Calcium and Phosphate Metabolism 15/11

Question 1

Why is plasma calcium (especially ionised calcium) maintained in narrow limits?

Answer 1

To maintain the integrity of the neuromuscular system

Question 2

What is hypocalcaemia and how does it effect the excitability of neurons?

Answer 2

Low plasma Ca2+ levels

Increases neuronal permeability to Na+ = neurons depolarise = nervous system becomes hyperexcitable

Question 3

What is hypercalcaemia and how does it effect the excitability of neurons?

Answer 3

High plasma Ca2+ levels

Depresses neuromuscular activity

Question 4

What are the 3 compartments of plasma calcium?

Answer 4

1. Ionized calcium Ca2+ - biologically active (50% of total Ca)
2. Complexed calcium - bound to phosphate, citrate, bicarbonate and other anions (5% of total Ca)
3. Protein-bound calcium - bound to albumin, globulins and lipoproteins (45% of total Ca)

Question 5

Describe the intracellular role of ionized calcium.

Answer 5

It is a critical intracellular signalling entity through movement from one intracellular compartment to another

It is part of the intracellular matrix holding cells together at tight junctions

Question 6

What are the inter and intra individual ranges for plasma calcium.

Answer 6

Interindividual (population) range = 2.10 - 2.55mmol/L

Intraindividual (individual) range = +/- 0.12mmol/L

Question 7

What are the inter and intra individual ranges for plasma phosphate.

Answer 7

Interindividual (population) range = 0.6 - 1.2mmol/L

Intraindividual (individual) range = +/- 0.15mmol/L

Question 8

Describe the CaSR and where is it expressed?

Answer 8

A G-protein 7TM receptor that responds to ionized calcium levels across a narrow concentration range

Expressed on parathyroid and thyroid glands, kidney, bone, gut, nervous system and many other organs

Question 9

What are the 3 major organs responsible for Ca homeostasis and what is their role?

Answer 9

Kidney - filters 250mmol of Ca per day but only 96-98% is reabsorbed
Bone - provides Ca to ECF during fasting (stores Ca)
Small intestine - involves saturable (vitamin D mediated) and non saturable absorption mechanisms

Question 10

How is calcium lost in the body and why is it an essential daily nutrient.

Answer 10

Ca is lost from the kidney (due to the inability to reabsorb 100% of filtered Ca), the intestine (lost through intestinal secretions and inability to reabsorb 100%), and the skin through sweat

The bone is a storage bank for calcium and daily Ca intake must be sufficient to maintain bone stores to meet its mechanical and structural roles of the body

Question 11

What are the 3 calciotropic (calcium regulating) hormones?

Answer 11

1. Parathyroid hormone (PTH)
2. Calcitonin
3. Vitamin D

Question 12

Where is PTH produced from?

Answer 12

Parathyroid gland

Question 13

Where is Calcitonin produced from?

Answer 13

Thyroid gland

Question 14

How does PTH regulate Ca levels?

Answer 14

Responds to a fall in Ca2+
Acts on kidney
- increase Ca reabsorption
- decrease phosphate reabsorption
- stimulate synthesis of 1,25D
Acts on bone
- acts on osteoblasts (bone forming) to activate osteoclastogenesis (osteoclast formation) and stimulates resorption on bone by osteoclasts

Question 15

How does Calcitonin regulated Ca levels?

Answer 15

Responds to increase in Ca2+
Acts on kidney
- inhibits tubular reabsorption of Ca
Acts on bone
- receptors localized on osteoclast cell surface inhibit osteoclast bone resorption of Ca

Question 16

How is Vitamin D synthesized?

Answer 16

UV rays act on 7-dehydrocholesterol to produce vitamin D3 - the liver converts vitamin D3 into 25D - the kidney converts 25D to active 1,25(OH)2D which circulates in the plasma

Question 17

How does Vitamin D regulate Ca levels?

Answer 17

Responds to increased and decreased Ca levels

Responds to increased levels by acting on the PTG to inhibit PTH synthesis

Responds to decreased levels by
Acting on intestine - to regulate saturable Ca absorption system
Acting on kidney - increase tubular reabsorption of Ca
Acting on bone - acts on osteoblasts to increase osteoclast bone resorption

Question 18

How is body phosphorous estimated?

Answer 18

By measuring total inorganic phosphate anions in plasma

Question 19

Where does regulation of plasma phosphate levels occur at?

Answer 19

The kidneys

Question 20

What causes hyperphosphataemia?

Answer 20

Chronic Kidney Disease
Diabetes (deranged glucose metabolism)
Release of phosphate from RBC haemolysis

Question 21

What causes hypophosphataemia?

Answer 21

Dialysis or renal leak
Starving or vomiting
High CHO meal

Question 22

What are the 3 hormones that regulate phosphate levels?

Answer 22

1. FGF23.
2. PTH
3. Vitamin D

Question 23

Where is FGF23 synthesized?

Answer 23

Osteoclasts

Question 24

How does FGF23 control phosphate levels?

Answer 24

Lowers plasma phosphate levels by decreased renal tubular reabsorption

Lowers plasma 1,25D levels by inhibiting renal synthesis (conversion of 25D to 1,25D)

Question 25

How does PTH control phosphate levels?

Answer 25

Increases excretion of phosphate in kidney by inhibiting tubular reabsorption

Question 26

How does vitamin D control phosphate levels?

Answer 26

Acts on small intestine to increase phosphate absorption from diet