GOOD MORNING

Calcium and phosphorus metabolism

OUTLINE
• INTRODUCTION • Minerals • Calcium – Functions – Sources and Distribution – Dietary requirements – Uses • Phosphorus – Functions – Sources – Dietary Requirements • Absorption of calcium and phosphorus • Regulation of absorption • Disorders of calcium and phosphorus metabolism • conclusion

Introduction • The 14 minerals - Calcium, Phosphorus, Magnesium, Sodium, Potassium, Chloride, and Sulfur, Iron, Manganese, Copper, Iodine, Zinc, Fluoride, and Selenium. • These 14 essential minerals are crucial to the growth and production of bones, teeth, hair, blood, nerves, skin, vitamins, enzymes and hormones; and the healthy functioning of nerve transmission, blood circulation, fluid regulation, cellular integrity, energy production and muscle contraction.

• Minerals are neither animal nor vegetable; they are inorganic • Types of Minerals • There are two types of minerals: – Macro minerals and Trace minerals • The macro mineral group- Calcium, Phosphorus, Magnesium, Sodium, Potassium, Chloride, and Sulfur • Trace minerals includes Iron, Manganese, Copper, Iodine, Zinc, Fluoride, and Selenium. • Calcium is the most abundant mineral in the human body and has several important functions. • The three major regulators of blood calcium are parathyroid hormone (PTH), vitamin D, and calcitonin

CALCIUM
• Calcium Status Atomic Number: 20 Atomic Symbol: Ca Atomic Weight: 40.08 Electron Configuration: [Ar]4s2 Atomic Radius: 197.3 pm Melting Point: 842 0C Boiling Point: 1484 0C Oxidation State: 2

Plasma calcium : Normal level -8.6-10.6 mg/dl i. 50% - present as ionized form ii. 40% - bound to proteins i.e. albumin iii. 10% - complexed calcium –calcium citrate, bicarbonate and phosphate. • • Ca X P in serum children – 50 and adults 30-40. Calcium: Phosphate ratio in diet: During growth – 1:1 After cessation of growth- 1: 2.

Recommended Daily Intake
• • • Infants- 600-900mg Adults- 400-500mg Pregnancy and lactation-1000-1200mg

Extra calcium is needed in
Menopausal Woman Amenorrheic Women and the Female Athlete Triad Lactose Intolerant Individuals Vegetarians

FUNCTIONS OF CALCIUM

– – – – – –

Functions of calcium:
Hormone secretion Hormone action : 2 Ca+ acts as second messenger, in the action of hormones Neuromuscular transmission Muscular contraction CBP- Calmoduli,Troponin and calbindin It is essential for the clotting of blood -. It helps in the formation of activated forms of factor IX, X, II and in the formation of prothrombin activator. Formation of bone and teeth It regulates the permeability of the capillary walls. cell division, mitosis and fertilization endocytosis, exocytosis, cellular motility

– – – –

RICH SOURCES OF CALCIUM
• • • • Dairy Products, such as Milk, Cheese, and Yogurt Canned Salmon and Sardines with Bones Leafy Green Vegetables, such as Broccoli, Spinach Calcium-Fortified foods - from Orange juice to Cereals and Crackers Ice Cream, Oysters, Ricotta.

CALCIUM BALANCE:
It is the net gain or loss of calcium by body over a specific period of time. Amount absorbed = Amount ingested - Amount egested in faeces Amount retained = Amount absorbed – Urinary calcium( excreted)

PHOSPHORUS
• Phosphorus is the second most abundant mineral in the body and 85% of it is found in the bones. • Non metallic element - blood, muscles, nerves, bones, and teeth component of adenosine tri-phosphate

• • • •

Functions hydroxyapatite. Phospholipids major structural components of cell membranes. energy production and storage - ATP Nucleic acids (DNA and RNA), enzymes, hormones, and cell-signaling molecules buffers.

• (2,3-DPG) binds to hemoglobin

Phosphate buffer system
• • • • • Composed of HPO4, H2PO4 More effective buffer in tubular fluid. Pk -6.8 It functions near its most effective range of pH of urine. Only 30-40mEq/day is available for buffering .

The Recommended Dietary Allowance (RDA) Life Stage Age Males(mg/day) Infants 0-6 months 100 Infants 7-12 months 275 Children 1-3 years 460 Children 4-8 years 500 Adolescents 14-18 years 1,250 Adults 19 years and older 700 Pregnancy 19 years and older Breast-feeding 18 years and younger Breast-feeding19 years and older Females 100 275 460 500 1,250 700 700 1,250 700

PHOSPHORUS RICH FOODS
• Food Milk, Yogurt, plain nonfat Cheese, Egg Chicken Fish, salmon Bread, whole wheat Serving 8 ounces 8 ounces 1 ounce 1 large, cooked 3 ounces, cooked* 3 ounces, cooked* 1 slice Phosphorus (mg) 247 385 131 104 155 252 57

BONE GROWTH AND CALCIUM METABOLISM
• Bone – organic-collagen.glycoproteins,phosphoprus inorganic-hydroxyapatite crystals.-strength and hardness. • Outer cortical layer and inner cancellous structure. • Cancellous bone – trabaculae • Osteoblasts, osteoclasts and osteocytes.

• BONE REMODELLING
– Osteoblasts secret interleukins osteoclasts acids proteases cavity formation
Ostoblasts Alkaline phosphatase

Estrogen-inhibits osteoclastic activity Glucocorticoids -inhibits Osteoblastic activity

collagen lysis

new bone formation

BONE GROWTH AND CALCIUM METABOLISM

Growth of epiphyseal plate IGF-1,tyroid,vitD,Growth harmone. OSSIFICATION Cartilagenous ossification Membranous ossification

ABSORPTION OF CALCIUM AND PHOSPHORUS
• • • • Ca+2 is poorly absorbed from intestine. Vitamin D and PTH promotes absorption Slight acidity or neutral pH is needed for Ca absorption Active transport – Where Ca absorption occurs against Ca concentration and is dependent on 1,25 (OH)2 cc.-Duodenum Passive diffusion occurs lower down in the small intestine and accounts only for 15%. • Renal excretion of calcium and phosphorus

CALCIUM METABOLISM

Factors affecting absorption :
• pH of intestinal contents
acidic pH – favors absorption alkaline medium - lowered

Composition of diet :
High protein diet favors absorption Fatty acids – decreases calcium absorption Sugars and organic acids Citric acid also increases absorption- chelator Phytic acid forms insoluble calcium salts Minerals : Excess phosphates lowers calcium absorption, high magnesium content decreases Ca absorption Health status Hormonal control : PTH, calcitonin, Vit-D, glucocorticoids decrease the intestinal transport of calcium.

• •

Sex harmones:
Increase intestinal absorption – Stimulate mineralization – Decrease renal excretion – – Hyperthyroidism-increased bone resorption

Thyroid harmones:

Factors regulating absorption
Three tissues– Three harmones– Three cells –

VITAMIN D

• Requirements
RDA – infancy through puberty -10 mcg of cholecalciferol/400 IU Adults- 7.5 mcg > 25 – 5 mcg Pregnancy and lactating – increase by 5 mcg.

Actions of Vitamin D
• Intestinal calcium absorption • Intestinal phosphorus absorption • Decreases Renal Calcium and Phosphorus excretion • Effect of Vitamin D on Bone and its relation to Parathyroid harmone
Bone absorption and Bone deposition Smaller quantities – bone calcifications.

VITAMIN DEFFICIENT RICKETS

Bones and Teeth 1. cessation of calcification of epiphyseal disks 2. Osteiod lay down 3. Children-bowing of legs, pigeon breast deformity, harrison’s groove 4. Developmental anomalies of dentin and enamel, delayed eruption.


1. 2. 3. 4. 5.

OSTEOMALACIA
Flat bones and diaphyses Post menopausal women Losers zone are milkmans fracture severe periodontitis Treatment: Dietary enrichment of Ca, harmonal therapy

• 1. 2. 3. 4. 5. 6.

VITAMIN D-RESISTANT RICKETS Renal tubular defects Inability to reabsorb some elements. X- linked dominant defect in renal phosphate metabolism. Hypophosphatemia Globular and hypo calcified dentin Pulp horns are elongated and extended high

Treatment : decreased vit D + oral phosphate

• 1. 2. 3.

RENAL RICKETS Inability of kidneys to synthesize 1-a-hydroxylase Calcium absorption is impaired-increase in fecal calcium excretion Treatment: administration of 1-a-OH-cholecalciferol

HYPERVITAMINOSIS D: 1. Feeling of well-being 2. Improved appatite 3. Digestive disturbances, fatigue weakness 4. Increased flow of urine containing calcium and phosphorus

PARATHYROID HARMONE

• The major hormone for regulation of the serum [Ca2+] • Synthesized and secreted by the chief cells of the parathyroid glands. • PTH-rp-produced by different genes • both elevates calium level • Also binds with PTH receptors

Biological Activity of PTH

• BONE
– PTH stimulates bone osteoblasts to increase growth & metabolic activity – PTH stimulated bone resorption releases calcium & phosphate into blood

• KIDNEY
– PTH increases reabsorption of calcium & reduces reabsorption of phosphate – Net effect of its action is increased calcium & reduced phosphate in plasma

• INTESTINE
– Increases calcium reabsorption via vitamin D

Secretion of PTH
• • • controlled by the serum [Ca2+] by negative feedback mild decreases in serum [Mg2+] also stimulate PTH secretion. severe decreases in serum [Mg2+] inhibit PTH secretion and produce symptoms of hypo parathyroidism. • the second messenger for PTH secretion by the parathyroid gland is cyclic AMP. Estimation: two sides immuno radiometric assay Degradation: kupffer cells of liver

• •

HYPOPARATHYROIDISM • Reduced amount of PTH • Surgical removal of parathyroid glands • Autoimmune destruction of parathyroid tissue • DiGeorge syndrome and endocrine –candidiasis syndrome CLINICAL FEATURES • Hypocalcemia • Pitting of enamel hypoplasia • Failure of tooth eruption Treatment : oral diseases of ergocalciferol. PSEUDOHYPOPARATHYROIDISM TYPE IA –ALBRIGHT’S HEREDITARY OSTEODISTROPHY • Result of defective G protein in kidney and bone, which causes end-organ resistance to PTH. • hypocalcemia and hyperphosphatemia

HYPERPARATHYROIDISM • Excss production of PTH • Primary hyperparathyroidism:
– Uncontrolled production of PTH – Parathyroid adenoma

• Secondary hyperparathyroidism:
– Chronic renal diseases

• Clinical features
• Triad of signs and symptoms-stones,bones, and abdominal groans

• Treatment:
• • • • hyperplastic tissue removed surgically Restriction of phosphate diet Use of phosphate binding agents calcitriol

• Calcitonin is a peptide hormone secreted by the parafollicular or “C” cells of the thyroid gland • It is synthesized as the preprohormone & released in response to high plasma calcium • Calcitonin acts on bone osteoclasts to reduce bone resorption. • Net result of its action is a decline in plasma calcium & phosphate

Calcitonin

Summary:

• PTH & calcitonin release are regulated by plasma Ca levels • Bone Ca & phosphate serve as a ready reserve for maintenance of plasma levels • Bone, kidney & intestine participate in the regulation of plasma calcium • PTH, Vitamin D, & calcitonin balance plasma [Ca++] for bone synthesis, muscle contraction, & cell signaling • Endocrine diseases result from pathway or glandular hypo or hyper secretion

Etiologies of Hypercalcemia
Increased GI Absorption Milk-alkali syndrome Elevated calcitriol Vitamin D excess Increased Loss From Bone/ Increased net bone resorption Elevated PTH Hyperparathyroidism Malignancy Osteolytic metastases PTHrP secreting tumor squamous cell bronchogenic carcinoma. Increased bone turnover Paget’s disease of bone Hyperthyroidism

Decreased Bone Mineralization Elevated PTH Aluminum toxicity

Decreased Urinary Excretion Thiazide diuretics Elevated calcitriol Elevated PTH

• Treatment:isotonic saline 6-8 lt/day
• • • Corticosteroids: Prednisone 40-80 mg/day in patients with sarcaidosis, lymphoma are hypervitaminoses D. biphosphonates (ctidronate, pamidronate) inhibits osteoclastic resorption. Gallium nitrate

Etiologies of Hypocalcemia
Decreased GI Absorption Poor dietary intake of calcium Impaired absorption of calcium Vitamin D deficiency Decreased conversion of vit. D to calcitriol Liver failure Renal failure Low PTH Decreased Bone Resorption / Increased Mineralization Low PTH (hypoparathyroidism)

PTH resistance (pseudohypoparathyroidism ) Vitamin D deficiency / low calcitriol Increased Urinary Excretion Low PTH

• Clinical signs of hypocalcemia
CHVOSTEK’S SIGN • Elicitation: Tapping on the face at a point just anterior to the ear and just below the zygomatic bone • Postitive response: Twitching of the ipsilateral facial muscles, suggestive of neuromuscular excitability caused by hypocalcemia TROUSSEAU’S SIGN • Elicitation: Inflating a sphygmomanometer cuff above systolic Hypocalcemic tetany in the hand, called blood pressure for several minutes carpopedal spasm • Postitive response: Muscular contraction including flexion of the wrist and meta carpophalangeal joints

• Diagnosis: serum phosphate and alkaline phosphatase levels are increased – vit D defficiency blood urea nitrogen , creatinine increased in renal diseases. • Treatment
In severe tetany - Acute cases, calcium chloride – 10% to exceed 1 ml/min. 10-30 ml IV not

• Dental manifestations of hypocalcimia :
Enamel hypoplasia, widened pulp chambers, pulp stones, shortened roots, delayed eruption and hypodontia

Etiologies of Hypophosphatemia
Decreased GI Absorption Decreased dietary intake (rare in isolation) Diarrhea / Malabsorption Phosphate binders (calcium acetate, Al & Mg containing antacids) Decreased Bone Resorption / Increased Bone Mineralization Vitamin D deficiency / low calcitriol Hungry bones syndrome Osteoblastic metastases

Increased Urinary Excretion Elevated PTH (as in primary hyperparathyroidism) Vitamin D deficiency / low calcitriol Fanconi syndrome Internal Redistribution (due to acute stimulation of glycolysis) Refeeding syndrome (seen in starvation, anorexia, and alcholism) During treatment for DKA

Etiologies of Hyperphosphatemia
Increased GI Intake Fleet’s Phospho-Soda Decreased Urinary Excretion Renal Failure Low PTH (hypoparathyroidism) Cell Lysis Rhabdomyolysis Tumor lysis syndrome

Etiologies of Hypophosphatemia
Decreased GI Absorption Decreased dietary intake
Phosphate binders Decreased Bone Resorption Vitamin D deficiency / low calcitriol Hungry bones syndrome Increased Urinary Excretion Elevated PTH (as in primary hyperparathyroidism) Vitamin D deficiency Internal Redistribution (due to acute stimulation of glycolysis) Refeeding syndrome

• Conclusion
Understanding bone physiology is important in orthodontic interventions involving manipulation of bone by the dentist should be carried out only when the patient is in positive calcium balance

• REFERENCES
Textbook of medical physiology tenth edition GUYTON & HALL Clinical Oral Physiology –Timothy s miles, Concise medical physiology- Chaudhuri Principles & Practice of medicine –Davidson , 6th edition