Muscle Skeletal Pathology of Domestic Animals
Prepared by Leslie D. McLaughlin DVM, PhD Louisiana State university SVM 2303 578-9717
Delayed Onset Muscle Soreness
Delayed onset muscle soreness - thought to be a result of microscopic tearing of the muscle fibers. The amount of tearing (and soreness) depends on the intensity, duration, and type of exercise. Eccentric muscle contractions (movements that cause muscle to forcefully contract while it lengthens) seem to cause the most soreness. Examples of eccentric muscle contractions include going down stairs, running downhill, lowering weights and the downward motion of squats and push-ups. In addition to small muscle tears there can be associated swelling in a muscle which may contribute to soreness
Basic Components of Muscle
Components of skeletal muscle Fasciculi muscle fibers grouped into bundles Endomysium delicate supporting tissue between each muscle fiber Perimysium loose collagenous tissue around each fascicle Epimysium dense collagenous tissue around entire muscle
Each myofibril has a repeating pattern of cross striations due to highly ordered arrangement of contractile proteins within each myofibril
Basic Components of Muscle
Perimysium (organizes myofibers into fascicles)
Myofiber
Endomysium - fine connective tissue stoma
Examination of Muscles
Muscle Biopsy useful aide in dx of muscle disease, see below for microscopic examination Gross examination at necropsy incise variety of muscles including active ones (tongue) and inactive ones (biceps femoris, semimembranosus) Clinical history should be used to determine if any additional specific muscles are to be examined Muscles undergoing degeneration/necrosis are pale and if mineralized have chalky white streaks
Examination of Muscles
Microscopic examination excise strip of affected muscle 510 mm wide, 3-5 mm thick and several cm in length place on wooden tongue depressor tie in place drop in 10% neutral buffered formalin fix 24-48 hrs Cut transverse and longitudinal sections Myofiber diameter and percentage of abnormal fibers best evaluated in transverse section Myofiber necrosis, nuclear morphology best evaluated on longitudinal section Enzyme histochemistry (succinic dehydrogenase, myosin ATPase, etc) Examine for lesions in blood vessel walls (ischemia, toxins, etc) and for lesions in motor nerves
Examination of Muscles
Histology of Skeletal Muscle
Longitudinal section: Elongated, unbranched cylindrical cells with flattened nuclei just beneath sarcolemma (plasma membrane)
Transverse section: Shows muscle fibers as polyhedral cells with flattening of adjacent cells Notice extreme peripheral location of nuclei P = perimysium C = capillary
Histology of Skeletal Muscle
Myofiber necrosis, nuclear morphology best evaluated on longitudinal section
Myofiber diameter and percentage of abnormal fibers best evaluated in transverse section
Muscle Fiber Types
Type 1 fiber aerobic (oxidative metabolism), small in cross section, with lots of mitochondria (A)
Also contain lots of myoglobin (Oxygen storage molecule) accounts for their red color Also have rich blood supply Slow contracting, slow fatiguing, low myosin ATPase
Type 2 fiber anaerobic (glycolytic metabolism), large in cross section, few mitochondria, little myoglobin, white in color (An)
Rich in glycogen, rich in myosin ATPase, fast contracting, fast fatiguing
Intermediate fibers (type 2A) mixed oxidative-glycolytic, fast contracting, slow fatiguing
Succinate dehydrogenase (Krebs cycle enzyme) stain for mitochondria
Skeletal Muscle Blood Supply
Large blood vessels enter epimysium and divide throughout muscle in perimysium fine branches arise so that each fiber has a surrounding capillary network
Skeletal Muscle Nerve Supply
Muscle contraction is controlled by the motor unit and includes the motoneuron consisting of cell body and axon in a peripheral nerve; the neuromuscular junction; and myofibers innervated by motoneuron Any one motor nerve supplies fibers of one type Each branch of axon of motor neuron terminates as a motor end plate near midpoint of each fiber
Tools Used for Diagnosis of Muscle Diseases
Physical examination thorough systemic and neurological examination is critical in evaluation of muscle or neuromuscular disorders
Weakness is common to all motor unit abnormalities can be evaluated by observing animals gait as it walks and after more strenuous exercise Ataxia failure of muscle coordination resulting in staggering and irregular muscular movements result of disruption of sensory pathways responsible for proprioception Paresis partial loss or impairment of motor function of a body part Paralysis complete loss or impairment of motor function of a body part Other clinical signs include dysphagia (pharyngeal dysfunction), regurgitation (esophageal dysfunction), and dysphonia and dyspnea (laryngeal dysfunction)
The goal should be to obtain a specific diagnosis and ultimately a specific therapy many muscular and neuromuscular diseases are treatable
Tools (Continued)
Routine and special laboratory tests
Complete blood count, serum chemistry profile including electrolytes (sodium, potassium, calcium and magnesium); muscle enzymes (serum creatine kinase CK); urinalysis Tests for thyroid and adrenal gland function myopathy associated with hypothyroidism, and myopathy and myotonia associated with hyperadrenocorticism are not uncommon in dogs Serum antibody titers for infectious agents (Toxoplasma gondii, Neospora caninum, etc) Plasma cholinesterase levels myasthenia-like syndromes and delayed neuropathies have been associated with organophosphate toxicity Serum antibodies against masticatory muscle type 2M fibers Serum antibodies against the acetylcholine receptor - diagnostic assay for acquired myasthenia gravis
Tools (Continued)
Radiography thoracic radiographs are useful for ruling out significant esophageal dysfunction; contrast studies and evaluation of swallowing and esophageal motility are indicated in some cases Electrodiagnostic testing Electromyography (EMG)- needle is inserted into muscle followed by a short burst of electrical activity evoked potential is measured on recording device Nerve conduction velocity, electroretinography, etc Muscle biopsy/peripheral nerve biopsy Molecular genetics testing limited tests available for animals (muscular dystrophy in certain breeds, etc) allows carriers to be detected for breeding prevention
Rigor Mortis
The stiffening of death best related to body temperature and metabolic activity at time of death Average onset of rigor is 2-6 hours; typically lasts 2-4 days Occurs when the rate of ATP utilization exceeds ATP production Ends with the loss of ADP (theorized) or degradation of the muscle tissue
Rigor Mortis
Factors speeding onset:
If death occurs during a high fever disease such as porcine stress syndrome in pigs, heat stroke in dogs, or anthrax in cattle, rigor can occur almost simultaneously with death Occurs rapidly in animals that are excited or severely stressed just before death High temperature
Factors slowing onset:
Occurs slowly or not at all in animals that are well rested/well fed Cold
Cachexic animals with little muscle mass may not show rigor Jaw muscles of dogs and most animals are the first to set up in rigor followed by the eyelids, tail, digits, distal limb muscles and finally the larger limb muscles they relax in similar sequence
Response of Muscle to Injury
Degeneration Necrosis Calcification Regeneration
Response of Muscle to Injury
Degeneration muscle fiber swells and looses striations, may see vacuoles if not reversed progresses to necrosis
Necrosis fiber fragments and becomes very eosinophilic invaded by macrophages (lyse and phagocytose necrotic debris and form clear space in sarcolemmal tube)
Response of Muscle to Injury
Calcification necrotic fibers calcify Necrotic myofibers from guinea pig heart Necrotic fibers are mineralized (calcified) Calcified fibers are surrounded by macrophages and fibrocytes Muscle regeneration is not evident If the animal survives this insult, healing will occur by fibrosis/scar formation
Response of Muscle to Injury
Regeneration satellite cells (embryonic cells that contain myosin) move into necrotic tissue and become myoblasts form a tube (myotube) that produces sarcoplasm, rows of central nuclei appear, sarcomeres formed (striations)
Regeneration by budding if muscle insult damages sarcolemmal tube of myofiber, regeneration is by budding (ineffectual regeneration) Myoblasts proliferate and extend to end of ruptured tube, sarcoplasm bulges from cut end, formation of multinucleated muscle giant cells
Atrophy
Implies either a reduction in the volume of the muscle as a whole or in the diameter of the myofiber Physiologic (Type II preferentially affected) Disuse Cachexia Aging Secondary to Endocrine Disease (Type II preferentially affected) Hypothyroidism (dogs) Hypercortisolism (dogs and horses) Denervation atrophy (Type I and Type II) Maintenance of normal myofiber diameter is dependant on trophic factors generated by an intact associated nerve Congenital Myopathy (Type I) - Human Dz
Atrophy
Atrophy decreased diameter of an entire muscle or of a myofiber Myofibrils disintegrate but sarcolemma does not, throwing it into redundant folds Rate of atrophy depends on lack of use, blood supply and presence or absence of nerve supply
Muscle Atrophy
Myofibers are decreased in size Nuclei are more numerous and are increased in size
Muscle Atrophy
Types of atrophy Denervation atrophy occurs rapidly following loss of innervation (2 to 3 weeks) usually involves both type I and type II myofibers; morphologic changes in nerves Disuse slow atrophy secondary to fracture, pain, etc., usually involves type I and type II fibers but type II go first and are more severely affected; nerves are normal Atrophy due to malnutrition, cachexia and senility - slow atrophy that usually spares muscles that support posture of trunk; affected muscles have loss of type II fibers first, then type I; nerves are normal
Denervation Injury
Muscle Atrophy
Grey pony mare with marked atrophy of gluteal muscles of left hindlimb She has no history of lameness therefore atrophy due to disuse can be ruled out, also there was no history of trauma The problem is most likely denervation she has polyneuritis equi (cauda equina neuritis) Equine protozoal myeloencephalitis (EPM) would also have to be considered
Muscle Hypertrophy
Increased myofiber diameter caused by increased workload Work hypertrophy due to increase in normal physiologic work (horses, dogs and humans during athletic training) Compensatory hypertrophy increased workload on individual fibers caused by loss of myofibers in an adjacent muscle due to physical injury or partial denervation atrophy, myopathy, etc.
Muscle Hypertrophy
Fiber Splitting of Hypertrophied Myofibers
Myofibers increase in diameter by addition of myofilaments Sarcolemmal ingrowth into the myofiber has resulted in multiple partitions with the formation of four myofibers; however, all myofibers are enclosed by one basal lamina.
Muscle Fiber Regeneration
Success of regeneration depends on:
Presence of an intact basal lamina Availability of viable satellite cells
Regeneration requires > 3 weeks in healthy animals Believed to recapitulate the embryologic development of skeletal muscle
Muscle Fiber Regeneration
A. Myofiber, longitudinal section; intact basal lamina Segmental coagulation necrosis. The necrotic segment of the myofiber has become floccular (hyalinized) and detached from the adjacent viable portion of the myofiber. The satellite cells are enlarging. The necrotic segment of the myofiber has been invaded by macrophages, and satellite cells are migrating to the center. The latter will develop into myoblasts. The plasmalemma of the necrotic
B. C.
D.
Muscle Fiber Regeneration
E. Myoblasts have formed a myotube, which has produced sarcoplasm. This extends out to meet the viable ends of the myofiber. The integrity of the myofiber is maintained by the sarcolemmal tube formed by the basal lamina and endomysium. Regenerating myofiber. There is a reduction in myofiber diameter with central rowing of nuclei. There is early formation of sarcomeres (cross striations), and the plasmalemma has re-formed. Such fibers stain basophilically with H&E. As the fiber grows and differentiates its diameter increases, cross striations continue to appear In several days to weeks the nuclei of the regenerating fibers move to the periphery
F.
Muscle Fiber Regeneration
Myofibers in various stages of regeneration Satellite cells forming myoblasts these have fused with each other to form myotubes Some myofibers have regenerated but still contain central nuclei
Types of Muscle Diseases
Congenital and inherited defects Degenerative Diseases
Ichemic (disturbances of circulation) Nutritional Toxic Exertional
Inflammatory Diseases
Infectious Idiopathic Parasitic
Neoplasia
Congenital and Inherited Defects of Muscle
Arthrogryposis
We have discussed this disease with bones and jointsit can also be due to nerve and muscle disorders.
Arthrogryposis
Possible causes include: 1. Primary nervous disorder resulting in secondary muscle contracture abnormal tension on joints and thus crooked joints Effects of primary muscle defect on the joints they attach to Prolonged lack of in utero movement Dysraphisms - abnormalities of the spinal cord can associated structures that can result in muscle abnormalities (normal muscle development requires normal innervation) Prolonged fixed flexion of the affected joint(s) late in gestation
2. 3.
4.
Arthrogryposis
Neonates with arthrogryposis or dysraphisms are frequently stillborn or die early after birth Congenital flexure of pasterns lambs, foals, calves
Often muscle and nervous abnormalities can not be demonstrated microscopically
Muscular Defects, Dystrophies, Dysfunctions
Myofibrillar Hypoplasia Disease of piglets and puppies (Swimming Puppy Disease) Idiopathic transient disease Neonates are unable to adduct their legs (splayleg) Animals that survive the first several weeks frequently return to normal muscle function
Muscular Defects, Dystrophies, Dysfunctions
Muscle Fiber Hyperplasia (Double Muscle Disease) European cattle breeds (esp Charlois) Dystocias usually seen in cows giving birth to affected calves
Muscular Defects, Dystrophies, Dysfunctions
Spastic Paresis
Idiopathic muscle dysfunction of cattle (1 bulls) Presents as a sudden stiffening and extension of the hind legs The dz appears to be progressive as episodes become more frequent and last longer Also a familial dz of 3-7 month old Holstein calves and Scottish Terrier dogs
Spastic paresis (Elso heel) is characterized by spastic contracture of the gastrocnemius muscle. It is usually unilateral and occurs more commonly in the right rear limb. Spastic paresis is a state of partial paralysis, or incomplete paralysis.
Muscular Defects, Dystrophies, Dysfunctions
Mysathenia Gravis
Neuromuscular disorder characterized by muscle weakness exacerbated by exercise and improved by rest Clinically see choppy stride followed by recumbency and refusal to move; after few minutes, animal usually gets up and walks again; megaesophagus, hoarse bark or meow, pupillary dilation, serum CK and AST are normal Posture adopted a cat with myasthenia gravis. Note the inability to support weight of the trunk and head. Passive ventroflecion of the head and neck is apparent when the cat's trunk is supported.
Mysathenia Gravis
Congenital form
Autosomal recessive disorder inherited in Jack Russell Terriers, Springer Spaniels, Smooth Fox Terriers, cats Due to failure of formation of acetylcholine receptors in postsynaptic muscle membranes Clinical signs appear at 3-8 weeks of age
Acquired form
Immune-mediated disorder where antibodies are directed against acetylcholine receptors of neuromuscular junctions Reported in dogs and infrequently in cats, with possible higher incidence in German Shepherds and Abyssinian and Somali cats Dogs are most commonly affected at 2-3 years or 9-10 years of age Older dogs and cats also frequently have thymoma
Microscopic examination may yield normal muscle or denervation atrophy depending on severity of disease
Bacterial infection is implicated as a trigger for myasthenia gravis in humans subunits of acetylcholine receptor share antigenic determinants with E. coli, Proteus vulgaris and Klebsiella pneumoniae; similar linkage not yet made in animals
Mysathenia Gravis (FYI)
Dx by intravenous administration of edrophonium (Tensilon) prolongs active life of acetylcholine at neuromuscular junction see marked, transient improvement in muscle strength Test is less reliable in cats than in dogs and may be negative in severely affected dogs due to internalization of all acetylcholine receptors (gives presumptive dx only) Assay for circulating anti-acetylcholine receptor antibodies in cats and dogs is available at reference lab in San Diego, CA (this is gold standard for dx of acquired) Removal of thymoma or hyperplastic thymus
Muscular Defects, Dystrophies, Dysfunctions
Muscular Dystrophy Genetically determined Progressive, primary degenerative muscular dz Rare in vet med - have been reported in cattle, dogs, cats Age of onset is variable
Muscular Defects, Dystrophies, Dysfunctions
Muscular Dystrophy (Dogs)
Progressive degeneration of skeletal muscle in many breeds of dogs (Golden retrievers, Samoyed, Rottweiler, etc) ***Genetic Disease*** due to inherited mutation that results in lack of dystrophin (crucial cytoskeletal protein in sarcolemma) in skeletal and cardiac muscle without dystrophin, membrane gaps allow calcium influx hypercontraction myofiber degeneration and necrosis Male puppies are stunted, bunny-hopping gait, muscle atrophy, megaesophagus Muscle strength deteriorates until approximately 6 months of age when signs can stabilize Muscle biopsy reveals marked myofiber size variation, necrosis, and regeneration with multifocal myofiber mineralization; in latter stages may see fibrofatty connective tissue replacement of muscle
Muscular Defects, Dystrophies, Dysfunctions
Muscular Dystrophy (Cats)
Sex-linked disease that first appears at 5-6 months of age Clinically, affected cats have marked generalized muscle hypertrophy with protrusion of the tongue, excessive salivation, bunny hopping, and megaesophagus is common Dx by marked increase in serum CK, muscle biopsy with dystrophin immunostaining
Muscular Dystrophy
Skeletal muscle from a 8 week-old male Australian Shepherd marked and diffuse muscle fiber degeneration (200x). There is also perimysial and endomysial fibrosis
Higher power (600x) to demonstrate fiber degeneration, fiber nuclei proliferation and macrophage infiltration
Muscular Defects, Dystrophies, Dysfunctions
Glycogen Storage Diseases
Systemic diseases that involve muscle Rare but have been reported on most domestic species Clinical signs variable - due to insufficient energy production by affected muscle fibers Equine polysaccharide storage myopathy - increased amounts of irregularly distributed glycogen
Muscular Defects, Dystrophies, Dysfunctions
Myotonia
Rare skeletal muscle disorder characterized by continued active muscle contraction and delayed relaxation Due to mutation of ion channels including Cl, Na (these 2 most often), also K and Ca. Seen in Chows, Staffordshire Bull Terriers, Labrador retrievers, Rhodesian Ridgebacks, Great Danes and very rarely in few other breeds Clinically see generalized muscle stiffness and hypertrophy that is first observed at 2-6 months of age Affected dogs may remain in rigid recumbency for up to 30 seconds if placed in lateral recumbency Dx: may see elevated serum CK, muscle biopsies indicate normal muscle morphology, EMG is diagnostic
Myopathies
Ischemic Nutritional Toxic Exertional
Background - Myopathies
Muscle degeneration (Zenkers necrosis) has a common final sequence of events regardless of the initiating cause - leading to cell degeneration and/or cell death Exhaustion of ATP results in Ca overload Mitochondrial Ca overload Fibril hypercontraction and coagulation Myofibers mineralize
Muscle damage can be detected by the release of CPK (creatinine phosphokinase)and myoglobin in the serum
CPK - serum Myoglobin - urine (turnsdark red/brown) **both of these will return to normal levels (rapidly) with cesation of muscle damage
Background - Myopathies
Grossly affected muscles may appear pale and possibly edematous Nutritional, toxic, and exertional damages repair well while ischemic damages repair poorly (espeically if > 6hrs) Since most myopathies have the same terminal sequence of events, their lesions (gross and micro) are similar **Causitive/etiological dx are frequently made on the basis of history and clinical findings rather than pathology
Ischemic Myopathies
Ischemic muscle necrosis due to thrombosis or embolism is uncommon because of the abundant capillary bed encircling muscle fibers Myofibers are most sensitive, followed by satellite cells; fibroblasts are least sensitive Transient ischemia of few hours duration coagulation of contractile proteins but other muscle elements survive rapid regeneration in 2-3 weeks Ischemia of 6-18 hours duration death of myofibers and satellite cells repair by proliferation of endomysial fibroblasts and endothelial cells patchy scarring complete by several weeks post-injury Ischemia of > 18-24 hours death of all cells in area slow healing from viable tissue at periphery of lesion repair by fibrosis over months to produce very large scars
Ischemic Myopathies
Causes of Muscle Ischemia 1. Occlusion of a major blood vessel 2. External pressure on a muscle 3. Swelling of a muscle in a nonexpandible compartment (compartment syndrome) 4. Vasulitis/vaculopathy
Compartment syndrome
Muscles surrounded by heavy aponeurotic sheath or by bone and sheath are vulnerable to ischemia when they contract vigorously Muscle in full contraction may increase up to 20% in volume Increased intramuscular pressure is created if muscle cannot expand
Collapse of venous channels while there is muscle activity causes increased inflow of arterial blood if arterial pressure exceeded, results in ischemia fluid leaks from vessels and lactic acid forms
Compartment syndrome
Examples : Infarction of supracoracoid muscles in broiler chickens and turkeys following brief but vigorous wing flapping Anterior tibial syndrome in animals and human athletes Swelling of pretibial muscles which are surrounded by a fascial sheath anteriorly and the tibia posteriorly; muscle can become infarcted unless fasciotomy performed to relieve pressure
Pectoral Muscles from Broiler Turkeys with deep pectoral myopathy (compartment syndrome)
Downer Syndrome
Downer cow syndrome and related conditions external compression of relaxed muscles can cause ischemic necrosis in following circumstances
Conscious recumbency external pressure on muscles due to body weight can exceed both venous and arterial pressure muscle ischemia Limb muscles in flexed or tucked positions most vulnerable Seen in downer cows as soon as 6 hours of recumbency Stasis of blood in vessels may cause thrombosis Reperfusion injury leading to hemorrhage may also exacerbate the lesion if animal regains its feet Tight-fitting plaster casts and bandages Prolonged anesthesia post anesthetic myopathy (horses) Marked increase in pressure in down-side muscles during anesthesia if dorsal recumbency, gluteal and longissimus muscles at risk; if lateral recumbency, proximal limb muscles at risk Affected muscles are swollen, hard and painful; appear dark and hemorrhagic at necropsy Halothane anesthesia may increase incidence
Example of Pressure Necrosis
Rear leg muscle from dairy cow in conscious recumbency external weight on muscles has caused pressure necrosis of muscle = multiple irregular foci of pale muscle
Downer Syndrome
Increased intramuscular pressure during prolonged periods of recumbency has resulted in localized muscle pallor from myofiber necrosis secondary to decreased blood flow caused by compression of arteries.
Crushed Muscle Syndrome
Occurs when extensive traumatic muscle damage results in edema and swelling of muscle tissue causes increased intramuscular pressure Traumatic laceration of muscle hemorrhage, edema, inflammation of muscle increased vascular pressure within muscle ischemic necrosis if muscle confined by sheath or bone a.k.a. traumatic rhabdomyolysis
Vascular Occlusive Syndromes
Thromboembolism of terminal aorta or iliac arteries in cats with cardiomyopathy Aortic-iliac thrombosis in young male TB or SB horses effects are usually transient because of effective collateral circulation any hindlimb muscle damage is usually rapidly and completely repaired Multifocal muscle infarction in sheep with virulent bluetongue virus infection due to vasculitis with subsequent thrombosis Multifocal muscle infarcts in equine purpura hemorrhagica due to immunemediated vasculitis and subsequent thrombosis Ischemic necrosis of internal abdominal oblique muscles in ewes carrying twins or triplets in late pregnancy due to stretching of or trauma to the internal iliac artery
Vascular Occlusive Syndromes
Feline hypertrophic cardiomyopathy
Thromboembolism at bifurcation of aorta
Muscle Trauma
**Not in notes** Common in veterinary medicine muscle rupture is more common than tendon rupture External trauma includes crushing, lacerations, surgical trauma, bullet or arrow wounds, burns, injections Diaphragm may rupture as result of sudden increase in intraabdominal pressure HBC (hit by car) Partial rupture of a muscle can result in a tear in the fascial sheath through which the muscle can herniate during contraction
Muscle Trauma
Spontaneous rupture of longissimus, quadriceps, biceps femoris, gracilis, triceps or gastrocnemius in racing greyhounds Tearing of fibers of adductor muscles in cattle doing splits on slippery floors Traumatic lesions are often associated with extensive interruption of sarcolemmal sheaths repair is by budding and fibrosis with reduced function
Example of Muscle Trauma
Adult dog hit by a car and presented to emergency clinic the animal died shortly after presentation Gross examination revealed rupture of the diaphragm with loops of small intestine (arrow) in the thoracic cavity causing severe atelectasis of lungs This is a traumatic diaphragmatic hernia
Nutritional Myopathies
Nutritional Myopathy
Commonly called White Muscle Disease see in sheep, cattle, pigs (most frequent), foals, poultry rare in dogs and cats Caused by deficiency of vitamin E and/or selenium both required as antagonists of free radicals Se is contained in glutathione peroxidase In deficiency, free radicals damage cell membranes and mitochondria influx of calcium into myofibers degeneration and mineralization of contractile proteins sarcolemma and satellite cells survive muscle regeneration in survivors
Nutritional Myopathy
Type I oxidative fibers primarily affected - randomly distributed pale, flabby, and wet may see some hemorrhage and or chalky white mineralization Diagnosis history, increased serum concentrations of CK and AST, decreased blood concentrations of Vitamin E and/or selenium with typical lesions are most diagnostic Gross and histopathology are suggestive of but not absolutely diagnostic
Nutritional Myopathy
Thigh muscle from 6 month-old beef calf with WMD An entire muscle is pale (left), the muscle to the right is normal Photomicrograph has numerous swollen, eosinophilic and vacuolated myofibers admixed among normal fibers Cardiac muscle degeneration can also occur - appears similar Muscle groups affected vary greatly between individuals
Nutritional Myopathy
Sheep can see congenital lesions especially in tongue and neck muscles High mortality in 2-4 week old lambs lesions in major muscles of shoulder, thigh, back, neck and respiratory muscles; may also see myocardial necrosis and mineralization, especially of right ventricle Lower mortality in 4-8 month old lambs; can subclinical be with fewer lesions Adults similar to 4-8 month olds with localized lesions
Nutritional Myopathy
Cattle similar pattern of muscle involvement as sheep but myocardial lesions mainly in left ventricle Calves, especially 4-6 week-old beef calves lesions may be localized to muscles of urethra, rectum and esophagus Also common in calves up to 6 months old but can occur in adults mineralization of skeletal muscle is not common and heart involvement is rare in older animals
Nutritional Myopathy
Pigs skeletal muscle lesions less common than mulberry heart disease or hepatosis dietetica Normal pallor of pig muscles may mask lesions Most commonly see in 620 week old pigs Pale myocardium with multiple hemorrhages on epicardium/myocardium young pig with mulberry heart disease Mulberry
Nutritional Myopathy
Hepatosis Dietetica Uncommon syndrome of massive hepatic necrosis in swine Pathogenesis understood; thought to be due lack of tocopherols and Selenium Also called Yellow Fat Disease degeneration of skeletal and cardiac muscle, serous effusions, gastric ulcers, finrinoid necrosis of arterioles
Centrilobular necrosis and congestion in young pig with hepatosis dietetica
Nutritional Myopathy
Horses primarily see in foals 1 day to 12 weeks of age also see in pony, zebra and donkey foals Bilateral and extensive involvement of shoulder, neck and thigh muscles unable to rise and suckle (tongue also affected); also see nodular steatitis in subcutis of foals but not adults In older animals usually have myocardial lesions (especially left ventricular wall) which may cause cardiac failure; multifocal lesions can also be present in a variety of muscles
Toxic Myopathies
Lesions are similar to those of other mypoathies May be difficult to detect grossly
Clinical work up Clinical history Feed analysis
Common associated toxins:
Gossypol Cassia spp (Coffee Senna) Monensin Iron
Toxic Myopathy
Gossypol yellow polyphenolic compound found in cotton seeds
Toxic to pigs, calves, lambs and dogs In pigs, if cottonseed meal or cake comprises > 10% of the ration, skeletal and cardiac muscle necrosis develops after ingesting toxic rations for a month or longer suggests need for cumulative buildup of toxin Death usually by heart failure Dx by history, lesions, knowledge of diet
Toxic Myopathy - Plants
Plants responsible for skeletal muscle (and often myocardial) necrosis include: Cassia occidentalis and C. obtusifolia (coffee senna) in cattle, horses, sheep, goats and pigs Grows throughout southeastern USA Lesion is skeletal muscle necrosis with minimal to no mineralization Toxic principles are anthraquinones and alkaloids Karwinskia humboldtiana (coyotillo) in sheep and goats Persea americana (avocado) in horses Eupatorium rugosum (white snakeroot) in cattle
Toxic Myopathy - Plants
Cassia obtusifolia
Downer Cow with Cassia Toxicosis
Toxic Myopathy - Ionophores
Ionophores such as monensin, salinomycin, narasin and lasolacid are often added to chicken (growth enhancing) effects Most information relates to monensin toxicity Toxic to monogastric animals but if doses high enough, cattle and poultry also susceptible reported in horses**, donkeys, mules, zebras, cattle, sheep, dogs, wallabies, camels and antelope Toxic effects are cumulative if sublethal doses fed and are potientiated by addition of tiamulin or sulphonamides to feed
Toxic Myopathy - Ionophores
Horses most sensitive (2-3 mg/kg BW/single dose) lethargy, stiffness, muscle weakness, colic, recumbency, may also see myoglobinuria Monensin disrupts membrane transport of sodium, potassium and calcium results in influx of calcium into skeletal and cardiac myofibers hypercontraction exhaust mitochondrial ATP muscle necrosis Gross lesions if visible, see poorly defined pale streaks in myocardium and skeletal muscle, especially hindlimbs If animal survives severe toxicity, myocardial fibrosis may lead to heart failure later in life Dx history, lesions, analysis of feed sample (aliquots of top, middle and bottom of feed container), stomach/rumen contents, heart, skeletal muscle
Toxic Myopathy - Ionophores
Myocardial necrosis
Myocardial Fibrosis
Toxic Myopathy
Injection of irritant drugs
Many therapeutic agents cause local muscle necrosis and/or inflammation when injected intramuscularly Examples include: prednisone, barbiturates, vincristine, doxorubicin, dimethyl sulphoxide (DMSO), chloramphenicol, oxytetracycline and lidocaine
Toxic Myopathies - Iron
Iron toxicity occurs when the sow is deficient in vitamin E and piglets are born as a consequence with low levels. The routine iron dextran injections become toxic and cause severe muscle reactions at the injection sites. Vitamin E deficiency in the sow occurs when fats in the diet become rancid or cereals or corn have fermented and spoiled and the vitamin E is destroyed. Two to four hours after injection most of the litter become acutely lame on the legs that have received the iron. The muscles are swollen and the piglets develop heavy breathing and look pale. Death occurs within 24 hours. At post-mortem the muscles are coagulated due to necrosis of the muscle fibers
Exertional Myopathies
Exertional Myopathies
Exact causes unknown; thought to occur secondary to the rapid utilization of glycogen in type II (fast twitch, white) muscle and the subsequent accumulation of lactic acid in the affected muscle Glycogen rapidly utilized producing local heat and lactic acid Causes degeneration of contractile proteins Results in coagulative necrosis of the local muscle fibers and accumulation of interstitial fluids (edema) Edema causes local interstitial pressure and causes ischemia (compartment syndrome) There are several types of exertional myopathies
Equine Rhabdomyolysis
Two clinical syndromes previously recognized Azoturia = paralytic myoglobinuria or Monday morning disease Tying-up = acute rhabdomyolysis (a more mild form of azoturia) Both conditions now regarded as part of spectrum of clinical severity of a single disease process, with azoturia being severe and tying up a less severe form Etiology is unknown but exercise precipitates a.k.a. paralytic myoglobinuria, Monday Morning Disease Seen when horses are worked hard after several days of rest
Equine Rhabdomyolysis
Azoturia develops shortly after beginning work or training following several days of rest on full working rations Signs are hindlimb weakness, stiff gait, sweating, generalized muscle tremors, reluctant to move, may see myoglobinuria in severe cases, elevated serum CK and AST Animals that struggle appear to do worse; there can be multiple attacks days to weeks apart Gross lesions are dark, firm swollen gluteal, femoral and lumbar muscle groups, may see pale streaks (affected muscle fibers are usually type II), may see swollen kidneys discolored red-brown by myoglobin (can result in acute renal failure see kidney notes) Microscopically see myofiber degeneration/necrosis, myoglobinuric nephrosis (necrosis of proximal tubule epithelium due to myoglobin), calcification of muscle does not usually occur
Equine Rhabdomyolysis
Tying-up is common in riding and racing horses lesions and sequelae are milder than in azoturia Usually a recurrent problem with multiple attacks days to weeks apart, often following rest periods Susceptible animals are often of a tense or nervous disposition Azoturia-like syndromes in other species Racing greyhounds involving lumbar muscles Sheep after being chased to exhaustion by feral dogs
Equine Azoturia
Pale streaks throughout gluteal muscle in adult Standardbred mare
Acute myofiber degeneration
Malignant Hyperthermia
Also called porcine stress syndrome (PSS) Reported in most swine breeds, but higher prevalence in Landrace, Pietrain and Duroc breeds; also in some breeds of dogs Syndrome involving skeletal muscle muscle rigidity, hyperthermia/fever, dyspnea, dysrhythmias, metabolic acidosis, and death Affected animals can die rapidly from a combination of metabolic acidosis and heart failure
Malignant Hyperthermia
Familial Disease - susceptibility determined by autosomal recessive gene mutation localized to a C to T transition on the gene that controls the Calcium release channel receptor on cell surface of skeletal muscle
Following stress, receptor allows excessive calcium into muscle cell results in hypercontracture of muscle depletion of ATP increased anaerobic metabolism - increased lactic acid and increased core body temp rhabdomyolysis death due to increased serum potassium which causes cardiac arrest
Dx clinical signs, DNA blood test that detects mutation in receptor gene Lesions - pale, swollen, wet skeletal musclescombined with leasion of heart failure **the practice of selecting animals for heavy muscling may result in increased prevalence in purebred seine herds**
Malignant Hyperthermia
Post mortem findings are rapid development of rigor mortis Pale soft, wet skeletal muscles, especially of back, loin, shoulder and thigh pale soft exudative pork May also see pale left ventricular myocardium
The affected muscles are pale pink, moist, and swollen and have a cooked pork appearance (parboiled).
Capture Myopathy
Occurs in wild animals and birds folllowing chase and capture events Clinically and grossly these animals appear similar to those with azotemia or PSS (Procine Stress Syndrome) Secondary renal failure is common as in myocardial necrosis
Capture Myopathy
Rear leg muscle from Ostrich that developed capture myopathy after a long chase and struggle There is marked and diffuse acute myofiber swelling and fragmentation characteristic of degeneration and necrosis There is also extravasation of blood (hemorrhage)
Hyperkalemic Periodic Paralysis of QH (HYPP)
Genetic Dz - point mutation involving the skeletal muscle sodium channel; autosomal dominant Common sire (Impressive) Affected horses have remarkably welldefined muscle groups Clinical - muscle fasciculations, recumbancy, ataxia, spasms Dx - high serum K, increased muscle activity on EMG (constant) **No gross or microscopic lesions** (other than prominent muscling)
Tx - low K diet (No alfalfa) and diuretics
Myositis
Bacterial Idiopathic Parasitic
Myositis
Important to distinguish true myositis from degenerative myopathy with a secondary inflammatory response In degenerative myopathy cytokines released from damaged muscle fibers recruit inflammatory cells These cells are not involved in muscle cell damage True myositis occurs when inflammatory cells are directly responsible for initiating and maintaining myofiber injury The inflammation is directed at the myofibers, not the stroma Products from inflammatory cells are directly responsible for initiating and maintaining myofiber injury Inflammation of muscle caused by wide variety of agents, bacteria, viruses, protozoa, helminths, immune-mediated mechanisms
Myositis
Lymphocyticplasmacytic myocardial inflammation and myofiber degeneration in an adult dog
Bacterial Myositis
Infrequent as most bacteria find healthy muscle an inhospitable environment Bacteria can cause suppurative and necrotizing, suppurative and fibrosing, hemorrhagic, or granulomatous lesions Bacteria introduced by direct penetration, hematogenous spread, spread from adjacent cellulitis, fasciitis, tendonitis, arthritis, osteomyelitis
Bacterial - Suppurative Myositis
Living muscle tissue is unsuitable site for most bacteria so myositis is rarely a complication of bacteremia or septicemia Introduction of pyogenic bacteria into muscle by penetrating wounds or by extension from adjacent cellulitis, tendonitis, arthritis, osteomyelitis or lymphadenitis may produce a local abscess or cellulitis Most common causes of muscle abscesses are: Streptococcus equi horses Corynebacterium pseudotuberculosis sheep and goats Arcanobacterium pyogenes cattle and pigs Pasteurella multocida cats usually produces rapidly expanding and destructive seropurulent and necrotizing cellulitis Staphylococci dogs similar lesions as for cats
Bacterial - Granulomatous Myositis
Rare in animals
Mycobacterium bovis cattle and pigs tuberculosis giant cells acid fast rod-shaped bacteria Actinobacillus ligniersii cattle (woody tongue) Actinomyces bovis cattle (lumpy jaw) Staphyloccus aureus horses (botryomycosis) most common in neck and pectoral muscles (breast boils), usually result of penetrating wounds; develops into hard fibrous tissue mass containing pockets of pyogranulomatous exudate surrounding bacterial colonies
Bacterial Myositis - Clostridial Myositis
Necrotizing myositis Devitalized muscle tissue is highly susceptible to infections by clostridial organisms that thrive in the anaerobic environments created Gram positive anaerobic bacilli survive in environment as resistant spores Spore germination and vegetative growth with toxin production require alkaline pH and low oxygen tension conditions best produced in deep penetrating wounds Clostridial spores are found in the soil and may be deposited in penetrating wounds Most clostridial infections are initiated by poor sanitation during invasive events such as castrations, dehorning, vaccinations, etc Clostridial myositis = malignant edema, gas gangrene and blackleg
Bacterial Myositis - Clostridial Myositis
Gas gangrene and malignant edema are wound infections with: Clostridium septicum, C. perfringens, C. novyi, C. sordelli, C. chauvoei See severe edema formation, gas bubbles (due to breakdown of tissue sugars and release of CO2), crepitus, discoloration of affected area and toxemia with prostration, circulatory collapse and sudden death Malignant edema is term used for lesions confined to subcutis and fascia as a cellulitis Gas gangrene term used for deeper infections involving muscle
Bacterial Myositis - Clostridial Myositis
Toxin production allows rapid spread of infection along fascial planes, aided by increased capillary permeability, edema and gas production Production of thrombi leads to local ischemia and further necrosis of tissue See marked serous to serosanguineous exudate and initial rancid odor and later foul odor See few leukocytes in wounds because of destruction by toxins Clostridial bacilli seldom numerous in wound but invade bloodstream terminally rapid carcass decomposition
Bacterial Myositis - Blackleg
Blackleg specific form of gas gangrenous myositis mainly seen in cattle and sheep caused by Clostridium chauvoei following activation of latent spores in muscle
Disease localized to certain regions or farms Mainly affects animals in good condition on pasture, especially cattle <2 years old Ingestion of spores from soil absorption across intestinal mucosa hematogenous dissemination to various tissues including muscle Subsequent muscle injury may permit germination of latent spores proliferation of vegetative bacilli with toxin production Clinical signs similar to malignant edema; affected animals usually found dead
Bacterial Myositis - Blackleg
Lesions often see fibrinohemorrhagic pleuritis and pericarditis with endocardial hemorrhage in right heart; muscle lesions most common in large muscle of pectoral and pelvic girdles but can see small lesions in most any muscle - affected muscle is red-black as is overlying subcutis Dx lesions, anaerobic culture, FA on affected muscle Pseudoblackleg - C. septicum; multiple sites, little gas formation
Bacterial Myositis - Blackleg
A B
C
A, The dark red areas are caused by hemorrhagic necrosis of the underlying muscle. These lesions are characteristic of blackleg. B, Clostridium chauvoei can also produce substantial quantities of gas within infected tissues as shown here by the numerous (pseudocystic) spaces within hemorrhagic and necrotic muscle. C, Gram-positive bacilli are present in the serous exudate.
Masticatory Myositis
Idiopathic myositis Common disorder of dogs, especially young to middle-aged German Shepherds, Dobermans, retrieving breeds and other large breeds Inflammatory disorder involving muscles of mastication with probable immunemediated mechanism Triggered by formation of autoantibodies directed against a unique myofiber (type 2M) found in masticatory muscles of adult dogs circulating IgG is directed against the unique myofiber myosin Dx by clinical signs, elevated serum CK, serum positive for antibodies against type 2M fibers (80% of dogs), muscle biopsy
Adult Vizsla with chronic MM
Masticatory Myositis
Acute stage (Eosinophilic myositis) Decurrent painful swelling of masticatory muscle, especially temporal, masseter and pterygoid; also see anorexia and resistance to mouth opening; may also see pyrexia and/or tonsillar and regional node swelling Affected muscles are multifocally infiltrated by eosinophils with some lymphocytes, plasma cells and neutrophils; may have peripheral eosinophilia Chronic stage (atrophic myositis) most commonly recognized Pr...