CALCIUM AND PHOSPHOROUS METABOLISM and po4 metabolism.pdf · CALCIUM AND PHOSPHOROUS METABOLISM...

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)


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


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


Dietary requirements

• Adults- 0.8 gms/day

• Children & pregnant and lactating women-

additional 1gm of Ca supplements/day

• Postmenopausal women


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


Distribution of Ca++`

• Essentially distributed extracellularly

• 1.2-1.4 kg in 70kg adult

• 99%-skeleton

• 1%- soft tissue+ body fluids


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


Blood Ca++

• Plasma, little in RBC

• 9-11mg/dl- constant

• In plasma-

1. Diffusible

o Ionised

o Non-ionised

2. Non diffusible


• 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


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.


L U M E N C E L L B L O O D

d ie ta ry C a2 +

C B P

C a C B P

C a2 +

F a c ilita te d

D iffu s io n

N a+

/C a2 +

E x c h a n g e

C a2 +

N a+

N a+

C B P = c a lc iu m b in d in g p ro te in

4

1,25-dihydroxycholecalciferol


Intake, Uptake and Excretion

D ie t

1 0 0 0 m g

G U T

8 0 0 m g

e x c re te d

a b s o rb s

3 5 0 m g

s e c re te s

1 5 0 m g

C a2 +

P o o l

B o n e

5 0 0 m g

5 0 0 m g

K id n e y 2 % f i l te re d

lo a d

2 0 0 m g

e x c re te d

C A L C IU M

5 Dr. Suhasini GP, Subharti Dental College, SVSU

• Positive Ca++ balance

• Negative Ca++ balance


FACTORS AFFECTING Ca ABSORPTION

(a) Factors affecting mucosal cells

♣ Vit D- increases absorption

♣ D2(ergocalciferol)- yeast bread

♣ D3- fish liver oils


• 1,25 dihydroxycholecalciferol- active form

• Acts as a hormone

• Acts by promoting synthesis of Ca binding protein (CaBP) in epithelium of intestinal villi


(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


(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


(f) Seasonal & unexplained effects-

• Max- July & august

• Min- Feb & March

• Emotional factors- Stress


PARATHYROID HARMONE

VIT D

CALCITONIN

bone

kidney

intestine

Action on


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


Regulation of PTH

Low serum [Ca+2] Increased PTH secretion

High serum [Ca+2] Decreased PTH secretion


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


Regulation of Calcitriol

INTESTINE KIDNEY BONE


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


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.


APPLIED ASPECTS


Hypercalcemia

• Fatigue, lethargy

• Anorexia, nausea, vomitting

• Constipation (muscle hypotonia)

• Cardiac abnormality

• Peptic ulcer

• Metastatic calcification etc


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


Hyperparathyroidism

• Primary- adenomas of PTH glands

• Secondary- renal diseases, rickets, osteomalacia, acromegaly, malabsorption syndrome


Hypoparathyroidism

• Postoperative

• Functional

• Idiopathic

• Hypomagnesemia

• Pseudohypoparathyroidism- PTH level high, serum Ca++ low- defect in target cell receptor or CBP


RICKETS

Rickets can be caused by lack of sunlight, but also from insufficient calcium. Vitamin D linked to calcium absorption.


• RENAL RICKETS


Pathologic calcification

• Dystrophic Calcification

• Metastatic calcification

• Calcinosis


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


Pulp calcification Calcifications in pulp:

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.


• 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


Local metabolic dysfunction

Hyalinization of injured cells

fibrosis

Trauma

Vascular damage

Mineralization

PULP STONE


Clinical & radiographic features

denticles and pulp stones are detected on intraoral radiographs

as radioopaque enlargements within the pulp chamber or

canals

May interfere with root formation leading to early periodontal

destruction and tooth loss

Histopath features

• Denticles –consist of tubular dentin surrounding a

nest of epithelium , 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


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


• 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)


Calcinosis cutis

• Presence of calcifications in or under the skin

• Calcinosis circumscripta

• Calcinosis universalis- scleroderma and dermatomyositis


PHOSPHOROUS


Distribution and Requirements

Phosphate

• 80% of Pi is in mineralized tissue

• The remainder is mostly intracellular

• RDA = 800-900 mg


Intake, Uptake and Excretion

D ie t

9 0 0 m g

G U T

3 0 0 m g

e xc re te d

P i

P o o lB o ne

2 5 0 m g

K id ne y

6 0 0 m g

e xc re te d

P H O S P H A T E

6 0 0 m g

2 5 0 m g

S o ft T is s u e

la rge and

rap id


DIGESTION

• Phosphorous- Organic esters- broken down in stomach

• Plant sources- phytates- liberated by phytate from intestinal bacteria

• High protein diet- meat, milk, eggs & legumes


• Absorbed from small intestine (jejunum)

• Active system

• Interferes with Ca absorption- insoluble CaPO4

• Fe & Al- form insoluble phosphates like some other

cations- absorption


• 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


• 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


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


• 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)


HORMONAL INFLUENCE OF PHOSPHOROUS METABOLISM


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


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


Overview of Calcium-Phosphate Regulation


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


Hyperphosphatemia

• Rhabdomyolysis

• Cardiomyopathy

• Respiratory insufficiency (P depletion)

• Erythrocyte dysfunction

• Nervous dysfunction

• Phosphate trapping

• Metabolic acidosis etc


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


Hypophosphatemia

• Interference with renal reabsorption of metabolites- ca, P, H20- interfers with matrix mineralisation- rickets/ osteomalcia


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


Thank you


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