Pathology: Liver, Gallbladder, And Exocrine Pancreas

Front 1

Physiologic jaundice of the newborn

Back 1

- noted in first week of life
- not usually clinically important
- increased bilirubin production and a relative deficiency of glucuronyl transferase in the immature liver
- exaggerated in premature infants

Front 2

Important differential of physiologic jaundice of the newborn

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Neonatal cholestasis - due to extrahepatic biliary atresia, alpha1-antitrypsin deficiency, CMV and many other conditions

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Gilbert syndrome

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- 5% of the population
- familial disorder characterized by a modest elevation of serum unconjugated bilirubin due to decreased bilirubin uptake by liver cells and reduced activity of glucuronyl transferase

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Crigler-Najjar syndrome

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- severe familial disorder characterized by unconjugated hyperbilirubinemia caused by a deficiency of glucuronyl transferase
- severe form --> kernicterus
- less-severe form --> treated by phenobarbital therapy

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Dubin-Johnson syndrome

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- AR form of conjugated hyperbilirubinemia characterized by defective bilirubin transport
- characterised by brown-to-black discoloration of the liver

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Rotor Syndrome

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Similar to Dubin-Johnson but not discolouration

Front 7

Which viruses can cause an acute viral hepatitis

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Hep A, B & C, CMV & EBV - all of which are RNA viruses except Hep B (DNA)

Front 8

How is HepA transmitted?

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Fecal-oral i.e close personal contact and contaminated food and water; parenteral infection has been documented to occur (rare)

Front 9

What is the incubation period of HAV?

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15-45 days, 3-6 weeks

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What kind of virus is HepA? And how do you diagnose a current illness? What are some rare complications of HAV?

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RNA picornavirus, 27nm RNA virus, single serotype worldwide, acute disease and asymptomatic; clinically as well as HAV IgM; fulminant hepatitis, relapsing hepatitis, cholestatic hepatitis

Front 11

What is the complete HBV virus particle also known as?

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The Dane particle

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What does the HepB virus consist of?

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A central core containing the viral DNA genome, DNA polymerase, hepatitis B core antigen (HBcAg), heptatitis B e entigen (HBeAg) and an outer lipoprotein coat containing the hepatitis B surface antigen (HBsAg)

Front 13

How is HBV transmitted?

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Parenteral, sexual and vertically

Front 14

What is the incubation period of HBV?

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60-90 days

Front 15

T/F HBV has a major association with hepatocellular carcinoma

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T

Front 16

Which virus is associated with the 'ground glass' appearance of hepatocytes?

Back 16

HBV

Front 17

Which of the antigens appear in serum before the onset of clinical findings?

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HBsAg - appears in serum some weeks before the onset of clinical findings, then decreases and generally persists for a total of 3-4 months - persistence as detectable serum antigen for more than 6 months denotes the carrier state. HBsAg elicits an antibody response (anti-HBsAg); antibody appears a few weeks after the disappearance of the antigen and indicates recovery, as well as immunity to future infection

Front 18

HBeAg

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Appears shortly after HBsAg and disappears before HBsAg - closely correlated with viral infectivity

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Anti-HBcAg

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Appears 4 weeks after the appearance of HBsAg is present during the acute illness and can remain elevated for several years - it is a marker of hepatitis infection during the "window period" between the disappearance of HBsAg and the appearance of anti-HBsAg

Front 20

HBV DNA

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can also be detected in serum and is an index of infectivity

Front 21

Can HBV be transmitted by breast milk?

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No

Front 22

What are the causes of chronic hepatitis?

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HBV, HCV, HDV autoimmune hepatitis, hemochromatosis, wilson's disease, alpha1-antitrypsin

Front 23

HDV

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HDV is replicatively defective, requiring simultaneous infection with HBV for replication (uses HBV's viral coat i.e. HBsAg)

Front 24

HEV

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Enterically transmitted form of viral hepatitis similar to HAV infection that occurs in water-borne epidemic form in underdeveloped countries. HEV has a high incidence of mortality (20%) when occurring in pregnancy

Front 25

What are the symptoms of viral hepatitis?

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- jaundice
- fatigue
- abdo pain
- loss of appetite
- nausea, vomiting and diarrhea
- low grade fever
- headache

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What type of virus is HCV?

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Human flavivirus, 6 distinct genotypes; 1b and 3a predominate in Australia

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HGV

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affects 1-2% of healthy blood donors but its pathologic significance is questionable

Front 28

What is autoimmune hepatitis clinically marked by?

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hypergammaglobulinemia and anti-smooth muscle antibodies

Front 29

Which virus causes an 'owl's eye appearance'?

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CMV

Front 30

Neonatal hepatitis

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Multinucleated giant cells; bile pigment and hemosiderin within parenchymal cells; may cause jaundice during the first few weeks of life

Front 31

HSV-1 in the liver?

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In infants and immunocompromised persons

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What do dying hepatocytes commonly exhibit?

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Councilman bodies - dying hepatocytes often condense into eosinophilic contracted forms

Front 33

Schistosomiasis

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Adult worms lodge in the portal vein and its branches - the eggs are highly antigenic and stimulate granuloma formation with resultant tissue destruction, scarring and portal hypertension

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Echinococcus granulosus

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Ingestion of tapeworm eggs from the excreta of dogs and sheep results in hyatid disease of the liver - in which large parasitic cysts invade the liver

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What are three causes of microvesicular fatty liver?

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Reye syndrome, (caused by administering aspirin to children with acute viral infections), fatty liver of pregnancy, tetracycline toxicity

Front 36

What are the three stages of alcoholic liver disease?

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1. Fatty change (reversible) - nonalcoholic fatty liver disease or NAFLD is related but unrelated to alcohol consumption
2. Alcoholic hepatitis
3. Alcoholic cirrhosis

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Alcoholic hepatitis

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Characteristics include fatty change, focal liver cell necrosis, infiltrates of neutrophils and the presence of intracytoplasmic eosinophilic hyaline inclusions (Mallory bodies) - these are not entirely specific for alcoholic hepatitis

Front 38

Where is the irreversible fibrosis of alcoholic hepatitis located?

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Surrounds central veins -- perivenular fibrosis

Front 39

Why do cirrhotics get retention of sodium and water?

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Aldosterone not degraded & activation of RAAS

Front 40

What causes encephalopathy in a cirrhotic?

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Accumulation of ammonia and other enteric degradation products

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What is the pattern of alcoholic cirrhosis?

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Micronodular --> hobnail liver with large, irregular nodules

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What causes macronodular cirrhosis?

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Postnecrotic (macronodular) = posthepatitic
leads to HCC more often than other types of cirrhosis

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Causes of biliary cirrhosis

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Primary and secondary

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Primary Biliary Cirrhosis

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- typically middle aged women
- autoimmune etiology 0 antimitochondrial antibodies are characteristics
- severe obstructive jaundice, itching, and hypercholesterolemia (xanthoma formation)
- increased parenchymal copper concentration of unknown significance

Front 45

Primary sclerosing cholangitis

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- rare except in association with IBD
- eventually develops into biliary cirrhosis
- associated increased incidence of cholangiocarcinoma

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Budd-Chiari

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-thrombosis of the major hepatic vv
-associated with PV, HCC and other abdominal neoplasms; also pregnancy

Front 47

Nutmeg liver is associated with...

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Right-sided heart failure, congested centrilobular areas

Front 48

What are benign tumors of the liver?

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Hemangioma and adenoma (related to OCP, if subcapsular in location, may rupture and result in severe intraperitoneal hemorrhage)

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What are the majority of hepatic malignancies?

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Metastases

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HCC

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Associated with preexisting cirrhosis of any kind, especially when associated with HBV infection; associated with aflatoxin B1 contamination thought to cause point mutations in p53 gene; alpha-fetoprotein, propensity for invasion of vascular channels with hematogenous dissemination

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Cholangiocarcinoma

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- Associated with clonorchis sinensis (liver fluke) infestation
- Originates from intrahepatic biliary epithelium
- Has a propensity for early invasion of vascular channels
- Occurs as a late complication of thorium dioxide (thorotrast)

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Hemangiosarcoma

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- associated with toxic exposure to polyvinyl (vinyl) chloride, thorium dioxide and arsenic

Front 53

What proportion of stones are mixed?

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75-80%

Front 54

Which stones can be visualised on xray?

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Mixed - due to their calcium content

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What causes pancreatitis?

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Gallstones and excessive alcohol intake

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What are the characteristics of acute pancreatitis?

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Hemorrhagic fat necrosis, deposition of calcium soaps, pseudocysts and autodigestion of the organ

Front 57

Which electrolyte is commonly affected by pancreatitis?

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Calcium -- you get hypocalcemia

Front 58

Chronic pancreatitis

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Progressive parenchymal fibrosis, calcification, pseudocysts - almost always associated with alcoholism

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Risk factors for carcinoma of the pancreas

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Smoking

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Clinical manifestations of pancreatic cancer

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Abdominal pain radiating to the back, weight loss and anorexia, migratory thrombophlebitis, common bile duct obstruction resulting in obstructive jaundice (accompanied by a distended, palpable gallbladder)