Kidney toxicity

Question 1

Acute kidney injury definition

Answer 1

abrupt decrease in kidney function including acute renal failure

Question 2

GFR formula

Answer 2

Kf (glomerular surface area x glomerular capillary) x net filtration pressure

Question 3

3 GFR reduction causes

Answer 3

1. afferent arteriole constriction
2. tubular obstruction
3. filtrate leakage

Question 4

how does afferent arteriole cause GFR reduction

Answer 4

constriction in the afferent artery decreases the blood that enters, decreasing the hydrostatic pressure in the glomerulus, reducing GFR

Question 5

how does tubular obstruction reduce GFR

Answer 5

increases hydrostatic pressure in the Bowman’s capsule, decreasing GFR

Question 6

changes to uninjured cells after nephron injury

Answer 6

1. hypertrophy
2. adaptation
3. proliferation

Question 7

Chronic kidney disease measurement parameters

Answer 7

measured by GFR and albumin-creatinine ratio

Question 8

3 reasons why kidneys are susceptible to toxicity

Answer 8

1. 20-25% of cardiac output, therefore receives higher amounts of drugs and chemicals
2. concentrated urine leading to more concentrated toxicants within tubular fluid. therefore, may be non-toxic in plasma but toxic in kidney
3. precipitation of insoluble compounds in the kidney leads to tubular obstruction which may cause acute kidney injury

Question 9

Most common form of mercury

Answer 9

elemental mercury

Question 10

elemental mercury targets

Answer 10

crosses BBB and affects CNS

Question 11

inorganic mercury target

Answer 11

kidney

Question 12

organic mercury target

Answer 12

brain

Question 13

3 sources of mercury

Answer 13

1. natural degassing of earth crust
2. sediment leaching
3. industrial release

Question 14

mechanism of action of mercury

Answer 14

interacts with SH group -> inactivate enzymes, structural proteins and permeability

Question 15

effects of mercury

Answer 15

oxidative stress
disrupt microtubule formation
interfere protein synthesis
interfere DNA synthesis
interfere calcium homeostasis

Question 16

Halogenated hydrocarbons such as chloroform targets

Answer 16

1. proximal tubule
2. liver

Question 17

effects of chloroform

Answer 17

increased proteinuria, glucosuria and blood urea
carcinogen

Question 18

mechanism of chloroform

Answer 18

metabolised by P450 to tri-chloromethanol, which breaks down to phosgene. phosgene binds to nucleophillic groups on cellular macromolecules

Question 19

acetaminophen toxic effects (list 5)

Answer 19

1. proximal tubular necrosis
2. increase blood urea nitrogen
3. decrease GFR and para-aminohippurate clearance
4. increase water, sodium and potassium excretion
5. increase urinary glucose, protein, and brush border enzymes

Question 20

acetaminophen mechanism in kidney

Answer 20

metabolised by P450 to NAPQI which is a reactive compound.
an overdose of acetaminophen leads to insufficient glutathione to conjugate NAPQI.
NAPQI will bind with proteins in kidney and lead to necrosis

Question 21

NSAID effects

Answer 21

constriction of blood vessels

Question 22

NSAID mechanism

Answer 22

inhibit COX enzyme which decreases the production of inflammatory agents and constricts blood vessels.
this reduces renal blood flow, causing ischemia

Question 23

symptoms of NSAIDS and acetominophen for more than 3 years

Answer 23

irreversible nephrotoxicity.
urinary concentration and acidification is impaired
forms primary lesion

Question 24

usage of NSAIDs for more than 5 months leads to

Answer 24

interstitial nephritis

Question 25

aminoglycosides act as

Answer 25

antibiotics against gram negative bacteria

Question 26

aminoglycosides cause decreased GFR, increased serum creatinine and blood urea nitrogen because of

Answer 26

acute proximal tubular necrosis and renal failure

Question 27

mechanism of aminoglycosides (gentamycine)

Answer 27

filtered from the glomerulus and enters the proximal tubule. It is uptaken by cells and fuses with lysosomes. It will break down the vesicle to release hydrolytic enzymes and damage cells.
it also deals direct mitochondria damage which decreases ATP production