renal physiology : maintaining electrolyte balance Flashcards
cortical vs juxtamedullary nephrons structure
- 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
what is the name of the capillary network downstream of glomerulus which surrounds the loop of henle and collecting ducts?
vasa recta
what is the descending limb impermeable to?
NaCl
what is the ascending limb impermeable to?
water
____ moves out but ____ doesnt, so fluid becomes sequentially more concentrated towards bottom of loop
- water
- nacl
NaCl is transproted out in the ascending limb due to the gradient set up by what?
NaK ATPase
what is the maximum horizontal osmotic gradient established by the NaCl transporters (NKCC2) in the ascending limb of the loop of henle?
200 mOsm/kg
where is ADH (vasopressin) produced/stored?
produced in hypothalamus and stored in psoterior pituitary
what detect dehydration? what happens?
osmoreceptors in hypothalamus — ADH released — makes collecting duct more permeable to water — water reabsorbed — concentrated urine
what is the main signal for ADH release?
an increase in plasma osmolality
how does aldosterone indirectly cause water reabsorption?
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
AQP2 vs AQP3/4
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
how does blood flow in vasa recta?
in opposite direction to tubular fluid
what does the length of the loop of Henle determine?
the max conc of urine
how does hyperglycaemia in diabetes lead to thirst?
- glucose is osmotically active — encourages water to stay in tubular fluid
- osmotic diuresis
- dehydration detected in hypothalamus
- angiotensin II release — stimulates thirst centres
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?
100 mOsm/kg
activation of V2 receptors in collecting duct by vasopressin leads to insertion of what?
AQP2 into apical membrane
where is msot of K+ found?
98% in cell, 2% in ECF
what moves K+ against its conc grad from ECF into cell?
NaK ATPase
what happens if there is a fall in ECF plasma K+ conc?
hypokalaemia —> hyperpolarisation —> paralysis —> death
what happens if there is an increase in ECF plasma K+ conc?
hyperkalaemia —> depolarisation —> paralysis —> death
how is excess K+ excreted?
92% in urine, 8% via colon
K+ in PCT, LoH, DCT/CD
- PCT — 65% K+ reabsorbed
- LoH — 25% K+ reabsorbed
- DCT + CD — variable K+ reabsorption AND secretion into tubular fluid in excess
how and why does the net charge of tubular fluid change?
starts more -ve and ends more +ve due to reabsorption of K+
how is K+ reabsorbed in the PCT
by the passive movement of K+ paracellulary down an electrochemical gradient back into blood
- K+ being repelled by +ve charge of tubular fluid
what happens to K+ in the thick ascending limb?
- taken back into cell through NKCC2 (SLC12A1)
- leaves cell on basolateral side through K+ channel
what channel allows K+ recycling in the thick ascending limb?
ROMK2 = renal outer medulla K+ channel — transports K+ out on apical side
what is the majority cell type in the collecting duct?
principal cells
what channel creates an osmotic gradient for water to be reabsorbed in the presence of ADH in principal cells?
ENaC
in hyperkalaemic states, what take K+ out of the cell into tubular fluid?
- KCl cotransporter
- ROMK1 and 3 — K+ channels
summarise the actions of aldosterone in the collecting duct
- 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
name the collecting duct cells that are less common than and interspersed with principle cells?
intercalated cells
in hypokalaemic states, K+ goes into cell in exchange for what in intercalated cells?
H+
what does insulin stimulate to help restore K+?
NaH exchanger — therefore more substrate for NaK ATPase
how do high/low calcium levels affect the depolarisation threshold?
hypocalcaemia — lowers depolarisation threshold
hypercalcaemia — raises depolarisation threshold
how do low/high magnesium levels affect heart rate?
hypomagnesaemia = raises HR
hypermagnesaemia = lowered HR
what take up Ca and Mg from ECF?
osteoblasts
what release Ca and Mg?
osteoclasts
what is the principle store of Ca++ and Mg++?
bone
how are Ca++ and Mg++ reabsorbed in the PCT/LoH and DCT?
PCT/LoH:
- 91% Ca++ reabsorbed - paracellular route
- 89% Mg++ reabsorbed - paracellular route
DCT:
- 3-7% Ca++ reabsorption
- 5-6% Mg++ reabsorption
why and how is Ca++ transported in the distal tubule cells?
bound to a carrying molecule = calbindin-D28k — because Ca++ is an intracellular signalling messenger by itself
via what does Ca++ enter the cell in the distal tubule?
TRPV5
what is TRPV5 opened by?
parathyroid hormone, vitamin D, sex hormones
Ca++ leaves the cell in the distal tubule on the basolateral side into the blood via what 1 of what 2 routes?
- NCX1 = Na/Ca exchanger
- PMCA1b = Ca++ ATPase pump
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?
Klotho
involved in ageing?
via what does Mg enter the cell in the distal tubule?
TRPM6
what is Mg++ uptake driven by
electrical gradient
K+ leaves cell down conc grad into tubular lumen — more +ve in tubular fluid — drives Mg++ into the more -ve cell
what binds on the basolateral membrnae of the distal tubule and stimulats Mg++ uptake through TRPM6 opening?
epidermal growth factor
how does Mg++ leave the cell on the basolateral side?
unknown
some sort of exchange r
the intracellular K+ conc is maintained at approx _______ by the actions of ________
- 150 mmol/L
- NaK ATPase pump
insulin can be used to _____ extracellular fluid K+ conc through its actions on _______
- lower
- NaH exchangers
