Calcium and phosphate are the body’s two main mineral ions. Calcium is used as a signal inside cells and is stored as the mineral of bone. Phosphate is also part of bone mineral, and it takes part in energy metabolism and in many intracellular reactions.
Calcium circulates in the extracellular fluid (the fluid outside cells, including plasma) within narrow limits. Those limits keep nerves, muscles and bone working, and even small departures disturb them. Phosphate is not held as tightly: it is buffered in the body and regulated more loosely, so it varies with the diet through the day.
How is the system organised?
If one ion is held tightly and the other loosely, something has to do the holding. The system has two layers. The first is the traffic of the ions themselves: where they are stored, and how the gut and kidney gain and lose them. The second is the hormones that adjust that traffic: PTH (parathyroid hormone), FGF23 (fibroblast growth factor 23), vitamin D and calcitonin. Calcium intake and excretion are tightly balanced, and bone is the reserve behind both. A hormone is a way of turning one of the traffic steps up or down. The hormones act on bone, kidney and intestine because these are the three places where calcium and phosphate are stored, gained or lost.
Where to start, and what does each note explain?
The order of the list is also the order in which the pieces depend on each other: the traffic comes before the hormones that adjust it. Start with calcium balance.
- Calcium Balance: Distribution, Absorption and Excretion: where the body’s calcium is, the concentration gradient between cytosol and extracellular fluid, plasma fractions and adjusted calcium, intestinal absorption, and renal handling with its modifiers.
- Phosphate Homeostasis: the body’s phosphate distribution, the two forms present at blood pH, intestinal absorption, and renal reabsorption with urinary buffering.
- Parathyroid Hormone (PTH): the calcium-sensing receptor and the feedback loop it runs, synthesis of PTH, its actions on bone, kidney and calcitriol production, its receptors, and the response to hypocalcemia over time.
- Fibroblast Growth Factor 23 (FGF23): a bone-derived hormone that promotes phosphate excretion and inhibits calcitriol formation, with its processing, receptor and Klotho co-receptor, and the stimuli that release it.
- Vitamin D and Calcitonin: vitamin D’s two forms, its activation to calcitriol and calcitriol’s effects on calcium and phosphate; and calcitonin, the thyroid hormone that lowers plasma calcium.
- Parathyroid Hormone-Related Protein (PTHrP): a peptide that activates the PTH receptor in many tissues and causes hypercalcemia of malignancy when tumors secrete it.
Where does the body’s calcium actually sit, and how does it get in and out?