Nephrotoxicology

Question 1

5 functions of the kidney

Answer 1

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

Question 2

there are three distinct regions of the kidney

Answer 2

cortex, medulla, papilla

Question 3

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

Answer 3

cortex

Question 4

functional unit of the kidney

Answer 4

nephron

Question 5

five parts of the nephron

Answer 5

glomerulus
proximal tubule
loop of henle
distal tubule
collecting duct

Question 6

a complex specialized capillary bed composed primarily of endothelial cells

Answer 6

glomerulus

Question 7

the glomerulus is a good barrier against what

Answer 7

macromolecules

Question 8

regulates the pressure in the nephron

Answer 8

macula densa

Question 9

the proximal tubule consists of three discrete segments

Answer 9

S1
S2
S3

Question 10

what is the job of the proximal tubule

Answer 10

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

Question 11

four characteristics of ultrafiltration

Answer 11

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

Question 12

facilitate filtration

large enough for fluids not white and red blood cells

Answer 12

fenestrae

Question 13

how is the glomerulus filtration rate regulated functionally

Answer 13

dilation or constriction of blood vessels

Question 14

what regulates the filtration rate chemically

Answer 14

direct nervous system 
angiotensin
vasopressin
adenosine
norepinephrin

Question 15

molecule to look for when checking for impaired kidney function

Answer 15

creatine

Question 16

how are molecule reabsorbed in the proximal tubule

Answer 16

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

Question 17

what is excreted from the proximal tubule and how

Answer 17

p-glycoproteins by active transport

Question 18

what is reabsorbed at the loop of henle

Answer 18

25% of filtered Na and K

20% of water

Question 19

what are two things that occur in the distal tubule

Answer 19

macula densa regulates filtration rate

further concentration of urine

Question 20

one of the most common manifestations of nephrotoxic damage is

Answer 20

acute renal failure

Question 21

what happens during acute renal failure

Answer 21

sudden drop in filtration rate

Question 22

causes for prerenal acute failure

Answer 22

renal vasoconstriction

loss of blood pressure

Question 23

causes for post renal acute failure

Answer 23

blockage of ureter

Question 24

causes for intrarenal acute failure

Answer 24

tubular cell death

tubular blockage

Question 25

what can cause tubular obstruction

Answer 25

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

Question 26

what is the kidneys first adaptation to damage

Answer 26

increase in GFR for unaffected nephrons

Question 27

what does the kidney do about damaged cells

Answer 27

induction of MT and HSP | cell repair or apoptosis

Question 28

how can kidney cells regenerate

Answer 28

no renal stem cells | some cells can go through dedifferentiation, proliferation, migration, and differentiation

Question 29

chronic renal disease has been postulated to be a consequence of

Answer 29

glomerular hemodynamic response to renal injury

Question 30

three characteristics of chronic renal failure

Answer 30

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

Question 31

four reasons for the susceptibility of the kidney

Answer 31

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

Question 32

site specific injury to glomerulus

Answer 32

change of membrane charge | vasoconstriction

Question 33

reasons for injury to glomerulus

Answer 33

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

Question 34

most susceptible portion of the nephron to injury

Answer 34

proximal tubule

Question 35

why is the proximal tubule the most susceptible

Answer 35

place of reabsorption concentration and biotransformation

Question 36

general parameters to check for renal damage

Answer 36

volume, pH, osmolality

Question 37

specific parameters to check for renal damage

Answer 37

glucose, proteins, creatine, enzymes

Question 38

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

Answer 38

urea nitrogen creatine inulin clearance

Question 39

types of nephrotoxicity

Answer 39

cardiovascular direct tubular effects nephritis

Question 40

causes of cardiovascular nephrotoxicity

Answer 40

diuretics beta-blockers vasodilators

Question 41

reasons for proximal tubular effects

Answer 41

certain antibiotics, cisplatin (chemotherapy)

Question 42

reasons for distal tubular toxicity

Answer 42

NSAIDs, cyclosporin (immunosuppressant)

Question 43

What causes acute nephritis

Answer 43

70-90% of cases caused by medications

Question 44

What causes chronic nephritis

Answer 44

lithium, cyclopsorin

Question 45

bind strongly to sylfhydryl groups | important for transport and protein damage

Answer 45

heavy metals

Question 46

bound to albumin, glutathione, and cysteine that mediates reuptake

Answer 46

mercury

Question 47

what does mercury toxicity do

Answer 47

reduce GFR damage to tubular cells mitochondrial damage ROS production

Question 48

bind to MT in liver and intestine | transport to kidney were reuptake can occur in the proximal tubule

Answer 48

cadmium

Question 49

what does cadmium toxicity do

Answer 49

lysosomal degradation | interference with cell signaling pathways

Question 50

halogenated hydrocarbons cause

Answer 50

proximal tubule cell damage

Question 51

inhibit prostaglandin production, causes acute vasoconstriction from overdose

Answer 51

NSAIDs

Question 52

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

Answer 52

aristolochic acid