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Skeletal muscles are composed of groups of muscle fasciculi; each fasciculus contain many individual muscle fibers (myocytes). The muscle fiber contain groups of myofibrils which are separated by mitochondria, aggregates of glycogen and lipid globules. The sarcoplasm reticulum (modified endoplasmic reticulum) and the tubular system ramify in the sarcoplasm between myofibrils. The myofibrils are constructed of two types of myofilaments (myosin and actin).
The cytologic separation of muscle fibers into type I (red) and type II (white) is based on differences in oxidative enzyme staining. In comparison to type II fibers, type I fibers are:
The larger type II fibers have fewer mitochondria and tend to predominate in less active muscles. Type I fibers are selectively affected in some of the myodystrophic diseases (white muscle disease, etc.). Type II fibers are preferentially involved in disuse atrophy, atrophy due to malnutrition and hyperadrenalcorticoidism. Both types of fibers are equally affected in most of the progressive muscular dystrophies, autoimmune muscle diseases and hypokalemic myopathy.
The motor unit (composed of the motor neuron, its axon and attached muscle fiber) is the functional unit in motor activity of muscle tissue. Each motor unit goes exclusively to either type I or type II fibers and a selective effect appears to be operative in some motor end plate diseases (when the motor unit is injured, severe and diffuse atrophy characterizes the muscles area supplied). Brain and spinal cord diseases are characterized by diffuse atrophy involving both type I and type II fibers. On the other hand, segmental or focal atrophy characterizes all primary myolytic diseases of muscles where short segments of myofibers, several sarcomeres in length, are destroyed (vitamin E deficiency, viral infection, and intracellular parasitism).
In order for students to gain a better understanding of the topics to follow, the following should be reviewed in respect to skeletal muscle: cloudy swelling, hyaline (Zenkers degeneration), fatty degeneration and pigmentation of muscle.
Atrophy is the decrease in size of cells that have gained full development. Thus, atrophy represents an adaptation to a changed environment for the cell. Cells tend to shrink when their level of work is diminished or when their source of nutrition or stimulation is removed. Obviously, when large numbers of cells shrink, the organ or tissue involved will decrease in size commensurably. Atrophic cells are smaller than normal and, except for lysosomes, their organelles are fewer in number and size. Autophagy (autophagocytosis) is the phenomenon by which cell atrophy occurs. Autophagic vacuoles, which develop from the Golgi complex, engulf degenerate cellular organelles.
8.2.1.1 DISUSE ATROPHY
Results from inactivity or from a limitation of movement. It is especially important in muscle when limbs are restrained in casts or other mechanisms. In disuse atrophy, type II fibers are preferentially involved.
8.2.1.2 ATROPHY OF CACHEXIA AND MALNUTRITION
Is very difficult to adequately separate from wasting syndromes that occur in senility, disuse and chronic infections. In atrophy due to cachexia and malnutrition, type II fibers are preferentially involved.
8.2.1.3 NEUROGENIC ATROPHY
Is the loss of innervation due to peripheral nerve injury or loss of central control due to brain or spinal cord damage. This atrophy is always accompanied by paralysis. Destructive lesions of the CNS are characterized by diffuse atrophy involving both type I and type II fibers (atrophic muscle changes are always chronic). Denervated muscle may be reinnervated and may readily do so if the neural sheaths are not physically disrupted. Regeneration of nerves take place as far as the node of Ranvier, proximal to the site of injury, in a peripheral nerve from which point axonal regeneration occurs. If functional connections between nerve and muscle fibers are reestablished, the process of muscle fiber atrophy is slowly reversed.
Hypertrophy of muscle denotes an increase in its size by an increase of fiber size. Although hypertrophy may be seen in any tissue, it occurs in "pure" form only in those tissues composed of cells that do not reproduce themselves (usually, hypertrophy and hyperplasia occur together). Skeletal muscle undergoes hypertrophy in response to an increased work load. Cellular organelles are larger that normal in involved cells.
Calcification of muscle is almost always a dystrophic process (calcium salts being deposited in dead or dying tissue). Metastatic calcification of supporting tissue of muscle commonly occurs in dogs with chronic renal disease and secondary hyperparathyroidism.
Steatosis refers to progressive replacement of muscle tissue by adipose tissue without alterations in the gross form of the affected muscle. The changes are usually localized, but symmetrical; however, almost all skeletal muscles may be involved. The condition occurs primarily in meat producing animals, being quite common in fattened pigs but rare in sheep and cattle. No clinical signs are produced and the condition is usually detected at slaughter.
Injuries to muscles are Common and usually result from external trauma. The effects of external trauma are quite variable and depend on the quality or severity of the applied force.
Myositis refers to inflammation of muscle and the condition may be caused by bacterial or viral agents. Living muscle is a poor medium for most bacterial infections (this is true even when infections are overwhelmingly septicemic or repeatedly bacteremic). However, pyogenic organisms may produce solitary or few abscesses of hematogenous origin in muscle, (but focal embolic polymyositis is a characteristic feature only of infection by hemophilus agni in lambs). On the other hand, members of the genus Clostridium grow well in muscles if the opportunity is provided. Viral infection of skeletal muscle is common, but serious disease limited to this tissue is not. Most serious systemic viral infections are capable of producing scattered foci of muscle necrosis (Newcastle disease, hog cholera, canine distemper, feline panleukopenia, foot & mouth disease and blue-tongue all produce focal muscle necrosis in which viral antigens can be demonstrated by fluorescent antibody procedures).
Blackleg is an acute gangrenous myositis of ruminants caused by Clostridium chauvoei and characterized by activation of a latent infection of the "spores" of the organisms. In cattle, the disease affects principally young animals (from 9 months to 2 years) which are in good nutritional condition. In sheep, however the disease is not restricted to the young. Cl. Chauvoei has as its principal habitat the intestinal tract of animals; it can remain viable in the soil for considerable periods. The pathogenesis of blackleg is not certain, but there is evidence to suggest that ingested spores gain access to the bloodstream and are than deposited in muscle and other tissues where they reside as latent infections. Activation and vegetation of spores occurs when muscles are injured in some manner with lowering of their oxidative-reduction potential. Clinical signs include acute lameness, fever, depression and crepitant swelling in various muscle groups. Grossly, the affected muscles are dark red to black, dry, spongy and have a sweetish odor. Lesions are usually found in large muscles of the pectoral and pelvic girdles, but they may be found in any striated muscle (heart, tongue, diaphragm, etc.). In addition to muscle lesions, there is often endocarditis and fibrinohemorrhagic pleuritis (when this lesion is present in the absence of pneumonia, blackleg should be considered as a possibility). Both Cl. chouvoei and Cl. septicum may be isolated from blackleg lesions, especially if the carcass is examined 24 hours or more after death.
Malignant edema is an acute toxemia of cattle, horses, sheep, goats and swine which is usually caused by Clostridium septicum; However, the disease may also be caused by Cl. perfringens and Cl. septicum. The infection occurs through contamination of wounds containing devitalized tissue or tissue debilitants. Deep wounds are more suitable for the development of this disease. The distinctive characteristics of malignant edema are severe edema, the formation of bubbles of gas, discoloration of the overlying skin and coldness of the affected part. Clinical signs include toxemia with prostration, circulatory collapse and death. There is large accumulations of edema in the subcutaneous and intermuscular connective tissue of the affected area. Muscles in such areas are dark-brown to black; accumulation of gas is not a common feature (however, the lesions may be quite similar to those of blackleg).
Rapid confirmation of a diagnosis of malignant edema can be made on the basis of fluorescent antibody test. This cannot be relied upon, however, if the animal has been dead for 24 hours or more because Cl. septicum is an extremely active postmortem invader from the intestine.
In both blackleg and malignant edema, the invading organisms elaborate exotoxins and the primary effects are:
In cattle, eosinophilic myositis is characterized by focal necrosis associated with large numbers of eosinophils. The cause in unknown (but the presence of degenerate Sarcocystis in the center of some lesions suggest that they may play a role). Grossly, the lesions are characteristic, being rather well-demarcated green foci (the green color will fade to "off-white" on exposure to air). Microscopically, the lesions may be acute or chronic; large numbers of eosinophils are characteristic (eosinophils impart the green color to muscle). There is focal necrosis and fibroplasia is prominent in more prolonged lesions. Eosinophilic granulomas may develop and these are characterized by a necrotic core surrounded by epithelioid cells with a few giant cells. The periphery of the granuloma is formed by eosinophils, lymphocytes and plasma cells (along with proliferating fibroblasts). Calcium salts are oftentimes deposited in the necrotic core.
In dogs, eosinophilic myositis is an acute relapsing myositis characterized by an infiltration of eosinophils. The condition occurs most frequently in the German Shepherd dog and affects chiefly the muscles of mastication (however, other skeletal muscles may also be involved). Clinically, the condition is characterized by recurrent attacks of pain, mandibular immobility and sometimes swelling of the affected muscles (predominantly the temporal, zygomatic and masseters). The mouth is held partially open and the animal eats with pain. The attack lasts from 1 to 3 weeks (periods between attacks may be weeks, months or 2-3 years). After each attack, the affect muscles become more atrophied. Grossly, the acutely affected muscles are swollen, dark red, doughy or hard with yellow or pale streaks or foci. In chronic cases, atrophy and fibrosis are prominent. Microscopically the acute lesions are characterized by the presence of large numbers of eosinophils and small numbers of mononuclear cells (chiefly plasma cells). In chronic cases, plasma cells are most numerous with fewer eosinophils. Atrophy of fibers and fibroplasia are prominent.
White muscle disease (WMD) is a myodegeneration that occurs most frequently in calves and lambs, being characterized by hyaline degeneration and necrosis of striated muscles. In addition to calves and lambs, the condition has been described in rabbits, swine, chickens, deer, foals, goats, dogs, as well as in other species. Clinical signs include stiffness, recumbency and death when skeletal muscles are involved. When heart lesions are present, there is usually sudden death without clinical signs. In calves, lesions are most frequently observed at 1 to 2 months of age (however, lesions may develop in utero). The basic lesions of WMD is hyaline degeneration and necrosis of striated muscle. The involvement of skeletal muscles is always bilateral and symmetrical. Grossly, the affected muscles are pale, inelastic, friable, dry and may exhibit distinct longitudinal striations or a pronounced chalky whiteness (associated with the deposition of calcium salts). Microscopically, the changes may vary from hyaline degeneration to coagulation necrosis. There is fragmentation and disappearance of many fibers.
In pigs, there is selective necrosis of type I fibers (type II fibers tend to remain viable). The ultrastructural injury appears in the mitochondria which are enlarged and distorted.
Classical WMD in animals is believed to be caused by a deficiency of vitamin E. The mechanisms of avitaminosis E induced injury are intimately related to dietary selenium. Both E and selenium protect cellular membranes against the destructive action of free radicals that arise from cellular metabolism. The free radicals attack lipid membranes to produce lipid peroxides and these, in turn, destroy membranes, sulfhydryl-containing enzymes and other substances. Selenium participates as a component of the enzyme glutathione peroxidase which acts in the cytoplasmic matrix to destroy lipid peroxides that would otherwise damage cellular membranes (glutathione peroxidase levels in plasma are directly related to dietary selenium). Vitamin E is a secondary defense against peroxidative injury. It acts within phospholipid membranes where it neutralizes free radicals and, thereby, prevents a chain reaction of auto-oxidation. Balance in the system (vitamin E and selenium) may be shifted by feeding large amounts of saturated fatty acids that accumulate in cellular membranes and render them increasingly susceptible to lipoperoxidation. This change usually can be counteracted by addition of supplemental vitamin E to the diet, but not by addition of selenium, implying that the detoxification capacity of the selenium-dependent glutathione peroxidase system may be exceeded if abundant lipoperoxidation develops.
Azoturia of horses (also referred to as paralytic hemoglobinuria) is a disease of unknown cause which is characterized by hyaline degeneration and necrosis of skeletal muscles (the condition commonly referred to as "tying-up" or "cording-up" is considered to be a mild form of azoturia). Even though the cause is unknown, some cases apparently respond to vitamin E and selenium therapy. Azoturia is directly associated with forced exercise after a period of rest during which feed has not been restricted. Clinically, the condition is characterized by profuse sweating, rapid pulse and stiffness. The affected muscles (gluteal, femoral, etc.) are swollen and "board-like." Dissolution of muscle tissue results in the release of myoglobin which is passed in the urine (giving the urine a dark color). Grossly, the changes in muscle may vary from slight paleness to well-defined yellowish gray streaks. Microscopically, the lesions are characterized by hyaline degeneration and necrosis with fragmentation of individual fibers.
Hereditary muscular dystrophies cause progressive destruction of striated muscle. These diseases are quite important in humans. In animals, only sporadic isolated cases have been reported. The most significant model of muscular dystrophy exists in a mutant strain of mice (dystrophia muscularies strain 129) bred at Jackson Laboratory, Bar Harbor, Maine. The disease is characterized by progressive atrophy of axial and limb muscles which begins at about 3 weeks of age; complete paralysis with death occurs in about 1 to 6 months. The initial lesion is located in the sarcoplasm reticulum but becomes widespread in the cell leading to myocyte necrosis with disorganization of the myofilaments and distortion of the mitochondria. The ability of the sarcoplasma reticulum to take up and store calcium for muscle contraction is impaired early in the disease.
Sarcosporidiosis is a disease caused by the invasion of striated muscles of mammals, birds and reptiles with protozoan sarcocystis (there is evidence to suggest that the causative agent is a fungus). The parasites invade muscle fibers and grow to form elongated spindle-shaped structures called "Misescher's tubes." Groups of organisms are surrounded by a thick cyst wall of both parasite and host origin. In many hosts, the parasite can only be observed microscopically. In sheep, cattle and ducks, the cyst can oftentimes be observed grossly as "white dots" or "streaks" in affected muscle. The tissues most commonly affected are skeletal muscles in general, tongue, heart, esophagus and diaphragm. In most animals, the disease is apparently harmless with no clinical signs produced. There is virtually no inflammatory reaction around encysted parasites.
Trichinella spiralis is the only nematode to enter cells as a part of its life cycle. The parasite is characterized by 2 major biological phases: enteric and visceral. The adult life of the parasite is spent in the intestine of many species of carnivores. Females deposit larvae directly into lymphatics from where they reach the bloodstream and ultimately end up in myocytes. Immunity is acquired in the enteric phase and during circulation of living larvae. The immune mechanism may reduce the number of larvae reaching muscle but does not affect the migration in muscle, encystment or larval development.
The muscle cells undergo striking transformation when invaded by larvae. Myofibrils within affected myocytes become disoriented and their myofilaments are detached and frayed at the Z line. Most organelles degenerate and disappear (especially the mitochondria and lysosomes). By the 21st day after infection, the cytoplasm of transformed cells is filled with large arrays of smooth endoplasmic reticulum. The larvae exist free in the cytoplasm and the host cell secretes the acidic mucopolysaccharides which form the dense hyaline cyst wall.
Neoplasms composed of muscle cells (rhabdomyomas and rhabdomyosarcomas) are rarely reported in animals. The precise diagnosis of these tumors requires the demonstration of myofibrils or cross striations in the neoplastic cells. Extreme care is necessary for one to distinguish primary muscle tumors from regenerating muscle fibers in areas of fibrosis. The most frequent metastatic neoplasms found in muscle tissue are malignant melanomas and those of lymphoreticular origin.
Arthrogryposis is a congenital anomaly characterized by deformities of the limbs (curvatures, articular rigidity, etc.) due to regressive changes in skeletal muscles (muscular dysplasia). The primary defect may be in skeletal muscle. However, in a majority of the cases, the primary defect is believed to be in the spinal column, spinal cord or brain (muscle lesions are secondary to altered innervation due to lesions in these sites). Abnormalities in the vertebral column that may lead to altered innervation and regressive muscle changes include scoliosis, spinal bifida, segmental aplasia of the vertebral column, etc. Spinal cord abnormalities (dysraphism) are associated with disordered closure of the neural tube. Arthrogryposis and dysplasia of muscle occur in all species but they are best documented in calves and lambs. The condition is most likely inherited but there is evidence to suggest that plant poisoning may be a factor in some cases. Grossly, the limbs of affected animals are fixed in a variety of abnormal flexions or extensions. Limb muscles are reduced in bulk.
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SLIDE 1: CANINE BODY: ATROPHY OF MUSCLE - This emaciated dog did not receive adequate nutrients; observe evidence of muscular atrophy with prominent ribs. This condition may be referred to as malnutrition atrophy. (What muscle fibers are preferentially involved in this condition? Would you expect to find generalized atrophy of this nature with destructive lesions in the brain? Explain. What changes do cell organelles exhibit when a cell undergoes atrophy? Define the following terms: ATROPHY, HYPOPLASIA, HYPERPLASIA, APLASIA, METAPLASIA, CACHEXIA, MOTOR UNIT. What is autophagocytosis? Explain the role of autophagocytosis in atrophy).
SLIDE 2: BOVINE BONE MARROW: -SEROUS ATROPHY - In wasting diseases, etc., Serous atrophy of bone marrow fat occurs; observe the dark red, fluid marrow. (What is a pathogenic mechanism for serous atrophy of body and bone marrow fat in a starved animal?).
SLIDE 3: CANINE HEAD: ATROPHY OF MUSCLE - Observe the atrophic muscles on one side of the head; compare normal and abnormal muscles. This unilateral atrophy was most likely due to nerve damage. (Would you expect type I or type II fibers to be preferentially involved? Is this condition acute or chronic?).
SLIDE 4: CANINE TONGUE: ATROPHY OF MUSCLE - This Tongue is from the same dog denoted in slide #3; observe the lyssa and atrophic muscles on one side of the tongue. (Give a likely pathogenic mechanism for this condition.).
SLIDE 5: EQUINE ILEUM: HYPERTROPHY OF SMOOTH MUSCLE - Observe the markedly thickened wall of the gut; the lumen is narrowed. (Would you expect to find both hypertrophy and hyperplasia in this organ/tissue? Why would an organ/tissue want to undergo hypertrophy?).
SLIDE 6: EQUINE ILEUM: HYPERTROPHY OF SMOOTH MUSCLE - Observe the markedly thickened wall of the ileum with stenosis of the lumen (hypertrophy).
SLIDE 7: CANINE RIBS/KIDNEYS: CALCIFICATION - Observe the yellowish deposits of calcium associated with the intercostal muscles. This dog had a chronic renal disease. (Would you expect to find calcium salts within muscle cells or in supporting tissue? Give a likely pathogenic mechanism for the calcification observed in the this slide. How would you differentiate dystrophic from metastatic calcification?).
SLIDE 8: PORCINE MUSCLES: STEATOSIS - Note the replacement of muscle tissue By fat (How would you differentiate this condition from steatitis? What clinical signs would you expect to observe in this pig ?).
SLIDE 9: EQUINE LIMB: TRAUMATIC INJURY - Observe the torn skin and muscle of the leg of this horse traumatized via a wire fence.
SLIDE 10: PORCINE BODY: TRAUMATIC INJURY - Observe the massive hemorrhage and necrosis; this pig was unable to out run a hungry Coonhound. (Would the term "gangrene" apply to this wound?).
SLIDE 11: OVINE BODY: BLACKLEG - Observe the massive hemorrhage over the thigh and rump muscles; the lesions extended deep into muscle tissue. (What clinical signs would you expect in this animal? Give a likely pathogenesis for this condition.).
SLIDE 12: BOVINE MUSCLE: BLACKLEG - This is an example of gangrenous myositis associated with Cl. chauvoei infection; observe the hemorrhage and necrosis; compare normal and abnormal tissues. (How would you confirm the diagnosis of blackleg? Give reason(s) why CL. septicum can oftentimes be recovered from normal and abnormal tissue.
SLIDE 13: BOVINE MUSCLE: BLACKLEG - This is a close-up view of the hemorrhage and necrosis caused by the blackleg organism; compare normal and abnormal tissue.
SLIDE 14: BOVINE HEART: BLACKLEG - Observe the well-defined hemorrhages over the epicardium (What lesion would you expect to find in the myocardium and endocardium of this young calf? Under what other circumstances would you expect to observe hemorrhages over the epicardium? What specific lesion(s) would you expect to find associated with the thoracic pleural?)
SLIDE 15: BOVINE HEART: BLACKLEG - Observe the well-defined hemorrhages extending into the myocardium.
SLIDE 16: OVINE TONGUE: BLACKLEG - Observe the hemorrhagic and gangrenous involvement of the tongue (Would you expect to observe blackleg in a focal lesion?)
SLIDE 17: BOVINE MUSCLE: EOSINOPHILIC MYOSITIS - Observe the distinct greenish discoloration of the affected muscles. (Give a reason for the greenish discoloration. What clinical signs would you expect in cattle and dogs affected with this disease? Discuss gross and microscopic changes that you would expect to see in affected dogs and cattle.).
SLIDE 18: BOVINE MUSCLE (micro): EOSINOPHILIC MYOSITIS - Observe the accumulation of eosinophils in the affected muscle. (What parasite has been incriminated as a possible cause of this condition in cattle? Why is it difficult to make a tentative diagnosis of this condition on gross inspection after affected muscles have been exposed to air? If you found a heavy accumulation of eosinophils in the brain of a pig, what disease would you consider?).
SLIDE 19: PORCINE BODY: WHITE MUSCLE DISEASE - This pig is exhibiting weakness, etc., associated with WMD. (What other diseases or conditions would you consider in your clinical diagnosis? Would you expect to find large deposits of calcium in affected muscles of this pig? Briefly discuss mulberry heart disease, hepatosis dietetica, and herztod).
SLIDE 20: PORCINE LIMB: WHITE MUSCLE DISEASE - Observe the pale streaks and hemorrhages in the muscles of this pig with WMD. (Would you expect type I or type II fibers to be more severely involved?).
SLIDE 21: DEER MUSCLE - WHITE MUSCLE DISEASE - Observe the severe necrosis of muscle in this 5 week old White Tailed deer. (Describe the gross and microscopic lesions that you would expect to see in this animal.).
SLIDE 22: BOVINE HEART: WHITE MUSCLE DISEASE - Observe the pale necrotic foci in the heart of this calf. Remember, in calves there is a tendency for lesions to occur most frequently in the left ventricle, whereas the right ventricle is chiefly involved in lambs.
SLIDE 23: EQUINE THIGH: WHITE MUSCLE DISEASE - Observe the pale yellowish thigh muscles. (At this time, you should be able to discuss the roles of vitamin E and selenium in preventing peroxidation of cell membranes.).
SLIDE 24: CHICKEN GIZZARD: WHITE MUSCLE DISEASE - (Name three diseases or conditions in birds which may be related to vitamin E deficiency. What factor(s) besides vitamin E is usually deficient in feed of chicks with the lesions observed in this slide?).
SLIDE 25: CHICKEN MUSCLE: WHITE MUSCLE DISEASE - Observe the poorly defined pale streaks in the muscles. (Could this condition be confused with lymphoid leukosis of birds? Explain. How can this condition be prevented in birds? Explain or give a reason for the greenish discolored area in this slide.).
SLIDE 26: CHICKEN MUSCLE: WHITE MUSCLE DISEASE - Observe the paleness, hemorrhage and edema in the affected tissue. (What factor(s) would you add to the ration of birds in order to prevent this condition? It may be necessary for you to refer to the handout on the CNS).
SLIDE 27/28: GIRAFFE MUSCLE: WHITE MUSCLE DISEASE - This microscopic section of muscle from a calf with WMD denotes the extensive necrosis with fragmentation and hyalinization of givers. (Would you expect type I or type II fibers to be less severely involved?).
SLIDE 29: EQUINE MUSCLE: AZOTURIA - There are several slices of involved muscle tissue in this slide; observe mild and rather severe lesions; compare normal and abnormal tissue. This horse was tied to a post, fell, was unable to get up and Was allowed to struggle for several hours. At necropsy, lesions were found in nearly all skeletal muscles.
SLIDE 30/31: SARCOSPORIDIOSIS - Observe the well-defined parasitic foci in skeletal muscles of a duck (30) and a sheep (31).
