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ENRE > Regulation of Calcium and Phosphate Metabolism > Flashcards

Regulation of Calcium and Phosphate Metabolism Flashcards

1
Q

Where is calcium distributed in the body?

What is the active form of calcium?

A

99% in bones and teeth

more in ICF than ECF

free, ionized Ca = active

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2
Q

What percentage of total Ca is free ionized?

A

50%

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3
Q

What is the the normal calcium level for adults?

How does it differ in children?

A

in the 9s = btw 9 and 10 mg/dl

higher in teens/puberty age

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4
Q

What are indicators of hypocalcemia?

A

numbness and tingling, spontaneous twitching

chvostek sign = twitching of facial ms from tapping on facial nerve

trousseau sign = carpopedal spasm upon inflation of bp cuff

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5
Q

What occurs to membrane potentials in hypocalcemia?

A

reduces threshold for na channels –> easier APs

can get hypocalcemic tetany

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6
Q

What occurs to membrane potentials in hypercalcemia?

A

harder to get APs –> nervous sys depressed and reflex responses slowed

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7
Q

How does plasma protein concentration affect Ca levels?

A

alter total Ca concentration in same direction (more protein, more total Ca)

no change in ionized Ca

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8
Q

How do changes in anion concetration affect Ca concentration?

A

changes fraction of Ca complexed w/ anions

if Pi increases, ionized Ca decreases

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9
Q

How does acid base affect ionized Ca?

A

acidemia –> H+ take up spots on albumin –> more free calcium

alkalemia –> decreased free Ca

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10
Q

To maintain Ca balance, what occurs?

A

kidneys must excrete the same amount of Ca that is absorbed by the GI tract

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11
Q

What is the relationship btw Ca and phosphate?

A

inversely related

extracellular concentration of Pi is regulated by same hormones that regulate Ca

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12
Q

Where is Pi distributed?

A

85% in bone

84% of plasma is ionized

more in ICF than ECF

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13
Q

Where is PTH synthesized and secreted?

A

from chief cells of the parathyroid gland

main stimulus is decreased plasma Ca

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14
Q

What type of hormone is PTH?

How is it synthesized?

A

peptide hormone

preproPTH(115 aa) –> proPTH (90 aa) –> PTH in golgi –> packaged in secretory granules

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15
Q

What does Vit D do to PTH signaling?

A

down regulates PTH gene

stimulates CaSR gene –> PTH can more sensitively respond to Ca

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16
Q

How does increased Ca influence PTH?

A

inhibits PTH synthesis and secretion

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17
Q

How do chronic hyper and hypocalcemia affect PTH?

A

chronic hyper –> decreased synthesis and storage of PTH, increased breakdown and relase of inactive fragments

chronic hypo –> increased synthesis and storage, hyperplasia of parathyroid glands

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18
Q

How does magnesium affect PTH?

A

parallel to Ca, but less significant effects

severe hypomagnesemia (seen in alcoholism) –> inhibition of PTH synthesis, storage and secretion

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19
Q

What type of receptor does PTH work on?

A

Gs GPCR

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20
Q

What are the actions of PTH on bone, kidney, and intestine?

A

Bone: increases bone resorption

kidney: decreased Pi reabsorption, increased ca reabsorption, increased urinary cAMP
intestine: increased Ca absorption

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21
Q

What type of hormone is Vit D?

A

steroid hormone

25 OH cholecalciferol = inactive circulating

1, 25 OH cholecalciferol = active

24,25 OH cholecalciferol = inactive

22
Q

How is Vit D activated?

A

via 1 alpha-hydroxylase in proximal tubule of kidney

23
Q

Where are PTH receptors located in bone?

What are its short and long-term actions?

A

on osteoblasts

short-term = bone formation

long-term = bone resorption indirectly via cytokines from osteoblast –> osteoclasts

24
Q

How does Vit D act on bone?

A

synergistically w/ PTH –> stim osteoclast activity and bone resorption

25
What two important signals act on osteoclasts to promote bone resorption?
IL-6 Rank ligand
26
What is M-CSF?
growth factor induces stem cells --\> differentiate into osteoclast precursors --\> mononuclear osteoclasts --\> mature multinucleated osteoclasts
27
What are RANK and RANKL?
RANK = cell surface protein on osteoclasts and osteoclasts precursors RANKL = cell surface protein produced by osteoblasts, bone lining cells, and apoptotic ostocytes they bind --\> osteoclasts form --\> bone resorption
28
What is OPG?
soluble protein made by osteoblasts decoy receptor for RANKL --\> inhibits RANKL/RANK and inhibits formation of osteoclasts and therefore resorption
29
How does PTH act on the kidney to affect Pi?
In the Proximal tubule PTH --\> **Gs** receptor --\> AC --\> cAMP --\> pKA --\> **inhibits Na-Pi symporter** **Pi cannot be reabsorbed** --\> complements Ca increase from bone resorption
30
How does Vit D Act on the intestines?
acts to stimulate calbindin synthesis --\> helps Ca get reabsorbed
31
How does PTH affect the kidney in general?
stimulates 1alpha-hydroxylase activity --\> activates Vit D stim Ca reabsorption by TAL and distal tubule inhibits Pi reabsorption by proximal nephrons (represses NPT2a)
32
How does PTH affect the small intestine?
no direct action (indirectly increases Ca absorption via activating Vit D)
33
How does Vit D act on the kidney?
stimulates NPT2a expression --\> promotes Pi reabsorption by proximal nephrons minimal actions of Ca
34
How does Vit D act on bone?
sensitizes osteoblasts to PTH regulates osteoid production and calcification
35
What does calcitonin do?
receptors on osteoclasts --\> decreases activity and number of osteoclasts --\> decreases blood Ca and Pi (inihibits resorption) reduces Ca uptake in kidneys no role in min to min regulation of plasma Ca
36
How does estrogen affect intestines and kidneys?
estradiol 17beta --\> stimulates intestinal Ca absorption and renal tubular Ca reabsorption
37
How does estrogen affect the bones?
estradiol 17-beta promotes survival of osteoblasts and death of osteoclasts = favors bone formation women after menopause --\> bone loss
38
How do glucocorticoids affect Ca?
promote bone resorption (favor RANKL over OPG) renal Ca wasting inhibit intestinal Ca absorption
39
What do you see in the urine of ppl w/ primary hyperpara?
excessive Pi, cAMP, and Ca
40
What are the main symptoms of primary hyperpara?
stones, bones, and groans hypercalcuria - stones increase bone resorption constipation (increased PTH, Ca, and Vit D, low Pi)
41
What occurs in secondary hyperparathyroidism?
low Ca --\> increase in PTH secondary to this caused by renal failure or Vit D deficiency
42
What are the labs you would see in secondary hyperparathyroidism from renal failure or Vit D deficiency?
in both: high PTH, low Ca and Vit D in renal failure: high Pi bc can't excrete it in Vit D def: low Pi
43
What are common symptoms of hypopara?
most associated w/ low ca: muscle spasm or cramping, numbness and tingling
44
What labs do you see in hypoparathyroidism?
low: pth, ca, vit d high: Pi
45
What is Albright hereditary osteodystrophy?
pseudohypopara type 1a inherited AD Gs for PTH in bone and kidney is defective --\> low calcium and high Pi; increased PTH
46
What are the labs and physical features you would see in Albright hereditary osteodystrophy?
high PTH and Pi low Ca and Vit D short stature, neck, obese, subcutaneous calcification, shortened metatarsals and metacarpals admin of PTH --\> no phosphaturia or increase in urinary cAMP
47
What occurs in humoral hypercalcemia of malignancy?
tumors create PTHrP --\> acts like PTH and stimulates the receptor in urine: high Ca, Pi, and cAMP in blood: high Ca, low blood Pi low PTH and vit D (in cancer Vit D levels are normally suppressed)
48
What is Familial hypocalciuric hypercalcemia?
AD disorder inactive CaSR in parathyroid glands and ascending LOH --\> decreased urinary Ca excretion and increased serum Ca basically body can't tell when your calcium is raised normal to high PTH
49
What are the congenital forms of rickets?
pseudoVit D-deficient rickets or Vit D dependent **type I = decreased 1alpha-hydroxylase** **type II = decreased Vit D receptor** either can't make active Vit D or cells can't use it
50
What labs do you see in Vit D deficiency?
high: PTH, urine Pi and cAMP, bone resorption low: Ca, Pi, and Vit D
51
What can RANKL inhibitors be used to treat?
osteoporosis
52
What is the cyp1a gene? How is it regulated?
The gene for 1alpha-hydroxylase that activates Vit D in the kidney PTH promotes scrip via Gs Ca inhibits via Gi

ENRE (21 decks)

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