B1 MSK

• Exocytosis


  1. Vesicles fuse with the plasma membrane and release their contents to the external cellular environment

  2. These can be substances for export, proteins, getting rid of waste products and removing toxins

  3. Active transport processes require energy

  4. Usually digestive enzyme, hormones and histamines are ejected via exocytosis
• Endocytosis


  1. Capturing a particle or substance from the external environment of the cell and engulfing it with the cell membrane

  2. The membrane folds over the substance and it becomes completely enclosed by the membrane

  3. Vesicle pinched/budded off to move into cytosol
• Phagocytosis


  Plasma membrane engulfs the solid material forming phagocytotic vesicle
• Pinocytosis


  1. Plasma membrane folds inward to form channel allowing dissolved substances to enter cell

  2. When the channel is closed = liquid encircled in pinocytic vesicle
• Skull


  • Composed of cranium, maxilla, mandible, hyoid apparatus
  • Cranium houses brain
  • Maxilla houses PM, M and canines
  • Mandible is lower dental arcade
  • Hyoid is a series of cartilages which attaches to the larynx and supports at base of the skull

  
• Functions of the skull

  • Protects and houses the brain in the cranium
  • Housing for sensory organs; nose ears eyes and tongue
  • Provide attachment for mandible
  • Provide attachment for the hyoid apparatus
  • Provides attachment for facial muscles
  • House the teeth
  • Attach the larynx – links to hyoid apparatus
• Spine passes through foramen magnum as it leaves the cranial cavity
• Nuchal ligament -> paired band of connective tissue which connects C1-T1
• Sinuses in the skull

  • Maxillary; caudal end of nasal cavity
  • Frontal; lies within frontal bone and varies in size dependent on skull shape and age
• Vertebrae


  • Unpaired bones separated by intervertebral discs
  • Protection of spinal cord
  • Aid support for the head
  • Provide attachment for muscles
  • Enable movement and posture
• Vertebrae shape changing from beginning to end

  • Atlas – C1 – unique shape no body no spinous process, two large transverse processes and articulates with skull allowing up and down movement of the head
  • Axis – C2 – elongated spinous process for attachment of neck muscles and nuchal ligament, articulates to the atlas via odontoid process allowing rotation of the head
  • Cervical vertebrae C3-C7 – similar appearance to the atlas of elongated spinous processes but with increasing length
  • Thoracic T1-T13 - shorter bodies with distinct tall spinous processes which gradually decrease in height, their transverse processes articulate with the ribs
  • Lumbar L1-L7 – longer bodies that increase in width, large transverse processes which point cranio-ventrally and suspend the abdominal muscles. Spinous processes point cranially
  • Sacrum – 3 fused vertebrae which articulates with the ilium of the pelvis at the sacroiliac joint
  • Coccygeal vertebrae C1-C23 (varied) – progressively smaller and less complex
• Intramembranous ossification


  1. Mesenchymal cells condense into sheets and the ossification center forms between the mesenchymal sheets which are surrounded by collagen fibres

  2. Osteoblasts then secret osteoid (unmineralized bone matrix) which is then mineralized by deposition of calcium and phosphorus, the new bone matrix is maintained by the osteocytes

  3. The trabecular matrix then begins to form, and the mesenchyme forms the periosteum with introduction of blood vessels

  4. Compact bone develops and crowded blood vessels condense into red marrow
• Endochondral ossification


  1. Mesenchymal cells condense and continue to proliferate into chondrocytes

  2. Chondrocytes then undergo hypertrophy = X collagen and proteoglycans and START secreting ALKP

  3. ALKP initiates the mineral deposition promoting secretion of growth factors and vascularization ot the site

  4. The perichondrium differentiates into periosteum

  5. Primary ossification site is formed within the diaphysis of the long bone

  6. Secondary ossification centers form at either end of the long bone within the epiphyseal regions with growth plates beneath to allowing lengthening. Osteoclasts break down the spongy bone via secretion of acids onto surface and this forms a medullary cavity in the center
• Regions within epiphyseal growth plate

  • Reserve zone; hyaline cartilage which anchors the growth plate to the epiphysis
  • Proliferative zone; chondroblasts will quickly divide and push the epiphysis away from the diaphysis which lengthens the bone
  • Hypertrophic zone; when chondrocytes enter this zone, they secrete ALKP which is important for calcium deposition and thus ossification. In this zone chondrocytes, mature, degrade and leave their lacunae which is then infiltrated by osteoprogenitor cells and become calcified whilst osteoblasts lay down new bony matrix which lengthens the bone
• Bone modelling


  Defines skeletal development and the re-shaping of bones. It occurs mainly during skeletal growth but also throughout life. Osteoblast and osteoclast activity is NOT coupled. Formation modelling and the resorption modelling will occur on different surfaces

  
• Bone remodelling


  Renewal of the bony skeleton continues throughout life. The bones adapt to meet the load that is placed on them. The process is cyclic and relies on coupled activity between osteoblasts and osteoclasts which occurs on the same surface
• Primary (direct) bone healing - Contact healing

  1. Osteoclasts congregate and tunnel across the fracture site

  2. Osteoblasts move to the fracture site deposit the bony matrix down in the lamellae along the length of the bone

  3. Blood vessels penetrate the lamellae = haversian system – blood vessels run through the middle
• Primary (direct) bone healing - Gap healing


  1. If the gap is small, it's a similar process but osteoblasts lay down new lamellae bone perpendicular to the longitudinal axis of the bone

  2. This would require remodeling within 7-8 weeks as its weaker and takes longer to heal
• Secondary (indirect) bone healing

  1. Fracture occurs

  2. Then a hematoma (bleeding) occurs at the facture site, this activates the coagulation cascade and forms a clot returning to hemostasis (normal blood)

  3. Clot releases cytokines which recruit inflammatory cells (lymphocytes, macrophages, neutrophils)

  4. Fibroblasts and MSCs (mesenchymal stem cells) migrate to the fracture site

  5. Granulation tissue forms around the ends of the fracture

  6. Angiogenesis (development of new blood cells) and neovascularization (new blood vessels) occur at site

  7. TNF-alpha drives MSC differentiation into chondrocytes and osteoblasts

  8. This leads to formation of a soft callus (primary callus)

  9. If the environment is stable intramembranous ossification will occur (osteocytes – mesenchymal template)

  10. If the environment is unstable endochondral ossification occurs which converts the soft callus -> hard callus

  11. Resorption of remaining cartilage woven bone replaced by lamellar bone
• Muscle types


  • Skeletal
  • Smooth
  • Cardiac
• Skeletal muscle


  • Striated, long cylindrical fibres, peripheral nuclei
  • Voluntary movement, heat production and organ protection
  • Attaches to bones and bodily entrance points (e.g., mouth, anus)
• Smooth muscle


  • Short, spindle shaped, no striation and single nuclei in each fibre
  • Involuntary movement, food movement, involuntary respiratory control movement of secretions, blood flow regulation
  • Walls of major organs and passageways
• Cardiac muscle


  • Striated, short branched with central nucleus. They contain gap junctions and branching fibres
  • Pumping blood via contraction
  • Heart
• Connective tissue in skeletal muscle

  • Endomysium; surrounds individual muscle fibres, made up of reticular fibres with small capillaries and nerve fibres, site for metabolic exchange
  • Perimysium; slightly thicker, Type II and III collagen surrounds the groups of fibres = fascicle, fascicles are the functional unit of skeletal muscle tissue
  • Epimysium; surrounds the bundle of fascicles making up an individual muscle, maintains structural integrity while allowing powerful contraction
• Components of a synovial joint


  • Hyaline cartilage on the bones which allows smooth gliding movement
  • Synovial fluid within the joint cavity produced by the surrounding synovial membrane, the membrane incasing the fluid helps to keep the environment sterile
  • Fibrous layer surrounding the membrane of the joint capsule is tough aiding protection of the cavity
  • Periosteum lines the outside of the bone with compact bone on the inner most surface
• Fibrous joints


  • Sutures; no movement permitted, fissure lines found in the skull/ Wormian sutures and they ossify with age, the bones are joined by the fibrous material
  • Syndesmoses; allow little to no movement and they're joined via ligaments, meaning the bones are very close together. An example is the radius and ulna
  • Gomphosis; specific joint found between the teeth and alveolar socket found within the jaw. It permits no movement, and the periodontal ligament holds the tooth in place
• Cartilaginous/fibrocartilaginous/synchondroses joints


  • Two bones are fused to limit movement
  • Some movement permitted = vertebrae
  • Little-no movement permitted = pubic & mandibular symphysis
  • Temporary movement = epiphyseal growth plates which possess a temporary cartilaginous which ossifies as age increases
• Skeletal excitation-contraction coupling


  1. De-polarisation of the pre-synaptic terminal induces release of acetylcholine as a result of increase in intracellular calcium concentration

  2. The acetylcholine released binds to receptors on the post-synaptic membrane which causes in increase in intracellular Na concentration which depolarises the membrane

  3. Membrane depolarisation induces an action potential which travels down the T tubule

  4. Ca is released from the sarcoplasmic reticulum in response to the change in voltage

  5. The increased Ca concentration allows a conformational change via binding of calcium to troponin C

  6. Calcium bound to troponin C frees the binding sites on actin and hence mysoin can now bind

  7. Cross-bridges form between actin and myosin

  8. Contraction occurs via inward sliding of the filaments, decreasing the length of the sarcomere
• Relaxation of skeletal muscle

  1. Acetylcholinesterase removes acetylcholine from the synaptic cleft

  2. Repolarisation of the membrane occurs

  3. Ca is transported back into the sarcoplasmic reticulum

  4. Tropomyosin binds the active site on actin causing detachment of the cross-bridges
• How ATP is released for muscle contraction

  • Creatine phosphate metabolism helps maintain a constant supply of ATP in the muscle during sudden bursts that would otherwise deplete the ATP concentration
  • Creatine kinase converts creatine phosphate and ADP into creatine and ATP
  • Anaerobic glycolysis breaks down glucose to produce ATP and pyruvate when oxygen is unavailable, slower rate than creatine phosphatase
  • Aerobic respiration in the mitochondria produces ATP when oxygen is available, inputs are glucose, fatty acids and pyruvic acid
• Major nerves of forelimb - brachial plexus


  • C6 = suprascapular nerve – innervates supra and infraspinatus
  • C6-C7 = musculocutaneous nerve – biceps, brachialis and coracobrachialis
  • C7-C8 = axillary – flexors of shoulder = teres minor and major and the deltoideus
  • C8-T1 = median nerve – flexors of the carpus and digits
  • C8-T1 = ulnar nerve – more caudal flexors of carpus and deep digital flexors
  • C7-T1 = radial nerve – extensors of the elbow, carpus and digits

  
• Major nerves of hindlimb - lumbosacral plexus

  • L4,5&6 = femoral nerve – quadriceps femoris and iliopsoas
  • L5,6 = obturator – adductor muscles (pelvis symphysis)
  • L6,7 & S1 = gluteal – gluteal, biceps femoris and semitendinosus – extend and abduct hip
  • L6,7, S1 & S2 = Sciatic – biceps femoris, semitendinosus and semimembranosus – extend hip
  • Tibial (sciatic origin) = popliteal – extend tarsus, flex stifle, flex digits
  • Peroneal (fibular) sciatic origin = flex hock extend digits

  
• ALKP (Alkaline Phosphatase)


  
  
• A region in the epiphyseal growth plate where chondrocytes mature, degrade, and leave their lacunae.
• Osteocytes

  
  
• Cells found in cartilage that play a crucial role in bone development.
• The process by which cartilage tissue is replaced by bone tissue.
• Endochondral Ossification


  
  
• Chondrocytes