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Toxicology > Nephrotoxicology > Flashcards

Nephrotoxicology Flashcards

1
Q

5 functions of the kidney

A 
waste excretion 
regulation of fluid volume
electrolyte composition
acid-base balance
hormone production
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2
Q

there are three distinct regions of the kidney

A

cortex, medulla, papilla

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3
Q

when toxicants are delivered to the kidney through the blood they will cause toxic effects more often in which part of the kidney

A

cortex

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4
Q

functional unit of the kidney

A

nephron

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5
Q

five parts of the nephron

A 
glomerulus
proximal tubule
loop of henle
distal tubule
collecting duct
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6
Q

a complex specialized capillary bed composed primarily of endothelial cells

A

glomerulus

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7
Q

the glomerulus is a good barrier against what

A

macromolecules

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8
Q

regulates the pressure in the nephron

A

macula densa

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9
Q

the proximal tubule consists of three discrete segments

A

S1
S2
S3

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10
Q

what is the job of the proximal tubule

A

to reabsorb approximately 60% to 80% of solute and water filtered at the glomerulus

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11
Q

four characteristics of ultrafiltration

A

driven by blood pressure
filtrate free of cells and large proteins
20% of blood is filtered in the glomerulus
filtration rate can be regulated

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12
Q

facilitate filtration

large enough for fluids not white and red blood cells

A

fenestrae

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13
Q

how is the glomerulus filtration rate regulated functionally

A

dilation or constriction of blood vessels

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14
Q

what regulates the filtration rate chemically

A 
direct nervous system 
angiotensin
vasopressin
adenosine
norepinephrin
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15
Q

molecule to look for when checking for impaired kidney function

A

creatine

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16
Q

how are molecule reabsorbed in the proximal tubule

A

active transport through Na-K-ATPase
passive diffusion for water along osmotic gradient
facilitated diffusion for glucose

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17
Q

what is excreted from the proximal tubule and how

A

p-glycoproteins by active transport

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18
Q

what is reabsorbed at the loop of henle

A

25% of filtered Na and K

20% of water

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19
Q

what are two things that occur in the distal tubule

A

macula densa regulates filtration rate

further concentration of urine

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20
Q

one of the most common manifestations of nephrotoxic damage is

A

acute renal failure

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21
Q

what happens during acute renal failure

A

sudden drop in filtration rate

22
Q

causes for prerenal acute failure

A

renal vasoconstriction

loss of blood pressure

23
Q

causes for post renal acute failure

A

blockage of ureter

24
Q

causes for intrarenal acute failure

A

tubular cell death

tubular blockage

25
Q

what can cause tubular obstruction

A

toxicant enters tubular cells
los of polarity, tight junction integrity and brush border
cell death by apoptosis or necrosis
sloughing off of viable cells into the intraluminal cavity where they can become lodged and form obstruction

26
Q

what is the kidneys first adaptation to damage

A

increase in GFR for unaffected nephrons

27
Q

what does the kidney do about damaged cells

A

induction of MT and HSP

cell repair or apoptosis

28
Q

how can kidney cells regenerate

A

no renal stem cells

some cells can go through dedifferentiation, proliferation, migration, and differentiation

29
Q

chronic renal disease has been postulated to be a consequence of

A

glomerular hemodynamic response to renal injury

30
Q

three characteristics of chronic renal failure

A

long term compensatory activity of healthy nephrons
mechanical damage in overworked nephrons
development of sclerosis

31
Q

four reasons for the susceptibility of the kidney

A

large blood supply needed
deliver and concentration of waste material containing potential toxicants
high biotransformation activity
high mitochondrial activity

32
Q

site specific injury to glomerulus

A

change of membrane charge

vasoconstriction

33
Q

reasons for injury to glomerulus

A

antibiotics impair filtration
interference by immune cells
local release of cytokines and ROS

34
Q

most susceptible portion of the nephron to injury

A

proximal tubule

35
Q

why is the proximal tubule the most susceptible

A

place of reabsorption concentration and biotransformation

36
Q

general parameters to check for renal damage

A

volume, pH, osmolality

37
Q

specific parameters to check for renal damage

A

glucose, proteins, creatine, enzymes

38
Q

what can be tested in the blood to check for renal damage

A

urea nitrogen
creatine
inulin clearance

39
Q

types of nephrotoxicity

A

cardiovascular
direct tubular effects
nephritis

40
Q

causes of cardiovascular nephrotoxicity

A

diuretics
beta-blockers
vasodilators

41
Q

reasons for proximal tubular effects

A

certain antibiotics, cisplatin (chemotherapy)

42
Q

reasons for distal tubular toxicity

A

NSAIDs, cyclosporin (immunosuppressant)

43
Q

What causes acute nephritis

A

70-90% of cases caused by medications

44
Q

What causes chronic nephritis

A

lithium, cyclopsorin

45
Q

bind strongly to sylfhydryl groups

important for transport and protein damage

A

heavy metals

46
Q

bound to albumin, glutathione, and cysteine that mediates reuptake

A

mercury

47
Q

what does mercury toxicity do

A

reduce GFR
damage to tubular cells
mitochondrial damage
ROS production

48
Q

bind to MT in liver and intestine

transport to kidney were reuptake can occur in the proximal tubule

A

cadmium

49
Q

what does cadmium toxicity do

A

lysosomal degradation

interference with cell signaling pathways

50
Q

halogenated hydrocarbons cause

A

proximal tubule cell damage

51
Q

inhibit prostaglandin production, causes acute vasoconstriction from overdose

A

NSAIDs

52
Q

from wild plants, used in Chinese herbal medicine, also potent mutagen

A

aristolochic acid

Toxicology (20 decks)

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