Normal calcium and phosphate homeostasis
You want to quickly explain normal Ca homeostasis so you can get onto explaining disorders of Ca metabolism and their orthopaedic manifestations.
Scene Setting
Say
Calcium is an important intra and extracellular ion:
- Structural - Inorganic component of bone
- Cell signalling - troponin-c in muscle contraction, neurotransmitter release
- Protein binding - clotting factors activation
Principally regulated by three main hormones:
- Parathyroid hormone
- Vitamin D
- Calcitonin
Acting on three main target organs:
- Bone
- Kidney
- Gut
Draw
Three by three grid of the hormones and target organs.
Parathyroid hormone
Say
Parathyroid hormone secreted by chief cells in the parathyroid in response to low Ca or low Mg levels.
Acts on bone to indirectly increase osteoclast activity and increases serum Ca and Phos by three mechanisms:
- Osteoblast differentiation which upregulate osteoclasts via RANK pathway
- Inhibit osteoprotegrin
- Increases RANKL
Acts on Kidney at the proximal tubule to increase serum Ca and lower serum Phos by:
- 1alpha hydrolase activity increasing Calcitriol
- Increase Ca resorption
- Increase excretion of Phos
Acts on gut to increase Ca and Phos absorption:
- Indirectly, via Calcitriol
Net effect: Increase serum Ca, decrease serum Phos
Draw
The source and stimulus for PTH, and it’s target organ effects, with global net effect on serum Ca/Phos.
1,25 Vitamin D
Say
25 Vit D is activated to 1,25 Vit D in the proximal tubule of the kidney under influence of PTH, low Ca or low Phos.
Acts on the bone to indirectly increase osteoclast activity.
Acts on the gut to strongly increase Ca and Phos absorption.
Net effect: Increase serum Cal and Phos
Draw
The source and stimulus for Vit D, and it’s target organ effects on bone and gut, with global net effect on serum Ca/Phos.
Calcitonin
Say
Secreted by thryroid parafollicular cells in response to raised Ca.
Acts on bone by directly downregulating osteoclast activity
Acts on Kidney to transiently increase Ca and Phos excretion.
Physiologically the role is not clear, but may assist in preventing post-prandial hypercalcaemia. Therapeutic calcitonin is used for Pagets disease and hypercalcaemia management, but this is in fact salmon derived which is 20-50 times more active than human derived.
Draw
The source and stimulus for calcitonin, and it’s target organ effects on bone and kidney, with global net effect on serum Ca/Phos.
That is the basic principles of Ca/Phos homeostasis, but use this as a prompt when discussing pathology.
