CALCIUM AND PHOSPHOROUS
METABOLISM
-DR. SUHASINI. G P Lecturer Dept. of Oral Pathology & Microbiology
Dr. Suhasini GP, Subharti Dental College, SVSU INTRODUCTION
• Metabolism (Greek, Metabote= change)
• Sum of the chemical and physical changes in tissue consisting of anabolism (reactions that convert small molecules into large) & catabolism (reactions that convert large molecules into small)
Dr. Suhasini GP, Subharti Dental College, SVSU Functions of Calcium
• Most abundant mineral
• Most important inorganic cation in mineralised tissue- structural role
• [Ca10(PO4)6(OH)2] in bone, dentin, cementum & enamel
Dr. Suhasini GP, Subharti Dental College, SVSU Functions
Formation of bone and teeth Controls secretion of glandular cells Muscle contraction Clotting of blood Neuromuscular excitability Cell-cell adhesion, cell integrity Intracellular second messenger in harmonal actions
Dr. Suhasini GP, Subharti Dental College, SVSU Dietary requirements
• Adults- 0.8 gms/day
• Children & pregnant and lactating women- additional 1gm of Ca supplements/day
• Postmenopausal women
Dr. Suhasini GP, Subharti Dental College, SVSU Sources • Milk & its products • Green leafy veg (oxalic acid and phytic acid- reduces absorption) • Raagi • Egg yolk • Legumes • Nuts • Dried fish • Pan chewing with slacked lime • Drinking water
Dr. Suhasini GP, Subharti Dental College, SVSU Distribution of Ca++`
• Essentially distributed extracellularly
• 1.2-1.4 kg in 70kg adult
• 99%-skeleton
• 1%- soft tissue+ body fluids
Dr. Suhasini GP, Subharti Dental College, SVSU Bone Ca++ Exists in 2 forms-
• Readily exchangeable form- simple exchange b/n newly deposited bone & exctracellular Ca++ • Stable form- constant formation & resorption of bone- – Controlled by PTH, calcitonin & vit.D
Dr. Suhasini GP, Subharti Dental College, SVSU Blood Ca++
• Plasma, little in RBC • 9-11mg/dl- constant • In plasma- 1. Diffusible o Ionised o Non-ionised 2. Non diffusible
Dr. Suhasini GP, Subharti Dental College, SVSU • Ionised diffusible form- physiologically active form
• Non ionised diffusible form- in the form of complexes as citrates, phosphates n bicarbonates
• Protein bound (albumin in plasma)- physiologically inactive
Dr. Suhasini GP, Subharti Dental College, SVSU Calcium balance
• Calcium absorption- • Active transport- against conc. gradient- duodenum • Passive diffusion- proximal jejunum & ileum • Normal secretion of HCL is necessary for optimal absorption • Achlorhydria, hypochlorhydria— decreased absorption.
Dr. Suhasini GP, Subharti Dental College, SVSU LUMEN CELL BLOOD 1,25-dihydroxycholecalciferol 2+ 2+ Ca CBP Ca
2+ d ie ta ry C a + + C a C B P Na Na
+ 2+ Facilitated Na /C a D iffu s io n E x c h a n g e
CBP = calcium binding protein
4 Dr. Suhasini GP, Subharti Dental College, SVSU Intake, Uptake and Excretion D ie t 1 0 0 0 m g
CALCIUM
a b s o rb s 5 0 0 m g GUT 3 5 0 m g 2+ Ca B o n e s e c re te s P o o l 5 0 0 m g 1 5 0 m g
Kidney 2% filtered load
8 0 0 m g 2 0 0 m g e x c re te d e x c re te d
5 Dr. Suhasini GP, Subharti Dental College, SVSU • Positive Ca++ balance • Negative Ca++ balance
Dr. Suhasini GP, Subharti Dental College, SVSU FACTORS AFFECTING Ca ABSORPTION
(a) Factors affecting mucosal cells ♣ Vit D- increases absorption
♣ D2(ergocalciferol)- yeast bread
♣ D3- fish liver oils
Dr. Suhasini GP, Subharti Dental College, SVSU • 1,25 dihydroxycholecalciferol- active form • Acts as a hormone • Acts by promoting synthesis of Ca binding protein (CaBP) in epithelium of intestinal villi
Dr. Suhasini GP, Subharti Dental College, SVSU (b) precipitating anions • Ca soluble form- absorbed • Contents- stomach Intestine- alkaline digestive juices- pH insoluble Ca salts- absorption • Acidic conditions in small intestine- favor absorption • Phosphate & long chain fatty acids, bile & bile salts are such anions • Very high or low Ca/P ratio or too high levels of both absorption
Dr. Suhasini GP, Subharti Dental College, SVSU (c) Complexing agents • Fat+ Ca – colloidal complexes- absorbed through intestinal wall (d) Carbohydrates &proteins • Disaccharide- lactose- absorption and bone calcification • Proteins- absorption (e) Hormones • Parathyroid hormone- stimulate intestinal transport • Controls formation of 1,25 dihydroxycholicalciferol • GH increases the absortion
Dr. Suhasini GP, Subharti Dental College, SVSU (f) Seasonal & unexplained effects- • Max- July & august • Min- Feb & March • Emotional factors- Stress
Dr. Suhasini GP, Subharti Dental College, SVSU PARATHYROID HARMONE VIT D
CALCITONIN bone
Action kidney on intestine
Dr. Suhasini GP, Subharti Dental College, SVSU Role of PTH
• Stimulates renal reabsorption of calcium • Stimulates bone resorption • Inhibits bone formation and mineralization • Stimulates synthesis of calcitriol- increased absorption from intestine
Net effect of PTH ↑ serum calcium
Dr. Suhasini GP, Subharti Dental College, SVSU Regulation of PTH
Low serum [Ca+2] Increased PTH secretion
High serum [Ca+2] Decreased PTH secretion
Dr. Suhasini GP, Subharti Dental College, SVSU Role of Calcitriol
• Stimulates GI absorption of calcium • Stimulates renal reabsorption of calcium • Stimulates bone resorption • (INCREASES SYNTHETIC ACTIVITY OF OSTEOBLASTS, NECESSARY FOR NORMAL CALCIFICATION • IN LARGE QUANTITIES- CAUSE RESORPTION OF BONE)
Net effect of calcitriol ↑ serum calcium
Dr. Suhasini GP, Subharti Dental College, SVSU Regulation of Calcitriol
INTESTINE KIDNEY BONE Dr. Suhasini GP, Subharti Dental College, SVSU Calcitonin
• Secreted by the type C cells(parafollicular) of thyroid.
• CT reduces Ca2+ by reducing transfer of Ca2+ to the blood and inhibiting bone resorption by decreasing the osteoclastic activity
• Used in the treatment of Paget’s disease & osteoporosis
Dr. Suhasini GP, Subharti Dental College, SVSU Other harmones
• GROWTH HARMONE-increases intestinal absorption • GLUCOCORTICOIDS-initially- inhibit osteoclstic activity- decreasing the plasma conc. Over prolonged periods- increases bone resorption and decreased bone formation • THYROID HARMONES- T3, T4- hypercalemia and hypercalciuria- osteoporosis • TESTOSTERONE-increases bone density & bone growth • ESTROGEN- inhibits osteoclastic activity, prevents osteoporosis.
Dr. Suhasini GP, Subharti Dental College, SVSU APPLIED ASPECTS
Dr. Suhasini GP, Subharti Dental College, SVSU Hypercalcemia
• Fatigue, lethargy • Anorexia, nausea, vomitting • Constipation (muscle hypotonia) • Cardiac abnormality • Peptic ulcer • Metastatic calcification etc
Dr. Suhasini GP, Subharti Dental College, SVSU Tetany
• Ca++ <6mg/dl • Chvostek’s sign-tapping of facial nerve- spasm of muscles • Trousseau’s sign- application of torniquet of sphygmomanometer on arm- carpopedal spasm • Accoucher’s hand-flexion of metacarpophalangeal joints while fingers remain extended • Laryngeal stridor
Dr. Suhasini GP, Subharti Dental College, SVSU Hyperparathyroidism
• Primary- adenomas of PTH glands • Secondary- renal diseases, rickets, osteomalacia, acromegaly, malabsorption syndrome
Dr. Suhasini GP, Subharti Dental College, SVSU Hypoparathyroidism
• Postoperative • Functional • Idiopathic • Hypomagnesemia • Pseudohypoparathyroidism- PTH level high, serum Ca++ low- defect in target cell receptor or CBP
Dr. Suhasini GP, Subharti Dental College, SVSU RICKETS
Rickets can be caused by lack of sunlight, but also from insufficient calcium. Vitamin D linked to calcium absorption.
Dr. Suhasini GP, Subharti Dental College, SVSU • RENAL RICKETS
Dr. Suhasini GP, Subharti Dental College, SVSU Pathologic calcification
• Dystrophic Calcification • Metastatic calcification • Calcinosis
Dr. Suhasini GP, Subharti Dental College, SVSU Dystrophic Calcification
• Calcification of dead and dying tissues. • The level of calcium in blood is usually normal. (There is no hypercalcemia). • In mouth- gingiva, tongue, cheek, pulp
Dr. Suhasini GP, Subharti Dental College, SVSU CalcificationsPulp in pulp: calcification Three types- I. Denticles - Denticles are formed as a result of an epitheliomesenchymal interaction within the developing pulp. II. Pulp stones- pulp stones are developed around the central nidus of pulp tissue III. Diffuse linear calcifications- they exhibit areas of fine, fibrillar, irregular calcification that often parallel the vasculature.
Dr. Suhasini GP, Subharti Dental College, SVSU • Classification by Hill-
• 1st - Nodular type- result of calcification of hyalinized CT – perivascular, perineural, associated with fibrosis
• 2nd type- Found in and around the necrotic cells • Inflammatory process
Dr. Suhasini GP, Subharti Dental College, SVSU Local metabolic Trauma dysfunction
Hyalinization Vascular of injured cells damage
fibrosis
Mineralization
PULP STONE
Dr. Suhasini GP, Subharti Dental College, SVSU Clinical & radiographic features denticles and pulp stones are detected on intraoral radiographs as radioopaqueHistopath enlargementsfeatures within the pulp chamber or canals May interfere• Denticles with root –consist formation of tubular leading dentin to early surrounding periodontal a destructionnest andof epithelium tooth loss , central epithelium degenerates with time and tubules undergo sclerosis.
• Pulp stones –a central amorphous mass of irregular calcification surrounded by concentric, lamellar rings of regular calcified material.
• Diffuse linear calcification – consist entirely of fine, fibrillar and irregular calcification that develop in the pulp chambers and canals
Dr. Suhasini GP, Subharti Dental College, SVSU Metastatic calcification
It is deposition of calcium salts in many tissues which may be normal. It is associated with disorders of calcium metabolism and there is hypercalcemia. • Metastatic calcification may occur in organ throughout the body. It is commonly observed in: • Organs which secrete or excretes acids like stomach, kidneys and lungs. • Calculi or stones in salivary glands, intestine, urinary tract, gall bladder etc
Dr. Suhasini GP, Subharti Dental College, SVSU • Aetiology: – Increased PTH » Hyperparathyroidism – Bone destruction » Tumour (MM, Leukaemia), Skeletal Mets (Breast Ca.) » Increased bone turnover (Pagets), Immobilisation. – Vitamin D related disorders » Excess Vitamin D » Sarcoidosis – Renal Failure » Retention of Phosphate, (secondary HyperPTH)
Dr. Suhasini GP, Subharti Dental College, SVSU Calcinosis cutis
• Presence of calcifications in or under the skin • Calcinosis circumscripta
• Calcinosis universalis- scleroderma and dermatomyositis
Dr. Suhasini GP, Subharti Dental College, SVSU PHOSPHOROUS
Dr. Suhasini GP, Subharti Dental College, SVSU Distribution and Requirements
Phosphate
• 80% of Pi is in mineralized tissue • The remainder is mostly intracellular • RDA = 800-900 mg
2 Dr. Suhasini GP, Subharti Dental College, SVSU Intake, Uptake and Excretion
D ie t 9 0 0 m g
Soft Tissue PHOSPHATE
la rg e a n d ra p id
2 5 0 m g GUT 6 0 0 m g Pi B o ne P o o l
2 5 0 m g
K id ne y
3 0 0 m g 6 0 0 m g e xc re te d e xc re te d 6 Dr. Suhasini GP, Subharti Dental College, SVSU DIGESTION
• Phosphorous- Organic esters- broken down in stomach • Plant sources- phytates- liberated by phytate from intestinal bacteria • High protein diet- meat, milk, eggs & legumes
Dr. Suhasini GP, Subharti Dental College, SVSU
• Absorbed from small intestine (jejunum)
• Active system
• Interferes with Ca absorption- insoluble CaPO4 • Fe & Al- form insoluble phosphates like some other cations- absorption
Dr. Suhasini GP, Subharti Dental College, SVSU • One third ingested phosphate- gut (unabsorbed)- lost with feces • Of the absorbed phosphate- major part excreted through kidney • Certain amount- secreted- digestive juice, and unabsorbed part appears with the feces
Dr. Suhasini GP, Subharti Dental College, SVSU • PTH- principal factor controlling renal excretion of phosphate • Inj of PTH into blood- increases excretion of phosphate- Decreased level in blood • Vit D- affects renal phosphate excretion • Deficiency of vitamin- increases excretion
Dr. Suhasini GP, Subharti Dental College, SVSU Functions
• 70 kg adult- 700 gms of phosphorous • 15% is present in soft tissue (100gm) • Component of many compounds essential to cellular processes Eg: Nucleic acids, ATP, Co- enzymes, phospholipids- cell membrane
Dr. Suhasini GP, Subharti Dental College, SVSU • Mineralized tissue • Phosphorylated metabolites (ATP) Degradation of glucose- glucose 6-phosphate, creatine phosphate, etc.) • DNA, RNA (part of genetic material) • Phospholipids • Free ortho- & pyro- phosphates • Phosphoenzymes (Enzymes, many are regulated, activated by phosphorylating/dephosphorylating)
Dr. Suhasini GP, Subharti Dental College, SVSU HORMONAL INFLUENCE OF PHOSPHOROUS METABOLISM
Dr. Suhasini GP, Subharti Dental College, SVSU Role of PTH
• Inhibits renal reabsorption of phosphate (Increased phosphate excretion in urine - decreases
reabsorption of PO4 in the proximal tubule Increased reabsorption of Ca in distal tubules)
• Stimulates bone resorption • Stimulates synthesis of calcitriol
Net effect of PTH ↓ serum phosphate
Dr. Suhasini GP, Subharti Dental College, SVSU Actions of Vit D (Calcitriol)
• Stimulates GI absorption of both calcium and phosphate • Stimulates renal reabsorption of both calcium and phosphate • Stimulates bone resorption (Mobilization of P from bone)
Net effect of calcitriol ↑ serum phosphate
Dr. Suhasini GP, Subharti Dental College, SVSU Overview of Calcium-Phosphate Regulation
Dr. Suhasini GP, Subharti Dental College, SVSU Etiologies of Hyperphosphatemia
Increased GI Intake Phospho-Soda
Decreased Urinary Excretion Renal Failure Low PTH (hypoparathyroidism) thyroidectomy I131 treatment for Graves disease of thyroid cancer Autoimmune hypoparathyroidism
Cell Lysis Rhabdomyolysis Tumor lysis syndrome
Dr. Suhasini GP, Subharti Dental College, SVSU Hyperphosphatemia
• Rhabdomyolysis • Cardiomyopathy • Respiratory insufficiency (P depletion) • Erythrocyte dysfunction • Nervous dysfunction • Phosphate trapping • Metabolic acidosis etc
Dr. Suhasini GP, Subharti Dental College, SVSU 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
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 Dr. Suhasini GP, Subharti Dental College, SVSU Hypophosphatemia
• Interference with renal reabsorption of metabolites- ca, P, H20- interfers with matrix mineralisation- rickets/ osteomalcia
Dr. Suhasini GP, Subharti Dental College, SVSU REFERENCES
• Textbook of medical physiology by Guyton & Hall; 10th Edition • The physiology & biochemistry of the mouth by G Neil Jenkins; 4th Edition • Textbook of physiology by Prof. A. K. Jain • Shafers.Textbook of oral pathology.Ed 6th
Dr. Suhasini GP, Subharti Dental College, SVSU
Thank you
Dr. Suhasini GP, Subharti Dental College, SVSU