Parathyroid Hormone & Calcium Regulation

PTH is synthesized as prepro PTH, processed to pro PTH, and finally to active PTH containing 84 amino acids. It is stored in secretory granules until needed.

Control of PTH Secretion

PTH secretion is regulated primarily by extracellular calcium concentration.

Key mechanism:

Low calcium activates PTH release.

High calcium inhibits PTH release.

The calcium sensing receptor on chief cells detects changes in ionized calcium and adjusts hormone secretion instantly.

Other Regulators

• Magnesium deficiency stimulates PTH but severe deficiency paradoxically inhibits it.

• High phosphate levels indirectly stimulate PTH.

• Active vitamin D (calcitriol) inhibits PTH through negative feedback.

A useful memory aid for PTH stimulators is L P M

• Low calcium

• Phosphate increase

• Mild low magnesium

PTH acts on bone to increase calcium and phosphate release.

Mechanism

PTH does not act directly on osteoclasts. Instead, it binds to receptors on osteoblasts, which then release signals that activate osteoclasts. Osteoclasts break down bone matrix, releasing calcium and phosphate into the bloodstream.

Intermittent vs Continuous PTH

• Intermittent PTH has anabolic effects on bone and is used therapeutically for osteoporosis.

• Continuous elevation leads to bone resorption and weakness.

PTH Actions on the Kidneys

The kidneys are essential targets for PTH in calcium regulation.

Effects on Calcium

• Increases calcium reabsorption in the distal tubule.

• Reduces calcium loss in urine.

Effects on Phosphate

• Decreases phosphate reabsorption in the proximal tubule.

• Leads to increased phosphate loss in urine.

Mnemonic:

PTH = “Phosphate Trash Hormone” because it reduces phosphate reabsorption.

Activation of Vitamin D

PTH stimulates 1-alpha hydroxylase in the kidneys, converting inactive vitamin D into active calcitriol. Calcitriol increases calcium absorption from the intestine.

PTH Effects on the Gastrointestinal Tract

PTH does not directly act on the intestines, but it increases calcium absorption indirectly.

Mechanism

• PTH stimulates activation of vitamin D in the kidneys.

• Vitamin D increases calcium and phosphate absorption from the intestines.

Vitamin D complements PTH in maintaining calcium balance.

Sources of Vitamin D

• Formed in the skin by ultraviolet light.

• Obtained from diet.

Activation Pathway

1. Vitamin D3 enters circulation.
2. Converted to 25 hydroxy vitamin D in the liver.
3. Converted to active 1,25 dihydroxy vitamin D in the kidneys through PTH stimulation.

Functions of Active Vitamin D

• Increases intestinal absorption of calcium and phosphate.

• Supports bone mineralization when calcium is sufficient.

• When calcium is low, it enhances bone resorption along with PTH.

Calcitonin: The Opposing Hormone

Calcitonin, produced by parafollicular C cells in the thyroid, lowers blood calcium by inhibiting osteoclast activity. However, its role in humans is limited compared to PTH.

Actions of Calcitonin

• Reduces bone resorption.

• Slightly increases renal calcium excretion.

Calcitonin is more important in childhood and pregnancy when bone turnover is rapid.

Calcium and Phosphate Balance

Calcium and phosphate regulation are linked through PTH and vitamin D.

Calcium Functions

• Muscle contraction

• Blood clotting

• Nerve impulse transmission

• Bone strength and structure

Phosphate Functions

• Energy molecules such as ATP

• Bone mineral matrix

• Cellular signaling

PTH maintains a balance by increasing calcium levels while reducing phosphate levels.

States of Calcium Balance

Positive Calcium Balance

Occurs during growth, pregnancy, or bone healing when intake exceeds loss.

Negative Calcium Balance

Seen in vitamin D deficiency, chronic kidney disease, or postmenopausal bone loss.

Hyperparathyroidism

Overproduction of PTH causes hypercalcemia.

Primary Hyperparathyroidism

• Caused by adenoma or hyperplasia.

• Leads to high calcium and low phosphate.

Secondary Hyperparathyroidism

• Often due to chronic kidney disease reducing vitamin D activation.

• Leads to low or normal calcium with high PTH.

Symptoms of Hypercalcemia

• Muscle weakness

• Constipation

• Kidney stones

• Bone pain

• Psychiatric symptoms such as lethargy

Hypoparathyroidism

Insufficient PTH causes hypocalcemia.

Causes

• Surgical removal of parathyroid glands

• Autoimmune destruction

• Magnesium deficiency

Symptoms of Hypocalcemia

• Numbness and tingling

• Muscle spasms

• Tetany

• Seizures

• Positive Trousseau and Chvostek signs