Midterm Studying: Bone Formation PDF

Bone Formation (Ossification) Process Overview: 1\. Introduction to Bone Fragments and Capillaries: Small fragments of bone (spicules or bony islands) grow and surround capillaries. As these spicules grow and merge, they form trabeculae, which is the foundational structure of spongy bone (also ca...

Bone Formation (Ossification) Process Overview: 1\. Introduction to Bone Fragments and Capillaries: Small fragments of bone (spicules or bony islands) grow and surround capillaries. As these spicules grow and merge, they form trabeculae, which is the foundational structure of spongy bone (also called trabecular bone). 2\. Step 1: Mesenchymal Cell Differentiation and Formation of Periosteum: Mesenchymal cells gather and condense, differentiating into osteogenic cells (osteoblasts), forming the periosteum. Periosteum: Outer fibrous layer and inner osteogenic layer. The outer layer is for protection, while the inner layer houses osteogenic cells that differentiate into osteoblasts. 3\. Step 2: Trabecular (Spongy) Bone Formation: Osteoblasts continue depositing bone matrix on the outer surface of the trabeculae. Osteocytes within the spongy bone begin condensing, forming more dense tissue in the center, while trabeculae continue to grow outward. 4\. Step 3: Compact Bone Formation: The periosteum forms fully around the spongy bone, and osteoblasts lay down compact bone along the outer surface. Over time, the osteons (functional units of compact bone) develop, arranging themselves in a repeating pattern. 5\. Step 4: Red Bone Marrow Formation: Red bone marrow begins forming inside the condensing spongy bone. The bone begins organizing into osteons, completing the structure of mature bone. Intramembranous Ossification: This type of ossification directly forms bones from mesenchymal cells without a cartilage model. Bones formed this way: Flat bones (e.g., skull bones, clavicle). Process Start: Around week 9 of development, mesenchymal cells differentiate into osteoblasts, which form an ossification center. Osteoblasts secrete osteoid (unmineralized bone matrix), which then undergoes calcification. As osteoblasts become trapped in the matrix, they differentiate into osteocytes. Steps of Intramembranous Ossification: 1\. Mesenchymal Cell Condensation: Mesenchymal cells cluster in areas where new bone will form and differentiate into osteoblasts. 2\. Ossification Center Formation: Osteoblasts secrete osteoid, forming the ossification center. 3\. Bone Matrix Secretion and Calcification: Osteoblasts continue secreting osteoid, which calcifies, forming spicules (small bone islands). 4\. Trabeculae Formation: The spicules grow together, forming trabeculae, which later becomes spongy bone. 5\. Periosteum Formation: The mesenchyme condenses around the newly formed bone, creating the periosteum with its two layers (outer fibrous and inner osteogenic). 6\. Formation of Compact Bone: Osteoblasts in the periosteum lay down compact bone around the trabeculae, forming the outer bone layer. 7\. Development of Red Bone Marrow: Spongy bone within the trabeculae houses red bone marrow, forming blood cells. Long Bone Development (Endochondral Ossification): Bones formed this way: All bones below the clavicle. Starts with a cartilage model around week 9 of development. Growth types: Interstitial growth: Growth in length. Appositional growth: Growth in width. Steps of Endochondral Ossification: 1\. Cartilage Model Formation: Mesenchymal cells differentiate into chondroblasts, forming a cartilage model of the future bone. 2\. Formation of Bone Collar: Osteoblasts secrete osteoid around the diaphysis of the cartilage model, forming a bone collar. 3\. Primary Ossification Center Formation: Chondrocytes in the center of the cartilage model enlarge (hypertrophy), secrete enzymes (alkaline phosphatase), and initiate calcification. As calcification occurs, the chondrocytes die, leaving behind a calcified matrix. 4\. Invasion of Blood Vessels and Osteoblasts: Blood vessels invade the calcified cartilage, bringing osteoblasts, which use the calcium to build new bone. This forms the primary ossification center in the diaphysis (middle of the bone). 5\. Secondary Ossification Centers: After birth, secondary ossification centers form in the epiphyses (ends of the bone). Cartilage continues to grow at the epiphyseal (growth) plates until the bone reaches its final length. 6\. Bone Remodeling: Osteoblasts and osteoclasts continue to remodel the bone throughout life, particularly during growth and after injury. Growth and Remodeling: Skull Growth: Osteoclasts on the inside of the bone and osteoblasts on the outside allow the skull to grow and accommodate the developing brain. Bone remodeling continues until around the age of 25 when bone development stabilizes. 1\. Primary Ossification: Begins around 9 weeks of gestation. Cartilage model forms first, with hypertrophic cartilage secreting alkaline phosphatase, which leads to calcification. Nutrient arteries penetrate the cartilage, delivering osteoblasts (boneforming cells) and initiating bone development. Initially, spongy bone is deposited along the diaphysis (the shaft of the bone). 2\. Secondary Ossification: Occurs after birth at the epiphyses (the ends of long bones). Cartilage remains at the growth plates and articular surfaces. Bone growth in length continues through interstitial growth at the epiphyseal plate, where cartilage is replaced by bone tissue. Growth continues until adulthood, driven by osteoblast activity on one side of the growth plate and cartilage proliferation on the other. 3\. Bone Remodeling: Occurs continuously throughout life to maintain bone strength and adapt to mechanical stress (Wolff\'s Law). Osteoclasts resorb bone, and osteoblasts deposit new bone, remodeling the internal structure. Remodeling also ensures calcium homeostasis, with hormones like calcitonin (decreasing blood calcium) and parathyroid hormone (increasing blood calcium) regulating bone resorption and formation. 4\. Nutrients and Hormones: Essential minerals for bone health include calcium, phosphorus, and magnesium. Vitamins like D (promotes calcium absorption), C (collagen formation), and K (bone protein synthesis) are crucial. Growth hormone stimulates bone growth, while thyroid hormones enhance metabolism and osteoblast activity. Insulinlike growth factors (IGFs) also promote bone development. Key Joints and Structures 1\. Temporomandibular Joint (TMJ) Type: Hinge and gliding joint (hinge and planar). Articulation: Between temporal bone and mandibular condyle. Movements: Depression, elevation, retraction, protrusion, and lateral movement. Significance: The only movable joint in the skull. 2\. Shoulder Joint (Glenohumeral Joint) Type: Ballandsocket, multiaxial (most flexible joint). Articulation: Head of the humerus with the glenoid fossa of the scapula. Movements: Flexion, extension, abduction, adduction, lateral rotation, medial rotation, and circumduction. Stability: Glenoid Labrum: Deepens the shallow glenoid fossa for added stability. Rotator Cuff Muscles (SITS): Supraspinatus, Infraspinatus, Teres Minor, and Subscapularis, essential in preventing dislocation. 3\. Elbow Joint Type: Hinge joint (allows flexion and extension only). Articulations: Humeroulnar Joint: Trochlear notch of ulna with the humerus. Humeroradial Joint: Head of the radius with the humerus. Key Ligaments: Annular Ligament: Encircles the head of the radius, permitting supination and pronation. Ulnar Collateral Ligament (UCL): Stabilizes the medial side, commonly injured in repetitive motion. 4\. Hip Joint Type: Ballandsocket, highly stable but less flexible than the shoulder. Articulation: Head of the femur with the acetabulum of the pelvis. Stability: Acetabular Labrum: Deepens the acetabulum, improving fit and stability. Ligamentum Teres: Links the femur to the acetabulum, aiding in stability. Fibrous Capsule: A strong, resistant structure that prevents dislocation. 5\. Knee Joint Type: Primarily a hinge joint with limited rotation when flexed. Articulations: Medial and lateral tibiofemoral joints (femurtibia). Patellofemoral joint (femurpatella). Stabilizing Ligaments: Extracapsular: Fibular (Lateral) Collateral Ligament (LCL): Prevents lateral displacement. Tibial (Medial) Collateral Ligament (MCL): Prevents medial displacement. Patellar Ligament: Reinforces anterior knee stability. Intracapsular: Anterior Cruciate Ligament (ACL): Prevents anterior sliding of the tibia and hyperextension. Posterior Cruciate Ligament (PCL): Prevents posterior sliding of the tibia. Joint Disorders Arthritis Definition: Joint inflammation that leads to pain, swelling, and reduced motion. Types: Osteoarthritis: Cause: Wear and tear on articular cartilage, resulting in pain, inflammation, crepitus, and reduced mobility. Rheumatoid Arthritis: Cause: Autoimmune disorder targeting the synovial membrane, leading to pain, stiffness, swelling, and joint deformity due to immune response. Audio file ========== [Your Recording 6.wav](https://lethbridgecollege-my.sharepoint.com/personal/kacey_paradis_lethpolytech_ca/Documents/Transcribed%20Files/Your%20Recording%206.wav) Skeletal Muscle Contraction and Crossbridge Cycle 1\. Basics of Muscle Contraction Sarcomere: The functional unit of contraction in skeletal muscle. Crossbridge Cycle: A series of molecular events that lead to muscle contraction. Key Components: Involves calcium ions, ATP, actin, and myosin. 2\. Initiation of Contraction Calcium Ions Release: Triggered from the sarcoplasmic reticulum. Binding to Troponin: Calcium binds to troponin, causing a conformational change. Exposure of Binding Sites: Tropomyosin shifts, revealing myosinbinding sites on actin. 3\. Crossbridge Cycle Steps Preparation (ATP Hydrolysis): ATP binds to the myosin head and hydrolyzes to ADP and phosphate (Pi), energizing the myosin head (cocked position). Step 1 Crossbridge Formation: Myosin head binds to actin, forming a crossbridge. Pi is released, strengthening the bond. Step 2 Power Stroke: ADP is released; the myosin head pivots, pulling the actin filament toward the sarcomere center. Step 3 Crossbridge Detachment: A new ATP binds to myosin, weakening the attachment and causing detachment. Step 4 Reactivation of Myosin: ATP is hydrolyzed, reenergizing the myosin head for another cycle. 4\. Muscle Shortening and Relaxation Sarcomere Shortening: Repeated cycles cause actin filaments to slide over myosin, shortening the sarcomere. Cycle Termination: Calcium ions are pumped back into the sarcoplasmic reticulum, tropomyosin recovers actin, and the muscle relaxes. ExcitationContraction Coupling 1\. Role of Action Potential Propagation: An action potential moves across the sarcolemma and into the Ttubules. TTubules: Conduct the action potential deep into the muscle fiber. 2\. Calcium Release Mechanism VoltageSensitive Proteins: Trigger a conformational change that opens calcium release channels in the sarcoplasmic reticulum. Calcium Floods Sarcoplasm: This influx initiates the contraction cycle by binding to troponin. Neuromuscular Junction (NMJ) 1\. Synapse Structure NMJ Components: The connection between a motor neuron and a skeletal muscle fiber. Steps at the NMJ: Step 1: Action potential reaches the axon terminal. Step 2: Voltagegated calcium channels open, allowing calcium ions to enter. Step 3: Calcium triggers vesicles to release acetylcholine (ACh) via exocytosis. Step 4: ACh diffuses across the synaptic cleft and binds to receptors on the muscle. Step 5: Ligandgated channels open, allowing Na+ influx, causing depolarization. Step 6: Action potential is generated across the sarcolemma. 2\. End of Signal Acetylcholinesterase: Breaks down ACh, terminating the signal and allowing the muscle to relax. Review Points Crossbridge Cycle: Understand each of the four steps. ExcitationContraction Coupling: Focus on how action potentials trigger calcium release. Neuromuscular Junction: Know the sequence of events and role of acetylcholine. 1\. Action Potential Initiation and Propagation An action potential begins in a motor neuron and travels along the nerve. Reaches the synaptic terminal of the neuron, also known as the synaptic knob or synaptic terminal. 2\. Calcium Channels and Acetylcholine Release The action potential triggers voltagegated calcium channels in the synaptic terminal to open. Calcium ions flow into the terminal, causing exocytosis of acetylcholine (ACh). ACh is released into the synaptic cleft. 3\. Binding to LigandGated Channels and Depolarization ACh crosses the synaptic cleft and binds to ACh receptors on the muscle fiber's membrane (sarcolemma). This receptor binding opens ligandgated channels for sodium and potassium. Sodium influx (greater than potassium outflux) leads to depolarization of the sarcolemma, propagating the action potential along the muscle. 4\. Propagation Along TTubules and Calcium Release Depolarization spreads through Ttubules to ensure uniform stimulation. This causes the sarcoplasmic reticulum (SR) to release calcium ions into the muscle cytoplasm. 5\. Calcium Binding and CrossBridge Formation Calcium binds to troponin, changing its shape and moving tropomyosin away from actin binding sites. Myosin heads attach to actin, starting the crossbridge cycle. 6\. ATP Hydrolysis and Power Stroke ATP hydrolysis energizes myosin heads. Myosin heads perform a power stroke, pulling the actin filaments inward, shortening the muscle. 7\. CrossBridge Detachment and Cycling ATP binds to myosin heads, causing them to release actin. This crossbridge cycling continues as long as calcium is present. 8\. Muscle Relaxation ACh removal: ACh diffuses away or is broken down by acetylcholinesterase (AChE). Calcium channels close in the sarcoplasmic reticulum, and calcium is actively pumped back. Without calcium, troponintropomyosin complex recovers actin sites, ending contraction. Energy Sources for Muscle Contraction 1\. Direct Phosphorylation Creatine phosphate donates a phosphate to ADP to form ATP, providing energy for about 1015 seconds. 2\. Anaerobic Glycolysis (Without Oxygen) Rapid ATP production from glucose without oxygen, producing lactic acid as a byproduct. Supports about 3040 seconds of highintensity activity. 3\. Aerobic Respiration (With Oxygen) Occurs in the mitochondria, fully oxidizing glucose to carbon dioxide and water. Provides sustained energy for extended periods, supporting prolonged activity. PostExercise Oxygen Consumption After highintensity activity, increased respiratory rate continues to restore oxygen, clear lactic acid, and replenish ATP and creatine phosphate levels.