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ITM 101 | HISTOLOGY LESSON # 6 - Striated Muscles Part 1 1st YEAR | A.Y. 2023-2024 | SEPTEMBER 14, 2023 DR. JOANNA MELISSA F MARQUEZ, MD, MPH, DPSP STRIATED MUSCLE The blood vessels supplying skeletal muscle ramify in...

ITM 101 | HISTOLOGY LESSON # 6 - Striated Muscles Part 1 1st YEAR | A.Y. 2023-2024 | SEPTEMBER 14, 2023 DR. JOANNA MELISSA F MARQUEZ, MD, MPH, DPSP STRIATED MUSCLE The blood vessels supplying skeletal muscle ramify in the epimysium and penetrate via the septa of the Skeletal muscle - striated and multinucleated perimysium to form, in the endomysium, a rich Smooth muscle - non-striated and uninucleated capillary network around the individual muscle Cardiac muscle - striated and uninucleated fibers. a muscle unit has a lot of mitochondria since it Skeletal Muscle Fibers requires lots of energy for muscle contraction (ATP - Units of organization of skeletal muscles generation) - Long cylindrical mutlinucleated cells unlike in smooth myosin has head and is thicker than actin that is uninucleated sarcoplasmic reticulum where Calcium goes out - Much larger than smooth muscle fibers, ranging from (needed for contraction) 10-30 cm in length and 0.1-0.5 mm in diameter Parallel Fibers - aggregated in bundles of fascicles large enough that they are visible to the naked eye *The picture above shows that the dark purple areas found at the periphery are the nucleus and the alternating light pink and dark pink lines are the striations of the muscle fibers. Connective tissue surrounding the muscles: ARRANGEMENT OF FASCICLES Epimysium - dense connective tissue surrounding the whole muscle; outermost layer varies from muscle to muscle Perimysium - thin septa that extend inward from it to In short muscles, fascicles are oriented parallel to the surround each of the fascicles direction of the pull Endomysium - the delicate reticulum investing the In very long muscles, fibers are usually shorter than individual fibers; surrounds the smallest unit and has the muscles as a whole and are connected to one or rich capillary blood supply more transverse bands of connective tissue Pennate type of muscle fiber arrangement in which each fiber attaches obliquely to a central tendon. This morphology is characterized by sarcomeres in parallel which has important implications for contractile properties 101 INTRODUCTION TO MEDICINE | HISTOLOGY AYURA 2027 1 ITM 101 | HISTOLOGY LESSON # 6 - Striated Muscles Part 1 1st YEAR | A.Y. 2023-2024 | SEPTEMBER 14, 2023 DR. JOANNA MELISSA F MARQUEZ, MD, MPH, DPSP Uni-pennate/uni-pinnate - fascicles are oriented Hypertrophy - happens when there is an increase in muscle obliquely with respect to a longitudinal band of function. connective tissue along one side of the muscle Bi-pennate/bi-pinnate- oblique fascicles radiate from a connective tissue core in the muscle; pattern resembles that of a barbs extending obliquely from the axial core of a feather Multi-pennate/multi-pinnate - oblique fascicles radiate from several longitudinal connective tissue strands and converge on the tendon; generally found in muscles where considerable power and a short range of motion are required DEVELOPMENT AND REPAIR Satellite cells, situated within the external lamina, participate in muscle repair after injury. However, skeletal muscle has only limited capacity for repair in adults. After minor injury, satellite cells within an intact endomysium may divide and fuse to restore damaged fibers. *The satellite cells become fibers. If the injury is more extensive, disrupting the endomysium, regeneration of muscle fibers does not occur. Instead, the damaged area is invaded by fibroblasts that deposit collagen, resulting in a fibrous scar. Restoration of muscle function after such an injury depends mainly on hypertrophy of the remaining undamaged fibers. *Speaker’s question: When do you amputate an arm? What will you look for? Answer: Blood Supply; Innervation Myoblast → uninucleate precursors that proliferate *When the extremity is involved, it is important to check if the and fuse to form myotubes. patient still has sensation on the most distal part. Myotubes → long multinuclear cells. The elongated syncytia then develop, in their cytoplasm called STRUCTURE OF MUSCLE FIBERS myofibrils. Myofibrils→ the contractile elements of Plasma membrane of muscle fibers is called differentiated muscle fibers. sarcolemma and the cytoplasm, the sarcoplasm. During postnatal growth, the muscle fibers increase Sarcolemma of the long cylindrical fibers is in length and thickness, reaching a diameter of 10-70 reinforced by an external lamina. *External lamina is um, depending on the muscle and the species. Fibers like the basement membrane in the epithelial cells. in the same muscle may vary considerably in their Myofibrils occupy the bulk of the sarcoplasm. *The thickness. cytoplasm of a muscle cell is full of actin and myosin. Atrophy – happens when there is decreased muscle Peripheral location of the nuclei (In cardiac muscle, function. nuclei are central) 400 kD protein dystrophin in the cytoplasm ○ provides mechanical reinforcement to the membrane ○ thereby protecting it against stresses developed during muscular contraction ○ X-linked Duchenne muscular dystrophy *Speaker’s question: Where do you see lack of dystrophin?* Answer: X-linked Duchenne muscular dystrophy 101 INTRODUCTION TO MEDICINE | HISTOLOGY AYURA 2027 2 ITM 101 | HISTOLOGY LESSON # 6 - Striated Muscles Part 1 1st YEAR | A.Y. 2023-2024 | SEPTEMBER 14, 2023 DR. JOANNA MELISSA F MARQUEZ, MD, MPH, DPSP Gowers' Sign *Mitochondria - on the side *Blue - Sarcoplasmic reticulum is blue due to the calcium and penetrates into the T tubule (The sarcoplasmic reticulum or SR membrane is a membranous network that surrounds the myofibrils and makes contact with the T-tubule at junctions called dyads. - ScienceDirect) The bands that appear dark in stained preparations are anisotropic (birefringent) when examined with No dystrophin to provide mechanical reinforcement to the the polarizing microscope and are, therefore, membrane and no protection against stresses developed designated A-bands, whereas the lighter-staining during muscular contraction. bands are isotropic and are called the I-bands. The relative lengths of the bands depend on the state *A person with Gowers’ Sign cannot overcome the stress on of contraction of the muscle. the muscle and is unable to stand on their own. They would The I-bands are very short during contraction, longer use their hands to push themselves up. during relaxation, and longest in muscle that has been passively stretched. THE STRUCTURE OF MUSCLE FIBERS The length of the A-bands remains constant in all phases of the cycle of contraction and relaxation. All of the common cell organelles are represented in the Each I-band is bisected by a transverse line, the Z-line sarcoplasm. or Z-disc. A small Golgi complex is associated with one pole of The segments of myofibrils between successive most of the nuclei. Z-lines are called sarcomeres and all of the Mitochondria (sarcosomes) congregate in the morphological changes during the contractile cycle juxtanuclear sarcoplasm and are also deployed in are described with reference to this structural unit. longitudinal rows between the myofibrils where they *Contraction refers to the contraction of the provide energy for muscle contraction (ATP). sarcomeres *Well supported on the sides where it is located. The sarcomere includes an A-band and half of the Lipid droplets are found in small numbers between two contiguous I-bands. the myofibrils or among the mitochondria at the poles of the nuclei. Glycogen can be demonstrated throughout the sarcoplasm. Myoglobin is present in low concentration. As required, oxygen dissociates from myoglobin and becomes available for oxidations. In longitudinal sections, stained with iron hematoxylin, the cross-striations that are barely detectable in fresh muscle are greatly accentuated, with heavily stained bands alternating with relatively pale bands. *Sarcomere - from Z to Z, one whole A, 2 halves of I (half per side) 101 INTRODUCTION TO MEDICINE | HISTOLOGY AYURA 2027 3 ITM 101 | HISTOLOGY LESSON # 6 - Striated Muscles Part 1 1st YEAR | A.Y. 2023-2024 | SEPTEMBER 14, 2023 DR. JOANNA MELISSA F MARQUEZ, MD, MPH, DPSP Generation of ATP depends on anaerobic glycolysis HETEROGENEITY OF SKELETAL MUSCLE FIBERS of glucose derived from abundant deposits of glycogen in the sarcoplasm 2 TYPES OF FIBER Innervated by larger axons that form motor end plates about twice the size of those red fibers 1. Twitch Fibers (fast fibers) *(Axons, a tail-like structure, also called nerve fiber, is which propagate an action potential and respond a portion of a nerve cell (neuron) that carries nerve with all-or-none contraction, impulses away from the cell body. -Britannica) 2. Tonic Fibers (slow fibers) Contract rapidly and generate large force but they which are unable to propagate an action potential fatigue rapidly. and require a series of nerve impulses. Their Best suited for brief bursts of intense muscle activity contraction is more prolonged than that of twitch Subsarcolemmal mitochondria are fewer and fibers. *Contraction takes time but it is more longitudinal columns are rare and often interrupted. sustained. 3. Intermediate Fibers 3 TYPES OF FIBER IN CYTOCHEMICAL STAINING METHOD Mitochondrial disposition in intermediate fibers is similar to that of red fibers, but thick mitochondrial 1. Red fibers (slow-twitch, oxidative fibers) columns are rarely found (Fawcett, 1994) relatively small in diameter, darker color ULTRASTRUCTURE OF STRIATED MUSCLE FIBERS greater myoglobin content rich supply of capillaries The structure of the common organelles is not numerous large mitochondria fundamentally different from that in other cells Lipid droplets are common in the sarcoplasm of The mitochondria have numerous closely spaced these fibers, owing to the abundance of their cristae and their distribution, in intimate relation to mitochondria, they stain intensely with the the myofibrils, brings the source of energy (ATP) cytochemical reaction for the enzyme succinic close to its site of utilization. dehydrogenase The endoplasmic reticulum consists of Z bands tend to be wider compared with other fiber membrane-bounded tubules occupying the narrow types spaces between the myofibrils. It’s largely devoid of Innervated by small axons with small and relatively associated ribosomes. simple motor end plates Specialized function: Site of calcium Motor units consisting of red fibers contract more sequestration (the process of binding or slowly than other types confining calcium ions such that they are Very resistant to fatigue due to their ability for separated from other components of a oxidative regeneration of ATP biological system) during muscle relaxation. ○ ATP - high energy compound needed to It is also where free calcium ions are recycle the contractile process released into the sarcoplasm to trigger These properties make them effective in postural contractions in response to nerve impulses maintenance (axons). Spherical subsarcolemmal mitochondria are large and abundant Slender, paired mitochondria are transversely oriented on either side of the Z-lines. In interfibrillar spaces, mitochondria, which is one sarcomere in length, form longitudinal columns. These may be thick with multiple mitochondria or thin consisting of rows of single mitochondria 2. White Fibers (fast-twitch fibers) Largest of all the fiber types Subplasmalemmal mitochondria are smaller and numerous compared to red fibers and interfibrillar mitochondria are relatively few Cytochemical reactions for succinic dehydrogenase is correspondingly weak 101 INTRODUCTION TO MEDICINE | HISTOLOGY AYURA 2027 4 ITM 101 | HISTOLOGY LESSON # 6 - Striated Muscles Part 1 1st YEAR | A.Y. 2023-2024 | SEPTEMBER 14, 2023 DR. JOANNA MELISSA F MARQUEZ, MD, MPH, DPSP Sarcoplasmic reticulum - Composed of tubules and cisternae surrounding each myofibril. - The elongated tubules are known as longitudinal SR (I-SR) which are dedicated to the removal of calcium (Ca2+) from the cytosol and are localized around the A and I band of each sarcomere. - At the borders between the A and I band, the I-SR merges to form the terminal cisternae. These are positioned at the opposite sides of a transverse tubule. - Transverse tubule (TT) - structure formed by two terminal cisternae - One TT is called a “triad” EXCITATION - CONTRACTION COUPLING - The region of the terminal cisternae that opposes the TT membrane is called the It begins at the myoneural junction with the junctional SR (i-SR). generation of an action potential that spreads over the sarcolemma and along the membrane of the Sarcotubules are longitudinal anastomosing lateral T-tubules into the interior of the muscle fiber. branches form a denser at the H-zone of each This activates events at the interface between the A-band. T-tubules and the terminal cisternae of the triads At the junction of the A-band with the I-band, the that result in the rapid release of calcium from the longitudinal sarcotubules are confluent with a sarcoplasmic reticulum. transversely oriented tubule of larger caliber, called The calcium released in the sarcoplasm binds to the the terminal cisterna. myofibrils and triggers shortening. The longitudinal tubules that span successive I-bands When depolarization of the sarcolemma by nerve and the intervening Z-line also terminate in a impulses ceases, calcium is actively transported back separate terminal cisterna at the A-I junction. into the lumen of the terminal cisternae. Thus, a pair of parallel terminal cisterna is associated The consequent lowering of the calcium with each A-I junction along the length of the concentration around the myofibrils brings about myofibril, two pairs to each sarcomere. muscle relaxation. *Sacrotubules meet to form the terminal cisternae. SUBSTRUCTURE OF THE MYOFIBRILS Myofibrils are composed of even smaller myofilaments (myosin and actin). Myosin filaments, 1.5 pm in length and 15 nm in diameter, oriented longitudinally in a parallel array, spaced about 45 nm apart, a principal constituent of the A-bands. They are held in the lateral register by slender cross-links in the middle of the Between each pair of terminal cisternae, there is a A-band. The transverse alignment of these slender transverse tubule (T-tubule) extending links creates a thin linear density called the inward from the sarcolemma M-line that bisects the paler H-band at the T-tubules are slender invaginations of the middle of each A-band. sarcolemma that penetrate deep into the interior of Enzymatic proteolysis of the myosin the muscle fiber crossing many myofibrils. molecule cleaves it into two fragments, a The two parallel terminal cisternae and the straight portion called light meromyosin intervening T-tubule form a complex referred to as (LMM), representing the greater part of the triad. the tail, and a shorter segment called heavy meromyosin (HMM), which includes the heads and a short portion of the backbone of the molecule. 101 INTRODUCTION TO MEDICINE | HISTOLOGY AYURA 2027 5 ITM 101 | HISTOLOGY LESSON # 6 - Striated Muscles Part 1 1st YEAR | A.Y. 2023-2024 | SEPTEMBER 14, 2023 DR. JOANNA MELISSA F MARQUEZ, MD, MPH, DPSP Actin filaments are the dominant component of the terminate at the edge of the disc. There, each I-band. They interdigitate with myosin filament in the filament is attached to four thin diverging neighboring A-bands to varying degrees depending Z-filaments. on the state of muscle contraction. In longitudinal sections, the connecting Z-filaments form a zigzag pattern across the myofibril. ADDITIONAL INFO: Filamin, an actin-binding protein, is also found in the When a heavy meromyosin fraction is added to Z-discs of skeletal muscle. isolated actin filaments, large numbers of these HMM fragments attach to the filaments decorating them in a distinctive arrow-head pattern. This demonstrates, in vitro, the actin-binding property of the heads of the myosin molecules that is essential for muscle contraction. Each myofibril is enclosed in a delicate sleeve of 10 nm filaments and the collars around the Z-lines of neighboring myofibrils are interconnected by short transverse filaments. Beneath the sarcolemma, there are inconspicuous rib-like bands, called costameres, seen in longitudinal sections as small densities that repeat along the fiber in register with the Z-lines of the peripheral myofibrils. In contracted or swollen muscle fibers, indentations occur along the length of the fiber at these subsarcolemmal densities which can be shown to Muscle exhibits a resistance to stretch that is contain the anchoring protein, vinculin. independent of the interaction of actin and myosin filaments and a third type of filament, responsible for this passive elasticity, was postulated. REFERENCES These extremely thin strands (~ 4 nm) consist of titin, an exceptionally large protein having a molecular Bloom, W., & Don Wayne Fawcett. (1994). A textbook of weight of about 3 x 10o D. The molecules are histology. Chapman & Hall. approximately 1 um long, spanning the distance from Britannica. (2019). Axon | anatomy. In Encyclopædia the M-line of the A-band to the Z-disc. Britannica. https://www.britannica.com/science/axon Titin is the main structural basis for myofibrillar Feher, J. (2012, January 1). 5.7 - The Cellular Basis of elasticity. It is believed to maintain the central Cardiac Contractility (J. Feher, Ed.). ScienceDirect; position of thick filaments in the sarcomere. Academic Press. https://www.sciencedirect.com/science/article/abs/pi i/B9780123821638000517 The myofilaments of successive sarcomeres are linked end-to-end by Z-disc. In very thin sections of muscle from a species with a relatively simple disc, the actin filaments appear to 101 INTRODUCTION TO MEDICINE | HISTOLOGY AYURA 2027 6

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