Pathophysiology of hyperparathyroidism and renal bone disease
Parathyroid hormone (PTH) is secreted by the parathyroid glands which are located in the thyroid gland.
Homeostasis of phosphate, calcium, vitamin D and PTH are interconnected via the kidneys, GIT, parathyroid glands, and the bones.
Apart from bone structure, calcium and phosphate have vital roles in biological functions and processes. Functions of Ca2+ includes muscle, heart and nerve functioning and blood clotting. Phosphate ([PO4]3-) is required for many processes and is in ATP and nucleic acids.
If calcium blood levels drop, the cell and biological functions are prioritised over bone density and calcium is released from the bones (bone pool) to try to maintain Ca2+ levels in the blood.
Phosphate deficiency is rare because it is abundant in food and easily absorbed from the GIT.
Calcium and phosphate are absorbed into the body via the GIT.
Activated Vitamin D is required for calcium absorption. Vitamin D needs to be activated by the kidneys.
The kidneys excrete phosphate and reabsorb calcium back into the body.
The regulation of calcium levels is performed by PTH. PTH secretion is triggered mainly by low calcium levels, but also by high phosphate and low Vitamin D levels.
The function of PTH is to restore Ca2+ levels in the blood
- Enhances calcium reabsorption and phosphate excretion by the kidneys
- Stimulates activation of vitamin D in the kidneys causing enhanced Ca2+ absorption from the GIT
- Stimulates osteoclasts to release calcium from the bones
(PTH is opposed by calcitonin which is secreted by the thyroid gland)
Chronic kidney disease causes low Ca2+ levels:
- Impaired kidneys are not able to secrete phosphate (hyperphosphotaemia) or reabsorb Ca2+
- Due to calcium and phosphate binding, hyperphosphataemia causes hypocalcaemia as there is more phosphate than Ca2+.
- There is reduced Vit D activation which reduces Ca2+ absorption from the GIT.
Hypocalcaemia causes hyperparathyroidism:
- Low calcium levels (as well as high phosphate and low Vit D) causes secretion of PTH
- Kidney contribution is deficient, deficiency in activated Vit D means there is low absorption of Ca2+ from the GIT. Bone pool alone is not enough to restore Ca2+ levels.
- As Ca2+ levels never get restored the parathyroid glands are continuously activated to keep secreting PTH, causing enlarged parathyroid glands and hyperparathyroidism.
Hyperparathyroidism causes renal bone disease
- Continuous PTH exposure causes the bones to keep releasing Ca2+ in the blood which over time cause bone disease and bone fractures.
- Renal bone disease is a classic complication of CKD.
Introduction to Renal Therapeutics Ashley and Morlidge