Pathology of the liver, biliary tract and pancreas

Question 1

Major characteristics of hepatic failure (3)

Answer 1

1. Hepatic encelopathy
2. Hepatorenal syndrome
3. Hemorrhagic diathesis
4. Hepatopulmonary syndrome
5. Hepatic cardiomyopathy

Question 2

Hepatic failure: clinical features

Answer 2

• Jaundice
• Malabsorption/weight loss
• Hypoalbuminema
• Hyperammonemia: decreased urea cycle
• Hyperestrogenemia: impaire estrogen metabolism
• Palmar erythema and spider angiomas in the skin
• Ascites, splenomegaly, gastroesophageal varices: due to portal HTN

Question 3

Difference in mechanisms of acute and chronic hepatic failure in causing hepatic encelopathy

Answer 3

Acute: elevated blood ammonia impairs the neuronal functioning and promotes brain edema

Chronic: altered amino acid metabolism causes deranged neurotransmission

Question 4

Major alterations that cause liver failure

Answer 4

1. Chronic liver disease: liver cirrhosis
2. Acute liver disease: associated with hepatic necrosis
3. Reye syndrome: causes liver failure without necrosis

Question 5

Types of jaundice (3)

Answer 5

1. Prehepatic: caused by hemolytic anemia - too much hemoglobin is degraded
2. Hepatic: caused by any liver disease (Criggler-Najjar, Gilbert syndrome, Dubin-Johnson syndrome)
3. Posthepatic: problems with excretion of bile (gall stones, tumor etc.)

Question 6

Primary biliary cirrhosis: pathogenesis

Answer 6

Autoimmune disorder. Antimitochondrial antibodies target intrahepatic bile ducts, causing inflammation and cholestasis.

Serum ALP and cholesterol are elevated. Hyperbilirubinemia develops later.

Question 7

Primary sclerosing cholangitis: pathogenesis

Answer 7

Autoimmune disease targeting extrahepatic and large intrahepatic bile ducts.

Associated with IBD, especially ulcerative cholitis.

Question 8

Processes causing formation of cholesterol stones (4)

Answer 8

1. Supersaturation of bile with cholesterol
2. Nucleation into monohydrate crystals
3. Stasis in the gallbladder
4. Mucous hypersecretion traps the crystals

Question 9

Cholesterol stones: morphology

Answer 9

Two types:

1. Pure cholesterol stones: pale yellow
2. Cholesterol stones containing calcium carbonate, phosphates and/or bilirubin: grey-white-black

Question 10

Pigment stones: pathogenesis

Answer 10

Presence of unconjugated bilirubin, which can occur with hemolytic anemias and infections of the biliary tree. Precipitates are insoluble calcium bilirubinate salts.

Risk factors - the four Fs:

• Age (Forty)
• Gender (Female)
• Heridetary (Familial)
• Obesity (Fat)

Question 11

Differences between black and brown pigment stones

Answer 11

Black:

• Found in sterile GB bile
• Small; in large quantities
• Crumble easily
• Radiopaque

Brown:

• In infected ducts
• Occur singly or in small quantities
• Soft and greasy, due to presence of fatty acids
• Radiolucent

Question 12

Circulatory disorders of the liver (3)

Answer 12

1. Impaired flow into the liver: hepatic artery inflow or portal vein obstruction and thrombosis
2. Impaired flow through the liver
3. Hepatic vein outflow obstruction

Question 13

Causes of extrahepatic portal vein obstruction

Answer 13

• Peritoneal sepsis
• Pancreatitis
• Tumor

Question 14

Consequences of portal vein obstruction

Answer 14

• Abdominal pain
• Ascites
• Esophageal varices
• Intestinal congetion
• Splenomegaly

Question 15

Symptoms of impaired blood flow through in the liver

Answer 15

• Ascites (cirrhosis)
• Esophageal varices (cirrhosis)
• Hepatomegaly
• Elevated transaminases

Question 16

Causes of impaired blood flow through the liver

Answer 16

• Cirrhosis (most common)
• Sickle cell disease
• DIC (occludes sinusoids)

Question 17

Hepatic manifestations of right-sided heart failure

Answer 17

Enlarged, tense and cyanotic liver. Congestion of centrilobular sinusoids. Centrilobular hepatocytes atrophy.

Question 18

Hepatic manifestations of left-sided heart failure

Answer 18

Can cause hepatic hypoperfusion and hypoxia. Hepatocytes undergo ischemic necrosis.

Question 19

Causes of obstruction of the hepatic vein

Answer 19

• Hepatic vein thrombosis (Budd-Chiari syndrome): thrombosis of two or more hepatic veins
• Sinusoidal obstruction syndrome: caused by toxic injury to sinusoidal epithelium

Question 20

Hepatitis A

Answer 20

• Benign, self-limiting
• Causes acute hepatitis, never becomes chronic
• Fecal-oral transmission

Question 21

Hepatitis B

Answer 21

• Pareneteral transmission (blood and body fluids)

Stages:

1. Acute (IgM)
2. Window (non-progressive)
3. Resolved
4. Chronic (IgG)
5. Immunization

Question 22

Hepatitis C

Answer 22

• Pareneteral transmission
• Acute; often becomes chronic
• No vaccination

Question 23

Chronic hepatitis: etiology

Answer 23

• Wilson disease: inherited disorder where copper deposits
• alpha1-antitrypsin deficiency
• Chronic alcoholism
• Drugs
• Autoimmunity

Question 24

Forms of alcoholic liver disease (3)

Answer 24

1. Hepatic steatosis
2. Alcoholic hepatitis
3. Cirrhosis

Question 25

What are Mallory bodies?

Answer 25

Eosinophilic cytoplasmic inclusions in degenerating hepatocytes. Appear in cases of alcoholic hepatitis.

Question 26

Hemochromatosis

Answer 26

AR disorder characterized by excess iron storage. Mutation in the HFE-gene leading to impaired function of hepcidin which inhibits iron absorption. Iron is toxic to tissues. Clinically: abdominal pain, hepatomegaly, diabetes mellitus.

Question 27

Wilson disease

Answer 27

AR disorder of copper metabolism, in which copper deposits in mainly the liver, eyes and brain. Mutation in a gene encoding an ATPase metal ion transporter. Commonly presents as acute or chronic liver failure.

Question 28

α1-antitrypsin deficiency

Answer 28

AR disorder marked by abnormally low AAT levels. AAT works to inhibit proteases as sites of inflammation. Can cause emphysema in the lungs.

Question 29

Cirrhosis: pathogenesis

Answer 29

- Hepatocellular death - Regeneration - Progressive fibrosis - Vascular changes

Question 30

Tumor-like lesions of the liver (3 types of nodules)

Answer 30

1. Focal nodular hyperplasia: response to vascular injury causing parenchymal atrophy 2. Macroregenerative nodules: appear in cirrhotic livers 3. Dysplastic nodules: proliferative hepatocytes

Question 31

Benign tumors of the liver

Answer 31

- Hepatic cavernous hemangioma

Question 32

Hepatocellular cc: etiology

Answer 32

- HBV/HCV - Aflatoxin exposure - Chronic alcoholism/cirrhosis

Question 33

Classification of cholecystitis

Answer 33

- Acute (calculous) cholecytitis: usually due to obstruction by gallstones - Acute non-calculous cholecystitis: associated with infections, autoimmune vasculitis and trauma - Chronic cholecystitis

Question 34

Complications of cholecystitis

Answer 34

- Bacterial superinfection - Gallbladder perforation - Gallbladder rupture - Biliary enteric fistula

Question 35

Acute pancreatitis: pathogenesis

Answer 35

Inappropriate activation of pancreatic enzymes, due to: - Pancreatic duct obstruction - Primary acinar injury - Defective intracellular transport of proenzymes within acinar cells

Question 36

Chronic pancreatitis: pathogenesis

Answer 36

- Ductal obstruction - Toxic-metabolic - Oxidative stress - Necrosis fibrosis

Question 37

Types of chronic pancreatitis (3)

Answer 37

1. Chronic autoimmune pancreatitis 2. Chronic obstructive pancreatitis: periductal fibrosis, ductal dilation 3. Chronic fibrotizing pancreatits (most common): seen in chronic alcoholic patients