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Endo Repro 1 > Calcium and Phosphate Regulation > Flashcards

Calcium and Phosphate Regulation Flashcards

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1
Q

What is the most active form of calcium?

A

free-ionized calcium, is important for vesicle formation/secretion

of total calcium: 60% is freely filterable. of that, 10% is complexed to anions (calcium phosphate), and 50% is ionized

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2
Q

What are the symptoms of hypocalcemia?

A

hyperreflexia, spontaneous twitching, muscle cramps, tingling/numbness

  • chvostek sign: twitching of facial muscles elicited by tapping on facial nerve
  • trousseau sign: carpopedal spasm upon inflation of a blood pressure cuff
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3
Q

What are the symptoms of hypercalcemia?

A

decreased QT internal, constipation, lack of appetite, polyuria, polydipsia, muscle weakness, hyporeflexia, lethargy, coma

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4
Q

How does hypocalcemia influence membrane excitability?

A
  • reduces the activation threshold for Na channels -> easier to evoke AP
  • results in increase in membrane excitability (spontaneous AP’s)
  • spontaneous AP are the physical basis for hypocalcemic tetany
  • produces tingling/numbness
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5
Q

How does hypercalcemia influence membrane excitability?

A
  • decreases membrane excitability

- nervous system becomes depressed and reflex responses are slowed

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6
Q

How do changes in plasma protein concentration alter total calcium concentration?

A
  • they move in the same direction: increase in plasma protein concentration will increase total calcium concentration
  • no change in ionized calcium
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7
Q

How do changes in anion concentration alter calcium concentration?

A
  • it changes the fraction of calcium complexed with anions: increase in phosphate concentration will decrease ionized calcium concentration
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8
Q

How do acid-base abnormalities alter calcium concentration?

A
  • it alters the ionized concentration by changing the fraction of calcium bound to albumin: decrease in pH (increase in free H) means less binding spots for calcium on albumin)
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9
Q

What is acidemia?

A

free ionized calcium concentration increases because less calcium is bound to albumin

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10
Q

What is alkalemia?

A

free ionized calcium concentration decreases, often accompanied by hypocalcemia

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11
Q

What stimulated the absorption of calcium from the intestines?

A

vitamin D

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12
Q

What stimulates bone resorption of calcium?

A

PTH, vitamin D

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13
Q

What inhibits bone resorption of calcium?

A

calcitonin

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14
Q

What stimulates reabsorption of calcium from the distal tubule of the nephron?

A

PTH

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15
Q

What is the relationship between calcium and phosphate?

A

extracellular phosphate concentration is inversely related to calcium
NOTE: they are regulated by the same hormones

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16
Q

What cells synthesize and secrete PTH?

A

chief cells of parathyroid glands

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17
Q

What does an increase in extracellular calcium (chronic hypercalcemia) concentration cause?

A
  • inhibits PTH synthesis and secretion

- increase breakdown of stored PTH and release of inactive PTH fragment into circulation

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18
Q

What does chronic hypocalcemia cause?

A
  • increase in synthesis and storage of PTH

- hyperplasia of parathyroid glands (secondary hyperparathyroidism)

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19
Q

What effect does alcoholism have on magnesium levels?

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A
  • can cause severe hypomagnesemia, which will inhibit PTH synthesis, storage and secretion

NOTE: parallel, but less significant effects on PTH secretion

20
Q

What does a decrease in plasma calcium levels, and thereby an increase in PTH secretion do to bone, kidneys and intestines?

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A

bone: increases bone resorption
kidney: decrease phosphate reabsorption, increase calcium reabsorption, increase urinary cAMP
intestine: increase calcium absorption (indirect via vitamin D)

-> all with the goal of increasing plasma calcium towards normal

21
Q

What is the most active form of vitamin D?

Study These Flashcards
A

1,25-hydroxycholecalciferol

22
Q

What is the enzyme that converts 25-hydroxy to the most active form?

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A

1alpha-hydroxylase (CYP1a) in renal proximal tubule

23
Q

What are the main stimuli for 1alpha-hydroxylase?

Study These Flashcards
A
  • decrease in calcium
  • increase in PTH
  • decrease in phosphate
24
Q

What is the main circulating form of vitamin D that has very low activity?

Study These Flashcards
A

25-hydroxycholecalciferol

25
Where are PTH receptors located?
osteoblasts NOT osteoclasts
26
What are the short-term actions of osteoblasts?
bone formation, PTH can be administered in osteoporosis treatment
27
What are the long-term actions of osteoclasts?
bone resorption, indirect action mediated by cytokines released from osteoblasts
28
How does vitamin D work synergistically with PTH?
to stimulate osteoclast activity and bone resportion
29
What are macrophage colony-stimulating factors (M-CSF)?
induce stem cells to differentiate into osteoclast precursors, mononuclear osteoclasts and multinucleated osteoclasts
30
What are receptor activator for NFKB ligand (RANKL)?
cell surface protein produced by osteoblasts, bone lining cells and apoptotic osteocytes NOTE: they are the primary mediator of osteoclast formation
31
What are RANK?
cell surface protein receptor on osteoclasts and their precursors
32
What are osteoprotegerins (OPG)?
soluble protein produced by osteoblasts, decoy receptor for RANKL, inhibits RNKl/RANK interaction
33
What causes osteoclast formation?
RANKL/OPG
34
What effect does PTH have one bone formation/resorption?
PTH increases RANKL, decreases OPG
35
What effect does vitamin D have on bone formation/resorption?
vitamin D increases RANKL
36
What will inhibition of the Na/phosphate transporter by PTH cause?
phosphaturia (increased excretion of phosphate in urine)
37
What are the actions of vitamin D on the kidney?
stimulates both calcium and phosphate reabsorption
38
What are the actions of PTH on calcium/phosphate homeostasis in bone?
- promotes osteoblastic growth - regulated M-CSF, RANKL, OPG production by osteoblast - sustained elevated levels of PTH shift the balance to a relative increase in osteoclast activity, thereby increasing bone turnover and reducing bone density
39
What are the actions of PTH on calcium/phosphate homeostasis in they kidneys?
- stimulates 1alpha-hydroxylase - stimulates calcium reabsorption by the thick ascending limb of LOH and the distal tubule - inhibits phosphate reabsorption by proximal nephrons
40
What are the actions of vitamin D on calcium/phosphate homeostasis in the small intestine?
- increases calcium and phosphate absorption by increasing calbindin expression
41
What are the actions of vitamin D on calcium/phosphate homeostasis in bone?
- sensitizes osteoblasts to PTH | - regulates osteoid production and calcification
42
What are the actions of vitamin D on calcium/phosphate homeostasis in the kidneys?
promotes phosphate reabsorption by proximal nephrons (stimulates NPT2a expression)p - minimal actions of calcium
43
What are the actions of vitamin D on calcium/phosphate homeostasis on the parathyroid gland?
- directly inhibits PTH gene expression | - directly stimulates CaSR gene expression
44
What are the actions of calcitonin on bone and kidneys?
- decrease blood calcium and phosphate concentration by inhibiting bone resorption (effects occur only at high circulating levels of hormone) - no role in chronic regulation of plasma calcium
45
What effect would thyroidectomy or thyroid tumors have on calcitonin?
- thyroidectomy would decrease calcitonin, but have no effect on calcium metabolism - thyroid tumors would increase calcitonin but have no effect on calcium metabolism
46
primary hyperparathyroidism
parathyroid adenoma secretes high levels of PTH - increases resorption of calcium and phosphate release into blood - increase in calcium reabsorption in kidneys - increase in phosphate excretion - increase in vitamin D and calcium absorption by intestinal mucosa - > leads to hypercalcemia/hypophosphatemia
47
secondary hyperparathyroidism
renal failure: increase in PTH, decrease in calcium, increase in phosphate, decrease in vitamin D vitamin D deficiency: increase in PTh, decrease in calcium, decrease in phosphate, decrease in vitamin D

Endo Repro 1 (6 decks)

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