diuretics

Question 1

DIAGRAM what occurs at proximal tubule- water and sodium

Answer 1

Na+ diffuses from tubule through cell into blood, maintained by NaK pump proteins are in blood to produce oncotic pressure, which causes water to go from lumen to blood- can either go transcellularly, or paracellulary

Question 2

DIAGRAM what occurs at proximal tubule- bicarbonate and glucose/a.a’s, and exogenous agents

Answer 2

H+ and HCO3- form CO2 and H20 using CA: they then move into cell and are converted back into H+ and HCO3- HCO3- moves out with Na+ in blood, H+ involved in NaH transporter= Na+ comes in together with glucose/a.a’s metabolised drugs go from blood into tubule here too

Question 3

what occurs in descending LoH

Answer 3

ONLY H20 moves into interstitium trans/paracellularly

Question 4

what occurs in ascending LoH

Answer 4

impermeable to water- NaCl absorption via triple NaClK transporter, maintained by NaK pump

Question 5

countercurrent effect and significance- bot LoH and collecting duct

Answer 5

sodium can’t leave ascending LoH, but leaves descending LoH- concentrates interstitium (hypertonic) and fluid leaving LoH hypo-osmolar (as Na+ has diffused out)- means max water can leave DESCENDING limb and be reabsorbed also means interstitium next to collecting duct concentrated- again max water from duct can be reabsorbed

Question 6

early and late distal tubule

Answer 6

NaCl reabsorbed via transporter, with NaK pump to maintain late- aldosterone also absorbed Na .water moves through ONLY via aqp- CANNOT move PARACELLULARLY due to tight junctions

Question 7

collecting duct

Answer 7

like distal tubule- Na via aldosterone, water ONLY via aqp

Question 8

two main mechanisms of diuretics

Answer 8

mainly inhibit reabsorption of Na/Cl - also increase osmolarity of tubular fluid (ie less water goes into interstitium)

Question 9

mechanism of loop diuretics eg furusemide with LOCATION

Answer 9

inhibit NaclK transpotter in ASCENDING LIMB, thus less Na+ goes into interstiitium, so countercurrent effect diminished as interstitium less concentrated= less water reabsorbed

Question 10

side effect of loop diuretics- K+ and Ca2+/Mg2+

Answer 10

more Na+ stays in, so in distal tubule more Na+ reabsorbed at the expense of K+ (due to NaK pump) . also less Ca2+/Mg2+ reabsorbed

Question 11

mechanism of thiazide diuretics eg bendroflumethiazide with LOCATION

Answer 11

inhibit NaCl transporter in EARLY DISTAL TUBULE= less water reabsorbed: less powerful as countercurrent effect not impaired

Question 12

side effect of thiazides

Answer 12

K+ loss like loop diuretics

Question 13

main problem with both thiazide and loop diuretics- which more powerful, and thus what drug given

Answer 13

less Na+ transported from tubule into macula densa, and also less renal perfusion pressure, so increased renin, ESPECIALLY loop diuretics . this leads to opposite effect of diuretics, thus ACE inhibitors given as well to inhibit RAAS

Question 14

how K+ sparing diuretics work

Answer 14

spironoclactone inhibits aldosterone= less Na+ channels and Nak Pumps in DISTAL TUBULE+ COLLECTING DUCT -alternatively, amiloride inhibits Na+ channel

Question 15

why K+ sparing called K+ sparing

Answer 15

least potent out o fall diuretics, and acts at end of tubule, so less K+ excretion

Question 16

side effects of loop diuretics/thiazides

Answer 16

hyponatremia, hypokalemia, hypovolemia, METABOLIC ALKALOSIS due to Cl- loss, and build up of URIC ACID

Question 17

side effect of K+ sparing diureitcs

Answer 17

not much, only hyperkalemia

Question 18

how does diuretic cause build up of uric acid

Answer 18

diuretic moves from blood to lumen as needs to act on APICAL side- uses same transporter that excretes uric acid, thus less uric acid excreted

Question 19

which diuretic used more for hypertension and why

Answer 19

problem with all diuretics- intiially redcues blood volume, but then due to RAAS, plasma volume back to normal .chronic use of thiazide decreases TPR (vasodilatory) due to less Ca2+ influx/eNOS activation, thus better than other diuretics

Question 20

why diuretic used for HF treatment/oedema and why

Answer 20

in heart failure, blood moves around less efficiently, so builds up in venous system= congestion= eg ankle oedema .LOOP diuretics reduce this congestion+ heart needs to pump less fluid

Question 21

problem with treatment for HF and solution

Answer 21

RAAS system counteracts this- thus K+ sparing diuretic given to help reduce convestion