Muscle Pathology II Lecture Notes PDF

Muscle Pathology II Moving Santiago Diab, DVM, DipACVP [email protected] Learning objectives • Learn CAUSES, PATHOGENESIS and the PATHOLOGY associated with DISEASES that cause MUSCLE NECROSIS • Learn CAUSES, PATHOGENESIS and the PATHOLOGY associated with DISEASES that cause MUSCLE INFLAMMATION...

Muscle Pathology II Moving Santiago Diab, DVM, DipACVP [email protected] Learning objectives • Learn CAUSES, PATHOGENESIS and the PATHOLOGY associated with DISEASES that cause MUSCLE NECROSIS • Learn CAUSES, PATHOGENESIS and the PATHOLOGY associated with DISEASES that cause MUSCLE INFLAMMATION • Learn terminology and biological behavior of skeletal muscle NEOPLASIA Muscle Necrosis What can cause muscle necrosis? ➢Ischemia (i.e. Downer Cow Syndrome) ➢Trauma (i.e. external trauma or sports injury) ➢Toxins (i.e. ionophores) ➢Nutritional deficiencies (i.e. Vit E/Selenium) ➢Metabolic diseases (i.e. Exertional Rhabdomyolyisis) Muscle necrosis - Gross features 1. Often unrewarding 2. Often confusing or misleading 3. Often needs histopathological confirmation BUT… ➢ Muscle is usually pale (locally extensive or streaks) ➢ There may be swelling (edema) ➢ May be reddish or red if there’s hemorrhage ➢ May be dark red to black (w/o hemorrhage) in one disease…. Muscle necrosis - Microscopic features ➢ Loss of cross striations ➢ Fragmented sarcoplasm ➢ Hypereosinophilia ➢ Regeneration and fibrosis common Muscle necrosis - Microscopic features ➢ Loss of cross striations ➢ Fragmented sarcoplasm ➢ Hypereosinophilia ➢ Regeneration and fibrosis common Ischemia - Downer Syndrome ➢ Humans and domestic animals ➢ External pressure of objects or by pressure created by the weight of body on a limb tucked under the body for prolonged periods ➢ Pressure collapses first veins and then arteries ➢ Horses and cows can have extensive ischemic necrosis in as short as 6 hours ➢ As pressure is removed, edema and reperfusion injury possible Ischemia - Downer Syndrome https://www.veterinary-practice.com https://homesteadsupplier.com/collections/cow-lifts Ischemia - Compartment Syndrome ➢ Muscles are surrounded by heavy aponeurotic sheath or by bone ➢ Vigorous muscle contractions increase fiber diameter up to 20% ➢ Collapse of venous outflow BUT increase in arterial blood flow to muscle ➢ Accumulation of interstitial fluid (edema) Infarction of supracoracoid muscle in a chicken (deep pectoral myhopathy) ➢ Increase intramuscular pressure and ischemia Ischemia - Compartment Syndrome Francisco Carvallo Trauma - Diaphragmatic rupture ➢ Max ➢ Male castrated ➢ Left the home for 3-days ➢ Upon arrival it didn’t eat ➢ Died during the night it came back to the house Trauma - Rupture of Gastrocnemius ➢ Gastrocnemius muscle is critical for normal rising and weight bearing in cattle ➢ Repeated efforts to rise o single force trauma (stampede) - Dairy cows trying to get up on slippery floors - Calves trapped in mud - Animals with neurological conditions ➢ Unilateral or (often) bilateral ➢ “Rabbit leg” The hock rests on the ground such that a 90-degree angle exists between the tibia and metatarsus Santiago Diab Trauma - Rupture of Gastrocnemius Calf from video in previous slide Santiago Diab Santiago Diab Toxins Ionophore (Monensin) toxicity, heart, bovine Ionophores – growth promoters / coccidiostats ➢ Monensin, Lasalocid, Salinomycin, others ➢ Toxicity results from Calcium overload ➢ Most used in ruminants and poultry ➢ Horses very sensitive to toxicity Toxic plants ➢ Cassia/Senna occidentalis (coffee senna). Southern USA ➢ Thermopsis spp. (goldenbanners or false-lupines) Adriamycin - Chemotherapeutic agent ➢ Cardiotoxic INTA Balcarce hydrothorax Ionophores ascites enema nutmeg liver pulmonary indicators of heart injury during necropsy ↑ Ionophore (Monensin) toxicity, skeletal muscle, horse A B Figure 15-33 Ionophore Toxicity, Monensin, Skeletal Muscle. A courtesy Dr. J. Wright, College of Veterinary Medicine, North Carolina State University; and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. B courtesy Dr. M.D. McGavin, College of Veterinary Medicine, University of Tennessee. Toxic plants – Cassia sp. and Thermopsis sp. ➢ Pastures or baled hay ➢ Skeletal muscle necrosis is usually polyphasic Thermopsis montana ➢ Cardiac myonecrosis may or may not be present Cassia occidentalis Figure 3-76 Segmental myodegeneration caused by Cassia occidentalis poisoning of a heifer. Courtesy M.D. McGavin. JKP Pathology of Domestic Animals Vitamin E and SE deficiency Virginia Salvai ➢ “Nutritional Cardiomyopathy” or “White Muscle Disease” ➢ Vit E/Se necessary to protect muscle from oxidative damage ➢ Young animals (less than a couple of months) more susceptible to the disease ➢ Gross lesions are not always evident (pale or “white” muscle) ➢ There may be changes suggestive of heart failure (pulmonary edema, hydrothorax, ascites, nutmeg liver) Nutritional deficiency – Vitamin E and SE ➢ “White Muslce Diasease” or “Nutritional Cardiomyopathy” ➢ Vit E/Se necessary to protect muscle from oxidative damage ➢ Young animals (less than a couple of months) more susceptible to the disease ➢ Gross lesions are not always evident ➢ There may be changes suggestive of heart failure (pulmonary edema, hydrothorax, ascites, nutmeg liver) Virginia Salvai Nutritional deficiency – Vitamin E and SE ➢ “White Muslce Diasease” or “Nutritional Cardiomyopathy” ➢ Vit E/Se necessary to protect muscle from oxidative damage ➢ Young animals (less than a couple of months) more susceptible to the disease ➢ Gross lesions are not always evident ➢ There may be changes suggestive of heart failure (pulmonary edema, hydrothorax, ascites, nutmeg liver) Figure 15-39 Nutritional Myopathy (White Muscle Disease), Skeletal Muscles of the Caudal Thigh, Sagittal Section, Calf. Courtesy Dr. G.K. Saunders, Virginia-Maryland Regional College of Veterinary Medicine Exertional Myopathies The Raptor Trust Facebook Page ➢ Exercise-induced myonecrosis in any species (can be massive) 1. Capture myopathy (wild animals) It causes the highest number of deaths associated with wildlife translocation* 2. Exertional rhabdomyolysis (horses more common) * Conserving wildlife in a changing world: Understanding capture myopathy – a malignant outcome of stress during capture and translocation. Breed et al. Conservation physiology, Vol. 7, 2019. Exertional Rhabdomyolyses ➢ Exertional Myopathy, Azoturia, Setfast, Blackwater, Monday Morning Disease, and Tying-up ➢ Sudden onset of stiff gait, reluctance to move, swelling of affected muscle groups (especially gluteal), sweating and non-specific signs of pain and discomfort ➢ Serum CK and AST often very elevated ➢ Pathogenesis not completely understood Abnormal calcium homeostasis Polysaccharide storage myopathy frequent in horses that develop exertional rhabdomyolysis Courtesy of Dr. LeRoith Exertional Rhabdomyolyses A ➢ Gross: Muscles can be pale or red-tinged ➢ Histo: Coagulative necrosis, macrophages, regeneration (hind leg muscles usually more severe) B ➢ Evaluate possible renal damage (myoglobinuric nephrosis) ➢ Diagnosis is clinical usually, but biopsies to check for EPPSM may be helpful Figure 15-35 Acute Rhabdomyolysis, Skeletal Muscle, Horse. A courtesy Dr. W. Crowell, The University of Georgia; and Noah’s Arkive. B courtesy Dr. B.J. Cooper, Oregon State University. Muscle Inflammation (Myositis) What can cause muscle inflammation? ➢Infectious agents Bacteria Virus Parasites Fungi ➢Immune mediated diseases Morphologic features of myositis ➢ Inflammation is the primary feature ➢ Necrosis may be concurrent but is secondary to inflammation (exceptions apply) ➢Fibrosis and/or repair may occur in chronic cases Myositis – Gross features ➢No change at all ➢Changes in color (pale tan, hemorrhagic, greenish) Well circumscribed Poorly circumscribed Small or big Diffuse or nodular ➢ Change in texture Myositis – Blackleg (Clostridium chauvoei) ➢ Spore-forming, Gram positive, anaerobic bacterium ➢ Young ruminants (cattle more common) ➢ Acute or sudden death, limb swelling, limping ➢ Pathogenesis Ingestion of spores from the soil > spores disseminate hematogenously > localize and stay in sk. and cardiac muscle > local hypoxia > germination of spores and toxic production Diego Rivoira inflammatory + & necrotising Myositis – Blackleg (Clostridium chauvoei) ( necrotising typical Lesion in can occur Skeletal muscle or the heart Photos: Santiago Diab myositis dark redblack lesion Photos: Santiago Diab Protozoal myopathy – Neospora caninum ➢ Often transmitted in utero to puppies ➢ Peripheral nervous system and muscles invaded by parasite (neuropathy and myositis) ➢ Denervation atrophy of muscles ➢ Progressive neuromuscular weakness in pups several weeks of age (more in pelvic limbs) ➢ Gross: Marked muscle atrophy (remember pelvic limbs more common) Muscles can be firm and pale ➢ Histo: Mixed inflammation of muscle and nerves Protozoal microorganisms can be hard to find Figure 3-101 Protozoal cyst in a dog with protozoal myositis. This organism could be either Neospora caninum or Toxoplasma gondii. H&E stain. JKP Pathology of Domestic Animals Toxoplasma gondii can produce similar protozoal myositis in multiple animal species Trichinella spiralis (Trichinosis) ➢ Major economic importance in porcine industry ➢ It is a serious zoonosis (Worldwide) ➢ Adult nematode in SI > Larvae enter bloodstream > Larvae encyst in myocytes ➢ Gross: usually unremarkable but occasionally very small white, sometimes gritty foci ➢ Active muscles (tongue, masseter, diaphragm, intercostal, laryngeal and extraocular muscles) ➢ Histo: encysted larvae, sometimes with inflammation (> eosinophilic). Larvae can die and mineralize Figure 15-41 Trichinosis, Encysted Larvae, Diaphragm, Bear. (Courtesy Dr. M.D. McGavin, College of Veterinary Medicine, University of Tennessee.) Myositis – Polymyositis ➢ Immune mediated / non-infectious ➢ Most common in adult dogs of various breeds ➢ Clinical Signs: Exercise intolerance, muscle Figure 3-82. Immune-mediated myositis in muscle from a dog. H&E stain. JKP Vol. 1. weakness, stiff gait, muscle atrophy ➢ Micro Path: Interstitial and perivascular lymphocytic infiltration, degeneration, fibrosis ➢ Differential dx is masticatory myositis Polymyositis > T Lymphocytes Masticatory myositis > B Lymphocytes Figure 3-83 Immune-mediated myositis in a dog. Frozen section, Gomori trichrome. JKP Vol. 1 Myositis – Masticatory myositis ➢ Immune mediated disease of dogs (antibodies against type 2M myosin) ➢ Masseter, temporal and pterygoid muscle affected ➢ Dogs unable to fully open the mouth, pain upon opening jaw ➢ Gross Path: Swelling (acute) or atrophic myositis of temporal and masseter muscle (chronic) ➢ Micro Path: Necrosis and interstitial and/or perivascular inflammation (eosinophils, lymphocytes, plasma cells, macrophages) ➢ If untreated it may progress to irreversible damage Myositis – Masticatory myositis Masseter, temporal and pterygoid muscle affected Figure 3-84 Chronic masticatory myositis in a dog; severe atrophy of masticatory muscles. (Courtesy W. Hornbuckle.). JKP Vol. 1 Neoplasia Primary skeletal/smooth muscle neoplasia ➢Skeletal (striated) muscle Benign = RHABDOMYOMA Malignant = RHABDOMYOSARCOMA ➢Smooth (no striations) muscle Benign = LEIOMYOMA Malignant = LEIOMYOSARCOMA Rhabdomyoma ➢ Most common in the heart of piglets - Incidental necropsy finding ➢ Larynx of adult dogs - Nodular masses protruding into the lumen of the larynx Dyspnea, stridor, altered bark Canine laryngeal rhabdomyoma Rhabdomyosarcoma ➢ Fleshy growths that occur in a Noah’s Arkive (Dr. Morris) variety of sites (even where no skeletal muscle is found) ➢ Urinary bladder of young dogs (botryoid rhabdomyosarcoma) Botryoid rhabdomyosarcoma in the trigone of the urinary bladder Leiomyoma ➢ GI tract ➢ Female reproductive tract Santiago Diab Santiago Diab Leiomyosarcoma ➢ May resemble leiomyomas grossly ➢ Invasive rather than well circumscribed ➢ Histology necessary to characterize intestinal stromal tumors Fig. 1-76. Leiomyosarcoma in the wall of the cecum in a cat. Courtesy of M. Yaeger. JKP, Vol.2 Primary “non-muscle” tumors of muscle ➢ Tumors that arise from supporting mesenchymal tissues of muscle • Fibrosarcoma • Undifferentiated sarcoma • Giant cell sarcoma • Hemangiosarcoma (dog and horse) • Nerve sheath neoplasm • Granular cell tumor (tongue of dogs and cats) ➢ Lymphomas What to focus on…. ➢ Causes of skeletal muscle necrosis ➢ Diseases that cause muscle necrosis ➢ Major mechanisms of muscle necrosis (is it ischemic, toxic, other?) ➢ Causes of muscle inflammation ➢ Cause and mechanisms of disease of diseases that cause muscle inflammation ➢ Terminology of primary skeletal muscle neoplasia ➢ Skeletal or smooth muscle neoplasm that are more common in specific animal species and/or organs Image Source: iStock Credit: bembodesign Any questions? [email protected] “Knowledge without practice is useless. Practice without knowledge is dangerous” Confucius Image Source: iStock Credit: Elenathewise