Examen 1 - Bone, Muscle, Optho PDF

Bone Pathology Anatomy & Response to injury -​ Compact = outer layers -​ Cortical bone -​ Osteon (primary unit of cortical bone) → lamellar bone -​ Cancellous = inside cavity -​ Spongy bone -​ Trabeculae (irregular meshwork) → c...

Bone Pathology Anatomy & Response to injury -​ Compact = outer layers -​ Cortical bone -​ Osteon (primary unit of cortical bone) → lamellar bone -​ Cancellous = inside cavity -​ Spongy bone -​ Trabeculae (irregular meshwork) → contain hematopoietic tissue and/or adipose tissue -​ Woven bone (eventually progresses into lamellar bone) -​ Immature animals → physiologic in growing -​ Abnormal in adults → pathologic -​ Bone microanatomy -​ Osteoblasts → create new bone -​ make osteoid (non-mineralized matrix of the bone) -​ Osteoclasts → break bone down -​ Osteocytes (living part of mature bone) → results when osteoblasts get trapped within lacunae creating the living part, resting to stressors to remodel bone as needed -​ REMODEL BONE BUT DON’T CREATE NEW -​ Periosteum (fibrous sheet that covers bone) has 2 parts -​ Inner osteogenic layer which produces bone by: -​ Intramembranous ossification (physiologically) -​ Non-specific bone response to injury (pathologically) -​ Produces woven bone -​ Process that replace tissue with bone Intramembranous ossification Endochondral ossification -​ Made bone directly from -​ Cartilage precursor osteoblasts -​ Cartilage is replaced by -​ Lacks cartilage precursor bone -​ Flat bones of skull -​ Length of long bone + -​ Width of long bone vertebrae -​ Vascular supply -​ Cartilage has capillary loop during development -​ This is why young animals are more predispone to suffer from joint infections/sepsis etc -​ Avascular in adults -​ Supplied by nutrient vessels, metaphyseal, periosteal and epiphyseal blood supplies  -​ Disruption can lead to infarction which can lead to sequestrum formation (piece of dead bone that has separated from healthy bone during necrosis) -​ Infarction Sequestrum -​ Loss of blood -​ Infarcted bone supply persist and is -​ Wedge shape, surrounded by pallor, necrotic viable bone -​ Purulent exudate -​ Neutrophilic inflammation → pathologic fracture -​ Epiphysis = septic arthritis -​ Bone Injury: Fractures -​ Traumatic Pathologic -​ Healthy bone -​ Weakened/diseased bone -​ Sharp outlines -​ Rounded edges -​ External force/trauma (neoplasia,osteomyelitis) -​ Sharp (osteoporosis) -​ -​ -​ Articular fracture = joints is involved (will cause joint dz eventually) -​ Avulsion type fractures = tendon/ligament pulls fragment away from bone -​ -​ Occurs in skeletally immature animals -​ Can result in angular limb deformities -​ V = CRUSHED FRACTURE -​ Bone Healing -​ Primary -​ Contact healing via osteon system -​ Cutting cones formed by osteoclasts -​ Goal of orthopedic sx -​ Secondary -​ Non-rigid fixation -​ 4 phases 1.​ Hematoma → granulation tissue (2w) 2.​ Granulation tissue → fibrocartilage → soft callus (2-6w) 3.​ Recruitment of osteoblast and osteoclasts → hard callus (6-8w) new via endochondral ossification 4.​ Bone remodeling (months-years) -​ Factors -​ Stability of fracture ends (instability can result in pseudoarthrosis = false joint) -​ Bone placement (close proximity is better) -​ Necrotic bone fragments (sequestra) → large fragments usually don’t resolve and delay healing -​ Infected bone fragments (infection delays healing) -​ Non neoplastic bone proliferation Name Description Exostosis Bone/cartilage growth on outer surface of bone Enostosis Bone/cartilage growth on inner surface -​ Ex. new woven bone secondary to inflammation Osteophyte Growth in the joint capsular margin -​ Sign of instability -​ Patients w OA or CCL tear -​ Enthesophyte Growth at tendon/ligament insertion -​ Osteochondroma Defect in skeletal (cartilage) development -​ Inherited (EXT1 or ETR2) horses and dogs -​ Young animals -​ Multiple exostosis in cartilage  -​ -​ Spinal cord compression, neuro problems -​ -​ Can transform to osteosarcoma/chondrosarcoma Hypertrophic Periosteal woven bone formation along diaphysis of long Osteopathy bone (periosteal bone proliferation) -​ Intrathoracic dz?? -​ Altered vasovagal input w intrathoracic dz -​ Ex. pulmonary carcinoma -​ Non-inherited disorder Metabolic and growth disorders -​ Bone growth disorders -​ Primary physis and metaphyseal (injury/development) -​ Physeal growth -​ Physis into metaphysis → primary trabeculae where cartilage beams are removed by osteoclasts → vessels in beams which allows osteoblasts to enter → osteoblasts lay down osteons → primary tuberculae remodeled into secondary ‘  Name Pathogenesis Cause Description Growth Osteoclast Canine distemper (CDV), Retained primary trabeculae retardation lattice dysfunction/destruction Bovine Viral Diarrhea create a dense band of bone -​ Young animals (BVDV) → infect osteoclasts under growth plate in development Lead toxicity → injures osteoclasts Growth arrest Disruption of Severe malnutrition, Linear region of more porous lines endochondral debilitating dz bone, in x-rays = growth ossification within the arrest line metaphysis -​ Body stops laying down bone Growth plate Premature close of the Hypervitaminosis A, closure plate → shorten bone Manganese deficiency Asymmetric Asymmetric closure of Injury to physis (trauma, Angular limb deformities closure of growth growth plates exercise, nutritional (ALD), Carpal vaLgus = lateral plates imbalance) or crushed deviation (adentro hacia cubital bones in afuera), Carpal vaRus = medial carpus/tarsus deviation (afuera hacia adentro) Carpal valgus Osteogenesis Disorder of bone Mutation → type 1 collagen Osteopenia (decreased Imperfecta formation -​ SERPHINH1 gene in bone mass), blue sclera, -​ Calves, lambs, the Dachshund loose tendons, abnormal kittens, puppies - dentin mild or severe Osteopetrosis Disorder of bone Genetic, BVDV, FeLV, avian Osteosclerosis (increased resorption leukosis virus bone mass), Can also affect Dysfunction in -​ Affects cattle (Angus), dog, bones of skull leading to osteoclast neurologic signs from cat, sheep horses,rats, production/function → compression on mice impaired resorption of brain/nerves, Fractures -​ Autosomal recessive trabeculae → diffuse reported due to impaired disorder in Angus cattle osteosclerosis cortical bone, Anemia due to -​ Peruvian Paso breed of compression of hematopoietic horses tissue (Genetico/Infeccioso) Osteosclerosis Secondary to an increased mechanical Dog with IVDD → loss increased mechanical use/force intervertebral disc space → use/force increased mechanical force *no underlying → osteosclerosis osteoclast dysfunction* Congenital Periosteal bone Autosomal recessive Enlarged forelimb Cortical proliferation Hyperostosis (pigs) Craniomandibular Peripheral bone Autosomal recessive Thickening of mandibles, osteopathy (west proliferation Young dogs (4-7 months) - occipital and temporal bones highland white can regress terriers) -​ Painful mastication → difficulty eating, mm atrophy Chondrodysplasia Inherited defects in FGF4 mutation in dogs → -​ FGF = fibroblast growth endochondral disproportionate dwarfism factor ossification (epiphyseal -​ dachshund , basset -​ FGFR = FGF receptor and metaphyseal) hound Spider lamb - vertebrae FGFR3 mutation in sheep → Spider lamb syndrome (excessive growth cartilage and multiple ossification centers) Osteochondrosis Acquired defect in Multifactorial -​ Osteochondrosis endochondral -​ Large size, growth latens ossification rate, diet (copper), Impaired vascular genetics, etc supply to physis → retention of necrotic growth necrosis → retained cartilage: due to failure to necrotic cartilage mineralize cartilage, without mineralization, it cannot be removed, leads to failure to replace with bone -​ Osteochondrosis manifesta -​ OsteochondrOSIS dissecans (OCD) Cervical Vertebral 2 forms: Congenital disorder in Dymic will show more severe Myelopathy -​ Static stenosis = horses and dogs clinical signs narrowed AKA “Wobblers” Dorsal vertebral body can vertebral canal impinge ventral spinal cord Caudal; C5-C6 in either form transient and C6-C7 ischemia and, over time, Horses aged 1-4 yr spinal cord degeneration -​ Dynamic = instability OCD of articular facets Cranial; C3-4 and C4-5 Horses 6-15 months old Epiphysiolysis Impaired endochondral Underlying OCD or physeal Epiphysis in acetabulum but ossification → weak dysplasia rest of the bone is out epiphysis → separation -​ Affects of epiphysis from pigs,dogs,cats metaphysis  -​ Metabolic bone disorders Name Pathogenesis Cause Description Osteopenia Reduced bone Normal bone → osteoporosis mass/density Abnormal bone → osteogenesis imperfecta, osteomalacia, fibrous osteodystrophy -​ note reduced metaphyseal trabeculae with porous cortical bone on right and thin cortical bone on left Osteoporosis Reduced bone quantity -​ Age, with normal bone -​ Nutritionals - starvations, quality calcium deficiency 1.​ Vit c deficiency Bone resorption >> 2.​ Copper deficiency formation 3.​ Phosphorus deficiency 4.​ Hypervitaminosis A -​ disuse/immobilization in weight bearing bones -​ endocrinopathies 1.​ Hyperadrenocorti cism 2.​ Hyperthyroidism 3.​ Sex hormone deficiency Osteomalacia Reduced bone quantity -​ Vit D deficiency with abnormal bone -​ Phosphorous deficiency quality in adult, -​ CKD skeletally mature -​ Chronic fluorosis animals Defective mineralization → softer bones → fractures Rickets Reduced bone quantity -​ Vit D deficiency >> Soft bones, fractures, with abnormal bone phosphorus deficiency thickened physis quality in young, skeletally immature animals Cartilage not mineralized → not resorbed by osteoclasts → thickened physis Fibrous Reduced bone quantity Chronic elevated PTH(rp) osteodystrophy with abnormal quality -​ Primary Elevated PTH → hyperparathyroidism osteoclast resorption of (functional tumor bone → bone replaced /hyperplasia) by fibro-osseous tissue -​ Secondary → soft bones hyperparathyroidism (Renal v nutritional) -​ Psudohyperparathyroid ms Fibrous osteodystrophy -​ Primary hyperPTH -​ Functional tumor/hyperplasia → ↑ PTH → -​ ↑ osteoclastic activity + ↑ GI Ca absorption +↑ renal Ca resorption → hypercalcemia with loss of neg feedback -​ Bone is resorbed faster than it can be replaced -​ Bone attempts to create stability with fibrous Tissue -​ Low/N Phos from PTH inhibition of renal resorption -​ -​ Secondary - Renal -​ hypocalcemia/hyperphosphatemia induces parathyroid hyperplasia → ↑ PTH -​ Combined with low renal excretion PTH will increase even more -​ Rubber jaw → painful, loose teeth  -​ -​ Secondary - nutritional -​ Poor diet → decreases Ca and increases Phosphorus → stimulates parathyroid hyperplasia → increases PTH -​ Jaw bones are most affected “big head” -​ Can affect exotics -​ LA = grain overload -​ Dogs = all meat diet -​ -​ Paraneoplastic -​ PTHrp production from tumor -​ Lymphoma > AGASACA >>> SCC, thymoma, others -​ Low/N endogenous PTH from parathyroid gland atrophy -​ Bone changes are not common -​ Hypercalcemia and low to normal phosphorus Inflammatory & Infectious Bone/Joint Disease -​ Terminology -​ Osteomyelitis → inflammation of the medullary cavity -​ Inflammation does always mean infection -​ For infectious causes of bone inflammation, there are several routes of entry: -​ Hematogenous -​ penetrating injury and fractures -​ direct extension (eg. tooth root abscess, joint infection, soft tissue infection) -​ Iatrogenic (eg. implants) -​ Osteomyelitis can vary in appearance  -​ Moth earth pattern (not sharp edges/irregular, not normal bone) to proliferative lesions -​ Osteolysis → thinning, scalloping and fragmentation of medullary trabecular bone = radiolucent on radiographs -​ Necrosis – areas of lytic medullary necrosis (asterix) due to inflammation induced tissue damage (also radiolucent) -​ Bone proliferation (white arrow) – anastomosing lakes of woven bone in attempts at repair = radiopaque on radiographs -​ Hematogenous osteomyelitis → a bone infection that occurs when an infection in another part of the body spreads to the bones through the bloodstream -​ Predispositions for physes -​ Hairpin loops -​ Turbulent blood flow -​ Leaky fenestrated endothelium -​ No collateral vessels -​ Thrombosis lead to necrosis, which promotes infection -​ Poor phagocytosis -​ Lesions: -​ Metaphyseal physitis → can lead to osteomyelitis -​ Epiphyseal physitis → can lead to epiphysitis -​ Can erode ito synovial space and lead to arthritis -​ Infectious osteomyelitis -​ Staph is the most common in dogs (hematogenous)  -​ Lumpy Jaw in cattle by Actinomyces bovis -​ Gram positive, facultative anaerobe (summit anaerobic culture) -​ Both osteonecrosis and proliferative bone -​ Pathogenesis: penetrating injury in oral mucosa → local extension (periostitis) → osteomyelitis -​ R. equi -​ Often presents as pyogranulomatous bronchopneumonia in 1-6 months -​ Gram positive -​ Lesions: pyogranulomatous bronchopneumonia and colitis -​ Pathogenesis: sepsis → hematogenous spread to physis → physitis → osteomyelitis +/- epiphysitis +/- arthritis -​ Foals usually breath the pathogen -​ Sepsis can lead to bone infection -​ Non infectious osteomyelitis -​ Metaphyseal osteopathy -​ Large breed dogs, 3-6 months -​ Cause: unknown -​ Suspected inappropriate immune-response -​ Lesions: necrosis and neutrophilic inflammation with microfractures at metaphysis -​ Double physis on rads -​ Affects long bones (above carpus and hocks) -​ Lameness, fever, swollen and painful metaphyses -​ Panosteitis -​ Large breed dogs, 5-12m -​ Cause unknown -​ Genetic? Diet? -​ German shepherds are predisposed -​ Lesions: medullary necrosis +/- fibrosis with endosteal +/- periosteal bone proliferation along the diaphysis -​ Usually long bones of forelimb (painful bones in palpation) -​ Eosinophilia (inconsistent feature) -​  -​ Necrosis of the femoral head -​ Small toy breed, 5-8m -​ Cause: genetics (inherited) -​ Lesions: disrupted blood supply to femoral head → osteonecrosis → replacement fibrosis – collapse of articular cartilage → aseptic arthritis -​ Often treated with FHO Joint Anatomy and terminology -​ articular surfaces = hyaline cartilage (70-80% water) -​ Nutrients from synovial fluid, no nerves or vessels -​ Joints are composed of: -​ Articular surfaces of bones -​ Joint capsule = synovial membrane -​ Synovial fluid -​ Articular cartilage responses to injury -​ Causes: -​ Joint dysplasia -​ Joint laxity -​ Prior orthopedic injury -​ Age-related degeneration\ -​ Goes from: -​ Normal -​ Fibrillation → frayed surface of eroded articular cartilage; grossly feels like roughening -​ Erosion → partial loss of articular cartilage -​ Ulcer → loss of articular cartilage to expose subchondral bone , very painful, lameness (heal by fibrocartilage repair) -​ Eburnation → sclerosis of exposed subchondral bone, red looking -​ Synovial membrane responses to injury -​ Causes: -​ joint instability (dysplasia, joint/tendon/ligament laxity) -​ Prior orthopedic injury (CCL) -​ Age-related degeneration (DJD) -​ Will see osteophytes (response to joint instability) and fibrosis (of joint capsule) -​ Response to injury: -​ Synovial villous hyperplasia -​ Pannus → fibrovascular membrane growth over articular surfaces (chronic infectious fibrinous synovitis or rheumatoid arthritis) -​ Decreased viscosity of synovial fluid -​ Supporting bone response to injury -​ Deformation (ex. flat femoral head that can lead to hip dysplasia) -​ Osteosclerosis → due to altered mechanical forces on subchondral bone (ex. IDD) -​ These happen after joint injury  -​ Infectious Arthritis -​ Route of entry -​ Hematogenous -​ Extension of osteomyelitis -​ Extension of soft tissue -​ Iatrogenic (sx in SA, injections in LA) -​ Direct penetrating injury Name Pathogenesis Cuase Description Bacterial arthritis Primary is E.coli → neonates Joint swelling, heat, hematogenous Staph → dogs (sx pian, lameness, Acute → implats) inflammatory serofibrinous arthritis, Histophilus somni → leukogram fibrinosuppurative cattle, brain and heart Chronic → cartilage B. burgdorferi → erosion, ulcers, Lyme hyperplasia, pannus, Pigs → see chart osteophytes below Diskospondylitis inflammation of the Causes of bacteria Loss of IVD, collapse vertebral disc and osteomyelitis of joint space, adjacent vertebrae Dogs → B. canis osteosclerosis of vertebral end plates +/- spondylosis *can cause abortion/stillbirths Caprine Arthritis Retrovirus (CAEV) Proliferative fibrinous Encephalitis Virus arthritis Progress to fibrosis overtime Encephalitis, mastitis, pneumonia Feline “Limping Viral antigens present Feline calicivirus Syndrome” Viral in synovial fluid, but -​ Natural Arthritis viral RNA not infection of vaccine-induc identified – supports ed an immune-complex pathogenesis  Don't Use front legs bc of pain -​ Fibrinous arthritis w synovial hyperplasia Poultry Viral Arthritis Lymphocytic Reovirus Lameness, unilateral tenosynovitis *vx available (no tx, or bilateral swollen need to cull) hock joints or shanks Immune-mediated Most commin -​ Breed polyarthirits (IMPA) polyartoicular dz in associated dogs -​ Systemic Immune-complex lupus depoition in synovium eryhtematous -​ Reactive -​ idiopathic Degenerative joint dz Physical damage to Secondary to poor (aka OA) articular cartilage (not comformation, due trauma or age immune-mediated damage) Aricular Gout Reptiles, birds Renal dz, Modular and/or *common is species dehydration, high plaques of white to that produce uric acid protein diet tan crystalline as primary mayerial (in tenons, nitrogenous waste fascial planes) -​ Bacterial Arthritis in pigs -​ E. Rhusiopathiae is the causative agent of “diamond-skin disease”  -​ Non infefctious Arthritis -​ Typically a Dx of exclusion! Rule out infectious causes first -​ Rheumatoid arhritis → inmune mediated process but differs form mediated polyrthritis in that in can xause articular catilage damage -​ IMPA is more common, RA is rare in dogs ​ -​ IMPA breeds: Akita, boxer, weimaraner, Bernese mountain dog, German shorthaired pointer, spaniel, and beagle breeds -​ Please note that these 4 categories are not the same as the 4 types of IMPA: -​ Type 1: idiopathic – no associated disease -​ Type 2: reactive – associated with inflammation/infection at other site -​ Type 3: hepatobiliary/gastrointestinal related -​ ,Type 4: neoplasia-related -​ Idiopathic is a dx of exclusion (most common in dogs) → neutrophils in synovial fluid Muscle Pathology ​ Anatomy, response to injury and neuromuscular junction disorders -​ Skeletal mm anatomy -​ Muscle attached to bone via tendons (bands of thick collagen) -​ Surrounded by thin coat of collagen (epimysium) and internally divided into smaller bellies called fascicle separated by perimysium -​ Only segments of myofiber can regenerate from satellite cells after an injury -​ Skeletal mm goes through hypertrophy (enlargement of cells that can’t divide rapidly) when physiologic demand increases -​ The neuromuscular junction -​ Neural action initiated → stimulates Ach from synaptic vessels → Ach binds to receptor on muscle → muscle contracts → ach-esterase stops signaling → choline recycled to nerve -​ Neuromuscular junction disorders -​ No gross or histologic lesion -​ Serum CK and AST initially normal -​ Causes: -​ Coral snake, spider envenomation -​ Drugs -​ Myasthenia gravis  -​ Botulism -​ Tick paralysis Name Pathogenesis Cause Description Myasthenia Gravis Acquired → Ab bind Acquired (auto Progressive to Ach receptor immune) → idiopathic weakness and May be Congenital → exercise intolerance paraneoplastic reduced # of Ach (if megaesophagus (Thymoma) → aspiration Reduced # of Ach pneumonia) receptor Botulism Neurotoxin cleaves Clostridium botulinum IRREVERSIBLE dz SNARE proteins → Activation of spore in Flaccid paralysis prevents fusion alkaline and Limber neck in birds of synaptic vesicle to anaerobic conditions Dysphagia, bloat in nerve cell membrane Routes: ruminants → Ach is not -​ GI released colonization -​ Ingest preformed toxin -​ Wound contamination Tick borne Paralysis Neurotoxin in tick Dermacentor and REVERSIBLE dz saliva → blocks Ach Ixodes sp. Hindlimb paralysis release → flaccid recumbency paralysis -​ Botulism: horses are most sensitive → GI in foals, Ingestion in adults usually bc of dead carcass (rodent) in hay/feed, wound → adults -​ Tick borne: remove tick and patients typically improve within 24-48 hours but can take up to 5-7 days -​ Rx to muscle injury 1.​ Necrosis 2.​ Regeneration 3.​ Atrophy 4.​ Hypertrophy 5.​ Fibrosis -​ Muscle necrosis = Zenker’s necrosis -​ Type of coagulative necrosis that only happen in skeletal muscle -​ Swelling and pallor -​ +/- mineralization bc of the release of Ca from sarcoplasmic reticulum (white gritty streaks in muscle) -​ Causes: ischemia, exertion, toxin, etc -​ Selective Non-selective Myofiber necrosis only Necrosis of ALL cells Regenerate via satellite cells Heals by fibrosis Causes can be: Causes can be: -​ Nutritional -​ Thermal -​ Toxic -​ Ischemia -​ Metabolic -​ Inflammation -​ Exertional -​ Clin path will see: -​ Serum enzyme elevations -​ CK -​ ALT -​ AST  -​ Hyperkalemia -​ Myoglobinuria -​ Small muscle changes don't cause detectable changes -​ - PTType Calcium Phosphoru Fff -​ Important to know the difference to interpret findings in reports -​ Mono -​ -​ Poly -​ -​ Causes of muscle atrophy -​ Denervation -​ Disuse → several lameness, arthritis, casted limb -​ Metabolic -​ Congenital myopathy  -​ Myositis -​ Symmetrical muscle atrophy -​ Endocrinopathies -​ malnutrition/cachexia -​ Muscle hypertrophy -​ Increased demand -​ Genetic - myostatin -​ Cats -​ Cattle (brahman breed) -​ Muscle fibrosis -​ Healing after nonselective necrosis Toxic, Nutritional & Exertional Myopathies -​ Direct muscle injury -​ Injection site injuries -​ Regional necrosis +/- xenobiotic deposits -​ Secondary infection/abscess -​ Clostridium spp. -​ C. septicum → malignant edema -​ Ischemic Muscle Injury 1.​ Disrupted blood flow (trauma, vasculitis) -​ Thromboembolism- induced muscle necrosis -​ Neoplastic emboli -​ DIC, sepsis -​ Pallor and striated appearance in picture to the left 2.​ External pressure (downer cows, dystocia, cats/bandages) -​ Terminal in 50% cases -​ Prolonged anesthesia, milk fever, pregnancy toxemia, calving or traumatic injuries -​ Muscle looks pale and striated but looks “drier” 3.​ Internal pressure (compartment syndrome) -​ Prolonged recumbency/trauma prolonged anesthesia -​ Excessive exertion -​ Intramuscular mass (uncommon) -​ Deep pectoral myopathy (in birds → biliverdin accumulations → flapping wings for a long time) -​ Nutritional myopathies 1.​ Vit E/Selenium deficiency -​ Pigs → neonates -​ Ruminants and horses -​ In ruminants mimics rabies, botulism (stiff gait, arched back, painful)  -​ Low antioxidant activity (both Vit E and Se are antioxidants) -​ Dx: blood or liver levels, AST/CK elevations -​ Gross: pallor, necrosis (polyphasic segmental), +/- mineralization 2.​ Se deficiency in horses -​ Foals >> adults -​ Low Se in hay (late winter to spring), or Mare is deficient -​ Weakness → postural mm -​ Weak sucking/dysphagia -​ Northwest soils are deficient all year round 3.​ Equine Motor Neuron Dz -​ (neurogenic) atrophy, +/- pallor, +/- yellow hue -​ Causes: Chronic Vit E deficiency -​ Oxidative injury to muscle → injured mitochondria → necrosis -​ Motor neuron degeneration → motor neuropathy (EMND) -​ Clinical signs: weakness, recumbency, trembling, lowered head 4.​ Vit E/Se deficiency in pigs -​ Young rapidly growing pigs (wks to several months) -​ 3 syndromes 1.​ White muscle disease (longissimus dorsi, hind limbs) 2.​ Mulberry heart dz (nutritional micro(vascular necrosis → thrombosis → hemorrhage a.​ Can cause sudden death b.​ Vit E responsive 3.​ Hepatosis dietetica a.​ Se responsive b.​ Can cause sudden death ​ ​ -​ Toxic myopathies : Plants 1.​ Primarily LA -​ Lesions to skeletal mm +/- heart necrosis -​ cause : Senna (cassia) occidentalis and Gossypol in cottonseed -​ Looks like white muscle dz 2.​ Seasonal Pasture Myopathy in horses -​ Skeletal mm necrosis + myoglobinuria -​ Cause: Box elder tree (Acer negundo) + Sycamore maple (Acer pseudoplatanus) -​ Seeds contain hypoglycin A → toxic metabolite MCPA → disrupts FA and AA metabolism → hypoglycemia → necrosis  -​ Stiffness, difficulty walking or standing, voiding dark urine, rapid breathing -​ Confused with colic and/or laminitis -​ Fatal 3.​ Ionophores -​ Lesions to skeletal mm +/- heart necrosis -​ causes : monensin > lasalocid -​ Horses are more predispose since have a lower LD50 toxicity index -​ DON’T MIX FEEDS -​ Monensin (growth promoter) is found in cattle and poultry -​ Exertional myopathy -​ Skeletal mm necrosis, myoglobinuria, +/- acute tubular injury bc of pigment -​ Bc of exertion :) horses and working dogs -​ Does not affect the heart -​ Genetic myopathies Name Pathogenesis Cause Description Dx Cx Equine Gain of function glycogen Symmetrical Biopsy + Rhaddomyolisis w Polysaccharide GLYS 1 synthesis 1 muscle atrophy genetic testing mild exercise, Storage Myopathy mutation → mutation Rhabdomyolysis shivers, Type 1 excessive *QH, stock cramping,lamene glycogen (reduce horses, draft ss, stiff gait production → starch/sugar breeds glycogen intake/increase inclusions in fat/exercise muscle Myofibrillary Unknown Variable genetic Desmin Look for Exercise Myopathy mutations aggregates and histologic intolerance, Late onset myofiber disarray diagnosis reluctant to move (around 11 forward under years of age) Muscle atrophy saddle, lameness mild w no ortho cause Glycogen GBE1 mutation Loss of function PAS+ inclusions in Genetic Abortion, stillbirth, Branching Enzyme → unable to GBE1 mutation, skeletal muscle testing??​ weak foals, 1 Deficiency release glucose autosomal heart and liver contracted of glycogen → recessive *QH and tendons, hypoglycemia american paint rhabdomyolysis, horse cardiac failure, seizures, death Hyperkalemic SCN4A Muscle Na+ Muscle *QH Myotonia Periodic Paralysis mutation → Na channel SCN4A hypertrophy (impaired muscle (HYPP) in, K out → mutation, High potassium relaxation) hyperkalemia → Autosomal diets, fasting, dominant anesthesia and  stress increase frequency of episodes Malignant RR mutation → Ryanodine Genetic testing Muscle pallor and Hyperthermia excessive Ca receptor swelling release → mutations, AD (rhabdomyolysis) excessive profuse contractions, sweating, muscle hyperthermia stiffness, elevated body temperature X-linked muscular Dystrophin Dystrophin Linear pallor DNA testing, Stiff stilted gait, Dystrophy mutation → mutation (necrosis), fibrosis biopsy, IHC exercise (Duchenne’s type) absent & fatty change → staining for intolerance, starting dystrophin → atrophy grossly dystrophin, 8-12 wks repeat necrosis Megaesophagus clinical signs Weakness and and muscle atrophy regeneration Joint contraction splaying of limbs typical CK and AST elevated -​ EPSSM Type 2 is similar, but the genetic mutation is unknown; has familial basis; similar breeds + warmbloods - Immune-mediated Myopathies Name Pathogenesis Cause Description Polymyositis Self-reactive Idiopathic Symmetrical lesions cytotoxic T cells → Systemic lupus Temporalis and muscle targeting → erythematosus masseter mm muscle necrosis Paraneoplastic (mostly) (thymoma, Esophageal mm dogs>>> cats lymphoma) (muscle necrosis - megaesophagus) Masticatory Myositis Self reactive B cell Idiopathic Bilateral muscle produce Ab towards swelling (acute) → type 2M myosin atrophy (chronic) isoform in type 2 myofiber → muscle Temporalis and necrosis masseter muscle ONLY!! Extraocular Muscle Self reactive cytotoxic Idiopathic Swollen extraocular Myositis T cells towards muscles → extraocular muscles exophthalmos (eyes → necrosis bulge) -​ Polymyositis -​ Dx, via biopsy -​ Tx of underlying dz or if idiopathic immunosuppressive therapy -​ Masticatory myositis -​ Dx: serology to detect anti-type 2M myosin Ab -​ Tx immunosuppression -​ Bacterial myopathies Name Pathogenesis Cause Description Tetanus Bacterial toxin Clostridium tetani Neurologic dz tetanospasmin, In dogs sustains blocks inhibitory spasms in facial neurons in spinal muscle cord → excessive motor neuron excitation – extensor rigi spastic paralysis Malignant Edema Penetrating injury Clostridium Muscular swelling, → local necrosis septicum > other necrosis, anaerobic hemorrhage, environment → edema and clostridial growth → emphysema bacterial toxin released → muscle *horse necrosis +/- toxemia Black leg Ingested bacterial Clostridium Muscle necrosis, spores → pass chauvoei > others hemorrhage, from GI to blood → edema +/- trauma to muscle emphysema → anaerobic environment→ *cattle, esp young spores activate → toxins released → muscle necrosis Pigeon Fever In soil → Corynebacterium Intramuscular penetrating injury, pseudotuberculosis abscess +/- fly infect wounds → lymphangitis abscess formation *pectoral muscles Tx: draining +antibiotics, no vx Wooden Tongue Commensal in oral Actinobacillus (pyo)granulomatou cavity→ penetrating lignieresii s myositis/glossitis injury from rough +/- fibrosis feed → bacteria (commensal of the infect deeper upper GI tract, tissues → (Pyo) gram neg bacilli) granulomatous myositis/glossitis  -​ Parasitic Myopathies -​ No gross lesions -​ Histo: pyogranulomatous +/-eosinophilic myositis -​ Causes : apicomplexan protozoa -​ Ophthalmic Pathology: Adnexa and cornea -​ Eyelids and Ocular Surface -​ Third eyelid (nictitating membrane) -​ Meibomian glands opening in a dogs (is a sx landmark) -​ Eyelid anatomy 1.​ Skin 2.​ Orbicularis oculi m. 3.​ Meibomian glands 4.​ Palpebral conjunctiva -​ Congenital diseases of the eyelids and ocular surface -​ Dermoid or choristoma -​ Normal tissue located in an abnormal place -​ Appear as hair or skin tissue that attached to the conjunctiva or the cornea -​ Causes irritation to the cornea due to hairs rubbing up against the corneal surface -​ Blepharitis = inflammation of the eyelids -​ Bacterial infection: Staph spp -​ Allergic dz: Atopy -​ Parasitic: Demodex -​ Immune mediated: puppy strangles, pemphigus -​ Meibomian gland disease -​ Meibomitis -​ Chalazion: chronic inflamed gland with substantial swelling -​ Meibomian gland adenomas: most common eyelid neoplasm in dogs -​ Eyelid neoplasia (dog) -​ Meibomian gland adenoma -​ Papillomas -​ Melanomas -​ SCC = most common eyelid neoplasia in CATS! Squamous Cell Carcinoma -​ Conjuntiva → goblet cells produces mucus (mucin) portion of tears -​ Conjunctivitis → Viral = feline herpes → most common in cats  -​ Chemosis = clinical findings -​ Conjunctivitis = diagnosis -​ Eyelid function -​ Protection -​ Spread tear film -​ Prevent evaporation -​ Produce portion of tear film -​ Tear drainage -​ Eyelid dz -​ Entropion → rolling in of eyelid (usually lower eyelid) -​ Tear film -​ 3 layers of tear film 1.​ Lipid layer a.​ Anterior layer b.​ Meibomian glands 2.​ Aqueous layer a.​ Middle layer b.​ Lacrimal and nictitating glands 3.​ Mucin layer a.​ Posterior layer b.​ Goblet cells -​ Dry eye disease -​ Keratoconjunctivitis sicca (KCS) -​ Ocular mucoid discharge -​ Conjunctivitis (chemosis/hyperemia) -​ Keratitis -​ Corneal pigmentation -​ Histo = corneal epithelial hyperplasia, Pigmentation, corneal vascularization, Corneal surface inflammatory infiltrate Outer, fibrous layer -​ Cornea → transparent surface -​ Sclera → white part -​ Limbus → junction in between Function -​ Protection -​ Transmission -​ Refraction  -​ Cornea 1.​ Epithelium -​ Squamous cells - anterior layer -​ cuboidal/wing cells - middle layer -​ Basal cells - posterior layer 2.​ Stroma -​ 90% of thickness -​ Collagen fibers -​ Keratocytes -​ Proteoglycans 3.​ Descement’s membrane -​ Collagen fibers -​ Anterior and posterior zones 4.​ Endothelium -​ One layer of cells -​ Descement’s membrane detachment = diffuse corneal edema ​ - seen in horses following trauma and intraocular sx -​ Congenital dz of the cornea -​ Dogs with the merle gene (MOD) -​ Microcornea -​ Microphthalmia (small globe) -​ Ulcerative keratitis → corneal ulceration -​ Simple corneal ulceration (still in epithelium, no infection) -​ Complicated corneal ulceration -​ Indolent ulcer (non-healing) but not infected -​ Infected ulcer (very deep and infected) -​ Fungal keratitis - Aspergillus or Fusarium -​ Can see fungal hyphae in histo -​ Melting corneal ulceration -​ Descemetocele (reeeally deep) -​ Perforation -​ Non-ulcerative keratitis -​ Chronic super keratitis or pannus (immune mediated dz that cause pigmentation to come into cornea) in dogs -​ Immune-mediated keratitis in horses (not ulcerative just have lymphocytes coming in and causing irritation) -​ Eosinophilic keratitis in cats (eosinophils invading the cornea causing irritation, no ulcerative) -​ Neoplasia -​ SCC (histo) in limbus and cornea -​ Lymphoma -​ Hemangioma/Hemangiosarcoma Ocular anterior segment (anterior chamber, uveitis, glaucoma) -​ Anterior chamber is composed of: uvea, anterior chamber, pupil, iris -​ Iris and pupil -​ Iris is part of uveal tract → loose connective tissue, blood vessels and musculature (will help constrict and dilate the pupil) -​ Dilates → sympathetic -​ Constricts → parasympathetic - Histology picture of the corpora nigra of a horse (black part) → in iris?? -​ Uveal tract 1.​ Iris and ciliary body = anterior uvea 2.​ Choroid = posterior uvea -​ Anterior chamber and aqueous humor -​ Aqueous humor → provides nutrition and removes waste products from the internal ocular structures and drains out the eye via the iridocorneal angle. -​ If you can't get rid of aqueous humor = Glaucoma -​ Five steps in the production and outflow of aqueous humor: (conventional way) 1.​ Produced by ciliary body epithelial 2.​ Runs into the posterior chamber 3.​ Runs through the pupil 4.​ Run into the anterior chamber 5.​ ‘Drains out through the iridocorneal angle -​ There’s another exit path called reabsorption via the uveal-scleral pathway (unconventional outflow) → some drugs will use this pathway -​ Iris → gets out via vessels -​ Congenital dz in anterior chamber -​ Iris colobomas → basically a hole in cornea :) → notch lie defect located at the 6 0’clock position (micro ophthalmia) -​ Merle dogs are predisposed -​ Persistent pupillary membrane (PPM) → remnants of the tunica vasculosa lentils (embryological development problem) → like vessels in the pupil? -​ Goniodysgenesis → congenital abnormal iridocorneal angle (doesn’t have the lines) -​ Glaucoma -​ Normal IOP: 10-25 mmHg -​ Blockage in the aqueous humor outflow = glaucoma (not about increased production) -​ Primary Glaucoma → iris tissue expands over ciliary cleft and blocks the flow → closed/narrow iridocorneal angle -​ Gonioscopy → diagnosis of glaucoma → looking at the good eye at the iridocorneal angle -​ Increased intraocular pressure leads to: (all end up in blindness) → 35-40 = blindness forever -​ Optic nerve degeneration -​ Retinal degradation -​ Chronic glaucoma → buphthalmos (large globe) -​ Uveitis → inflammation of uveal tissue → breakdown of the blood-ocular barrier -​ Blood ocular barrier (BAB) → prevent movement of proteins, low molecular weight solutes (no inflammation in anterior chamber and uvea) -​ Blood aqueous barrier (non pigmented + iris vessel) → breakdown = anterior uveitis (more common bc of weaker barrier) -​ Blood retinal barrier (pigmented + retinal capillaries) → breakdown = posterior uveitis (inflammation of the choroid) -​ Anterior uveitis -​ Episcleral convention -​ Deep corneal vascularization -​ Corneal edema (endothelial cells stop working)  -​ Aqueous flare: -​ Flare = Proteins or inflammatory debris inside the anterior chamber floating around in aqueous -​ Presence of flare = anterior uveitis -​ Miosis (small/constricted pupil) → due to spasm of the ciliary muscles (that's why we give atropine) -​ Uveitis miosis can be resistant to pharmacologic dilation -​ Hypopyon → WBC in the anterior chamber → sterile pus in the eye -​ Hyphema → presence of blood in the anterior chamber -​ Trauma, inflammation, neoplasia (lymphoma), etc -​ Iris swelling/congestion (can be due to lymphoma) -​ Anterior chamber fibrin → tan-color strands (acute inflammation) -​ Keratic precipitates (KP) → chronic inflammation → bc of white cells attached to the posterior side of the cornea in the ventral aspect (triangle shape) -​ Rubeosis iridis → congested blood vessels in the iris -​ Iris color change → blue turns yellow, brown turns hyperpigmented -​ Iris hemorrhage -​ Posterior synechiae → posterior side of iris attached to anterior lens capsule -​ Anterior synechiae → iris attached to the cornea -​ Phthisis bulbi → eye was normal size but bc of chronic inflammation now is smaller -​ Often blind (bc usually of retinal detachment) -​ Infectious dz can also cause uveitis (tick borne, fungal, parasites) -​ Secondary glaucoma → due to obstruction of outflow -​ Secondary to uveitis, intraocular tumor or lens luxation  -​ Cx: 3+ flares, fibrin in anterior chamber, iris bombe (360 degree posterior synechiae), miotic pupil -​ Dx: anterior uveitis +/- secondary glaucoma → consider underlying causes like infectious, neoplasia, immune related Diseases of the lens, vitreous, retina and optic nerve -​ Lens -​ Capsule → barrier function -​ Epithelium → multiply, becomes lens fiber cells (on anterior side of capsule) -​ Fiber cells → transparent, protein antigenic (looks like an onion bc of the layers) -​ Central nuclear area -​ Anterior and posterior cortex -​ Equator -​ Zonule fibers → what hold in place the lens (prevent lens luxation) if you see the fiber = problem -​ If you see fibers in the posterior lens capsule its a sign of cataracts -​ Lens dont have blood vessels, if seen = problem (most likely behind the lens in the retina) -​ Lends dz -​ General signs of aging or dz -​ Nuclear sclerosis = age related changes to the lens -​ Normal aging change -​ Constant lens fiber production -​ 7+ yr old dogs -​ Rainbow effect happened bc nucleus is tight and you can see the edges -​ Cataracts = lens opacity -​ Significant cause of blindness in dogs -​ Due to disruption of orderly arrangement of lens fiber cells -​ Classifications (stages) -​ Incipient (