James S. Lowe BMedSci, BMBS, DM, FRCPath , Peter 1000. Anderson DVM, PhD , in Stevens & Lowe'southward Human Histology (Fourth Edition), 2015
Basement Membrane and External Lamina
Basement membranes and external lamina are specialized sheets of extracellular matrix that lie between parenchymal cells and back up tissues
Basement membranes and external lamina are specialized sheet-like arrangements of extracellular matrix proteins and GAG, and act as an interface between parenchymal cells and support tissues.
They are associated with epithelial cells, muscle cells and Schwann cells, and also form a limiting membrane effectually the central nervous organisation. Basement membrane and external lamina have similar structures.
Basement membranes have five major components: type Four collagen (Fig. 4.xi), laminin, heparan sulfate, entactin and fibronectin. With the exception of fibronectin, these are synthesized past the parenchymal cells. In addition, at that place are numerous pocket-size and poorly characterized protein and GAG components.
The full general structure of basement membrane has been well characterized (Fig. iv.12). Superimposed on this, minor protein and sugar components are specific to certain tissues. Thus, for example, the renal basement membrane differs from that of the skin.
The chief functions of basement membrane are cell adhesion, diffusion barrier and regulation of cell growth
Basement membrane has three chief functions:
Kickoff, it forms an adhesion interface between parenchymal cells and underlying extracellular matrix, the cells having adhesion mechanisms to ballast them to basement membrane, whereas basement membrane is tightly anchored to the extracellular matrix of support tissues, specially collagen. Where such an interface occurs in non-epithelial tissues, for example effectually muscle cells, it is referred to every bit an external lamina.
Second, the basement membrane acts as a molecular sieve (permeability bulwark) with pore size depending on the charge and spatial arrangement of its component GAG. Thus, the basement membrane of claret vessels prevents large proteins leaking into the tissues, that of the kidney prevents protein loss from filtered blood during urine product, and that of the lung permits gaseous diffusion.
Third, basement membrane probably controls cell organization and differentiation by the mutual interaction of cell surface receptors and molecules in the extracellular matrix. These interactions are the subject of intense inquiry, particularly in the investigation of mechanisms that might forestall the spread and proliferation of cancer cells throughout the body.
Brian R. Berridge , ... Eugene Herman , in Haschek and Rousseaux'due south Handbook of Toxicologic Pathology (Third Edition), 2013
Ultrastructural Appearance
The cobweb surface is covered past the plasma membrane (sarcolemma) and external lamina. The elongated subsarcolemmal nuclei are surrounded by accumulation of mitochondria, lipid aerosol, glycogen granules, elements of sarcoplasmic reticulum, and the Golgi apparatus. The fiber contains arable contractile material that is organized as many myofibrils of 0.five–1.0 μm in diameter. Myofibrils are composed of repeating units, termed sarcomeres, of 2–3 μm in length. Sarcomeres end at dumbo Z lines that incorporate αα-actinin, actin, and tropomyosin. Thin sixty-Å bore myofilaments containing actin, troponin, and tropomyosin extend on both sides of the Z line to form I bands. The middle one-half of the sarcomere contains thick (160-Å diameter) myofilaments that are composed of myosin and interdigitate with the adjacent thin filaments. The center of the sarcomere, with just thick filaments, is the H band and is bisected by the relatively dense M line. Fiber contraction results in shortening of sarcomeres due to sliding of thick and thin filaments over each other to produce narrowed I and H bands. Cross-sections of myofibrils show variable appearance depending on the location in the sarcomere, just the edges of the A band volition have thick filaments surrounded by a hexagonal array of thin filaments. The sarcoplasm surrounding myofibrils contains elements of the transverse (T) tubular system and sarcoplasmic reticulum (SR), mitochondria, lipid droplets, glycogen granules, and cytosol. The T tubules are invaginations of the sarcolemma that are ofttimes seen at the border of the I band with 2 next elements of SR to course a "triad." The T-tubular system functions as a channel to allow rapid spread of an electric impulse from the motor end plate to the residual of the fiber to elicit release of calcium stored in the SR, with subsequent bounden to regulatory proteins and interaction of actin and myosin to initiate contraction.
James Schumacher , in Equine Surgery (Fifth Edition), 2019
Fractional Phallectomy by en Bloc Resection With Penile Retroversion
Removal of the portion of the penis that resides within the preputial cavity, the internal and external lamina of the prepuce, and regional lymph nodes may be indicated when these structures, peculiarly the external lamina of the prepuce, are extensively affected with neoplasia.103En bloc resection has also been advocated when lesions necessitating partial phallectomy extend proximal to the preputial band.120,151 Proponents of this recommendation maintain that amputating the penis proximal to the preputial band results in excessive tension on the peel sutures at the site of amputation when the penis is retracted into the preputial cavity, making the sutured site of amputation prone to dehisce. This author has not observed this complication to partial phallectomy performed proximal to the preputial ring.
To remove the free portion of the penis and prepuce past en bloc resection, a fusiform incision is created around the preputial orifice. The incision begins about vi cm cranial to the orifice and ends about 10 cm caudal to it. The incision is carried to the deep fascia of the intestinal tunic, and if neoplasia has metastasized to the superficial lymph nodes, dissection is extended through this airplane to both superficial inguinal rings, and the superficial inguinal lymph nodes are removed. The penis is amputated 6 to 8 cm caudal to the fornix of the prepuce, and the amputated portion of the penis and the prepuce are removed en bloc. The penile shaft is amputated using a method similar to that described by Scott, leaving four cm of urethra protruding from the penile stump (Figure 61-30, A).99
By bluntly separating penile fascia, the stump of the penis is retroverted through a 6-cm subischial incision created approximately 20 cm ventral to the anus, so that the distal stop of the penile stump points caudad and extends just beyond the subischial incision (see Effigy 61-30, B). The tunica albuginea of the CCP and the fascia of the penis are sutured to the subcutaneous tissue of the subischial incision. The dorsal aspect of the protruding stump of the urethra is incised longitudinally over its 4-cm length, and the edges of the urethra are sutured to the surrounding edges of the incised subischial pare. Penrose drains are placed deeply at the cranial incision, if deemed necessary, and the subcutaneous tissue and peel are each closed separately (Figure 61-31). The technique tin be modified past amputating the penis using the Williams or Vinsot technique of fractional phallectomy, rather than the technique described past Scott.152
Fractional phallectomy by en bloc resection with penile retroversion is a lengthy procedure, merely having one surgeon close the abdominal incision while another sutures the penile stump to the subischial incision decreases the time of surgery substantially.
Just outside the myocyte cell membrane, or sarcolemma (arrows in Figure 5.ane), lies the external lamina or glycocalyx (arrowheads in Effigy 5.2) which binds cations, primarily Ca2+. The sarcolemma is continuous with and invaginates (T on right in Figure v.4d) into the myocyte interior as an extensive membranous network known every bit T-tubules (t in Figure 5.1, * in Figure v.2) that are ~0.2 µm in bore. This occurs at the level of the sarcomere Z-disc in cardiac myocytes only at the A–I junction in skeletal muscle cells. The system of T-tubules in cardiac myocytes is sometimes referred to as the Transverse-Centric Tubular System (TATS) since longitudinally oriented T-tubules are also observed (11). Surface glycocalyx extends into T-tubules, lining their inner surface and distinguishing them from SR (* in Figure five.2, T in Figures 5.4c and d). The surface glycocalyx does non extend into the intercellular junction at the intercalated discs (IDs).
IDs are specialized intercellular junctions at the ends of myocytes that are important in relaying mechanical force and conduction of the electrical impulse. Fascia adherens junctions grade almost of the ID region and are the internal site of actin filament insertion. Desmosomes (double pointer in Figure 5.5a) have a much denser mat and are the site of insertion for longitudinally oriented desmin filaments. Desmosomes and fascia adherens (less dumbo areas of membrane specialization betwixt double arrows in Effigy v.5a) junctions play an important role in cellular adhesion. Depending on the intensity of staining, it is sometimes difficult to distinguish between fascia adherens and desmosomes. Gap junctions (arrows in Effigy 5.5a), comprised of connexons, appear as closely associated areas of plasma membranes and are of import in electrical conduction.
Another tubular system, the sarcoplasmic reticulum (SR), wraps around myofibrils, and forms junctions with T-tubules and the surface sarcolemma. SR is frequently divided into three components: network SR (effectually myofibrils, S in Figure 5.4c), junctional SR (forms couplings with T-tubules: arrowhead in Figure 5.4d; and sarcolemma: arrow in Figure 5.4d), and corbular SR (ovoid bodies attached to network SR) (12). The ratio of T-tubules to SR is higher in cardiac muscle than in skeletal musculus where SR is relatively more abundant. In cardiac muscle, diads (junction of one SR profile with one T-tubule) are mutual while triads (junction of ii SR profiles with an intervening T-tubule) are mutual in skeletal muscle. T-tubules occupy near one% and SR near 2% of cardiac myocyte cytoplasm (13). Interestingly, Page and McAllister reported that total myocyte surface to book ratio was maintained during cardiac hypertrophy past excess proliferation of T-tubules (xiv). Additionally, they reported that the ratio of SR to myofibrils is maintained during cardiac hypertrophy. A recent study implicates maladaptive remodeling of this membranous system in progression from hypertrophy to middle failure (15). The shut relationship between SR and myofibrils, related to Ca2+ handling and wrinkle, has been appreciated for some time. However, the shut proximity and interaction between SR and mitochondria is as well of import since mitochondria produce ATP necessary for SR function.
James Due south. Lowe BMedSci, BMBS, DM, FRCPath , Peter 1000. Anderson DVM, PhD , in Stevens & Lowe'southward Man Histology (Fourth Edition), 2015
Myoepithelial Cells
Secretions from glands are expelled past the contractile function of myoepithelial cells
Myoepithelial cells are plant in exocrine glands, including highly developed glands, such as the breast, where they form a major population surrounding glandular acini and ducts, and clasp secretions from the glandular lumina.
Myoepithelial cells are generally camouflaged in routine H&Eastward sections, appearing as a layer of flat cells running around acini and ducts. They have dark-staining, rounded nuclei and clear or vacuolated cytoplasm.
Around acini, myoepithelial cells have a stellate, multiprocessed morphology in three dimensions and grade a contractile meshwork, which encloses secretory units of glands. Effectually ducts they are fusiform in shape and surround the periphery of ducts in a way analogous to barrel hoops.
Ultrastructurally, myoepithelial cells comprise contractile proteins arranged in a similar style to that in smoothen muscle and take numerous desmosomal connections with adjacent cells.
Immunohistochemically, they can be detected by their content of the musculus-specific intermediate filament desmin (Fig. 5.13).
Myoepithelial cells are controlled past the autonomic nervous organisation and on stimulation contract and expel glandular secretions.
For online review questions, please visithttps://studentconsult.clue.com.
Stop of Affiliate Review
True/fake Answers to the MCQs, as well as Case Answers, can be Found in the Appendix in the back of the Volume.
i.
Which of the following features are seen in the skeletal musculus cells?
(a)
Accept thin filaments made of actin which are anchored to the Z band
(b)
Have thick filaments made of desmin which are anchored to the M band
(c)
Regulate contraction by control of calcium release from sarcoplasmic reticulum
(d)
Are surrounded by an external lamina
(e)
Contain multiple nuclei in each cell
2.
Which of the following are true of cardiac muscle cells?
(a)
Are mononuclear and linked by intercellular junctions to form a fibre
(b)
Are striated in a similar mode to skeletal muscle
(c)
Tin can regenerate following cell damage
(d)
Regulate contraction past release of calcium from sarcoplasmic reticulum
(e)
Have communicating junctions linking fibres to facilitate contraction
iii.
Which of the following features are specific for smooth muscle cells?
(a)
Have unmarried nuclei
(b)
Use actin and myosin to develop contractile forces
(c)
Are surrounded by an external lamina
(d)
Accept membrane receptors for hormones
(e)
May generate their own level of rhythmic contraction
4.
Myofibroblasts, pericytes and myoepithelial cells are all types of specialized contractile cells with which of the following features?
(a)
Myoepithelial cells are found in exocrine glandular tissue such equally the breast
(b)
Myoepithelial cells are stellate cells, with multiple processes, which surround secretory units of glands
(c)
Myoepithelial cells are controlled past autonomic innervation
(d)
Pericytes may assume the office of primitive mesenchymal cells
(e)
Myofibroblasts proliferate and are involved in repair following tissue impairment
Instance v.1 Sudden Cardiac Decease
A 24-year-quondam male is brought into infirmary past ambulance having collapsed while running in a local one-half-marathon. Paramedics had attended and he was establish to have no cardiac output and was in asystole. He was pronounced expressionless and an autopsy requested to plant the cause of death.
The pathologist plant that the heart was greatly enlarged and showed hypertrophy of the left ventricle. The left ventricular wall was much thicker than normal. Histology showed that myocardial cells were greatly enlarged and had an abnormal blueprint of myofibres. A diagnosis of hypertrophic cardiomyopathy was fabricated. Further genetic testing showed a mutation in one of the genes coding for cardiac-specific myosin.
Q. Explicate the human relationship between the mutation in the gene and cardiac affliction.
James South. Lowe BMedSci, BMBS, DM, FRCPath , Peter G. Anderson DVM, PhD , in Stevens & Lowe'southward Human Histology (Fourth Edition), 2015
Skeletal Muscle
Skeletal muscle is responsible for voluntary motion
The histological characteristics of skeletal muscle cells and the structural ground of musculus contraction are described on pages 71–76.
Individual muscle cells are arranged into large groups to form anatomically distinct muscles. These are characterized by:
•
An orderly alignment of the constituent cells to generate a directional force post-obit contraction
•
Anchorage to other structures by highly organized fibrocollagenous support tissues
•
A rich claret supply reflecting loftier metabolic demands
•
Innervation and command by specialized neurons (motor neurons) that terminate on muscle cells at specialized nerve endings (motor endplates)
•
Incorporation of specially adapted skeletal muscle cells into structures called spindles, to act every bit sensors of musculus stretch.
Embryologically, muscle fibres develop from mesenchymal tissues
In embryogenesis, skeletal musculus develops from primitive mesenchymal tissues of the mesoderm. Pocket-sized spindle-shaped or strap-shaped cells with a single nucleus and arable pink-staining cytoplasm develop from primitive mesenchymal cells. These are skeletal musculus cell precursors, the rhabdomyoblasts (Fig. 13.i). Numerous individual rhabdomyoblasts then fuse to course multinucleate muscle fibres, the cells enlarging in size when they become continued to the nervous system and receive motor stimulation.
Residual cells with the part of rhabdomyoblasts (i.e. capable of differentiating further into functional striated musculus cells) persist in developed skeletal muscle every bit satellite cells (see Fig. 13.half dozen). Following musculus impairment and loss of fibres, these cells proliferate and may produce new muscle cells.
A muscle is composed of many muscle fibres
A mature muscle fibre is equanimous of large numbers of myofibrils bounded by a prison cell membrane termed 'the sarcolemma' (see Figs 5.two, xiii.2).
Each skeletal muscle cell is typically extremely long (up to 10 cm in length), and it is therefore more usual to utilize the term 'skeletal muscle fibre' rather than jail cell.
Many musculus fibres are arranged together to form a muscle (Fig. 13.3). Despite existence elongated, individual muscle cells practice non extend the full length of a muscle but are bundled in overlapping bundles, the force of contraction being transmitted through the organization of the support tissues.
Different muscles are characterized by different physiological and metabolic properties
The physiological and metabolic properties of private skeletal muscles are determined by differences in the construction of their elective musculus fibres.
In both animals and man, information technology has been possible to define several subtypes of musculus fibre by macroscopic, physiological, biochemical and histochemical criteria, but there are marked interspecies variations.
Histochemical staining for specific enzymes delineates several types of fibres and is a useful method for analysing muscle. Two main types of fibres are identified (types 1 and 2), and type 2 fibres tin exist subdivided into types 2A, 2B and 2C (Fig. thirteen.iv). Type 2C fibres are thought to be a primitive form of type 2 fibre and, with advisable innervation, are probably capable of developing into 2A or 2B fibres. Such histochemical staining is used routinely in the report of muscle pathology and allows the histological diagnosis of certain muscle diseases.
Histochemical staining tin can also be correlated with other functional and biochemical attributes of muscle (Fig. xiii.4c).
Not all muscles have the same proportions of type 1 and blazon two fibres. In general, muscles with a role in maintaining posture (e.g. calf muscles) have a high proportion of type 1 fibres, whereas muscles used for short bursts of power have abundant type 2 fibres.
Different individuals are genetically endowed with variable proportions of musculus fibre types in defined muscles, and this may limit athletic prowess at a particular sport; training does not affect the proportion of fibres in whatever given muscle, but does influence their size.
Muscle has a rich blood supply because of the high energy demands of contraction
Big arteries penetrate the epimysium and dissever into modest branches that run in the perimysial support tissues, forming perimysial arteries and veins. These branches terminate in a vast capillary network, which runs in the endomysium. Each muscle fibre is served by several capillary vessels.
Normal adult skeletal muscle cells do not undergo cell partition
Whatsoever increased demands placed on a musculus, for example past weight training, result in increased musculus size because the cells themselves increase in size (i.e. hypertrophy).
Information technology is possible, however, for skeletal musculus cells to regrow because the pool of inactive stem cells in adult muscle called 'satellite cells' tin can be stimulated to divide post-obit impairment. These cells are non discernible by light microscopy, but may be seen ultrastructurally (Fig. 13.half-dozen). They are exceptional and appear equally small spindle-shaped cells lying just beneath the external lamina of a musculus fibre.
Clinical Example
Diseases of Muscle
Several diseases of muscle accept been attributed to specific metabolic or structural abnormalities (Fig. 13.5a).
Duchenne muscular dystrophy is the well-nigh common inherited muscle disease and characteristically affects male children. Such individuals go unable to stand unaided in early childhood and develop progressive muscle weakness, becoming wheelchair-bound by their mid-teens and typically dying in early developed life.
The abnormality in Duchenne muscular dystrophy is due to a defect in the factor coding for a protein termed 'dystrophin' (Fig. xiii.5b). This protein links the actin cytoskeleton of muscle to the external lamina; its absence leads to aberrant muscle fibre fragility.
Fibres that accept regenerated in adult life following harm to a muscle tin be detected histologically considering they commonly incorporate centrally placed nuclei, rather than the peripheral nuclei typical of normal fibres.
Musculus contains stretch receptors
Although in that location are no pain receptors in skeletal muscle, at that place are receptors sensitive to stretch, which function as function of a feedback arrangement to maintain normal muscle tone (i.eastward. the spinal stretch reflex arc).
Sensory fibres that provide data on the tension of skeletal musculus arise from two sources:
•
Encapsulated nerve endings responding to stretch in the tendon associated with a muscle
•
Spiral nerve endings (sensory afferent fibres) sensing stretch and tension of specialized muscle fibres independent in a special sense organ in muscle chosen the muscle spindle (Fig. 13.7).
The muscle spindle sensory machinery maintains normal tone and musculus coordination.
Motor nerves to muscle finish in motor endplates
Large nerves, containing both motor and sensory axons, enter muscles by penetrating the epimysium and branch to form pocket-sized nerves, which run in the perimysium.
Perimysial nerves comprise axons to fulfil both motor and sensory functions. The motor axons destined to innervate skeletal muscle (α efferent fibres) enter the endomysium every bit nerve twigs and branch to innervate several fibres.
At the end of each twig, the axon becomes modified to grade a motor endplate, and it is this that activates skeletal muscle wrinkle (Fig. 13.viii).
Activation of the motor axon causes the release of acetylcholine from its storage granules by exocytosis. Acetylcholine then diffuses across the gap between the axon and musculus fibre and interacts with specific membrane receptors to cause depolarization of the muscle fibre, which initiates contraction (run into p. 73).
The activeness of secreted acetylcholine is rapidly curtailed by the action of an enzyme chosen 'acetylcholinesterase', which is bound to the basement membrane investing the junctional folds.
In add-on to nervus fibres decision-making voluntary movement, specialized motor axons (γ efferent fibres) innervate fibres in the musculus spindle.
Clinical Example
Myasthenia Gravis
Myasthenia gravis is a disease acquired by the formation of antibodies to the acetylcholine receptor on the sarcolemma in the junctional folds of the motor endplates. The antibodies demark to the acetylcholine receptors and thereby forbid released acetylcholine from interacting with the receptors and causing depolarization.
Affected individuals develop tremendous muscle weakness manifest past fatiguability, inability to lift the artillery, failure to maintain an upright posture of the head, and drooping of the eyelids.
Treatment is past the administration of drugs (anticholinesterases) that inhibit the activity of the enzyme acetylcholinesterase. This potentiates the action of released acetylcholine and allows it to demark to receptors non blocked by antibody.
Brian R. Berridge , ... Eugene Herman , in Fundamentals of Toxicologic Pathology (Tertiary Edition), 2018
Response to Injury
Skeletal muscle volition answer to insults with a limited number of morphological reactions. In fact diseases of differing etiologies may showroom similar types of lesions. Thus information technology may not exist possible to render a specific etiologic diagnosis for a given skeletal muscle lesion even following careful microscopic written report from a given instance.
Many injuries of skeletal muscle heal by regeneration rather than by fibrosis—which is a distinguishing feature of repair in skeletal versus cardiac musculus. This is especially true for the mutual monophasic or polyphasic polyfocal myopathies (see subsequent text) such as those associated with nutritional deficiencies, metabolic disorders, and myotoxicities. In these diseases, although all-encompassing muscle fiber necrosis may occur, the scaffolding of external lamina that surrounds the degenerated muscle fiber and the innervation and blood supply to the damaged muscle are preserved, permitting myofiber regeneration within the external lamina (which is often virtually complete). Regeneration is further promoted in these weather condition by the brusk-term nature of the insult responsible for the muscle injury. In contrast, prolonged insults such equally denervation or genetic derangements frequently induce muscular diseases in which regeneration is limited. In astringent myopathic diseases (i.e., those in which muscle tissue is directly damaged), extensive disruption of endomysial connective tissues and "tubes" of external laminae from damaged myofibers may occur from trauma, hemorrhage, or infection. In such cases, the effect of healing volition be express regeneration accompanied by extensive fibrosis and scarring.
The cellular events of skeletal muscle regeneration are well characterized and centre on the proliferation of mononucleated myogenic stem cells, termed myoblasts (Figure 10.three). Myoblasts arise from satellite cells, a population of resting and undifferentiated cells that persist in mature skeletal muscle and appear morphologically as very thin subsarcolemmal cells that lie between the sarcolemma and the external lamina of myofibers. For unknown reasons, satellite cells tend to exist resistant to many insults that destroy mature myofibers. Following selective destruction of skeletal muscle fibers, the sarcoplasmic debris is removed rapidly by invasion of macrophages and phagocytic lysis (Effigy 10.4). The persisting sarcolemmal "tubes" of external laminae rapidly get populated by elongated myoblasts with large vesicular nuclei and prominent basophilic sarcoplasm that reflects the numerous polyribosomes supporting intense synthesis of cellular proteins in these cells. Myoblasts fuse to grade multinucleated cells termed sarcoblasts, which further elongate to form myotubes that apace bridge the gap of disrupted sarcoplasm in damaged myofibers. Myotubes have rows of centrally located nuclei and peripheral masses of forming contractile myofilaments that soon become oriented into sarcomeres and myofibrils with restoration of cross-striations in the immature myofibers (Effigy ten.5). Subsequently the cardinal nuclei will migrate to their normal subsarcolemmal location (as seen in mature fibers), and the regenerated muscle fibers may and so be indistinguishable from adjacent fibers that accept not suffered injury.
Figure 10.3. Schematic diagram of segmental myofiber necrosis and regeneration. (A) Myofiber, longitudinal section, demonstrating normal histologic features. (B) Segmental coagulation necrosis. (C) The necrotic segment of the myofiber has become floccular (i.due east., dissolving) and discrete from the adjacent viable portions of the myofiber. The satellite cells are enlarging. (D) The necrotic segment of the myofiber has been invaded past macrophages to remove the necrotic droppings, and satellite cells are migrating to the center to develop into myoblasts. The sarcolemma (cell membrane) of the necrotic segment has disappeared. (Eastward) Myoblasts take formed a myotube, which has produced sarcoplasm. This extends out to see the viable ends of the myofiber. The integrity of the myofiber is maintained by the sarcolemmal tube formed by the basal lamina and endomysium. (F) Regenerating myofibers have a reduced diameter and central rowing of nuclei. At that place is early germination of sarcomeres (cross-striations), and the sarcolemma has reformed. Such fibers stain basophilic with routine hematoxylin and eosin (H&E) staining.
Source: A–F, Redrawn with permission from Dr. M.D. McGavin, College of Veterinary Medicine, University of Tennessee.
Effigy x.4. Section of soleus muscle from a rat given a myotoxic xenobiotic. The necrotic muscle fibers are replaced by a mixed mononuclear inflammatory cell infiltrate. Regenerating myoblasts are basophilic and multinucleated. Formalin fixation, paraffin embedding, hematoxylin and eosin (H&Eastward) staining.
Source: Figure reproduced from Haschek, W.Yard., Rousseaux, C.G., Wallig, One thousand.A. (Eds.), 2013. Handbook of Toxicologic Pathology, third ed. Academic Press, Fig. 46.25, p. 1647, with permission.
Figure 10.5. Acute segmental myofiber necrosis of skeletal muscle from a sheep with monensin toxicosis. (A) Longitudinal and (B) cross-sections demonstrating a monophasic polyfocal reaction characterized past segmental hypercontraction of myofibers, which appear bloated and hyalinized (arrows), with loss of cross-striations and fragmentation. Formalin fixation, alkane series embedding, hematoxylin and eosin (H&E) staining.
Source: Figure reproduced from Haschek, W.M., Rousseaux, C.1000., Wallig, M.A. (Eds.), 2010. Fundamentals of Toxicologic Pathology, 3rd ed. Academic Press, Fig. 12.24, p. 372, with permission.
Pathologic Alterations in Skeletal Musculus
Degeneration and Necrosis. Unlike many tissues the deviation betwixt the reversible sublethal alterations of degeneration and the irreversible lethal changes of necrosis is difficult to detect by microscopic study. Skeletal muscle fibers are large multinucleated cells, and it is frequently not possible to view the unabridged length of the fiber in the plane of a tissue section to determine whether the sarcoplasmic impairment involves the entire fiber or only a segment of the cobweb. Information technology seems probable that segmental degeneration occurs oft, only necrosis of entire myofibers is uncommon. In any outcome the causes of both degeneration and necrosis are like.
Specific morphologic types of skeletal muscle degeneration have been described. The most common type is then-chosen hyaline-type or waxy degeneration. Affected muscles may exist detected grossly by diffuse pallor or scattered pale streaks (i.e., "white muscle illness;" Figure 10.6), specially if secondary calcification has occurred in damaged fibers. Microscopically, affected fibers appear swollen and hypereosinophilic with loss of cross-striations (Figures 10.5 and 10.7). The altered contractile textile oft becomes fragmented into large blocks or disks scattered along the "tube" of persisting external lamina of the degenerating muscle fiber. Within 24 hours the affected areas volition be invaded by an occasional polymorphonuclear leukocyte and numerous macrophages. Macrophages are observed in the interstitium and too within injured muscle fibers. Ultrastructurally the affected myofibers prove tangled masses of disrupted contractile material with damaged membranes of mitochondria, SR, and sarcolemma. The "tube" of external lamina persists to guide regenerative events and may be focally disrupted to let entry of macrophages.
Figure 10.half dozen. Necrosis of the muscles of the correct neck and shoulder in a hog is indicated past multifocal white streaks running parallel to the management of the muscle fibers. This gross appearance is consistent with both ionophore-induced myotoxicity (e.thou., monensin formulation error) and dietary vitamin East/selenium deficiency.
Source: Courtesy: Dr. Brian Chiliad. Caserto, VetPath Services, Rock Ridge, NY, from the Veterinarian Pathology Forum blog (https://vetpath.wordpress.com/2010/06/14/skeletal-musculus-necrosis-in-a-squealer-2/), with permission.
Figure x.vii. Acute monensin toxicosis in a pig. Regenerating skeletal muscle fibers show multiple large, vesicular, centrally located nuclei (arrowheads). Formalin fixation, plastic embedding, toluidine blue staining. Bar=50 μm.
Source: Figure reproduced from Haschek, W.K., Rousseaux, C.G., Wallig, M.A. (Eds.), 2013. Handbook of Toxicologic Pathology, third ed. Academic Press, Fig. 46.26, p. 1647, with permission.
Another blazon of degeneration described in skeletal muscle is granular degeneration. The microscopic advent differs from hyaline degeneration considering the damaged sarcoplasm appears as small basophilic granules that make full the "tube" of external lamina and are identified as mineralized mitochondria by ultrastructural written report. The causes of granular and hyaline degeneration are similar and include nutritional deficiencies (such equally selenium/vitamin Eastward deficiency), various myotoxic drugs and plants, and metabolic disorders such as azoturia and capture myopathy.
The spatial distribution and temporal pattern of degeneration and necrosis in skeletal musculus have been used to classify reactions as (1) monophasic monofocal, (2) monophasic polyfocal, (iii) polyphasic monofocal, and (4) polyphasic polyfocal. Monophasic monofocal reactions result from an isolated, single mechanical injury such as external trauma or needle insertion. In monophasic polyfocal reactions (Figures x.5 and ten.vii) a unmarried insult such as exposure to various myotoxic drugs or chemicals or diverse metabolic disorders may initiate widespread muscle lesions, but all the lesions are in the aforementioned phase of injury. Polyphasic monofocal reactions would be the event of repeated localized mechanical injury. Polyphasic multifocal reactions are frequent in muscular diseases of animals, and result from connected insults applied intermittently or continuously over a prolonged time (e.g., from nutritional deficiencies and from genetic disorders like muscular dystrophies); the lesions are widespread in the musculature, and diverse pathological reactions indicative of differently timed insults will occur concurrently, including necrosis (acute reaction), leukocyte invasion during resolution (often subacute response), and regeneration (subacute to chronic outcome). Xenobiotic-induced toxic myopathies tend to be monophasic polyfocal responses.
Other less common types of degeneration in skeletal muscle fibers include vacuolar or hydropic degeneration and fatty degeneration. Vacuolar or hydropic-type degeneration occurs with cortisol excess. The afflicted fibers have vacuolated, lace-like areas in the sarcoplasm. Fat degeneration is uncommon. Information technology is seen as a nonspecific response to injury, and results in abundant small spherical lipid vacuoles scattered betwixt myofibrils. Similar appearing but less abundant lipid deposits are normally present in type I musculus fibers.
Table 10.2 summarizes the chemical and biological agents that have been associated with necrosis or degeneration of skeletal muscle in animals and humans. Many of these agents also produce myocardial injury.
Table 10.2. Toxic Chemic and Biological Agents That Cause Necrosis or Degeneration of Skeletal Muscle in Animals and Humans
Clostridium chauvoei, C. septicum, C. novyi, C. perfringens
+
+
ND
Cow, sheep, equus caballus, sus scrofa
Uremic toxins
+
+
ND
Rat, human
+, present; −, absent-minded; ND, not determined.
Table modified from Haschek, Due west.Thou., Rousseaux, C.G., Wallig, M.A. (Eds.), 2013. Handbook of Toxicologic Pathology, third ed. Academic Press, Tabular array 46.6, pp. 1649–1652 with permission.
Drug-Induced Neuromuscular Occludent. A number of drugs may interfere with neuromuscular manual in homo patients. Three clinical syndromes have been recognized: drug-induced myasthenic syndrome, which is uncommon; drug-induced aggravation or unmasking of existing myasthenia gravis; and postoperative respiratory depression from direct effect of the drug or from potentiation of muscle relaxants. Drugs implicated in these syndromes include aminoglycoside antibiotics (neomycin, kanamycin, streptomycin, gentamycin); polypeptide antibiotics (polymyxin B, colistins); other antibiotics (oxytetracycline, rolitetracycline, lincomycin, clindamycin); antirheumatic drugs (d-penicillamine, chloroquine); cardiovascular drugs (oxprenolol, practolol, quinidine, procainamide, propranolol); anticonvulsants (trimethadione, phenytoin); psychotropic drugs (lithium, chlorpromazine, promazine, phenelzine); anesthetics (diazepam, ketamine, propenidid, ether); and other drugs (busulfan, oral contraceptives, methoxyflurane, adrenocorticotropic hormone (ACTH), corticosteroids, thyroid hormones, anticholinesterases, oxytocin, aprotinin, procaine, lidocaine). These drug-induced clinical syndromes take not been associated with morphologic alterations in skeletal musculus. The mechanisms of these drug-induced neuromuscular blockades include (1) presynaptic local anesthetic-like action, (ii) postsynaptic receptor blockade, (3) interference with ACh release, and (four) impairment of muscle membrane conductance.
Drug-Induced Myotonic Syndrome. Myotonia is the failure of normal muscular relaxation following contraction. Myotonic syndrome occurs in human patients, rats, and goats administered twenty,25-diazacholesterol and its analogs as hypocholesterolemic agents. Propranolol and suxamethonium may precipitate or exacerbate myotonia in man patients.
Drug-Induced Denervation Atrophy. Over 50 drugs used clinically in human patients have been reported to produce peripheral neuropathies. Damage to the nerve supply leads to myofiber atrophy of affected motor units and eventually progression to the distinctive morphologic alteration of "fiber grouping cloudburst" (Effigy 10.viii). Neurogenic atrophy represents a loss of myofiber mass every bit an indirect response acquired past biochemical or structural interruption that prevents nerve impulses from depolarizing the myofiber. Key morphologic attributes of neurogenic lesions include clusters of modest angulated myofibers (i.due east., foci of denervation atrophy) intermingled with big oval myofibers (i.east., those retaining an intact somatic nerve supply). Drugs implicated include antimicrobial agents (isoniazid, nitrofurantoin, sulfonamides, clioquinol, metronidazole, amphotericin B); antineoplastic agents (vincristine, procrabazine, nitrofurazone, cytosine arabinoside, podophyllir, chlorambucil); antirheumatic drugs (gold, colchicine, chloroquine, indomethacin, phenylbutazone); hypnotics and psychotropics (thalidomide, methoqualone, glutathimide); cardiovascular drugs (perhexiline, amiodarone, hydralazine, diisopyramide, clofibrate, digitalis); and other drugs (phenytoin, disulfiram, dapsone, ergotamine, methimazole, propylthiouracil, methylthiouracil).
Figure x.8. The spectrum of skeletal musculus lesions differentiates myopathic lesions (left console) from neurogenic (or denervation) atrophy (right panel). Myopathic lesions, resulting from direct damage to muscle tissue, are characterized by rounded, randomly sized myofibers with central nuclei and variable degrees of myofiber necrosis, regeneration, and/or mineralization sometimes accompanied past inflammation (typically mononuclear cells) and fibrosis. In dissimilarity, neurogenic lesions, which are an indirect effect on muscle tissue secondary to a primary injury the nervus supply, feature groups of athwart pocket-size myofibers (i.e., foci of denervation atrophy) with peripheral, relatively large nuclei interspersed with big oval myofibers (i.e., those retaining an intact somatic nervus supply), but usually no evidence of myofiber devastation (e.one thousand., myofiber necrosis or regeneration, inflammation or fibrosis). Human skeletal muscle biopsies; formalin fixation, paraffin embedding, hematoxylin and eosin (H&E) staining.
Source: Courtesy: Dr. Mark L. Cohen, Case Western Reserve University, Cleveland, Ohio, with permission.
Muscle Repair. Evidence of repair typically is a feature of myopathic lesions (i.e., those in which musculus tissue is direct injured), simply normally is not present in neurogenic lesions (i.e., those in which muscle is affected secondarily every bit a consequence of principal impairment at an extra-muscular site) (Figure 10.8). Successful restoration of muscle parenchyma leads to myofiber regeneration within intact external laminae (to restore necrotic muscle cells; Figures 10.4 and 10.7). More extensive myopathic lesions that event in both myofiber necrosis and interruption of external laminae may evoke inflammation (typically mononuclear cells), expansion of interstitial fibrous connective tissue, and sometimes mineralization of damaged myofibers. Over time the inflammatory reaction may recede, but fibrosis and mineralization stand for permanent changes.
Jyoji Yamate , in Boorman'south Pathology of the Rat (2d Edition), 2018
6.four Neurogenic Neoplasms
6.four.1 Malignant Schwannoma
The term peripheral nerve sheath tumor (PNST) includes schwannoma, neurilemoma, and neurofibroma. Schwannoma is more than common in rats, and the occurrence of neurilemoma and neurofibroma are very rare. Schwannoma is about normally seen as a grayness or cerise mottled edematous mass in the subcutis of the flank or neck area near the salivary glands; the incidence is greater in males than in females. Schwannoma also occurs in the thoracic and abdominal cavities, spinal cord, and cranial cavity (associated with cranial nerves) and in the centre (arising on the subendocardium and within the muscle wall). In the subcutis, schwannoma is generally considered malignant. Both Antoni type A and type B tissue patterns may exist present in the aforementioned tumor; the highly cellular regions are eventually referred to as Antoni A design (Figure 19.33), whereas loosely arranged neoplatic proliferation with microcystic tissue is known to exist the Antoni type B design. In larger mass of malignant schwannomas, there are ofttimes cystic or microcystic lesions consisting of spindle or pleomorphic cells supported by a poorly stained edematous or myxomatous matrix (Figure 19.34). Neoplastic cells with granules like to those in granular cell tumors are present in some schwannomas. Ultrastructural features of schwannoma cells include the presence of a variable amount of external lamina, abundant cytoplasmic organelles, and interdigitating cell processes. Divided external lamina may exist a characteristic of a more than malignant blazon. Immunohistochemically, schwannoma-constituting cells bear witness a positive reaction to Southward-100 protein.
Figure 19.33. Cutaneous malignant schwannoma consisting of higher cellular region formed past round and polygonal cells with hyperchomatic nuclei (referred to as Antoni A pattern).
Figure nineteen.34. Cutaneous cancerous schwannoma consisting of spindle-shaped or pleomorphic cells supported by poorly-stained edematous or myxomatous matrix area including cystic spaces (referred to equally Antoni B pattern).
In rats, Neural crest tumors most unremarkably occur on the pinna. This tumor is detectable grossly as a thickened peel or nodule on the pinna. Larger masses may exceed several centimeters in bore and extend into the soft tissue of the head, with ulceration, tissue necrosis and hemorrhage. Many cases evidence histologic bear witness of malignancy such as local invasion and a number of mitoses; metastasis to the lung may occur. Neural crest tumors consist predominantly of interlacing bundles of circular or fusiform cells and intermingled collagens (Figure 19.35); immunohistochemistry, tumor cells stain strongly positive for S-l00 protein. Considering of these histopathological features, the neural crest tumor has been diagnosed as schwannoma, neurofibroma or neurofibrosarcoma. Nevertheless, some parts of this tumor are quite similar histologically to the blue nevus (unpigmented melanoma) or desmoplastic melanoma of humans. The neural crest tumor has ultrastructural features of melanotic cells including interdigitating cytoplasmic processes, desmosomes betwixt cells, and numerous premelanosomes. The presence of premelanosomes has not been reported in PNSTs. Based on these findings, the neural crest tumor is regarded equally amelanotic melanoma in albino rats. Information technology is important to remember that cancerous schwannoma, fibrosarcoma and MFH may have areas of interlacing bundles similar to this neural crest tumor; therefore, the differential diagnosis should be made carefully when the light microscopy only is used. When neural crest tumors occur in other sites, there may be areas consisting of polygonal or epitheloid cells which are characteristic of amelanotic melanoma. Masson-Fontana stain and staining for tyrosinase-related protein 2 (TRP-2) may exist useful for the demonstration of melanosomes. In addition to the ear pinna, the predilection sites for amelanotic melanomas in rats include eyelid, iris, scrotum, and perianal area.
Figure nineteen.35. Neural crest tumor arising in the pinna (an asterisk indicates pre-existing cartilaginous tissue in the pinna). Pleomorphic neoplastic cells form interlacing growth pattern with various corporeality of collagen fibers.
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