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Calcium facts
• Soft grey alkaline earth metal • Symbol Ca• Number 20 • Group II• Divalent cation• Atomic weight 40 g/mol• Single oxidation state +2• Fifth most abundant element in Earth´s crust• Essential for living organisms
Calcium history
• Latin calx or calcis meaning ”lime”• Known as early as first century when ancient
Romans prepared lime as calcium oxide• Isolated in 1808 by Englishman Sir Humphrey
Davy- Electrolyzed a mixture of lime & mercuric acid• In 1883 demonstrated Sydney Ringer the
biological significance of calcium
- Frog hearts needed the presence of calcium in the bathing solution in order to continue beating
Calcium occurrence
In nature• Does not exist freely • Occurs mostly in soil systems as limestone
(CaCO3), gypsum (CaSO4*2H2O) & fluorite (CaF2)In the body• The most abundant mineral• Average adult body contains app. 1 kg• 0,1 % in the extra cellular fluid• 1 % in the cells• The rest (app. 99 %) in the skeleton
(Bones can serve as large reservoirs, releasing calcium when extracellular fluid concentration decreases and storing excess calcium)
Measuring calcium
• Atomic absorption spectrometry (AAS) can measure total amount of Ca2+ in tissue
• Fluorescent dyes can be used to measure Ca2+ in vivo• Calcium sensor (GFP-based) fluorescent protein
“cameleon” is non invasive and can be targeted to various cellular compartments – enabling a study of spatial and organellar aspects of calcium homeostasis
• Neutron activation analysis enables total body calcium to be measured in living persons
• Bone mineral content (BMC) and bone mineral density (BMD) are used as indicators of calcium insufficiency and as predictors of increased risk of fracture, when compared to a reference range, adjusted for age and gender
Calcium functions
• Major structural element in the vertebrate skeleton (bones and teeth) in the form of calcium phosphate (Ca10(PO4)6(OH)2 known as hydroxyapatatite
• Key component in the maintenance of the cell structure
• Membrane rigidity, permeability and viscosity are partly dependent on local calcium concentrations
Calcium functions (Bone)
• Osteoclasts (bone cells) remodel the bone by dissolving or resorbing bone
• Osteoblasts (bone forming cells) synthesize new bone to replace the resorbed bone
- Found on the outer surfaces of the bones and in the bone cavities
Calcium functions
Plays important regulatory roles in the bodyA passive role: - As a cofactor for many enzymes (e.g. Lipase) and proteins - As component in the blood clotting cascade
An active role: as an intracellular signal - In the relaxation and constriction of blood vessels- In cell aggregation and movement- In muscle protein degradation - In secretion of hormones as insulin- In cell division- In nerve impulse transmission
Interactions
• Phosphate: ↓ calcium excretion in the urine• Caffeine: ↑ urinary and fecal excretion of calcium• Sodium: ↑ sodium intake, ↑ loss of calcium in urine• Dietary constituents: Phytic acid can reduce
absorption of calcium by forming an insoluble salt (calcium phytate)
• Iron: calcium might have inhibitory effect on iron absorption
Absorption and excretion• Usual intakes is 1000 mg/day• About 35 % is absorbed (350
mg/day) by the intestines• Calcium remaining in the intestine
is excreted in the feces• 250 mg/day enters intestine via
secreted gastrointestinal juices and sloughed mucosal cells
• 90 % (900 mg/day) of the daily intake is excreted in the feces
• 10 % (100 mg/day) of the ingested calcium is excreted in the urine
• Calcium must be in a soluble and ionized form before it can be absorbed
Absorption and excretion factors
• Absorption increased by:- Body need- Vitamin D- Protein- Lactose- Acid medium• Absorption decreased by:- Vitamin D deficiency- Calcium-phosphorus imbalance- Oxalic acid- Phosphorous- Dietary fiber- Excessive fat- High alkalinity- Also stresses and lack of exercise
• Excretion increased by:- Low parathyroid hormone (PTH)- High extracellular fluid volume- High blood pressure- Low plasma phosphate- Metabolic alkalosis• Excretion decreased by:- High parathyroid hormone- Low extracellular fluid volume- Low blood pressure- High plasma phosphate- Metabolic acidosis- Vitamin D3
Transport mechanism
Active and passive transport mechanisms• Active: is a saturable, transcellular
process which involves calbindin (calcium-binding protein) – regulated by the active form of vitamin D
• Passive: is a nonsaturable, paracellular low efficiency process, which is not affected by calcium status or parathyroid hormone
• Both processes occur throughout the small intestine
Regulation
Vitamin D, parathyroid hormone and calcitonin• Vitamin D (in active form)- Has several effects on the intestine and kidneys that increase
absorption of calcium and phosphate into the extracellular fluid
- Important effects on bone deposition and bone absorption
• Parathyroid hormone (PTH)- Provides powerful mechanism for controlling extracellular calcium
and phosphate concentrations by regulating intestinal reabsorption, renal excretion and exchange between the extracellular fluid and bone of the two ions
• Calcitonin (a peptide hormone secreted by the thyroid gland)
- Tends to decrease plasma calcium concentration
- In general, has effects opposite to those of PTH (quantitative role is far less than that of PTH in regulating Ca ion concentration)
RegulationActivation of vitamin D3
- Cholecalciferol formed in the skin by sun
- Converted in liver
(feedback effect)
- 1,25 DHCC formation in kidney
- Controlled by PTH- Plasma calcium
concentration inversely regulates 1,25 DHCC
Regulation
• Compensatory responses to decreased plasma ionized calcium concentration mediated by PTH & vitamin D
• PTH regulates through 3 main effects:- By stimulating bone resorption- By stimulating activation of vitamin D → ↑ intestinal Ca reabsorption- By directly increasing renal tubular calcium reabsorption
Adequate daily intake (AI)
Life Stage Age Males (mg/day) Females (mg/day)
Infants 0-6 months 210 210
Infants 7-12 months 270 270
Children 1-3 years 500 500
Children 4-8 years 800 800
Children 9-13 years 1,300 1,300
Adolescents 14-18 years 1,300 1,300
Adults 19-50 years 1,000 1,000
Adults 51 years and older 1,200 1,200
Pregnancy 18 years and younger - 1,300
Pregnancy 19 years and older - 1,000
Breastfeeding 18 years and younger - 1,300
Breastfeeding 19 years and older - 1,000
Calcium sources
• Rich calcium sources (600-961mg/100g)- Cheese
- Wheat-soy flour
- Blackstrap molasses
• Good sources (122-354mg/100g) - Dairy products as milk, yoghurt, sour cream, ice cream
- Green leafy vegetables as collard, kale and raw turnip
- Fish as trout, salmon and sardines
- Almonds, brazil nuts, dried figs, hazel nuts
- Also soybean flour and cottonseed flour
• Poor sources- Most fresh fruit
Deficiency• A negative calcium balance occurs when net
calcium absorption is unable to replace losses• The most dramatic symptoms are manifested in
the teeth and bones of young humans and animals → stunted growth, poor quality of bones and teeth and malformation of bones
• Hypocalcaemia (low serum calcium levels in the blood cause the nervous system to become more excited)
• Osteoporosis (bone resorption exceeds formation)- Occurs particularly in women. Increases in bone loss and
osteoporotic fracture with age is a consequence of calcium deficiency
• Osteomalacia, tetany and kidney stones are other calcium related diseases
Causes of deficiency
• Low Ca2+ intake• Vitamin D deficiency• Insufficiency or failure of parathyroid gland• Chronic kidney failure• Low blood magnesium level (in cases with
severe alcoholism)• Diet high in phytate
Toxicology
• The UL for calcium is 2500 mg/day• MAS (Milk alkali syndrome)
- Rare and potentially life threatening condition in individuals consuming large quantities of calcium and alkali
- Characterized by renal impairment, alkalosis and hypercalcemia: cause progressive depression of the nervous system
Human health studies
• Resent studies showed- Calcium may play a substantial contributing role in reducing
the incidence of obesity and prevalence of the insulin resistance syndrome
- High calcium intake is associated with a plasma lipoprotein-lipid profile predictive of a lower risk of coronary heart disease compared with a low calcium intake
- Dairy product intake (with recommended calcium levels) protect women consuming oral contraceptives from spine and hip bone loss
- Children who avoid drinking cow milk have low dietary calcium intakes and poor bone health
Conclusion
• Calcium is essential!!!• A important mineral for human health• Must meet adequate daily intake in order
to maintain a healthy skeleton• A very exciting area for research
Additional slide
• Interaction with iron• An absorption depressing effect of calcium on iron
absorption has been clearly demonstrated in single-meal studies and short-term diet intervention studies (Hallberg et al. 1991)
• An addition of 150 mg of calcium to bread or a hamburger meal reduced iron absorption by 50 %. The interaction is suggested to take place within the mucosal cells as both haem and nonhaem iron is affected (Hallberg et al. 1993)
• Long term calcium supplementation studies have failed to demonstrate any negative effect on iron status (Ilich-Ernst et al. 1998; Kalkwarf & Harrast, 1998; Minihane & Fairweather-Tait, 1998; Sokoll & Dawson-Hughes, 1992; Yan et al, 1996)
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