Calcium & Phosphate

metabolism

Presented by: Dr. Neetu Singh 2nd yr pg

ContentsI. IntroductionII. Calcium and phosphorus DistributionIII. SourceIV. FunctionV. Dietary requirementsVI. AbsorptionVII.ExcretionVIII.Factors affecting absorptionIX. Factors affecting calcium metabolismX. DietXI. ParathormoneXII.CalcitoninXIII.Clinical considerationXIV.SummaryXV.references

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

Harrison et al., "Ionic and Metallic Clusters of the Alkali Metals in Zeolite Y", J. Solid State Chem., 54, 330-341 (1984).

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 through the electrolysis of a mixture of lime (CaO) and mercuric oxide (HgO

• In 1883 demonstrated Sydney Ringer the biological significance of calcium

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)

Calcium Orthophosphates: Occurrence, Properties and Major Applications

Sergey V. Dorozhkin*

Distribution of calcium

• Skeleton - 99%

• Muscle – 0.3%

• Other tissues – 0.7%

• 800mg of calcium is absorbed /day

Source of calcium

Recommended calcium intake

Age Amount of calciumInfantsBirth to six months 400mg6 months to 1 year 600mg

Children / young adults 1 – 10 years 800 – 1200mg11 – 24 years 1200 – 1500mg

FAO/WHO Expert Group. 1962. Calcium Requirements. Rome, FAO.

Recommended calcium intake

Adult womenPregnant and lactating 1200 – 1500mg

25 - 49 yrs(premenopausal) 1000mg

50 – 64 yrs (post menopausaltaking estrogen ) 1000mg

50 – 64 yrs(post menopausalnot taking estrogen ) 1500mg

Over 65 yrs old 1500mg

Recommended calcium intake

Adult men

25 – 64 yrs old 1000mg

Over 65 yrs old 1500mg

FUNCTIONS OF CALCIUM

Muscle contractionFormation of bone and teeth Coagulation of bloodNerve transmission: Integrity of cell

membrane by maintaining the resting

membrane potential of the cellsRelease of certain hormones

The Role of Calcium in Coagulation and Anticoagulation M. E. Mikaelsson Volume 26, 1991, pp 29-37

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

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

Three in Calcium

3 Sites – Intestines, bones, blood.

3 hormones – Parthormone, Calcitonin, Vitamin D.

3 chemical forms – protein bound, ionic calcium, crystalline form.

3 crystalline forms – Hydroxyapatite(ha), calcium pyrophosphate dihydrate(CPPD), Calcium oxalate.

3 forms of pathological calcification –dystrophic calcification, metastatic calcification, calcium stone

(lithiasis)

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

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

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

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)

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

Factors regulating plasma calcium level

Calcitriol: 1, 25 DHCC

Increases intestinal absorption.

Stimulates calcium uptake by bone and

promotes calcification

Parathyroid Hormone:

• Action on bone

• Action on kidney

• Action on intestine

Plasma Ca9-11mg/dl

Intestinal Ca

Bone Ca Renal Ca

Calcitriolcalcitonin

PTH PTH

calcitriol Vit D

PTH

Phosphate

Phosphate

85% is present in bone(500 – 600gm)

Present in the form of hydroxyapatite and in

some areas as amorphous calcium phosphate.

Distribution of phosphorus

2.5 to 4.3mg/100ml is present in adults

5 to 6 mg/100ml is present in children

Source of phosphorus

Present in all foods

Milk

Meat

Fish

cereals

Pulses and nuts

Daily requirement

Adults – 900 mg

Infants – 240mg

Pregnant and lactating women – 1200mg

Functions of phosphorus

Development of bone and teeth

Formation of high energy compounds

Required for formation of phospholipids, phospho-proteins and DNA and RNA

Several enzymes and proteins are activated by phosphorylation.

Clinical considerations

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

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

• Blood and urine calcium measurements cannot tell how much calcium is in the bones. A test similar to an X-ray, called a bone density or "Dexa" scan, is used for this purpose.

Who Needs a Calcium Blood Test?A calcium blood test can be part of a screen for a variety of diseases and conditions, including osteoporosis, cancer, and kidney diseases. This blood test may also be required to monitor ongoing treatments of other conditionsedications you are taking don’t have any unintended side effects.

Your doctor may order this test if he or she suspects any of the following conditions:bone diseases, such as osteoporosis or osteopeniacancerchronic kidney or liver diseasedisorders of the parathyroid glandmalabsorption or a disorder that affects how your body absorbs nutrientsan over or underactive thyroid gland

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

The role of cell calcium in current approaches to toxicology.J G Pounds

high total calcium (hypercalcemia)• Two of the more common causes of hypercalcemia are:• Hyperparathyroidism, an increase in parathyroid gland function: • this condition is usually caused by a benign tumor of the parathyroid gland. • Cancer: cancer can cause hypercalcemia when it spreads to the bones and

causes the release of calcium from the bone into the blood or when a cancer produces a hormone similar to PTH, resulting in increased calcium levels.

• Some other causes of hypercalcemia include:• Hyperthyroidism• Sarcoidosis• Tuberculosis• Prolonged immobilization• Excess vitamin D intake• Thiazide diuretics• Kidney transplant• HIV/AIDS

Low total calcium (hypocalcemia)• The most common cause of low total calcium is:• Low blood protein levels, especially a low level of albumin, which

can result from liver disease or malnutrition, both of which may result from alcoholism or other illnesses. Low albumin is also very common in people who are acutely ill. With low albumin, only the bound calcium is low. Ionized calcium remains normal, and calcium metabolism is being regulated appropriately.

• Some other causes of hypocalcemia include:• Underactive parathyroid gland (hypoparathyroidism)• Inherited resistance to the effects of parathyroid hormone• Extreme deficiency in dietary calcium• Decreased levels of vitamin D• Magnesium deficiency• Increased levels of phosphorus• Acute inflammation of the pancreas (pancreatitis)• Renal failure

Causes of Vitamin D deficiency

•Dietary insufficiency

•Poor exposure to sunlight

•Malabsorption

•Liver/ kidney disease (synthesis)

•Resistance to hormone receptor (rickets)

Ricket refers to disorder in

vitamin – D

(calcium –phosphorous ratio)

Resultant hypo-mineralization

Three types: Infantile ,Adult

and familial

rickets

Longo, Dan L. et al. (2012). Harrison's principles of internal medicine. (18th ed. ed.). New York: McGraw-Hill. ISBN 978-0-07174889-6.

Femoral and tibial bowing

Growth retardation

weakness

tetany

Susceptibility to fracture

Irritability

Clinical features of rickets

Longo, Dan L. et al. (2012). Harrison's principles of internal medicine. (18th ed. ed.). New York: McGraw-Hill. ISBN 978-0-07174889-6.

Oral manifestation

Mellanby:

•Developmental abnormalities of

dentin and enamel

•Delayed eruption

•Misalignment of teeth in the jaw

•High caries index

•Enamel hypoplasia

Osteomalacia

Clinical featuresBone pain and

tenderness

Peculiar waddling or

“penguin”gait

Tetany

Greenstick bone

fractures

Myopathy

Severe Periodontitis

Thin or absent trabeculae

Loosened teeth

Weakened jaw bones

Oral manifestation

Hypervitaminosis DCLINICAL FEATURES

Gastrointestinal

disturbances

Nausea

Vomiting

Loss of appetite

Thirst

Polyuria

Fatigability

Radiological features

•Metastatic deposits of

calcium almost

anywhere in the body

most commonly around

joints

Management

Cortisone – increases urinary excretion of calcium

Hypocalcemia

Condition where there is decreased calcium

level in serum of blood

Classification based on the mechanism

1. Chronic hypocalcemia

causes

chronic renal failure

Hereditory and acquired hypothyroidism

Vitamin D deficiency

2. Transient hypocalcemiaCauses

Severe sepsisBurnsAcute renal failureExtensive transfusions with citrated blood .

3. acute hypocalcemiaCertain medications like protamine,

heparin

Causes of hypocalcaemia

Low parathyroid hormone levels (hypoparathyroidism)Parathyroid agenesisParathyroid destruction Surgery Radiation Infiltration by metastasis or systemic diseaseAutoimmune

Clinical features

•Muscle spasms, carpopedal spasms,•Facial grimacing (a expression of pain)•Bronchospasm, laryngospasm, •Convulsions•Respiratory arrest•Increased intracranial pressure•Irritability, depression, psychosis•Intestinal cramps•Chronic malabsorption•Arrhythmias •Seizures of all types

Management of hypocalcaemia

Calcium gluconate 10ml 10%IV diluted in 50ml

of 5% dextrose 0.9% Nacl by slow injection

Vitamin D - if hypocalcaemia persist

HypoparathyroidismDefinition Disorder of mineral metabolism caused by insufficient activity of parathyroid glands

Types

Heriditary

pseudoAquired

Clinical features

Paresthesia

Muscle cramps

Seizures

Tetany

Chovestek’s sign

Trousseau’s sign

Accouchers hand

Oral manifestation

Enamel hypoplasiaMalformed teethAnodontiaShort blunt root apicesElongated pulp chambersMultiple impacted teethMandibular exostosis

•Short (less than 5 feet tall) built and round

face.

•Shortening of metacarpal joints and

presence of dimples in the joint.

•Mental retardation

Clinical features

•Enamel hypoplasia

•External root resorption

•Delayed eruption

•Root dilaceration

Radiographic features

Ash, Major M., Jr. and Nelson, S.J (2003). Dental anatomy, physiology, and occlusion (8th ed.). Philadelphia: W.B. Saunders. ISBN 0-7216-9382-2.

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

Shafers.Textbook of oral pathology.Ed 6th

Guyton and Hall. Textbook of medical physiology.Ed11th

Telfer, S.V. 1926. Studies in calcium and phosphorus metabolism. Q. J. Med., 20:1-6. Heaney, R.P. 1993. Protein intake and the calcium economy. J. Am. Diet. Assoc., 93: 1259-1260.

REFERENCES

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