Regulation of Calcium and Phosphate Flashcards
calcium is in the body in 3 ways
protein-bound (albumin)
complexed to anions (phosphate, sulfate, citrate)
ionized free Ca2+
which is the active form of calcium
ionized Ca2+
symptoms of hypocalcemia
hyperrelexia, spontaneous twitching, muscle cramp, tingling and numness
chvostek sign
indicator of hypocalcemia: twitching of facial muscles eliicted by tapping on facial nerve
Trousseau sign
hypocalcemia: carpopedal spasm upon inflation of BP cuff
hypercalcemia symptoms
decreased QT, constipation, decrease appetite, hyporelexia, lethargy, coma
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
high extracellular Ca2+ and membrane excitability
decreases excitability
NS becomes depressed and reflex responses are slowed
increase in plasma protein concentration ____ total Ca2+ concentration
-ionized effect?
increases
no change in Ca2+ ionized
change in anion concentration: if increase phosphate concentration the ___ inoized Ca2+ concentration
decrease
in acedemia there is a __ of free ionized Ca2+
increase
in alkalemia there is a ___ in free ionized Ca2+ concentration
decrease
calcium homeostasis: GI tract and kidney
kidneys must excrete the same amount of Ca2+ that is absorbed in GI tract
what positively stimulates bone resorption
PTH and Vitamine D
distribution of Pi
bone-85%
ICF- 15%
Plasma-
extracellular concentration of Pi is ____ related to that of calcium
inversely
what cells of the parathyroid glands secrete PTH
chief cells synthesize and secrete
regulation of PTH gene expression Ca2+ high
calcium binds to receptor linked to Gq and Gi activates IP3 and DAG which inhibits PTH
chronic hypercalcemia and PTH
causes decreased synthesis and storage of PTH
increased breakdown of stored PTH
release of inactive PTH fragment into circulation
chronic hypocalcemia and PTH
causes increased synthesis and storage of PTH
hyperplasia of parathyroid glands (2ndary hyperparathyroidism)
magnesium and PTH
hypomagnesemia, elicits PTH
hypermagnesemia, inhibits PTH
severe hypomagnesemia inhibits PTH synthesis, storage, and secretion
effect of PTH on kidney
increased calcium reab
increased urinary cAMP and Pi
-decreased Pi reabsorption
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
