Endocrinology/Objectives/Lecture 24
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Objectives: 13 - 14 - 15 - 16 - 17 - 18 - 19 - 20 - 21 - 22 - 23 - 24 - 25
Endocrine regulation of calcium homeostasis
Understand the physiological importance of maintaining calcium homeostasis.
Calcium is a second messenger involved in a number of physiological signaling pathways (e.g. muscle contraction). Maintaining a low resting intracellular calcium concentration is necessary to allow minor elevations in calcium concentration to have rapid, dramatic physiological effects.
On another level, calcium homeostasis is necessary to maintain a healthy musculoskeletal system. As bone houses some 99% of the body's calcium stores, chronic dysregulation of calcium homeostasis can have deleterious effects on bone growth and maintenance.
Describe the relationship between the bones, kidneys, and gastrointestinal system in regulating calcium homeostasis.
As mentioned above, the bones are the body's main source of calcium. When calcium is needed, bone is resorbed, releasing calcium into the blood from its hydroxyapetite stores. Under hypercalcemic conditions, calcium storage is enhanced by increased bone deposition.
Maintaining bone composition and calcium levels requires that calcium intake balances its excretion. The regulation of intake is governed by both intestinal absorption and by renal reabsorption. Calcium excretion is regulated by the kidneys.
Explain the roles of parathyroid hormone, vitamin D, and calcitonin in the regulation of plasma calcium levels.
- Parathyroid hormone
- Normally, the kidneys reabsorb some 99% of the filtered calcium, but this can be nominally enhanced via the actions of parathyroid hormone (PTH), which increases calcium absorption and phosphate excretion. PTH also indirectly (via osteoblasts) enhances osteoclast activity, resulting in the resorption of bone and the liberation of calcium into the blood. The net effect of PTH is to elevate blood calcium levels.
- Vitamin D
- Intestinal absorption of calcium, which is more variable than renal reabsorption, is enhanced by vitamin D. Vitamin D would be expected to elevate blood calcium levels.
- Calcitonin
- Calcitonin depresses blood calcium levels by inhibiting bone resorption, enhancing renal excretion of calcium, and enhancing renal absorption of phosphate. Calcitonin's role in calcium maintenance is negligible; PTH is the main controller of calcium homeostasis.
Name the sources of PTH, vitamin D, and calcitonin.
- An 84-amino acid peptide, PTH is derived from the parathyroid gland.
- Vitamin D is a lysosteroid synthesized in multiple steps from 7-dehydrocholesterol in the skin, liver, and bone.
- Calcitonin, a peptide, is synthesized by parafollicular C ("clear") cells in the thyroid gland.
Name the sites of action of PTH, vitamin D, and calcitonin.
| Hormone | Site of action |
|---|---|
| PTH |
Kidney
Bone
|
| Vitamin D |
Small intestine
Kidney
Bone
|
| Calcitonin |
Kidney
Bone
|
Name and describe the functions of the various forms of vitamin D in calcium regulation.
As far as I know, we did not learn about the various forms of vitamin D, including vitamin D1, D2, etc. We did, however, discuss the roles of the various intermediates in the synthesis of 1,25-(OH)2 vitamin D3; perhaps that's what this objective is after...
25-Hydroxycholecalciferol is synthesized by the liver from cholecalciferol. It is not potently active by itself, but can be converted into the potent secosteroid, 1,25-(OH)2 vitamin D3 by 1-hydroxylase in the kidney. A less active, but more highly soluble form of vitamin D3, 24,25-(OH)2 vitamin D3 may also be produced by the kidney by 24-hydroxylase. It is considered a waste product because of its negligible activity and short half-life.
Explain how various levels of plasma calcium influence the secretion of PTH, vitamin D, and calcitonin.
| Calcium level | Effect on PTH secretion | Effect on vitamin D secretion | Effect on calcitonin secretion |
|---|---|---|---|
| ↑Ca2+ | ↓PTH from parathyroids | ↓Vitamin D (via downregulation of renal 1-hydroxylase) | ↑Calcitonin from thyroid |
| ↓Ca2+ | ↑PTH | ↑Vitamin D | ↓Calcitonin |
Know the other hormones that influence the actions and/or levels of vitamin D, PTH, and calcitonin.
Vitamin D synthesis stimulants: Prolactin and PTH (indirectly)
PTH secretion stimulus: Low serum Ca2+, high serum phosphate
Describe the conditions of hypoparathyroidism, hyperparathyroidism, and rickets.
- Hypoparathyroidism
- Characterized by a deficiency of PTH secretion. Would result in decreased bone resorption, increased bone deposition, and hypocalcemia. True hypoparathyroidism may be caused by enzyme deficiencies or iatrogenically (e.g. following removal of the thyroid gland). Pseudohypoparathyroidism is a related syndrome resulting from the inability of the body to respond to PTH (PTH insensitivity), often due to impaired PTH receptor function.
- Hyperparathyroidism
- Characterized by clinically elevated PTH secretion. Would result in increased bone resorption, decreased bone deposition, hypercalcmia. Can result from a primary PTH-secreting tumor of the parathyroid, or from a secondary source (e.g. hypocalcemia due to renal failure, a tumor that secretes a product similar to PTH, etc.).
- Rickets
- Characterized by decreased deposition of inorganic bone matrix relative to organic components (e.g. collagen) in children. The result is highly flexible bones that are resistant to fracture but prone to bowing; symptoms include bow-leggedness and impaired bone growth. In contrast to certain other bone disorders, rickets (called osteomalacia in adults) is due to improper bone composition rather than simply a deficiency in bone deposition. Rickets is usually caused by a deficiency in vitamin D, but liver disease (impairing the production of 25-hydroxycholecalciferol from 7-dehydrocholesterol), renal tubular acidosis, and other diseases may result in rickets.
