Notes
Parathyroid Hormone
Sections
Overview
Calcium & Phosphate Overview
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.
Calcitonin
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.
Elevated calcium triggers calcitonin secretion; lower calcium inhibits it.
Calcium Physiological Roles
Physiological Roles of Calcium
Calcium plays a key role in various cellular processes, including:
- Muscle contraction
- Nerve conduction
- Blood clotting
- Bone and tooth formation
- Enzyme activation and deactivation.
Calcium Storage
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.
Serum Calcium Range
Normal range for calcium concentration in the extracellular fluid is 2.2-2.6 mmol/L (8.5 to 10.5 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.
Calcium Ingestion
We ingest approximately 1000 mg of calcium each day, and excrete most of this in the feces and some in the urine.
Hypocalcemia & Hypercalcemia
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
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).
Physical Exam Findings in Hypocalcemia
Interesting and helpful exam signs in hyopcalcemia are Trousseau's sign and Chvostek's sign.
Trousseau's sign
Trousseau's sign is 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.
Chvostek's sign
Chvostek's sign is characterized by hyper excitable facial muscle twitching in response to tapping the facial nerve.
Hypercalcemia
Hypercalcemia, too much calcium in the blood, is characterized by muscle weakness, polyuria, lethargy, and even coma.
Hyperparathyroidism
You can learn more about each of these conditions in our Pathology tutorials on parathyroid hormone disorders and calcium imbalances:
Phosphate
Phosphate is part of the ATP molecule, and therefore plays a key role in cellular energy metabolism.
Calcium & Phosphate Regulation
Now, let's explore calcium and phosphate regulation; we'll use reduced calcium levels as our starting point.
Parathyroid Gland
We show the thyroid gland in posterior view with four parathyroid glands.
Target Sites
Show the target sites for calcium and phosphate regulation: the kidneys, small intestine, and bones.
Parathyroid Gland (PTH)
Parathyroid hormone, PTH, is secreted in response to low calcium levels.
Parathyroid Gland
PTH Effects on Bone
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.
PTH Effects on the Kidney
Parathyroid hormone has multiple effects in the kidney:
- Inhibits phosphate reabsorption
- Increases calcium reabsorption
- VItamin D activation
Phosphaturia
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.
Vitamin D
Vitamin D 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.
Ricket's
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.
PTH Inhibition
Elevated calcium levels will inhibit further PTH secretion via negative feedback loops; this protects us from hypercalcemia and bone depletion.
Other hormonal mediators
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.
Summary - Parathyroid Hormone & Vitamin D
PTH raises ECF calcium levels directly via its actions on the bones and kidneys, and indirectly via Vitamin D's actions on the intestines.