BC 12/4/23: Regulation of Calcium, Magnesium, and Phosphate from Vander’s renal physiology 8th Flashcards
(36 cards)
What is the most important hormone/factor in regulating urinary calcium and phosphorous reabsorption/excretion? And what is its net effect?
PTH. Overall net effect is to promote calcium reabsorption phosphorous excretion
What are the effects of acidaemia and alkalaemia on calcium homeostasis in the kidney?
Acidaemia: increases urinary calcium excretion (stimulation of TRPV5 channel)
Alkalaemia: reduces urinary calcium excretion (inhibition of TRPV5 channel)
What are the functions of iCa?
Ionized calcium is required for:
-Enzymatic reactions
-Membrane transport and stability
-Blood coagulation
-Nerve conduction
-Neuromuscular transmission
-Muscle contraction
-Vascular smooth muscle tone
-Hormone secretion
-Bone formation and resorption
-Control of hepatic glycogen metabolism
-Cell growth and division
Major are the 2 major calcium homeostasis regulators?
- PTH (minute-to-minute)
- Calcitriol (day-to-day)
What other hormones influence calcium homeostasis?
-FGF23
- Adrenal corticosteroids
-Estrogens
-Thyroxine
-Growth hormone
-Glucagon
-Prolactin
What are the major target organs affected by calcium regulatory hormones?
- GI
- bone
- kidneys
How is totCa distributed in the body?
-99% in skeleton as hydroxyapatite, Ca10(PO4)6(OH)2
-ECF (<1%)
-intracellular (0.01%)
How can you find Calcium in plasma?
3 fractions:
- iCa (56%)
- Complexed Ca (10%)= bound to P, bicarbonate, sulfate, citrate, lactate) (10%)
- Protein bound (34%)
How does low Ca cause tetany?
Hypocalcemia causes increased neuromuscular excitability by decreasing the threshold needed for the activation of neurons. As a result, neurons become unstable and fire spontaneous action potentials that trigger the involuntary contraction of the muscles, which eventually leads to tetany.
(From Vander’s: low levels of calcium fool sodium channels
into sensing more depolarization than actually exists, leading to spontaneous
firing of motor neurons. In turn, this firing triggers inappropriate muscle contraction,
called low-calcium tetany.)
How does pH influences calcium level?
Increased pH (alkalosis)= increases protein binding, which decreases free calcium levels.
Acidosis= decreases protein binding, resulting in increased free calcium levels
How is moment to moment regulation of plasma calcium achieved?
by moving calcium in and out of bone.
T/F most of the dietary calcium is reabsorbed at the level of the jejunum.
F: Most dietary calcium simply passes through the GI tract to the feces.
How is Ca absorbed in the small intestine?
Duodenum: active transcellular process= Calcium enters duodenal cells passively through Ca-selective channels (members of the TRP family), binds reversibly
to mobile cytosolic calcium binding proteins (calbindins), and is then
actively transported out the basolateral side via a Ca-ATPase and, to some extent, by a Na-Ca antiporter.
Lower small intestine: paracellular diffusion
How much of the Ca is reabsorbed in the kidneys? And how much is secreted?
Reabsorbed 98% (65% in PCT, 20% in loop of Henle, rest in CDT and collecting duct), Secreted 0%
How is Ca reabsorbed in the different portions of the kidneys?
- PCT: passive and paracellular transport. Water reabsorption in
the PCT concentrates Ca and drives paracellular flux - Thick ascending limb Henle’s loop: passive and paracellular transport. The
lumen-positive potential is the major driving force. - Distal tubule: active transcellular (same as GI tract= entrance via Ca-specific TRP channels, diffusion bound
to calbindins and active exit across basolateral memb by a combination of
Ca-ATPase and Na-Ca antiport activity.
Why is saline the fluid of choice in hypercalcemia?
Increase Na= increase GFR= large amounts
of Ca-containing fluid pass through the kidneys to the urine.
Independent,
calcium-specific regulation of calcium excretion is exerted in the distal tubule via control of active calcium reabsorption.
How is phosphate distributed in the body?
- bone (85%)= inorganic hydroxyapatite
- soft tissue (15%)= phospholipids, nucleic acids, phosphoprot.
T/F most of the dietary phosphate is reabsorbed at the level of the small intestine.
T: 65%
How is phosphate reabsorbed by the GI tract?
By paracellular diffusion and by transcellular active transport. The active component uses several different Na-phosphate symporters in the apical
membrane to bring phosphate into the intestinal enterocytes. The exit step is not characterized, but is presumed to be via a phosphate uniporter.
T/F: the majority of phosphate in the blood is protein bound
F: only 5-10% if protein bound.
How much of the filtered phosphate is reabsorbed in the PCT and how?
75%, Na-phosphate symporters (like in the GI tract) - tubular maximum-limited system= can be saturated
How is the active form of vit D called? How is it produced?
Calcitriol. precursor is hydroxylated at the 25th position by the liver and then hydroxylated again at the first position by proximal tubular cells within the kidneys to yield the active form,.
How do PTH and FGF23 redulate the production of calcitriol?
PTH stimulates it VS FGF23 inhibits it.
What are the effects of calcitriol?
- stimulate transcellular
absorption of Ca and, to a lesser extent, phosphate, by the duodenum - stimulates the renal-tubular reabsorption
of both calcium and phosphate
= bone promoting hormone - inhibits PTH (negative feedback)
- stimulated FGF23
