JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2018940): A broiler breeder chicken
HISTORY: This chicken received a new feed 2 weeks prior to showing weakness and reluctance to move.
HISTOPATHOLOGIC DESCRIPTION: Skeletal muscle: Approximately 80% of the myofibers have undergone one or more of the following changes: have hypereosinophilic, fragmented sarcoplasm with disorganized or hyalinized myofibrils (which is often invaded by heterophils and macrophages) with nuclear pyknosis and rare contraction bands (necrosis); have swollen, vacuolated sarcoplasm with loss of cross striations and faded, occasionally internalized nuclei (degeneration); have a proliferation of satellite cells, slightly basophilic sarcoplasm and internalization and rowing of nuclei (regeneration); or are lost and replaced with necrotic debris and deeply basophilic granular or fragmented material (mineral). Multifocally expanding the endomysium and perimysium and surrounding necrotic myofibers are low to moderate numbers of macrophages and heterophils admixed with eosinophilic cellular and karyorrhectic debris and fibroblasts with associated collagen (fibrosis).
MORPHOLOGIC DIAGNOSIS: Skeletal muscle, myocytes: Degeneration, necrosis, loss and regeneration, multifocal to coalescing, moderate, with heterophilic and histiocytic inflammation and fibrosis, chicken, avian.
ETIOLOGIC DIAGNOSIS: Ionophore myodegeneration and necrosis
CAUSE: Ionophore (monensin) toxicosis
- Monensin is a fermentation product of Streptomyces cinnamonenis and is commonly used as an antibiotic
- Acts as an ionophore (ion carrier) that facilitates transport of cations (Na+) across cell membranes
- Commonly used ionophore antibiotics are monensin, salinomycin, lasalocid, maduramicin (poultry) and naracin
- Used primarily as a coccidiostat in poultry and livestock; causes influx of sodium into sporozoites which then swell and burst
- Promotes growth in ruminants by increasing production of ruminal propionic acid
- Monogastrics, especially horses, are especially sensitive to toxicity, and may suffer intoxication (causes K+ to leave and Ca+2 to enter cells, particularly myocytes, resulting in cell death) by being fed ionophore-containing cattle rations
- Sulfonamides and tiamulin (antibiotic used for swine dysentery) potentiate toxic effects
- Myocardial lesions in monensin toxicity are not reparable
- Ionophore antibiotics bind cations such as sodium and potassium and create movement across cell membranes
- Toxic monensin levels cause abnormal cellular Na+ intake and loss of hydrogen ion; calcium enters the cell secondarily with a loss of membrane ion gradients
- Calcium is sequestered in mitochondria leading to failure of oxidative phosphorylation, ATP depletion, loss of Na/K pumps, and mitochondrial swelling and disruption
- Increased cytosolic calcium leads to myofibrillar hypercontraction and degeneration
- Skeletal and cardiac muscle, experience rapid-onset necrosis
TYPICAL CLINICAL FINDINGS:
- Anorexia, lethargy, stiffness, weakness, tremors, recumbency in 24 hours
- Acute heart failure without clinical signs
- Chronic sublethal doses are cumulative with delayed onset of clinical signs
- Early signs in horses are colic, apprehension, and profuse sweating
- Birds may have decreased egg production, depression, weakness with drooping wings, posterior paralysis, extended legs and neck, and sternal recumbency
- Elevation of aspartate aminotransferase (AST), creatinine phosphokinase (CPK), and lactate dehydrogenase (LDH)
- Myoglobinuria reported in swine, dogs and horses
TYPICAL GROSS FINDINGS:
- No signs may be evident in acute toxicity cases
- In 3-4 days skeletal and myocardial muscle pallor is present
- Lesions consistent with congestive heart failure (hydrothorax, pulmonary edema, ascites) may be present
- Myocardial fibrosis and muscle atrophy, especially of the hindlimbs, may occur in older lesions
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Monophasic, multifocal degeneration by 48 hours after exposure
- Multifocal segmental necrosis of skeletal and myocardial muscle
- After 3-4 days, infiltration by macrophages and myofiber regeneration
- In chronic cases, skeletal muscle may be normal, but myocardial fibrosis may be extensive
- Swelling and disintegration of mitochondria occur early in the course
- Both type 1 and type 2 fibers are involved with necrosis and macrophage infiltration
- Swollen sarcoplasmic reticulum and mitochondria, lipid globule accumulation, z-lines no longer parallel, myofibrillolysis, formation of myeloid bodies, separation of desmosomes
ADDITIONAL DIAGNOSTIC TESTS:
- Analysis of feed or stomach contents (in cases where feed cannot be measured, the heart can be a useful diagnostic specimen for postmortem confirmation)
- The measured monensin concentrations often don’t correlate with clinical outcome
DIFFERENTIAL DIAGNOSIS for myopathy in birds:
- Nutritional myopathy (vitamin E/selenium deficiency): Usually more mineralization; polyphasic necrosis
- Deep pectoral myopathy: Diffuse edema of the entire muscle, with necrosis of the middle third
- Horses: Exquisitely sensitive with acute heart failure and cardiac necrosis predominating
- Ruminants are less susceptible than horses
- In cattle, skeletal and cardiac muscles are equally affected
- In sheep and swine, skeletal muscles are the main site of damage and myoglobinuria is generally present
- Adult poultry, especially turkeys, are more susceptible than broilers
- In pigs, monensin poisoning is associated with dyspnea, anorexia, ataxia, paresis, myoglobinuria and cyanosis, diarrhea, tympany, and pruritus; death follows in about 6 hours; continuous feeding of monensin to male pigs (50 ppm for 52 days) reduces blood levels of testosterone, and is associated with dystrophy of seminiferous tubules and reduced sperm counts
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