calcium & phosphorus metabolism and its applied aspects

1

CALCIUM & PHOSPHORUS METABOLISM

DEPARTMENT OF ORAL PATHOLOGY AND

MICROBIOLOGY

2

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

3

INTRODUCTION

4

TOTAL BODY CALCIUM-

1100-1200gms

Skeleton(99%)

Intracellular(1%)

Extracellular(0.1%)

Ca10(PO4)6(OH)2

PLASMA : 2.5mmol/L

5

TYPES OF CALCIUM

6

CALCIUM IN BONES

• RAPIDLY EXCHANGEABLE CALCIUM : Small quantity

Exchangeable Ca

Maintain plasma Ca level

• SLOWLY EXCHANGEABLE CALCIUM : Large quantity

Stable calcium

Bone remodelling

7

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%

9

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

10

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

12

13

14

PARACELLULAR PATHWAY

• Passive• Nonsaturable• Altering structure of intercellular

tight junctions

TRANSCELLULAR ROUTE

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

15

FACTORS INFUENCING CALCIUM & PHOSPHORUS IN GUT

• Vitamin D

• PTH

• Calcitonin

• Steroid hormones

• Fats

• Bile salts

• Protein diet

• Phosphorus

• pH

• Estrogen & androgen

16

VITAMIN D IN CALCIUM ABSORPTION

17

PARATHYROID HORMONE

18

19

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

FUNCTIONS

20

Regulating intestinal absorption

Renal excretion

Exchange between extracellular fluid and bone

EFFECT OF PTH ON CALCIUM AND PHOSPHATE CONCENTRATIONS

21

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

22

PTH INCREASES CA ABSORPTION

Late distal tubules

Collecting tubules

Early collecting ducts

Ascending loop of Henle (lesser extent)

23

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

24

• 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

25

MECHANISM OF BONE CALCIFICATION

26

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

27

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

28

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.

29

PTH increases Ca & P absorption from bone

Rapid phase

Slow phase

30

RAPID PHASE

Removal of bone

Bone matrix in vicinity of osteocytes

Vicinity of osteoblasts along bone surface

31

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.

32

SLOW PHASE

Activation of slow phase

Already formed osteoclasts

New osteoclasts

33

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.

34

PHOSPHORUS

35

• 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

36

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)

37

PHOSPHORUS METABOLISM

38

39

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.

40

DEPLETION OF PHOSPHATE

• Skeletal muscle weakness

• Cardiac & respiratory muscle dysfunction

• Loss of red blood cell membrane integrity

• Abnormal formation of bone

41

42

43

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

45

TROUSSEAU’S SIGN

46

ERBS SIGN

• Hyperexcitability of muscles to electrical stimulation

47

ACCOUCHER’S HAND

• Muscular spasm leading to uncontrolled prolonged flexion of

metacarpophalangeal joints while the fingers remain extended.

48

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)

49

50

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

51

PSEUDOHYPOPARATHROIDISM

• Deficiency of receptors for PTH in the target cells

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

52

TREATMENT

• Parathyroid hormone

• Vitamin D (1,00,000 units)

• 1-2 gram intake of Calcium

53

HYPERPARATHYROIDISM

• Primary hyperparathyroidism

• Secondary hyperparathyroidism

• Tertiary hyperparathyroidism

54

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.

55

BROWN TUMOR

56

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

57

• 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.

58

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

59

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.

60

SECONDARY HYPERPARATHYROIDISM

• Vitamin D deficiency

• Chronic renal disease

• Hypocalcemia, hyperphosphatemia & increased serum alkaline

phosphatase

61

TERTIARY HYPERPARATHYROIDISM

• Parathyroid tumor develop from long standing secondary

hyperparathyroidism.

• Serum calcium is increased

• Phosphorus is normal to increased

• Alkaline phosphatase is increased

62

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.

63

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

64

ETIOLOGY

• Ageing

• Hereditary

• Nutrition & lifestyle

• Medications & other illness

• Decrease in muscle activity

65

RADIOGRAPHIC FEATURES

• Decrease in density of bone

• Loss of normal trabecular pattern

• Thinning of matrix

66

Types of osteoporosis

PostmenopausalSenile

67

RICKETS

• THE PRIMARY DEFECTS :

1. MINERALISATION INTERFRENCE

2.DERANGED BONE GROWTH

68

OSTEOMALACIA

• Accumulation of osteoid in place of mineralized bone

• Etiology

Vitamin D deficiency

Calcium mal-absorption

Liver & renal disorders

Prolonged anticonvulsive drugs

Hypophosphatemic rickets

69

CLINICAL FEATURES

• Weakness & generalized bone pain

• Pseudofracture

• Partial or complete fracture without displacement

70

RADIOGRAPHIC FEATURES

• Generalized rarefaction

• Cortical thinning

• Homogenous granular appearance throughout the maxilla &

mandible

• Lamina dura absent or less prominent

71

OSTEITIS DEFORMANS

• Early

• Intermediate

• Late

• Etiology

Genetic link

Viral infection

Inflammatory

Vascular disorders

Autoimmune connective tissue

72

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)

73

LABORATORY FINDINGS

• Serum Ca & Phosphatase level – normal limits

• Serum alkaline phosphatase – elevated

• Urine hydroxyproline - elevated

74

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

75

• 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

76

HYPERPHOSPHATEMIA

77

• 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

78

DENTAL

CONSIDERATIONS

79

DENTINAL SCLEROSIS

Sclerosis of primary dentin is a regressive alteration in tooth

substance that is characterised by calcification of the dentinal tubules

80

DEAD TRACTS

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

manifested as a black zone by transmitted light

81

SECONDARY DENTIN

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

dentin has been completed , is characterised by its irregular

morphological pattern

82

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

83

• CAUSES OF METASTATIC CALCIFICATION :

hyperparathyroidism

hypervitaminosis D

excessive absorption of calcium

84

• 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.

85

PULP CALCIFICATION

• 1.PULP STONES

• 2.DIFFUSE CALCIFICATION

PULP STONES CLASSIFIED AS

TRUE

FALSE

TRUE DENTICLE : localized masses of calcified tissue resembling tubular structure

86

87

• FALSE DENTICLES : do not exhibits dentinal tubules

• FREE & ATTACHED DENTICLES

FREE DENTICLES : lying entirely within pulp tissue

ATTACHED DENTICLES : continuous with dentinal walls

88

DIFFUSE CALCIFICATION

89

• 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

90

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

91

92