Calcium Homeostasis & Parathyroid Hormone

Calcium and Phosphate minerals are tied together because: Together, they comprise the main minerals in bone, and, their homeostatic levels are regulated by the same hormones (parathyroid hormone & vitamin D), which act on the bones, kidneys, and intestines. Be aware that some texts also discuss the role of calcitonin in calcium homeostasis; In this tutorial, we'll focus on the roles of parathyroid hormone and Vitamin D, as the role of calcitonin is uncertain.

• Elevated calcium triggers calcitonin secretion; lower calcium inhibits it.

Calcitonin appears to be important in bone resorption via inhibitory actions on the osteoclast; it also promotes calcium and phosphate excretion in the nephrons, thus reducing calcium ECF levels. Calcium plays a key role in various cellular processes, including:

• Muscle contraction
• Nerve conduction
• Blood clotting
• Bone and tooth formation
• Enzyme activation and deactivation.

Most of the calcium in our bodies is stored in the bone and is inactive; as we'll see, bone formation and resorption can be altered to increase or decrease the availability of active calcium. Normal range for calcium concentration in the extracellular fluid is 2.2-2.6 mmol/L (about 10 mg/dL).

• 40% is bound to plasma proteins
• 60% is ultrafilterable. Of the ultrafiltrable calcium, some is complexed to anions, but most is free, ionized calcium – this is the biologically active form.

We ingest approximately 1000 mg of calcium each day, and excrete most of this in the feces and some in the urine. Given calcium's role in key cellular processes, it's no wonder that our bodies tightly regulate ECF concentrations to avoid muscle, nerve, bone, and other body system dysfunction. Hypocalcemia, when calcium levels fall too low, causes muscle weakness and cramping (tetany when severe), tingling, among others (see notes for full list of signs and symptoms).

• Interesting and helpful exam signs in hyopcalcemia:
• Trousseau's sign, characterized by involuntary hand and feet spasms, carpopedal spasms, which can be provoked by the examiner by inflating a blood pressure cuff to cause prolonged brachial artery occlusion.

• The Chvostek sign, characterized by hyper excitable facial muscle twitching in response to tapping the facial nerve.

Hypercalcemia, too much calcium in the blood, is characterized by muscle weakness, polyuria, lethargy, and even coma. You can learn more about each of these conditions in our tutorials on parathyroid hormone disorders and calcium imbalances: Hyperparathyroidism Hypoparathyroidism Learn more about Hypocalcemia Management Phosphate is part of the ATP molecule, and therefore plays a key role in cellular energy metabolism. Now, let's explore calcium and phosphate regulation; we'll use reduced calcium levels as our starting point. We show the thyroid gland in posterior view with four parathyroid glands. Target sites for calcium and phosphate regulation: the kidneys, small intestine, and bones. Parathyroid hormone, PTH, is secreted in response to low calcium levels. Exposure-dependent:

• In response to prolonged exposure to PTH, bone resorption occurs; this process releases calcium and phosphate from the bone to the extracellular fluid.
• However, in response to episodic exposure to PTH, new bone synthesis occurs, which takes calcium and phosphate from the ECF to build more boney tissue.

This is why we can use parathyroid hormone to treat osteoporosis, which is a disorder characterized by too much bone resorption and, as a result, weakened and brittle bones. Parathyroid hormone has multiple effects in the kidney:

• Inhibits phosphate reabsorption
• Increases calcium reabsorption
• VItamin D activation

Thus, PTH causes phosphaturia (excretion of phosphate in the urine) and calcium retention, leading to an elevation in ECF calcium. Note that the excretion of phosphate in the urine prevents calcium-phosphate salt formation, which would remove the active calcium from the blood at a time when we need to elevate it. Within the kidney, vitamin D is synergistic with PTH, but it also has extra-renal effects. Intestines: Activated Vitamin D acts in the small intestine to increase calcium and phosphate reabsorption, leading to elevated ECF calcium. Bones: Vitamin D increases bone turnover, which contributes to the release of calcium and phosphate initiated by PTH. As a clinical correlation, denote that Vitamin D's influence on bone turnover is evident in Rickets, a childhood disorder in which Vitamin D deficiency leads to impaired bone growth; affected children have soft, deformed bones. Elevated calcium levels will inhibit further PTH secretion via negative feedback loops; this protects us from hypercalcemia and bone depletion. Sex steroid hormones and glucocorticoids are also important for maintaining bone mass; this is why we see more osteoporosis in post-menopausal and Cushing syndrome patients who have lower estradiol and cortisol, respectively. PTH raises ECF calcium levels directly via its actions on the bones and kidneys, and indirectly via Vitamin D's actions on the intestines.