Calcium and Phosphate Metabolism and Homeostasis Flashcards

1
Q

How is calcium distributed in the body?

A
  • 99% of total Ca is in bones

- Rest is intracellular and in extracellular fluid (eg. blood)

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2
Q

What is the total calcium in the body?

A

Around 25000 mmol

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3
Q

What are the biological roles of calcium?

A
  • Muscle contraction
  • Nerve excitation
  • Blood coagulation
  • Intracellular messenger
  • Enzymes of intermediary metabolism
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4
Q

How is calcium distributed in the blood ?

A
  • Around 47% free (ionised/bound)
  • Around 47% bound to albumin
  • Around 6% complexed
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5
Q

In blood what calcium distribution area is important physiologically and why?

A

-Free calcium is important as it regulates feedback mechanisms

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6
Q

What are the main organs involved in calcium homeostasis?

A
  • Kidney
  • Gut
  • Bone
  • Parathyroid glands
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7
Q

What are the main homones involved in metabolic control of calcium?

A
  • PTH

- 1.25 DHCC/ calcitriol/ active vit D

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8
Q

What is our dietary intake of Ca and how much of this is absorbed and where?

A
  • Around 25mmol/day
  • Around 6mmol/day absorbed
  • In duodenum and jejenum mainly
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9
Q

How much Ca does our kidneys filter and reabsorb and how much is lost in urine?

A
  • Filters around 240mmol/day
  • Around 234mmol/day reabsorbed.
  • Urine around 6mmol/day
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10
Q

How much Ca does the skeleton release and how?

A
  • Around 8 mmol/day, a similar amount is also laid back down in bone
  • Through resorption
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11
Q

Which of the major hormones control absorption of Ca?

A

-1.25 DHCC

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12
Q

Which of the major hormones control reabsorption of Ca?

A

-PTH

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13
Q

Which of the major hormones control ressorption of Ca?

A
  • 1.25 DHCC

- PTH

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14
Q

What measurements can we take for calcium in blood?

A

We can either measure free calcium of total calcium (bound and free).

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15
Q

If a patient has low albumin Ca conc then what implication does this have on results?

A

Total Ca will also be low but free Ca may still appear quite normal

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16
Q

If albumin conc is low can we still calculate what serum total would have been if it was normal and if so how?

A
  • Yes

- Ca (adj) = Ca (tot) + [0.02(45-alb)]

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17
Q

What is normal serum calcium usually and what do values above and below this indicate?

A
  • 2.2 - 2.6 mmol/L
  • Below is hypocalcaemia
  • Above is hypercalcaemia
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18
Q

Describe the pathways for calcium absorption?

A
  • Cell mediated active transport controlled bhy 1.25DHCC.

- Passive diffusion which depends on luminal conc. of Ca and is unaffected by 1.25DHCC.

19
Q

How does 1.25 DHCC influence absorption?

A

-It increases fractional absorption if:
Dietary intake falls
During growth, pregnancy and lactation

20
Q

What proportion of Ca is usually absorbed?

A

-20-60%

21
Q

How and where in the kidneys is Ca reabsorbed?

A
  • 65% in PCT (coupled to bulk transport of molecules such as Na and water)
  • 20% in ascending loop of henle, this can be increased by effects of PTH
  • 15% in PCT, can be increased by effects of PTH.
22
Q

Where is PTH produced?

A

-Parathyroid glands

23
Q

What are the actions of PTH?

A
  • Promotes bone resorption
  • Stimulates renal tubular Ca reabsorption
  • Stimulates formation of 1.25DHCC in kidney, to enhance Ca absorption in gut.
24
Q

What regulates secretion of PTH?

A

-Free Ca sensed by Ca sensing receptors

25
Q

What type of receptors are Ca sensing receptors?

A

-G-protein coupled

26
Q

Where can Ca sensing receptors be found?

A
  • Parathyroid cells

- Renal tubule

27
Q

What do Ca sensing receptors in parathyroid cells do?

A

Mediates effect of EC ionised Ca on PTH release.

28
Q

What do Ca sensing receptors in renal tubule do?

A

Mediates effect of high peritubular ionised Ca to inhibit Ca reabsorption

29
Q

Describe the action of PTH if there is a decrease in ionised Ca?

A
  • Stimulates Ca reabsorption in renal tubule
  • Stimulates formation of 1.25DHCC in kidney to enhance Ca absorption from gut and bone resorption.
  • Promotes bone resorption
30
Q

What are the possible causes for hypocalcaemia?

A

-PTH problem (not enough); maybe due to neck surgery, Mg deficiency, hypoparathyroidism
-Vit D problem; deficiency (malabsorption, little sunlight exposure)
Renal disease (kidneys fail to make active vit D)

31
Q

What are the possible causes for hypercalcaemia?

A

-PTH problem (too much); maybe due to hyperparathyroidism (adenoma of parathyroid gland)
This would cause both PTH and Ca levels to increase.
-Malignancy; lung cancer, breast cancer, multiple myeloma (effect of PTH related peptide)
This would increase Ca but PTH would be supressed.
-Vit D problem; innapropriate dosage

32
Q

What is phosphate important for?

A
  • Skeletal development, bone mineralisation

- Composition of cell membranes, nucleotide structure, cell signalling

33
Q

How is phosphate distributed in cells?

A
  • 85% is mineralised matrix of bone
  • Rest mainly intracellular , bound to lipids and proteins eg. ATP, cell membranes
  • 1% in EC fluids
34
Q

Does serum PO4 represent true PO4 stores?

A

No because phosphate is capable of shifing in and out of cells.
From the organic and inorganic pool.

35
Q

What factors impact the value of serum phosphate?

A
  • It is nadir before noon and peaks after midnight
  • Dietary effects (rises post prandially then falls due to effect of insulin rise)
  • Age related changes (highest values in infancy when growth velocity high.
36
Q

What are the main organs invilved in Phosphate homeostasis?

A
  • Kidney
  • Gut
  • Bone
37
Q

What are main hormones involved in phosphate metaboic control?

A
  • PTH
  • 1.25 DHCC
  • FGF 23
38
Q

What is our dietary intake of phosphate and how much of this is absorbed and where?

A
  • Around 45mmol/day of which 32mmol/day is absorbed
  • However 7mmol/day of this is returned to gut
  • Less rigidly regulated than Ca absorption, occurs in whole small intestine
39
Q

How much phosphate does our kidneys filter and reabsorb and how much is lost in urine?

A
  • 15-20% phosphate is protein bound, rest filtered by kidney (thats not in bone)
  • Around 160mmol/day of which 135mmol/day is reabsorbed.
  • Urine about 25mmol/day
40
Q

How much phosphate is released from resorption?

A

-Around 7mmol/day, similar amount also laid back down.

41
Q

Where exactly in the kidney does phophate reabsorption occur?

A
  • 75% in PCT

- 5-20% in DCT

42
Q

What do PTH and FGF 23 do in phospahte reabsorption?

A

Inhibit reabsorption of phosphate by renal tubule.

43
Q

What can disorders of Ca sensing receptors cause?

A

-Abnormalities in Ca serum concentrations.

44
Q

How can PTH secretion be reduced clinically?

A

Activators for Ca sensing receptors given for patients with parathyroid cancer or hyperparathyroidism for example.