Drug-Induced Hepatic Injury Exam 3 Flashcards

1
Q

What supplies the liver with blood?

A
  • portal vein

- hepatic artery

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2
Q

portal vein

A
  • 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
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3
Q

hepatic artery

A

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

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4
Q

sinusoids

A

where the blood from the hepatic artery and portal vein mixes

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5
Q

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

A

oxygen content diminishes

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6
Q

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

A
  • Hepatic lobule

- Acinus

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7
Q

Hepatic lobule

A
  • 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.
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8
Q

What makes up the portal triad?

A
  • portal vein
  • common bile duct
  • hepatic artery
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9
Q

Acinus

A

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

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10
Q

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

A
  • Hepatocytes
  • Endothelial cells
  • Kupffer cells
  • Stellate (Ito) cells
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11
Q

Hepatocytes component

A
  • liver parenchyma cells

- make up 80% of liver mass

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12
Q

Functions of hepatocytes

A
  • Glycogen storage and gluconeogenesis
  • Formation of bile and biliary excretion
  • Biotransformation and detoxification
  • Synthesis of plasma proteins (clotting factors, protein)
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13
Q

Endothelial cells characteristics

A
  • Thin and fenestrated
  • Carrying blood; secrete cytokines
  • May produce reactive oxygen and nitrogen compounds in response to various stimuli
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14
Q

Kupffer cells function

A
  • 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
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15
Q

Stellate (Ito) cells function

A
  • 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
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16
Q

presenting symptoms of hepatic damage

A
  • Fatigue
  • Anorexia
  • Nausea
  • Vomiting
  • Weight loss
  • Abdominal pain
  • Ascites and portal hypertension; also peripheral edema
  • Dark urine and/or jaundice (bilirubin)
17
Q

What are tests that are indicative of hepatic damage?

A
  • Elevated liver-specific enzymes
  • Jaundice from elevated bilirubin; itching
  • Low plasma albumin or increased prothrombin time
18
Q

Elevated (relatively) liver-specific enzymes

A
  • transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for hepatocyte injury
  • alkaline phosphatase for bile duct injury
19
Q

Jaundice

A

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

20
Q

Coagulation in hepatic damage

A

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

21
Q

Therapy for DILI

A
  • 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