Chemical Injury

Question 1

Xenobiotics

Answer 1

Biologically active chemicals found in an individual with an origin that is exogenous to the individual

Question 2

Poison

Answer 2

Toxic chemical

A chemical from the environment which causes cell injury

Question 3

Carbon tetrachloride

Answer 3

CCl4
Formerly widely used in fire extinguishers, as a precursor to refrigerants, and as a cleaning agent
One of the most potent hepatotoxins

Question 4

Centrilobular necrosis

Answer 4

Coagulative necrosis centered around the central veins of the liver
See (in to out) central vein, coagulation necrosis (dead cells with pyknotic nuclei), swollen cells with some fat vacuoles, normal cells

Question 5

Lipid peroxidation

Answer 5

Refers to the oxidative degradation of lipids
The process in which free radicals “steal” electrons from the lipids in cell membranes -> cell damage
Proceeds by a free radical chain reaction mechanism: the basis for PROPAGATION of the injury (becomes part of a cycle)

Question 6

Antibiotic

Answer 6

Agents with a variety of biochemical activities which are toxic to other microorganisms, and often also to mammalian cells
Usually produced by microorganisms

Question 7

Antimetabolite

Answer 7

Poisons that function because they are analogs of molecules normally active in cellular metabolism

Question 8

Metabolic activation

Answer 8

When chemicals are metabolized in cells to form toxic metabolites (indirect acting poisons)

Question 9

Name seven categories of causes of cell injury.

Answer 9

Physical agents: trauma, radiation, heat, cold
Toxic chemicals
Nutritional deficiency
Anoxia
Immune reactions
Microbiologic agents (bacterial, fungal, viral)
Inherited genetic abnormalities

Question 10

Explain the difference between etiology and mechanism in cell injury.

Answer 10

Etiology: study or description of cause (hypoxia, CO, cyanide, etc.); important in planning treatment

Mechanism: pathogenesis (reduced oxidative phosphorylation, reduced ATP production, etc.); tend to fall into a number of common patterns which may be initiated by more than one etiologic factor (like free radical induced injury)

Question 11

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

Answer 11

Anoxia and CO poisoning: no O2 = no ATP via ox phos

Cyanide poisoning: inhibits ETS

Question 12

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

Answer 12

1. CCl4 enters parenchymal cells (liver, kidney tubules) -> metabolized to form free radicals (CCl3 ‘ )
2. Free radicals -> lipid peroxidation -> membrane damage -> cell swelling
3. Damaged RER in liver -> disrupted protein synthesis -> accumulation of TG in cytoplasm (steatosis)
4. Possible lethal effects -> necrosis

Question 13

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

Answer 13

The hydroxy free radical is the critical feature
With unsaturated lipids -> lipid peroxidation
With DNA -> base damage
With proteins -> enzyme inactivation

Question 14

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

Answer 14

CCl4 -> free radicals are toxic metabolites

Acetaminophen

Question 15

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

Answer 15

NaOH: always corrosive; denatures macromolecules and dehydrates tissues, destroying all contacted cells
Carbon monoxide
Strong acids
Heavy metals

Question 16

Use the example of cis-platinum in describing the various mechanisms of molecular damage/alterations that lead to cell death.

Answer 16

Cis-platinum -> cross-linking/covalent bonds with many macromolecules, including DNA
Toxic to any tissue where DNA synthesis is required or where it achieves high concentrations (intestines

• DNA synthesis shut down
• Cell division stops
• DNA repair begins
• Cells with unrepairable DNA damage undergo apoptosis
• Severely damaged cells die (necrosis)

Question 17

Why does CCl4 cause centrilobular necrosis?

Answer 17

Cells around central vein more vulnerable, less well oxygenated
Might metabolize more CCl4 in these cells