calcium & phosphate metabolism
TRANSCRIPT
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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