Regulation of Calcium and Phosphate Metabolism Flashcards
Percent distribution of calcium in:
ECF
Plasma
ICF
Bones and teeth
ECF = 0.1%
Plasma = 0.5%
ICF = 1%
Bones and teeth = 99%
What forms of calcium exist in the blood?
Calcium exists in ionized form, bound to plasma proteins, or complexed in non-ionized form
Protein bound = 40%
Unfilterable = 60%
Of the unfilterable Ca, 10% is complexed to anions and 50% is ionized calcium
T/F: changes in plasma protein concentration alter the total Ca concentration in the opposite direction
False: changes in plasma protein concentration alter the total Ca concentration in the same direction as protein concentration
What are 3 ways of altering forms of Ca in the plasma?
Altering total Ca by changing plasma protein concentration (changes in same direction)
Altering ionized Ca by changing the fraction of Ca complexed with anions (changes anion concentration)
Altering ionized Ca by changing the fraction of Ca bound to proteins (albumin binds Ca and H)
If plasma [Pi] increases, the fraction of Ca that is complexed ________, thereby _______ ionized [Ca]
Increases; decreasing
How does plasma [Ca] change in conditions of acidemia vs. alkalemia?
Acidemia = high plasma [Ca] — high plasma [H], albumin binds more H, thereby increasing Ca
Alkalemia = low plasma [Ca] — low plasma [H], albumin binds more Ca, thereby decreasing Ca
What effect does hypocalcemia have on neuromuscular excitability?
Increases it, because more Ca is inside the cells
May lead to hypocalcemic tetany/spasticity
What effect does hypercalcemia have on neuromuscular excitability?
Depresses it; threshold shifts away from resting membrane potential
What are the regulators of plasma levels of calcium, thus controlling neuromuscular excitability?
PTH
Calcitonin
Calcitriol
Primary hyperparathyroidism and malignancy are clinical conditions related to _____levels of serum Ca
Elevated
Hypoparathyroidism, renal disease, and vit D deficiency are clinical conditions related to ___ serum Ca
Low
What are the 3 coordinated organ systems primarily involved in Ca homeostasis?
Bone
Kidney
Intestines
What hormone is responsible for bone formation from body calcium pool
Calcitonin
What hormones are responsible for bone resorption into body calcium pool?
PTH
Calcitriol
What hormones inhibit Ca excretion from kidneys?
PTH
Calcitriol
Calcitonin
What hormone is responsible for absorption of calcium from the GI tract into the body calcium pooL?
Calcitriol
About 1500 mg of Ca is taken in daily via the diet. The majority of this is excreted where?
Stool = 1300 mg
[200 mg excreted in urine]
Extracellular concentration of Pi is inversely correlated to that of _____.
Ca
Where is the majority of our phosphate stored?
85% in bone
[14% in cells, less than 1% serum]
What system primarily controls the fine tuning of phosphate levels?
Renal excretion
[renal tubular reabsorption is inhibited by PTH; reabsorption depends on transport maximum]
What are the 4 classic regulators of phosphate metabolism?
Dietary
Calcitriol
PTH
Renal tubular
Calcitriol regulation of phosphate metabolism
Calcitriol increases phosphorus resorption from bone and absorption from intestine
INCREASES Pi reabsorption in kidney
PTH regulation of phosphate metabolism
Phosphorus resorption directly from bone, and indirectly activates intestinal absorption through stimulation of calcitriol production
What endocrine factors directly or indirectly control NaPi cotransporter activity in the apical membrane?
PTH
Vitamin D
FGF23
What effect do insulin, GH, and thyroid hormone have on renal phosphate reabsorption?
Increase it
What effect do calcitonin, glucocorticoids, and ANP have on renal phosphate reabsorption?
Decrease it
What effect does a gain of function mutation have in FGFR3?
Achondroplasia
Endocrine FGF derived from bone, regulated by phosphate and vitamin D levels, which in turn regulate phosphate homeostasis
FGF23
3 renal effects of FGF 23
Directly downregulates NaPi transporters in kidney
Stimulates PTH to downregulate NaPi transporters in kidney
Decreases Calcitriol production in kidney
Where is PTH synthesized and secreted?
Chief cells of parathyroid gland
Low plasma (ionized) [Ca] has what effect on PTH secretion?
Stimulates it
What is the role of the calcium sensing receptor (CaSR) in regulating release of PTH and reabsorption of Ca in the nephron?
Increased ECF [Ca] inhibits PTH secretion, bc calcium activates Gq pathway leading to inhibition of PTH expression at gene level
Low ECF [Ca] stimulaltes PTH secretion — when Ca is not present, CaSR gene is upregulated so that more calcium can bind
Mutations in CaSR can cause what condition?
Familial hypocalciuric hypercalcemia (FHH)
Effect of chronic hypercalcemia on PTH levels
Decreases synthesis/storage PTH
Breaks down any stored PTH, releases inactive PTH fragments into circulation
Effect of chronic hypocalcemia on PTH levels
Increases synthesis/storage of PTH
Results in hyperplasia of parathyroid glands (aka secondary hyperparathyroidism)
What effect does magnesium have on PTH?
Same effects as calcium, but to a lesser extent (so typically decreases synthesis/storage of PTH)
Exception = severe hypomagnesemia may inhibit PTH synthesis, storage, and secretion
What three signaling molecules are responsible for the physiologic actions of PTH?
PKA
ionized [Ca]
PKC
Decreased plasma [Ca] —> _______ PTH secretion —> ______ bone resorption and ____ Ca and Pi in blood
Increased; increased; increased
Decreased plasma Ca —> _______ PTH secretion; _____ Pi reabsorption in kidney, ______ Ca reabsorption, and _____ urinary cAMP
Increased; Decreased; increased; increased
Decreased plasma Ca —> ______ PTH secretion —> ______ Ca absorption in intestine
Increased; increased
What effect does vitamin D have on plasma concentrations of calcium and phosphate via action from bone?
Increases both