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Musculoskeletal System Year 1 Year 4all 2440051B@student.gla.ac.ukILOs Extracellular matrix Describe the nature and function of extracellular matrix (ECM) components, including proteoglycans and fibrous proteins Briefly describe how ECM is synthesised and degraded Identify the location and nature of ECM components in different tissues Briefly describe the composition of osteoid and cartilage (ECM in bones and joints) Give examples of medical conditions associated with defects in ECM components Muscle excitation Describe ionic distribution across cell membranes Explain its maintenance using metabolic energy Describe its electrical consequences (a) in resting cells (b) in electrically active nerve or muscle Contrast transmission of a signal from nerve to skeletal muscle with propagation along the length of either individual cellMuscle Contraction Describe the microscopic structure of skeletal muscle fibre. Describe the organisation of contractile proteins, and (a) their participation in muscle length change (b) how they make muscle contract Explain how electrical excitation leads to contraction Osteoarthritis Describe the normal anatomy of joints ( hip and knee as examples) Define osteoarthritis and understand the changes in articular cartilage Discuss clinical signs and x-ray findings in osteoarthritis List the medical and surgical treatment options for osteoarthritisMusculoskeletal System 1 Describe the general features of joints Describe the general features of skeletal muscles Appreciate the arrangement of the superficial layers of the body i.e. skin, subcutis Describe trapezius and latissimus dorsi Appreciate the importance of understanding muscle attachment in order to understand muscle actionECM ● The ‘stuff’ that surrounds cells (interstitial connective tissue) and makes up the barrier between epithelium and stroma (basement membrane) ● Made up of ○ Fibres I.e. elastin and collagen ○ Ground substance I.e. proteoglycans, glycosaminoglycans, glycoproteinsQuestion… Collagen I Dermis Collagen Tendons Ligaments Bones Fibrocartilage ● An insoluble fibrous protein found in the Collagen II Hyaline cartilage ECM that provides high tensile strength Collagen III Liver ● Triplet repeat of Gly-X-Y amino acid Bone marrow sequence forms s triple helix Lymphoid organs Granulation tissue e.g. reticulin – e.g. in wound healing Collagen IV Basement membranes Collagen V CorneaQuestion…ECM in Clinical Context Marfan’s Syndrome - Fibrillin-1 causing skeletal, ocular and cardiovascular abnormalities Ehlers-Danlos Syndrome - Collagen causing joint and skin abnormality Macular Corneal Dystrophy - Keratan sulphate causing corneal transparency Cancer - epithelial tumors are malignant once the BM is breached, cancer cells release Matrix Metalloproteinases (MMPs) which degrade collagen Diabetes Mellitus - thickening of BM of kidney, glomerulus changes permeability GoodPasture's Syndrome - autoantibodies to collagen IV destroy BM in glomerulus and lung *Epidermolysis bullosa - Attachment of epidermis to BM causing blisters *common MCQEhlers Danlos Syndrome: skin hyperextensibility and joint hypermobility due to defect of fibrillar collagens (I, V, III) Marfan's Syndrome: tall, thin stature, arachnodactyly and ectopia lentils due to defect of fibrillin 1Question…Composition of Bone ● Osteoclast - bone breakers ● Osteoblast - bone builders ● Osteocyte - tired osteoblasts ● Inorganic component is mostly calcium phosphateQuestion…Cartilage An avascular, aneural connective tissue matrix Produced by chondrocytes, which mainly produce Collagen II and Aggrecan (heavily glycosylated protein) Hyaline Cartilage - type II collagen + aggrecan; ends of articular bone Elastic Cartilage - type II collagen + aggrecan + elastin; external ear, auditory tube + epiglottis Fibrocartilage - type I collagen + type II collagen + aggrecan; between vertebraeJoints Fibrous ● Sutures (skull) ● Gomphoses (teeth) ● Syndesmosis (radius + ulna) Cartilaginous ● Synchondroses (epiphyseal growth plates) *hyaline cartilage ● Symphysis (pubic symphysis + intervertebral disc) * fibrocartilage and hyaline cartilage Synovial ● Many types ● Diarthrosis meaning articulation that permits free movement ● Hips and elbowSynovial Joint ● Articular cartilage made of hyaline cartilage ● Synovial fluid enclosed by synovial membrane and outer fibrous capsule ● Additional features in specific joints: ○ Knee - menisci (fibrocartilage) ○ Ligaments ○ Tendons ○ BursaeTypes of Synovial JointsOsteoarthritis Definition: Degenerative disease of joints (synovial) resulting in loss of articular cartilage, remodelling of adjacent bone to produce osteophytes and inflammation. Pathophysiology: Presentation: ● Activity related movement ● Short lived morning stiffness <30 mins or no morning stiffness ● Functional impairment Signs: ● Bouchard's nodes (PIPJs) ● Heberden nodes (DIPJs) ● Crepitus ● Reduced ROM and painPathophysiology Risk Factors: ● Obesity Progressive loss of articular cartilage and ● Advancing age ● Female remodelling of bone (subchondral sclerosis, ● Manual labour/long term cysts, osteophytes) intensive exercise ● Trauma 1. Inflammation in joint causes activation of chondrocytes and nearby inflammatory cells 2. Degradation of collagen and proteoglycans of articular cartilage 3. Exposure of underlying bone causes reactive remodelling i.e. cysts, sclerosis and osteophytesX Ray Presentation (LOSS): Loss of joint space Osteophytes subchondral sclerosis subchondral cystsManagement of OA ● Self-care strategies: ○ Weight loss ○ Local muscle strengthening exercises and aerobic fitness training ○ Appropriate footwear ○ Local heat or cold packs ○ Transcutaneous electrical nerve stimulation (TENS) ● Medical management: ○ Paracetamol or oral NSAIDs PRN ○ Topical NSAIDs e.g. ibuprofen/diclofenac gel ○ Step-up therapy: paracetamol + NSAIDs, co-codamol ○ Intra Articular Steroid injections ● Surgical management ○ Arthroplasty ○ Osteotomy ○ Arthrodesis Muscle COMMON EXAM Q - LABEL THE SARCOMEREMuscle Stimulation 1. An impulse travels along somatic motor neurons from the central nervous system 2. At the neuromuscular junction, the motor neurons synapse with a group of skeletal muscle fibres 3. The action potential triggers the release of ACh 4. ACh diffuses across the synaptic cleft to the ligand gated ion channel receptors in the motor end plate 5. An AP it triggered in the muscle 6. Acetylcholinesterase in synaptic cleft breaks down ACh so another action potential is not stimulated until a further AP reaches the motor neurone 7. The AP travels along the T-tubule system 8. This open Ca channels in the SR membrane 9. Ca ions flood into the sarcoplasm troponin promotes muscle contraction, tropomyosin blocks Muscle Contraction muscle contraction 1. Ca ions bind to the troponin in the thin filament 2. The binding sites on actin filament (for myosin) are exposed 3. Myosin head binds to the actin sites, rotates slightly and releases a. It is the hydrolysis of ATP that releases the energy for detachment of the head b. This repeats as a ratchet mechanism along the length of the actin filament 4. Thin filament pulled towards the centre of sarcomere 5. Ca ion channels in SR close and Ca active transport channels pumps use ATP to restore the low level of Ca in the sarcoplasm 6. Troponin-tropomyosin complex slides back into the position where it blocks the myosin binding sites 7. Muscle relaxesQuestion…Trapezius Muscle Origin: Just above the superior nuchal line and spinous press C1-T12 (in part via the nuchal ligament) Insertion: 1. Descending: lateral Ill of the clavicle 2. Ascending: scapular spine 3. Horizontal: acromion Action: ● Descending: keeps shoulder girdle up, tilts the scapula for arm elevation ● Horizontal and ascending: depress ad pull scapula medially Nervous supply: accessory nerve + cervical plexusLatissimus Dorsi Origin: ● Spinous processes T7-T12 ● Thoraco-lumbar aponeurosis ● Dorsal surface of the sacrum ● Dorsal Ill of the iliac crest ● 10th-12th ribs ● Inferior angle of the scapula Insertion: intertubercular sulcus of humerus Innervation: thoracodorsal nerve Actions: extends, adducts and medially rotates upper limbFeedback FormResources for Year 1 ● For anatomy: https://teachmeanatomy.info/ ● For some surgical conditions (e.g. OA): https://teachmesurgery.com/ ● Clinical info (more useful in phase 2): https://patient.info/ ● DrawItToKnowIt: https://www.drawittoknowit.com/ Textbooks ● Kumar and Clark’s Clinical Medicine ● Langman’s Medical Embryology ● Wheater’s Functional Histology Youtube ● Armando: https://www.youtube.com/user/armandohasudungan ● ZeroToFinals: https://www.youtube.com/c/ZeroToFinals ● Osmosis: https://www.osmosis.org/