Lecture 8 continued Flashcards
PTH is secreted in response to ____ serum Ca++ levels. What effect might this have on the bone? How about on the production of 1,25 diOH D3?
Keep in mind PTH also Inhibits ______ reabsorption.
LOW
It promotes bone resorption to realease Ca++.
It INCREASES the production of 1,25 diOH D3
It inhibits PHOSPHATE resorption (phosphate can combine with Ca++, effectively decreasing free Ca++ in the blood, so decreasing Phosphate effectively increases free Ca++).
In Primary hyperparathyroidism, serum Ca++ is elevated, but so too is URINE Ca++ (despite the fact that PTH promotes Ca++ reabsorption –> this is because there are Ca++ receptors on the _______ side of tubular cells –> they detect increased Ca++ –> override PTH and DECREASE Ca++ reabsorption in the kidney).
Basolateral side
CaSR (Ca Sensing Receptors) can be found on cells in the TAL where they ______ (increase or decrease?) cAMP, and thus decrease the activity of the _______ cotransporter –> this decreases the movement of K+ out of the cell –> less positive charge in the lumen –> less driving force for paracellular reabsorption of Ca++.
Decrease cAMP
Decrease NA/K/2Cl transporter
______ (Sensipar) is a CaSR AGONIST –> decreases PTH and plasma Ca++. It is approved for treatment of ________ hyperparathyroidism and parathyroid carcinoma.
Cinacalcet
Secondary
In Familial Hypocalciuric Hypercalcemia (FHH) there is a loss of function mutation of the ______ –> increases PTH but ALSO increases reabsorption of Ca++ in TAL cells irrespective of PTH. What effect would this have on Urine Ca++ concentration?
CaSR
This would result in LOW urine Ca++ –> can distinguish between FHH and Primary Hyperparathyroidism
Both Thiazide diuretics and Amiloride _______ (depolarize or hyperpolarize?) cells in the DCT (Thiazide via indirectly increasing intracellular ______, and Amiloride by directly decreasing intracellular _____). This INCREASES Ca++ reabsorption.
Hyperpolarize
Thiazide –> indirectly increases intracellular Cl-
Amiloride –> directly decreases intracellular Na+
In both cases, intracellular becomes MORE negative –> driving force for positive Ca++ to move in.
About 80% of Phosphate is reabsorbed in the ______ of the nephron via a Phosphate / _______ antiporter. This antiporter is inhibited by ______ via its activation of PKA –> increases Phosphate excretion. ______ has the opposite effect (promotes Phosphate retention).
PCT
Phosphate/Na+ antiporter
PTH
Vit D
Low serum Mg++, similar to Ca++, will cause ______ (hyper or hypo?)-excitability of cells.
Where does most (about 70%) of Mg++ reabsorption take place?
HYPERexcitability
Mostly in the TAL via paracellular transport –> remember it’s the positive lumen charge here that drives paracellular transport of Ca++ and Mg++
Mg++ reabsorption in the TAL can be decreased by mutations in ______ 16 and 19, proteins that comprise the tight junctions through which paracellular transport occurs in the TAL.
Claudin 16 and 19
About `10% of Mg++ reabsorption occurs in the ______ via trancellular transport through TRPM6 Mg++ channel. Mutations in this channel results in Hypomagnesemia and secondary _________.
DCT
Hypocalcemia
