Your SlideShare is downloading. ×
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Calcium metabolism
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Calcium metabolism

981

Published on


Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.

Published in: Health & Medicine
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
981
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
19
Comments
0
Likes
1
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. DEPARTMENT OF CONSERVATIVE DENTISTRY AND ENDODONTICSDEPARTMENT OF CONSERVATIVE DENTISTRY AND ENDODONTICS COLLEGE OF DENTAL SCIENCES,COLLEGE OF DENTAL SCIENCES, DAVANGERE.DAVANGERE. SEMINAR ONSEMINAR ON CALCIUM METABOLISMCALCIUM METABOLISM Presented by : DrDr. Manju KoshyManju Koshy
  • 2. CALCIUM METABOLISM CONTENTS  INTRODUCTION  DISTRIBUTION OF CALCIUM IN THE BODY  BONE  BLOOD  LYMPH, CSF, AQUEOUS HUMOUR  MUSCLES  ORAL CAVITY – ENAMEL, SALIVA  SOURCE, ABSORPTION, EXCRETION  CALCIUM BALANCE  FUNCTIONS OF CALCIUM IN THE BODY  BONE RIGIDITY  ECF CALCIUM  CLOTTING OF BLOOD  ICF CALCIUM  MUSCLE CONTRACTION  VASOSPASM OF SMOOTH MUSCLES  NEUROTRANSMISSION  FACTORS AFFECTING THE CALCIUM LEVEL IN BODY 1) PARATHYROID HORMONE • EFFECTS ON BONE • EFFECTS ON KIDNEY • EFFECTS ON INTESTINE • REGULATION OF PTH SECRETION 2) VITAMIN D • EFFECTS ON GIT • EFFECTS ON BONE • EFFECTS ON KIDNEY 3) CALCITONIN  BONE  REGULATION OF BLOOD CALCIUM LEVEL  DISORDERS OF CALCIUM METABOLISM  HYPOPARATHYROIDISM  HYPERPARATHYROIDISM  PRIMARY HYPERPARATHYROIDISM  SECONDARY HYPERPARATHYROIDISM  TERTIARY HYPERPARATHYROIDISM  ECTOPIC - PTI SYNDROME
  • 3.  HYPOCALCEMIA  HYPERCALCEMIA  VITAMIN D DEFICIENCY  RICKETS  OSTEOMALACIA  OSTEOPOROSIS  HETEROTOPIC CALCIFICATION  DYSTROPHIC CALCIFICATION  METASTATIC CALCIFICATION  CALCINOSIS IN PULP  REFERENCES  CONCLUSION CALCIUM METABOLISM INTRODUCTION : Calcium is a very important mineral in our body. It provides rigidity to bones, muscle contraction, affects permeability of cells, blood clotting mechanism etc. Metabolism of calcium is intimately associated with parathyroid hormone, calcitonin and vitamin D. Importance of studying calcium metabolism has increased because : - (i) In old people, one of the major curses happens to be osteoporosis which can cause fracture of bones. (ii) Calcium play vital roles in contraction of heart as well as skeletal muscles and smooth muscles. Therefore drugs affecting calcium ion metabolism can be used to treat hypertension or cardiac contractility. DISTRIBUTION : An average sized man has about 1 Kg of calcium in his body. About 99% of this calcium is in the bone and teeth. The remaining is distributed in different tissues as follows ; Muscles : 8 mg per 100 gm of fresh muscle. Plasma or serum : 9-11 mg per 100 ml of blood RBC : Minute traces Lymph and aqueous humour : Slightly less than plasma. CSF : 5.3 mg per 100 ml. Enamel ; 96% inorganic content – Hydroxyapatite crystals Dentin : 65% inorganic content Cementum : 45-50% inorganic content Saliva : Minute traces. BONE CALCIUM : Since bone constitutes the main repository for calcium, it plays a vital part in calcium metabolism and any upsets in calcium balance can cause severe bone disease. 3
  • 4. Calcium in the bone mostly is in the form of calcium phosphate and partly as calcium carbonate. The osteoid tissue of bone is manufactured by osteoblasts and after maturation, this osteoid undergoes mineralization with the deposition of calcium salts in the form of Hydroxyapatite. The bone has 2 major functions : i) Mechanical - Supporting the body weight - Providing surfaces for muscle attachment - Protecting vital organs from trauma Eg. Skull protecting brain, Ribcage protecting the heart, lungs etc. ii) Buffer : Prevents wide fluctuations of serum calcium concentration. The ionic calcium level in the serum must remain within narrow range. If there is fall of calcium serum, bone releases calcium. If serum calcium level is high, calcium from serum is deposited in the bone. All these occur under the influence of hormones mainly PTH, Vitamin D (Calcitriol), other hormones like estrogen, calcitonin and chemicals like interleukins (IL). SERUM CALCIUM : The normal serum calcium concentration is between 9-11 mg/100 ml of blood. It exists in 3 forms : i) Ionized calcium : This is the active form and constitutes about 50% of the serum calcium (4.5 mg/100 ml). ii) Protein – bound calcium : Bound mostly to albumin, therefore it is non- diffusible (4 mg/100 ml). iii) Non- ionized, diffusible calcium : Smallest fraction and is present for the most part as citrate. In clinical practice, we only measure the concentration of serum calcium and not of the whole blood because ; 1) Intracellular i.e. inside the RBC  Concentration of calcium is very low. 2) All clinical information can be obtained by estimating calcium serum instead of measuring that of the whole blood. In clinical view : It is only the ionic calcium which matters as they are active. Therefore : - a) In severe hypoprotinemia of blood : Protein bound calcium falls, ionic calcium does not fall. Therefore total serum calcium concentration is low, but still no tetany develops. b) In alkalosis (eg. After severe hyperventilation) the protein bound calcium increases, but ionic calcium decreases. Therefore total serum calcium 4
  • 5. concentration remains unchanged but signs and symptoms of hypocalcemia develops. Lymph Calcium : Lymph has a lower protein content, therefore contains less calcium than blood. CSF Ca 5.3 mg per 100 ml. Has only traces of proteins. Almost whole of CSF Ca is in diffusible active form. Calcium of CSF fluid is constant. SOURCES : Milk and milk products are excellent sources of food calcium. Other sources include water, especially hard water, eggs, cheese and green vegetables. Fish and meat are poor sources. DAILY REQUIREMENTS : The Food and Nutrition Board of the National Academy of Sciences, National Research Council, recommends daily dietary calcium intake : - For newborn infants : 360 mg/day For children and adults : 800 mg/day Adolescents and pregnant : 1200 mg/day women and lactating women ABSORPTION : a) Site of Absorption : Absorption of calcium occurs mainly from upper jejunum and duodenum. The absorption is by : - i) A carrier mediated mechanism ii) Passive diffusion i) Carrier mediated mechanism: The carrier molecule resides in the “brush border” of the jejunal mucosa. A derivative of Vitamin D  1, 25 DHCC (Calcitriol) facilitates this carrier mediated transport. ii) Passive Diffusion : Small amount of calcium is also absorbed via passive diffusion i.e. molecules move according to a chemical gradient i.e. from a solution of higher concentration towards a solution of lower concentration. b) Form of Absorption :  Soluble inorganic forms are much better absorbed.  Thus the organic calcium of food is converted into inorganic form before it can be absorbed.  Insoluble calcium compounds are never absorbed. Therefore presence of phytic acid in cereals produces formation of Caphytate which is insoluble.  Caphosphates are not absorbed. c) Factors Affecting Calcium Absorption : 1) Vitamin D : Increases absorption of calcium from the intestine. 2) Parathyroid hormone : Increases calcium absorption 5
  • 6. 3) Thyroid : Increase calcium absorption 4) Calcitonin : Decreases calcium absorption 5) Steroid hormones : Decreases calcium absorption. Glucocorticosteroids retard calcium absorption from GIT. Earlier, glucocorticosteorid therapy was given for rheumatoid arthritis  resulted in osteoporosis and fracture. 6) Fats (in normal amount) : Increases calcium absorption. But when fats lost through excretion eg. Steatorrhea  Calcium is lost through faeces as Ca soaps. 7) Bile salts : Increases calcium absorption by their hydrotropic action on calcium soaps. 8) High protein diet : Increases calcium absorption. Proteins digested into amino acids Aminoacids + Calcium  Forms soluble calcium compounds. 9) High Phosphorous content in diet : Decreases calcium absorption because it forms insoluble Caphosphate which cannot be absorbed. 10) pH : If pH is decreased i.e. acidic  Increased calcium absorption because calcium salts become soluble in acid medium. If pH is increased i.e. alkaline  Insoluble calcium salts therefore decreased calcium absorption. Lactose increases acidity due to its conversion into lactic acid  Therefore increased calcium absorption. Oxalic acid : Insoluble Caoxalate  Therefore decreased calcium absorption. Spinach contains sufficient oxalic acid  Therefore decreased calcium absorption. Phytic Acid : Commonly present in cereals precipitates calcium in the bowel as insoluble Caphytate. Therefore decreases its absorption. But many vegetables contain phytase which nullifies the inhibitory action of phytic acid. Hydrochloric acid : Increased calcium absorption. Therefore in cases of hypochlorhydria or achlorhydria  Decreased calcium absorption. 11) Sex hormones  Eg. Oestrogen and androgen. Increased calcium absorption. Women during menopause suffer from negative calcium balance i.e. less calcium is absorbed from blood. Excretion : a) Through the faeces b) Through urine a) Faeces : with an ordinary diet, the calcium content in human faeces is about 200 mg daily. This is believed to be totally exogenous (i.e. unabsorbed calcium). b) Urine : About 150-200 mg are excreted through urine mainly in form of calcium chloride and calcium phosphate. The renal threshold for calcium is approximately 7 mg /100 ml of serum calcium. Role of Kidney in Calcium Excretion : 6
  • 7. 4) Diffusible calcium is filterable while protein bound calcium is not. 99% of calcium is reabsorbed mostly in the proximal convoluted tubule and little in the distal part of the nephron. 5) The renal reasborption of calcium in the distal nephron is dependent on PTH. CALCIUM BALANCE : In the adult, the calcium intake and loss are same. This is called calcium balance. - When the intake exceeds the excretion, the person is in positive calcium balance. - Here calcium deposition in bone is occurring. - Seen in cases of during growth, pregnancy, lactation, acromegaly etc. - When the intake is less than excretion, the person is in negative (-ve) calcium balance. - Here there is rarefaction of bones – Osteoporosis. - Seen in cases of rickets, osteomalacia, calcium deficiency, hyperactivity of thyroid and parathyroid etc. FUNCTIONS OF CALCIUM : 1) Bone : Bone rigidity 2) ECF : Clotting of blood 3) ICF : Muscle contraction – Skeletal, Cardiac  Vasospasm of smooth muscle  Neurotransmission 1) Bone : Calcium metabolism in bone has two divisions : • Bone remodeling • Calcium homeostasis a) Bone Remodeling : - Calcium gives strength to bones. - Throughout life, small portions of bone are removed and replaced by new bone deposition. - For bone remodeling – A set of locally acting chemicals like interleukins, prostaglandins, estrogen and other hormones are necessary. - Calcium acts as second messenger for initiation of formation of bone cells namely osteoclasts and osteoblasts which are responsible for bone remodeling. Eg. In orthodontic tooth movement. - When a force is applied onto a tooth, it results in bone deformation and compression of the periodontal ligament. - This leads to the release of some extracellular signaling molecules called FIRST MESSENGERS which include PTH, PG (Chem mediator), VIP (Vasoactive Intestine Polypeptide). 7
  • 8. - These bind to receptors present on cell surface of target cells and initiate a process of intra cellular signaling leads to formation of second messengers which include cyclic AMP, cyclic GMP and calcium. - These 2nd Messengers initiate formation of bone cells namely osteoclasts and osteoblasts which are responsible for bone remodeling. BONE REMODELLING Force ↓ Bone deformation ↓ 1st Messengers (PTH, PG, VIP) ↓ 2nd Messengers  (for cellular permeability) + ↓ Cyclic AMP, cyclic GAMP, Ca. Osteoblasts and ostoeclasts ↓ remodeling Bone Remodeling : Bone resorption and bone deposition. Bone resorption : By osteoclasts (multinucleated giant cells) Ruffled border (produce acids)  Citric acid, lactic acid & H+ ions Decalcification (Protease E) Degradation of matrix Bone deposition : Osteoblasts Osteoid matrix Calcification Bone remodeling is a necessity as it keeps the bone in proper physiological state (neither excessive nor too little). Defective bone remodeling can lead to osteoporosis, brittleness of bone, refusal to unite the fractured bone ends etc. b) Calcium homeostasis : Bone mobilizes calcium ion from itself to restore calcium level of serum when it falls. Calcium deposition occurs in the bone when serum calcium level becomes high. 2) Clotting of Blood : Clotting of blood is an important hemostatic mechanism because the clot formed : 1) Prevents further bleeding. 8
  • 9. 2) Seals the wound against further infection. Normally blood contains 2 sets of materials : 1) Procoagulants – Help in clotting. 2) Inhibitors (anticoagulants) of coagulation  Oppose the clotting. Eg. Heparin present in mast cells. Normally, the effect of the inhibitors dominate but after a cutting injury, at the local site, the effects of pro-coagulants dominate. Mechanism of Coagulation : Fibrinogen is present in blood and it has to be converted to fibrin for blood clot formation. For this conversion factor Xa is necessary. Factor Xa can be produced by any of the 2 paths. - Intrinsic path - Extrinsic path Intrinsic Path : Injury of blood vessels leading to contact of Factor XII with blood vessel. Extrinsic Path : Injury of vascular and other cells causing release of tissue thromboplastin also called tissue factor. INTRINSIC Surface contact ↓ XII XIIa ↓ XI XIa ↓ IX IXa Ca++ Ca++ VIII Phospholipid X Xa Ca++ Phospholipid V (II) Prothrombin Thrombin (IIa) ↓ XIII XIIIa ↓ Fibrinogen Fibrin Stabilized fibrin 9
  • 10. EXTRINSIC Tissue Damage Tissue Factor X Xa V Va VIII II IIa VIIIa I Ia XIIIa Stable Fibrin 3) Muscle contraction : For muscle contraction  myosin filament should get attached with actin muscle filament  for this calcium ions are required. Action potential on Sarcolemma Ca2+ Channels open up Ca release (from ECF to ICF) AP T Tubule Ap to Cistern Ca Release  Normally, in relaxed state, actin filament is covered by tropomyosin which prevents contact of myosin with actin.  Tropomyosin covers the active sites of actin filament which are supposed to bidn with the heads of myosin.  Calcium released after AP, binds with troponin and thus tropomysin moves away. Sites for myosin becomes uncovered  myosin gets attached with active head of actin  Cross bridges are formed  muscle contraction. Excitation – Contraction Coupling : 10
  • 11. AP leads to  Contraction AP excitation electric phenomenon Calcium coupling agents Contraction Mechanical phenomena Calcium acts as coupling agent between AP and contraction. FACTORS AFFECTING THE CALCIUM LEVEL IN BODY : 1) Parathormone : Parathormone is secreted by the chief cells of the parathyroid glands. It is a protein in nature. Actions of PTH : The primary function of parathormone is to maintain the blood calcium level within the critical range of 9 to 11 mg%. 1) It increases the blood calcium level by mobilizing calcium from bone  bone resorption. 2) It decreases the excretion of calcium through the kidneys. 3) It increases absorption of calcium from GIT. 4) It facilitates the conversion of vitamin D into its final product Calcitriol  1, 25 DHCC which causes increase absorption of calcium from GIT. Effects on the Bone : Bone resorption causes Increased calcium in blood Resorption of calcium from bones occurs in 2 phases. - Rapid phase - Slow phase Rapid Phase : - Occurs within minutes after the release of parathyormone from parathyroid glands. - Immediately after reaching the bone, the parathormone gets attached with the receptors on the cell membrane of osteoblasts and osteocytes. - Osteocytic activity - The hormone receptor complex increases the permeability of the membranes of these cells for calcium ions. - This increases the calcium pump mechanism allowing calcium ions to diffuse from these cells into the plasma. Slow Phase : - By activation of ostoeclasts  Osteoclastic activity - Proteolytic enzymes, citric acid and lactic acid are released from these cells. - The organic matrix of bone is dissolved, thus releasing the calcium ions which diffuses into plasma. - PTH causes calcium resorption and phosphate absorption from bones. Effects on the Kidneys : - PTH increases the reasborption of calcium from the renal tubules. - It increases the excretion of phosphates from renal tubules. 11
  • 12. Effects on GIT : - PTH increases absorption of calcium from GIT - This is due to formation of 1, 25 DHCC from Vitamin D by kidney. - PTH increases the absorption of phosphate ion - For absorption of calcium from GIT, Vitamin D is necessary. For activation of Vitamin D, PTH is necessary. Regulation of PTH Secretion : A) Negative feed back Chief cells produce PTH and there are 2 substances which exert a negative feed back effect on the production of PTH. 1) Serum calcium level : Higher the serum calcium level, lower is the production of PTH and viceversa. Chief cells have calcium receptor in their membrane. 2) Calcitriol : Vitamin D is converted into calcitriol by PTH. High calcitriol level inhibits PTH production and viceversa. B) Other Regulators : Plasma phosphates and magnesium levels can also affect the PTH production. VITAMIN D : Vitamin D was discovered in 1910 by McCollum. Source of Vitamin D : 1) From 7 dehydrocholesterol present naturally in the skin. 2) Food sources like fish liver oils, particularly fish liver oils of sea fishes, milk, egg etc. 3) Medicinal Vitamin D Vitamin D - Vitamin D2 : From plant sterols - Vitamin D3 : 7 Dehydrocholesterol, fish liver oils, milk, egg etc. Daily Requirements : For grown up males : Who are exposed to sunshine, may require no dietary supplement of Vitamin D. Pregnant, lactating women, infants, persons confined within indoor, old persons may require Vitamin D supplements. Chapati flour contains much phytic acid and may hinder Vitamin D absorption. Daily supplement of 400 IU (International unit) is recommended. “Multivitamins” sold in India may contain 1000 IU causing dangers of hypervitaminosis D  Hypercalcemia. Cholecalciferol is converted into 25, hydroxycholecalciferol in liver. This process is limited and can be inhibited by 25 HCC itself by feedback mechanism. This inhibition is essential for 2 reasons : a) Regulation of the amount of active vitamin D. b) Storage of Vitamin D for months together. This is because, if Vitamin D3 is converted into 25 hydroxycholecalciferol, it remains in the body only 2 to 5 days. Whereas, Vitamin D3 can be stored in the liver for months together. 12
  • 13. Role of Calcium Ion in Regulating 1, 25 DHCC : If calcium increase in blood, it inhibits the formation of 1, 25 DHCC. The mechanism involved in the inhibition of formation of 1, 25 DHCC is as follows : - a) Increase in calcium ion concentration, directly suppresses the conversion of 25 HCC into 1, 25 DHCC (mild effect). b) Increase in calcium ion concentration  Decreases PTH secretion which suppresses the conversion of 25 HCC into 1, 25 DHCC. This regulates the calcium ion concentration of plasma itself i.e. if the PTH synthesis is inhibited, the conversion of 25 HCC into 1, 25 DHCC is also inhibited. Lack of this in turn, decreases the absorption of calcium ions from the intestine, from the bones and from the renal tubules as well. This makes the calcium level in the plasma to fall back to normal. Functions of Vitamin D : a) On GIT : Calcitirol increases the absorption of calcium and phosphate from the lumen of intestine. One possible mechanism of increased calcium absorption is : Calcitriol has receptors in the cytosol of intestinal epithelium, calcitriol binds with its receptor  this leads to formation of calbindin within these cells  calbindin facilitates transport of calcium from GIT to blood. b) On Bone : Vitamin D deficiency: Demineralization of bone. Therefore conclusion : Vitamin D causes deposition of calcium phosphate in the bone. However, the real picture is ; Direct effect of calcitriol on bone is resorption of bone. But, so much calcium and phosphate are absorbed by the help of vitamin D from the GIT. Mechanism of Bone Resorption by Calcitriol : 1) Calcitriol receptors are present in the osteoblasts but not in the mature osteoclasts. Calcitriol by acting on immature osteoclasts cause increase in number and thus increased activity of mature osteoclasts. Increased osteoclastic activity causes bone resorption. 2) Calcitriol by acting on osteoblasts causes release of ILs (Interluekine) from osteoblasts  ILs by acting on osteoclasts, increase the ostoeclastic activity. 3) Kidney : Vitamin D rather calcitriol, increases the absorption of both calcium and phosphate from the renal tubules. CALCITONIN : - Is secreted by the parafollicular or C cells of the thyroid. - Is a single chain polypeptide hormone containing 32 AA. - Its effects are opposite to those of PTH. i) It inhibits osteoclastic activity  Bone resorption is therefore inhibited. ii) Promotes calcium deposition in bone iii) Lowers serum calcium level. REGULATION OF CALCITONIN LEVEL : High calcium serum stimulates secretion of calcitonin and vice-versa. I.e. feed back mechanism for controlling the plasma calcium ion concentration, works in a way 13
  • 14. opposite to that of parathyroid hormone system. There are two major differences between the calcitonin and parathyroid feed back systems. First the calcitonin mechanisms operates more rapidly, reaching peak activity in less than 1 hour, in contrast to the 3 to 4 hours required for peak activity to be attained after the onset of parathyroid secretion. The second difference is that the calcitonin mechanism acts only weakly and only as a short term regulator to calcium ion concentration because it is rapidly overridden by the much more powerful parathyroid control mechanism. Also, the calcitonin receptors on the osteoclasts seem to down regulate within minutes to hours in response to a calcitonin stimulus. Therefore, over a prolonged period of time, it is almost entirely the parathyroid system that sets the long term level of calcium ions in the ECF. When the thyroid gland is removed, and calcitonin is no longer secreted, the long term blood calcium ion concentration is not measurably altered, which again demonstrates the overriding effect of the parathyroid hormonal system of control. DISORDERS OF CALCIUM METABOLISM : Hypoparathyroidism : Can occur due to accidental damage or removal of the parathyroids during surgery of the thyroid or in cancer of larynx. - Spontaneous hypoparathyroidism can occur which may be hereditary. - DiGeorge syndrome (very rare) – in some cases of hereditary hypoparathyrodisim, more than 1 endocrine gland Eg. parathyroid, ovary, adrenal cortex and thymus may be involved. Pseudohypoparathyyroidism : - PTH level is high but serum calcium level is low. - There is some fault in the PTH receptors of the target cell – Thus producing signs and symptoms characteristic of hypoparathyroidism. TETANY : - The outstanding sign of calcium deficiency is tetany. - When serum calcium level falls, the irritability of nerves and NMJ rises and the muscle contracts when subjected to subthreshold stimulus. - Basic feature of tetany is uncontrolled, painful, prolonged contraction (spasm) of the voluntary muscles. - When the ECF concentration of calcium ions falls below normal, the nervous system becomes excitable because this causes increased neuronal membrane permeability to Na++ ions, allowing easy initiation of action potential. - If calcium concentration in plasma is about 50% below normal, peripheral nerve fibres become so excitable that they begin to discharge spontaneously, initiating trains of nerve impulses that pass to the peripheral skeletal muscles to elicit tetanic muscle contraction. - Tetany occurs in hand before it develops in other parts of the body. This is called carpopedal spasm or Accoucher’s hand. a) Accoucher’s Hand : - There is muscular spasm leading to uncontrolled prolonged flexion of the metacarpophalangeal joints while the fingers remain extended. 14
  • 15. - The term ‘accoucher’ means obstetrician in charge of a labour room (sometimes the obstetrician has to bring out intrauterine contents like retained placenta by fingers. During such procedures, the accouchers hand assumes the above described posture). b) Laryngismus stridulous / laryngeal stridor : - There is spasm of the larynx, the breathing stops and patient tries violently to inspire. - After sometime, the spasm disappears, the air enters the layrnx with a characteristic crowing sound. - This crowing sound during inspiration, after a phase of forcible stoppage is called laryngeal stridor. c) Chvostek’s Sign : Tapping the facial nerve at the ramus of the mandible, in front of the ear, produces painful spasm of the facial muscles. d) Trousseau’s sign : The sphygmomanometer cuff/BP cuff is applied to the upper arm and inflated to above the systolic blood pressure for upto 3 minutes  the hand goes into spasm and develops the posture of accoucher’s hand. Diagnosis : Serum calcium level usually < 7 mg%. Treatment : 1. Temporary measures : Injections of soluble calcium salt. 10 ml of 10% calcium gluconate should be given slow intravenous. 2. Long term measures – Large dose of Vitamin D (100,000 units /day), along with 1-2 gms of calcium. At times it might be necessary to administer 1, 25 DHCC instead of the non-activated form of Vitamin D because of its much more potent and much more rapid action. This can also cause the unwanted effects because it is sometimes difficult to prevent overactivity by the activated form of Vitamin D. NOTE : - PTH injections in tetany are not recommended because too expensive. - Its effect lasts only for a few hours at the most. - Such injections lead to antibody formation against PTH which nullifies the PTH injected. II. HYPERPARATHYROIDISM : Due to increase activity of parathyroids : Classification : - Primary - Secondary - Tertiary Primary Hyperparathyroidism : - Increased PTH  Increased serum calcium Causes : 1) Parathyroid adenoma 2) Hyperplasia 3) Carcinoma. Clinical Features : a) Osteitis Fibrosa Cystica or Von Recklinghausen’s Disease : 15
  • 16. - Here intense osteoclastic resorption leads to destructive cystic changes involving many bones. Bone pain is a prominent symptom, pathological fractures are common, and sometimes tumour –like masses of osteoclasts are formed. - These brown tumours, closely resemble giant cell tumours of bone and are seen typically at sites which normally contain hematopoietic tissue, skull, jaw, ribs and spine. - Called as browns’ tumour because of haemorrhage and hemosiderin pigmentation within the tumour. - The first indication of the condition is a cyst like lesion of the jaw. The radiographic description is of a ‘ground glass’ appearance of the affected bone. There is resorption of bone, and although the lamina dura may be lost, the teeth are not usually affected. b) Generalized osteoporosis c) Death is due to hypercalcemic crisis : There is shock, hemoconcentration, anuria, and death preceded by confusion and coma. d) Renal calculus formation / Nephrolithiasis : Due to increased serum calcium level  there is increased calcium absorption from the kidneys  Patient prone to develope renal stones  can cause renal ischemia. Metastatic calcifications are also seen in other soft tissues like blood vessels. e) Abdominal groans : Calcium stimulates gastrin which is the powerful stimulator of acid which may result in pain abdomen, due to peptic ulcer. f) Psychic moans : Altered mental status ranging from weakness and lethargy to confusion and dementia. Secondary Hyperparathyroidism : Increased PTH, Decreased serum calcium causes a) Renal diseases b) Malabsorption Hyperplasia of the parathyroids occurs in many types of osteomalacia and rickets. In some cases, the PTH secretion is sufficiently marked to initiate osteoclastic activity in the bones, and therefore in addition to the changes or rickets or osteomalacia, there develop those of osteitis fibrosa cystica. Real disease is the usual antecedant. Renal rickets : Chronic renal disease, especially in young people is sometimes attended by skeletal lesions and calcification defects  Osteomalacia and osteitis fibrosa cystica. Tertiary hyperparathyroidism : Increased PTH, Increased serum calcium. Cause : Adenoma or enlargement of gland (Permanent damage). Ectopic parathyroid – Hormone syndrome; A number of patients with malignant disease have hypercalcemia without evidence of metastatic bone disease. This syndrome is due to the elaboration by the tumour of a substance resembling parathyroid hormone. Squamous cell CA of the lung and CA of the kidney are the usual culprits. Diagnosis : 16
  • 17. - Clinical examination of the neck may not reveal any parathyroid enlargement. - Diagnosis by various symptoms - Serum calcium levels are always raised - Serum PTH levels are raised detected by immunoassay  tumour marker. Treatment : 1) Surgical removal of some part of parathyroid gland. 2) Adenoma excision 3) Active Vitamin D metabolism 4) Renal transplantation 5) For renal stones  Solubility of most renal stones is slight in alkaline media, tendency for formation of renal calculi is greater in alkaline urine than in acid urine. Therefore acidic diets and acidic drugs are used for treating renal calculi. HYPOCALCEMIA : The following are important causes of hypocalcemia : 1) Hypoparathyroidism 2) In association with hypoalbuminemia 3) Renal failure : Phosphate retention leads to hyperpohosphatemia and a reciprocal lowering of the plasma calcium. Another important factor is the deficient formation of 1, 25 HCC with a consequent impairment in the intestinal absorption of calcium. 4) Vitamin D deficiency 5) Widespread osteoplastic metastasis – These may utilize so much calcium that hypocalcemia results. The usual primary source of the tumour is the prostate. 6) Infantile hypocalcemia : Neonatal tetany is well recognized and is due to functional immaturity of the parathyroid glands during the first 2 days of life. 7) Acute pancreatitis : Hypocalcemia in this condition can be attributed partly to the deposition of calcium salts in the foci of fat necrosis (dystrophic calcification), and partly to the release of glucagon from the damaged pancreas. Effects of Hypocalcemia : 1) Tetany : Trousseau’s sign Chvostek’s sign Laryngeal stridor Mental disturbances 2) Abdominal pain of obscure origin. It may be due to smooth – muscle spasm. 3) A predisposition to eczema in chronic cases. There is also an increased incidence of candida albicans infections of the skin. 4) Cataract, a well known complication of chronic hypocalcemia. The cause is uncertain. 5) Electrocardiographic changes : A prolonged QT interval principally in the ST segment. Treatment : Same as that of hypoparathyroidism. 17
  • 18. HYPERCALCEMIA : Causes for hypercalcemia : 1) Primary hyperparathyroidism 2) Hypervitaminosis D : excessive administration of vitamin D leads to hypercalcemia and generalized metastatic calcification. The parathyroid – hormone like activity of vitamin D potentiates this action. 3) Vitamin D sensitive states : The hypercalcemia sometimes encountered in sarcoidosis is probably due to increased sensitivity to Vitamin D. 4) Destructive bone lesions : Extensive destruction of the skeleton by osteolytic metastases of carcinoma, multiple myeloma, or Hodgkin’s disease may lead to the release of excessive amounts of calcium. 5) Miscellaneous causes : a) Milk alkali syndrome : Where excess milk and antacids like NaHCO3 are given to treat peptic ulcers. b) Excess thiazide therapy – Like in cases of congestive cardiac failure, can cause hypercalcemic state. c) Prolonged immobilization d) Hyperthyroidism e) Congenital hypophosphatasia Effects of Hypercalcemia : 1) Fatigue, lethargy and muscle asthenia 2) Anorexia, nausea and vomiting. Constipation is prominent, possibly due to the muscular hypotonia. 3) Pruritus 4) Psychotic manifestations 5) Symptoms of progressive renal dysfunction starting with polyuria due to an unresponsiveness of the distal and collecting tubules to antidiuretic hormone. There is an accompanying thirst, which may also be due to the high plasma calcium directly stimulating the hypothalamus. Ultimately leads to disturbances in glomerular function  Renal failure. 6) Metastatic calcification. 7) ECG changes : Shortened QT interval and depressed T waves. 8) Peptic ulceration : The excess plasma calcium releases gastrin. 9) Pancreatitis, both acute and chronic  Common with primary hyperparathyroidism. Etiology is unknown but suggested factors include stones forming in the pancreatic ducts and ioinised calcium favouring the conversion of trypsinogen to trypsin in the pancreatic ducts. VITAMIN D DEFICIENCY : Deficiency of vitamin D may result from : i) Reduced endogenous synthesis due to inadequate exposure to sunlight. ii) Dietary deficiency of Vitamin D iii) Malabsorption of lipids due to lack of bile salts such as biliary obstruction, pancreatic insufficiency and malabsorption syndrome. 18
  • 19. iv) Derangement of Vitamin D metabolism as occur in kidney disorders, liver disorders etc. v) Resistance of end-organ to respond to Vitamin D. Vitamin D Deficiency: - Rickets in growing children - Osteomalacia in adults - Hypocalcemia tetany due to neuromuscular dysfunction Rickets : The primary defects in rickets are : - Interference with mineralisation of bone. - Deranged endochondral and intramembranous bone growth. In the growing child, calcification of the epiphyseal cartilage does not occur at the growing ends of the long bones. The cartilage therefore does not die and instead continues to grow, so that the epiphyses undergo enlargement at the bone ends with greatly delayed ossification. Skeletal Changes : i) Craniotabes : In infants there is thickening of the frontal and parietal eminentia, and flattening and thinning of the occipital region. The skull looks square and box-like. ii) Harrison’s sulcus : Appears due to indrawing of soft ribs on inspiration. iii) Rickety rosary : Deformity of chest due to cartilaginous overgrowth at costochondral junction. iv) Pigeon-Chest Deformity : Is the anterior protrusion of sternum due to action of respiratory muscles. v) Brew Legs : Occur in ambulatory children due to weak bones of lower legs. vi) Knock Knees : May occur due to enlarged ends of the femur, tibia and fibula. vii) Lower epiphyses of radius may be enlarged Treatment : - Supplying adequate calcium and phosphate in the diet. - Administering large amounts of vitamin D. If vitamin D is not administered, little calcium and phosphate are absorbed from the gut. OSTEOMALACIA : - Also called as adult rickets - There is failure of mineralisation of the osteoid matrix Cause of Osteomalacia : - Dietary deficiency - Poor endogenous synthesis of vitamin D. It is more common in women, because pregnancy imposes an additional drain on the supplies of calcium. In the normal adult, bone is continually being remodelled it is removed by osteoclasts and replaced by osteoblasts laying down osteoid which promptly calcifies. If this calcification fails, the bones consist largely of osteoid and the result is osteomalacia i.e. there is an abundance of osteoid but poor calcification. 19
  • 20. (Note : Osteoporosis  Where the matrix is normally calcified but reduced in quantity). Clinical Features : - Muscular weakness - Vague bony pains - Fractures following trivial trauma - Green stick fractures RENAL RICKETS : - Renal rickets is a type of osteomalacia that results from prolonged kidney damage. The cause of this condition is mainly failure of the damaged kidneys to form 1, 25 DHCC, the active form of vitamin D. In patients whose kidneys have been removed or destroyed and who are being treated by hemodialysis, the problem of renal rickets is often a severe one. Another type of renal disease that leads to rickets and oteomalacia is congenital hypophosphatemia resulting from congenitally reduced reabsorption of phosphates by the renal tubules. This type of rickets must be treated with phosphate compounds instead of calcium and Vitamin D, and it is called Vitamin D resistant rickets. TETANY IN RICKETS :In the early stages of rickets, tetany almost never occurs because the parathyroid glands continually stimulate osteoclastic resorption of bone and therefore maintain an almost normal level of calcium in the ECF. However, when the bones finally become exhausted of calcium, the level of calcium may fall rapidly. As the blood level of calcium falls below 7 mg/100 ml of blood, the usual signs of tetany develops and the child may die of tetanic respiratory spasm unless intravenous calcium is administered, which relieves the tetany immediately. OSTEOPOROSIS : Osteoporosis is the most common among all bone diseases in adults, especially in old age. Here there is diminished organic bone matrix rather than poor bone calcification. In osteoporosis, the osteoblastic activity in the bone usually is less than normal and consequently the rate of bone osteoid deposition is depressed. This reduction in bone mass results in fragile skeleton which is associated with increased risk of fractures and consequent pain and deformity.The condition is particularly common in elderly people and more frequent in post-menopausal women. The condition may remain symptomatic or may cause only backache. However more extensive involvement is associated with fractures. Pathogenesis : Osteoporosis is classified into 2 major groups.  Primary – Idiopathic, involutional.  Secondary Primary ostoeporosis : Results primarily from osteopenia without an underlying disease or medication. Increased osteoclastic resorption and slow bone formation. Idiopathic type : - In young and juveniles 20
  • 21. - Less common Involutional type : - Postmenopausal women and elderly people - More common Risk Factors : 1. Sex : More frequent in females than in males. 2. Decreased physical activity: As in old age. 3. Deficiency of sex hormones :  Oestrogen deficiency (Postmenopausal osteoporosis) in women Androgen deficiency in men 4. Combined deficiency of calcitonin and estrogen 5. Hyperparathyroidism 6. Vitamin D deficiency Secondary Osteoporosis : Due to number of factors and conditions. - Immobilization - Chronic anemia - Acromegaly - Hepatic disease - Hyperparathyroidism - Starvation - Medications like administration of anticonvulsant drugs, heparin (large dose). Diagnosis : - Radiographic evidence becomes apparent only after more than 30% of bone mass has been lost. - Levels of serum calcium, inorganic phosphorous and alkaline phosphatase are usually within normal limits. HETEROTOPIC CALCIFICATION : - Is defined as the deposition of calcium salts in tissue other than osteoid or enamel. - Detected by radiographs because of its radiopacity. Heterotopic Calcification can be of 2 types : - Dystrophic calcification - Metastatic calcification DYSTROPHIC CALCIFICATION : It is the deposition of calcium salts in dead or degenerated tissues. Eg. areas of tuberculous necrosis, blood vessels in arteriosclerosis, scars and areas of fatty degeneration. Pathogenesis : This type of calcification is not dependent upon an increase in the amount of circulating blood calcium, but appears to be related to a change in the local condition of the tissues. A local alkalinity in comparison with adjacent undamaged tissues 21
  • 22. appears to be an important factor in initiating the precipitations of calcium in degenerating or non-vital tissues. Clinical Features : It may be found, intraorally in gingiva, tongue or cheek, pulp of teeth. Calcific degeneration of pulp can be classified into 2 types : i) Nodular type - Found in coronal portion of the pulp chamber - Calcification of hyalinized connective tissue - Increase in size of calcium deposition along the collagenous fibrils. ii) Calcitonin around necrotic cells - Radicular portion of pulp canal - Nidus in the centre - Increase in size by concrescence Pulp Stones : - True - False True denticles / pulp stones : Localized masses of calcified tissue that resemble dentin because of their tubular structure. True Pulp Stones : - Free denticle - Attached denticles. Free Denticles : Denticles lying entirely within the pulp tissue and not attached to the dentinal walls are called free denticles. Attached Denticles : Denticles which are continuous with dentinal walls. False Denticles : Localized masses of calcified material and unlike true denticles, do not exhibit dentinal tubules. METASTATIC CALCIFICATION : - Calcium salts are precipitated in previously undamaged tissue. - This precipitation is due to an excess of blood calcium. Sites commonly seen : Kidney - Most frequent and important site - Deposition occurs especially around the tubules, called nephrocalcinosis  can lead to renal failure. - Lung, stomach, blood vessel wall, cornea, etc. Causes of Metastatic Calcification : - Hyperparathyroidism - Excessive absorption of calcium from the bowel - Hypervitaminosis D - Destructive bone lesions  Eg. metastatic carcinoma in bone and multiple myeloma. 22
  • 23. CONCLUSION : Calcium ions play an important role in many physiological functions  bone rigidity, permeability, muscle contraction, blood clotting, and prevention of many disorders. But excess of calcium is harmful to the body. Thus calcium balance in the body should be maintained.    23

×