JPC SYSTEMIC PATHOLOGY

MUSCULOSKELETAL SYSTEM

April 2025

M-T01 (NP)

 

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: 80% of the myofibers have undergone one or more of the following changes: myocyte sarcoplasm is hypereosinophilic and fragmented with disorganized or hyalinized myofibrils (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 necrotic 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

GENERAL DISCUSSION:

• Common ionophores used in agriculture include the antibiotics monensin, lasalocid, salinomycin, marasin, and maduramicin
  • Monensin is a fermentation product of Streptomyces cinnamonenis and is used as a coccidiostat in poultry and ruminants; often added to the feed; toxicity often due to mixing errors and may involve many animals
  • Maduramicin is used as a coccidiostat in poultry; cardiotoxic in cattle and sheep
  • Also used to enhance growth in poultry and ruminants
• They alter membrane permeability to electrolytes by acting as an ion carrier (ionophore) that facilitates transport of cations (Na+) across cell membranes; therapeutic use as a coccidiostat causes sporozoites to swell and burst due to Na+ influx
• If used in excess, cause skeletal and cardiac muscle damage; monogastrics have low tolerance to these drugs; horses are extremely susceptible (LD50 of 2-3mg/kg vs poultry who have an LD50 of 90-200mg/kg)
  • Other species: Dogs, 5-8 mg/kg; sheep and goats, 12-24 mg/kg; cattle, 50-80 mg/kg; Pigs, 16-50 mg/kg

PATHOGENESIS:

• Ionophores form lipid-soluble bipolar reversible complexes with cations (Na+, K+), allowing movement of cations across cell membranes (often against the concentration gradient)
• The influx of Na+ leads to abnormalities in electrolyte-modulated calcium channels, ultimately resulting in calcium overload and death of skeletal and cardiac muscle
  • Calcium sequesters in mitochondria and cytosol > mitochondrial failure and myofiber hypercontraction > necrosis and degeneration
• Toxic effects potentiated by other antibiotic feed additives, including tiamulin, triacetyloleandomycin, and sulfonamides
• Myocardial lesions are not reparable; skeletal muscle can regenerate

TYPICAL CLINICAL FINDINGS:

• Single large dose: anorexia, lethargy, stiffness, weakness, tremors, marked signs of colic (equids), apprehension, and recumbency within 24 hours
• Sublethal doses are cumulative with delayed onset of clinical signs (days to weeks); initially scour and lose weight, leading to evidence of progressive cardiac failure +/- renal failure and poor weight gain
• Elevation of aspartate aminotransferase (AST), creatinine phosphokinase (CPK), and lactate dehydrogenase (LDH)
• +/- myoglobinuria (especially in sheep and swine)

TYPICAL GROSS FINDINGS:

• First 48 hours: none evident in acute toxicity cases
• Days to weeks: skeletal and/or myocardial muscle pallor is present +/- lesions consistent with congestive heart failure (hydrothorax, pulmonary edema, ascites)
• If they recover from the toxicity, may see myocardial fibrosis and muscle atrophy, especially of the hindlimbs

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Monophasic, multifocal skeletal muscle and myocardial necrosis by 48 hours after exposure; both type 1 and type 2 fibers affected
• A few days post-exposure, infiltration by macrophages and skeletal myofiber regeneration
• In chronic cases, skeletal muscle may be normal (regenerates), but myocardial fibrosis may be extensive (does not regenerate)

ULTRASTRUCTURAL FINDINGS:

• Swelling and disintegration of mitochondria occur early in the disease course
• Both type 1 and type 2 fibers are involved with necrosis and macrophage infiltration

DIFFERENTIAL DIAGNOSIS for myopathy in birds:

• Nutritional myopathy (vitamin E/selenium deficiency): Usually more mineralization; polyphasic necrosis (vs monophasic necrosis in ionophore toxicity)

COMPARATIVE PATHOLOGY:

• Horses: Exquisitely sensitive; acute heart failure and cardiac necrosis are predominating lesions
• Ruminants are less susceptible than horses
  • In cattle, skeletal and cardiac muscles are equally affected
  • In sheep, skeletal muscles are the main site of damage and myoglobinuria is generally present
• Adult poultry, especially turkeys, are more susceptible than broilers; breast muscle not affected
• Swine: skeletal muscle damage and myoglobinuria predominate
• Rabbits: anorexia, weakness, diarrhea, respiratory distress, and opisthotonus; predominantly affects skeletal muscle
• Toxicity also reported in donkeys, mules, zebras, dogs, wallabies, camels, blesbok, Stone sheep, ostriches, quail, and African wild birds
• Western Australian Carnaby’s black Cockatoos: Hindlimb paralysis syndrome (Chips)- Annual outbreaks of hindlimb paralysis with occasional loss of deep pain and cloacal tone, typically occurring between January and March; mono- to polyphasic myopathy of hindlimb and wing muscles; ddx include neurotoxicoses (eg, organophosphate, organochlorine and carbamate) and, less likely, mycotoxicosis (eg, ionophore toxicosis), nutritional myopathy (eg, vitamin E/selenium deficiency) or botulism.(Coiacetto J Comp Path 2024)

REFERENCES:

1. Abdul-Aziz T, Fletcher OJ. Chapter 5: Cardiovascular System. In: Abdul-Aziz T, Fletcher OJ, Barns HJ, eds. Avian Histopathology. 4th ed. Madison, WI: Omnipress; 2016: 145, 159.
2. Barnes HJ, Abdul-Aziz T, Fletcher OJ. Chapter 4: Muscular System. In: Abdul-Aziz T, Fletcher OJ, Barns HJ, eds. Avian Histopathology. 4th ed. Madison, WI: Omnipress; 2016: 109, 123 -124.
3. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4^th Ames, IA: John Wiley and Sons, Inc; 2016:316.
4. Coiacetto FJ, Rossi G, Stephens N, Vaughan-Higgins RJ. Gross and histopathological findings in hindlimb paralysis syndrome in wild Carnaby's black cockatoos (Zanda laitirostris). J Comp Pathol. 2024;210:38-46.
5. Cooper BJ, Valentine BA. Muscle and Tendon. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2016:219.
6. Fenton H, McManamon, Howerth EW. Anseriformes, Ciconiiformes, Charadriiformes, and Gruiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:699.
7. Gal A, Castillo-Alcala F. Cardiovascular system, pericardial cavity, and lymphatic vessels. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St Louis, MO: Elsevier; 2022:652, 667-668.
8. Schmidt RE, Struthers JD, Phalen DN. Pathology of Pet and Aviary Birds. 3rd ed. Hoboken, NJ: John Wiley & Sons, Inc.; 2024: 348.
9. Valentine BA. Skeletal muscle. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St Louis, MO: Elsevier; 2022:1009, 1018-1019, 1025,1027, 1029.

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