renal physiology W1

Question 1

how does the macula densa interact with the rest of the body?

Answer 1

JG cells release renin

Question 2

what is renin

Answer 2

a protease!

Question 3

what causes JG cells to release renin

Answer 3

macula densa cells pump out more NaCl than usual

baroreceptors in JGA respond to elevated glom bp

Question 4

what does renin convert?

Answer 4

angiotensinogen -> angiotensin I

Question 5

what converts angiotensin 1 to angiotensin 2? where?

Answer 5

ACE (angiotensin converting enzyme) on surface of pulmonary and renal endothelium

Question 6

what does angiotensin 2 stimulate?

Answer 6

sympathetic activity
arteriolar vasoconstriction (increase in bp)
salt resorption in kidney tubules
secretion of aldosterone from adrenal gland
secretion of AVP from posterior pituitary

Question 7

how does angiotensin 2 stimulate salt resorption in kidney tubules?

Answer 7

binds to receptor in the proximal convoluted tubule, this increases the activity of the Na+/H+ exchanger.
leads to more sodium uptake.

Question 8

action of aldosterone on kidney cells?

Answer 8

affects gene transcription (as it is a steroid)
affects 2 different cells in collecting duct:

coll duct principal cell (most common): affects 2 genes
causes Na+/K+ and ASC expression

coll duct alpha-intercalated cell:
gene expression of H+ channels that allow exit from the cell without K+ (which is required in absence of aldosterone)

Question 9

affect of AVP on kidney cells? (aka ADH/vasopressin)

Answer 9

in collecting duct, causes aquaporin to move from vesicles to membrane which allows water uptake (elevating bp)

Question 10

end results of RAAS system?

Answer 10

increase in BP!! (due to…)
water and salt retention!

effective circulating volume increases. perfusion of the juxtaglomerular apparatus (JGA) increases

Question 11

affect of increased sympathetic activity caused by angiotensin 2 on the kidneys?

Answer 11

sympathetic renal nerves secrete noradrenaline, constricts both afferent and efferent arterioles so reduces flow (therefore reduced filtration, therefore reduced water loss). also directly promotes renin release

Question 12

when is ANP produced and what does it block?

Answer 12

produced when bp is too high. blocks activity of RAAS.

Question 13

parathyroid hormone response to Ca+ in blood?

Answer 13

parathyroids respond to low blood Ca+ by secreting parathyroid hormone (PTH) which acts on the kidney

Question 14

actions of PTH on the kidney? (overall picture)

Answer 14

increased Ca2+ recovery in distal collecting duct
decreased phosphate recovery in proximal convoluted tubule

Question 15

actions of PTH in distal collecting duct?

Answer 15

calcium uptake through channel (activated by PTH), binds to calcium binding proteins (eg calbindin). takes calcium to exit channel (activated by PTH).

Question 16

what components in the calcium path in the kidney require vitamin D? what through this pathway can vitamin D deficiency lead to?

Answer 16

calbindin
calcium exit channel into body

vit D deficiency leads to rickets due to this pathway

Question 17

actions of PTH in the proximal tubule?

Answer 17

inhibition of sodium and phosphate cotransporter (prevents uptake)

this increases free calcium ions as calcium can either be a free ion in the blood or circulate as calcium phosphate

Question 18

fall in intracellular pH causes what?

Answer 18

apical Na+/H+ exchangers more active (Na+ in, H+ out)
H+ excreted (complexed with buffers once in urine)

Question 19

potassium in alkalosis?

Answer 19

H+ out pumping by intercalated cells reduced, so less K+ reuptake (and apical K+ channel activity increased in principal cells and so is the Na+/K+ ATPase -> more K+ loss.

—-> hypokalaemia

Question 20

potassium in acute acidosis?

Answer 20

H+ out-pumping by intercalated cells increases so K+ reuptake increases. Also, apical K+ channels on Principal cells less active (by an effect on their intracellular regulation) so K+ secretion falls.

—-> hyperkalaemia

Question 21

what does aldosterone drive in terms of K+?

Answer 21

export out of the body in some cells, non recovery in others

Question 22

4 causes of clinical intervention in renal function?

Answer 22

control of oedema (in this lecture)
control of hypertension (in this lecture)
control of ion imbalances
control of acid-based disturbances

Question 23

what is diuresis?
(eg what is the effect of diuretics)

Answer 23

increasing the amount of water (+ salts) lost from the body (if you lose them together, you don’t mess up plasma salinity)

Question 24

action of loop diuretics?

Answer 24

block 2Cl-/K+/Na+ uptake channel.
this stops area of kidney medulla being salty, therefore stopping the drive of water resorption

increases urine output!

Question 25

loop diuretics features

Answer 25

powerful!
result in loss of Na+, K+, and Cl+ because of failure to recover
the inhibit Na uptake in the macula densa (uses same channel)
can result in hypercalcuria (due to less pull for calcium recovery because it follows other ions) and kidney stones
more Na+ getting to collecting duct, meaning more uptake and more K+ loss

Question 26

why is loop diuretics inhibiting sodium uptake in the macula densa a bad thing?

Answer 26

inhibiting salt uptake at macula densa makes kidney think there’s hardly any salt in the urine. concludes bp must be low for the flow to be this low, therefore increases renin (which increases bp, opposing our attempts to lower it)

Question 27

what conditions are loop diuretics good and bad for?

Answer 27

good for oedema
bad for hypertension

Question 28

thiazides mechanism of action?

Answer 28

thiazides - target channel in distal tubule that uptakes Ca- and Na+, causing reduced salt uptake and water recovery. the macula densa isn’t affected

also seem to directly affect vascular tone (reduce bp)

Question 29

thiazides and the macula densa?

Answer 29

macula densa is before thiazides cause there effect, therefore isn’t affected

Question 30

potassium sparing diuretics mechanism of action?

Answer 30

act on ASC (amiloride sensitive sodium channel) in collecting duct to prevent uptake of Na+
happens after macula densa so no effect there

Question 31

example of potassium sparing diuretics?

Answer 31

amiloride

Question 32

what drug affects aldosterone action? mechanism of action?

Answer 32

spironolactone blocks action of aldosterone (which activated transcription of the gene which coded for the ASC)
therefore reduces sodium uptake

Question 33

problem with spironolactone?

Answer 33

in males - antiandrogenic hormone, competes with eg dihydrotestosterone therefore affects normal signalling, pushes body into female type development (can get gynaecomastia - formation of female breast on male body)

therefore not usually prescribed to males

Question 34

carbonic anhydrase inhibitors?

Answer 34

block carbonic anhydrase, blocks bicarbonate recovery. urine more concentrated than it would be, so less of an osmotic pull to take water and other things into body.

Question 35

osmotic agents?

Answer 35

molecules that irreversibly filter from blood to urine.
make urine more concentrated than it would be otherwise, reducing concentration differences between urine and body space, therefore reduce water reuptake.

Question 36

summary of site of action of different diuretics?

Answer 36

carbonic anhydrase inhibitors - PCT
loop diuretics - LoH, col duct
thiazides - DCT
amiloride and spironolactone - ASC in col duct