Target organ lecture:

Question 1

what are the major functions of the kidney?

Answer 1

1. excretion of metabolic wastes 2. Regulation of extraceullar fluid volumne 3. Electrolyte homeostasis 4. Acid-base balance 5. Blood pressure regulation 6. Metabolizes vitamin D to active form

Question 2

describe cholestais example clinical marker

Answer 2

descreased bile formation and biliar secretion. Symptoms are yellowish tinge in skin and eyes due to bilirubin (normal breakdown product of heme catabolism) e.g., ethanol, certain metals, steroids, and certain drugs Clinical marker: GGT and bilirubin in plasma

Question 3

describe emphysema:

Answer 3

somewhat the opposite of fibrosis; lungs get larger and loose. Due to breakdown of lung elastin. Results in impaired alveolar gas exchange

Question 4

describe cirrhosis example clinical marker

Answer 4

extensive fibrosis throughout liver e.g., chronic ethanol consumption Clinical marker: plasma GGT

Question 5

what are the 3 regions of the lungs as a target organ?

Answer 5

1. Nasal passges 2. Conducting airways (trachea and bronchi) 3. Gas exchange region (alveoli)

Question 6

describe fibrosis

Answer 6

increased extraceeular matric protein production by fibroblasts, build up in alveoli. Lungs get smaller and stiffer

Question 7

4 types of chronic effects:

Answer 7

1. Fibrosis 2. Emphysema 3. Asthma 4. Neoplasia

Question 8

what are two examples of acute effects?

Answer 8

1. Airway reactivity 2. Pulmonary edema

Question 9

are chronic effects reversible or irreversible?

Answer 9

usually irreversible

Question 10

Creatinine clearance:

Answer 10

presence of creatinine in blood indicates impaired kidney fucntion

Question 11

describe pulmonary edema and 3 examples

Answer 11

Fluid accumulation in lung which reduces O2/CO2 exchange. e.g., Cl2, NH3, gas

Question 12

Blood urea nitrogren (BUN):

Answer 12

increased urea in blood indicates reduced glomerular filtration rate (GFR)

Question 13

PM2.5 (particulate matter <2.5 um) is associated with what? Also what is size most important?

Answer 13

is associated with human respiratory toxicity, including death. Size is most important because of the decreasing diameter of all these pipes to the smallest alveoli.

Question 14

do kidneys or livers have more expression of biuotransformation enzymes?

Answer 14

liver! Kidney has moderate expression

Question 15

describe steatosis, examples and the clinical marker?

Answer 15

fatty liver, >5% lipid within cells Very common effect that occurs, can be due to both acute or chronic exposure. ex.) ethanol (binge drinking or chronic drinking) Clinical markers: serum triglycerides

Question 16

are acute effects reversible or irreversible?

Answer 16

can be both!

Question 17

examples of stuff that causes neoplasia

Answer 17

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

Question 18

———— is a common form of liver cancer

Answer 18

Hepatocellular

Question 19

what are the amjor examples of nephrotoxicants?

Answer 19

certain heavy metals, halogenated hydrocarbons and drugs.

Question 20

what does nephrotoxicity mean?

Answer 20

kidney

Question 21

describe airway reactivity, and the major concern over it?

Answer 21

bronchial smooth muscle is target cell type, usually effects muscle contraction. The major concern is astham and air pollution

Question 22

Urinalysis: Glycosuria:

Answer 22

increased glucose in urine indicates tubular dysfunction (inasence of hyperglycemia)

Question 23

why is the liver susceptible to toxicity arising from xenobiotic exposure? 10 reasons!

Answer 23

1. First pass effect 2. High metabolic activity 3. High perfusion rate 4. The liver contains a variety of different binding proteins ex.) metallothionein 5. The liver has a very high expression of phase 1 and phase 2 enzymes. Therefore, the potential for a xenobitoic to be bioactivated into a toxic metabolite. 6. Enterohepatic cycling 7. Resident macrophages and T cells 8. Active transport systems, can result in higher concentrations of drugs in the liver. 9. Underlying pathology 10. High cell division

Question 24

what does hepatotoxicity mean?

Answer 24

liver

Question 25

what is a drug that is not used anymore because of high incidences of kidney toxicity?

Answer 25

cephalosporins

Question 26

urinalysis: function enzyme tests:

Answer 26

e.g., GGT in urine

Question 27

what does steatosis, necrosis, cholestasis, cirrhosis and neoplasia have in common?

Answer 27

1. easily produced in lab animals 2. Many xenobitoics can cause several or all of these toxic effects!

Question 28

describe necrosis example of necrosis climical marker:

Answer 28

Can be focal (central, midzone or peripheral) or massive (throughout the liver). Usually acute exposure and is irreversible. It involves ATP and/or altered Ca2+ regulation. E.g., acetaminophen (Tylenol) E.g., carbon tetrachloride (CCL4) Clinical marker: gamma glutamyl transpeptidase (GGT) in blood plasma

Question 29

what are three sources of lung damage and examples?

Answer 29

1. Oxidative stress (e.g. ozone, NOx, smoke) 2. Gases and vapors (e.g., chlorine, ammonia, volatile solvents) 3. Particles and aerosols

Question 30

what is the most susceptible to nephrotoxicants and why?

Answer 30

proximal conoluted tubule (PCT) cells because: 1. Tubular transport of many xenobitoics occurs here. Can result in accumulation in cells 2. Greatest CYP enzyme activity among kidney cells 3. High metabolic activity (lots of mitochondria)

Question 31

urinalysis: proteinuria:

Answer 31

Increased levels of small proteins indicates loss of PCT reabsorption, indicating toxicity to PCT cells. Increased levels of large proteins indictes effects on glomerular cells

Question 32

whats the danger of tubular secretion:

Answer 32

Xenobitoics can get trapped in the PCT cells. Therefore, you get an increase of that xenobitoic in that cell.