Chapter 1. Cell Injury - Free Radicals

Question 1

how do drugs like acetaminophen make free radicals? how is this harmful? what is a good treatment method?

Answer 1

acetaminophen is converted into acetaminophen FR in the liver

• may cause diffuse chemical hepatitis
• -liver cell necrosis initially occurs around central vein (zone III) and can occur at nontoxic levels in alcoholics
• -produces transient decrease in functional factor VII to prolong PT
• -treat with N-acetylcysteine to increase glutathione synthesis
• may cause renal papillary necrosis (NSAIDs)

Question 2

how does carbon tetrachloride make FRs? how is this harmful?

Answer 2

converted into CCl3 FRs in the liver

-produces liver cell necrosis with fatty change

Question 3

what FR does cigarette smoke make?

Answer 3

• quinone/hydroquinone FRs made from tar

- makes NO, which reacts with other reactive species to make more FR

Question 4

how are free radicals neutralized? (5 ways)

Answer 4

1. superoxide dismutase (SOD)
   - converts superoxide to peroxide and O2
2. glutathione peroxidase in PPP
   - neutralizes H2O2, hydroxyl, and acetaminophen FR
3. catalase (in peroxisomes)
   - degrades peroxide into O2 and water
4. vitamins
   - E prevents lipid peroxidation in membranes and neutralizes ox-LDL
   - C is best neutralizer of hydroxyl FR in smokers
5. selenium
   - neutralizes FRs in cytosol

Question 5

what might happen if you treat RDS (respiratory distress syndrome) with an O2 concentration > 50%?

Answer 5

retinopathy of prematurity (blindness)

Question 6

how are Fe VS Cu overload disorders similar and different in regards to FR injury?

Answer 6

Fe: intracellular Fe makes HO. FRs that damage parenchymal cells to cause cirrhosis, exocrine/endocrine pancreatic dysfunction
Cu (Wilson’s disease): inability to excrete Cu into bile
-excess in hepatocytes increases production of HO. FRs to cause cirrhosis