Bone Physiology, Hormonal Control of Calcium Metabolism, and Osteoporosis
Bone physiology & regulation of calcium metabolism
-
Upload
mohan-phaneendra-akana -
Category
Education
-
view
110 -
download
1
Transcript of Bone physiology & regulation of calcium metabolism
![Page 1: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/1.jpg)
BONE PHYSIOLOGY & REGULATION OF CALCIUM METABOLISM
-MOHAN PHANEENDRA AKANA 9TH SEMESTER 2012 BATCH ROLL NO:2 NOV 5TH 2016
![Page 2: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/2.jpg)
ORGANIC & INORGANIC CONSTITUENTS OF BONE
MATRIX• ORGANIC MATRIX: 35% GROUND SUBSTANCE GAGs , Proteoglycans , water GLYCOPROTEINS OSTEONECTIN , OSTEOCALCIN TYPE II COLLAGEN
• INORGANIC IONS : 65 % CALCIUM + PHOSPHATE + HYDROXYL IONS = Ca10(PO4)6(OH)2 {CALCIUM HYROXYAPATITE}
![Page 3: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/3.jpg)
REQUIREMENTS FOR BONE GROWTH
• CALCIUM• PHOSPHORUS• VITAMIN D & CALCITRIOL• PTH• CALCITONIN• VITAMIN A (FOR GROUND SUBSTANCE)• VITAMIN C• SEX STEROIDS• AMINOACIDS
![Page 4: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/4.jpg)
MARKERS OF BONE DISEASE• GENERAL MARKERS: SERUM CALCIUM SERUM INORGANIC PHOSPHORUS SERUM MAGNESIUM URINARY EXCETION OF Ca & P TOTAL ALKALINE PHOSPHATASE TOTAL ACID PHOSPHATASE
![Page 5: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/5.jpg)
• MARKERS OF BONE RESORPTION: TARTARATE RESISTANT ACID PHOSPHATASE(TRAP) TELOPEPTIDES & PYRIDINIUM CROSS LINKS DERIVED FROM
COLLAGEN URINARY HYDROXYPROLINE EXCRETION SERUM CARBOXY TERMINAL TELOPEPTIDE OF TYPE-1 COLLAGEN (s-
CTx) N-TELOPEPTIDE OF TYPE-1 COLLAGEN
![Page 6: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/6.jpg)
• MARKERS OF BONE FORMATION: SERUM BONE SPECIFIC ISOENZYME OF ALKALINE PHOSPHATASE SERUM OSTEOCALCIN PROCOLLAGEN TYPE-1 PEPTIDASE
![Page 7: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/7.jpg)
CELLS INVOLVED IN BONE PHYSIOLOGY
• OSTEOPROGENITOR CELLS
• OSTEOBLASTS & LINING CELLS
• OSTEOCYTES
• OSTEOCLASTS
![Page 8: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/8.jpg)
OSTEOPROGENITOR CELLS• Pleuripotent mesenchymal cells
• Vicinity of all bone surfaces
• Stimulated by growth factors
• Differentiated into osteoblasts
• By the process,RUNX2/CBFA1 transcription factor network & WNT/B-catenin signaling pathway
![Page 9: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/9.jpg)
OSTEOBLASTS & LINING CELLS• Locate on the surface of the cells
• Synthesize , transport & arrange many proteins of matrix
• Initiate the process of mineralization
• Posses receptors that bind regulatory harmones ,cytokines , growth factors ,extracellular matrix proteins
![Page 10: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/10.jpg)
• Several factors that regulate the differentiation & function of osteoclasts
• If these are surrounded by newly deposited organic matrix , they transform into osteocytes
• DEPOSIT BONE: RANDOM WEAVE WOVEN BONE ORDERLY LAYERED MANNER LAMELLAR BONE
![Page 11: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/11.jpg)
OSTEOCYTES• Communicate with each other on the bone surface by means of
CANALICULI
• Control of calcium & phosphate levels
• mechanotransduction
![Page 12: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/12.jpg)
OSTEOCLASTS• Responsible for bone resorption
• M-CSF,IL-1,TNF(CYTOKINES & GF)HUMAN OSTEOCLAST DIFFERENTIATION & MATURATION
• Binds to bone surface by INTEGRINS
• Forms resorption pit(RESORPTION BAYS or LACUNAE OF HOWSHIP)
• Removes mineral by generating an acidic environment utilizing proton pump system & digests the organic component by releasing PROTEASES
![Page 13: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/13.jpg)
PARACRINE MOLECULAR MECHANISM
1)The transmembrane receptor RANK (RECEPTOR ACTIVATOR FOR NF-KB)
2)RANK LIGAND(expressed on osteoblasts & marrow stromal cells)
3)OSTEOPROTEGRIN
• NF-KBGENERATION & SURVIVAL OF OSTEOCLASTS• TYROSINE KINASE ACTIVITYGENERATION OF OSTEOCLASTS• BONE RESORPTION & BONE PRODUCTION DEPENDS ON RANKL:OPG RATIO
![Page 14: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/14.jpg)
![Page 15: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/15.jpg)
MARROW STROMAL CELLS
WNT PROTEINS
BINDS TO LRP-5 & LRP-6 RECEPTORS ON OSTEOBLASTS
ACTIVATION OF B-CATENIN PRODUCTION
OSTEOPROTEGRIN
![Page 16: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/16.jpg)
PROTEINS OF BONE MATRIX• OSTEOBLAST DERIVED PROTEINS: TYPE-1 COLLAGEN CELL ADHESION PROTEINSOSTEOPONTIN FIBRONECTIN THROMBOSPONDIN CALCIUM BINDING PROTEINSOSTEONECTIN BONE SIALOPROTEIN PROTEINS INVOLVED IN MINERALIZATIONOSTEOCALCIN ENZYMES COLLAGENASE,ALKALINE PHOSPHATASE
GROWTH FACTORS IGF-1,TGF-B,PDGF CYTOKINES IL-1,IL-6,RANKL
![Page 17: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/17.jpg)
• PROTEINS CONCENTRATED FROM SERUM: B2-MICROGLOBULIN ALBUMIN
![Page 18: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/18.jpg)
BONE MODELING,REMODELING &PEAK BONE MASS
• Local collection of osteocytes , osteoblasts & osteoclasts work together to control bone formation and resorption creating a functional unit
BASIC MULTICELLULAR UNIT(BMU)
![Page 19: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/19.jpg)
EARLY IN LIFE
BONE FORMATION PREDOMINATES
SKELETON GROWS & ENLARGES
MODELING
LATER IN LIFE
SKELETAL MATURITY
BREAKDOWN & RENEWALOF BONE
SKELETAL MAINTAINANCE
REMODELING
![Page 20: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/20.jpg)
BONE GROWTH & DEVELOPMENT INTIAL BONES ARE CARTILAGENOUS
OSTEOCLAST-TYPE CELLS REMOVAL OF CARTILAGE
ENCHONDRAL OSSIFICATION
![Page 21: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/21.jpg)
• PRIMARY CENTRE OF OSSIFICATION: periosteum in the mid-shaft generates osteoblasts that deposit the beginning of cortex
• SECONDARY CENTRE OF OSSIFICATION:• sequence of events occurs in the EPIPHYSIS,resulting in the removal
of cartilage & deposition of bone in centrifugal fashion
• GROWTH PLATE: A plate of cartilage entrapped between centres of ossification
![Page 22: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/22.jpg)
FACTORS REGULATING CALCIUM LEVEL
• 3 HARMONES: VITAMIN-D PARATHARMONE CALCITONIN
• 3 PRINCIPAL TISSUES: INTESTINES KIDNEYS BONE
![Page 23: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/23.jpg)
STEPS IN VITAMIN-D3(CALCITRIOL) METABOLISM
• Photochemical synthesis of VIT-D from 7-dehydrocholestrol in the skin & absorption of VIT-D from foods & supplements in the gut
• Binding of VIT-D from both sources to PLASMA ALPHA 1 GLOBULIN (D-Binding protein or DBP) & transport to liver
• Conversion of VIT-D into 25-HYDROXY CHOLECALCIFEROL(25-OH-D) in the liver,through the effect of 25-Ohases
• Conversion of 25-OH-D into 1,25-DIHYDROXYVITAMIN D
![Page 24: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/24.jpg)
![Page 25: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/25.jpg)
• VITAMIN-D is acting independently on bone• VIT-D increases & activity of OSTEOBLASTS , the bone forming cells• CALCITRIOL stimulates
osteoblast
secrete ALKALINE PHOSPHATASE
the local concentration of phosphate is increased
Ionic product : calcium + phosphorus mineralization
![Page 26: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/26.jpg)
PARATHARMONE(PTH) PTH activates adenyl cyclase to form cAMP
cAMP increases synthesis of lysosomal enzymes
Enzymes break the bony organic matrix and releases calcium
Net effect of PTH is increase serum Ca & decrease serum phosphate
![Page 27: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/27.jpg)
CaSR
![Page 28: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/28.jpg)
PARATHARMONE
• BONE OSTEOCLASTS
DEMINERALIZATION &DECALCIFICATION
NUMBER INCREASED RELEASE OF LACTATE SECRETION OF COLLAGENASE
SOLUBILIZES COLLAGEN LOSS OF BONE MATRIX & RESORPTION
![Page 29: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/29.jpg)
![Page 30: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/30.jpg)
CALCITONIN• Calcitonin decreases serum calcium level
• It inhibits resorption of bone
• It decreases the activity of osteoclasts and increases that of osteoblasts
• PTH & CALCITONIN are directly antagonistic
![Page 31: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/31.jpg)
![Page 32: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/32.jpg)
VITAMIN-DSTIMULATIONelevated PTH Decreased serum calciumdecreased serum phosphate
INHIBITIONDecreased PTH Increased serum calcium increased serum phosphate
PARATHORMONE(PTH)STIMULATIONdecreased serum ca levels
INHIBITIONelevated serum ca levels and 1,25(OH)2D
CALCITONINSTIMULATIONIncreased Calcium levels
INHIBITIONDecreased serum calcium levels
![Page 33: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/33.jpg)
CLINICAL PEARLS• OSTEOPOROSIS
• PAGET’S DISEASE
• OSTEOPETROSIS
• OSTEOMALACIA
• RENAL RICKETS
![Page 34: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/34.jpg)
OSTEOPOROSIS• Most common metabolic bone disease.
• Rate of resorption > rate of bone formation.
• SERUM CALCIUM• SERUM PHOSPHATE NORMAL LIMITS• ALKALINE PHOSPHATASE{if there is hypercalcemia primary hyperparathyroidism should be ruled out}
![Page 35: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/35.jpg)
PAGET’S DISEASE• Osteoclasts become abnormally activated
• Irregular pattern of resorption
• Intense osteoblastic response with irregular new bone formation is seen.
• ELEVATED ALKALINE PHOSPHATASE LEVELS
• SERUM Ca & PHOSPHATE LEVELS ARE USUALLY NORMAL
![Page 36: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/36.jpg)
OSTEOPETROSIS
• Rare hereditary disorder .
• Defective osteoclastic function and overgrowth of bone.
• SERUM ALKALINE PHOSPHATASE & PTH ARE INCREASED
• SERUM CALCIUM IS USUALLY NORMAL
![Page 37: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/37.jpg)
OSTEOMALACIA• Bone softening of bone in adult due to deficiency of vitamin D.
• when vitamin d is lowdecreased resorption and decreased absorption from intestine.
• LOW SERUM Ca LEVEL & PHOSPHATE
• ALKALINE PHOSPHATASE IS HIGH
![Page 38: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/38.jpg)
RENAL RICKETS [RENAL OSTEODYSTROPHY]
Patients with chronic renal failure
Liable to bone change that affect bone formation and mineralization Signs of secondary hyperparathyroidism is severe
Biochemical features like low serum calcium &high serum phosphate
![Page 39: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/39.jpg)
• ELEVATED ALKALINE PHOSPHATASE LEVELS.
• URINARY EXCRETION OF CALCIUM AND PHOSPHATE IS DIMINISHED
• PLASMA PTH IS RAISED.
![Page 40: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/40.jpg)
REFERENCES:• PATHOLOGIC BASIS OF DISEASE– ROBBINS & COTRAN (8TH EDITION)
• TEXT BOOK OF BIOCHEMISTRY FOR MEDICAL STUDENTS-DM VASUDEVAN(6TH EDITION)
• HARRISON’S PRINCIPLES OF GENERAL MEDICINE (19TH EDITION)
• TEXT BOOK OF HUMAN HISTOLOGY--INDERBIR SINGH (6TH EDITION)
• HUMAN EMBRYOLOGY– INDERBIR SINGH (9TH EDITION)
![Page 41: Bone physiology & regulation of calcium metabolism](https://reader036.fdocuments.us/reader036/viewer/2022062823/58737f821a28ab272d8b47cd/html5/thumbnails/41.jpg)
THAN’Q’ 1 & ALL
NO SUPER COMPUTER IS SUPERIOR THAN HUMAN BRAIN,ONLY THING IS WE HAVE TO SORT OUT OUR OWN PASSWORD!!!