Extracellular calcium homeostasis is maintained by parathyroid hormone
For students new to the endocrine system, plasma calcium regulation is a good place to start learning how endocrine feedback loops work. This feedback system is simpler than some because it does not include a brain component.
It is critical that free Ca++ in plasma, and therefore in interstitial fluid around cells, is maintained at a dependable level. Action potentials of cardiac muscle require a higher concentration of Ca++ in the extracellular fluid than within the cell. Likewise, release of neurotransmitter at neuron synapses depends upon a reliable diffusion of Ca++ into neuron terminals through voltage-gated calcium ion channels.
Ca++ moves freely at capillaries between blood and the interstitial fluid. Thus, the concentration of Ca++ remains similar in blood and interstitial fluid. Calcium enters the body regularly from the diet through the gastrointestinal tract. When dietary calcium drops, or if the kidney’s ability to reabsorb Ca++ after blood filtration becomes impaired, bone acts as a Ca++ reservoir. Crystals of bone’s calcium phosphate are broken down to maintain this ion’s plasma set point.
Ca++ regulation begins at the parathyroid gland. The parathyroid gland, composed of four small structures, sits on the surface of the thyroid gland. The hormone it secretes is called parathyroid hormone (PTH).
The rate of PTH secretion increases above its constant basal rate when Ca++ in plasma falls below a critical level. Blood flow delivers PTH to bone compartments. PTH receptors in bone exist on the surface of osteoblasts, the cells building bone. Increased PTH stimulates osteoblast secretion of secondary molecules to trigger osteoclasts to breakdown bone’s calcium phosphate crystals.
Plasma concentrations of Ca++ and phosphate ion rise in the presence of PTH at bone. To prevent recrystallization of calcium phosphate, the phosphate ion must be eliminated. To accomplish this PTH has an additional effect at the kidney. At the distal tubules and collecting duct of the nephrons PTH inhibits reabsorption of phosphate ions back into blood.
PTH at the kidney also stimulates kidney conversion of the inactive form of vitamin D in blood to its active form. In turn, an increased amount of active vitamin D binds to its receptors in intestinal cells and enhances absorption of Ca++ from digested food.
Parathyroid Negative Feedback
The cells of the parathyroid gland have a receptor on their surface for binding Ca++. This calcium-sensing receptor connects to intracellular pathways regulating the synthesis of PTH. When interstitial fluid Ca++ rises above 10 mg/dl due to bone re-absorption and increased uptake from the intestine, calcium-sensing receptor activity slows PTH synthesis and release. PTH falls to its low basal level in blood.
The adjacent thyroid gland also produces a hormone named calcitonin. Calcitonin works in opposition to PTH to lower plasma Ca++ when it is too high. While calcitonin paired with PTH remains an important regulator of plasma Ca++ in some animals, calcitonin does not appear to play a significant role in human Ca++ regulation. In those where calcitonin has a role, it inhibits osteoclast activity by binding to a receptor embedded in the osteoclast membrane. And, it inhibits re-absorption of Ca++ and phosphate ion.
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Margaret Thompson Reece PhD, physiologist, former Senior Scientist and Laboratory Director at academic medical centers in California, New York and Massachusetts and CSO at Serometrix LLC is now CEO at Reece Biomedical Consulting LLC.
Dr. Reece is passionate about helping students, online and in person, pursue careers in life sciences. Her books “Physiology: Custom-Designed Chemistry” (2012), “Inside the Closed World of the Brain” (2015) and the workbook (2017) companion to her online course “30-Day Challenge: Craft Your Plan for Learning Physiology” are written for those new to life science. More about her books is available at https://www.amazon.com/author/margaretreece.
Dr. Reece offers a free 30 minute “how-to-get-started” phone conference to students struggling with human anatomy and physiology. Schedule an appointment by email at DrReece@MedicalScienceNavigator.com.by