renal homeostasis - Ca2+, Mg2+, Pi, HCO3, Nh4+

Question 1

what are the different functions of kidney

Answer 1

filter - at glomerus
rebsorb and secrete - whole nephron
excrete - as urine

Question 2

what are some roles of calcium in the body?

Answer 2

formation of bones and teeth
synaptic transmission
blood clotting
contraction of neuro and cardio cells

Question 3

why does calcium need to be regulated? Why is calcium homeostasis important?

Answer 3

there is a huge concentration gradient between intra and extracellular calcium
100nM vs 2.5mM

which drives calcium influx and signalling pathways

Question 4

what are the 2 ways ions can travel from filtrate/lumen and reabsorb back to blood? How are these regulated?

Answer 4

paracellular transport - regulated by tight junctions or an electrochemical force

transcellular transport - through cell cytoplasm regulated by transporters (active or passive)

Question 5

how do parathyroid and calcitriol/VitD3 affect calcium homeostasis?
> generally?

Answer 5

SYNERGYSTIC relationship and act to increase calcium plasma levels

Question 6

How do calcitriol influence calcium homeostasis?

Answer 6

increase intestinal uptake by acting on its receptor -> transcriptional regulation
> increases Ca channel on apical
> increase calbindin protein
> increase PMCA activity

Question 7

what are claudins?

Answer 7

proteins that form tight junctions and affect permeability of cell membrane to ions

affect paracellular transport of ions

Question 8

how do PTH and calcitonin act in calcium homeostasis? (simple)

Answer 8

they use negative feedback loops

calcitonin = tone it down
PTH = increase plasma calcium levels

Question 9

how does calcitonin influence calcium homeostasis? (detailed)

Answer 9

Increases bone deposition and reduces intentine absorb and renal reabsorb

gastrin in stomach can increase calcitonin secretion

Question 10

how are changes in calcium plasma conc sensed?

Answer 10

via the Calcium sensing receptor (CaSR) which is a GPCR

Question 11

how does the CaSR act?

Answer 11

lowers calcium plasma levels

becomes activated when all calcium binding sites are occupied -> triggers signalling pathways to reduce PTH synthesis and production

negative feedback loop

Question 12

what gene is responsible for the conditions fo FHH1 and ADH1?

Answer 12

loss of function or gain of function of calcium sensing receptor

results in hypo or hyper calcemia and LOF often coincides with hyper parathyroidism

Question 13

why are claudins important?

Answer 13

a KO of claudin reduced calcium permeability so can influence homeostasis of ions

crucial for the vitamin d3 dependent calcium absorption in intestine

Question 14

what are the main ways that PTH and VitD3 affect calcium homeostasis (detailed)

Answer 14

increase intenstine absorption and kidney reabsorption of Ca2+

increase activity of osteoclasts to degrade bone and stored calcium

Question 15

how does the function of CaSR change in the kidney?

Answer 15

CaSR acts independently of PTH.

CaSR reduces paracellular calcium transport in the TAL by increasing claudin expression making membrane less permeable

also CaSR blocks ROMK channels lowering the electrochemical repellant driving force for paracellular transport

Question 16

what causes gitelmans syndrome (genetic disorder)

Answer 16

Loss of function of NCC cotransporter on the DCT apical side

Question 17

describe movement of ions in gietelmanns syndome

Answer 17

as sodium entry is decreased, there is less sodium inside of cell

The function of basal NCX1 is easier to exchange sodium and calcium

More calcium is reabsorbed

Question 18

what are the consequences of gitelmans syndrome?

Answer 18

hypercalciaemia - more reabsorb

hypotensive disorder

Question 19

what is a unique mechanism about Bartters syndrome?

Answer 19

the defect is in the thick ascending limb but the actual effects are seen downstream in the DCT

Question 20

why do loop diuretics reduce calcium reabsorption in the kidney?

Answer 20

loop diuretics target the NKCC2 cotransporter in the TAL

this reduces the electrochemical force to drive paracellular calcium movement

Question 21

what is the genetic defect in barterrs syndrome

Answer 21

the NKCC2 in the TAL is non-fuctional so

Na, K and Cl remain in filtrate

Question 22

what are the consequences of Barterrs syndrome?

Answer 22

excess ions in filtrate travel to DCT. Sodium is cotransported with Cl into cell

This makes the NCX1 exhcanger harder to function so less calcium reabsorb

hypercalciuria a consequences

Question 23

what channels in collecting duct drive calcium reabsorption?

Answer 23

ENAC channels create electrochemical gradient to drive water and calcium reabsorption

Question 24

how can ammonium (NH4+) be reabsorpbed in nephron?

Answer 24

instead of potassium, ammonium can take the place in various cotransporters/channels/eexchangers

Question 25

is ammonium transport affected in barrters sydrome?
What is a consequence?

Answer 25

No!
Which is odd as the NKCC2 mutation would affect ammonium transport too

likely NH4+ transport is compenstated by other transporters

Question 26

is bicarbonate homeostasis affected in Barterrs Syndrome?
What is a consequence?

Answer 26

Yes.
As NKCC2 nonfucntional there is high sodium in the filtrate

so more Na+ H+ exchange occurs in the TAL. So there is lesss hydrogen in cell, less acidic

higher retention of bicarbonate = metabolic acidosis

Question 27

what are TRM6/7 channels used for?

Answer 27

used to move Mg2+ from apical to basal down a conc. gradient

found in intestine and DCT

Question 28

how is magnesium transported out of cell and back to blood (reabsorbed)

Answer 28

via SLC family transporters which exchange mg2+ with na+

kinda new

Question 29

where is bulk of phosphate reabsorbed in nephron?

Answer 29

in the PCT

using 3 sodium cotransporters to move the different isoforms of phosphate

Question 30

how does PTH affect phosphate homeostatis

Answer 30

acts to lower absorption by reducing the availiabiltiy of the sodium co transporters

Question 31

how does FGF23 affect phosphate homeostasis

Answer 31

directly acts on kidney to decrease VitD3 synthesis and availbility of cotransporters

indirectly affects by acting on parathyroid gland to reduce PTH synthesis

overall reduction in phosphate in serum

Question 32

what is klotho?i

Answer 32

it is a cofactor produced in kIDNEY needed for fgf23 to function as they dimerise

reduce availality of cotransporters in PCT

Question 33

in CKD is there hyper or hypophosphatemia

Answer 33

as kidneys are failing the GFR is low so kidney function diminishes

eleveted serum phosphate as feedback loop of PTH release canot rescue. Also release of FGF23 in osteblasts too

can result in 2nd hyperparathyroidism

Question 34

where is fgf23 made?

Answer 34

released from bone osteoblasts in response to high phosphate level