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Y1B4M1L2 HISTOLOGY OF INTEGUMENTARY & MUSCULOSKELETAL SYSTEMS ● Sarcomere: repetitive functional subunit of the skeletal muscle ○ Extends from Z disc to Z disc ○ 2.5 μm in resting muscle Figure 49. TEM showing one contractile unit (sarcomere) in the long series that comprises a myofibril. In its m...

Y1B4M1L2 HISTOLOGY OF INTEGUMENTARY & MUSCULOSKELETAL SYSTEMS ● Sarcomere: repetitive functional subunit of the skeletal muscle ○ Extends from Z disc to Z disc ○ 2.5 μm in resting muscle Figure 49. TEM showing one contractile unit (sarcomere) in the long series that comprises a myofibril. In its middle is an electron dense A band bisected by a narrow, less dense region called the H zone. On each side of the A band are the lighter-stained I bands, each bisected by a dense Z disc which marks one end of the sarcomere. Mitochondria M , glycogen granules, and small cisternae of SER occur around the Z disc. Figure 47. Skeletal Muscle Anatomy, b MOLECULAR STRUCTURE OF SKELETAL MUSCLE FIBERS ● Longitudinal sections of skeletal muscle show striations of alternating light and dark bands Figure 48. Structure of Muscle Fibers ● Sarcoplasm is highly organized, containing primarily long cylindrical filament bundles called myofibrils that run parallel to the log axis of the fiber ○ A bands (dark) → Anisotropic or “birefringence” character in polarized light microscopy → Myosin filament ■ Principal constituent; transverse alignment of links creates M-line that bisect H-band ○ I bands (light) → Isotropic → Do not alter polarized light → Actin filaments ■ dominant component; interdigitate with myosin A to varying degree depending on muscle contraction site ● In electron microscopy, each I (light) band is seen to be bisected by a dark transverse line, the Z disc ○ Band region: elastic connection between thick filaments and Z line. ● Myofibrils ○ Long cylindrical filamentous bundles ○ 1 to 2 μm diameter, parallel to long axis of muscle fiber ○ Consists of end to end chainlike arrangement of sarcomere ○ Striations of muscle fiber are due to lateral registration of sarcomeres in adjacent myofibrils ○ The A and I banding pattern in sarcomeres is due mainly to the regular arrangement of thick and thin myofilaments, composed of myosin and F-actin organized within each myofibril in a symmetric pattern containing thousands of each filament type → Myosin: large complex 500kDa) with two identical heavy chains and two pairs of light chains ■ Heavy chains: thin, rodlike motor proteins twisted together as myosin tail ■ Globular projections containing the four myosin light chains form a head at one end of each heavy chain ■ Myosin heads bind both actins, forming transient cross bridges between the thick and thin filaments, and ATP, catalyzing energy release actomyosin ATPase activity) ■ Several hundred myosin molecules are arranged within each thick filament with overlapping rodlike portions and the globular heads directed towards either end Figure 50a). ■ The thin filaments are found between the thick filaments. Each G-actin monomer contains a binding site for myosin Figure 50b). ○ The thin filaments have two highly associated regulatory proteins: → Tropomyosin ■ 40 nm long coil of two polypeptide chains located in the groove between the two twisted actin strands → Troponin ■ Bound to each molecule are a complex of three troponin peptides for shifting filaments during muscle contraction ⎻ TnT - attaches to tropomyosin ⎻ TnC - binds to Ca2 ⎻ TnI - regulates the actin-myosin interaction AGULAN, ARENGA, BOLAÑO, DUARTE, FRANCISCO, NACIONALES, PIONELO, SEÑALISTA, TRESPECES, VIAJE | MG 9 13 of 26 Y1B4M1L2 HISTOLOGY OF INTEGUMENTARY & MUSCULOSKELETAL SYSTEMS ● ATP generation depends on anaerobic glycolysis of glucose derived from glycogen deposits in the sarcoplasm ● Innervated by larger axons that form motor end plates about twice the size of those of red fibers ● Contract rapidly and generate large force but they get fatigue easily ● Best suited for brief bursts of intense muscle activity INTERMEDIATE FIBERS ● Mitochondrial disposition is similar in red fibers ● Thick interfibrillar columns of mitochondria are seldom found MUSCLE CONTRACTION Figure 50. Structure of (a) Thick and (b) Thin Filaments From Dagitab Notes: ● Gelsolin - depolymerized actin filaments; delicate strands seen extending the full length of I-band are called titin ○ Titin - main structural basis for myofibrillar elasticity; maintains central position of thick filaments in sarcomere ● Filamin - actin-binding protein found in smooth muscle and Z line of skeletal muscle MUSCLE DIVERSITY ● Vary in color, diameter, cytochemical and physiological properties Two major categories of muscle fibers: ● Twitch fibers Fast) - all or none contraction ● Tonic fibers Slow) - unable to propagate action potential; needs series of nerve impulse; prolonged contractions RED FIBERS ● Slow twitch fibers and oxidative fibers ● Relatively small in diameter ● Darker color, attributable to their great content of myoglobin and rich supply of capillaries ● Contains numerous large mitochondria beneath the sarcolemma and between the myofibrils ○ Liquid droplets are common in the sarcoplasm → Stain intensely with the cytochemical reaction for the enzyme succinic dehydrogenase ● Z-bands are wider compared to other fibers ● Innervated by small axons with small and relatively simple motor end plates ● Contract more slowly ● Resistant to fatigue due to its ability for oxidative regeneration of ATP ● Effective in postural maintenance WHITE FIBERS ● Fast-twitch fibers ● Largest of the fiber types ● Smaller mitochondria and less numerous than those of red fibers ● Relatively few interfibrillar mitochondria ● Stains weakly with enzyme succinic dehydrogenase Figure 51. Skeletal Muscle Contraction Pathway. For detailed events of muscle contraction please refer to Figure 10 11 of Junquieraʼs Basic Histology 2016 . ● Sliding filament mechanism of contraction ● Thick and thin filaments maintain the same length as in resting muscle ● Thin filaments are moved relative to thick filaments >sliding more deeply in A-band > shortening sarcomeres Figure 52. Sliding Filament Mechanism ACTIVATION OF SKELETAL MUSCLE CONTRACTION ● Activated by an AP at myoneural junction ● Generated into the Sarcolemma ● Touching on the T-tubules and terminal cisternae; with opening of the channels ● Initiation and Release of Ca2 into sarcoplasm ● Result in binding to troponin C in the actin filaments ● Heads of myosin molecules bind to actin filaments ○ shortening and contraction process ● Activates myosin ATPase ● Flexion of myosin head ● Sliding of actin filaments toward the middle of A band ● Myosin heads then detach and reattach to the next binding sites ● New cycle of bridge making and breaking INNERVATIONS OF THE SKELETAL MUSCLE ● Axons from spinal cord ● Divides into multiple branches in a muscle penetrating the interior via perimysial septa ● Into the endomysium forming nerve endings (myoneural junctions) penetrating on muscle fibers AGULAN, ARENGA, BOLAÑO, DUARTE, FRANCISCO, NACIONALES, PIONELO, SEÑALISTA, TRESPECES, VIAJE | MG 9 14 of 26 Y1B4M1L2 HISTOLOGY OF INTEGUMENTARY & MUSCULOSKELETAL SYSTEMS ● Motor unit ○ Axons and muscle innervated (motor end plate) ○ Axoplasm of each ending contains small vesicles (acetylcholine) ● Synaptic cleft ○ Narrow space between axon terminal and sarcolemma and where ACh is released ● Pathway 1. Acetylcholine release 2. Acetylcholine receptors in sarcolemma 3. Open channels permitting entry of Na in sarcolemma 4. Depolarization of membrane 5. Generates electrical signal of action potential 6. Furthers to T-tubules 7. Release of Ca2 Figure 56. Synaptic Vesicles Figure 53. Pathway of Innervation Figure 54. Neuromuscular Joint Figure 57. Muscle Contraction B. CARDIAC MUSCLES Figure 55. Acetylcholine (ACh) Opens Na+ Channel Figure 58. Cardiac Muscles, a AGULAN, ARENGA, BOLAÑO, DUARTE, FRANCISCO, NACIONALES, PIONELO, SEÑALISTA, TRESPECES, VIAJE | MG 9 15 of 26 Y1B4M1L2 HISTOLOGY OF INTEGUMENTARY & MUSCULOSKELETAL SYSTEMS Figure 59. Cardiac Muscles, b ● Unlike skeletal muscle, they consist of separate cellular units about 80 um in length and 15 um in diameter ● Cardiac myocytes ● Joined end to end at junctional complexes (intercalated discs); hence, appearing branch ● Branch and form oblique interconnections with neighboring columns ● Ovoid central nucleus ● Lipochrome is abundant in elderly 20% of dry weight of myocardium) ○ pigment of wear and tear - lipofuscin (lipochrome) ● Less sarcoplasmic reticulum than skeletal muscle ○ Corbular reticulum - subsarcolemmal network with large caliber T-tubules Figure 62. Cardiac Muscle Cell – Intercalated Disc ● No terminal cisternae thus no triads ● Unending branching ● Dyads ○ Saccular dilatations of certain longitudinal tubules of the reticulum with close contact to T-tubules CARDIAC MUSCLE CONTRACTION ● Muscle Excitation ○ T-tubules via spanning proteins ○ Transmembrane particles bridge gap of T-tubule and terminal saccules ○ Calsequestrin + dyads of sarcoplasmic reticulum ● Increase in calcium concentration----depolarization of sarcolemma and T-tubules MYOCARDIAL CONDUCTION TISSUE Figure 60. Cardiac Muscle Nucleus and Lipofuscin Pigment ● Sinoatrial node SA node ○ Where electrical impulse starts ○ Specialized myocytes ○ Pacemaker → Results in contraction ○ Located in the right atrium ● Atrioventricular AV node ○ Impulse conduction ○ Richly vascularized ○ Connected by Purkinje fibers (impulse conducting fibers) ○ Between the right ventricle and atrium ● Purkinje fibers ○ Wider than ordinary cardiac myocytes ○ Few myofibrils ○ Nucleus have large amount of glycogen ○ Branches through myocardium ● Human heartbeat rate is 60 100 times a minute ● Contraction is myogenic (independent of nervous stimulation) ● All cardiac myocytes are capable of spontaneous rhythmic depolarization and repolarization of their membrane CONDUCTION SYSTEM OF THE HEART Figure 61. Cardiac Muscle – Branching Appearance ● The contraction of the atria must be completed slightly before the onset of ventricular contraction ● All myocytes are autonomously excitable cells that undergo rhythmic depolarization and repolarization independent of nervous influences, but the inherent rate of this activity in myocytes of the atria is greater than that of the ventricle ● Sinoatrial node ○ The site of initiation of excitation ○ “Pacemaker” of the heart AGULAN, ARENGA, BOLAÑO, DUARTE, FRANCISCO, NACIONALES, PIONELO, SEÑALISTA, TRESPECES, VIAJE | MG 9 16 of 26 Y1B4M1L2 HISTOLOGY OF INTEGUMENTARY & MUSCULOSKELETAL SYSTEMS ● Nodal myocytes ○ The pale-staining branched cells that makes up the sinoatrial node ● Transitional myocytes ○ More slender and having more fibrils than nodal myocytes. It is relatively slow thus contributing to the atrioventricular delay which is essential for optimal filling of the ventricles. ● Purkinje myocytes ○ Found at the periphery, increases the area of cell to cell contact due to their irregular shape CARDIAC MUSCLE INNERVATIONS ● The heart is innervated and its rate is modulated by the autonomic nervous system ● Parasympathetic nerve fibers ○ From the vagus and fibers from the sympathetic trunk form extensive plexuses as the base of the heart ● Ganglion cells and numerous nerve axons ○ Found in the wall of the right atrium, especially in the regions of the sinoatrial and atrioventricular nodes ● The heart rate is slowed by stimulation of the vagus and accelerated by the sympathetic nerve stimulation ● Autonomic nervous system ○ Acts on the myocardium indirectly by modifying the inherent rhythm of the pacemaker Figure 63. Structure of smooth muscle C. SMOOTH MUSCLE ● Smooth muscles are found in: ○ Contractile portion of the wall of the digestive tract from the middle of the esophagus to the internal sphincter of the anus → Motive power for mixing the ingested food with digestive juices → Propulsion of food through the tract ○ Walls of the ducts in the glands that are associated with the alimentary tract ○ Walls of respiratory passages from the trachea to the alveolar ducts ○ Blood vessels ● Spindle-shaped or fusiform that has blunt ends (cigarette butt) ○ Other spindle shaped: → Collagen fibers which is secreted by fibroblast → Fibroblast have pointed ends → Neural cells have curved s-shaped or comma-shaped cell ● Central elongated nucleus ○ The nucleus follows the shape of the cell ● Contractile elements in the peripheral sarcoplasm ● Cytoplasmic dense bodies ● Contain actin-binding protein alpha-actinin ● Contraction is slow ● Process of contraction: 1. Influx of calcium ion via calmodulin 2. Binding to myosin light chain kinase 3. Phosphorylation of myosin light chain 4. Interact with actin 5. Contraction ● Use markers (receptors) when identifying the classification of the origin of the cell Figure 64. Structure of smooth muscle, A Figure 65. Structure of smooth muscle, B AGULAN, ARENGA, BOLAÑO, DUARTE, FRANCISCO, NACIONALES, PIONELO, SEÑALISTA, TRESPECES, VIAJE | MG 9 17 of 26 Y1B4M1L2 HISTOLOGY OF INTEGUMENTARY & MUSCULOSKELETAL SYSTEMS ● Figure 66. Structure of smooth muscle, C ● ● Figure 67. Structure of smooth muscle Contact of Smooth Muscle Cells with One Another ● Smooth muscle fibers are scattered singly or in small groups in the ordinary connective tissue ○ Closely welded to the collagenous bundles surrounded by thin elastic fibers ○ During contraction they throw the tissue into fine folds and wrinkles → This can be well seen in the skin of the mammary papillae or the scrotum ○ Several parallel fibers unite to form a small cylindrical bundle whose ends are covered by elastic fibers. → An example is the smooth muscles connected with the hairs ○ In other cases the smooth muscle fibers are arranged parallel to one another in one plane → As in small arteries, because of the small lumen, each fiber bends sharply to surround the vessel ○ The smooth muscle cells are arranged in layers or bundles in the walls of certain large hollow organs: → Intestine → Bladder → Uterus ○ The direction of the fibers is the same in each layer, but varies between the different layers or bundles ○ The cells are so arranged that the thick, middle portion of one cell is opposite the thin ends of adjacent cells ● ● → In cross sections through a smooth muscle bundle, some of the cells have nuclei in the plane of section, and some do not ○ The connective tissue fibers outside the muscle cells continue into the spaces between the cells and bind them into bundles Loose connective tissue is present in small amounts. Between the thicker bundles and layers of smooth muscle cells. ○ It contains: → fibroblasts and wandering cells → collagenous and elastic fibers → a network of blood vessels and nerves ○ Connective tissue cells, however, do not occur in the narrow slit like spaces between the individual smooth muscle cells Reticular fibers - branch irregularly and pass longitudinally and transversely between the bodies of the smooth muscle cells ○ They can be stained with: → Mallory's aniline blue method → Silver impregnation methods ○ A characteristic of smooth muscle all over the body is the intimate association it bears with elastic fibers → This is so extensive that some authors consider them as forming a "myoelastic" tissue In smooth muscles: ○ The pull of each contracting cell is first transmitted to the surrounding sheath of reticular fibers and continues directly into those of the surrounding connective tissue. ○ Permits the force of the contraction of the entire layer of the smooth muscle to be uniformly transmitted to the surrounding parts → Narrowing of the lumen of blood vessels → Peristalsis of the intestine If a bit of fresh smooth muscle is stimulated by an electric current: ○ Each spindle-shaped cell shortens and becomes thicker ○ Sarcoplasm flows to a central point which thickens In the spontaneous contraction of smooth muscle ○ The nucleus and the mitochondria move passively ○ No fibrils can be seen in such living cells When living smooth muscle is fixed, some cells are often fixed in contraction, while adjacent cells are in relaxation Pathway ● Influx of calcium ion via calmodulin ● Binding to myosin light chain kinase ● Phosphorylation of myosin light chain ● Interact with actin ● Contraction Figure 68. Pathway of Smooth Muscle Contraction MUSCLE CONTRACTION SUMMARY ● Nerve impulse reaches myoneural junction ● Acetylcholine is released from the motor neuron ● Ach binds with receptors in the muscle membrane to allow sodium to enter AGULAN, ARENGA, BOLAÑO, DUARTE, FRANCISCO, NACIONALES, PIONELO, SEÑALISTA, TRESPECES, VIAJE | MG 9 18 of 26

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