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Endo Repro 1 > Calcium and Phosphate Regulation > Flashcards

Calcium and Phosphate Regulation Flashcards

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?

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?

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?

A

1,25-hydroxycholecalciferol

22
Q

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

A

1alpha-hydroxylase (CYP1a) in renal proximal tubule

23
Q

What are the main stimuli for 1alpha-hydroxylase?

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?

A

25-hydroxycholecalciferol

25
Q

Where are PTH receptors located?

A

osteoblasts NOT osteoclasts

26
Q

What are the short-term actions of osteoblasts?

A

bone formation, PTH can be administered in osteoporosis treatment

27
Q

What are the long-term actions of osteoclasts?

A

bone resorption, indirect action mediated by cytokines released from osteoblasts

28
Q

How does vitamin D work synergistically with PTH?

A

to stimulate osteoclast activity and bone resportion

29
Q

What are macrophage colony-stimulating factors (M-CSF)?

A

induce stem cells to differentiate into osteoclast precursors, mononuclear osteoclasts and multinucleated osteoclasts

30
Q

What are receptor activator for NFKB ligand (RANKL)?

A

cell surface protein produced by osteoblasts, bone lining cells and apoptotic osteocytes
NOTE: they are the primary mediator of osteoclast formation

31
Q

What are RANK?

A

cell surface protein receptor on osteoclasts and their precursors

32
Q

What are osteoprotegerins (OPG)?

A

soluble protein produced by osteoblasts, decoy receptor for RANKL, inhibits RNKl/RANK interaction

33
Q

What causes osteoclast formation?

A

RANKL/OPG

34
Q

What effect does PTH have one bone formation/resorption?

A

PTH increases RANKL, decreases OPG

35
Q

What effect does vitamin D have on bone formation/resorption?

A

vitamin D increases RANKL

36
Q

What will inhibition of the Na/phosphate transporter by PTH cause?

A

phosphaturia (increased excretion of phosphate in urine)

37
Q

What are the actions of vitamin D on the kidney?

A

stimulates both calcium and phosphate reabsorption

38
Q

What are the actions of PTH on calcium/phosphate homeostasis in bone?

A
  • 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
Q

What are the actions of PTH on calcium/phosphate homeostasis in they kidneys?

A
  • stimulates 1alpha-hydroxylase
  • stimulates calcium reabsorption by the thick ascending limb of LOH and the distal tubule
  • inhibits phosphate reabsorption by proximal nephrons
40
Q

What are the actions of vitamin D on calcium/phosphate homeostasis in the small intestine?

A
  • increases calcium and phosphate absorption by increasing calbindin expression
41
Q

What are the actions of vitamin D on calcium/phosphate homeostasis in bone?

A
  • sensitizes osteoblasts to PTH

- regulates osteoid production and calcification

42
Q

What are the actions of vitamin D on calcium/phosphate homeostasis in the kidneys?

A

promotes phosphate reabsorption by proximal nephrons (stimulates NPT2a expression)p
- minimal actions of calcium

43
Q

What are the actions of vitamin D on calcium/phosphate homeostasis on the parathyroid gland?

A
  • directly inhibits PTH gene expression

- directly stimulates CaSR gene expression

44
Q

What are the actions of calcitonin on bone and kidneys?

A
  • 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
Q

What effect would thyroidectomy or thyroid tumors have on calcitonin?

A
  • thyroidectomy would decrease calcitonin, but have no effect on calcium metabolism
  • thyroid tumors would increase calcitonin but have no effect on calcium metabolism
46
Q

primary hyperparathyroidism

A

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
Q

secondary hyperparathyroidism

A

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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