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Calcium & phosphorous metabolism
Dr. D.V.S. REVATH VYASPG 1ST YEARDEPT OF ORAL MEDICINE AND RADIOLOGY
-INTRODUCTION
-CALCIUM REGULATION IN BODY
-CALCIUM METABOLISM
-FACTORS REGULATING CALCIUM METABOLISM
-TOOTH MINERALISATION
CONTENTS
CONTENTS
-PHOSPHOROUS REGULATION IN BODY
-PHOSPHOROUS METABOLISM
-FACTORS REGULATING PHOSPHOROUS METABOLISM
-APPLIED ASPECTS
The rigidity of skeleton which provides support and
protection for soft tissues, muscle contraction , the
hardness and fitness of the teeth, the stability of the
cell membranes, as activator of many hormones and last
but not the least the heart beat it self, is dependent on
CALCIUM. With its myriads of functions and complex
mechanisms of control, calcium in both ionized and
unionized form is arguably one of the most important
body components.
INTRODUCTION
CALCIUMSymbol : Ca
Atomic number: 20
Atomic weight:40.078g
Group number : 2
Group name: Alkaline earth metal
Colour : Silvery white
Classification: Metallic
1% of total body calcium
TOTAL BODY CALCIUM 1100-1200gms(1.5 % of body weight)
99% in the skeleton 4-5gms in soft tissue 1gm in ECF
NORMAL SERUM CALCIUM 8.8-10.4mg%
PLASMA CALCIUM occurs in 2 forms Diffusible : 5.36mg% or 54-55%
o Ionized 47%o Non-ionized 5%
Non diffusible : 4.64mg% or 45-46%
MOST ABUNDANT MINERAL OF OUR BODY
ESTIMATION OF CALCIUM CONCENTRATION
• Ionized Ca concentration can be estimated from routine laboratory tests, usually with reasonable accuracyeg: plasma Ca is often low - Hypoalbuminemia
plasma Ca increases - Multiple myeloma
• Measured total plasma Ca decreases or increases by about 0.8 mg/dL (0.20 mmol/L) for every 1-g/dL decrease or increase in albumin
8-ounce glass of milk = 300mg of calcium 2 ounces of Swiss cheese = 530mg of calcium 6 ounces of yogurt = 300 mg of calcium
2 ounces of sardines with bones = 240mg of calcium
6 ounces of cooked turnip greens = 220mg of calcium 3 ounces of almonds = 210mg of calcium “Avoid foods causing calcium loss.. For example
excess salt and caffeine”
ADULT MALES AND FEMALES ….800mg
WOMEN DURING PREGNANCY AND LACTATION ….1200mg
INFANTS UNDER 1 YEAR ….360-540mg
CHILDREN(1-18 YEARS) ….800-1200mg
DAILY REQUIREMENTS OF CALCIUM
.
Dietary calcium intake is inversely related to body weight and body fat mass. It has the potential to increase faecal fat excretion to an extent that could be relevant for prevention of weight (re-)gain. (Nutrition Reviews. 66(10):601-
605, October 2007)
Factors Increasing Absorption : - Calcitriol - Paratharmone - Acidity (Low PH)- Growth Hormone - Pregnancy, Lactation - Lactose, Arginine, Lysine
Factors Decreasing absorption : - Oxalates & phytates – form Ca salts - High dietary fats & fibers formm Ca soaps - Phosphates - Alkalinity - Chronic renal failure ( impaired activity of vitamin – D)
CALCIUM REGULATION IN THE BODY
-Before the fifth month of IUL very little calcium is found in the fetus because bone formation is only starting.
-60% of the total deposition occurs in the last trimester which is the period of rapid and extensive ossification
-One year old baby contains about 100 g of calcium, a gain of 70 g over the total calcium content at birth.
-The adult human weighing 70 kg contains about 1.2 to 1.4 kg of calcium that is 1.5% of the body weight, 99% of which is present in bones and teeth.
Mature fetus contains about 30 g of calcium which constitutes about 3 to 4% of maternal calcium
Much greater drainage occurs after birth during lactation
TYPES OF CALCIUM
Calcium in plasma 3 forms:
Ionized (50%) Nonionozed (8-10%) Calcium bound to plasma protein (40-42%)
Calcium in bones: 2 forms:
Rapidly exchangeable calcium Slowly exchangeable calcium
ABSORPTION & EXCRETION OF CALCIUM IN BODY
35-40% of average daily dietary Ca is absorbed from gut, mainly duodenum and first half of jejunum by a carrier mediated active transport under the influence of vitamin D
After oral administration absorption is completed within 4hrs
1000 mg/day
INCREASED BY DECREASED BY Acidity in stomach Calcium phosphate
ratio Hypocalcemia during
pregnancy & lactation Vitamin D3- (1, 25-
DHCC) Parathyroid hormone Lactose
Intestinal alkalinity Excess of oxalate Excess of phytic acid Hypercalcemia Fats Alcohol and smoking Lack of exercise Emotional stability Glucocorticoids
FACTORS AFFECTING CALCIUM ABSORPTION FROM GIT
EXCRETION
• As calcium is both filtered and reabsorbed but not secreted, the rate of renal calcium excretion is calculated as
Renal calcium excretion= calcium filtered – calcium
reabsorbed99% of filtered calcium (Glomerulus) is reabsorbed by the tubules, 1% gets excreted
65% is reabsorbed in proximal tubules, 25-30% in loop of henle and 4-9% in distal and collecting tubules
Daily loss of Ca in sweat is about 15mg.
FACTORS CONTROLLING EXCRETION
• Calcium concentration in the body• PTH (loop of henle and distal tubules)• Plasma concentration of phosphate
↓CALCIUM EXCRETION
↑ PTH ↓ Extracellular fluid
volume ↓ Blood pressure ↑ Plasma phosphate
↑CALCIUM EXCRETION
↓ PTH ↑ Extracellular fluid
volume ↑ Blood pressure ↓ Plasma phosphate
HORMONES INFLUENCING CALCIUM ABSORPTION
• GROWTH HORMONE
• “PROLACTIN (Prolactin has been shown to stimulate intestinal calcium absorption, increase bone turnover, and reduce renal calcium excretion)”
Canadian Journal of Physiology & Pharmacology. 85(6):569-581, June 2007)
• GLUCOCORTICOIDS
FUNCTIONS OF CALCIUM
• Bone and teeth formation• Neuronal activity• Muscle activity• Cardiac activity• Cell division and growth• Blood coagulation• Excitability of nerves and muscles• Maintains integrity of cell membrane
Constituent of bone and teeth
• Calcium and phosphorous are the principal
constituent minerals of bone and teeth.
• They occur in the bone matrix, enamel, dentin and
cementum of teeth mainly as rod shaped or platelet
shaped crystals of calcium hydroxyapatites. These
give the hardness, strength and concrete like elastic
modulus to these tissues
Physiology of bone
• Bone is composed of tough organic matrix that is greatly strengthened by deposits of calcium salts
• Average compact bone contains by weight about 30% matrix and 70% salts
• Organic matrix of bone:
BONE SALTS
The crystalline salts deposited in the organic matrix of bone are composed principally of calcium and phosphate.
The major crystalline salt is known as hydroxyapatite [Ca10(PO4)6(OH)2].
Bone is constantly being reabsorbed and reformed, under the cellular control….
Osteoblasts
Osteocytes
Osteoclasts.
Neuronal activity
Excitation-contraction coupling of all types of muscles
THE ATTACHMENT OF CALCIUM TO TROPONIN AND MOVEMENT OF TROPONIN-TROPOMYSIN COMPLEX RESULTING IN EXPOSURE OF BINDING SITES ON ACTIN MYOSIN CROSS BRIDGING CAUSING A POWER STROKE
Muscle contraction
Membrane permeability
• Ca2+ reduces membrane permeability to ions and water, probably by binding with calmodulin of cell membranes and consequently changing the conformation and hydration of membrane proteins.
Blood coagulation
factors REGULATING CALCIUM METABOLISM
Vitamin D
Calcitonin
Parathyroid hormone
PARATHORMONE
-it provides a powerful mechanism for controlling extracellular calcium and phosphate concentrations
Secreted by Chief cells of parathyroid gland
On blood calcium level:
1. Increases bone resorption/absorbtion
2. Increases renal Ca ++ absorption in distal tubules
3. Increases absorption of intestinal Ca++
On blood phosphate level:
1. Stimulates resorption of phosphate from bone
2. Increases urinary excretion
3. Increases absorption of phosphate from GIT through calcitriol
ACTIONS OF PTH
↓ BONE RESORPTION
↑ URINARY LOSS
↓ 1,25,(OH)2 D PRODUCTION
↓NORMAL BLOOD CALCIUM
↑
↑ BONE RESORPTION
↓ URINARY LOSS
↑ 1,25,(OH)2 D PRODUCTION
SUPPRESS PTH
RISING BLOOD CALCIUM
FALLING BLOOD CALCIUM
STIMULATE PTH↑
↑↑
↑
ON BONE:
- RAPID PHASE - SLOW PHASE
ON KIDNEYS:
ON GASTROINTESTINAL TRACT
Role of PTH in the activation of VITAMIN D
VITAMIN D IS A HORMONE BY CLASSIC CRITERIA: MADE IN ONE PLACE (OR SEQUENTIALLY SEVERAL PLACES!), AND ACTING IN OTHER
DAILY DIETARY ALLOWANCE RECOMMENDED:
- From infancy till puberty is 10 mcg of cholecalciferol (400 IU of vitamin D)- In young adulthood, its 7.5 mcg- After 25 yrs, 5 mcg required
Pregnancy and lactation 10 mcg
ACTIVATION Of VITAMIN D
OCCURS IN TWO STEPS
BONESTIMULATE TERMINAL DIFFERENTIATION OF OSTEOCLASTSSTIMULATE OSTEOBLASTS TO STIMULATE OSTEOCLASTS TO MOBILIZE CALCIUM
KIDNEYIT INCREASES RE-ABSORPTION OF Ca FROM DCT & INCREASES RE-ABSORPTION OF PHOSPHATE ION FROM PCT
ACTIONS OF 1,25-Dihydroxycholecalciferol
1.Increases absorption of Ca from intestine
2.Increases synthesis of Ca induced ATPase in the intestinal epithelium
3.Increases synthesis of alkaline phosphatase in the intestinal epithelium
4.Increases absorption of phosphate from intestine.
Role of Ca ion in regulating 1,25 Dihydroxycholecalciferol
ca ion 25 Dihydroxycholecalciferol
ca ion - PTH secretion
Regulation of PTH secretion:
Blood level of calcium: -inversely proportional conditions when PTH secretion decreases
Blood level of phosphate: - directly proportional
CALCITONIN
• It is a 32 amino – acid polypeptide, secreted from clear cells or parafollicular cells of thyroid glands therefore also, known as THYROCALCITONIN
• It is not secreted until the plasma calcium exceeds 9.5mg/dl
• Normal secretion is 0.5mg/day; • half life less than 15 mins; • molecular weight 3000;• Normal plasma level 0.2ngm/ml
ACTIONS
ON BLOOD CALCIUM LEVEL-It reduces the blood calcium concentration
ON BONE Stimulates osteoblastic activity Inhibits osteoclastic activity
Increases excretion of Ca through urineInhibits reabsorption of Ca from renal tubules
ON GITInhibits intestinal absorption of Ca++and PO4
---
ON KIDNEYS
ON BLOOD PHOSPHATE LEVEL-
On bones: Inhibits resorption of phosphate from bone
On kidneys: Increases excretion of phosphate through urine
PTH 1,25-DHCC CT
ON BONE Bone resorptionincreases
Mobilize Ca & P
Bone resorptiondecreases
ON GIT Ca & P absorptionincreases
Ca & P absorption increases
Ca & P absorption decreases
ON KIDNEY P absorption decreasesCa reabsorption increases
Ca resorption increases
1,25-DHCC decreasesCa & P excretion increases
ON S.Ca+2 Increases Increases Decreases
ON S.PO4-3 Decreases Increases Decreases
Applied physiology –
Disorders of parathyroid glands ( two types )
1. HYPOPARATHYROIDISM -causes: Parathyroidectomy Thyroidectomy Deficiency of receptor for PTH
2. HYPERPARATHYROIDISM Primary hyperparathyroidism Secondary hyperparathyroidism Tertiary hyperparathyroidism
Hypoparathyroidism- Hypocalocemia
Hypocalcemic tetany: signs and symptoms 1. hyper-reflexia and convulsions 2. carpopedal spasm 3. laryngeal stridor 4. cardiovascular changes 5. other features
Late or subclinical tetany: 1. trousseau’s sign 2. chvostek’s sign 3. erb sign
Hyperparathyroidism- hypercalcemia signs and symptoms: 1. depression of the nervous system 2. sluggishness of reflex activities 3. reduced ST segment and QT interval in ECG 4. lack of appetite 5. constipation
Parathyroid function tests: Measurement of blood Ca level Chvostek’s sign and trousseau’s sign for hypoparathyroidism
CALCIUM AND DENTAL CARIES
if it occurs when teeth are still forming, following abnormalities may occur:
-Enamel hypoplasia-Poorely mineralised dentin-Malformed teeth-Elongated pulp chambers-Anodontia or impacted teeth
CALCIUM AND SALIVA
• Calcium content of submandibular saliva is almost double the parotid content. This probably contributes to marked prevalence of calculus on lingual aspect of mandiblular incisors
• Concentration of calcium lessens as salivary flow increases. This probably results from the increased parotid contribution in rapid salivary flow rates
-Principal salivary calcium phosphates salts are dicalcium phosphate dihydrate, octacalcium phosphate, tricalcium phosphate and hydroxyapatite
Phosphorous
Symbol : PAtomic number: 15Atomic mass:
30.97376amuMelting point: 44.1o C
(317.25K, 111.38o F)Boiling point: 280.0oC
(553.15K, 536.0oF)ColourClassification: Non-metal
: White
PHOSPHOROUS• Key element in all the known forms of life
• Plays a major role in biological molecules such as RNA and DNA
• Main structural component of all the cellular membranes
• Living cells also utilize phosphate to transport cellular energy via ATP
• Average person contains little less than 1 kg of phosphorous, about 3quater present in bones and teeth in form of apatite crystal
PHOSPHATE METABOLISM
It is found in ATP, cAMP, 2, 3-DPG (diphosphoglyceric acid)
Total body phosphate is 500-600gms, 80-85% is in skeleton Remaining is in intracellular phosphate
pool.
Serum inorganic phosphate level:In adults: 2.5-4mg%In children: 5-6mg%
Sources of Phosphorus
Phosphorus: Requirements
Adequate Intake•0-6 months 100 mg/day•6-12 months 275 mg/day
Estimated Average Requirements•1-3 years 380 mg/day•4-8 years 405 mg/day•9-18 years 1,055 mg/day•19-70+ years 580 mg/day•Pregnant & Same as for nonpregnant & lactating women nonlactating women
Reference : Dietary Reference Intakes, Food and Nutrition Board, National Academy of Sciences-Institute of Medicine, 1997
DistributionTotal phosphate:500-
800 mg
Bones and teeth 80-85%
Inorganic(0.5-1mg/dl)
(Adults:3-4mg/dl)
(children:5-6mg/dl)
Normal plasma levels: 2.5-4.5 mg/dl
Organic
Phosphate Absorption
Mechanism– co-transport NaP is absorbed in duodenum and
other parts of small intestine by active transport and passive diffusion.
DISTRIBUTION AND FATE
Approximately 3mg/kg/day of Phosphorous enters the bone .
In plasma is filtered in glomeruli of which 85-95% gets reabsorbed actively in PCT. Its excretion in urine is:
INCREASED BY: Vitamin D excess;
hyperparathyroidism; high phosphate diet.
DECREASED BY: GH, during lactation; hypoparathyroidism; low phosphate diet.
DAILY REQUIREMENT OF PHOSPHOROUS
EXCRETION OF PHOSPHOROUS
• It is excreted in urine and feaces
• Urine phosphate constitutes about 60% of total excretion and rest is excreted in feaces.
Infant 240 - 400mgChildren 800 - 1200mg/day
Adults 800mg/day
Pregnancy & Lactation 1200mg/day
IN BONE
STRUCTURAL COMPONENT
INTERMEDIATE METABOLISM
GENETIC MATERIAL
FUNCTIONS OF PHOSPHOROUS
Important Functions to note are………..
Gives rigidity to bones and teeth
Helps in regulation of pH of blood
In regulation of glycolysis and energy metabolism
Forms a part of DNA, RNA, Phospholipids & nucleotides.
PHOSPHATE TURNOVER
Overview of Phosphate Balance
Conditions arising from disruption / irregularities of phosphate metabolism
Etiologies of Hyperphosphatemia
Increased GI Intake :Fleet’s Phospho-Soda
Decreased Urinary Excretion :Renal FailureLow PTH (hypoparathyroidism)
Thyroidectomy Autoimmune hypoparathyroidism
Cell Lysis :RhabdomyolysisTumor lysis syndrome
Etiologies of Hypophosphatemia
Decreased GI Absorption
Decreased dietary intake Diarrhea / Malabsorption Phosphate binders (calcium acetate, Al & Mg containing antacids)
Decreased Bone Resorption / Increased Bone Mineralization
Vitamin D deficiency / low calcitriolHungry bones syndromeOsteoblastic metastases
Increased Urinary Excretion
Elevated PTH (as in primary hyperparathyroidism)
Vitamin D deficiency / low calcitriolFanconi’s syndrome
Internal Redistribution (due to acute stimulation of glycolysis)
Refeeding syndrome (seen in starvation, anorexia, and alcoholism)
During treatment for Diabetic keto acidosis
Etiologies of Hypophosphatemia
Applied physiology
Rickets • Age• Site• Pathology -
calcium phosphate
Dental findings in Rickets
Rickets causes hypoplasia or hypocalcification
Pigeon chest deformity
Rachitic rosary
Knock knees and bow legs
Harrisons sulcus & lumbar lordosis
OSTEOMALACIA OR ADULT RICKETS
• The amount of mineral accretion in bone per unit bone matrix is deficient due to inadequate absorption of Ca and decreased amount of phosphorous owing to deficiency of vitamin D&C in diet.
• Disease is limited to females, usually after multiple pregnancies &lactation but symptoms tend to clear up after lactation is completed.
• The bones especially pelvic girdle, ribs & femur become soft, painful & deformed.
PSEUDOHYPOPARATHYROIDISM
The patients have normal parathyroid glands, but they fail to respond to parathyroid hormone or PTH injections
Autosomal dominantSymptoms and signs
HypocalcemiaHyperphosphatemiaCharacteristic physical appearance: short stature, round
face, short thick neck, obesity, shortening of the metacarpals
Resistance to parathyroid hormone
Symptoms begin in children of about 8 yearsTetany and seizuresHypoplasia of dentin or enamel and delay or absence of
eruption occurs in 50% of people with the disorder
Rx: Vitamin D and calcium Adequate amount of phosphorous in diet
PSEUDOHYPOPARATHYROIDISM
Pseudohypoparatyhroidism- induced dental anomalies
-ENAMEL HYPOPLASIA-DENTIN DYSPLASIA-SHORT BLUNTED ROOTS-IMPACTED TEETH-ALTERED TOOTH ERUPTION PATTERN-PARTIAL ANODONTIA Elfin facies
Osteoporosis
Osteoporosis
osteoporosis
PRIMARY HYPERPARATHYROIDISM
• Women (especially postmenopausal) are more commonly affected than men (Scutellari et al, 1996).
• Causes– SPORADIC ADENOMA(s) MOST COMMON CAUSE– MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 (MEN-1):
PARATHYROID TUMORS (AND PITUITARY AND PANCREAS)
– MEN-2a: PARATHYROID TUMORS, MEDULLARY THYROID CANCER (OR HYPERPLASIA), AND PHEOCHROMOCYTOMA
– FAMILIAL HYPERPARATHYROIDISM: 1o HPT WITHOUT THE OTHER TUMORS SEEN IN MEN-1 OR MEN-2a
– FAMILIAL BENIGN HYPOCALCIURIC HYPERCALCEMIA
Characterized by:
• ↑ serum Ca2+• ↓ serum phosphate
• ↑ urinary phosphate excretion (phosphaturic effect of PTH)
• ↓ urinary Ca2+ excretion (caused by ↑ Ca2+ reabsorption)
• ↑ urinary (nephrogenous) cAMP• ↑ bone resorption
• Osteoblastic activity increases in an attempt to make for the resorbed bone. They secrete large quantities of alkaline phosphatase
Clinical features
“Painful Bones, Renal Stones, Abdominal Groans, Psychiatric Moans”
• Pain Due To # Of Bones
• Renal Stones (Nephrolithiasis) With Pain And Obstructive Uropathy
• GI Disturbances -Constipation, Pancreatitis, Nausea,
Peptic Ulcrs
• CNS Alterations Including Depression, Lethargy And
Seizures
• Neuromuscular Abnormality Including Weakness And
Hypotonia
• Metastatic calcifications seen in subcutaneous soft tissues, sclera, dura and region around joints
• Brown tumor
• Affect mandible, clavicles, ribs and pelvis
• Osteitis fibrosa cystica- develops from central degeneration and fibrosis of long standing brown tumor
Clinical picture of browns tumour
Brown tumour
Dental Features of Browns Tumour
Histo-pathological features of browns tumour
Radiological features
• First radiological sign is subperiosteal resorption of phalanges of index and middle fingers
• Unilocular or multilocular cystic radiolucencies in bone
• Generalized Attenuation or loss of lamina dura surrounding the teeth
• Decrease in trabecular density and blurring of normal trabecular pattern, giving ‘ground glass’ appearance
Granular appearance of skull in patient having renal osteodystrophy
Solitary “punched out” radiolucency in calvarium represents a Brown tumour in secondary hyperparathyroidism
Generalized Loss Of Lamina Dura
Metastatic calcifications in hand and wrist of patient with primary hyperparathyroidism
Detail of calcification adjacent to thumb
Right humerus shows coarse internal trabeculation in primary hyperparathyroidism
Osteitis fibrosa cystica:Multilocular radiolucencies in skull
Treatment:
• Hyperplastic parathyroid tissue or functional tumor is removed surgically to reduce PTH levels to normal
SECONDARY HYPERPARATHYROIDISM
• Secondary hyperparathyroidism results in excess secretion of parathyroid hormone due to parathyroid hyperplasia compensating for a metabolic disorder that has resulted in retention of phosphate or depletion of the serum calcium level
(Ganibegovic, 2000).
• Renal osteodystrophy refers to skeletal changes that result from chronic renal failure
• In patients with secondary hyperparathyroidism caused by end stage renal disease, striking enlargement of jaw occurs
Palatal enlargement is a characteristic of renal osteodystrophy associated with secondary hyperparathyroidism
• Bone lesions in digits, clavicle
• Mottling of skull, erosion of the distal clavicle, rib fractures and necrosis of femoral head.
• Children show osteomalacia
Treatment
• Restriction of dietary phosphate• Use of phosphate binding agents (calcium carbonate or
calcium acetate)
• Use of calcimimetic agents like cinacalcet (Nephrol Dial Transplant (2002) 17: 204-207)
• Treatment with an active vitamin D metabolite• Synthetic salmon calcitonin can be used
• Renal transplant: An ideal treatment
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
–Textbook of Endodontics - Ingle
Thank you…