0626 - Ca and Pi Homeostasis

Question 1

How is Ca++ balance achieved?

Answer 1

Uptake - Proximal small bowel (duodenum>jejunum) vs defecation (of unabsorbed)
Storage - Bone deposition and resorption,
Exchange - ICF vs ISF
Excretion - Kidney (urine)
50% bound, 50% unbound.

Question 2

How is Ca++ Deposition and Resorption achieved from bone? (mechanism and control)

Answer 2

Deposition via osteoblasts, resorption via osteoclasts.
Hormonally controlled (PTH/Calcitonin`.  
Guarantees a rapidly exchangeable pool (4g) from freshly made bone.

Question 3

Describe dietary uptake of Ca++

Answer 3

Duodenum>Jejunum
Net absorption through day - demand is 1g/day depending on age and gravidity - more than doubles in pregnancy or lactation.

Question 4

Outline role of extracellular Ca++

Answer 4

Necessary for muscle function - tetany without free serum Ca++.
Role in extracellular signalling
Determines membrane excitability.
Essential for bone and teeth formation

Question 5

Recognise principles of storage of Ca++ in different compartments

Answer 5

How is Ca++ stored (intra- and extra-cellularly)?
Massive intracellular buffer capacity due to proteins. Binds immediately, so needs to be unbound to be excreted from cell. 10g storage in ER/Mitochondria
Extracellular - Stored in bone (hydroxyapatite). 1-2kg total storage, 10g readily available from freshly-made bone.

Question 6

Describe how extracellular Ca++ is sensed and signalled

Answer 6

Sensed by many proteins
NCS (Neuronal Calcium Sensor) is most important, particularly in peripheral tissue. Has 4 “EF Hands” for Ca++ binding (but can only bind 3).
NCS binds through membrane to a host of adaptor proteins, each with a different signalling cascade/transduction pathways.
That then regulates secretion (including of Ca++-regulating hormones), synaptic plasticity (memory), proliferation, differentiation, apoptosis, gene expression.

Question 7

What are the major factors determining extracellular Ca++

Answer 7

Short term - pH
Acidosis - H+ displaces Ca++ within seconds, raising free serum Ca++ - where one can bind, so can the other.
Alkalosis - Ca++ displaces H+ within seconds, lowering free serum Ca++
Long-term - Hormones
PTH, Calcitonin, Calcitriol (Vit D)

Question 8

What are the three key hormones in regulating Ca++ homeostasis?

Answer 8

Calcium - PTH, Calcitonin, Calcitriol (active Vit D3)

Question 9

How does PTH regulate Ca++ and Pi homeostasis?

Answer 9

PTH - Increases serum Ca, decreases Pi. Secreted only in hypocalcaemia.
Ca - Activates bone (osteoclasts), kidney (Calcitriol synthesis), and indirectly assists absorp/resorption of calcium in gut/kidney. Net increase in serum Ca++.
Pi - Increase in serum Pi is more than offset by increase in Pi inhibiting renal phosphate resorption.

Question 10

How does Calcitonin regulate Ca++ and Pi homeostasis?

Answer 10

Calcitonin - Constitutively released from thyroid, with release directly proportional to Ca++ concentration. Reduces serum Ca++.
Ca++ - Inhibits osteoclasts and stimulates osteoblasts, Also triggers kidney to produce inactive vitamin D.
Pi - Unimportant. Slight lowering of Pi due to increased bone formation and renal filtration.

Question 11

How does Calcitriol (1,25-OH-cholecalciferolactive Vitamin D) regulate Ca++ and Pi homeostasis?

Answer 11

Calcitriol (active Vit D) - On expression of PTH, calcidiol hydroxylated in kidney to form active hormone, via PTH.
Primarily leads to increased gut uptake of Ca++. Targets many other areas (bone, kidney, placenta, breasts, hair, skin etc) secondarily.
Deficiencies arise from diet (lack of oils), reduced absorption (alcohol/kidney disease), lack of sunlight.
Also causes increased gut absorption of Pi and renal reabsorption, and bone resorption, increasing serum Pi.

Question 12

How is phosphate homeostasis regulated by hormones?

Answer 12

PTH - Most important. Secreted in ?hyperphosphataemia - Increases bone resorption, but also increases renal filtration. Decrease net Pi.
Calcitriol - Increases gut absorption, bone resorption, renal reabsorption. Increase net Pi.
Calcitonin - Not important, increases bone formation and renal filtration. Decrease net Pi.

Question 13

What is the effect of each of the 3 hormones on serum Ca and Pi levels?

Answer 13

PTH (most important) - Increase Ca, lower Pi
Calcitriol - Increase both Ca and Pi
Calcitonin - Decrease both Ca and Pi.

Question 14

What are some differences in Ca and P regulation?

Answer 14

Uptake - Ca++ strictly regulated, Pi poorly regulated.

Hormones have different effects.