Chemical Injury

Question 1

etiology is the ____ of cell injure while pathogenesis is the _____

Answer 1

cause; mechanism

Question 2

what is the mechanism for cellular anoxic injury?

Answer 2

absence of oxidative phosphorylation, reduced ATP production

Question 3

what does puromycin do to cells?

Answer 3

antibiotic that causes chain termination &raquo_space; incomplete proteins that damage cell

Question 4

This chemical can, like ETOH, cause steatosis in the liver:

Answer 4

CCl4

Question 5

how do hydroxy radicals affect cells?

Answer 5

mutations in DNA/RNA; enzyme inactivation; lipid peroxidation (» fragmentation of FA peroxides&raquo_space; influx Ca&raquo_space; membrane damge&raquo_space; Death)

Question 6

What is cisPlatinimum? what type of cellular damage does it cause?

Answer 6

chemotherapy drug. Results in DNA cross linking and inhibition of DNA synthesis. damages intestinal villi and kidney tubules.

Question 7

what is hormesis?

Answer 7

biologic effect of low does xenobiotic that would be toxic at higher doses

Question 8

The EPA (Environmental Protection Agency) lowered mandated tolerable levels in drinking water for which of the following in 2001?

Answer 8

arsenic

Question 9

When analyzed in conjunction with aspartate aminotransferase level, Alanine aminotransferase level can confirm:

Answer 9

liver origin of toxicity (if both are high)

Question 10

What is NAC (n-acetylcysteine)? how does it work?

Answer 10

n-acetylcysteine; antidote for acetaminophen (APAP). contains thiol and gets converted to cysteine&raquo_space; glutathione. glutathione is an antioxidant and reducing agent that binds toxic agent produced by APAP.

Question 11

what is the toxic metabolite produced by overdose of acetaminophen? what must it bind to to be excreted in urine?

Answer 11

N-acetyl-p-benzoquinoneimine (NAPQI); glutathione or other thiols

Question 12

what is the difference between unconjugated and conjugated bilirubin?

Answer 12

unconjugated: no glucuronide, insoluble.
conjugated: w/ glucuronide, soluble.

Question 13

what is lactulose used to treat?

Answer 13

nitrogenous hepatic encephalopathy. it lowers the pH of the colon and “traps” ammonium there

Question 14

What is DIC (disseminated intravascular coagulation)?

Answer 14

DIC is dessiminated intravascular coagulation— disorder characterized by bleeding
DIC arise from consumption of clotting factors due to liver failure (failure of liver synthetic function)

Question 15

What is Barrett’s esophagus?

Answer 15

pathophysiologic response to chronic gastrointestinal reflux which causes inflammatory injury to the esophagus. The epithelial response to the process starts with hyperplasia followed by intestinal type metaplasia called Barrett esophagus . In untreated people Barrett esophagus may lead to dysplasia (pre-neoplasia) and ultimately cancer (adenocarcinoma).

Question 16

1) Name seven categories of causes of cell injury. One example is toxic chemicals.

Answer 16

1. Anoxia
2. Congenital
3. Invasive (fungal, bacterial, etc)
4. Trauma/physical agents
5. Chemical
6. Autoimmune and immune responses
7. Nutritional deficiencies

Question 17

2) Explain the difference between etiology and mechanism in cell injury.

Answer 17

etiology: study of the cause of cell injury
mechanism: pathogenesis, the mechanism of cell injury

Question 18

3) Explain the mechanism of cellular ATP deficit caused by anoxia, carbon monoxide
poisoning, and cyanide poisoning.

Answer 18

decreased oxidative phosphorylation in cells because of decreased O2 (or, in cyanide poisoning, blockage of oxidative phosphorylation by the chemical)

Question 19

4) State the molecular mechanism for CCl4 toxicity, and explain why gut lining cells escape
toxic effects of CCl4.

Answer 19

enter cells, are metabolized to form FREE RADICALS that then cause: lipid peroxidation&raquo_space; membrane damage, swelling, base damage of DNA > mutations, enzymatic deactivation > decreased protein synthesis. results in steatosis and ultimately, coagulative necrosis around central vein in liver. can resolve after 48 hours if organism survives.

Question 20

5) State the critical feature of molecular structure of a free radical.

Answer 20

Unpaired electron in outer shell

Question 21

6) List an example of a poison that is made toxic by metabolic alteration.

Answer 21

CCL4, benzopyrene

Question 22

7) List an example of a poison that does not require metabolic activation in order to become toxic.

Answer 22

strong acids/bases,
CO,
heavy metals

Question 23

8) Define: xenobiotics, poison, centrilobular necrosis (liver), lipid peroxidation, antibiotic,
antimetabolite, metabolic activation.

Answer 23

xenobiotics: external substances
poison: anything toxic to the body
Centrilobular necrosis: necrosis around central vein
Lipid peroxidation: free radical-induced per oxidation of lipids resulting in membrane damage
antimetabolite: poisons that function because they are analogs of molecules normally active in cellular metabolism. ex: anti-cancer drugs

Question 24

9) Use the example of cis-platinum (a chemotherapeutic agent) in describing the various
mechanisms of molecular damage/alterations that lead to cell death.

Answer 24

Cis-platinum: alkylating agent that forms covalent bonds with DNA. causes DNA cross-linking, shuts down DNA synthesis, shuts down Cellular division. Cells with irreparable damage undergo apoptosis.