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Endocrine system > Calcium homeostasis > Flashcards

Calcium homeostasis Flashcards

1
Q

What are the functions of calcium in the body?

A 
Signalling 
Blood clotting
Apoptosis
Skeletal strength 
Membrane excitability
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2
Q

What is the clinical significance of hypocalcaemia?

A

Hypocalcaemia increases neuronal Na+ permeability leading to hyperexcitation of neurons. In extreme cases causes tetany, if spreads to larynx and respiratory muscles – asphyxiation.

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3
Q

What is the clinical significance of hypercalcaemia?

A

Hypercalcaemia decreases neuronal Na+ permeability which will reduce excitability and depress neuromuscular activity and in extreme cases, trigger cardiac arrhythmias.

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4
Q

How is calcium distributed in the body?

A

Bones contain 99% of calcium in the body

Intracellular fluid 0.9% - Mostly stored inside mitochondria and Sarcoplasmic Reticulum. Free [Ca2+ ]ic very low

Extracellular fluid 0.1% - Nearly half ECF Ca2+ is bound to protein.

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5
Q

How is calcium is stored in bones?

A

~1Kg (99%) calcium is stored in the calcified extracellular matrix of bone, mostly in the form of hydroxyapatite (Ca10(PO4)6(OH)2) so phosphate homeostasis is also important in determining calcium balance.

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6
Q

What % of calcium in plasma is bound?

A

40% is bound to plasma proteins

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7
Q

In what 3 forms is calcium found in the blood?

A

40% is protein bound, 80% of this to albumin and 20% to globulin.

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8
Q

How does pH affect calcium binding to plasma proteins?

A
  • An important consideration for Ca2+ is that the binding capacity of plasma proteins changes with pH.
  • Binding capacity is increased under alkalotic conditions.
  • So e.g. if hyperventilate, then plasma pH rises and plasma proteins bind more Ca2+ causing plasma concentration to fall and therefore may precipitate hypocalcaemic tetany.
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9
Q

What do osteoblasts do?

A
  • Osteoblasts are the bone-building cells. They are highly active cells which lay down a collagen extracellular matrix which they then calcify.
  • They differentiate to form osteocytes in established bone. Osteocytes are much less active than osteoblasts but appear to regulate the activity of osteoblasts and osteoclasts.
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10
Q

From what cells do osteocytes differentiate from?

A

Osteoblasts

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11
Q

What do osteoclasts do?

A

• Osteoclasts are the cells that are responsible for mobilizing bone. They secrete H+ ions (pH ≈ 4) to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix

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12
Q

What two hormones increase plasma calcium concentrations?

A

Parathyroid hormone (PTH) polypeptide hormone produced by the parathyroid glands

Calcitriol (active form of Vit D3) steroid hormone produced from Vitamin D by the liver and kidneys

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13
Q

How is calcitriol produced?

A

Calcitriol (active form of Vit D3) steroid hormone produced from Vitamin D by the liver and kidneys

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14
Q

Describe the location of parathyroid glands and how many you have

A

• There are usually 4 lying on the posterior surface of the thyroid gland, although variations in number and location of are common, 1 in 10 people have aberrant distribution, (important if need to remove overactive thyroid gland!).

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15
Q

What stimulates the secretion of parathyroid hormone?

A

Decrease in free plasma calcium levels

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16
Q

How does PTH increase free plasma calcium?

A

o Stimulating osteoclasts to ↑ resorption (release) of Ca2+ and phosphate in bone (effects seen within 12-24hrs)
o Inhibiting osteoblasts to reduce Ca2+ deposition in bone.
o Increasing reabsorption of Ca2+ from the kidney tubules, therefore decreasing its excretion in the urine.
o Increasing renal excretion of phosphate. This elevates free [Ca2+ ] by preventing it from being deposited back into bone, a process that requires phosphate.
o Stimulates the kidney to synthesise calcitriol from vitamin D which promotes calcium absorption at the gut and kidney.

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17
Q

How is calcitriol also called?

A

Aka active Vitamin D3 or 1,25 dihydroxycholecalciferol (1,25(OH)2D3)

18
Q

How is calcitriol produced?

A

A steroid hormone produced in two steps (1. liver, 2. kidneys) from dietary vitamin D or from precursors activated by sunlight on skin. Active vitamin D3 is formed from cholesterol derivatives by the action of UV light on the skin, but Vit D can also be gained from the diet.

19
Q

What stimulates calcitriol production in pregnant woman?

A

Formation stimulated by hormone prolactin in lactating women.

20
Q

How do we get vitamin D from our diet?

A

Fat-soluble vitamin, dietary sources are fatty fish eg mackerel and tuna, fish liver oils and egg yolks.

21
Q

Describe the actions of calcitriol?

A

Binds to nuclear receptors on target cells (fat soluble)

Increases active absorption of calcium from the gut

Facilitates renal absorption of Ca2+

Mobilises calcium stores in bone by stimulating osteoclast activity

22
Q

Describe how calcium is absorbed from the gut via the influence of calcitriol?

A

The active transport system which moves Ca2+ from the intestinal lumen to the blood is under the control of calcitriol.

23
Q

What hormone stimulates calcitriol secretion?

A

PTH

24
Q

Define vitamin D deficiency

A

Circulating vitamin D levels fall to less than 20ng/ml

25
Q

What can cause vitamin D deficiency?

A 
Clothing
UVB sunscreen
Diet
Low fat 
Age - >65yo due to reduced gut absorption and Ca mobility
26
Q

What diseases can vitamin D deficiency?

A

Rickets in children

Osteomalacia in adults (soft bones)

27
Q

How does Vitamin D3 deficiency lead to Ca2+ and phosphate deficiency?

A

Vitamin D3 deficiency → intestinal malabsorption of Ca2+, this ↓ [Ca2+ ]plasma which ↑ PTH which then promotes phosphate deficiency – aggravates Ca2+ loss from bone.

28
Q

Who is more at risk of vitamin D3 deficiency leading on to Ca2+ and phosphate deficiency, and why?

A

Elderly and Asian populations are the most at risk

Chapatti flour contains phytate which binds dietary Ca2+.
There may be dietary deficiency of vitamin D3
Pigmented skin is less able to make vitamin D3 in response to UV light.

29
Q

In what diseases is vitamin D deficiency implicated in?

A

Vit D deficiency implicated in MS, cancer, arthritis, CVD

30
Q

What hormone decreases free plasma calcium?

A

Calcitonin

31
Q

What type of hormone is calcitriol?

A

Peptide

32
Q

What type of hormone is calcitonin, and where is it produced?

A

Peptide hormone produced by the thyroid gland

33
Q

What stimulates calcitonin secretion by the thyroid gland?

A

Increase in free calcium in plasma

34
Q

How does calcitonin decrease free plasma calcium?

A

Its main actions are to bind to osteoclasts and inhibit bone resorption as well as ↑ renal excretion so preventing a further ↑ in Ca2+ .

35
Q

What hormone can be used to treat Pagets disease?

A

Calcitonin

Paget’s disease (overactive osteoclasts)

36
Q

How does cortisol affect calcium balance?

A

Cortisol inhibits osteoblasts, increases renal excretion of Ca2+ and phosphate and reduces intestinal absorption of Ca2+ →↓ plasma [Ca2+ ] →↑ PTH →↑ bone resorption. This together with the reduced bone formation can, over time, produce osteoporosis.

37
Q

How does insulin affect calcium balance?

A

Insulin increases bone formation, and antagonises the action of cortisol. Diabetics have significant bone loss.

38
Q

What hormone antagonises the effect of cortisol on calcium balance?

A

Insulin

39
Q

How does oestrogen affect calcium balance?

A

Oestrogen promotes bone formation via oestrogen receptors on osteoblasts. Post-menopausal osteoporosis a major problem.

40
Q

How does GH affect calcium balance?

A

Growth Hormone – constant stimulus for bone formation.

41
Q

How does prolactin affect calcium balance?

A

Prolactin – promotes calcium absorption from the gut by stimulating synthesis of calcitriol.

Endocrine system (27 decks)

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