Mechanism of Action of Hormones Regulating Water and Mineral Metabolism

Mechanism of Action of Hormones Regulating Water and Mineral Metabolism

Introduction

Water and mineral metabolism is tightly regulated to maintain extracellular fluid volume, osmolarity, and electrolyte balance. Several hormones coordinate renal, cardiovascular, and endocrine responses to achieve homeostasis. Key hormones involved in this regulation include antidiuretic hormone (ADH), aldosterone, atrial natriuretic peptide (ANP), and parathyroid hormone (PTH).

Antidiuretic Hormone (ADH)

Source: Secreted by the posterior pituitary (synthesized in hypothalamus).

Stimuli for Secretion:

- Increased plasma osmolarity

- Decreased blood volume or pressure

Mechanism of Action:

- Binds to V2 receptors on principal cells of the renal collecting duct.

- Activates cAMP pathway → insertion of aquaporin-2 water channels into the apical membrane.

- Increases water reabsorption → concentrates urine and reduces plasma osmolarity.

Aldosterone

Source: Secreted by the zona glomerulosa of the adrenal cortex.

Stimuli for Secretion:

- Activation of the renin-angiotensin-aldosterone system (RAAS)

- Increased plasma potassium

Mechanism of Action:

- Binds to intracellular mineralocorticoid receptors in distal tubules and collecting ducts.

- Increases transcription of sodium channels (ENaC) and Na⁺/K⁺-ATPase pumps.

- Promotes Na⁺ reabsorption and K⁺ secretion → increases blood volume and pressure.

Atrial Natriuretic Peptide (ANP)

Source: Secreted by atrial myocytes in response to atrial stretch (increased blood volume).

Mechanism of Action:

- Binds to guanylyl cyclase receptors → increases cGMP.

- Dilates afferent arterioles and constricts efferent arterioles in glomerulus → increases GFR.

- Inhibits renin, aldosterone, and ADH secretion.

- Promotes natriuresis and diuresis → reduces blood volume and pressure.

Parathyroid Hormone (PTH)

Source: Secreted by the parathyroid glands.

Stimuli for Secretion:

- Decreased plasma calcium concentration

Mechanism of Action:

- Increases bone resorption to release calcium and phosphate.

- Enhances renal calcium reabsorption and phosphate excretion.

- Stimulates activation of vitamin D (calcitriol), which increases intestinal calcium absorption.

Integration and Feedback Mechanisms

- ADH and aldosterone act synergistically during hypovolemia.

- ANP acts as a physiological antagonist to RAAS.

- Calcium-phosphate balance is maintained by interplay between PTH, calcitriol, and calcitonin (minor role).

Clinical Relevance

Dysregulation of these hormones can lead to disorders such as hyponatremia, hyperkalemia, dehydration, edema, and osteoporosis. Understanding hormonal mechanisms is essential for managing conditions like heart failure, adrenal insufficiency, and hyperparathyroidism.

Conclusion

Hormones regulating water and mineral metabolism act on the kidneys, bones, and vasculature to maintain homeostasis. Their coordinated actions ensure stable blood pressure, electrolyte levels, and hydration status.

References

1. Guyton and Hall Textbook of Medical Physiology, 14th Edition

2. Lehninger Principles of Biochemistry, 7th Edition

3. Lippincott Illustrated Reviews: Biochemistry, 7th Edition