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Endocrying > Calcium homeostasis > Flashcards

Calcium homeostasis Flashcards

1
Q

What are the roles of calcium in the body?

A

Signalling

Blood clotting

Apoptosis

Skeletal strength

Membrane excitability

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2
Q

What signalling roles does calcium carry out?

A
  • exocytosis of hormones, neurotransmitters etc
  • in muscle fibre contraction
  • alters enzyme function
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3
Q

What role does calcium play in blood clotting?

A

Essential component of the clotting cascade - used in conversion of the ‘Factors’

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4
Q

In what way does calcium contribute to membrane excitability?

A

Ca2+ decreases Na+ permeability

This is a very critical role in short-term homeostasis

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5
Q

Describe the effects of calcium imbalances in the blood on membrane excitability?

A

Hypocalcaemia leads to increased neuronal permeability which causes hyperexcitation

  • Can cause tetany, or asphyxiation

Hypercalcaemia leads to decreased neuronal permeability which reduces the excitability of neurones

  • This depresses neuromuscular activity
  • May cause cardiac arrhythmias
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6
Q

Describe the distribution of calcium throughout the body

A

99% - in bones

  1. 9% - intracellular
  2. 1% - extracellular fluid
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7
Q

Describe the containment of intracellular calcium

A

0.9% of total calcium content

Mostly stored inside mitochondria and Sarcoplasmic Reticulum. Free [Ca2+]ic very low

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8
Q

Describe how calcium exists in extracellular fluid

A

0.1% of total body calcium

Nearly half of ECF Ca2+ is bound to protein

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9
Q

In the entire body, how much Ca2+ is free? (ie not in a molecule and not bound to etc)

A

So only 0.05% of the calcium in the body is free in solution and physiologically active

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10
Q

How does calcium exist in the bone?

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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11
Q

What is the normal concentration of calcium in the plasma?

A

2.2-2.6 mM in plasma (0.1%)

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12
Q

Why does a lot of the extracellular calcium exist bound to proteins?

A

Calcium has a very high affinity for proteins - (small positive charge attracted to large negative charge)

in plasma, around 40% is bound to plasma proteins.

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13
Q

Why is [Ca2+]plasma not an accurate measurement of physiologically active calcium?

A

[Ca2+]plasma does not account for the Calcium that is bound to proteins or in other ways unavailable

free ionised, and therefore physiologically active [Ca2+] is only about 1.2mM and accounts for ~50% of plasma calcium.

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14
Q

What are the reasons for Calcium in plasma not being physiologically available?

A

Most are bound to plasma proteins (40% of total)

The remaining 10% of plasma calcium ions bind to plasma anions.

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15
Q

What plasma proteins does calcium bind to?

A

Albumin - 80%

Globulin - 20%

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16
Q

What anions can calcium bind to?

A

HCO3

H2PO4

HPO4

Sulphate

Citrate

Lactate

17
Q

What is the effect of pH on the binding capacity for Calcium?

A

Binding capacity is increased under alkalotic conditions

18
Q

If someone is hyperventilating - what is the effect on the pH of the blood and what can this precipitate?

(and vice versa)

A

hyperventilation means that plasma pH rises - becomes more alkaline

Alkaline means increased binding capacity

This means more calcium is bound to - removing Calcium ions from blood

This would precipitate Hypoglycaemic tetany

19
Q

How does alkalosis increase the binding capacity for plasma proteins?

A

If a solution becomes more alkaline - then the [H+] decreases

This means less [H+] ions are available to bind to plasma proteins - meaning there are more available to Ca2+

20
Q

How does calcium leave the body?

A

Ca2+ excretion at kidney and faeces

21
Q

What is more important - keeping calcium in the bones or maintaining Ca2+ balance?

A

Maintaining balance

99% of Calcium stored in bone - but this can be removed when required to maintain said balance

22
Q

What types of cells are responsible for maintaining our bone turnover?

A

Osteoblasts - Bone builders

  • Lay down collagen Extracellular bone matrix and then calcify it

Osteocytes - Exist in established bone

  • less active than osteoblasts but appear to regulate the activity of osteoblasts and osteoclasts

Osteoclasts - Bone removal

  • secrete H+ ions (pH » 4) to dissolve the calcium salts
  • provide proteolytic enzymes to digest the extracellular matrix.
23
Q

What are the 2 key hormones related to maintaining calcium homeostasis?

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
24
Q

Where are the parathyroid glands?

Describe their basic anatomy

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)

Supplied by Left/Right, Superior/Inferior arteries

25
Q

What stimulates the release of Parathyroid hormone?

A

Released in response to DECREASE in free [Ca2+]plasma

26
Q

What is the action of PTH?

A

Parathyroid hormone acts to increase [Ca2+] by:

BONES:

  • Stimulate osteoclast resorption and release of Calcium
  • Inhibit Osteoblast deposition in bone

KIDNEYS:

  • Increases reabsorption of Ca2+ from kidney tubules - decreasing excretion into urine
  • Increases renal phosphate excretion. This elevates free [Ca2+] by preventing it from being deposited back into bone
  • Stimulates calcitriol synthesis which promotes calcium absorption at the gut and kidney.
27
Q

What is Calcitriol?

A

aka active Vitamin D3 or 1,25 dihydroxycholecalciferol

Complements action of PTH - ­[Ca2+] plasma

Steroid hormone produced in two steps (1. liver, 2. kidneys) from dietary vitamin D or from precursors activated by sunlight on skin.

Formation is also stimulated by hormone prolactin in lactating women.

28
Q

What diet advice would you give to patients to increase their dietary vitamin D intake

A

fatty fish eg mackerel and tuna

fish liver oils

egg yolks.

29
Q

Describe the action of calcitriol?

A

Binds to nuclear receptors in its target tissues - Intestines, bone, kidneys

Actions:

1) - Increase absorption of Ca2+ from the gut
2) - Facilitates renal absorption of Ca2+
3) - Stimulates osteoclast activity to mobilise calcium stores

30
Q

Describe how calcitriol increases the level of calcium absorption from our food?

A

The active transport system for Ca2+ absorption from intestinal lumen is under the control of calcitriol

So PTH production - leads to Calcitriol production - leads to increased intestinal absorption of Ca2+

31
Q

In what states is calcium absorption from the lumen increased?

A

Normal individual - 30% of Calcium absorbed

Pregnant women, Lactation, growth spurts - 45-55% Ca2+ absorbed from lumen

Due to high levels of circulating Calcitriol - 1,25 (OH)2D3

32
Q

How common is vitamin D deficiency?

A

~75% of Scots are Vit D “insufficient” in summer, rising to 92% in the winter

Lack of sunlight and poor diet are the main causes of this

33
Q

What is the overall effect of vitamin D3 on the body?

(why is it so important)

A

Direct effect of Vit D3 is to release Ca2+ from bone,

However - its effect on Ca2+ absorption from gut/ reabsoption at kidneys, means the net Vitamin D3 effect is to increase plasma [Ca2+] and ­ mineralization of bone

34
Q

What are the problems associated with Vitamin D deficiency?

A

Rickets in children

Osteomalacia in adults (softening of bones)

Vitamin D3 deficiency generates Ca2+ and phosphate deficiency

35
Q

What endocrine hormone acts the reduce [Ca2+] in the blood?

A

Calcitonin

Peptide hormone produced by the thyroid gland, its secretion is stimulated by ­increased [Ca2+]plasma

36
Q

How does calcitonin work?

A

Binds to osteoclasts to reduce bone resorption

Stimulates renal Ca2+ secretion

However - its actually pretty arbitrary as a hormone and isnt really necessary to maintain Ca2+

37
Q

What other endocrine hormones affect Calcium levels in the blood?

A

Cortisol

Insulin

Oestrogen

Growth hormone

Prolactin

cba writing out how

38
Q
A

Endocrying (21 decks)

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