M edSci 4 10/8/08 Slide 1 Slide 2 Bone LECTURE 4 — Structure and Function Learning Outcomes Outline • Rigid for support and transmission of forces To be able to: • Properties of Bone • General structure 1. list the names and functions of the principal bone cells 2. describe the events of the principal stages of bone formation 3. state the origin of new bone cells in growth and repair 4. Outline the hormonal regulation of serum calcium concentration. • Bone formation – Roles of cells • Bone as a calcium reservoir • Calcium regulation (bone) Medic al Sc ienc es Physiology 2008/09 • Rigidity conferred by large concentration of inorganic calcium salts in the matrix • Important role as calcium reservoir. Stanfield & Germann 21.11 1 Medic al Sc ienc es Physiology 2008/09 Dr Alan Tuffery — Physiology 2 Dr Alan Tuffery — Physiology Slide 3 Slide 4 Cells and Terminology Bone Formation Osteoblasts Chondrocyte in lacuna • Most commonly by replacement of cartilage – i.e. ‘intracartilaginous ossification’ • Two processes: • No blood vessels • Semisolid matrix • Little/no Ca2+ salts 1. Increase in length of the ‘bone’ • by addition of cartilage on outside 2. Replacement of cartilage by bone • at epiphyseal disc. Medic al Sc ienc es Physiology 2008/09 Dr Alan Tuffery — Physiology • Anatomical bone – Epiphysis — heads of the bone – Diaphysis — shaft of the bone www.gcarlson.com Hyaline cartilage • Chondrocytes — cartilage cells • Bone cells – Osteoblasts — immature, boneforming cells; become… – Osteocytes — mature bone cells; maintain bone – Osteoclasts — break down bone Osteoclasts • Trabeculae/spicules — little spikes of cartilaginous matrix/bone. 3 Medic al Sc ienc es Physiology 2008/09 4 Dr Alan Tuffery — Physiology 1 M edSci 4 10/8/08 Slide 5 Slide 6 Growth of Cartilage Summary of Bone Formation Ross Fig. 8.12 • Growth in length by addition of cartilage • Formation of bone under periosteum (CT sheath) • Primary ossification centre • Bone formation at interface • Secondary ossification centre creates epiphyseal disc • Removal of discs — growth stops. Sherwood 18-11 Medic al Sc ienc es Physiology 2008/09 5 Medic al Sc ienc es Physiology 2008/09 Dr Alan Tuffery — Physiology 6 Dr Alan Tuffery — Physiology Slide 7 Slide 8 Erosion of Bone Bony spicule osteocyte Mature (compact) Bone • Structural units — osteons — • Erosion of bony spicules by osteoclasts — marrow osteoblasts osteoclast • cylinders composed of bony lamellae (rings) • large, eosinophilic (red), multinucleate; • Enclosed osteoblasts are osteocytes • Osteons are dynamic • Central and transverse canals contain blood vessels and nerves. • (Marrow cavity filled with early blood cells). Sherwood 19-20 Medic al Sc ienc es Physiology 2008/09 Dr Alan Tuffery — Physiology 7 Medic al Sc ienc es Physiology 2008/09 8 Dr Alan Tuffery — Physiology 2 M edSci 4 10/8/08 Slide 9 Slide 10 Remodelling of Bone Bone and Calcium Regulation Bone Turnover (Susan Ott, 2006) • In bone formation • 99% of body’s calcium is in bone (~1 kg) – Bone formed on cartilaginous trabeculae – Bony spicules eroded by osteoclasts – Bone added on outside (periosteum) – Bone removed from inside (endosteum) • Stable calcium-ion concentration [Ca2+] in interstitial fluid vital for membrane function Sherwood. 19-21 Ground section • Throughout life – Bone responds to forces – Bone is Ca2+ reservoir. http://courses.washington.e du/bonephys/ophome.html 9 Medic al Sc ienc es Physiology 2008/09 Dr Alan Tuffery — Physiology • Calcium-ion concentration maintained by balance of osteogenic and osteoclastic activity. Spaces (lacunae) occupied by osteocytes and their processes (in canaliculi) are filled with carbon in preparation See Sherwood pp 735-740 10 Medic al Sc ienc es Physiology 2008/09 Dr Alan Tuffery — Physiology Slide 11 Bone & Calcium Slide 12 (negative feedback loop) Parathyroid Hormone (PTH) Write down the item next to italics PTH is vital Stimulus — [Ca2+] falls • Two Ca2+ compartments 1. Controlled variable – Bone fluid 2. Sensor • fast exchange — pumps – Mineralised bone [Ca2+]IF 3. Integrator Sherwood. 19-21 • Slow — osteoclasts. PTH 4. Signal 5. Effectors 2+ pumps, osteoclasts Osteoclast Ca 6. Compensatory response Medic al Sc ienc es Physiology 2008/09 Dr Alan Tuffery — Physiology 11 Sherwood Dr Alan Tuffery Fig. 1-7 — Physiology Medic al Sc ienc es Physiology 2008/09 [Ca2+]IF rises. 12 3 M edSci 4 10/8/08 Slide 13 Do not attempt to learn this! Slide 14 Hormonal Regulation of Bone Bone Growth Increased growth Vitamin D – Promotes differentiation of osteoblasts Growth Hormone – Increase osteoblast function Decreased breakdown Oestrogen – Inhibits osteoclasts Calcitonin – Inhibits osteoclast function (minor role in Ca2+ Vitamin D (cholecalciferol) An example of complex interactions Bone Loss Increased breakdown Parathyroid hormone (PTH) • A (steroid) hormone – stimulates osteoclasts Thyroid absorption from gut – Stimulates osteoclasts • PTH increases Vitamin A Vitamin D activation – Stimulates osteoclasts Decreased growth • Vitamin D increases Cortisol • Vitamin D is activated by kidney • PTH inhibits renal Ca2+ reabsorption the sensitivity of – Osteoblast death (apoptosis). bone to PTH. regulation) Medic al Sc ienc es Physiology 2008/09 Renal Effects • Essential for Ca2+ 13 Dr Alan Tuffery — Physiology Medic al Sc ienc es Physiology 2008/09 14 Dr Alan Tuffery — Physiology Slide 15 Slide 16 Learning Outcomes — 1 Learning Outcomes — 2 To be able to : 1. list the names and functions of the principal bone cells • • • 2. To be able to : Osteoblasts — form bone Osteocytes — mature bone cells (enclosed) Osteoclasts — break down bone 3. state the origin of new bone cells in growth and repair • Growth: ‘stem’ cells from ingrowth of CT and blood vessels • Repair: ‘stem’ cells in the periosteum describe the events of the principal stages of bone formation • Cartilage growth, erosion; bone deposition, remodelling 3. state the origin of new bone cells in growth and repair 4. Outline the hormonal regulation of serum calcium concentration Medic al Sc ienc es Physiology 2008/09 Dr Alan Tuffery — Physiology 4. Outline the hormonal regulation of serum calcium concentration • PTH (vital) — fall in [Ca2+], activates osteoclasts • Calcitonin (extreme demand) — rise in [Ca2+] inhibits ostoeoclasts. 15 Medic al Sc ienc es Physiology 2008/09 16 Dr Alan Tuffery — Physiology 4 M edSci 4 10/8/08 Slide 17 Slide 18 Fracture Repair Remodelling • Recall that: http://courses.washington.e du/bonephys/ophome.html – all CT cells are closely related – stem cell is mesenchymal. • Precursor cells in periosteum. • Fracture triggers differentiation and growth of CT and blood vessels… • …Repair and remodelling. Medic al Sc ienc es Physiology 2008/09 Dr Alan Tuffery — Physiology 17 Medic al Sc ienc es Physiology 2008/09 18 Dr Alan Tuffery — Physiology 5
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