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CALCIUM & PHOSPHORUS METABOLISM

DEPARTMENT OF ORAL PATHOLOGY AND

MICROBIOLOGY

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PRESENTED BY

Dr G SHYAM RAJ

CONTENTS• INTRODUCTION

• CALCIUM METABOLISM

FUNCTIONS

NORMAL VALUES AND TYPES

SOURCES AND REQUIREMENTS

ABSORPTION AND EXCRETION

REGULATION

• PHOSPHORUS METABOLISM

FUNCTIONS

NORMAL VALUES AND SOURCES

ABSORPTION AND EXCRETION

REGULATION

• APPLIED ASPECTS

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INTRODUCTION

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TOTAL BODY CALCIUM-

1100-1200gms

Skeleton(99%)

Intracellular(1%)

Extracellular(0.1%)

Ca10(PO4)6(OH)2

PLASMA : 2.5mmol/L

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TYPES OF CALCIUM

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CALCIUM IN BONES

• RAPIDLY EXCHANGEABLE CALCIUM : Small quantity

Exchangeable Ca

Maintain plasma Ca level

• SLOWLY EXCHANGEABLE CALCIUM : Large quantity

Stable calcium

Bone remodelling

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DAILY REQUIREMENTS OF CALCIUM

• 1-3 years :- 500 mg

• 4-8 years :– 800 mg

• 9-18 years :- 1300 mg

• 19-50 years :- 1000 mg

• 51 years and above :- 1200 mg

• Pregnant ladies and lactating mothers :- 1200 mg8

SOURCES

• Whole milk : 10%

• Low fat milk : 18%

• Cheese : 27%

• Other diary products : 17%

• Vegetables : 7%

• Others ( meat, egg, grains, sugar, coffee, tea, chocolate etc) : 21%

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FUNCTIONS OF CALCIUM

• Contributes to hardness of bone

• Maintenance of excitability of nerve and muscle

• Normal skeletal and cardiac muscle contraction

• Hormone response coupling

• Cell division and growth

• Blood coagulation

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CALCIUM METABOLISM

• A complex regulatory system maintains the normal amounts of Ca,

phosphate in the body.

• Key hormone to regulate the amounts of Ca & phosphate are

1. Parathormone,

2. 1,25 – dihydroxycholecalciferol(calcitriol),

3. calcitonin

These hormones act on 3 organ system

Intestinal tract

The bone

Kidney 11

ABSORPTION & EXCRETION OF CALCIUM

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PARACELLULAR PATHWAY

• Passive• Nonsaturable• Altering structure of intercellular

tight junctions

TRANSCELLULAR ROUTE

• Active• Saturable• 1,25-dihydroxy vitamin D3

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FACTORS INFUENCING CALCIUM & PHOSPHORUS IN GUT

• Vitamin D

• PTH

• Calcitonin

• Steroid hormones

• Fats

• Bile salts

• Protein diet

• Phosphorus

• pH

• Estrogen & androgen

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VITAMIN D IN CALCIUM ABSORPTION

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PARATHYROID HORMONE

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Normal plasma level : 1.5-5.5 ng/dL60-70% - degraded by kupffer cells of liver by proteolysis20-30% - occurs in kidneys

FUNCTIONS

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Regulating intestinal absorption

Renal excretion

Exchange between extracellular fluid and bone

EFFECT OF PTH ON CALCIUM AND PHOSPHATE CONCENTRATIONS

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CONTROL OF PARATHYROID SECRETION BY CALCIUM ION CONCENTRATION

• Decrease in Ca ion conc. in ECF causes the PTH gland to increase the

rate of secretions within minutes.

• Hypertrophy – rickets, pregnancy, lactation

• Decrease in PTH secretions

Excess quantity of Ca in diet

Increased Vitamin D in diet

Bone absorption caused by factors other than PTH

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PTH INCREASES CA ABSORPTION

Late distal tubules

Collecting tubules

Early collecting ducts

Ascending loop of Henle (lesser extent)

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CALCITONIN

• Parafollicular cells or clear cells ( C cells ) – follicles in thyroid

• In lower animals – parafollicular cells ultimobranchial glands

pharyngeal pouches

• Polypeptide chain- 32 aminoacids

• Plasma level : 1-2ng/dL

• Half life : 5-10 mins

• Degraded and excreted by liver and kidney

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• Decreases blood calcium levels by acting on bones, kidneys and

intestine

• Facilitates deposition of calcium on bones

• Increases excretion of calcium through urine

• Prevents absorption of calcium from intestine

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MECHANISM OF BONE CALCIFICATION

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Osteoblasts secrete collagen & ground substance

Polymerization

Osteoid (collagen)

Osteoblasts entrapped –osteoids

Ca salt ppt. on the surface

Amorphous compounds (non-crystalline)

Reabsorption & reprecipitation

Hydroxyapatite crystals

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MECHANISM OF CA SALTS TO BE DEPOSITED IN OSTEOIDS

• Collagen fibers causes precipitation of Ca salts

• Osteoblasts secrete a substance into osteoids that neutralizes the

inhibitor(pyrophosphate)

• Natural affinity of collagen fibers for Ca salts causes precipitations

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BONE & EXTRACELLULAR FLUID

• Bone contains a type of exchangeable Ca that is always in

equilibrium with Ca ions in the extra-cellular fluids.

• Accounts for 0.4 – 1% of total bone Ca.

• Provides a rapid buffering mechanism to keep Ca ion conc. in

extracellular fluid.

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PTH increases Ca & P absorption from bone

Rapid phase

Slow phase

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RAPID PHASE

Removal of bone

Bone matrix in vicinity of osteocytes

Vicinity of osteoblasts along bone surface

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RAPID PHASE

• Osteocytes and osteoblasts form a system of interconnected cells.

• Osteocytic membrane system( separates the bone from ECF)

• Osteocytic membrane pumps Ca ions from the bone fluid into

extracellular fluid, creating Ca ion conc. 1/3rd that of extracellular

fluid.

• Osteolysis – Osteocytic pump becomes excessive activated.

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SLOW PHASE

Activation of slow phase

Already formed osteoclasts

New osteoclasts

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SLOW PHASE

• Osteoblasts & osteocytes send a secondary signal to osteoclasts.

• Osteoclastic resorption of bone lead to weakened bones &

secondary stimulation of osteoblasts.

• Prolonged administration or secretion of PTH over a period of

months to years results in evident resorption in all bones & even

development of large cavities filled with large multinucleated

osteoclasts.

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PHOSPHORUS

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• Essential mineral

• Diet : peas, dried beans, nuts, milk, cheese and butter

• Inorganic form – phosphate(PO4)

• Most abundant intracellular anion.

FUNCTIONS

• Important component – ATP, DNA, RNA and many intermediates of

metabolic pathways

• Important constituent – bones and teeth

• Buffer – acid base balance

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NORMAL VALUES

• Total amount in body :– 500-800 gms

• 80% - bones and teeth

• 10.9% - Viscera

• 9% - skeletal muscle

• 0.1% - extracellular

• Normal plasma level : 0.84 – 1.44mmol/L (2.8-4.5 mg/dL)

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PHOSPHORUS METABOLISM

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FUNCTIONS

• Formation of bone & teeth

• Important constituent of high energy phosphate compounds.

• Helps in regulation of glycolysis

• Phosphorylation of lipids & sugar

• Urinary buffer, which regulates urinary pH.

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DEPLETION OF PHOSPHATE

• Skeletal muscle weakness

• Cardiac & respiratory muscle dysfunction

• Loss of red blood cell membrane integrity

• Abnormal formation of bone

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HYPOCALCEMIA

• Neuromuscular irritability

• Numbness and tingling sensation

• Tetanic muscle contraction in hands & feet

• Spasm of muscles of larynx & consequent airway obstruction.

• CNS causes seizures

• Marked dilatation of heart

• Changes in cellular enzyme activity

• Increased in membrane permeability in some cells

• Impaired blood clotting44

CHVOSTEK’S SIGN

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TROUSSEAU’S SIGN

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ERBS SIGN

• Hyperexcitability of muscles to electrical stimulation

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ACCOUCHER’S HAND

• Muscular spasm leading to uncontrolled prolonged flexion of

metacarpophalangeal joints while the fingers remain extended.

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HYPERCALCEMIA

• Level above 12mg/dl & become marked at 15mg/dl

• Depresses nervous system & muscle activity

• Decreases the QT interval of heart causes constipation & lack of

appetite.

• Polyuria, nausea, tiredness

• Impaired mentation

• Coma

• Parathyroid poisoning (>17mg/dl)

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HYPOPARATHYROIDISM

• PTH glands are suddenly removed, Ca level 6 – 7 mg/dl within 2-3

days.

• Blood phosphate conc. Doubles

• Signs of tetany develop.

• Osteocytic reabsorption of exchangeable Ca decreases & the

osteoclasts become totally inactive

• Ca reabsorption is depressed

• Bone is usually strong

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PSEUDOHYPOPARATHROIDISM

• Deficiency of receptors for PTH in the target cells

• EVENTHOUGH – PTH secretion is increased – cannot act on target cells

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TREATMENT

• Parathyroid hormone

• Vitamin D (1,00,000 units)

• 1-2 gram intake of Calcium

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HYPERPARATHYROIDISM

• Primary hyperparathyroidism

• Secondary hyperparathyroidism

• Tertiary hyperparathyroidism

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PRIMARY HYPERPARATHYROIDISM

• Tumor of one of PTH gland.

• Mostly seen in women than men & children

• Extreme osteoclastic activity in bones

• Elevates Ca ion conc. in ECF which depresses phosphate ions.

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BROWN TUMOR

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Hyperparathyroidism results in disorders of bone and mineral metabolism.

Diffuse and focal lesions may arise in multiple bones.

On occasion, a patient with undiagnosed hyperparathyroidism presents with a lytic lesion that may be mistaken for a tumor.

These lesions are termed "Brown Tumors" due to the presence of old hemorrhage in the lesion.

BONE DISEASE IN HYPERPARATHYROIDISM

• In mild disease new bone is deposited along with osteoclastic effect.

• In severe form osteoclastic absorption soon far outstrips

osteoblastic activity.

• Osteitis fibrosa cystica

• Slight trauma cause fracture.

• Alkaline phosphatase is increased

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• Jaw bone

Normal trabecular pattern is lost & replaced by granular or

ground glass appearance.

Moth-eaten like appearance.

Teeth are mobile and migrate.

Lamina dura diminished or completely absent in 10% of cases.

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PARATHYROID POISONING

• Ca level must rise above 17 mg/dl

• CaHPO4 crystals deposit

Alveoli of lungs

Tubules of kidney

Thyroid gland

Wall of arteries throughout the body

• Death occurs in few days

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KIDNEY STONES IN HYPERPARATHYROIDISM

• CaPO4 crystals tend to ppt. in kidneys, forming CaPO4.

• More in alkaline urine than acidic urine

• Acidotic diets and acidic drugs are used for treating renal calculi.

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SECONDARY HYPERPARATHYROIDISM

• Vitamin D deficiency

• Chronic renal disease

• Hypocalcemia, hyperphosphatemia & increased serum alkaline

phosphatase

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TERTIARY HYPERPARATHYROIDISM

• Parathyroid tumor develop from long standing secondary

hyperparathyroidism.

• Serum calcium is increased

• Phosphorus is normal to increased

• Alkaline phosphatase is increased

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MANAGEMENT

• Primary and tertiary require excision of parathyroid tumor.

• Secondary type - Subtotal parathyroidectomy is beneficial

• Renal osteodystrophy – high Ca diet, Vit.D supplementation and

reduction in dietary phosphate.

• Recent studies – use of calcitriol an inhibitor of PTH synthesis &

secretion.

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OSTEOPOROSIS

• Primary deficit of bone matrix with a secondary deficit of minerals

• Develop in 3 ways

Slight increase in bone resorption with slight decrease in

formation

Severe increase in bone resorption with normal rate of

formation

Normal resorption with severe decrease in formation

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ETIOLOGY

• Ageing

• Hereditary

• Nutrition & lifestyle

• Medications & other illness

• Decrease in muscle activity

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RADIOGRAPHIC FEATURES

• Decrease in density of bone

• Loss of normal trabecular pattern

• Thinning of matrix

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Types of osteoporosis

PostmenopausalSenile

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RICKETS

• THE PRIMARY DEFECTS :

1. MINERALISATION INTERFRENCE

2.DERANGED BONE GROWTH

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OSTEOMALACIA

• Accumulation of osteoid in place of mineralized bone

• Etiology

Vitamin D deficiency

Calcium mal-absorption

Liver & renal disorders

Prolonged anticonvulsive drugs

Hypophosphatemic rickets

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CLINICAL FEATURES

• Weakness & generalized bone pain

• Pseudofracture

• Partial or complete fracture without displacement

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RADIOGRAPHIC FEATURES

• Generalized rarefaction

• Cortical thinning

• Homogenous granular appearance throughout the maxilla &

mandible

• Lamina dura absent or less prominent

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OSTEITIS DEFORMANS

• Early

• Intermediate

• Late

• Etiology

Genetic link

Viral infection

Inflammatory

Vascular disorders

Autoimmune connective tissue

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CLINICAL FEATURES

• Non specific headaches

• Impaired hearing

• Involved bone become warm to touch

• Maxilla involved more

Alveolar ridge becomes widened & the palate is flattened

Teeth become loose & migrate, producing spacing

Mouth may remain open, exposing the teeth (lips are too small)

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LABORATORY FINDINGS

• Serum Ca & Phosphatase level – normal limits

• Serum alkaline phosphatase – elevated

• Urine hydroxyproline - elevated

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HYPOPHOSPHATEMIA

• Serum phosphate < 0.80 mmol/L

• MODERATE : - 0.32-0.65 mmol/L

• SEVERE :- <0.32 mmol/L

• Results from

1. Internal redistribution of phosphorus

2. Increased urinary excretion

3. Decreased intestinal absorption

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• CLINICAL FEATURES:-

• MUSCLE DISORDERS: Proximal myopathy, dysphagia and ileus

• Myocardial dysfunction

• Respiratory failure and failed weaning from ventilators

• Hemolysis, thrombocytopenia

• Metabolic acidosis and metabolic encephalopathy

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HYPERPHOSPHATEMIA

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• Occurs due to

1. Increased phosphate load due to endogenous and exogenous

sources – exceeds – renal excretory ability

2. Decreased urinary excretion

CLINICAL MANIFESTATIONS

• Tetany and seizures due to hypocalcemia

• Elevation of calcium x phosphate product – soft tissue calcification

• Nephrocalcinosis, cardiac and pulmonary calcification

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DENTAL

CONSIDERATIONS

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DENTINAL SCLEROSIS

Sclerosis of primary dentin is a regressive alteration in tooth

substance that is characterised by calcification of the dentinal tubules

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DEAD TRACTS

• dead tracts in dentin are seen in ground sections of teeth and are

manifested as a black zone by transmitted light

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SECONDARY DENTIN

• secondary dentin , which is formed after deposition of the primary

dentin has been completed , is characterised by its irregular

morphological pattern

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HETEROTOPIC CALCIFICATION

• it is defined as deposition of calcium salts in tissue other than

osteoid or enamel

• it is of 2 types

1.METASTATIC CALCIFICATION :

calcium salts are precipitated in undamaged tissue

it is commonly seen in kidney

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• CAUSES OF METASTATIC CALCIFICATION :

hyperparathyroidism

hypervitaminosis D

excessive absorption of calcium

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• DYSTROPHIC CALCIFICATION

• it is deposition of calcium salts in dead or degenerating tissues

• Pathogenesis : related to change in local condition of the tissues

• Clinical features :

it is found intraorally in gingiva , tongue , pulp of the teeth.

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PULP CALCIFICATION

• 1.PULP STONES

• 2.DIFFUSE CALCIFICATION

PULP STONES CLASSIFIED AS

TRUE

FALSE

TRUE DENTICLE : localized masses of calcified tissue resembling tubular structure

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• FALSE DENTICLES : do not exhibits dentinal tubules

• FREE & ATTACHED DENTICLES

FREE DENTICLES : lying entirely within pulp tissue

ATTACHED DENTICLES : continuous with dentinal walls

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DIFFUSE CALCIFICATION

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• Most common – root canals

• Resembles calcifications seen in other tissues following degeneration

• Calcific degeneration

• Amorphous unorganized linear strands paralleling blood vessels and nerves

HYPERCEMENTOSIS

• It may be regarded as a regressive change of teeth characterised by

the deposition of excessive amounts of secondary cementum on

root surface

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REFERENCES

• Textbook of Medical physiology – Guyton & Hall (10th edition)

• Anthony’s textbook of anatomy & physiology – Gary.A.Thibodeau (14th

edition)

• Textbook of physiology – Robert.M.Beene

• Differential diagnosis of Oral & Maxillofacial lesions – Woods & Goaz.

• Applied Oral physiology ( 2nd edition) – Christopher L.B Lavelle

• JAPI - Vol 56 – Aug 2008 - Disorders of Calcium, Phosphorus and

Magnesium Metabolism – Amit K Ghosh , Shashank R Joshi

• ATLAS OF DISEASES OF KIDNEY - Robert W. Schrier VOL 1

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