Regulation of Calcium and Phosphate Flashcards by Daniel Aaron

calcium is in the body in 3 ways

protein-bound (albumin)
complexed to anions (phosphate, sulfate, citrate)
ionized free Ca2+

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which is the active form of calcium

ionized Ca2+

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symptoms of hypocalcemia

hyperrelexia, spontaneous twitching, muscle cramp, tingling and numness

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chvostek sign

indicator of hypocalcemia: twitching of facial muscles eliicted by tapping on facial nerve

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Trousseau sign

hypocalcemia: carpopedal spasm upon inflation of BP cuff

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hypercalcemia symptoms

decreased QT, constipation, decrease appetite, hyporelexia, lethargy, coma

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low extracellular Ca2+ and excitability

reduces activation threshold for Na+ channels, easier to evoke AP

increase in membrane excitability
generation of spontaneous AP is basis for hypocalcemic tetany
produces tingling and numbness and spontaneous muscle twitches

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high extracellular Ca2+ and membrane excitability

decreases excitability

NS becomes depressed and reflex responses are slowed

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increase in plasma protein concentration ____ total Ca2+ concentration
-ionized effect?

increases

no change in Ca2+ ionized

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change in anion concentration: if increase phosphate concentration the ___ inoized Ca2+ concentration

decrease

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in acedemia there is a __ of free ionized Ca2+

increase

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in alkalemia there is a ___ in free ionized Ca2+ concentration

decrease

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calcium homeostasis: GI tract and kidney

kidneys must excrete the same amount of Ca2+ that is absorbed in GI tract

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what positively stimulates bone resorption

PTH and Vitamine D

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distribution of Pi

bone-85%
ICF- 15%
Plasma-

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extracellular concentration of Pi is ____ related to that of calcium

inversely

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what cells of the parathyroid glands secrete PTH

chief cells synthesize and secrete

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regulation of PTH gene expression Ca2+ high

calcium binds to receptor linked to Gq and Gi activates IP3 and DAG which inhibits PTH

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chronic hypercalcemia and PTH

causes decreased synthesis and storage of PTH
increased breakdown of stored PTH
release of inactive PTH fragment into circulation

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chronic hypocalcemia and PTH

causes increased synthesis and storage of PTH

hyperplasia of parathyroid glands (2ndary hyperparathyroidism)

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magnesium and PTH

hypomagnesemia, elicits PTH
hypermagnesemia, inhibits PTH

severe hypomagnesemia inhibits PTH synthesis, storage, and secretion

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effect of PTH on kidney

increased calcium reab
increased urinary cAMP and Pi
-decreased Pi reabsorption

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how does PTH inhibit reabsorption of Pi and enhance its secretion

blocks Na+/Pi cotransporter from lumen into cell
(phosphaturic effect)
-important so that phoshpate does not combine with calcium and decrease free calcium ion levels

PTH effect on intestine

PTH stimulates kidney to make 1a-hydroxylase which is an enzyme that makes active form of Vitamin D which stimulates intestinal Ca2+ absorption

Vitamin D effect on pi and calcium

increases the absorption of both and promotes mineralization of new bone

2 sources of Vitamin D

ingested in the diet | synthesized in skin from 7-dehydrocholesterol in presence of UV light

what positvely stimulates 1a hydroxylase to become active

decrease in Pi decrease in Calcium increase in PTH

1a hydroxylase and increased calcium txn level path

increased calcium binds receptor Gq/Gi stimulated-->IP3 and Ca++ stimulated inhibits CYP1a gene-->no 1a-hydroxylase

1a hydroxylase and increased PTH txn level path

PTH binds kidney cell receptor with Gs protein--->Gs pathway--->cAMP--> stimulates CYP1a gene to make 1a-hyrdoxylase

short term actions of PTH

bone formation via direct action on osteoblast

long term actions of PTH on bone

increased bone resorption (indirect action on osteoclasts)

Vitamin D and bone formation/resorption

Vitamin D acts synergistically with PTH to stimulate osteoclast activity and bone resorption

what increases RANKL and decreases OPG

PTH

what just increases RANKL

vitamin D

mechanism of PTH on the kidney

PTH binds receptor and creates cAMP (excreted in urine) activates PK which phosphorylates Na+/Pi+ transporter and turns off. -second renal action is on DCT to reabsorb calcium

vitamin D effect on intestine

calcium comes down concentration gradient, calbindin binds it and shuttles it to Ca2+ ATPase into the blood

where in the kidney does Ca2+ reabsorption occur when stimulated by PTH

TAL and DCT

Vitamin D action on kidney

promotes Pi reabsoroption by proximal nephrons by stimulating NPT2a expression

calcitonin actions

decrease blood calcium and phosphate concentrations by inhibiting bone resorption -decreases activity and number of osteoclasts

estradiol stimulates what

intestinal Ca2+ absorption and renal tubular Ca2+ reabsorption -promotes survival of osteoblasts and apoptosis of osteoclasts

adrenal glucocorticoids (cortisol) and bones

promote bone resorption and renal Ca2+ wasting and inhibit intestinal ca2+ absorption -patinets treated with high levels of glucocorticoid can develop osteoporosis

hyperparathyroidism urine

increase in Pi, calcium, and cAMP

hyperparathyroidism: stone, bones, groans | - treatment

calcium stones, bone resorption, constipation treat with parathyroidectomy

secondary hyperparathyroidism

increase in PTH is secondary to hypocalcemia - renal failure - vitamin D defeciency

albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a)

inherited autosomal dominant disorder, Gs for PTH in BONE and KIDNEY is defective - hypocalcemia, and hyperphophatemia - Increased PTH - administration of exogenous PTH produces no phosphaturic response and no increase in urinary cAMP

albright hereditary osteodystrophy phenotype

frank reynolds | -short stature, short neck, obesity, subcut calcifaction, shortened metatarsals and metacarpals

humoral hypercalcemia of malignancy

PTHrP is produced by tumors with close homology to PTH -increase urinary Ca2+, Pi, and cAMP -increase in blood calcium decrease in blood Pi -decrease in PTH -decrease in vitamin D (vitamin D levels are normally suppressed in cancer)

treatment for humoral hypercalcemia of malignancy

furosemide (inhibits Ca2+ reabsorption and increases calcium excretion) etidronate: inhibits bone resorption

familial hypocalciuric hypercalcemia

autosomal dominant disorder mutation inactivates CaSR in parathyroid glands -decrease in urinary calcium -increase in serum calcium senstivity is lost in renal and parathyroid receptors

rickets

insufficient amount of Ca2+ and Pi available to mineralize growing bone - dietary deficiency of vitamin D - vitamin D resistance (defecient 1a-hydroxylase) - mutations in vitamin D receptor

osteomalacia

in adults | new bone fails to mineralize

vitamin D dependent rickets type I

decrease 1a-hyrdoxylase

vitamin D-dependent rickets type II

decrease in vitamin D receptor

treatment for rickets-osteomalacia

- Vitamin D2 - Ca2+ - sunlight - calcitriol

osteoporosis treatment

-antiresoptive therapy -estrogens -SERMs -calcitonin -RANK inhibitors PTH