Calcium and Phosphate Metabolism

Question 1

Explain how levels of ionized calcium affect the excitability of neurons (low Ca2+ and high Ca2+)

Answer 1

Low Ca2+ (hypocalcemia) - neuronal permeability to Na+ increases, neurons depolarise and the nervous system becomes hyperexcitable

High Ca2+ (hypercalcemia) - depresses neuromuscular activity

Question 2

What is plasma Ca2+ a cofactor for?

Answer 2

Blood coagulation

Question 3

What narrow limits are plasma Ca levels maintained within?

Answer 3

2.10-2.55mmol/L

Question 4

Name the 3 compartments of plasma calcium

Answer 4

1. ionised calcium - biologically active (around 50% of total plasma calcium)
2. complexed calcium - bound to phosphate, bicarbonate, citrate and other anions (around 5% of total plasma calcium)
3. protein bound calcium - bound to albumin, globulins and lipoproteins (around 45% of total plasma calcium)

Question 5

What type of calcium is sensed by the organs?

Answer 5

Ionized calcium

Question 6

What is the receptor that responds to ionized Ca levels?

Answer 6

Calcium Sensing Receptor (CaSR)

Question 7

What is the Calcium Sensing Receptor (CaSR)

Answer 7

A Gprotein 7TM receptor that responds to ionised calcium levels

Question 8

Where is the CaSR expressed?

Answer 8

Parathyroid and thyroid glands, kidney, gut, bone, nervous system

Question 9

Is calcium largely an intracellular or extracellular cation?

Answer 9

Extracellular cation

Question 10

What does maintenance of Ca balance require?

Answer 10

Requires Ca dietary intake to equal Ca loss in urine and feces

Question 11

What are the 3 major organs responsible for Ca homeostasis?

Answer 11

1. Kidney
2. Intestine
3. Bone

Question 12

What are the 3 major calciotropic hormones?

Answer 12

1. PTH
2. Calcitonin
3. Vitamin D

Question 13

How does PTH control plasma Ca?

Answer 13

PTH responds to a fall in Ca - stimulates reabsorption from kidney and bone to increase plasma Ca by secretion from the parathyroid gland (acts in minutes)

Question 14

How does Calcitonin control plasma Ca?

Answer 14

Calcitonin responds to an increase in Ca - inhibits reabsorption from kidney and bone to decrease plasma Ca by secretion from the thyroid gland (acts in minutes)

Question 15

How does Vitamin D control plasma Ca?

Answer 15

Reponds to an increase and decrease in Ca levels through modulation of renal metabolism (acts in hours)

Question 16

What are the 3 endocrine activities of 1,25(OH)2D

Answer 16

Intestine - regulate saturable Ca absorption system
Kidney - increases tubular reabsorption of Ca
Bone - acts on osteoblasts to increase osteoclast bone resorption

Question 17

Is phosphate largely an intracellular or extracellular anion?

Answer 17

Largely an intracellular anion

Question 18

What organ is the major regulator of plasma phosphate levels?

Answer 18

The kidney

Question 19

What are the 3 major phosphate regulating hormones?

Answer 19

1. FGF23
2. PTH
3. Vitamin D

Question 20

What is FGF23?

Answer 20

A major polypeptide hormone synthesized by bone cells (osteocytes)

Question 21

Explain how FGF23 regulates plasma phosphate levels

Answer 21

FGF23 responds to an increase in phosphate and acts to lower plasma phosphate by decreasing renal tubular reabsorption

Also lowers plasma 1,25(OH)2D (vitamin D) by inhibiting renal synthesis (vitamin D usually increases tubular reabsorption)

Question 22

Explain how PTH regulates plasma phosphate levels

Answer 22

Same as FGF23 - responds to an increase in phosphate and acts on the kidney to inhibit reabsorption and increase excretion of phosphate

Question 23

Explain how Vitamin D regulates plasma phosphate levels

Answer 23

Responds to low levels of phosphate - acts on small intestine to increase phosphate reabsorption from diet