Target Organ Toxicity

Question 1

why is the liver so susceptible to toxicity arising from xenobiotic exposure?

Answer 1

lots of metabolism; lots of perfusion; enterohepatic cycling; first pass effect; binding proteins; active transport pumps; high rates of cell mitosis;

Question 2

what is BUN?

Answer 2

blood urea nitrogen– increased urea in blood indicates reduced GFR

Question 3

what is GFR?

Answer 3

glomerular filtration rate

Question 4

3 regions of the respiratory system

Answer 4

nasal passages; conducting airways (trachea and bronchi); gas exchange region (alveoli)

Question 5

sources of lung damage

Answer 5

oxidative stress (ozone–from motor vehicle exhaust); gases and vapours; particles and aerosols

Question 6

what is PM2.5

Answer 6

particulate matter less than 2.5 um – associate with human respiratory tract toxicity– including death

Question 7

What are the toxic responses of the liver?

Answer 7

steatosis; necrosis; cholestasis; cirrhosis; carcinogenesis

Question 8

what is steatosis?

Answer 8

fatty liver; >5% fat accumulation in liver; can be due to chronic or acute exposure; reversible; –>e.g ethanol (binge drinking or chronic drinking); c

Question 9

what is the clinical marker of steatosis?

Answer 9

serum triglycerides (storage form of lipids);

Question 10

what is necrosis?

Answer 10

focal (central, midzone, or peripheral) or massive (throughout the river); usually acute exposure; irreversible; involves decreased ATP or altered Ca regulation;

Question 11

what are some examples of liver necrosis-causing agents?

Answer 11

acetominophen (Tylenol); produces active quinonamine– produces ROS; CCl4 (carbon tetrachloride); liquid at R; disinfectant

Question 12

what is a biomarker for liver necrosis?

Answer 12

gamma glutamyl transpeptidase; GGT in blood plasma

Question 13

what is cholestasis of the liver?

Answer 13

canicular cholestasis–decreased bile formation and biliary secretion;

Question 14

symptoms of liver cholestasis?

Answer 14

jaundice–>due to excess bilirubin in blood

Question 15

examples of xenobiotics that cause liver cholestasis?

Answer 15

ethanol, certain metals, steroids, certain drug

Question 16

clinical marker of liver cholestasis?

Answer 16

GGT and plasma bilirubin

Question 17

what is liver cirrhosis?

Answer 17

extensive fibrosis throughout the liver;

Question 18

what causes cirrhosis of the liver?

Answer 18

chronic alcohol consumption; ethanol–>mitochondrial damage–> steatosis; necrosis–>fibrosis

Question 19

what is the clinical marker of liver cirrhosis?

Answer 19

plasma GGT

Question 20

what is carcinogenesis of the liver/

Answer 20

common form of cancer–> most common;

Question 21

what can cause liver cancer

Answer 21

improper storage of grains–> creates aflotoxins; alfotoxins + common disease hepatitis= cancer of the liver

Question 22

can produce all 5 stages of liver toxicity very easily in lab animals–> better to use a fish than a dog; also many xenos cause all 5 stages

Answer 22

ya

Question 23

major function of the kidney?

Answer 23

excretion of metabolic (nitrogenous) waste; regulation of EC fluid volume (bp regulation); electrolyte homeostasis; acid-base balance; blood pressure regulation; metabolizes vit D to active form

Question 24

what are nephrotoxicants?

Answer 24

affect the nephrons in the kidney

Question 25

examples of nephrotoxicants

Answer 25

certain heavy metals (Cadmium); organochlorines; (halogenated hydrocarbons); and drugs--especially antibiotics and analgesics

Question 26

why are PCT cells the most susceptible to nephrotoxicants?

Answer 26

tubular transport of many xenos occur in PCT cells-->can result in accumulation; have the greatest CYP activity among kidney cells; high metabolic activity (lots of mito) --glomerular cells also susceptible

Question 27

how can one test kidney function?

Answer 27

urinalysis; blood analysis;

Question 28

what tests does urinalysis involve?

Answer 28

proteinuria; glycosuria; functional enzyme tests;

Question 29

what does proteinuria test for?

Answer 29

increased levels of small proteins indicates loss of PCT reabsorption, indicating toxicity to PCT cells; increased amounts of large proteins indicates damage to glomerular cells;

Question 30

what does glycosuria measure?

Answer 30

increased glucose in urine-->indicates tubular dysfunction (in absence of hyperglycemia)

Question 31

what does functional enzyme tests measure?

Answer 31

amount of GGT in urine-->indicates cells are dying (like with liver)

Question 32

what does blood analysis measure?

Answer 32

blood uria nitrogen; creatine clearance;

Question 33

what is creatine clearance?

Answer 33

presence of creatine in the blood indicates impaired kidney function

Question 34

what are the acute effects of resp toxicity?

Answer 34

can be reversible or irreversible; airway reactivity; pulmonary edema;

Question 35

what is airway reactivity?

Answer 35

usually bronchial sm muscle is targeted--> effect is usually muscle contraction; a major concern for asthmatics when there is a lot of air pollution (gases and fine particles) in hot, urban areas

Question 36

what is pulmonary edema and what can cause it?

Answer 36

fluid accumulation in the lungs--> reduces O2/CO2 exchange; Cl2; NH3; gas

Question 37

what are chronic effects of resp toxicity?

Answer 37

usually irreversible; fibrosis; emphysema; asthma; neoplasia

Question 38

what is fibrosis of the lungs?

Answer 38

increased ECM protein (collagen) production by fibroblasts, builds up in alveoli--> lungs become smaller and stiffer

Question 39

what is emphasyma of the lungs?

Answer 39

kind of opposite to fibrosis-- lungs become more stretchy and larger--> due to break down of elastin; results in impaired alveolar gas exchange

Question 40

what can cause neoplasia of the lungs?

Answer 40

tobacco smoke; metallic dusts; and fumes (As, Cd, Ni, Cr); asbestos, radon gas