Target Organ Toxicity Flashcards

1
Q

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

A

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

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2
Q

what is BUN?

A

blood urea nitrogen– increased urea in blood indicates reduced GFR

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3
Q

what is GFR?

A

glomerular filtration rate

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4
Q

3 regions of the respiratory system

A

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

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5
Q

sources of lung damage

A

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

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6
Q

what is PM2.5

A

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

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7
Q

What are the toxic responses of the liver?

A

steatosis; necrosis; cholestasis; cirrhosis; carcinogenesis

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8
Q

what is steatosis?

A

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

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9
Q

what is the clinical marker of steatosis?

A

serum triglycerides (storage form of lipids);

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10
Q

what is necrosis?

A

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

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11
Q

what are some examples of liver necrosis-causing agents?

A

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

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12
Q

what is a biomarker for liver necrosis?

A

gamma glutamyl transpeptidase; GGT in blood plasma

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13
Q

what is cholestasis of the liver?

A

canicular cholestasis–decreased bile formation and biliary secretion;

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14
Q

symptoms of liver cholestasis?

A

jaundice–>due to excess bilirubin in blood

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15
Q

examples of xenobiotics that cause liver cholestasis?

A

ethanol, certain metals, steroids, certain drug

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16
Q

clinical marker of liver cholestasis?

A

GGT and plasma bilirubin

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17
Q

what is liver cirrhosis?

A

extensive fibrosis throughout the liver;

18
Q

what causes cirrhosis of the liver?

A

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

19
Q

what is the clinical marker of liver cirrhosis?

A

plasma GGT

20
Q

what is carcinogenesis of the liver/

A

common form of cancer–> most common;

21
Q

what can cause liver cancer

A

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

22
Q

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

A

ya

23
Q

major function of the kidney?

A

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

24
Q

what are nephrotoxicants?

A

affect the nephrons in the kidney

25
Q

examples of nephrotoxicants

A

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

26
Q

why are PCT cells the most susceptible to nephrotoxicants?

A

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

27
Q

how can one test kidney function?

A

urinalysis; blood analysis;

28
Q

what tests does urinalysis involve?

A

proteinuria; glycosuria; functional enzyme tests;

29
Q

what does proteinuria test for?

A

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;

30
Q

what does glycosuria measure?

A

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

31
Q

what does functional enzyme tests measure?

A

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

32
Q

what does blood analysis measure?

A

blood uria nitrogen; creatine clearance;

33
Q

what is creatine clearance?

A

presence of creatine in the blood indicates impaired kidney function

34
Q

what are the acute effects of resp toxicity?

A

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

35
Q

what is airway reactivity?

A

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

36
Q

what is pulmonary edema and what can cause it?

A

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

37
Q

what are chronic effects of resp toxicity?

A

usually irreversible; fibrosis; emphysema; asthma; neoplasia

38
Q

what is fibrosis of the lungs?

A

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

39
Q

what is emphasyma of the lungs?

A

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

40
Q

what can cause neoplasia of the lungs?

A

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