Drug-Induced Hepatic Injury Exam 3

Question 1

What supplies the liver with blood?

Answer 1

• portal vein

- hepatic artery

Question 2

portal vein

Answer 2

• approximately 75% of the blood supply to the liver is derived from the portal vein, which drains the intestinal tract, spleen, and pancreas
• blood is enriched with nutrients and other absorbed xenobiotics and is poor in oxygen

Question 3

hepatic artery

Answer 3

the remainder of the hepatic blood flow (~25%) comes from the hepatic artery, which delivers well-oxygenated blood from the systemic circulation

Question 4

sinusoids

Answer 4

where the blood from the hepatic artery and portal vein mixes

Question 5

How does oxygen content change going from the portal area to the central hepatic vein?

Answer 5

oxygen content diminishes

Question 6

What are the concepts that help describe the appearance and function of the liver?

Answer 6

• Hepatic lobule

- Acinus

Question 7

Hepatic lobule

Answer 7

• A hexagon with the central vein at the center and the portal triads at the angles.
• The portal triad
• Cords of hepatocytes are oriented radially around the central hepatic vein.

Question 8

What makes up the portal triad?

Answer 8

• portal vein
• common bile duct
• hepatic artery

Question 9

Acinus

Answer 9

Located between two central veins and subdivided into three metabolically distinct zones: Zone 1, 2, 3

Question 10

What are the cells and cell types that make up the liver?

Answer 10

• Hepatocytes
• Endothelial cells
• Kupffer cells
• Stellate (Ito) cells

Question 11

Hepatocytes component

Answer 11

• liver parenchyma cells

- make up 80% of liver mass

Question 12

Functions of hepatocytes

Answer 12

• Glycogen storage and gluconeogenesis
• Formation of bile and biliary excretion
• Biotransformation and detoxification
• Synthesis of plasma proteins (clotting factors, protein)

Question 13

Endothelial cells characteristics

Answer 13

• Thin and fenestrated
• Carrying blood; secrete cytokines
• May produce reactive oxygen and nitrogen compounds in response to various stimuli

Question 14

Kupffer cells function

Answer 14

• aka fixed macrophages
• Scavenge cell debris, particulates, endotoxin, etc
• Secretion of cytokines (e.g. tumor necrosis factor) and reactive oxygen and nitrogen radicals in response to endotoxin lipopolysaccharide (LPS) or ischemiareperfusion

Question 15

Stellate (Ito) cells function

Answer 15

• Primary site for storage of fat and vitamin A
• Produce collagen, proteoglycans, and adhesive glycoproteins
• Are causal in fibrosis and are associated with the development of cirrhosis

Question 16

presenting symptoms of hepatic damage

Answer 16

• Fatigue
• Anorexia
• Nausea
• Vomiting
• Weight loss
• Abdominal pain
• Ascites and portal hypertension; also peripheral edema
• Dark urine and/or jaundice (bilirubin)

Question 17

What are tests that are indicative of hepatic damage?

Answer 17

• Elevated liver-specific enzymes
• Jaundice from elevated bilirubin; itching
• Low plasma albumin or increased prothrombin time

Question 18

Elevated (relatively) liver-specific enzymes

Answer 18

• transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for hepatocyte injury
• alkaline phosphatase for bile duct injury

Question 19

Jaundice

Answer 19

development of jaundice in association with evidence of hepatocellular damage is a poor prognostic sign with a greater than 10% incidence of death of the patient

Question 20

Coagulation in hepatic damage

Answer 20

no improvement in coagulation status after administration of vitamin K also is a poor prognostic sign

Question 21

Therapy for DILI

Answer 21

• stop administration of suspected drug
• cholestyramine to increase bile salt excretion to help with the itching
• Ascites, etc. are treated medically
• Acetylcysteine may help in cases of hepatic damage by acetaminophen
• liver transplant