renal system

Question 1

what areas in kidney are targeted by diuretics

Answer 1

proximal tubule, loop of Henle, distal tubule

Question 2

structure of proximal tubule cell

Answer 2

surround lumen with microvillis, with intersitium and capillaries outside of basal interdigitation

Question 3

physiology of proximal tubule cells: transcellular movement of H2O and Na+

Answer 3

H2O and Na+ diffuse across apical membrane of proximal tubule cell (through channels), with Na+ being exchanged for K+ (Na+/K+-ATPase) at basal membrane to ensure Na+ concentration gradient, with interstitium having oncotic pressure to draw H2O across via channels

Question 4

physiology of proximal tubule cells: paracellular movement

Answer 4

H2O, Na+, Cl-, HCO3- move into interstitium due to oncotic pressure gradient

Question 5

physiology of proximal tubule cells: transcellular movement of glucose and amino acids

Answer 5

associate with Na+ and pumped across apical membrane of proximal tubule cell in exchange for H+

Question 6

physiology of proximal tubule cells: transcellular movement of HCO3-

Answer 6

HCO3- and H+ react in lumen by carbonic anhydrase on apical membrane to form CO2 and H2O, which diffuse across apical membrane of proximal tubule cell; broken down IC to H+ and HCO3- by carbonic anhydrase, with H+ exchanged for Na+ (and amino acids/glucose) at apical membrane (H+ out, Na+ in), and with HCO3- pumped out of basal membrane along with Na+

Question 7

physiology of proximal tubule cells: exportation of exogenous agents

Answer 7

exogenous agents e.g. glucoronides attached to drugs exported into lumen

Question 8

% of filtered Na+ absorbed in proximal tubule

Answer 8

65-70%

Question 9

physiology of descending limb of loop of Henle: transcellular pathway

Answer 9

H2O permeable, ion impermeable; H2O diffuses across cell from isotonic lumen to hypertonic interstitium via channels

Question 10

physiology of ascending limb of loop of Henle: transcellular pathway

Answer 10

H2O impermeable, ion permeable; Na+, 2Cl- and K+ pumped in across apical membrane of ascending limb cell via triple transporter, with Na+ pumped out in exchange for K+, and K+ and Cl- pumped out together, across basal membrane (K+ can diffuse across apical membrane also, and Cl- can diffuse across basal membrane also)

Question 11

physiology of ascending limb of loop of Henle: paracellular pathway

Answer 11

Na+ absorbed

Question 12

describe countercurrent effect of kidney in loop of Henle

Answer 12

loop filled with isotonic fluid -> Na+ pumped from ascending limb (so fluid in ascending lumb decreases osmolarity) -> descending tubule increases osmolarity (permeable to water so water drawn into medullary interstitium) -> more fluid enters and forces fluid from descending to ascending limb, which has increased osmolarity -> second/third etc. round of Na+ pumping

Question 13

how is countercurrent effect important in collecting duct

Answer 13

when aquaporins inserted, water flows into interstitium down concentration gradient

Question 14

physiology of distal tubule cell: transcellular pathway H2O

Answer 14

late: early stage is H2O impermeable, but in late stage H2O diffuses in through AQP2 (apical) and into interstitium through AQP3/4 (basal), in presence of ADH (and V2)

Question 15

physiology of distal tubule cell: transcellular pathway ions

Answer 15

early: Na+ and Cl- contransported across apical membrane, with Na+ exchanged for K+ at basal membrane, and K+ and Cl- cotransported across basal membrane; late: aldosterone binds to MR, increasing Na+ absorption

Question 16

physiology of collecting duct cell: transcellular pathway

Answer 16

similar as distal tubule cell with regard to water and ions, with H2O reabsorbed in presence of ADH (and V2)

Question 17

2 methods of action of diuretics in kidney

Answer 17

inhibit reabsorption of Na+ and Cl- (increase excretion), increase osmolarity of tubular fluid (decrease osmotic gradient across epithelia)

Question 18

5 main classes of diuretics

Answer 18

osmotic diuretics, carbonic anhydrase inhibitors, loop diuretics, thiazides, K+-sparing diuretics

Question 19

location of action of osmotic diuretics

Answer 19

proximal tubule, descending limb of loop of Henle, collecting duct

Question 20

location of action of carbonic anhydrase inhibitors

Answer 20

proximal tubule

Question 21

location of action of loop diuretics

Answer 21

ascending limb of loop of Henle

Question 22

location of action of thiazides

Answer 22

distal tubule (early)

Question 23

location of action of K+-sparing diuretics

Answer 23

distal tubule (late) and collecting duct

Question 24

example of osmotic diutetic

Answer 24

mannitol

Question 25

example of carbonic anhydrase inhibitor

Answer 25

acetazolamide

Question 26

example of loop diuretic

Answer 26

frusemide

Question 27

action of frusemide on Na+ reabsorption from ascending limb of loop of Henle

Answer 27

inhibit Na+ and Cl- reabsorption in triple transporter, interfering with counter current effect

Question 28

action of frusemide on H2O reabsorption from ascending limb of loop of Henle

Answer 28

increase tubular fluid as interferes with counter current effect, increases tubular fluid osmolarity and decreases osmolarity of medullary interstitium, causing decrease of H2O reabsorption in collecting duct; powerful so can cause large amounts of water loss

Question 29

what action does frusemide have in common with thiazides

Answer 29

increased delivery of Na+ to distal tubule, increasing K+ loss (increase Na+/K+ exchange), causing hypokalaemia

Question 30

effect of frusemide on Ca2+ and Mg2+ reabsorption and why

Answer 30

loss of K+ recycling, so as K+ recycling drives positive lumen potential, Ca2+ and Mg2+ less well absorbed through paracellular route

Question 31

example of thiazide

Answer 31

bendrofluazide

Question 32

action of bendrofluazide on Na+ reabsorption from early distal tubule

Answer 32

inhibit Na+ and Cl- reabsorption (cotransport protein) in early distal tubule

Question 33

action of bendrofluazide on H2O reabsorption from distal tubule

Answer 33

increase tubular fluid osmolarity so decrease H2O reabsorption in collecting duct; less powerful as not affecting counter current effect

Question 34

what action does bendrofluazide have in common with loop diuretics

Answer 34

increased delivery of Na+ to distal tubule, increasing K+ loss (increase Na+/K+ exchange), causing hypokalaemia; less so than loop diuretics as affects later on and affect countercurrent

Question 35

effect of thiazides on Mg2+ and Ca2+

Answer 35

increase Mg2+ loss (hypokalaemia causing inhibition of distal tubular cell Mg2+ uptake), increase Ca2+ reabsorption (increased proximal Na+ and H2O reabsorption due to volume depletion, leading to increased passive proximal Ca2+ reabsorption)

Question 36

problem of thiazides and loop diuretics in macula densa cells (RAAS)

Answer 36

if take long-term, promote Na+ and water loss, so as reduced renal perfusion pressure and loss of Na+ concentration at distal convoluted tubule, more renin released from granular cells (bigger issue with loop diuretics as stops Na+ entering macula densa cell)

Question 37

2 examples of K+-sparing diuretics

Answer 37

amiloride, spironolactone

Question 38

S47

Answer 38

S47

Question 39

2 classes of K+-sparing diuretics

Answer 39

aldosterone receptor antagonists (spironolactone), inhibitors of aldosterone-sensitive Na+ channels (amiloride)

Question 40

mechanism of action of spironolactone

Answer 40

inhibits aldosterone action of pumping Na+ into distal tubule cell (blocks new Na+ channels being created), and Na+ pumping across basal membrane into interstitium (blocks new Na+/K+-ATPase being created)

Question 41

mechanism of action of amiloride

Answer 41

prevent Na+ being pumped into distal tubule cell through Na+ channels

Question 42

action of K+-sparing diuretics on Na+ reabsorption from distal tubule

Answer 42

inhibit Na+ reabsorption (and concomitant K+ secretion) in early distal tubule

Question 43

action of K+-sparing diuretics on H2O reabsorption from distal tubule

Answer 43

increase tubular fluid osmolarity so decrease H2O reabsorption in collecting duct (as furthest along, worst diuretic at preventing water reabsorption)

Question 44

action of K+-sparing diuretics due to decreased Na+ reabsorption from distal tubule

Answer 44

increased H+ retention (as reduced Na+/H+ exchange)

Question 45

5 common side effects of loop diuretics and thiazides

Answer 45

metabolic alkalosis (Cl- loss), hypovolemia, hyponatraemia, hypokalaemia, hyperuricemia

Question 46

common side effect of K+-sparing diuretics

Answer 46

hyperkalaemia (less Na+/K+ exchange)

Question 47

how is hyperuricemia a common side effect of diuretics

Answer 47

diuretic must get from bloodstream to other side of lumen, so excreted by kidney into lumen (accesses target); transport protein is same that excretes uric acid, so diuretic competes, so uric acid builds up in blood