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 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

CALCIUM

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 inMenopausal Woman Amenorrheic Women and the Female Athlete Triad Lactose Intolerant IndividualsVegetarians

FUNCTIONS OF CALCIUM

• Functions of calcium:– Hormone secretion

Hormone action :– Ca+2 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)  Females

 Infants  0-6 months 100 100

Infants  7-12 months  275   275

Children  1-3 years  460  460 

Children  4-8 years  500  500

Adolescents 14-18 years  1,250  1,250 

Adults  19 years and older 700  700

Pregnancy  19 years and older 700

 Breast-feeding 18 years and younger  1,250 

Breast-feeding19 years and older  700     

PHOSPHORUS RICH FOODS

• Food Serving Phosphorus (mg)

Milk, 8 ounces 247

Yogurt, plain nonfat 8 ounces 385

Cheese, 1 ounce 131

Egg 1 large, cooked 104

Chicken 3 ounces, cooked* 155

Fish, salmon 3 ounces, cooked* 252

Bread, whole wheat 1 slice 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 collagen lysis cavity formation

new bone

formation

OstoblastsAlkaline phosphatase

Estrogen-inhibits osteoclastic activity

Glucocorticoids -inhibitsOsteoblastic activity

BONE GROWTH AND CALCIUM METABOLISM

Growth of epiphyseal plate IGF-1,tyroid,vitD,Growth harmone.

OSSIFICATIONCartilagenous 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

• Thyroid harmones:– Hyperthyroidism-increased bone resorption

• 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.

• OSTEOMALACIA1. Flat bones and diaphyses

2. Post menopausal women

3. Losers zone are milkmans fracture

4. severe periodontitis

5. Treatment: Dietary enrichment of Ca, harmonal therapy

• VITAMIN D-RESISTANT RICKETS

1. Renal tubular defects

2. Inability to reabsorb some elements.

3. X- linked dominant defect in renal phosphate metabolism.

4. Hypophosphatemia

5. Globular and hypo calcified dentin

6. Pulp horns are elongated and extended high

Treatment : decreased vit D + oral phosphate

• RENAL RICKETS

1. Inability of kidneys to synthesize 1-a-hydroxylase

2. Calcium absorption is impaired-increase in fecal calcium excretion

3. 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• 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

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 AbsorptionIncreased GI AbsorptionMilk-alkali syndromeMilk-alkali syndromeElevated calcitriolElevated calcitriolVitamin D excessVitamin 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 HypocalcemiaEtiologies of Hypocalcemia

Decreased GI AbsorptionDecreased GI Absorption

Poor dietary intake of calciumPoor dietary intake of calcium

Impaired absorption of calciumImpaired absorption of calcium

Vitamin D deficiencyVitamin D deficiency

Decreased conversion of vit. D to Decreased conversion of vit. D to calcitriolcalcitriol

Liver failureLiver failure

Renal failureRenal failure

Low PTHLow PTH

Decreased Bone Resorption /Decreased Bone Resorption /

Increased MineralizationIncreased Mineralization

Low PTH (hypoparathyroidism)Low PTH (hypoparathyroidism)

PTH resistancePTH resistance(pseudohypoparathyroidis(pseudohypoparathyroidis

m)m)Vitamin D deficiency / Vitamin D deficiency / low calcitriollow calcitriol

Increased Urinary Excretion

Low PTH

Hypocalcemic tetany in the hand, called carpopedal spasm

• Clinical signs of hypocalcemiaCHVOSTEK’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 blood pressure for several minutes

• 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% - 10-30 ml IV not to exceed 1 ml/min.

• Dental manifestations of hypocalcimia :

Enamel hypoplasia, widened pulp chambers, pulp stones, shortened roots,

delayed eruption and hypodontia

Etiologies of HypophosphatemiaEtiologies of Hypophosphatemia

Decreased GI AbsorptionDecreased 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 calcitriolHungry bones syndromeOsteoblastic metastases

Increased Urinary ExcretionIncreased Urinary ExcretionElevated PTH (as in primary Elevated PTH (as in primary hyperparathyroidism)hyperparathyroidism)Vitamin D deficiency / low D deficiency / low calcitriolcalcitriol

Fanconi syndromeFanconi syndrome

Internal Redistribution (due to acute Internal Redistribution (due to acute stimulation of glycolysis)stimulation of glycolysis)Refeeding syndrome (seen in Refeeding syndrome (seen in starvation, anorexia, and starvation, anorexia, and alcholism)alcholism)During treatment for DKADuring 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 HypophosphatemiaEtiologies of Hypophosphatemia

Decreased GI Absorption

Decreased dietary intake Phosphate bindersPhosphate binders

Decreased Bone ResorptionDecreased Bone Resorption Vitamin D deficiency / low calcitriolVitamin D deficiency / low calcitriol Hungry bones syndromeHungry bones syndrome Increased Urinary ExcretionIncreased Urinary Excretion Elevated PTH (as in primary hyperparathyroidism)Elevated PTH (as in primary hyperparathyroidism) Vitamin D deficiencyVitamin D deficiency Internal Redistribution (due to acute stimulation of glycolysis)Internal Redistribution (due to acute stimulation of glycolysis)

Refeeding syndromeRefeeding 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

• REFERENCESTextbook of medical physiology tenth edition GUYTON & HALLClinical Oral Physiology –Timothy s miles,Concise medical physiology- ChaudhuriPrinciples & Practice of medicine –

Davidson ,6th edition