FMD002 Skeletal Anatomy and Physiology 2024-25 PDF

Introduction to Skeletal Anatomy and Physiology Dr Simon Fox [email protected] Check in code  Learning objectives By the end of this session and following further appropriate reading you should be able to. – Describe the basic structure, function and orga...

Introduction to Skeletal Anatomy and Physiology Dr Simon Fox [email protected] Check in code  Learning objectives By the end of this session and following further appropriate reading you should be able to. – Describe the basic structure, function and organization of the human skeletal system – Detail the major stimuli impacting on bone and the response of the skeleton to these – Consider the main cell types of bone osteoblasts, osteocytes and osteoclasts Why have we evolved a skeleton? Muscle attachment, locomotion and body shape. Protection. Mineral Storage. Adaptive biological system. Detects and processes multiple inputs to produce an appropriate response. Skeleton Types of bone- Long Bones Long Bone Anatomy Epiphysis Metaphysis Diaphysis  Flat Bones (skull, ribs and sternum) Bone types Bone types Sesamoid Short Irregular  Types of bone tissue Compact / cortical Main weight bearing structure. Trabecular Trabecular / spongy / Cortical cancellous. Main site of calcium exchange. Optimised to provide the greatest amount of support for minimum mass. Cortical and trabecula r bone distributi on Composition of Bone Matrix ~25% water ~25% organic ~50% components inorganic Type I collagen fibres components Calcium Chondrotin sulfate Hydroxyapatite, metals Proteins- cytokines, growth factors  Bone developm Intramembranous ent formation- Skull, parts of clavicle Bone forms directly from mesenchymal cells Endochondral ossification- Long bones Bone forms Morphogenes from a is and growth cartilaginous phases template Intramembranou s formation Mesenchymal condensations form early in embryogenesis Differentiate into osteoblasts which form osteoid, which is then mineralised Appositional growth Genetically regulated by patterning genes encoding transcription factors such as homeobox (HOX) or paired box (PAX) Growth plate organisation Resting Zone Pre Hypertrophic zone Site of longitudinal growth. Chondrocytes arranged in columns. Distinct zones. Proliferation and differentiation are tightly regulated. Any questions? Bone marrow Erythrocytes, lymphocytes and cells of the myeloid lineage Osteoblastic lineage (Stromal) Osteoblasts (responsible for bone Osteoclast formation and mineralization) Osteocyte Bone lining cells (may detect changes in loading environment Osteoblast and expose bone surface for resorption) Osteocytes (likely to be the main mechano-sensitive cell) Osteoclastic lineage (Myeloid) Osteoclasts (responsible for bone resorption) Bone cells  Physiological factors that impact on bone homeostasis Fluctuations in serum calcium Changes in mechanical loading Repair of microdamage Hormonal status  Osteoclasts and Ca2+ homeostasis Fall in [Ca 2+] leads to PTH release from parathyroid glands. This elevates [Ca 2+] through a variety of mechanisms 1. Promotes bone resorption. 2. Activates 1,25 Vit D3 in kidney which increase intestinal uptake of Ca 2+. Calcitonin also regulates osteoclast activity. Increased [Ca2+] stimulates 3. Increases renal reabsorption of Ca 2+ calcitonin formation which directly inhibits osteoclast activity.  Bone is a dynamic structure Bone structure is optimised to provide the minimal mass for its current structural/mineral requirements. If these change then bone mass and structure must adapt to meet these new requirements. (Kozlovskaya and Grogoriev 2004) Hormonal status  Remodelling Cycle www.meduniwien.a c.at Bone formation and resorption are coupled Osteoblastic lineage Derived from stromal precursors that can form either osteoblasts or adipose cells Osteoblasts synthesise the organic matrix of bone (osteoid) and control its mineralization When osteoblasts finish making new bone they can differentiate into Osteocytes Bone lining cells or undergo apoptosis  Sequential process Osteoid formation – organic Mineralization – Calcium hydroxy-apatite Goldner’s stain of bone (Medscape education.com) Bone formation  Osteoclasts Form from pluripotent CD34+ mononuclear phagocyte precursors that can form many myeloid cell types. Precursor differentiation is controlled by the cytokines/growth factors that it osteoclast encounters at a specific stage of its development. Osteoclasts Responsible for bone resorption. Can be multinuclear. Are TRAP positive, express calcitonin receptors, cathepsin K and other proteinases.  Osteoclast Physiological Pathological regulators of osteoclast regulators differentiation Low and serum Ca2+ levels. (Calcium Disruption of steroid hormone bone homeostasis) resorption levels Decreases in mechanical loading Inflammation Cancer  Process of bone resorption 1. Attaches to surface through a5b3 integrin interaction with RGD containing proteins. 2. Polarisation of osteoclast formation of ruffled border, actin ring and sealed zone. 3. Acidification of the sealed zone by active transport of H+ to breakdown mineral component of 4. Release of cathepsin K and bone. Oc pH maintained by other proteases that digest Cl-/HCO3– exchanger on collagen. basolateral surface. 5. Creates a resorption pit 4-5 mM deep. Aberrant turnover leads to skeletal pathologies Paget’s Disease Primary bone sarcomas Osteolytic secondary Osteoporosis: cancers BRONJ. Anticancer Research 2011 31 62313-2318 multi-factorial Quiz  Summary Bone structure is Osteoclast and remodeled by the Bone is a dynamic osteoblast coordinated action of tissue. differentiation are osteoblast and tightly regulated. osteoclast. Suggested Aberrant bone supplementary reading formation or resorption Marieb E. Essentials of Human anatomy and Physiology, (8 leads to skeletal and 9th editions) Chapter 5, pathology. The skeletal system. Pearson Publishers