Calcium Homeostasis

Calcium Homeostasis

Key Points

Total Body Calcium

  • Approximately 1,000 grams of calcium in the human body.

    • 99% is found in the bone (Crystalline Form).

    • 1% is found in non-bone areas (e.g., extracellular fluid, intracellular fluid, blood, interstitial fluid).

Hormonal Control Systems

Increases Blood Calcium Concentrations

  1. Parathyroid Hormone (PTH)

  2. Vitamin D

Reduces Blood Calcium Concentrations

  • Calcitonin (allegedly)

Anatomy References

Parathyroid and Thyroid Glands

  • Thyroid Gland

    • Anterior View and Posterior View

    • Structures: Right Thyroid Lobe, Isthmus, Trachea, Right Inferior Parathyroid, Recurrent Laryngeal Nerve.

Calcium Regulation Mechanism

  • Parathyroid Gland Functions:

    • ↑ VD CaSR: Vitamin D Calcium Sensing Receptor increases likelihood of calcium absorption and activation.

    • ↑ Ca²+: PTH secretion increases calcium levels in blood, stimulates vitamin D activation, enhances Ca²+ reabsorption, and decreases phosphate reabsorption.

    • Bone Turnover: PTH influences both resorption and formation of bone.

Homeostatic Regulation of Calcium

Diagram:

  • Calcium levels in blood can be disturbed or restored:

    • Rising Calcium Levels:

    • Trigger calcitonin production (thyroid gland).

    • Promotes calcium deposition in bone.

    • Falling Calcium Levels:

    • Trigger PTH secretion from the parathyroid gland.

    • Leads to release of stored calcium from bone, enhanced renal reabsorption of calcium, and stimulation of calcitriol production at kidneys.

    • Normal Calcium Levels: 8.5-11 mg/dl.

Factors Influencing PTH Secretion

Relationships

  • Increased Calcium Levels → Increased PTH Secretion (extraction from bones, enhanced renal & dietary absorption).

  • Lowered Calcium Levels → Decreased PTH Secretion (opposite mechanisms).

Diagram of Hormonal Effects

Visual Representation of Calcium Homeostasis

  • Shows hormone interactions during calcium levels disturbance and restoration processes.

Biochemical Pathways

PTH and Vitamin D Interactions

  • Calcium Loading → PTH secretion stimulated.

  • Calcium Deprivation → PTH secretion inhibited.

  • Vitamin D: Production is stimulated by increased PTH, whereas low PTH suppresses it.

Bone Cells' Roles

  • Osteoclasts: Derived from monocyte-macrophage lineage, responsible for bone resorption.

  • Osteoblasts: Express PTH receptors, mediate bone formation.

  • Osteocytes: Terminally differentiated osteoblasts embedded in bone matrix, regulate bone metabolism, sense hormonal and mechanical changes, produce FGF23 (Fibroblast Growth Factor 23).

Vitamin D Metabolism

  • Skin: Converts 7-dehydrocholesterol to Cholecalciferol (Vitamin D3) through exposure to UV light.

  • Liver: Converts Vitamin D3 to 25-hydroxy vitamin D3.

  • Kidney: Activated by 1-alpha hydroxylase into the active form of Vitamin D3 (1,25(OH)2D3). This enhances intestinal calcium absorption and mobilizes calcium from bones.

Calcium Disorders

Hypercalcemia

  • Definition: Total plasma Ca concentration > 10.4 mg/dL.

  • Principal Causes:

    • Hyperparathyroidism (especially with lithium).

    • Vitamin D toxicity.

    • Certain cancers.

Symptoms of Hypercalcemia

  1. Stones: Renal stones, nephrocalcinosis, polyuria, polydipsia, uremia.

  2. Bones: Osteitis fibrosa presenting as subperiosteal resorption, osteoclastomas, radiologic osteoporosis, osteomalacia/rickets, arthritis.

  3. Abdominal Groans: Symptoms include constipation, nausea, vomiting, peptic ulcers.

  4. Psychic Moans: Symptoms include lethargy, fatigue, depression, and in severe cases, memory loss, psychoses, and coma.

Diagnosis and Treatment

Diagnosis of Parathyroid Disorders

  • Assessment of intact PTH levels in pg/mL against total serum calcium levels in mg/dL.

  • Range examples include:

    • Hypoparathyroidism low, normal levels, primary hyperparathyroidism
      affected by malignancy.

Treatment Options for Hypercalcemia

  • 4 main strategies to lower plasma calcium:

    1. Decrease intestinal calcium absorption.

    2. Increase urinary calcium excretion.

    3. Decrease bone resorption.

    4. Remove excess calcium through dialysis.

  • Treatment depending on the degree and cause of hypercalcemia.

Hypocalcemia

  • Definition: Total plasma Ca concentration < 8.8 mg/dL with normal plasma protein concentrations.

  • Causes:

    • Hypoparathyroidism.

    • Pseudohypoparathyroidism (types I, Ib, and II).

    • Vitamin D deficiency.

    • Excessive secretion of calcitonin.

Causes of Hypoparathyroidism

  • Injury to the parathyroid glands (e.g., during head and neck surgeries).

  • Blood magnesium level deficiencies or high blood pH (metabolic alkalosis).

  • DiGeorge syndrome: Congenital disorder leading to total absence of parathyroid glands.

Strategies to Increase Calcium

  • Natural Sources: Sunshine exposure, Vitamin D supplementation; dietary calcium.

Additional Disorders Related to Calcium Homeostasis

Rickets and Osteomalacia

  • Visual representation and conditions related to these diseases (e.g., pseudofractures found in osteomalacia).

Type II Vitamin D Dependent Rickets

  • Example of hereditary resistance to 1,25(OH)2D leading to total alopecia and oligodentia.

Molecular Structures and Interactions

  • Comparison of modeled structures of 1,25(OH)2D3 and its receptor (VDR).

Conclusion

  • Calcium homeostasis is critical for various physiological processes, regulated by hormonal systems, and disturbances lead to significant health issues.