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ENDOCRINE > 5. Calcium Homeostasis > Flashcards

5. Calcium Homeostasis Flashcards

1
Q

What are the 5 main roles of calcium in the body

A
  1. signalling
  2. blood clotting
  3. apoptosis
  4. skeletal strength - 99% Ca in bone
  5. membrane excitability
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2
Q

why do people not die directly of clotting in response to low Ca

A

Ca levels never fall low enough in living people to allow clotting - would die of something else before Ca gets that low

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3
Q

what role of Ca is the most critical in short term homeostasis

A

membrane excitability - Ca2+ decreases Na+ permeability - can be a medical emergency if not working

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4
Q

what is hypocalcaemia

A

low calcium in the blood - increases neuronal Na+ permeability leading to hyper excitation of neurons

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5
Q

what can happen in extreme cases of hypocalcaemia

A

tetany - if spreads to larynx and respiratory muscles causes asphyxiation

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6
Q

what is hypercalcaemia

A

high calcium in blood - decreases neuronal Na+ permeability which reduces excitability and depresses neuromuscular activity

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7
Q

what can happen in extreme cases of hypercalcaemia

A

can trigger cardiac arrhythmias

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8
Q

what is the calcium distribution in the body

A

99% in bone - acts as a store, can sacrifice Ca to maintain plasma levels

1% in blood - (TIGHTLY REGULATED)

  • Intracellular = 0.9%
  • Extracellular fluid = 0.1%
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9
Q

how is calcium stored intracellularly (inside cells)

A

mostly stored inside mitochondria and sarcoplasmic reticulum

free [Ca2+]ic very low

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10
Q

how is calcium stored in the extracellular fluid (in plasma)

A

nearly half bound to protein

= only 0.05% Ca in the body is free in solution and physiologically active

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11
Q

how is calcium stored in bone

A

99% calcium (~1kg) stored calcified extracellular matrix of bone - in the form of HYDROXYAPATITE
(Ca10(*PO4)6(OH)2)

*phosphate homeostasis therefore very important for Ca balance

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12
Q

what three forms does Ca exist in in the blood

A
  1. protein bound - 40% (80%to albumin, 20% to globulin)
  2. free (ionised) - 50%
  3. complexed - 10% (eg Ca carbonate, Ca phosphate, etc)
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13
Q

what form of calcium in the blood is physiologically active

A

free(ionised) Ca

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14
Q

what can change the binding capacity of Ca2+ to plasma proteins

A 
pH
Increased pH (alkaline) = increased binding capacity of Ca2+

Decreased pH (acidic) = decreased binding capacity of Ca2+

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15
Q

how does increasing pH lead to increased binding capacity of Ca2+

A

in alkalosis when pH increases (decreased [H+] in plasma) proteins are deprotonated = overall -ve charge allows Ca to bind to protein

reduces overall amount of ionised Ca BUT total Ca remains constant

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16
Q

how does decreasing pH lead to decreasing binding capacity of Ca2+

A

in acidosis when pH decreases (increased [H+] in plasma) - increase in protons = displaces Ca from protein

increases overall amount of ionised Ca BUT total Ca remains constant

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17
Q

what principle determines total body Ca2+

A

total body calcium = calcium in from diet - calcium out excreted at kidney and faeces

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18
Q

how does the Ca stored in bone help maintain Ca balance

A

at low Ca - bones release Ca (by osteoclasts) into plasma at expense of strength - leads to weak/brittle bones but allows plasma Ca to be maintained (which is more important)

19
Q

what are osteoBLASTS

A

bone BUILDING cells - highly active cells - lay down a collagen extracellular matrix which they then calcify

20
Q

what are oseoCLASTS

A

bone “CLEARING” cells - responsible for mobilising bone - secrete H+ ions (pH~4) to dissolve Ca salts - provide proteolytic enzymes to digest extracellular matrix - allow for Ca to be released into plasma

21
Q

what are osteocytes

A

cells in established bone - much less active than osteoblasts - regulate activity of osteoblasts and osteoclasts

22
Q

what are the two key hormones that increase [Ca2+] in plasma

A
  1. parathyroid hormone (PTH)

2. calcitriol (active form of VitD3)

23
Q

what is parathyroid hormone

A

a polypeptide hormone produced by the parathyroid glands

24
Q

what are the parathyroid glands and where are they found

A

usually 4 lying on the posterior surface of the thyroid gland - produce parathyroid hormone

variations in number and location are common though - essential for life, be careful to not remove them when removing overactive thyroid gland

25
Q

what stimulates secretion of PTH

A

released in response to decrease in free [Ca2+] in plasma

26
Q

How does PTH act to increase free [Ca2+] in the plasma

A
  1. stimulates breakdown of bone
  2. stops bone being laid down
  3. increases reabsorption of Ca from kidneys
  4. Increases renal excretion of phosphate
  5. stimulates kidneys to synthesise calcitriol from vit D
27
Q

how does PTH stimulate the breakdown of bone

A

stimulates osteoclasts to increase resorption (release) of Ca2+ and phosphate in bone (effects seen within 12-24hrs)

28
Q

how does PTH stop bone being laid down

A

inhibits osteoblasts to reduce Ca2+ deposition in bone

29
Q

how does PTH increasing renal excretion of phosphate keep Ca in the plasma

A

increasing renal excretion of phosphate elevates free [CA2+] by preventing it from being deposited back into bone - a process that requires phosphate

30
Q

what is calcitriol

A

the active form of vitamin D3 - steroid hormone produced in two steps (1. liver 2. kidneys)

31
Q

what stimulates calcitriol production

A
  1. sunlight (UV light) on skin

2. prolactin in lactating women

32
Q

how can vit D be gained from diet

A

fatty fish e.g. mackerel and tuna, fish liver oils, egg yolks

33
Q

what are the three main actions of calcitriol to increase [Ca2+] in the plasma

A
  1. increases absorption of Ca2+ from the gut
  2. facilitates renal absorption of Ca2+
  3. mobilises Ca stores in bone by stimulating osteoclast activity

*actions complement those of PTH to increase [Ca2+] in the plasma

34
Q

how does calcitriol act to increase absorption of Ca2+ from the gut

A

calcitriol controls the active transport system that moves Ca2+ from the intestinal lumen to the blood

LOW PLASMA Ca
= increased PTH = increased calcitriol = increased intestinal absorption

HIGH PLASMA Ca
= inhibited PTH = increased osteoblast deposition and decreased osteoclast resorption

35
Q

how much dietary Ca is absorbed in a healthy individual

A

levels of calcitriol normal = 30% Ca absorbed

36
Q

how much dietary Ca is absorbed in a Vit D deficient individual

A

levels of calcitriol low = 10-15% Ca absorbed

37
Q

how much dietary Ca is absorbed during pregnancy, lactation and growth spurts

A

levels of calcitriol high = 45-55% Ca absorbed

38
Q

what is the DIRECT effect of vit D3

A

to release Ca2+ from bone

39
Q

what is the NET effect of vit D3

A

increase plasma [Ca2+] and increase mineralisation of bone

this is because of its effect on Ca absorption from the gut/kidneys

40
Q

what happens in Vit D deficiency

A

PTH works hard to maintain plasma [Ca] - continually removes Ca from bone = bones that are soft/brittle and, if still growing, bent.

children - rickets
adults - osteomalacia (early fracture bones)

41
Q

how does vit D deficiency lead to Ca2+ and phosphate deficiency

A

vit D deficiency = intestinal malabsorption of Ca2+ = decrease in plasma [Ca2=] = increased PTH = promotes phosphate deficiency = aggravates Ca2+ loss from bone

42
Q

what key hormone acts to decrease plasma [Ca2+]

A

calcitonin - peptide hormone produced by the thyroid gland

43
Q

what stimulates the secretion of calcitonin

A

increased [Ca2+] in the plasma

44
Q

what are 2 main actions of calcitonin

A
  1. bind to osteoclasts and inhibit bone resorption

2. increase renal excretion so preventing further increase in Ca2+

ENDOCRINE (13 decks)

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