Veterinary Systemic Pathology - Musculoskeletal System PDF

VETERINARY SYSTEMIC PATHOLOGY MUSCULOSKELETAL SYSTEM Mia Nur Farida, DVM, M.Sc. DEPARTMENT OF PATHOLOGY FACULTY OF VETERINARY MEDICINE UNIVERSITAS GADJAH MADA 2024  MUSCULOSKELETAL SYSTEM The s...

VETERINARY SYSTEMIC PATHOLOGY MUSCULOSKELETAL SYSTEM Mia Nur Farida, DVM, M.Sc. DEPARTMENT OF PATHOLOGY FACULTY OF VETERINARY MEDICINE UNIVERSITAS GADJAH MADA 2024  MUSCULOSKELETAL SYSTEM The skeleton (bones, ligaments, tendons, and cartilage) and muscles that are attached to it make up the musculoskeletal system. Musculoskeletal system gives the body its structure and support, lets the body to move around (locomotion), and protects important organs. Injuries and many illnesses can damage bones, muscles and joints. Normal Muscle at a glance Wdkbwlkbc;q Muscle Fiber Typing  PATHOLOGY OF MUSCULAR SYSTEM Portals of Entry Pathways of Spread into the Muscular System Injury to muscle can occur secondary to trauma or infection. Muscle lying superficially can be damaged by penetrating wounds. Muscles located deeply are often injured after bone fracture. Muscles are endowed with an extensive vascular network that can allow entry of blood- borne pathogens, immune complexes, antibodies and toxins, and inflammatory cells. Some muscular disorders are genetically determined. Inherited or acquired dysfunction of motor neurons or nerves causes muscle injury in the form of atrophy. Toxins or an altered endocrine or electrolyte status can affect muscle, and physiologic damage can be caused by exhaustive or overexuberant exercise. Defense Mechanisms and Barrier Systems of Skeletal Muscle Examination of Muscle Gross examination Gross examination includes evaluation of changes in size (atrophied, hypertrophied, or normal), color, and texture. Microscopic examination Histological examination to identify muscular structure changes. Special staining (IHC) to identify myosin ATPase activity, mitochondrial activity (NADH-TR, SAD, etc.) Muscle Necrosis Muscle necrosis refers to the condition where muscle tissue undergoes cell death, either totally or in segments, due to various pathological factors (trauma, ischemia, infectious agents, and myotoxins). Myofiber necrosis (myonecrosis) is histologically characterized by swollen, deeply eosinophilic, homogeneous myofibers that lack cross striations (hyalinization). Affected fibers are often vacuolated and fragmented with pyknotic nuclei. Muscle fiber necrosis histologic features & stages: https://neuromuscular.wustl.edu/pathol/necrosis.htm Are those injured muscle, reversible? Muscle Regeneration Alteration in Myofiber Size Atrophy The term atrophy is used to imply either a reduction in the volume of the muscle as a whole or a reduction in the diameter of a myofiber. The causes of muscle fiber atrophy include physiologic and metabolic processes and denervation. Muscle atrophy is reversible provided the cause is corrected. Alteration in Myofiber Size Hypertrophy Myofibers increase in diameter by the addition of myofilaments. Physiologic hypertrophy is the normal process of myofiber enlargement that occurs with exercise conditioning. Compensatory hypertrophy occurs because of pathologic conditions that: (1) decrease the number of functional myofibers and therefore increase the load on remaining fibers or (2) interfere with normal cellular metabolic or other physiologic processes. Cytoarchitectural Changes Vacuolar change Vacuolar change is a common cytoplasmic alteration. Vacuoles can be an early manifestation of processes leading to necrosis, they can reflect underlying sarcotubular dilation as occurs in many myotonic conditions and they can be caused by abnormal storage of carbohydrate or lipid, or they can reflect underlying myofibrillar abnormalities. Cytoarchitectural Changes Internal nuclei Myonuclei of mature myofibers in domestic animals are normally found peripherally, just beneath the sarcolemma. Nuclei located one nuclear diameter or more from the sarcolemma are known as internal nuclei. In most species, myonuclei return to the normal peripheral location early in regeneration, within days of myotube formation. Rodents are the exception. In rodents, internal nuclei are retained after regeneration, which, in these species, provides a handy marker for identification of fibers that have undergone necrosis and regeneration. Cytoarchitectural Changes Whorled and ring fibers Whorled fibers contain spirals of cytoplasm with Ring fibers (also known as ringbinden) contain a internally located nuclei. Whorled fibers can be peripheral rim of sarcomeres oriented seen in areas of chronic denervation and also in perpendicular to their normal orientation, areas in which myofiber necrosis with incomplete resulting in peripheral radiating striations. They regeneration has occurred. are seen in myotonic dystrophy, other myopathic and in neuropathic conditions. Chronic Myopathic Change Aging The term sarcopenia refers to generalized reduction in muscle mass, strength, and function related to aging, in the absence of underlying disease. Aged animals often exhibit mild to severe muscle atrophy. Old cattle can accumulate lipofuscin within skeletal muscle, which can cause a tan-brown discoloration, but there is no apparent clinical significance to this change. Common Muscle Disorders in Domestic Animals Muscle disorder (myopathy) can be inherited or acquired. Inherited disorders can affect muscle metabolism or myofiber structure. Acquired muscle disease in livestock is often associated with nutritional deficiency or with ingestion of myotoxins, whereas immune-mediated inflammatory conditions most often cause acquired muscle disease in the dog. Other causes of acquired myopathies include ischemia, infectious agents, hormonal or electrolyte abnormalities, and trauma. Common Muscle Disorders in Domestic Animals Degenerative - Ischemia Because of the numerous anastomoses, blockage of capillaries causes less severe ischemia but can result in segmental myofiber necrosis, which is usually multifocal and if the cause is ongoing, polyphasic, with regenerating and necrotic myofibers. However, when larger arteries are blocked, whole areas of muscle, including the satellite cells, are killed, resulting in a monophasic necrosis and healing by fibrosis. Ischemia can also cause peripheral nerve damage and neuropathy, leading to denervation atrophy of intact myofibers. Causes of muscle ischemia Common Muscle Disorders in Domestic Animals Degenerative – Nutritional and Toxic Myopathies Ionophore toxicity Common Muscle Disorders in Domestic Animals Degenerative – Exertional Myopathies and Trauma The ionic and physical events associated with myofiber Exertional rhabdomyolysis contraction can under certain circumstances predispose a myofiber to necrosis. Exercise-induced myonecrosis, which can be massive, can occur because of simple overexertion. The term exertional rhabdomyolysis (also known as exertional myopathy, azoturia, setfast, blackwater, Monday morning disease, and tying up) has long been applied to a syndrome recognized in horses. External trauma to muscle includes crush injury, lacerations and surgical incisions, tearing caused by excessive stretching or exercise, burns, gunshot and arrow wounds, and certain injections. Some of these result in complete or partial rupture of a large muscle. A partial rupture of a muscle results in a tear in the fascial sheath, through which the muscle can herniate during contraction. Common Muscle Disorders in Domestic Animals Inflammatory Myopathies (Myositis, Myositides (plural)) Bacterial Myopathies Viral Myopathies Parasitic Myopathies  Common Muscle Disorders in Domestic Animals Inflammatory Myopathies (Myositis, Myositides (plural)) Clostridial myositis Sarcocystosis Under anaerobic conditions, clostridia proliferate and produce toxins that damage blood vessels, resulting in hemorrhage and edema, and cause necrosis of adjacent muscle fibers. Common Muscle Disorders in Domestic Animals Inflammatory Myopathies (Myositis, Myositides (plural)) Trichinosis PATHOLOGY OF SKELETAL SYSTEM  BONE (at the cellular level) Osteoblasts are cells on any bone surface. They produce bone matrix, initiate bone matrix mineralization, Osteoclasts are and initiate the bone multinucleated cells matrix resorptions by that are derived from osteoclasts hematopoietic stem cells of the monocyte- macrophage series Osteocytes are and are responsible osteoblasts that have for bone resorption. been surrounded by mineralized bone matrix. BONE (at the cellular level) Osteocytes are elliptical, mildly basophilic and contain an oval nucleus with fewer organelles than osteoblasts Active osteoblast are plump, with abundant basophilic cytoplasm that is rich in rough endoplasmic reticulum (RER) and contains prominents Golgi apparatus and numerous mitochondria. Osteoclasts are multinucleated cells with abundant eosinophilic cytoplasm and a specialized brush border along the margin of the cell that is adjacent to the resorbed bone surface. BONE (as a tissue) BONE (as an organ) Individual bones of the skeleton vary in their manner of formation, growth, structure, and function. Flat bones of the skull develop by the process of intramembranous ossification, in which mesenchymal cells differentiate into osteoblasts and produce bone directly, in the absence of a preexisting cartilage model. In contrast, most bones develop from cartilaginous models by the process of endochondral ossification, in which cartilage is invaded by blood vessels, undergoes mineralization, and forms primary (diaphyseal) and secondary (epiphyseal) centers of ossification. Bones forming by endochondral ossification, such as the long bones of the appendicular skeleton and the vertebral bodies, are divided anatomically into epiphyses, metaphyseal growth plates (physes), metaphyses, and diaphyses Bone Development and Vascularization Portals of Entry Pathways of Infection Spread into the Skeletal System Adult animal Young animal Infectious agents enter bone Bloodborne bacterial infection of bone in the directly through the periosteum and perinatal animal may originate from the cortex or through the vasculature. umbilicus (e.g., omphalitis/ omphalophlebitis/ Blood vessels gain access to the omphaloarteritis) or, more commonly, by the marrow cavity of the diaphysis and oral-pharyngeal route. metaphysis through the nutrient foramen. Infection localized typically at the zone of vascular invasion on the metaphyseal side of the growth plate or immediately subjacent to the articular-epiphyseal cartilage complex (AECC). From this nidus, the inflammation can extend into other structures, including the overlying joint cavity for AECC lesions and the epiphysis, periosteum, or joint cavity for physeal lesions. Defense Mechanisms and Barrier Systems of Skeletal System The cells of bone tissue are capable of the same basic cellular responses as most other tissues, including atrophy, hypertrophy, hyperplasia, metaplasia, neoplasia, degeneration, and necrosis. Depending on the stimulus, the response may be localized or generalized but, in general, the magnitude of skeletal response is greater in young growing animals than in adults. Bone-Specific Reactions to Injury Common Skeletal Disorders in Domestic Animals Abnormalities of Growth and Development Disorders of Bone Resorption Osteopetrosis Osteopetrosis is a heterogeneous group of conditions that is characterized by an increase in bone density due to a failure in bone resorption by osteoclasts. Although trabecular bone accumulates in epiphyses, metaphyses, and diaphyses, there is a reduction in cortical bone quantity and quality due to a failure of bone modeling at this site. In severe forms of osteopetrosis, the insufficient bone marrow cavity is unable to support hematopoiesis, resulting in thrombocytopenia, anemia, and susceptibility to infections. Common Skeletal Disorders in Domestic Animals Abnormalities of Growth and Development Disorders of Bone Formation Osteogenesis Imperfecta (OI) Osteogenesis imperfecta is characterized by excessive bone fragility, which in severe cases may result in multiple intrauterine fractures due to osteopenia, marked skeletal deformity, and either stillbirth or perinatal death. Milder forms may be inapparent at birth but lead to an increased incidence of postnatal fractures and bowing of the limbs. Many cases of OI are associated with mutations in COL1A1 or COL1A2, which are genes that encode the pro-α1 or pro-α2 chains of type 1 procollagen. Common Skeletal Disorders in Domestic Animals Abnormalities of Growth and Development Disorders of Bone Modeling Craniomandibular Osteopathy Craniomandibular osteopathy, also known as lion jaw, typically occurs as an autosomal recessive condition in West Highland white terriers. Lesions are bilaterally symmetric, resulting in diffuse, irregular thickening of the mandible(s), occipital and temporal bones, and, occasionally, other bones of the skull. The tympanic bullae are often severely affected. The disease often becomes apparent at 4 to 7 months of age and can regress. For affected dogs, mastication is painful and difficult, and the muscles of the skull become atrophic from disuse. Common Skeletal Disorders in Domestic Animals Abnormalities of Growth and Development Disorders of Endochondral Ossification Chondrodysplasias Chondrodysplasias are hereditary disorders of bone growth that occur as a result of primary lesions in growth cartilage. Chondrodysplasias can result in disproportionate dwarfism. Affected animals usually are short-legged with normal-sized heads because the bones of the calvarium (but not the maxilla and mandible) arise from intramembranous, rather than by endochondral, ossification. Common Skeletal Disorders in Domestic Animals Metabolic Bone Disease Common Skeletal Disorders in Domestic Animals Metabolic Bone Disease Osteoporosis Osteoporosis is a disease in which bone fractures occur secondary to a reduction in bone density or mass. When there is reduced bone mass but no clinical disease (fractures), the term osteopenia is more appropriate; however, once fractures occur, the disease is called osteoporosis. Osteoporosis affects both cortical and trabecular bone. The loss of trabecular bone occurs earlier because of its higher surface area, which creates a greater opportunity for osteoclastic bone resorption Common Skeletal Disorders in Domestic Animals Metabolic Bone Disease Rickets and Osteomalacia Failure of mineralization with subsequent bone deformities and fractures is called rickets in the growing skeleton and osteomalacia (soft bone) in the adult. Rickets is a disease of bone and epiphyseal (growth) cartilage in immature animals, whereas osteomalacia is a disease of adults in which the lesions are confined to bone. Affected animals have bone pain, pathologic fractures, and deformities such as kyphosis and scoliosis. The most common causes of rickets and osteomalacia are deficiencies of vitamin D or phosphorus. Common Skeletal Disorders in Domestic Animals Bone Necrosis