Calcium homeostasis

Question 1

What are the roles of calcium in the body?

Answer 1

Signalling

Blood clotting

Apoptosis

Skeletal strength

Membrane excitability

Question 2

What signalling roles does calcium carry out?

Answer 2

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

Question 3

What role does calcium play in blood clotting?

Answer 3

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

Question 4

In what way does calcium contribute to membrane excitability?

Answer 4

Ca2+ decreases Na+ permeability

This is a very critical role in short-term homeostasis

Question 5

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

Answer 5

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

Question 6

Describe the distribution of calcium throughout the body

Answer 6

99% - in bones

0. 9% - intracellular
1. 1% - extracellular fluid

Question 7

Describe the containment of intracellular calcium

Answer 7

0.9% of total calcium content

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

Question 8

Describe how calcium exists in extracellular fluid

Answer 8

0.1% of total body calcium

Nearly half of ECF Ca²⁺ is bound to protein

Question 9

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

Answer 9

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

Question 10

How does calcium exist in the bone?

Answer 10

~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.

Question 11

What is the normal concentration of calcium in the plasma?

Answer 11

2.2-2.6 mM in plasma (0.1%)

Question 12

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

Answer 12

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.

Question 13

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

Answer 13

[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.

Question 14

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

Answer 14

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

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

Question 15

What plasma proteins does calcium bind to?

Answer 15

Albumin - 80%

Globulin - 20%

Question 16

What anions can calcium bind to?

Answer 16

HCO₃

H₂PO₄

HPO₄

Sulphate

Citrate

Lactate

Question 17

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

Answer 17

Binding capacity is increased under alkalotic conditions

Question 18

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

(and vice versa)

Answer 18

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

Question 19

How does alkalosis increase the binding capacity for plasma proteins?

Answer 19

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⁺

Question 20

How does calcium leave the body?

Answer 20

Ca2+ excretion at kidney and faeces

Question 21

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

Answer 21

Maintaining balance

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

Question 22

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

Answer 22

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.

Question 23

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

Answer 23

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

Question 24

Where are the parathyroid glands?

Describe their basic anatomy

Answer 24

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

Question 25

What stimulates the release of Parathyroid hormone?

Answer 25

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

Question 26

What is the action of PTH?

Answer 26

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.

Question 27

What is Calcitriol?

Answer 27

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.

Question 28

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

Answer 28

fatty fish eg mackerel and tuna fish liver oils egg yolks.

Question 29

Describe the action of calcitriol?

Answer 29

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

Question 30

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

Answer 30

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+

Question 31

In what states is calcium absorption from the lumen increased?

Answer 31

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

Question 32

How common is vitamin D deficiency?

Answer 32

~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

Question 33

What is the overall effect of vitamin D₃ on the body? (why is it so important)

Answer 33

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

Question 34

What are the problems associated with Vitamin D deficiency?

Answer 34

Rickets in children Osteomalacia in adults (softening of bones) Vitamin D₃ deficiency generates Ca²⁺ and phosphate deficiency

Question 35

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

Answer 35

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

Question 36

How does calcitonin work?

Answer 36

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+

Question 37

What other endocrine hormones affect Calcium levels in the blood?

Answer 37

**Cortisol** **Insulin** **Oestrogen** **Growth hormone** **Prolactin** cba writing out how