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Introduction to Calcium Homeostasis A. Hypocalcemia- low blood calcium conc. 1. Muscle spasms, heart dysfunction B. Hypercalcemia 1. Conc. of blood higher than normal 2. Diffuse precipitation of calcium phosphate in tissues, leading to organ dysfunction

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Major pools of calcium A. Intracellular 1. Mitochondria/ endoplasmic reticulum 2. Release from cellular stores/ influx from ECF 3. Intracellular signaling, enzyme activation, muscle contractions B. Calcium in blood/ ECF 1. Half of calcium in blood is bound to proteins 2. Conc. of phosphorus is equal to that of calcium C. Bone Calcium 1. Majority of body calcium is in bone 2. 99 percent tied up in mineral phase, 1% can rapidly exchange w/ extracellular calcium 3. Most of phosphate is in mineral phase of bone

III.

Functions of Skeleton A. Structural support for heart, lungs, marrow B. Protection of the brain, uterus C. Attachment sites for muscles allowing movement of limbs D. Mineral reservoir for calcium/ phosphorus E. Defense against acidosis F. Trap dangerous materials G. Bone Architecture 1. Spongy- trabecular, gives strength to the ends 2. Cortical- solid bone on the outside forms the shaft of long bone H. Mineral reservoir 1. Bone stores 99% of the bodys calcium, 85% of phosphorus

IV.

Bone Cells

A. Osteoclasts 1. Dissolve or reabsorb bone 2. Precursors circulate in the blood/bone marrow 3. Precursors have RANK receptors activated by RANK ligand, which was secreted by osteoblasts 4. Secrete acid/ enzymes which degrade the bone B. Osteoblasts 1. Form bone 2. Cuboidal/columnar in shape 3. Gap junctions 4. Come from precursor cells that can be osteoblasts or fat cells 5. Receptors for vit. D, estrogen, parathyroid hormone 6. PHEX- helps regulate phosphate excreted by the kidney V. Fluxes of Calcium and Phosphate A. Small intestine 1. Dietary calcium is absorbed B. Bone 1. Reservoir of calcium 2. Reabostion of bone mineral releases calcium and phosphate into blood, suppressing this effect allows calcium to be doposited C. Kidney 1. Important in calcium homeostasis 2. Glomerular filtrate is reabsorbed from tubular system VI. Hormonal Control Systems A. Parathyroid hormone 1. Increases blood conc. of calcium 2. Stimulates production of vit. Di in kidney 3. Moves calcium and phosphate in bone 4. Can eliminate phosphate in kidney 5. Maximize reabsoprtion of Ca in kidney ( little calcium loss in pee) B. Calcitonin 1. Reduces calcium levels

2. Secreted in response to hypercalcemia 3. Enhances excretion of calcium into urine 4. Stops bone reabsorption C. Vitamin D 1. Made through activity of parathyroid hormone 2. Facilitate absorption of calcium from small intestine VII. The Calcium sensing Receptor A. Calcium sensor is a component of the system responsible for calcium homeostasis B. Calcium sensing receptor 1. G protein receptor family 2. Activation of phospholipase C which can make second messengers DAG/IP3 3. Stop adenylate cyclase, which suppresses conc. oc cAMP C. Parathyroid cells/ C cells in thyroid gland involved with control of parathyroid hormone and calcitonin D. Mutations 1. Different mutations in the calcium sensor gene have been id 2. S by a type of calcium resstance (hypocalcciuric hypercalcemia) 3. Abnormal set point in sensitivity of the parathyroid gland to blood calium conc. 4. Activating mutations 1. Elevated sensitivity to calcium 2. Hypercalciruic hpyocalcemia which is the opposite of what is seen with inactivating mutations VIII. Parathyroid Gland/ Hormone A. Most important endoc