HBV e antigen; anti-Has, anti-HBV surface antibody; HBsAg, hepatitis B surface antigen;
HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; IgG, immunoglobulin G; /gM, immunoglobulin M
Chapter 18 Hepatobiliary and Pancreatic Disorders 227
TABLE 18-4 Serologic Studies in Hepatitis B
HBeAg, IgM IgG
HBsAg HBV DNA Anti-HBc Anti-HBc Anti-HBs Interpretation
+ - Earliest phase of acute HBV
+ + + - Acute or chronic HBV
- + - - Window phase (serologic gap)
- - + + Recovery from HBV
- - - + Immunization against HBV
HBV, hepatitis B virus.
d. Anti-HBV surface antibody (anti-HBs): protective antibody; only marker of immunization after HBV vaccination
e. Chronic HBV: persistence of HBsAg more than 6 months (1gM anti-HBc remains positive)
(1) "Healthy" chronic carriers: presence of HBsAg and absence of infective particles (HBV DNA, HBeAg)
(2) Infective chronic carriers: presence of both HBsAg and infective particles (HBV DNA, HBeAg); increased risk of cirrhosis and hepa- tocellular carcinoma
3. Hepatitis C virus (HCV): presence of IgG or IgM anti- HCV indicates infection.
4. Hepatitis D virus (HDV): presence of IgG or IgM anti- HDV indicates active infection.
5. Hepatitis E virus (HEV): presence of 1gM anti-HEV in- dicates active infection; IgG anti-HEV indicates recovery (protective antibody).
E. Vaccination against HBV decreases the risk of HBV and HDV and decreases the risk of hepatocellular carcinoma.
III. Other Inflammatory Hepatic Disorders A. Autoimmune hepatitis
1. Occurs most often in young women
2. Clinical findings: fever, jaundice, hepatosplenomegaly 3. Laboratory findings: positive serum antinuclear anti-
body, anti—smooth muscle antibodies B. Neonatal hepatitis
1. Idiopathic or associated with infections (e.g., cyto- megalovirus) or inborn errors of metabolism (e.g., galactosemia)
2. Characterized by the presence of multinucleated giant cells
C. Reye's syndrome
1. Usually develops in children younger than 4 years of age; often follows chickenpox or influenza
228 Pathology
TABLE 18-5 Some Infectious Diseases That Affect the Liver Disease Causal Pathogen(s) Characteristics
Entamoeba histolytica Escherichia coli in adults,
Streptococcus pneumoniae in children
Mycobacterium tuberculosis, Histoplasma capsulatum Echinococcus granulosus
(sheepherder's disease) Schistosoma mansoni Eggs incite a fibrotic response
in the portal vein ("pipestem cirrhosis")
Amebiasis; abscess usually involves right lobe Develops in ascites (e.g.,
cirrhosis, nephrotic syndrome)
Sign of miliary spread Single or multiple cysts
containing larval forms Complications of cirrhosis:
portal hypertension, ascites, and esophageal varices Liver abscess
Spontaneous peritonitis Granulomatous
hepatitis Echinococcosis Schistosomiasis
2. Pathogenesis: mitochondrial damage (may be caused by viral infection or salicylates), with disruption of the urea cycle (increase in serum ammonia) and defec- tive 13-oxidation of fatty acids
3. Pathology: microvesicular type of fatty liver (small cytoplasmic globules without nucleus displacement) 4. Clinical findings: encephalopathy (cerebral edema,
coma, convulsions); hepatomegaly
5. Laboratory findings: elevated serum transaminases (ALT > AST), normal to slightly elevated total bilirubin D. Other infectious diseases affecting the liver (Table 18-5) IV. Circulatory Disorders of the Liver
A. Prehepatic obstruction to blood flow