renal physiology : maintaining electrolyte balance

Question 1

cortical vs juxtamedullary nephrons structure

Answer 1

• cortical — dip a little into outer part of the medulla
• juxtamedullary — located much lower down in cortex - have long loops of henle that dip low into medulla. responsibel for concentrating

Question 2

what is the name of the capillary network downstream of glomerulus which surrounds the loop of henle and collecting ducts?

Answer 2

vasa recta

Question 3

what is the descending limb impermeable to?

Answer 3

NaCl

Question 4

what is the ascending limb impermeable to?

Answer 4

water

Question 5

____ moves out but ____ doesnt, so fluid becomes sequentially more concentrated towards bottom of loop

Answer 5

• water
• nacl

Question 6

NaCl is transproted out in the ascending limb due to the gradient set up by what?

Answer 6

NaK ATPase

Question 7

what is the maximum horizontal osmotic gradient established by the NaCl transporters (NKCC2) in the ascending limb of the loop of henle?

Answer 7

200 mOsm/kg

Question 8

where is ADH (vasopressin) produced/stored?

Answer 8

produced in hypothalamus and stored in psoterior pituitary

Question 9

what detect dehydration? what happens?

Answer 9

osmoreceptors in hypothalamus — ADH released — makes collecting duct more permeable to water — water reabsorbed — concentrated urine

Question 10

what is the main signal for ADH release?

Answer 10

an increase in plasma osmolality

Question 11

how does aldosterone indirectly cause water reabsorption?

Answer 11

needs ADH

• aldosterone generates and inserts ENaC into apical membrane of late distal/collecting duct
• aldosterone opens K+ channels allowing K+ put into tubular fluid
• ADH released and binds to V2 receptors on collecting duct cells
• V2 activation by ADH leads to insertion of H2O channels (esp AQP2) into apical membrane
• when present, AQP2 allows H2o to enter down osmotic gradient created by Na+ entry through ENaC

Question 12

AQP2 vs AQP3/4

Answer 12

AQP2 = apical membrane of late distal/collecting duct, ADH leads to its insertion

AQP3/4 = permanently inserted into basolateral (blood) membrane — basolateral side therefore always permeable to water

Question 13

how does blood flow in vasa recta?

Answer 13

in opposite direction to tubular fluid

Question 14

what does the length of the loop of Henle determine?

Answer 14

the max conc of urine

Question 15

how does hyperglycaemia in diabetes lead to thirst?

Answer 15

• glucose is osmotically active — encourages water to stay in tubular fluid
• osmotic diuresis
• dehydration detected in hypothalamus
• angiotensin II release — stimulates thirst centres

Question 16

following a head trauma, a patient develops central diabetes insipidus which is associated with a reduction in vasopressin secretion. the osmolality of a spot urine sample is expected to be what?

Answer 16

100 mOsm/kg

Question 17

activation of V2 receptors in collecting duct by vasopressin leads to insertion of what?

Answer 17

AQP2 into apical membrane

Question 18

where is msot of K+ found?

Answer 18

98% in cell, 2% in ECF

Question 19

what moves K+ against its conc grad from ECF into cell?

Answer 19

NaK ATPase

Question 20

what happens if there is a fall in ECF plasma K+ conc?

Answer 20

hypokalaemia —> hyperpolarisation —> paralysis —> death

Question 21

what happens if there is an increase in ECF plasma K+ conc?

Answer 21

hyperkalaemia —> depolarisation —> paralysis —> death

Question 22

how is excess K+ excreted?

Answer 22

92% in urine, 8% via colon

Question 23

K+ in PCT, LoH, DCT/CD

Answer 23

• PCT — 65% K+ reabsorbed
• LoH — 25% K+ reabsorbed
• DCT + CD — variable K+ reabsorption AND secretion into tubular fluid in excess

Question 24

how and why does the net charge of tubular fluid change?

Answer 24

starts more -ve and ends more +ve due to reabsorption of K+

Question 25

how is K+ reabsorbed in the PCT

Answer 25

by the passive movement of K+ paracellulary down an electrochemical gradient back into blood - K+ being repelled by +ve charge of tubular fluid

Question 26

what happens to K+ in the thick ascending limb?

Answer 26

- taken back into cell through NKCC2 (SLC12A1) - leaves cell on basolateral side through K+ channel

Question 27

what channel allows K+ recycling in the thick ascending limb?

Answer 27

ROMK2 = renal outer medulla K+ channel — transports K+ out on apical side

Question 28

what is the majority cell type in the collecting duct?

Answer 28

principal cells

Question 29

what channel creates an osmotic gradient for water to be reabsorbed in the presence of ADH in principal cells?

Answer 29

ENaC

Question 30

in hyperkalaemic states, what take K+ out of the cell into tubular fluid?

Answer 30

- KCl cotransporter - ROMK1 and 3 — K+ channels

Question 31

summarise the actions of aldosterone in the collecting duct

Answer 31

- opens ENaC - opens ROMK — to allow loss of K+ from IC space to tubular fluid - reverse direction of basolateral K+ channel - K+ goes into cell to allow movement of K+ pout throguh ROMK1 and 3

Question 32

name the collecting duct cells that are less common than and interspersed with principle cells?

Answer 32

intercalated cells

Question 33

in hypokalaemic states, K+ goes into cell in exchange for what in intercalated cells?

Answer 33

H+

Question 34

what does insulin stimulate to help restore K+?

Answer 34

NaH exchanger — therefore more substrate for NaK ATPase

Question 35

how do high/low calcium levels affect the depolarisation threshold?

Answer 35

hypocalcaemia — lowers depolarisation threshold hypercalcaemia — raises depolarisation threshold

Question 36

how do low/high magnesium levels affect heart rate?

Answer 36

hypomagnesaemia = raises HR hypermagnesaemia = lowered HR

Question 37

what take up Ca and Mg from ECF?

Answer 37

osteoblasts

Question 38

what release Ca and Mg?

Answer 38

osteoclasts

Question 39

what is the principle store of Ca++ and Mg++?

Answer 39

bone

Question 40

how are Ca++ and Mg++ reabsorbed in the PCT/LoH and DCT?

Answer 40

PCT/LoH: - 91% Ca++ reabsorbed - paracellular route - 89% Mg++ reabsorbed - paracellular route DCT: - 3-7% Ca++ reabsorption - 5-6% Mg++ reabsorption

Question 41

why and how is Ca++ transported in the distal tubule cells?

Answer 41

bound to a carrying molecule = calbindin-D28k — because Ca++ is an intracellular signalling messenger by itself

Question 42

via what does Ca++ enter the cell in the distal tubule?

Answer 42

TRPV5

Question 43

what is TRPV5 opened by?

Answer 43

parathyroid hormone, vitamin D, sex hormones

Question 44

Ca++ leaves the cell in the distal tubule on the basolateral side into the blood via what 1 of what 2 routes?

Answer 44

1. NCX1 = Na/Ca exchanger 2. PMCA1b = Ca++ ATPase pump

Question 45

what is the name of the endocrine regulator in tubular fluid that helps open TRPV5 on the apical membrane of the distal tubule for Ca++ entry into teh cell?

Answer 45

Klotho involved in ageing?

Question 46

via what does Mg enter the cell in the distal tubule?

Answer 46

TRPM6

Question 47

what is Mg++ uptake driven by

Answer 47

electrical gradient K+ leaves cell down conc grad into tubular lumen — more +ve in tubular fluid — drives Mg++ into the more -ve cell

Question 48

what binds on the basolateral membrnae of the distal tubule and stimulats Mg++ uptake through TRPM6 opening?

Answer 48

epidermal growth factor

Question 49

how does Mg++ leave the cell on the basolateral side?

Answer 49

unknown some sort of exchange r

Question 50

the intracellular K+ conc is maintained at approx _______ by the actions of ________

Answer 50

- 150 mmol/L - NaK ATPase pump

Question 51

insulin can be used to _____ extracellular fluid K+ conc through its actions on _______

Answer 51

- lower - NaH exchangers