Chapter 10 - Hepatic Toxicology Flashcards

1
Q

The liver is the first organ to encounter all of the following except…

A. Waste products of gut bacteria

B. Inhaled gases

C. Ingested metals

D. Oral drugs

A

B. Inhaled gases

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2
Q

Zone 3 of the hepatic acinus is characterized by…

A. High bile acid conc.

B. Relative hypoxia

C. Proximity to the portal vein

D. Proximity to the hepatic artery

A

B. Relative hypoxia

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3
Q

Zone 1 of the hepatic acinus is chara by…

A. High levels of GSH

B. Higher levels of P450

C. Prox to hepatic vein

D. Low bile acid extraction

A

A. High levels of GSH

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4
Q

CYP 2E1 is highest in acinus zone…

A. 1

B. 2

C. 3

D. 4

A

C. 3

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5
Q

Decreased protein synthesis by the liver would cause all of the following conditions except…

A. Ascites

B. hypoglycemia

C. Bleeding

D. Increased free fraction of drug

A

C. Bleeding

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6
Q

All of the following are components of bile except…

A. Glutathione

B. cholesterol

C. Uric acid

D. Bilirubin

A

C. Uric acid

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7
Q

Bile acid formation plays a key role in all of the following except…

A. The innate immune system

B. Excretion of endogenous cmpds

C. Uptake of lipid nutrients from sm intestine

D. Protection of the sm intestine from ox stress

A

A. The innate immune system

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8
Q

Rats lacking functional MRP2 biliary exporter would be resistant to…

A. Fibrosis from EtOH

B. Intestinal ulceration from diclofenac

C. Carcinogenicity of androgens

D. Fatty liver from tamoxifen

A

B. Intestinal ulceration from diclofenac

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9
Q

A major site for vitamin A storage is…

A. Hepatocyte

B. cholangiocyte

C. Kupffer cell

D. Stellate cell

A

D. Stellate cell

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10
Q

Hepatic sinusoids are lined with all of the following except…

A. Stellate cells

B. Endothelial cells

C. Kupffer cells

D. Enterocytes

A

D. Enterocytes

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11
Q

All of the following are true of hepatic fenestrae except…

A. Molecules smaller than 250 kDa can cross

B. albumin can cross

C. The space between hepatocytes and endothelium is called the space of Disse

D. They are similar to pores in skeletal muscle

A

B. albumin can cross

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12
Q

Which of the following statements is true?

A. The liver cannot regenerate

B. Methylmercury is reabsorbed from the gallbladder

C. Zn toxicity is manifested by cholestasis

D. All of the above

A

B. Methylmercury is reabsorbed from the gallbladder

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13
Q

A transport pump that moves chemicals from hepatocytes into bile caniculi is…

A. OAT

B. BSEP

C. OCT

D. all of the above

A

B. BSEP

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14
Q

Which of the following statements is true?

A. Arsenic is enterohepatically recirculated

B. Microcystin disrupts the hepatic cytoskeleton

C. Billary epithelial cells possess biotransformation enzymes

D. All of the above

A

D. All of the above

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15
Q

The most common cause of fatty liver is…

A. Valproic acid

B. fialuridine

C. Insulin resistance

D. CCL4

A

C. Insulin resistance

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16
Q

All of the following statements are true regarding steatosis and steatohepatitis except…

A. Cyclohexamide causes fat accum. and cell necrosis

B. Steatohepatitis can progress to fibrosis

C. The presence of steatosis can make the liver more sensitive to other insults

D. Steatohepititis can progress to hepatocellular carcinoma

A

A. Cyclohexamide causes fat accum. and cell necrosis

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17
Q

Dilation of the hepatic sinusoid or peliosis hepatis is caused by…

A. Aminodarone

B. danazol

C. Tetracycline

D. Halothane

A

B. danazol

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18
Q

Vanishing bile duct syndrome is asso w/ all of the following except…

A. Ethanol

B. carbamazepine

C. Anabolic steroids

D. Contraceptive steroids

A

A. Ethanol

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19
Q

All of the following have been shown to inhibit the bile salt export pump (BSEP) except…

A. Rifampicin

B. Bosentan

C. Troglitazone

D. Acetominophen

A

D. Acetominophen

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20
Q

In the liver, the difference between oncotic necrosis and secondary necrosis is…

A. Cell swelling

B. Cell content release

C. Identification of apoptotic cells

D. None of the above

A

C. Identification of apoptotic cells

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21
Q

A pancaspase inhibitor would be expected to…

A. Prevent apoptosis-induced liver injury

B. induce oncotic liver injury

C. Deplete cellular ATP by damaging the mitochondrial membrane

D. None of the above

A

A. Prevent apoptosis-induced liver injury

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22
Q

Vitamin C causes…

A. Fatty liver

B. canalicular cholestasis

C. Bile duct damage

D. None of the above

A

D. None of the above

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23
Q

Drug-induced steatosis is mainly caused by cmpds that…

A. Accum in lysozymes and break down cellular lipids

B. Accum in mito and inhibit beta-oxidation

C. Accum in cytosol and stim lipid synth

D. None of the above

A

B. Accum in mito and inhibit beta-oxidation

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24
Q

Bile duct and gallbladder cancer is increased in individuals exposed to…

A. Phenacetin

B. bromobenzene

C. Vinyl chloride

D. Radioactive thorium dioxide

A

D. Radioactive thorium dioxide

25
Q

All of the following statements are true regarding hepatocellular carcinoma except…

A. Malignant trans can result from increased cell turnover and persistent inflammation

B. DNA mods leading to activation of oncogenes

C. The cancer cells are highly sensitive to alkylating chemotherapy

D. Stimulation of prolif expands preneoplastic population prior to transformation

A

C. The cancer cells are highly sensitive to alkylating chemotherapy

26
Q

Central to the development of fibrosis is…

A. Activation of hepatic stellate cells

B. Suppression of Kupffer cells

C. Stimulation of antibody response

D. Formation of DNA adducts

A

A. Activation of hepatic stellate cells

27
Q

All of the following are true regarding hepatic fibrosis except…

A. Stimulation of apop in causative cells may lead to gradual reversal

B. It is caused by increased membrane collagen type 4

C. It can interfere with the exchange of nutrients and waste material

D. Viral hepatitis is the primary cause of hepatic fibrosis/cirrhosis worldwide

A

B. It is caused by increased membrane collagen type 4

28
Q

Iron overload causes preferential damage in…

A. Zone 1 hepatocytes

B. Zone 2 hepatocytes

C. Zone 3 hepatocytes

D. Zone 4 hepatocytes

A

A. Zone 1 hepatocytes

29
Q

Methylene dianiline is preferentially toxic to…

A. Hepatocytes

B. stellate cells

C. Kupffer cells

D. Bile duct cells

A

D. Bile duct cells

30
Q

Cadmium hepatotoxicity is related to…

A. Valence of cadmium ion

B. Induction of CYP2E1

C. Saturation of metallothionein with cadmium

D. Low serum iron

A

C. Saturation of metallothionein with cadmium

31
Q

The hepatic toxicity of acetominophenis enhanced by all of the following except…

A. Malnutrition

B. fasting

C. Induction of CYP2E1

D. Hypertension

A

D. Hypertension

32
Q

Steatosis from chronic alcohol consumption is thought to result from…

A. Stimulation of beta-oxidation of fatty acids

B. excess supply of acetate and NADH

C. Excess supply of pyruvate and NADP+

D. Inhibitory effect of acetaldehyde on fatty acid breakdown

A

B. excess supply of acetate and NADH

33
Q

Which of the following is an important factor in the pathology of alchohol-induced liver disease?

A. Inflammation

B. Lipid peroxidation

C. Oxidative stress

D. All of the above

A

D. All of the above

34
Q

Allyl alcohol is metabolized by ADH to..

A. Benzaldehyde

B. Acrolein

C. Acetic anhydride

D. Butyraldehyde

A

B. Acrolein

35
Q

Endotoxin and GdCl3 preferentially activate…

A. Stellate cells

B. Kupffer cells

C. Zone 3 hepatocytes

D. Bile duct cells

A

B. Kupffer cells

36
Q

Most of a therapeutic dose of acetaminophen is…

A. Metabolized to NAPQI

B. acetylated

C. Conjugated with glycine

D. None of the above

A

D. None of the above

37
Q

Which of the following express the recent thinking with respect to neutrophils and liver damage?

A. Detrimental liver effects can occur from neutrophil mobilization to other organs

B. injury occurs by the killing of distressed cells that would otherwise survive

C. Neutrophils participate in the same way in all types of toxic liver injury

D. Damage is exacerbated by the mass killing of healthy liver cells

A

B. injury occurs by the killing of distressed cells that would otherwise survive

38
Q

All of the following cause nonimmune idiosyncratic liver toxicity except…

A. Tienilic acid

B. isoniazid

C. Aminodarone

D. Ketoconazole

A

A. Tienilic acid

39
Q

All of the following statements are true regarding idiosyncratic drug-induced hepatotoxicity except…

A. Involves failure to adapt to mild drug advese effect combined with a genetic defect

B. Traditional animal toxicology studies may not detect it

C. Carbon tetrachloride is an example

D. Preclinical studies may need to be done in genetically deficient animals to detect some examples

A

C. Carbon tetrachloride is an example

40
Q

Ethyl alcohol is metabolized in humans by all of the following except…

A. CYP3A4

B. CYP2E1

C. ADH

D. peroxisomal catalase

A

A. CYP3A4

41
Q

All of the following hepatic sites are matched with the appropriate preferential toxicant except…

A. Zone 1 hepatocyte / iron

B. Bile duct cells / ethanol

C. Stellate cells / vitamin A

D. Zone 3 hepatocyte / carbontetrachloride

A

B. Bile duct cells / ethanol

42
Q

All of the following are true regarding ethanol and the liver except…

A. EtOH inhibits the transfer of triglycerides from liver to adipose tissue

B. EtOH dehydrogenase is the only inducible enzyme in chronic alcoholics

C. An inactive form of aldehyde dehydrogenase is found in 50% of asians

D. The catalase pathway is a minor route for EtOH metabolism

A

B. EtOH dehydrogenase is the only inducible enzyme in chronic alcoholics

43
Q

All of the following are true regarding the hepatotoxicity of CCl4 except…

A. The reactive metabolite is formed by cytochrome P450 3A4

B. The reactive metabolite is a free radical

C. Chronic EtOH exposure can enhance injury

D. The injury involves lipid peroxidation

A

A. The reactive metabolite is formed by cytochrome P450 3A4

44
Q

Idiosyncratic liver injury is characterized by all of the following except…

A. It can be immune or nonimmune

B. it has a clear dose-response relationship

C. It is relatively rare

D. It has a probable genetic basis

A

B. it has a clear dose-response relationship

45
Q

Wilson’s disease is due to…

A. Increased intestinal absorption of copper

B. decreased biliary excretion of copper

C. Decreased renal excretion of copper

D. Increased sensitivity to normal levels of copper

A

B. decreased biliary excretion of copper

46
Q

The liver cell process asso w/ cell swelling, leakage of cell contents and an influx of inflammatory cells is…

A. Apoptosis

B. Fibrosis

C. Necrosis

D. Steatosis

A

C. Necrosis

47
Q

Fatty liver is caused by all of the following except…

A. EtOH

B. vinyl chloride

C. CCl4

D. Insulin resistance

A

B. vinyl chloride

48
Q

Which cell is located in the Space of Dis?

A. Stellate cell

B. Endothelial cell

C. Kupffer cell

D. Bile duct cell

A

A. Stellate cell

49
Q

Hepatacellular carcinoma is asso w/ all of the following except…

A. Doxycycline

B. Aflatoxin

C. Viral hepatitis

D. Androgen abuse

A

A. Doxycycline

50
Q

Albumin is…

A. Elevated in liver disease and hemolysis

B. decreased in chronic liver and bone disease

C. The most sensitive indicator of acute liver disease

D. Demonstrates extrahepatic bile duct dilation

A

B. decreased in chronic liver and bone disease

51
Q

Aspartate transaminase is…

A. Decreased in chronic liver disease

B. Distinguishes bone from liver disease

C. The most sensitive indicator of acute liver disease

D. Elevated in liver and bone disease

A

C. The most sensitive indicator of acute liver disease

52
Q

Prothrombin time can…

A. Reflect the level of coagulation factors

B. distinguish bone from liver disease

C. Be elevated in 60-80% of patients w/ hepatic encephalopathy

D. Be elevated in liver disease and hemolysis

A

A. Reflect the level of coagulation factors

53
Q

Ammonia is…

A. Decreased in chronic liver disease

B. elevated in liver and bone disease

C. Elevated in liver disease and hemolysis

D. Elevated in 60-80% of patients with hepatic encephalopathy

A

D. Elevated in 60-80% of patients with hepatic encephalopathy

54
Q

Alkaline phosphatase is…

A. Elevated in liver and bone disease

B. the most sensitive indicator of acute liver disease

C. Elevated in liver disease and hemolysis

D. Decreased in chronic liver disease

A

A. Elevated in liver and bone disease

55
Q

Ultrasound can…

A. Distinguish bone from liver disease

B. Reflect the level of coagulation factors

C. Demonstrate extrahepatic bile duct ligation

D. Be decreased inchronic liver disease

A

C. Demonstrate extrahepatic bile duct ligation

56
Q

Gamma glutamyl transpeptidase can…

A. Distinguish bone from liver disease

B. reflect the level of coagulation factors

C. Be elevated in liver disease and hemolysis

D. Be elevated in liver and bone disease

A

D. Be elevated in liver and bone disease

57
Q

Bilirubin is…

A. Elevated in liver disease and hemolysis

B. Decreased in chronic liver disease

C. The most sensitive indicator of acute liver disease

D. Elevated in bone and liver disease

A

A. Elevated in liver disease and hemolysis

58
Q

Early stages of ethanol abuse are chara by…

A. Inability to degrade lipids

B. Inability to transport lipids out of the liver

C. Increased lipid synthesis

D. All of the above

A

B. Inability to transport lipids out of the liver