Muscle Pathology (AH) Flashcards
Type I mm fibers
red -slow twitch - small - more mitochondria - no glycogen - no clycolytic.
Type II mm fibers
White - fast twitch - large - less mitochondria - more involved in atrophy - II a = oxitative + glycolytic. II b = glycolytic.
***What is the process that leads to Rigor Mortis?
decreased O2 –> decreased ATP –> decreased Ca2+ ATPase pump activity –> decreased Ca removal –> sustained contraction.
How does Rigor Mortis progress?
Start - 2hrs, Max - 24-48 hrs, Dissipates - 72 hrs. Starts at jaw and trunk and then goes to extremities.
What spp. get muscular Hyperplasia?
Calves and Lambs
In what breeds of cattle is muscular hyperplasia hereditary? Why does it happen?
Charolais and Belgian Blue. Mutation of myostatin gene –> double muscling
What spp. gets myofibrillar hypoplasia?
Pigs
Etiology of myofibrillar hypoplasia?( 3)
- Hereditary - decreased number of myofibrils in muscle fibers. 2. Teratogenic - Toxins (F. graminearum = F-2 toxin = mycotoxicosis) –> depressed growth in utero. 3. Choline or methionine deficiency –> decreased Ach synthesis and energy production.
Lesions of myofibrillar hypoplasia?
mm are atrophic, flabby, pale and wet.
Pathogenesis of Polysaccharide storage myopathy in horses?
Carbohydrate metabolic disorger –> insufficient energy production –> decrease in mm.
What can occur secondary to Polysaccharide storage myopathy in horses?
Acute myoglobinuric nephrosis (Pigment nephrosis) - tubule damage from myoglobin
Etiology of Glycogenoses (glycogen storage Dz)?
Missing or defective enzyme (inherited) –> accumulation of glycogen
What is Myotonia?
Channelopathy. Inability of myofibers to relax resulting in spasmodic contractions.
Etiology of HYPP?
Genetic mutation of skeletal mm sodium channel gene –> delayed inactivation of sodium channel activity –> uncontrolled twitching and kyperkalemia in bloodstream.
HYPP sequelae?
Laryngeal mm dysfunction. Trembling, weakness, collapse. Metabolic acidosis –> cardiotoxicity, pumonary edema. Can be fatal.
Although it occurs in all domestic spp., what two species are prone to Arthrogryposis?
calves and lambs
What is Arthrogyposis?
Muscle hypoplasia due to lack of muscle innervation during gestation.
What do the limbs look like of animals with Arthrogyposis?
small limbs with rigid joints –> crooked looking limbs.
Etiology of Arthrogyposis?
Infectious –> 1. viral (BVD, Akabane), 2. vaccinations druing 1st trimester (ruminants) for Rift Vally fever, wesselbron virus, bluetongue. Non-infectious –> 1. inherited in suffolk lambs, 2. Plant poisoning (lupinus spp.) causes decreased movement in
What is the primary defect associated with Arthrogyposis?
Always associated with spinal and brain abnormalities.
What are the categories of mm disterbances of growth?
Atrophy, hypertrophy, metaplasia, infiltration, muscular dystrophy
What is mm atrophy?
decrease in size of cells that have gained full development
Mm atrophy pathogenesis?
- Diminished level of work or 2. Removal of source of nutrition or stimulation (more common)
What are the types of mm atrophy?
Denervation - lack of tonic stimuli. Disuse - decrease of tonic stimuli. Malnutrition and cacexia - small, thin, dark mm. Senile- similar to malnutrition + lipofuscin. Pressure
Which type of atrophy effects both type I and II fibers. What about the others?
Denervation = I and II fibers. The rest = only type II.
Etiology of denervation atrophy?
Lack of tonic stimuli due to : 1. Damage to PNS (trauma, neoplasia, abscesses, pressure by disks) or 2. Damage to CNS (disk protrusion, chronic meningitis, trauma, metastatic lesions, localized spinal malacia)
Give three examples of denervation atrophy syndromes
-Equine lyaryngeal hemiplegia (roaring). -Damage to suprascapular nerve in horses (sweeny). -Radial or brachial paralysis in dogs associated with trauma.
Lesions of denervaiton atrophy?
diffuse atrophy involveing BOTH type I and II fibers
Etiology of Disuse atrophy?
Loss of tonic stimuli (but still intact) secondary to inactivity or limitation of movement (fractures, upper motor neuron damage, recumbency) Usually localized.
Lesions of Disuse atrophy?
Mainly involves Type II fibers. Flabby shruken muscles.
What is the most common form of Atrophy?
Atrophy of malnutrition and cachexia.
Etiology of atrophy of malnutrition and cachexia?
malnutrition, starvation, severe helminthosis, chronic debilitating diseases (TB, Johne’s Dx), Neoplasia
Lesions of atrophy of malnutrition an cachexia?
type II fibers involved. Small, thin, darm sticky, flabby mm.
What type of atrophy is similar to malnutrition and cachexia atrophy?
Senile atrophy
Lesions of senile atrophy?
Lipofuscin –> yellow brown color, especially in diaphram.
What causes pressure atrophy?
prolonged pressure of muscles from abscesses, tumors, parasitic cysts
What is Hypertrophy?
Incease in size of mm by an increase in fiber size. No new cells, just bigger size.
Etiology of hypertrophy?
- physiologic - athletic training, pregnant uterus. 2. Pathologic (left cardiac ventriclular hypertrophy. Idiopathic (esophagus, ileum - horses). 4. Iatrogenic - steroids.
Lesions of hypertrophy?
Dark red. Increase in myofiber diameter. Increased myoglobin. Larger cellular organelles.
What is steatosis?
defective myofiber development –> replacement of muscle tissue by adipose tissue.
How does steatosis alter the gross form the affected muscle?
It doesn’t
What spp. is steatosis seen in?
pigs, sheep, cattle
How do mm affected by steatosis appear?
soapy, marbling appearance
Is steatosis clinically significant?
no, congenital defect with no clinical significance.
What is muscular dystrophy?
Progressive degeneration due to abnormal muscle proteins (ex: dystrophin).
Etiology of muscular dystrophy?
Idiopathic (intact innervation, inadequate regeneration, primary myofiber defect) or Hereditary
General lesions of muscular dystrophy?
degeneration and failed attempts to regenerate –> fibrosis.
What animals get hereditary muscular dystrophy?
Marino sheep. Dogs - Canine X-linked mm dystrophy. Labradory retrieveres - HMLR (early in life)
Clinical presentation of HMLR? Lesions?
In young dogs. Bunny hopping. +/-megaesophagus –> aspiration pneumonia. Lesions: Type II myofiber deficiency –> decreased mm mass. Segmental necrosis and regeneration.
What is the defect in dogs with Canine X-linked mm dystrophy?
Dystrophin deficiency. Duchenne type
Lesions of ruptured mm?
Swollen by edema and hemorrhage. Tearing of mm.
What specific condition is associated with mm rupture?
Fibotic and ossifying myopathy (torn hamstring in quarter horses).
Sequelae of ruptured mm.?
Diaphragmatic rupture –> eventration. Rent in the cascial sheath –> eventration. In racing greyhounds –> muscle ruptrue during strenuous activity.
Lesions of congestion?
swollen red to black.
What is an example of mm congestion?
Bovine ruminal tympany (bloat)
Lesions associated with bloat?
cervical esophagus is red. Thoracic esophagus is pale (white). Extensiive congestion of ciervical region extending to the head. ==> bloat line.
Thrombosis, Embolism, and infarction lesions?
hemorrhage and necrosis in infarcted muscle, thrombus
What are the three responses of mm to injury?
degeneration, necrosis, regeneration
What is true about etiology of degeneration/necrosis?
There is a stereotyped response making it hard to determine etiology.
Histopathological interpretation of degeneration/necrosis
Monofocal monophasic - local trauma. Monofocal multiphasic - repeated local trauma. Multifocal monophasic - single exposure to mycotoxins or metabolic disorders. Multifocal, multiphasic - nutritional deficiency or muscular dystrophy.
Gross lesions of mm degeneration?
Degenerated mm. appear pale. ** 1. Chalky/white = severe calcification. Red = hemorrhage/ rhabdomyolysis (myoglobin release)**
Micro lesions of mm degeneration?
***1. Hypereosinophilia (green). 2. Dystrophic calcification (bluish granules in myofibers w/ von kossa stain). 3. Vacuoles and loss of striations. 4. Swelling. 5. Glassy or hyaline appearance (zenker’s degeneration). 6. Segmental rupture of fibers.
Types of mm degeneration?
Hyaline/waxy = Zenker’s (most common) - irreversible. Granular. Vacuolar (hydropic) = increased glycogen. Fatty. Lipofuscin (xanthomatosis) = yellow/brown.
When is mm degeneration irreversible?
once necrosis ensues
Ddx for degeneration?
gross lesion = pallor. Muscle pallor can also indicate pale muscles of veal calves, enemia, exsanguination, fat.
What are the mechanisms of cell injury that lead to necrosis?
- Ischemic and hypoxic injury –> ATP depletion. 2. Generation of reduced oxygen species –> Free radical injury . 3. Defects in membrane permeability –> membrane damage. 4. Disruption of calcium homeostasis –> calcium influx –> mitochondrial damag
What causes segmental necrosis?
physical insult, toxemia, myopathy, ischemia/infaction, bacterial emboli
What causes total necrosis?
extensive infarcts, massive trauma, large burns
Gross/Micro lesions of necrosis?
Gross: pallor, dry gritty. Micro: swollen, hypereosinophilic, fragmented sarcoplasm, persistent basal lamina, magrophage invasion, regeneration or fibrosis.
What are the main categories of degenerative myopathies?
Nutritional, Exertional, Toxic, Electrolyte, Stress, Ischemic, Endocrine, (Muscular Dystrophy)
List all nutritional myopathy syndromes?
While muscle Dz, Stiff lamb Dz, Porcine vit E/Se responsive disease complex, Pansteatitis in cats, Brown dog gut, Masticatory myopathy and polymyopathy in foals, muscle necrosis and steatitis in rabbits
TQ What is the pathogenesis of nutritional myopathies?
Decrease in Se / Vit E–> –> Lipid peroxidation –> damage to CM –> Ca2+ influx –> Mitochondrial damage –> segmental necrosis
What type of mm. is most effected by WMD?
Muscles with higher activity (type I) are affected most = diaphragm, intercostals, tongue, heart.
Histopathology of WMD?
Hypereosinophilia, Calcification, segmental degeneration (zenker’s), proliferation of myostatellite cells, macrophages, fiber framentation(retraction caps) ==> features of necrosis
What animals get white muscle disease (WMD) most often?
calves and lambs. Also in pigs.
What other selenium/ vit E deficiencies may coexist with WMD?
Mulburry heart and heptatitis dietetica
Where in the heart are lesions of WMD seen in calves and sheep?
RV in sheep, LV in calves
What lesions give Nutritional Myopathy the name WMD?
Severe calcification following necrosis –> Patchy white streaks with pronouned chalkey whiteness.
In pigs, where are lesions of Nutritional myopathy seen?
Selective of type I fibers = diaphragm, intercostal, tongue, heart. (diaphram and heart are most severe b/c they can cause death)
What is exertional myopathy?
Dz resulting in severe muscle degeneration following strenuous exercise.
Lesions of exertional myopathy?
Similar to WMD but affecting type II fibers. Acute degeneration –> rhabomyolysis. Type II fibers affected (glycolytic).
Pathogenesis of Exertional myopathy?
Strenuous activity –> utilization of glycogen –> accumulation of lactic acid –> acid denatures protein structure –> loss of water –> interstitial edema –> compressive circulatory disturbances –> ischemia –> Hyaline degeneration and necrosis of sk
* TQ Exertional Myopathy Syndromes by Spp.?*
Horses - azoturia and tying-up. Cattle - azoturia- like syndrom. Wildlife - capture myopathy
By what other names is Azoturia known in horses?
Eq. paralytic myogobinuria, Monday morning dz, sacral paralysis, exertional rhabdomyolysis.
CS of Azoturia?
Sudden onset of stiff gate due to mm weakness. Sweating. Death from Cardiac or renal failure. Myoglobinuria. Acidosis.
Azoturia etiology?
Forced exercise after period of rest w/o feed restriction (#1 cause) Electrolyte imbalances, Se deficiency, polysaccharide dz.
Azoturia lesions?
Moist, swollen, dark red, hemorrrhage. Hyaline degeneration and necrosis of sk. Mm. Later: fibrosis, atrophy, mm pallor. Myoglobinuric nephrosis –> DARK BLACK KIDNEYS
Sequelae of Azoturia?
death from cardiac or renal injury. Recovery w/ atrophy. Recovery with mm regeneration.
What is the less severe form of Azoturia?
Tying-up/setfast/ acute rhabdomyolysis in horses.
What form of Azoturia is associated with wild cattle/ zebu?
Azoturia-like syndrome. (also in racing greyhounds) Linked to unusual transportation/ confinement –> fighting and struggling.
Which form of Exertional Myopathy presents with pronounced Acidosis?
Capture Myopathy
Lesions of Capture myopathy?
Bilateral Symetry, Pale, swollen, edematous muscles. Hemorrage, ruptured tendons, myocardial injury (congestive HF)
Lesions of muscle toxicity?
Ill defined pale streaks in skeletal and or myocardium. Sometimes myoglobinuria in presence of extensive necrosis.
What are the main Toxins that can cause mm toxicity?
Ionophores (monesin salinomycin, narasin, lasalocid), Gossypol -cotton seed. Toxic plants (coffee senna) in horses, cattle, sheep and goats.
What spp. is most suseptable to Ionophores? What ionophore in particular?
Horses, in particular Monesin.
Pathogenesis of Ionophor mm. toxicity?
ionophores facilitate moevement of cations –> disruption of normal ionic equalibrium –> Ca2+ overload –> necrosis, death from cardiovascular shock/collapse
List all Elecrolyte abnormality myopathies.
Hyopkalemia, hypernatremia, hypophosphatemia
What spp. get Hypokalemia related myopathy?
Cattle and Cats
What effect on muscle does Hypokalemia have in cattle?
Profound weakness and recumbancy
Etiology of Hypokalemic myopathy in cattle? (3)
- Hypokalemia due to Anorexia and Ketosis. 2. Glucocorticoids w/ increased mineralcorticoid activity. 3. IV glucose/insulin = increase in cellular K inflow
MM Pathologenesis of Hypokalemic myopathy?
Decrease in muscle K+ –> altererd mitochindrial function and/or vasoconstriction (ischemia) –> myofiber necrosis. Hypokalemia also –> Abnormal cardiac conduction
Lesions of hypokalemic myopathy?
ischemic necrosis (from recumbancy), myofiber necrosis and vacuated myofibers.
What effect on mm does hypokalemia have in cats?
Generalized weakness w/ ventroflexion of the neck
Etiology of hypokalemia in cats
Abnormal skeletal mm metabolism. Ischema due to vasoconstriction, decrease in dietary K+ intake. Increased urinary exretion of K+ followeing chronic renal dz. 2* to GIT dz or inappropriate fluid therapy. Hyperthyroidism
Pathology of hypokalemia effect on mm in cats?
hyperpolarization of CM –> 2* excess NA permeability –> altered mitochondrial function –> ischemia -> mm necrosis. Also Abnormal cardiac conduction from decreased K+
What can hypokalemia eventually lead to in cats?
+/- chronic interstitial nephritis.
what spp. is prone to hypernatremia?
Cats
Pathology of Hypernatremia?
increased muscle Na+ –> abnormal energy metabolism. Increased blood Na+ –> vasoconstriction –> ischema. Both lead to transient myofiber necrosis and regeneration.
Hypophophatemia is linked to what spp?
Cattle
CS of Hypophosphatemia related myopathy?
Profound mm weakness, neurologic signs, and Hemolytic anemia.
What is the major stress induced myopathy?
Porcine Stress Syndrom (PSS)
Besides pigs, what other spp. can get PSS?
pigs, dogs, horses can all get PSS
Which mm fibers are effected in PSS?
Type II
Etiology of PSS?
Hereditary enzyme deficiency (Hal gene)–> hypermetabolic syndrome
Pathology of PSS?
Defect in uptake, storage and release of Ca2+ due to Enzyme deficiency –> increase in intracellular Ca2+ via ATPase –> increased glycolysis/ increase in body temp –> Lactate buildup –> denaturing of sarcoplasmic proteins –> movement intracellular H2O
What are the Ischemic injury myopathies?
Campartment syndrome and Deep pectoral myopathy
How is compartment syndrome characterized?
Degeneration and necrosis of mm that are surrounded by heavy aponeurosis (connective tissue). Ex: well conditioned athletes and poultry deep pectoral musculature.
What spp. gets Deep Pectoral Myopathy ?
Poultry
Etiology and Pathogenesis of Deep Pectoral Myopathy?
Vigorous flapping of wings –> muscle expansion –> vascular compression –> eschemia –> infarctions
What is downer syndrome?
ischemic necrosis of ventral and limb muscles following prolonged recumbency. Lesions appear as early as 6-12hrs.
What is Eq. post-anesthetic hypotensive myopathy?
Anesthesia induced hypotension –>severity varies from mm swelling with lameness to paresis with renal failure and shock. Sequelae = perm. Loss of mm function.
muscle crush syndrome
acute degenerative myopathy caused by severe trauma to a mm group. Similar to downer syndrom in pathogenesis and lesions.
What two endocrine disorders cause myopathy?
Hypothyroidism, Hypercortisolism
What type of atrophy results from endocrine myopathies?
Denervation Atrophy
How does myopathy caused by hypothyroidism present?
generalized weakness, muscle atrophy (type II fibers), megaesophagus, normal CK and AST.
Pathologenesis of hypothyroidism related myopathy?
- Decrease in thyroid hormone –> decreased mm metabolism –> myofiber wekaness and atrophy. 2. Peripheral neuropathy (axonal degeneration) –> damage to motor nerves –> denervation atrophy
Lesions of hypothryroidism?
marked type II atrophy in dogs
How does hypercortisolism related myopathy present?
stiff pelvic limbs gait, increased bulk and tone of proximal thigh muscles. (cushingoid pseudomyotonia). And muscle weakness.
Path of hypercortisolism related myopathy
increased cortisol production –> peripheral neuropathy –> denervation atrophy with regeneration.
What is myositis?
mm inflammation
What types of myositis are there?
Infectious - bacterial viral parasitic. Immune-mediated - eosinophilic. Idiopathic.
What causes Hemorragic myositis?
Clostridium sp.
Common examples of hemorragic myositis caused by Clostridium sp.?
Blackleg -ruminants. Gas grangrene - horse. Malignant edema - horses, ruminants and pigs.
Pathogenesis of Hemorrhagic myositis?
Clostridium sp. –> activation of spores –> proliferation of bacilli –> toxin production –> vascular damage –> edema, hemorrhage, necrosis, myositis and emphysema.
What causes suppurative myositis?
Pyogenic bacteria: -T. pyogenes, Strep spp., Staph spp., Corynebacterium. Psuedotuberculosis in horses.
What causes granulomatous myositis?
Actinobacillus lingieresii - wooden tongue (pale granulomas). Actinomyces bovis –> Lumpy jaw (caseous granulomas)
Protozoan parasitic myositis?
Sarcosystis spp (horse, cattle, sheep, camilids, pigs) Neospora caaninum (dogs, fetal cattle.)
Nematode parasitic myositis?
Trichinella spiralis (pigs.)
Cestode parasitic myositis?
Cysticercus spp (cattle, sheep, goats, pigs) - large visible cysts
2 Eosinophilic types of myositis?
Eosinophilic myositis of ruminants, Masticatory muscle myositis of dogs (GSD)
lesions of eosinophilic myositis?
Green!
Etiology of eosinophilic myositis?
sarcosystosis, immunologic injury - immune reaction to type II muscle fibers. Idiopathic.
Immune mediated myosistis examples?
Polymyositis of dogs and purpura hemorrhagica in horses
Polymyositis of dogs lesions?
Lymphoplasmacytic inflammation –> 1. megaesophagus. 2. Atrophy, degeneration, necrosis. 3. infiltraion of lymphocytes and plasma cells.
Pupura hemorrhagica in horses etiology?
Post-streptococcal infection following strangles –> immune complexes
Lesions of purpura hermorrhagica?
edema of the head and limbs. Leukocytoclastic vaculitis. Petechiae, +/- glomerulonephritis.
What are the three main neoplasias of muscle?
Rhabdomyoma, Rhabdomyosarcoma, Botyroid Rhabdomyosarcoma.
Etiology/origin of Rhabdomyoma?
Congenital. Origin = 66% heart
Lesions of Rhabdomyoma?
Large pedunculated mass made up of cells that resemble skeletal mm (cross striations) found embeded in heart. Benign
Rhabdomyosarcoma =?
Malignant form of rhabdomyoma
Rhabdomyosarcoma gross pathology?
tumors are poorly encapsulated spherical nodules formed by pink/grey tissue. Metastasis to lung, spleen, lymph nodes and kidneys are common.
Botryoid rhabdomyosarcoma is found in what spp?
large breed dogs.
Origin of BRS?
embryonic myoblasts –> urinary trigone –> urinary bladder
Disorders of neuromuscular junction?
Myasthenia gravis, botulism
What is Myasthenia gravis?
weakness and severe muscle fatigue from mildest exercise due to reduction of Ach receptors
Congenital myasthenia gravis etiology?
Low # of Ach receptor.
Lesions of congenital myasthenia gravis?
- no change. 2. disuse atrohpy. 3. fibrous.
Aquired Myasthenia gravis etiology?
Autoimmune - IgG to Ach receptors.
Lesions of aquired A MG?
muscle weakness –> 2* 1. Megaesophagus –> asperiation pneumonia. 2. Dysphagia. 3. Thymoma
Tx of A MG?
Anti-Cholinergic drugs (neostigmine) –> dramatic improvement
Etiology of Disorders of Tendons?
Congenital anomalies (contracted tendons), Physical injury (Perosis of bird), Inflammation (tendonitis, parasitic.)
Perosis of birds is what?
displacement of tendons - gastrocnemiusm Due to dietary Mn or Choline deficiency.
Tendonitis etiology
trauma or penetrating wound.
Bowed tendon =?
thickened lateral deviation
Parasitic tendonitis is caused by what?
Onchocerca spp. –> ligamentum nuchae
Lesions of parasitic tendonitis?
Fibrous nodules = “worm nodules or worms nest”
