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Calcium Homeostasis
Calcium Physiology
Calcium’s Role in Physiology
The following are some of the key processes that rely on appropriate calcium levels in the blood.
- Bone mineralization
- Cardiac conduction
- Neuromuscle transmission
- Neuronal excitation
- Second messenger signaling (endocrine pathways)
- Blood clotting
- Interestingly, it is rare of abnormal calcium blood levels to clinically impact blood clotting, however.
Extra-skeletal Organs Involved in Calcium Homeostasis
Key calcium and vitamin D physiology:
Skin
- Vitamin D is synthesized in the skin.
- Specifically, UVB radiation converts 7-dehydrocholesterol into vitamin D₃ (cholecalciferol).
Gastrointestinal System
- Vitamin D is hydroxylated in the liver.
- Specifically, vitamin D₃ (cholecalciferol) is hydroxylated in the liver to 25(OH)D (calcidiol or 25-hydroxycholecalciferol).
- Calcium is absorbed in the small intestine (duodenum and jejunum, primarily).
Kidneys
- Vitamin D is activated in the kidneys.
- Specifically, 25(OH)D is activated in the kidneys to 1,25(OH)2D (calcitriol).
- Calcium is reabsorbed (in the proximal tubule)
Calcium Storage in Bone
High Calcium Promotes Bone Growth
When serum calcium is high, calcium is pulled from the blood to form bone.
- Excessively high calcium levels (hypercalcemia) can cause multiple physiological issues, which we’ll soon address, including cardiac dysrhythmias, muscle weakness, and renal stones and renal injury.
Low Calcium Promotes Bone Breakdown
When serum calcium is low, bone is broken-down and push calcium into blood.
- Serum calcium must be available for numerous physiological processes beyond just bone growth, which we’ll address in detail, including cardiac muscle contraction, neuromuscle activation, and nerve transmission.
Calcium Serum Range
A healthy physiological blood calcium level range is ~ 8.5 to 10.5 mg/dL.
Osteoclast Activation (Hypocalcemia)
Low Blood Calcium (Hypocalcemia)
Low blood calcium levels (less than 8.5 mg/dL) activates osteoclasts.
Parathyroid Hormone (PTH)
Hypocalcemia stimulates parathyroid hormone release of parathyroid hormone (PTH), which indirectly stimulates osteoclast activation.
RANKL Release
PTH stimulates osteoblast release of RANKL, which binds to RANK.
Osteoclast Differentiation/Activation
RANK activation of osteoclast lineage cells (preosteoclasts) and osteoclasts stimulates osteoclast activity: break-down of bone and release of calcium into the blood stream.
Osteoclast Inactivation (Hypercalcemia)
High Blood Calcium (Hypocalcemia)
High blood calcium levels (greater than 10.5 mg/dL) inactive bone resorption.
Key Structures
Thyroid gland
Parafollicular cells (aka clear (C) cells) exist on the thyroid gland.
Calcitonin
Next, include a calcitonin receptor on the surface of the osteoclast.
Calcitonin Activation
Hypercalcemia
Hypercalcemia triggers parafollicular cells to release calcitonin.
Calcitonin
Calcitonin binds calcitonin receptors on osteoclasts and inactivates them. This allows for calcium to be pulled from the blood and used in the mineralization of bone, without the compensatory break-down of bone and release of calcium into the bloodstream.
Summary
Low Blood Calcium
LOW blood (plasma) calcium levels:
- Inhibit osteoblast-mediated building of bone.
- Stimulate osteoclast activity (to break-down bone).
High Blood Calcium
HIGH blood (plasma) calcium levels:
- Stimulate osteoblast-mediated bone-building.
- Inhibit osteoclast activity (to prevent bone break-down).