Calcium homeostasis

Question 1

Role of Ca2+ in the body (5)

Answer 1

Signalling

Blood clotting - essential component of clotting cascade

Apoptosis

Skeletal strength

Membrane excitability

Question 2

Ca2+ involvement with signalling

Answer 2

Ca2+ = important signalling molecule

exocytosis of synaptic vesicles e.g. neurotransmitters/ hormones etc

contraction of muscle fibres

alters enzyme function

Question 3

What % of calcium in the body is wrapped up in bone? and what form is it in?

Answer 3

99%
Ca10(PO4)6(OH)2

Calcium phosphate hydroxyapatite

Question 4

How is Ca2+ involved with membrane excitability?

Answer 4

Ca2+ decreases Na+ permeability

Question 5

Which of Ca2+ roles is the most critical in short term homeostasis?

Answer 5

Membrane excitability

Question 6

Effect of Hypocalcaemia

Answer 6

increases neuronal Na+ permeability leading to hyperexcitation of neurons.

In extreme cases causes tetany, if spreads to larynx and respiratory muscles – asphyxiation.

Question 7

Effect of Hypercalcaemia

Answer 7

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

Question 8

Calcium distribution within the body excluding the Ca2+ in bone

Answer 8

0. 9% intracellular

0. 1% extracellular fluid - 2.2-2.6 mM in plasma

Question 9

Where is intracellular Ca2+ stored?

Answer 9

inside mitochondria and sarcoplasmic reticulum

very low levels of free calcium in the cytoplasm

Question 10

How is Extracellular Ca2+ further divided?

Answer 10

nearly half (40%) ECF Ca2+ is bound to protein (small + charge attracted to large - charge of proteins)

so only 0.05% of Ca2+ in the body is free in solution and physiologically active

Question 11

What % of Ca2+ is physiologically active in the body?

Answer 11

0.05%

Question 12

Other than Ca2+ itself, what else needs to be carefully controlled to determine calcium balance?

Answer 12

Phosphate homeostasis

Question 13

What are the 3 forms ca2+ exists in in the blood?

Answer 13

Protein bound (40%)

Free (ionised) - active (50%)

Complexed (10%) - free +anion =complexed e.g CaCO3 etc (not active)

Question 14

How does pH affect Ca2+ binding

Answer 14

the binding capacity of plasma proteins changes with pH

Binding capacity is increased under alkalotic conditions

Opposite occurs with acidosis where binding capacity reduces and free [Ca2+]plasma rises (hypercalcaemia)

Question 15

If you hyperventilate what happens to plasma pH

Answer 15

plasma pH rises as you blow off CO2 so becomes less acidic

plasma proteins bind more Ca2+ causing plasma concentration to fall and therefore may precipitate hypocalcaemic tetany

Question 16

Summary of pH and Ca2+ binding

Answer 16

low pH - acidic environment - lower binding capacity of plasma proteins - more Ca2+ in plasma - hypercalcaemia

high pH - alkaline environment - better higher binding capacity of plasma proteins - less Ca2+ in plasma - hypocalcaemic tetany

Question 17

What happens to Ca2+ in bone if plasma need more Ca2+

Answer 17

Bone will be sacrificed despite important functions in order to maintain plasma calcium levels

Question 18

Function of osteoblasts

Answer 18

bone-building cells - blast out new bone

They are highly active cells which lay down a collagen extracellular matrix which they then calcify

Question 19

Function of osteocytes

Answer 19

Osteocytes are much less active than osteoblasts but appear to regulate the activity of osteoblasts and osteoclasts

Question 20

Function of Osteoclasts

Answer 20

Cells that are responsible for mobilizing bone.

They secrete H+ ions to dissolve the calcium salts and also provide proteolytic enzymes to digest the extracellular matrix.

Question 21

2 hormones that act increase plasma concentration of Ca2+

Answer 21

Parathyroid hormone - (dominant) peptide

Calcitriol - steroid

Question 22

What produces calcitriol

Answer 22

produced from vitamin D by the liver and kidneys

Question 23

What is the active form of calcitriol in

Answer 23

Vitamin D3

Question 24

Describe the secretion of PTH - released in response to a decrease in free plasma Ca2+

Answer 24

Stimulating osteoclasts to increase resorption (release) of Ca2+ and phosphate in bone

Inhibiting osteoblasts to reduce Ca2+ deposition in bone.

Increasing reabsorption of Ca2+ from the kidney tubules, therefore decreasing its excretion in the urine.

Increasing renal excretion of phosphate. This elevates free [Ca2+ ] by preventing it from being deposited back into bone, a process that requires phosphate.

Stimulates the kidney to synthesise calcitriol from vitamin D which promotes calcium absorption at the gut and kidney.

Question 25

Calcitriol

Answer 25

Complements action of PTH - increase plasma Ca2_

A 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.

Active vit D3 is formed from cholesterol derivatives by the light on the skin but vit D can also be gained from the diet

Question 26

How does calcitriol increase absorption of Ca2+ from the gut

Answer 26

Unlike many substances, such as water, Na+ and K+ which are completely absorbed from the gut, much of the Ca2+ in the diet passes straight through and is excreted in the faeces.

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

low plasma Ca2_+ - increased PTH - increased Calcitriol - increase in intestinal absorption of ca2+

Question 27

Actions of calcitriol (3)

Answer 27

Increase absorption of Ca2+ from the gut.

Facilitates renal absorption of Ca2+

Mobilises calcium stores in bone by stimulating osteoclast activity.

Collectively these actions, complement those of PTH and increase [Ca2+ ]plasma

Question 28

What are calcitriol’s target tissues

Answer 28

intestine

bone

kidney

Question 29

What happens when there is an increased demand for Ca2+ for milk production in lactation?

Answer 29

Prolactin stimulates Calcitriol synthesis

Question 30

Define vit D deficiency

Answer 30

when vit D levels in the blood fall less than 20 ng/ml

Question 31

What is rickets?

Answer 31

Common in children

Soft bones due to vit d deficiency

PTH works hard to maintain plasma [Ca2+] and in doing so continually removes Ca2+ from bone resulting in bones which are soft and, if still growing, become bent.

Question 32

Osteomalacia

Answer 32

bones become easily fractured due to vit D deficiency

Question 33

Vit D3 deficiency - what happens? who is most at risk?

Answer 33

leads to intestinal malabsorption of Ca2+ which decreases [Ca2+]plasma

this increases PTH which then promotes phosphate deficiency - aggravates Ca2+ loss from bone

elderly and asian populations are 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.

Question 34

What is the only hormone that decreases plasma concentration of Ca2+

Answer 34

Calcitonin

Peptide hormone produced by thyroid gland - released when [Ca2+]plasma increases

Question 35

Main action of calcitonin

Answer 35

Binds to osteoclasts and inhibits bone resorption as well as increasing renal excretion so preventing a further increase in Ca2+

however, little evidence it is of much importance in humans - can have high calcitonin levels (due to tumours etc) and still have normal Ca2+ levels

any excess of calcitonin is overridden by PTH

Question 36

Other endocrine hormones altering ca2+ balance

5

Answer 36

Cortisol

Insulin

Oestrogen

GH

Prolactin

Question 37

Cortisol

Answer 37

inhibits osteoblasts, increases renal excretion of Ca2+ and phosphate and reduces intestinal absorption of Ca2+

decreases plasma [Ca2+ ] which increases PTH and increases bone resorption.

over time - can produce osteoporosis

Question 38

Insulin and Ca2+

Answer 38

Insulin increases bone formation, and antagonises the action of cortisol.

Diabetics may have significant bone loss.