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بسم الله الرحمن الرحيم

بسم الله الرحمن الرحيم. Calcium Homeostasis. By Amr S. Moustafa, M.D., Ph.D. Ass. Prof. & Consultant Clinical Biochemistry & Molecular Biology College of Medicine and Obesity Research Center King Saud University. Objectives:. Physiological importance of calcium

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بسم الله الرحمن الرحيم

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  1. بسم الله الرحمن الرحيم

  2. Calcium Homeostasis By Amr S. Moustafa, M.D., Ph.D. Ass. Prof. & Consultant Clinical Biochemistry & Molecular Biology College of Medicine and Obesity Research Center King Saud University

  3. Objectives: • Physiological importance of calcium • Distribution and forms of calcium • Regulation of blood level of calcium • Measurement of calcium level • Clinical problems: Hypo- and hyper-calcemia

  4. Calcium: Physiological importance • Neuromuscular excitability • Blood coagulation • Mineralization of bones • Release of hormones & neurotransmitters • Intracellular actions of some hormones

  5. Distribution and Forms of Calcium • One Kg of calcium in human body • 99% in bone (mainly, hydroxyapatite crystals) • 1% in blood and ECF 45% Free, ionized form 40% Bound to protein (mostly albumin) 15% Bound to HCO3-, PO4-, citrate, lactate

  6. Distribution and Forms of Calcium CONT’D • Effects of pH on forms of blood calcium Acidosis favors ionized form & alkalosis enhances protein binding Numbness and tingling in hyperventilation • Avoid use of tourniquet for collection of blood samples for measurement of calcium • Importance of direct measurement of ionized calcium Vs (calculated) or (total calcium) in acutely ill subjects

  7. Regulation of Blood Level of Calcium • Parathyroid hormone (PTH) • Calcitriol: Active form of vitamin D • ? Calcitonin

  8. (1) Parathyroid Hormone (PTH) • Secreted by parathyroid glands • Molecular mass: 9.5 kDa • Full biologic activity: NT 1/3 (PTH 1-34) • Acts via membrane-bound receptor (G-protein stimulation and increase intracellular cAMP) • Target organs: Bone, kidney, intestine

  9. Parathyroid Hormone (PTH) CONT’D • Stimulus: Decrease of ionized Ca2+ • Effects: Bone: Bone resorption Activated osteoclasts break down bone and releases calcium into ECF Kidneys: Tubular reabsorption of calcium Renal production of active vitamin D Phosphate excretion (Phosphaturic effect) Intestine: Intestinal absorptionof calcium (Indirect) (Bone: Largest effect; Kidney: Rapid changes)

  10. Parathyroid Hormone (PTH) CONT’D Signal Transduction: G-protein Coupled Membrane Receptor

  11. Actions of cAMP 1 AMP 1Phosphodiesterase

  12. (2) Calcitriol • Intestinal absorption of calcium (& phosphate) • Enhances the effects of PTH on bone and kidney to blood calcium level • Acts via intracellular receptors of steroid/thyroid superfamily • Hormone/receptor complex binds to HRE of DNA & gene expression of important proteins for calcium homeostasis, e.g., CBP

  13. Steroid/Thyroid Superfamily: Steroid Hormones Thyroid Hormones Calcitriol (Vitamin D) Retinoic acid (Vitamin A)

  14. Calcitriol and Calcium Homeostasis

  15. Calcium Homeostasis: PTH & Calcitriol Response to low blood calcium

  16. (3) Calcitonin • Secretion: Medullary cells of thyroid gland Peptide hormone (32 amino acids) • Stimulus: Increase of blood level of ionizedCa2+ • Effects:Inhibits the actions of both PTH & calcitriol in hypercalcemic state • Physiological role in adult humans: Uncertain

  17. Measurement of Calcium Types:Total calciumIonized Ca2+: direct *(ISE) and ? calculatedCorrected calcium (adjusted to albumin) Specimen: Avoid use of tourniquetSerum or Lithium-heparin plasmaUrine: Acidified with HCl (1 ml/100 ml urine)*ISE: Ion selective electrode

  18. Reference Ranges: Serum total calcium: Child (< 12 years): 2.20 – 2.7 mmol/L Adult: 2.15 – 2.5 Serum ionized calcium: Child (< 12 years): 1.20 – 1.38 mmol/L Adult: 1.16 – 1.32

  19. Thank You

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