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Physiology > Calcium and Phosphate Regulation > Flashcards

Calcium and Phosphate Regulation Flashcards

1
Q

What is the normal range of Ca?

A

Tightly regulated range in plasma (2.2 - 2.6 mM)

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2
Q

What is the most abundant cation?

A

Calcium

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3
Q

What is the function of phosphate?

A 
Cellular energy metabolism (ATP)
Intracellular signaling pathways 
Nucleic acid backbone
Bone structure
Enzyme activation/deactivation
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4
Q

What is the function of calcium?

A 
Membrane stability and cell function
Neuronal transmission
Bone structure/formation 
Blood coagulation
Muscle function Hormone secretion
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5
Q

What is Ca found as in the plasma?

A

Half Ca is bound to albumin

Half is ionized

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6
Q

What is Pi found as in the plasma?

A

Most of Pi is ionized

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7
Q

What does hypocalcemia result in?

A

Muscle failure, tetany, convulsions, death

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8
Q

What does hypercalcemia result in?

A

Renal dysfunction, calcification of soft tissues, muscle weakness, coma

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9
Q

What often causes hyperphosphatemia?

A

Result of severe tissue injury “crush”

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10
Q

What are the main 2 regulators of calcium?

A

PTH

Vitamin D

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11
Q

What is the function of the chief/principal cells in the parathyroid gland?

A

Make PTH

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12
Q

What is the function of the oxyphil cells in the parathyroid gland?

A

No known function, increase with age and chronic kidney disease

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13
Q

What is the function of the 1-34 PTH fragment (N terminal)?

A

N-terminal fragment 1-34 biologically active – binds to PTH receptor

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14
Q

What is the function of the 35-84 PTH fragment?

A

C-terminal fragment 35-84 has longer half-life than other fragments – inactive

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15
Q

What is the clinical importance of the 1-84 PTH fragment?

A

Intact 1-84 fragment: half-life of 4 min and is clinically measured.

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16
Q

How is PTH synthesized?

A

The signal peptide directs it to the ER for processing after translation

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17
Q

What is the function of PTHrP (related peptide)?

A

Parathyroid hormone-related peptide (PTHrP) is highly homologous to PTH 1-34 AA.

It mimics the action of PTH in the bone and kidney.

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18
Q

What is the relationship of PTHrP to disease?

A

Many tumors produce PTHrP (renal, bladder, lymphoma, head/neck) resulting in hypercalcemia

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19
Q

What are the PTH receptors?

A

PTH 1R

PTH 2R

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20
Q

Describe PTH 1R.

A

Primary receptor and is found in the osteoblasts and kidney and it is a GPCR.

Binds 1-34 fragment, 1-84, PTHrP

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21
Q

Describe PTH 2R.

A

Physiological importance in humans unclear

Binds 1-34
Does not bind PTHrP

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22
Q

What are the targets of PTH?

A

Bone and Kidney

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23
Q

What are the effects of PTH?

A

Increase plasma Ca2+, decrease plasma Pi

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24
Q

What is the function of osteoclasts?

A

Bone reabsorption

Do not express PTH receptors

25
Q

What is the function of osteoblasts?

A

Bone formation and mineralization

High expression of PTH receptors

26
Q

What is the mechanism of PTH action?

A
  • PTH stimulates macrophage colony-stimulating factor (M-CSF) in osteoblasts by binding the PTH receptor.
  • M-CSF stimulates differentiation of osteoclast precursors
27
Q

What is the the type of action PTH has on osteoclasts?

A

Indirect via M-CSF from the osteoblasts

28
Q

What is the effect of PTH on RANK ligand?

A

PTH stimulates RANK ligand – leads to maturation of osteoclast and bone reabsorption. Bone degradation releases Ca2+ and Pi to systemic circulation.

29
Q

What is Osteoprotegerin (OPG)?

A

It is an antagonist of RANK ligand which leads to the down regulation of osteoclasts

30
Q

How does increased cortisol lead to osteoporosis?

A

Cortisol inhibits OPG -> more bone breakdown and can lead to osteoporosis

31
Q

How does PTH affect the kidney?

A

Stimulates CYP1α – encodes 1alpha-hydroxylase

32
Q

What is the function of 1alpha-hydroxylase?

A

Converts Vitamin D into its active form

33
Q

How does the active form of Vitamin D affect the kidney?

A

Stimulates Ca2+ channel insertion in apical membrane of distal tubule

34
Q

What is the main regulator of PTH?

A

Ca concentration in the plasma

35
Q

How does the parathyroid gland detect changes in Ca?

A

CaSR - the calcium sensing receptor

36
Q

What is the function of the CaSR?

A

Located in chief cells, kidney tubules, C cells and it binds ionized Ca2+.

It has 2 functions:
• Inhibits PTH synthesis at
promoter level
• Stimulates degradation of preformed PTH

37
Q

How does Vitamin D regulate PTH?

A

Binds nuclear receptor - VDR

  • Inhibits PTH synthesis at promoter level
  • Stimulates CaSR gene transcription – indirect regulation of PTH
38
Q

What is Calciferol?

A

General term for vitamin D and other natural structural analogs.

39
Q

What is Cholecaciferol?

A

Vitamin D3 from animals

40
Q

What is Calcidiol?

A

25-D

41
Q

What is Calcitriol?

A

1,25-D (active form)

42
Q

What binds Vitamin D in the plasma?

A

Vitamin D- binding protein

43
Q

What are the targets of Vitamin D?

A

Bone
Kidney
Intestine

44
Q

What target of Vitamin D does PTH NOT act upon?

A

Intestine. PTH acts on the intestine via the effects of Vitamin D.

45
Q

How does Vitamin D directly affect the bone?

A

Mobilize Ca2+ from bone

Osteoblasts and osteoclasts have VDRs so Vitamin D stimulates osteoclast proliferation/differentiation.

46
Q

What is an indirect effect of Vitamin D on the bone?

A

It increases the plasma Ca so it then causes bone mineralization to occur

47
Q

How does Vitamin D affect the intestine?

A

Increases transcellular Ca2+ absorption in duodenum

Stimulates Pi reabsorption from small intestine

48
Q

What is osteoporosis and what causes it?

A

Reduced bone density – mainly trabecular bone

Causes: genetic, menopause (low estrogen), glucocorticoid therapy/chronic stress, low dietary Ca2+

49
Q

What are the causes of hyperparathyroidism?

A

Hyperplasia, carcinoma of parathyroid gland

50
Q

What are some of the effects of hyperparathyroidism?

A

Hypercalcemia, kidney stones and renal failure which leads to reduced Vitamin D -> excess PTH synthesis.

51
Q

What is the function of bisphosphonates used in treatment of osteoporosis and what is their problem?

A

Bisphosphonates inhibit osteoclasts so that

bone cannot be broken down and it can cause hairline fractures that will not be fixed by bone cycling

52
Q

What are some of the effects of hypothyroidism?

A

Hypocalcemic tetany -> due to increased excitability of neurons

53
Q

What causes rickets in children and osteomalacia in adults?

A

Unmineralized bone due to Vitamin D deficiency

54
Q

What is pseudohypoparathyroidism?

A

Congenital defect in G protein that associates with PTHR1.

It causes a generalized resistance to PTH, TSH, LH, and FSH which leads to these symptoms:

  • low Ca++
  • high phosphate
  • elevated PTH
  • short stature
55
Q

What is the normal serum Pi level?

A

0.8-1.45 mM

56
Q

What is the role of calcitonin in Ca regulation?

A

Normal physiological importance is unclear

57
Q

What is the use for calcitonin clinically?

A

Inhibits osteoclast reabsorption of and slows bone turnover

58
Q

What is the escape phenomenon associated with calcitonin therapy that can prove problematic?

A

“Escape” phenomenon – rapid downregulation of calcitonin receptors cause the antiosteoclastic actions of calcitonin to diminish within a few hours making this a less effective treatment option.

Physiology (81 decks)

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