1 BONE Formation o Cortical bone o Trabecular Bone o Dense compact hard outer shell o More metabolically active at times of deficiency o Higher turnover rate o Hips and vertebrae o Become embedded in matrix and become osteocytes to maintain integrity of bone o Ca phos mg enter bone fluid from blood and attach to bone proteins and ground substance o Calcium salts make hydroxyapatite Hydroxyapatite crystal lattice found in bones and teeth made of calcium salts laid on top of Types of Bone cells o Osteoblasts o Osteocytes o Osteoclasts Osteoblasts o Bone building o Originate in bone marrow o Controlled by o PTH calcitriol o Secrete o Collagen o Bone matrix osteoid Osteocytes o mid interior bone maintenance cells o maintain integrity of surrounding bone o form membrane system o during mineralization matrix o Proteins in bone o Collagen o Osteonectin binds both calcium and collagen o Osteopontin binds hydroxyapatite and bones cells Osteoclasts o Reabsorbs bone o Large multinucleated o Contains lysosomes o Release acids proteases etc that break down bone o Respond to PTH calcitriol and calcitonin o Upregulated by PTH and calcitrol o Downregulated by calcitonin o Help maintain blood calcium Other bones in cells o Fibroblasts o Form collagen 2 Long rod shaped protein that gives strength Requires iron Vit C and Vit D o Form ground substances for bone tendons and ligaments o Involved in healing o Chondrocytes o Reticulocytes o Make RBC s o Make leukocytes Bone remodeling o Consistently remodeled throughout life o Growth and maintenance o Fracture repair o Maintain serum calcium levels o Bone mass o Peak in early adulthood o Adolescents greatest activity best time to add density coincidentally also when calcium consumption drops off o Postmenopausal estrogen loss of bone mass Hormone replacement therapy helps but does estrogen tie to breast cancer HRT should be used through menopause symptoms but should not be used throughout life o DEXA dual xray absorptiometry o Factors affecting bone mass Protein intake increase intake associated with increase in calcium excretion Caffeine Sodium intake Mechanical loading Smoking decreases absorption Alcohol Calcium intake Vitamin D Phosphorous Needed for bone mineralization good for ATP bad for phosphoric acid in sodas etc Weight loss Decreases bone density Sources of Vitamins and Minerals for bones o Calcium sources o Phosphorous sources o Magnesium o Vitamin D Vitamin D Sources o Beef eggs milk and dairy fortified saltwater fish salmon tuna Animal Sources Fortified Plants o Breads and cereals o almost none 3 Sunlight o 10 min in sun 10mcg Vit D o Darker pigmentation more adiposity less Vit D made o Place on earth varies with amount of Vit D able to be made o If you wear sunscreen you WILL NOT make Vit D RDA s o Males Females 19 30 9 18 yrs o 50 yrs 20ug d 15 ug d Forms Vitamin Forms o Ergocalciferol D2 from plants sold commercially o Cholecalciferol D3 from cholesterol found in animal products Metabolites o Plants Sterol irradiated Vitamin D2 o Cholesterol UV light Vitamin D3 Functions Vit D UV light 3 liver 25 OH Cholesterol Regulates calcium and phosphorus details later in SG Insulin secretion Thyroid hormone synthesis Proliferation and differentiation of immune cells Treatment of psoriasis o Inhibits proliferation of keratinocytes o Enhances differentiation of epidermis 2D3 kidney 1 25 OH 2D3 Calcidiol Cholecalciferol Calcidiol Location LIVER Calcidiol Major form in BLOOD Calcitriol Calcidiol 1 hydroxylase Calcitriol Location KIDNEY Calcitriol ACTIVE hormone Activity increased by low plasma calcium and PTH Activity decreased by high calcitriol concentration and dietary phosphorous Functions of Calcium and Phosphorus Functions of calcium o Non osseous 1 Enzyme activation free calcium induces phospholipase A liberates FA from glycerol backbone Blood clotting Muscle contraction requires MG Tetiny intermittent muscle contractions that fail to relax Nerve impulses Hormones Functions of Phosphorus o Skeletal o Energy ATP o phosphorylase reactions Maintenance of Calcium and Phosphorus via Vit D Transcaltachia o 3 main target tissues intestine bone kidney all used to maintain Ca in blood o Calcitriol and PTH work to INCREASE blood calcium o Decrease serum calcium to increase PTH which increases 1 hydroxylase which increases calcidiol which o Intestine osteoblasts skeletal muscle PTH increases calcitriol Intestine o Intestinal absorption of calcium Increased synthesis of CaBP calbindin will increase Ca absorption o Calcitriol acts as a steroid hormone to stimulate transcription of mRNA s for CaBP 4 Changes to brush border increase Ca absorption Transcalthachic response o Rapid increase in Ca absorption via endocytosis o Intestinal absorption of Phosphorous Alkaline phosphatase Bone resorption Kidney Reabsorption o Calcitriol stimulates resorption of calcium and phosphorous from bone o Calcitriol stimulates Ca resorption in the distal renal tubes of the kidney Increasing Blood Calcium Low serum calcium signals parathyroid gland to secrete PTH o PTH then signals Kidney Calcidiol 1 hydroxylase calcitriol Reabsorption of Calcium in Kidney Resorption of Bone o Calcitriol Increased intestinal absorption Increased resorption of bone Decreasing Blood Calcium High blood calcium signals thyroid gland to secrete Calcitonin o Calcitonin Kidney Bone Decreases 1 hydroxylase decrease resorption Stimulates osteoblasts inhibits osteoclasts Vitamin D Deficiency Children o Rickets failure of bone to mineralize Epiphysial cartilage grows but no bone matrix Long bones of legs can bow Spinal pelvic and thoracic deformities Adults o Osteomalacia Vit D deficiency decreased calcium absorption Decline in serum calcium PTH which promotes bone resorption Bone matrix is spared but remineralization is impaired Results in bone pain and soft bones Those at risk o Elderly poor dietary intake more time spent indoors o Climate o Fat malabsorption 5 o Renal disease Kidney makes 1 hydroxylase Decrease in renal activity decrease in renal 1 hydroxylase Less 1 hydroxylase less calcitriol less Vit D o Breastfed infants American academy of pediatrics supplement 400 IU Treatment vitamin D supplements Vitamin D toxicity Overexposure to sun will NOT cause Vit D toxicity because the body will just stop making it General Symptoms include o Weakness nausea vomiting o Diarrhea headache More severe symptoms o Hypertension o Renal dysfunction Calcification of soft tissues heart lungs blood vessels kidney
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