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39 Cards in this Set
- Front
- Back
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Functions of Bone
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Framework for muscle movement
Protect internal organs and marrow Adapt to changing physical stress Reservoir for Calcium and Phosphate (also contains magnesium and sodium) |
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Mechanical Strength of Bone due to
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light weight
High tensile strength Rigid but not brittle (slightly deformable) Accomplished by mineralization of collagen matrix |
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Growth
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Increase in tissue mass
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Trophic Growth
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= nourishment - size of cells
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Plastic Growth
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to form - number of cells (mitotic)
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Differentiation growth
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acquisition of distinct characters (phenotype)
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Sequential Differential Gene Expression in Growth Processes
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Sequential Differential Gene Expression in Growth Processes
TO Progenitor (committed to a particular line of differentiation) TO Clonal Expansion (mitotic increase in differentiated cell number) |
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Directive Hormone Actions
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-Directive action elicits a specific physiological response
-Transduction activates or inhibits a particular pathway that controls the response |
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Permissive Hormone Actions
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Permissive action makes a target tissue responsive to a different hormone
Does not elicit a specific physiological response by itself Controls synthesis of receptors or response elements in target |
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Growth Hormone (GH or STH)
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stimulates hepatic Insulin-like Growth Factors (IGF) and has a direct influence on substrate mobilization (permissive)
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Insulin-like Growth Factors (IGF)
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directive to bone growth
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Insulin
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metabolic substrates for growth (permissive)
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Fibroblast Growth Factor (FGF)
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fibroblasts collagen deposition, extracellular matrix
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Platelet-derived Growth Factor (PDGF) -
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vascular smooth muscle proliferation
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Glucocorticoids
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Promote osteoblast differentiation
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Prostaglandin E2
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– Local regulation, inhibition of osteoclasts, response to mechanical force
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Cortical (compact) bone
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dense outer layer provides tensile strength
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Trabecular (cancellous) bone
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arbors of bone provide strength against compression and lower bone density (weight)
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Metabolic responses (calcium balance)
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occur mainly on the trabecular bone surfaces and inner (endosteal) surface of the cortical bone
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Membranous bone formation(skull, long bone periosteum)
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– mesenchymal cells differentiate into osteoblasts around cartilage “prototype”
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Endochondral bone (long bone shaft)
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epiphyseal cartilage growth plates form mineralized extracellular matrix followed by surface osteoblast deposition of new bone (primary spongiosa) and replacement of deep spicules (secondary spongiosa)
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Dynamics of Bone Metabolism
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Bone is constantly undergoing remodeling
Local structural modifications respond to mechanical force Systemic endocrine regulation of osteoblasts and osteoclasts maintains serum calcium concentration |
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Osteoblast
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bone forming cells, deposit calcium and phosphate as hydroxyapetite on collagen and osteocalcin matrix
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Osteoclast
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bone “breaking” cells, dissolve hydroxyapetite with lysosomal enzymes to release calcium and phosphate
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Osteocyte
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Mature bone cell trapped within the bone matrix
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Macrophages
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Phagocytic cells that assist in matrix digestion and local hormone production
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To Raise plasma [Ca2+]
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Increase absorption by GI tract
Increase net movement out of bone Increase renal reabsorption of Ca2+ Decrease renal reabsorption of PO43- |
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To Lower plasma [Ca2+]
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Increase net movement into bone
Increase transport out of body |
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1,25 Dihydroxycholecalciferol Vitamin D3
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Nuclear-acting steroid hormone
Promotes Ca2+ mobilization to serum Synthesis stimulated by PTH (low Ca2+) Stimulates intestinal and renal Calcium Binding Protein synthesis (CBP) Promotes bone growth (osteoblasts) Promotes clastogenesis (osteoclasts) Inhibits parathyroid PTH (neg. feedback) |
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Parathyroid Hormone PTH
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Preprohormone (protein) produced by Parathyroid Chief Cells
115 aa 90 aa 84 aa PTH aa1-34 active + aa35-84 inactive Direct response to low Ca2+ (inhibition lost) Short Half-life T1/2 = 3-4 minutes ****Raises serum Ca2+ by indirect stimulation of osteoclasts via induction of IL-6 secretion from osteoblasts |
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Calcitonin CT
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Prohormone (protein) produced by Thyroid Parafollicular C-cells (Clear cells)
Variable sequences yield 32aa CT Direct response to high Ca2+ via cAMP ****Inhibit bone demineralization by osteoclasts Lowers serum Ca2+ |
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CT Transduction
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CT Receptor is homologous to PTH receptor
Uses opposite G-proteins (Gs or Gi) Counter-regulation of same pathways controlled by PTH |
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Indicators of Bone Activity
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Serum Alkaline Phosphatase originates from bone (osteoblasts) and liver (isoform)
Serum osteocalcin (osteoblasts) Urinary hydroxyproline from collagen turnover (60% of body collagen is in bone) |
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Osteomalacia (Ricketts in children
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autosomal recessive, 1 alpha hydroxylase deficiency yields low Vit D3 or defective Vit D3receptor, bone not mineralized
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Hypoparathyroidism
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X-linked (children) autoimmune (adult), no PTH, Vit D3 deficiency, hypocalcemia
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Pseudohypoparathyroidism
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PTH receptor defect, hypocalcemia
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Hyperparathyroidism
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unknown cause, adult, hyperplasia, excess PTH, periosteal demineralization, hyperalcemia
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Paget’s Disease
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autosomal dominant, excessive osteoclast differentiation, bone demineralization, hypercalcemia
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Osteoporosis
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post-menopausal, decrease in PTH, VitD3, and sex steroids, loss of E2 -and DHT-mediated osteoblast apoptosis suppression and osteoclast apoptosis promotion, trabecular demineralization in cancellous bone, extranuclear transduction pathway
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