MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Overview: Mineral and Bone Metabolism

Calcium Homeostasis Organs involved Origin Reservoir Small intestine Skeleton Hydroxyapatite ( calcium+ phosphorus+ hydroxide) Kidneys Origin Diet Reservoir Bone

Forms of Calcium Bound to albumin–45% Free “ionized”–50% Reversible process Binding is pH dependent Free “ionized”–50% Complexes with anions -5%

Ionized Calcium Free calcium in blood Tightly regulated Biologically active form Advantage Not associated with proteins or anions

Functions of Calcium Nerve impulse transmission Cofactor in certain enzymes Coagulation of blood Skeletal mineralization Preservation of cell membrane integrity and permeability

Regulation of Calcium Homeostasis Parathyroid hormone- PTH Vitamin D3 Calcitonin

Parathyroid Hormone- PTH Originates from the parathyroid gland Secretion based on levels of free calcium Activities/Roles Stimulation of osteoclastic bone reabsorption and release of calcium and phosphate from bone Stimulation of calcium reabsorption and inhibition of phosphate reabsorption from the renal tubules Stimulation of renal production of 1,25(OH)2 vitamin D3, which increase intestinal absorption of calcium and phosphate

Regulation of Calcium Homeostasis

Vitamin D3/ Cholecalciferol Synthesis occurs in skin, liver, kidneys Affects gut, bone, and parathyroid Actions/ Roles Increases plasma calcium and phosphate concentration by increasing the absorption of calcium and phosphate from the gastrointestinal tract Increases bone resorption and enhances the effects of PTH in the nephron to promote renal tubular calcium reabsorption Stimulates osteoclasts to metabolize bone calcium

Physiology of vitamin D in the body. Michal L. Melamed, and Ravi I. Thadhani CJASN 2012;7:358-365 ©2012 by American Society of Nephrology

Vitamin D: Where Does it Come From? Sources of: Diet Animal tissues and products ( liver) Irradiated milk Sunlight

Sufficiency Of Vitamin D Levels of vitamin D on the decline Sun avoidance/ use of sun screen Deficiency of vitamin D in the diet Obesity

Calcitonin Secreted by the thyroid gland Secreted when blood calcium rises Inhibits PTH and Vitamin D Inhibits bone resorption, promotes bone formation

Phosphorous Origin Inverse relationship with Calcium Diet Bone Phosphate ion is distributed equally. Intracellular Component of macromolecules Extracellular Inverse relationship with Calcium

Functions of Phosphorous Component of bones & teeth Essential part of cell membranes Contributes to enzyme function Storage and transfer of energy Component of many compounds

Phosphorous Regulation Kidneys Excrete or reabsorb Other factors PTH Increases renal excretion Vitamin D increases levels Phosphate absorption in intestine Phosphate reabsorption in kidneys Growth Hormone, calcitonin, acid-base status

Magnesium 2nd most abundant intracellular cation Location Origin 50-60% found in bone 40-50% muscle & soft tissue 1% in the RBC Origin Diet Nuts, hard water, meat, green vegetables, fish, dry cereal

Forms of Magnesium Free or ionized (~55%) Bound to proteins (~30%) Complexed with phosphate, citrate and other ions (~15%)

Functions of Magnesium Important co-factor in reactions using ATP Carbohydrate metabolism Muscle contraction Blood coagulation Membrane stabilization Nerve conduction Maintenance of potassium

Magnesium Regulation Primary regulatory factor Amount of magnesium in the plasma Regulatory control Kidney Excrete or reabsorb magnesium depending on condition Parathyroid hormone Increases renal reabsorption Enhances absorption in intestines

References Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins. http://rickets.stanford.edu/ http://scrink.com/blog/wellness/2009/02/vitamin-d-cold- flu-correlation.html Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .