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CALCIUM. FCSFN 648. Introduction. Ca is the most abundant mineral in the body Ca (latin “calx” means limestone) was known as early as the first century when the Ancient Romans prepared lime as calcium oxide. Distribution & function in the body - bone . Over 99% Ca exists in the skeleton
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CALCIUM FCSFN 648
Introduction • Ca is the most abundant mineral in the body • Ca (latin “calx” means limestone) was known as early as the first century when the Ancient Romans prepared lime as calcium oxide
Distribution & function in the body - bone • Over 99% Ca exists in the skeleton • Structural role • Functional role • Castatus can be assessed by measuring BMC by bone densitometry
Distribution & function in the body - bone • Bone remodeling occurs throughout life • Bone formation is > than resorption during growth (especially adolescence)* in girls - 90% total BMC (17 y) & 99% (26 y)* boys - occurs 18.5 y • In W onset of bone loss occurs * 48 y (spine) & 37 y (femoral neck) • Maximal loss in W occurs * bet 54-58 (hips, spine etc)
Distribution & function in the body - bone • On average - bone Ca pool turns over every 5-6 y • 2 types of bones * cortical* trabecular • Cortical bone
Distribution & function in the body - bone • Trabecular bone
Functions • Mineralization - bone & teeth • Blood clotting
Functions • Other functions
Solubility • Ca is absorbed only in ionized form (Ca+2) • Ca in food & dietary supplements - insoluble salts • Solubility - mildly acidic pH • Solubility doesn’t ensure better absorption • In alkaline pH, Ca may complex with minerals or other dietary components
Calcium location & quantity • Average adult ~ 1 kg Ca (99% - skeleton)as calcium phosphate salts • ECF has ~ 22.5 mmol of which 9 mmol is inthe serum • Every 24 hours, 500 mmol Ca is exchanged bet bone & ECF
Normal ranges • Normal serum levels (8.5-10.5 mg/dL) • Normal ionized level (4.5-5.6 mg/dL) • Amount of total calcium is dependent on albumin • Biologic effect of Ca is determined on the amount of ionized Ca rather than the total calcium
Corrected Ca level • Corrected Ca level is used when albumin is abnormal • Corrected Ca (mg/dL) = measured total Ca (mg/dL) + 0.8 (4.0 - serum albumin [g/dL]), where 4.0 represents the average albumin level • With hypoalbuminemia corrected level is higher than the total Ca
Absorption • Absorption - Ca has to be in the ionized form • Generally 20-50% ingested Ca is absorbed • Amount of Ca absorbed depends • Intake
Absorption • Physiological factors
Absorption • Occurs along the length of the small intestine • Generally 2 routes of absorption • Other route of absorption
Saturable system (Transcellular) • This is active & saturable system (fig) • Takes place mainly in the duodenum & proximal jejunum • Occurs actively when Ca is in short supply (↓ dietary) • Ca moves from brush border into the enterocyte as unbound Ca+2 • Ca+2 binds with intracellular protein (calbindin or CPB) which takes Ca+2 into the mitochondria & other subcell compartments • Ca+2 leaves the enterocyte in exchange for Naor by calcium activated ATPase
Saturable system (Transcellular) • Saturable process occurs
Passive & Non-saturable (Paracellular) • This is passive & non-saturable system • Takes place mostly jejunum & ileum • Is dependent on vit D • Occurs passively when there is adequate dietary Ca • Ca enters into the enterocyte with the help of vit D
Colon • Bacteria in the colon releases Ca bound fermentable fibers • ~ 4% (~ 8 mg/d) of dietary Ca is absorbed by this route • Amount is higher in people who are unable to absorb more Ca from the small intestine
Factors that enhance Ca absorption • ↑ lactose • ↑ vit D • ↑ acidic environment • ↓ stress • Distribution of Ca intake • ↑ physiological need
Absorption enhanced - lactose • From breast milk & formula • Infants fed lactose • Research - rats fed diets with differentCHOs, i.e. 25%* lactose, glucose, sucrose, maltose or starch* lactose only ↑ Ca absorption (Bergeim et al., 1926)
Absorption - enhanced • Vitamin D • Acidic conditions • Lack of stress
Absorption - enhanced • Distribution of Ca intake • Increased physiological need
Factors that inhibit Ca absorption • Non-fermentable fibers • Phytate • Oxalate • Magnesium • Dietary fatty acids • Physical activity • Potassium
Factors that inhibit Ca absorption • Non-fermentable fibers • Phytate • Oxalates
Factors that inhibit Ca absorption • Magnesium • Dietary fatty acids
Factors that inhibit Ca absorption • PA • Potassium
Transport • In the blood, Ca is transported in 3 forms* ~ 40% Ca is bound to protein mainly albumin* ~ 10% is complexed with sulfate, phosphate or citrate* ~ 50% of Ca is found free in blood (ionized Ca+2)
Storage • Skeleton is the major storage site* since ~ 99% of the body's Ca is in the bone • Short term • Long term, chronic removal of skeletal calcium
Excretion • Primarily in the urine and feces • Urinary losses range from 40-200 mg/d occurs: • Urinary Ca excretion is ↓ • Urinary Ca excretion is ↑
Excretion • Most Ca is filtered and reabsorbed by the kidneys
Excretion • Fecal losses range from 45-100 mg/d • ↑ fecal losses are ↑ with • Skin losses 60 mg/d
Regulation - calcium balance (Extracellulary) • The level of ionized calcium in plasma is controlled by 3 factors:* PTH* Calcitonin* Calcitriol (1,25-(OH)2D3 ) (i.e. vit D)
Parathyroid Hormone (PTH) • ↓ in ECF (serum) Ca concentrations • PTH from the PT gland is released • PTH ↑ Ca in the ECF by* ↑ Ca absorption from the intestine (through calbindin)* mobilization of Ca from the bone via stimulation of osteoclasts* ↓ kidney excretion of Ca & ↑ renal tubular reabsorption of Ca
Calcitonin • Calcitonin, is synthesized by the thyroid gland • ↑ serum Ca levels stimulates calcitonin • Calcitonin ↓ serum Ca concentration by* inhibiting osteoclast activity* prevents mobilization of Ca from bone
Calcitriol (1,25-(OH)2D3 ) • Vit D enters circulation after synthesis inthe skin or consumption in the diet • Vit D is transported through the body bound to a vitamin D-binding protein • Vit D is taken to the liver, undergoes hydroxylation forms 25(OH)D • 25 (OH)D is bound again to the bindingprotein kidney where it is furtherhydroxylated 1,25(OH)2D3, the most active vitamin D metabolite
Calcitriol (1,25-(OH)2D3 ) • In Ca deficiency, more 1,25 (OH)2D3 is produced causing enhanced* intestinal absorption of Ca* renal reabsorption of Ca* ↑ bone formation & resorption
Regulation - calcium balance (Intracellulary) • Calcium Pumps* ATP dependent calcium pumps found* mitochondria * endoplasmic reticulum * nucleus * these enable movement of Ca from extracellular to intracellular fluid
Interactions with other nutrients • Phosphorus • Magnesium
Interactions with other nutrients • Potassium • Protein
Interactions with other nutrients • Sodium • Fiber
Interactions with other nutrients • Caffeine
Interactions with other nutrients • Alcohol • Sodium & Protein
Deficiency - Causes • Inadequate intake • Poor Ca absorption and/or excessive Ca losses • Observed
Hypo - & Hypercalcemia • Hypocalcemia • Hypercalcemia • Fatal levels:
Deficiency - observed • Disease states • Individuals who have ↑ need
Calcium & disease prevention • Osteoporosis • 2 types of osteoporosis
Calcium & disease prevention • Type I • Type II
Calcium & disease prevention • Hypertension • Cardiovascular Disease • Colon Cancer