renal homeostasis - Ca2+, Mg2+, Pi, HCO3, Nh4+ Flashcards
what are the different functions of kidney
filter - at glomerus
rebsorb and secrete - whole nephron
excrete - as urine
what are some roles of calcium in the body?
formation of bones and teeth
synaptic transmission
blood clotting
contraction of neuro and cardio cells
why does calcium need to be regulated? Why is calcium homeostasis important?
there is a huge concentration gradient between intra and extracellular calcium
100nM vs 2.5mM
which drives calcium influx and signalling pathways
what are the 2 ways ions can travel from filtrate/lumen and reabsorb back to blood? How are these regulated?
paracellular transport - regulated by tight junctions or an electrochemical force
transcellular transport - through cell cytoplasm regulated by transporters (active or passive)
how do parathyroid and calcitriol/VitD3 affect calcium homeostasis?
> generally?
SYNERGYSTIC relationship and act to increase calcium plasma levels
How do calcitriol influence calcium homeostasis?
increase intestinal uptake by acting on its receptor -> transcriptional regulation
> increases Ca channel on apical
> increase calbindin protein
> increase PMCA activity
what are claudins?
proteins that form tight junctions and affect permeability of cell membrane to ions
affect paracellular transport of ions
how do PTH and calcitonin act in calcium homeostasis? (simple)
they use negative feedback loops
calcitonin = tone it down
PTH = increase plasma calcium levels
how does calcitonin influence calcium homeostasis? (detailed)
Increases bone deposition and reduces intentine absorb and renal reabsorb
gastrin in stomach can increase calcitonin secretion
how are changes in calcium plasma conc sensed?
via the Calcium sensing receptor (CaSR) which is a GPCR
how does the CaSR act?
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
what gene is responsible for the conditions fo FHH1 and ADH1?
loss of function or gain of function of calcium sensing receptor
results in hypo or hyper calcemia and LOF often coincides with hyper parathyroidism
why are claudins important?
a KO of claudin reduced calcium permeability so can influence homeostasis of ions
crucial for the vitamin d3 dependent calcium absorption in intestine
what are the main ways that PTH and VitD3 affect calcium homeostasis (detailed)
increase intenstine absorption and kidney reabsorption of Ca2+
increase activity of osteoclasts to degrade bone and stored calcium
how does the function of CaSR change in the kidney?
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
what causes gitelmans syndrome (genetic disorder)
Loss of function of NCC cotransporter on the DCT apical side
describe movement of ions in gietelmanns syndome
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
what are the consequences of gitelmans syndrome?
hypercalciaemia - more reabsorb
hypotensive disorder
what is a unique mechanism about Bartters syndrome?
the defect is in the thick ascending limb but the actual effects are seen downstream in the DCT
why do loop diuretics reduce calcium reabsorption in the kidney?
loop diuretics target the NKCC2 cotransporter in the TAL
this reduces the electrochemical force to drive paracellular calcium movement
what is the genetic defect in barterrs syndrome
the NKCC2 in the TAL is non-fuctional so
Na, K and Cl remain in filtrate
what are the consequences of Barterrs syndrome?
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
what channels in collecting duct drive calcium reabsorption?
ENAC channels create electrochemical gradient to drive water and calcium reabsorption
how can ammonium (NH4+) be reabsorpbed in nephron?
instead of potassium, ammonium can take the place in various cotransporters/channels/eexchangers
is ammonium transport affected in barrters sydrome?
What is a consequence?
No!
Which is odd as the NKCC2 mutation would affect ammonium transport too
likely NH4+ transport is compenstated by other transporters
is bicarbonate homeostasis affected in Barterrs Syndrome?
What is a consequence?
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
what are TRM6/7 channels used for?
used to move Mg2+ from apical to basal down a conc. gradient
found in intestine and DCT
how is magnesium transported out of cell and back to blood (reabsorbed)
via SLC family transporters which exchange mg2+ with na+
kinda new
where is bulk of phosphate reabsorbed in nephron?
in the PCT
using 3 sodium cotransporters to move the different isoforms of phosphate
how does PTH affect phosphate homeostatis
acts to lower absorption by reducing the availiabiltiy of the sodium co transporters
how does FGF23 affect phosphate homeostasis
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
what is klotho?i
it is a cofactor produced in kIDNEY needed for fgf23 to function as they dimerise
reduce availality of cotransporters in PCT
in CKD is there hyper or hypophosphatemia
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
where is fgf23 made?
released from bone osteoblasts in response to high phosphate level
