Hormonal regulation of extracellular calcium and phosphate concentrations by the parathyroid glands.

Key Principles

Free calcium participates in various cellular processes, including:

• Skeletal, cardiac, and smooth muscle contraction
• Nerve conduction
• Blood clotting
• Bone and tooth formation
• Enzyme activation and deactivation

Phosphate is a part of ATP

• Participates in cellular metabolism
• Plays a role in enzyme activation and deactivation

Storage and Release:

Calcium and phosphate are stored within hydroxyapatite crystals of bone

• When bone is resorbed, calcium and phosphate are released into the extracellular fluid
• Calcium and phosphate levels are regulated by the same hormones:
  • Parathyroid hormone, which is secreted by chief cells of the parathyroid glands
  • Vitamin D (in activated form)

(The physiologic role of calcitonin, a hormone released by the thyroid gland in response to increased calcium concentrations, is as of yet uncertain, and, therefore, omitted in this tutorial.)

PARATHYROID HORMONE PATHWAYS:

In response to lowered extracellular calcium concentration, the parathyroid glands secrete parathyroid hormone (PTH).

Bone:

• In bone, episodic, transient binding of parathyroid hormone causes an increase in new bone synthesis
• Prolonged exposure to parathyroid hormone promotes resorption of old bone, and, therefore, the release of calcium and phosphate into extracellular fluid

Clinical consequences of these dichotomous effects:

• Osteoporosis, which is characterized by loss of bone density, can be treated with intermittent PTH administration
• Continuous release of PTH in individuals with hyperPARAthyroidism causes excessive bone resorption

Kidneys:

• Increased calcium reabsorption in the distal convoluted tubule of the nephrons
• Decreased phosphate reabsorption in the proximal convoluted tubule, which leads to phosphaturia, an increase in phosphate in the urine
  – This action is important because, otherwise, reabsorbed phosphate would complex with the reabsorbed calcium, which would negate its physiologic effects in the body.

PTH STIMULATES RENAL ACTIVATION OF VITAMIN D

Kidney

• Vitamin D acts increases renal reabsorption of both calcium and phosphate

Small Intestine

• Vitamin D increases calcium and phosphate reabsorption

Bones

• Vitamin D works with parathyroid hormone to facilitate skeletal remodeling, which requires both synthesis and resorption of bone.

Clinical correlation:

Vitamin D deficiency in children causes rickets, in which skeletal development is impaired, the bones are weak, and, consequently, growth is often stunted.

System-wide consequences of calcium imbalances:

Hypocalcemic individuals experience hyperreflexia, muscle twitching and cramping, numbness and tingling

• 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.

Hypercalcemic individuals experience hyporeflexia, muscle weakness, lethargy, and, polyuria.