Veterinary Pathology Exam 5 PDF

Veterinary Pathology – Exam 5 Starred Slides Skeletal Muscle System Bacterial Myositis - Clostridium septicum (malignant edema) o Equine, pigs, cattle, sheep, goats o Sometimes multiple clostridiums o Gas, hemorrhage, necrosis o Often fatal – death fr...

Veterinary Pathology – Exam 5 Starred Slides Skeletal Muscle System Bacterial Myositis - Clostridium septicum (malignant edema) o Equine, pigs, cattle, sheep, goats o Sometimes multiple clostridiums o Gas, hemorrhage, necrosis o Often fatal – death from septicemia, toxemia in 48 hours o Often secondary to penetrating wound (injection site) o Rapid treatment – surgical incisions into affected muscle (drainage & oxygenation; antibiotics & supportive care - Clostridium chauvoei (Blackleg) o Cattle, goats, sheep o Acute death o Pathogenesis o Necrohemorrhagic myositis (myocarditis too) with emphysema o Rancid butter smell (sweet) o Vaccinate! - Corynebacterium pseudotuberculosis (Pigeon Fever) o Equine o Penetrating wounds (injection site) o Different Coryne from that in sheep & goats o Pectoral muscles o Can rarely lead to purpura hemorrhagica Immune Mediated Muscle Disorders - Characteristic histopathology pattern of immune-mediated myositis: o Interstitial & perivascular lymphocytic infiltration - Dogs: o Polymyositis § Can occur with thymomas +/- SLE § Atrophy of temporal & masseter muscles most obvious, but all muscles are affected § Megaesophagus (acquired myasthenia gravis) o Masticatory myositis localized tofacemasticatorymm § Autoantibodies to type 2M myosin (only type found in masticatory muscles) § Bilaterally symmetrical swelling/pain of masticatory mm Cannot open jaw, +/- trouble eating Muscles will end up atrophying § Diagnosis via testing for type 2M myosin autoantibodies o Extraocular muscle myositis - Cats: o FIV – cause of immune mediated myositis o Acquired myasthenia gravis - Horses: o Streptococcus equi subsp. equi (purpura hemorrhagica) o Equine influenza Hyperkalemic Periodic Paralysis (HYPP) - “Impressive” descendants - Autosomal dominant – affected horses are heterozygous or homozygous o Homozygous foals: laryngospasm & labored breathing o Genetic defect: point mutation in a subunit of skeletal muscle Na+ channel o Hyperkalemia: due to not eating; not always a consistent finding o Transient myotonia (delayed/inability to relax muscle after contraction) - No gross findings other than prominent muscling - Diagnosis via: o Characteristic clinical signs: muscle spasms often leading to flaccid paralysis o Clinicopathologic findings: hypokalemia o Horse of impressive breeding line o DNA-based test – most reliable test Malignant Hyperthermia - Unregulated release of Ca2+ from sarcoplasmic reticulum à excessive contraction à heat à increased body temperature à death, “cook themselves” - Ryanodine receptor defect (genetic defect) – in pigs & horses o Can have defect but not contract disease - Pigs: clinically normal until inciting cause, like halothane anesthesia o Porcine stress syndrome o Pale, soft, exudative muscle (“cooked”) - Dogs - Horses: during general anesthesia (aka hypermetabolism) o Usually from inhaled anesthesia Skeletal System Embolic Osteomyelitis - Most susceptible site: metaphysis (because of vascular loop) - Lesions: o Showering (embolic) – something within vasculature, emboli form, cause thromboemboli & then infarct § Acute – scattered throughout body § Subacute – hyperemic rim bordering a central area of necrosis § Chronic o Suppurative lesions & necrosis around surrounding tissue - Patterns of spread of embolic osteomyelitis from the physis: o Capillary/vascular loops in the metaphyseal side of the physis serve as a predilection site for septic emboli to lodge o Lysis of metaphyseal bone & growth plate cartilage secondary to inflammation may cause mechanical instability, to which the periosteum responds by producing reactive bone o Lysis of the cortex at its thinnest point (metaphyseal cut back zone) may lead to extension of inflammation/pus into the periosteum (periostitis), perichondrium & cartilage canal vessels, or into the joint (arthritis) Metaphyseal Osteopathy (Hypertrophic Osteodystrophy) - Non-infectious inflammation o But is a fibrinosuppurative metaphyseal osteomyelitis o Initial lesion is inflammatory o Infectious agents have not been identified § Does not have to be bacterial - Dogs: 3-6 months, giant/large breed - Site: distal radius, ulna (ddx: OSA due to location) - Clinical signs: lameness, fever, painful – can resolve Actinomyces bovis (Lumpy Jaw) - Ruminants o Not to be confused with Wooden Tongue (Actinobacillus lignieresii) - Commensal organism in GI & reproductive tract - Opportunistic organism - Trauma to mucosa – FB, erupting teeth, dental malocclusions, eating rough feed - Suppurative osteomyelitis (pus, necrosis of bone – honeycomb appearance) Osteopetrosis - Increased bone density due to decreased bone resorption by osteoclasts o Due to depositing more bone than we need, by either: § Osteoclasts aren’t working/breaking down bone, decreased resorption § Osteoblasts are overstimulated & doing other things - Butterfly appearance - More dense, but not stronger – poor quality bone - No growth plate lesions - Trabecular bone can fill medullary cavity, destroying hematopoiesis capability - All species are affected o Inherited o Acquired – BVDV, FeLV, avian leukosis virus Osteochondrosis - Defect in endochondral ossification o Multifactorial – trauma, genetic, rapid growth rate, vascular factors o Cartilage is firm & has poor vascular supply – prone to injury - Pigs, dogs, horses, cattle, poultry - Bilaterally symmetrical - Hallmark: focal retention of growth cartilage - Osteochondrosis Latens: histo diagnosis, cannot diagnose grossly; well-demarcated area of necrosis epiphyseal cartilage centered on necrotic blood vessels o May form a cyst - Osteochondrosis Manifesta: failure of ossification over an area of epiphyseal cartilage o Retained necrotic cartilage is visible grossly probably triable - Osteochondrosis dissecans (OCD): clefting of the retained necrotic cartilage – cartilaginous flap (dead cartilage) o Articular – epiphyseal cartilage complex (not growth plate) o Highly painful, lameness o Progression to degenerative joint disease o “Joint mice”: articular/cartilaginous flap breaks off & “floats” around in joint  - Common locations for osteochondrosis: o Pigs: § Distal femur – medial femoral condyle § Humerus – humeral condyles & head o Horses: § Distal femur – medial condyle, trochlear ridges § Distal tibia – cranial intermediate ridge, medial malleolus § Talus – trochlear ridges § Cervical vertebrae – articular processes o Dogs: § Humerus – medial condyle & head § Distal femur – both condyles § Talus – trochlear ridges o Cattle: § Distal femur – trochlear ridges § Talus – trochlear ridges Cervical Vertebral Stenotic Myelopathy - Horses, giant breed dogs - “Wobbler’s Disease” - Narrowing of spinal canal (compression of spinal cord) - Abnormally developed cervical vertebrae – osteochondrosis o Deformation in spinal canal or facets of vertebrae o Equine: C3-C4, C4-C5, C5-C6, C6-C7 o Dogs: C5-C6, C6-C7 - Cervical vertebral static stenosis: constant compression o No matter what position the neck is in - Cervical vertebral instability (dynamic stenosis): compression on neck flexion o On necropsy, may need to flex the neck in different regions to locate lesion Hypertrophic Osteopathy (Hypertrophic Pulmonary Osteopathy) - Progressive, bilateral periosteal, new bone formation in diaphyseal & metaphyseal regions (especially distal limbs) o Targets long bones - Secondary reaction to primary space occupying lesion o Intrathoracic neoplasm (hence “pulmonary”) - Other, less commonly associated diseases: o Endocarditis o Heartworms o Rhabdomyosarcoma of urinary bladder § Young, giant breed dogs o Right-to-left shunting (PDA) in dogs o Ovarian neoplasms in the horse Salter Harris Fractures - Growth abnormalities (stunting, angular limb deformity – valgus, varus) - Type I: growth plate (physis) - Type II: physis & metaphysis - Type III: physis & epiphysis - Type IV: physis, metaphysis & epiphysis - Type V: compression of physis Joints - Limited vasculature & nerves - Limited healing response - Injury to articular cartilage is not painful o Except when synovium or subchondral bone is involved - Cartilage erosions “scraping of cartilage” (ulcerations) - Cartilage atrophy (with compensatory subchondral bone sclerosis) - Fibrillation: fraying of collagen fibers within cartilaginous matrix - Terms: o Synovitis: synovium o Arthritis: articular cartilage & synovium o Polyarthritis: multiple joints § Young animals § Through omphalitis (umbilical infection) or oral entry Degeneration of Intervertebral Discs - Many species, age-related change - Distinction between nucleus pulposus & annulus fibrosis is obscured à may herniate (mostly dorsally) - Gross: central part of degenerated disk is yellow-brown, composed of friable fibrocartilaginous material - Rarely, disk material extruded through end plate into vertebral body, producing a “Schmorl’s node” lesion - Chondrodystrophic breeds: calcification of nucleus pulposus à disk prolapse, with total rupture of annulus fibrosus, extension of disk material into vertebral canal à Hansen type I herniation - Hansel type II: non-chondrodystrophic breeds - Rotational/compressive types of movement may further injure annulus fibrosus Ankylosing Spondylosis & IVDD - Spondylosis: ventral vertebral bridging (bony proliferations) o Ankyloses when fused, provides “brace”/stabilization for spine o May bulge/prolapse into spinal canal & cause pressure atrophy of spinal cord o In many animals – dogs, cattle, pigs, horses - Spondylitis: inflammation – do not confuse with spondylosis Luxating Patellas - Dogs (toy breed dogs), horses o Medial luxation most common - Luxation: complete dislocation of a joint - Subluxation: partial dislocation of a joint - Due to: o Developmental defects o Hypoplasia of one of both trochlear ridges Nervous System White & Grey Matter - Brain: o White matter: centrally located § Myelinated axons o Grey matter: peripherally located § Neuronal bodies o Brainstem has mixed areas - Spinal cord: o White matter: peripherally located § Funiculi, axons o Grey matter: centrally located § Neurons Lissencephaly - Neuronal migration disorder o Lhasa Apso, kittens, lambs - Lack of normal cerebral gyri & sulci – smooth brain - Exception: birds, rabbits, rats & mice lack gyri & sulci o Agyria is normal in these species o No functional significance Cerebellar Hypoplasia - Small cerebellum - Parvovirus/panleukopenia o Kittens & puppies o Can cause brain defects if infected in utero - Pestivirus (classical swine fever, BVD, border disease) o Piglets, calves, lambs - Viruses infect & destroy mitotic cells o External granule cell layer of cerebellum o Still dividing during late gestation, early neonatal periods o Brain does not develop - Clinical sigs: wide-based stance, unable to stand, vision problems, blindness, head tremors Brain Abscesses - Infection extension from: o Nasal sinuses (dehorning) o Vertebral osteomyelitis (docking tails) o Otitis externa o Bacteremia/septicemia, etc. - Variation in color: o Streptococcus spp., Staphylococcus spp., Corynebacterium spp. § Yellow, watery to creamy o E. coli & Klebsiella spp. § White/grey, watery to creamy o Pseudomonas spp. § Green to blue/green o Abscesses are surrounded by a hyperemic border - Liquefactive necrosis; highly vascularized, easily goes into bloodstream Meningitis - Meninges: dura matter, pia matter, arachnoid - Photo: o Suppurative meningitis o Not a true meningitis – leptomeningitis § Pia matter & arachnoid o Opaque – something is being added Transmissible Spongiform Encephalopathy (TSE) - Microscopic diagnosis, do not see gross lesions o May need to use electron microscopy - Etiology: proteinaceous infections particles (prions) o PrPC (expressed throughout body) à conformational change à a-helical portion PrPC diminishes, b-sheet increases à formation of PrPSc § “Sc” is derived from scrapie, prototype prion disease o Resist inactivation – heat, UV irradiation, enzymes - Ovine Spongiform Encephalopathy (Scrapie) o Degenerative disease – Scrapie (sheep), limited to CNS (goats) o Occurs naturally in the domestic goat o Change in behavior – scratching, rubbing (pruritis) – loss of wool selftrauma o Clinical signs: incoordination, weight loss (despite appetite), trembling, recumbency, death (1-6 months) § Can be variable neurologic signs o Diagnosis: use medulla oblongata - Bovine Spongiform Encephalopathy (BSE) - Chronic Wasting Disease (CWD) o Saliva, blood, urine à prions ingested à replicate (Peyer’s patches, macrophages) à WBC trafficking (LNs to blood) à CNS, neurons à neurons accumulate PrPSc (takes years) à neuro clinical signs à death § Adaptive immune system recognizes it as foreign – no immune response or notable inflammation within the CNS - No gross lesions of nervous system - Histo: neuronal degeneration – increased basophilia, cytoplasmic vacuolation o Astrocytosis: abnormal protein – prion amyloid protein § First accumulates in astroglial cells in scrapie o Spongiform change tends to affect grey matter Equine Viral Neuropathies - Arboviruses – family Togaviridae o Lymphocytes & plasma cells respond - Eastern Equine Encephalomyelitis (EEE) o Also reported in cattle, sheep, camelids & pigs - Western Equine Encephalomyelitis (WEE) - Venezuelan Equine Encephalomyelitis (WEE) - Target cell: neuron; also vasculitis, thrombosis - Pathogenesis: mosquito bite à hematogenous spread à endothelial replication à monocyte-macrophage system, muscle, CT à lymphoid tissue, bone marrow – cellular depletion & necrosis à second viremia à hematogenous à CNS (neurons, lesser extent glia) - In CNS, all 3 viruses induce a polioencephalomyelitis - Clinical signs: fever, tachycardia, anorexia, muscle weakness, aggression, head pressing, blindness, paralysis of facial muscles  - Gross lesions: +/- present in grey matter, appreciated best in spinal cord - Histo: grey matter of brain, spinal cord; perivascular cuffing; neuronal degeneration; cerebrocortical necrosis; perivascular edema; hemorrhage; necrotizing vasculitis; thrombosis; choroiditis; leptomeningitis West Nile Viral Encephalomyelitis - West Nile Virus (WNV): Flavivirus - Bird-mosquito cycle o Wild songbirds, crows, American robins (propagation, dissemination) o Birds: fulminate viremia à systemic viremia § Birds are amplifying host o Horses: dead-end species, only infections of CNS - Target cell: neurons, microglial cells - Pathogenesis: similar to equine encephalomyelitis viruses - Gross lesions: in grey matter; hyperemia & hemorrhage, especially lower brain stem & ventral horns of thoracolumbar spinal cord o WNV hemorrhage > EE, WEE< VEE (nearly impossible to quantify this) - Histo (birds & horses): acute polioencephalomyelitis, hemorrhage o Mononuclear cells (lymphocytes, plasma cells, macrophages) +/- neutrophils o Lesions outside of nervous system in affected horses do not occur - Clinical signs: fever, ataxia, weakness to paralysis of hindlimbs, tetraplegia, convulsions, coma, death Feline Infectious Peritonitis - Mutated coronavirus; worldwide distribution - Domestic cats, wild felids (similar viruses in ferrets, similar lesions in CNS) - Two coronaviruses – antigenically & morphologically indistinguishable; strains of the same basic feline coronavirus o Feline enteric coronavirus (FECV) – avirulent insignificantinfection o Feline infectious peritonitis virus (FIPV) – virulent - Saliva, feces, direct (cat bites, wounds), in utero à replicates in macrophages à liver, serosal surfaces, uvea, meninges, ependyma, spinal cord - FIP: all ages, mostly between 3 months & 3 years à death - Clinical signs caused by involvement of blood vessels (vasculitis) o Behavioral changes, coma, ataxia, paralysis, seizures - Disease development depends on type, degree of immunity & immune response - Strong cell-mediated immunity – virus containment, resistance - Wet (effusive) form: no cell-mediated immunity (humoral is not protective) o Two proposed mechanisms: § Ag-Ab complement complexes: infected macrophages around small blood vessels à inflammation, type III hypersensitivity à effusion § AB dependent enhancement: Ag-Ab complement complex infected macrophages à cytokines à increased vascular permeability, edema o Serositis, ascites, pleural effusion, inflammation § Modified transudate, can progress to an exudate - Dry (non-effusive) form: partial cell-mediated immunity (type IV hypersensitivity) o Leptomeningitis, chorioependymitis, encephalomyelitis, ophthalmitis o CNS: pyogranulomatous vasculitis § Leptomeninges, periventricular white matter – especially 4th ventricle, uvea, retina, optic nerve sheath - Lesions (both forms): preferential small & medium sized veins; pyogranulomatous, vasculitis, vascular necrosis, infarction Rhabdoviruses - Rabies virus - Replication at inoculation site (skeletal muscle) o Myocytes are first site of replication - Retrograde movement along axons to spinal cord & brain (12-100mm/day) - Spreads to salivary glands - Histo: lymphocytes, plasma cells, macrophages, microgliosis - Intracytoplasmic inclusion bodies (Negri bodies) - Rabies suspect necropsy protocols: o Additional protection: double gloves, mask, eye protection, proper ventilation o Collection of CNS tissues: hippocampus, cerebellum, medulla & optionally spinal cord – for examination by IFA, sometimes mouse inoculation § Know what samples to send for different species o Remainder of brain: fixed in 10% neutral buffered formalin for histopath Systemic Fungi - Coccidiodes immitis o Extracellular &/or intracellular o Composed of spherules (200-300 µm) containing endospores (< 5 µm) o Replicate via endosporulation - Blastomyces dermatiditis o ~ 15-25 µm in size with a double contoured wall o Replicate via broad-based budding - Histoplasma capsulatum o Often intrahistiocytic o Spherical (2-4 µm) containing a 1-2 µm basophilic nuclei, surrounded by a clear zone (on histo) o Replicate via narrow-based budding - Cryptococcus neoformans o Has particular affinity for CNS o Most common in cats, dogs & horses o ~ 15-25 µm (large) & spherical to crescent-shaped with a 15-20 µm thick mucicarmine staining capsule o Look like fried eggs o Replicate via narrow-based budding - Granulomatous to pyogranulomatous inflammation o Neutrophils, macrophages (epithelioid type), MNGC - Nodular granulomas (caseous to pyogranulomatous) Opportunistic Fungi - Opportunistic implies that some form of tissue damage precedes fungal invasion - Zygomycetes group (non-septate fungal hyphae) o Absidia corymbifera o Mucor spp. o Rhizomucor pusillus o Rhizopus arrhizus - Aspergillus sp. (septate fungal hyphae) - Angioinvasive à vascular thrombosis & infarcts in the CNS Feline Ischemic Encephalopathy - Associated with aberrant migration of Cuterebra fly larvae à nasal cavity à brain o Larvae can migrate & cause parasitic infarcts o Middle cerebral artery is affected most § Random distribution otherwise - Any age can be affected - Unilateral, white & grey matter of the cerebrum o Necrosis (ischemic necrosis) o Hemorrhages in CNS or leptomeninges - Histo: vasculitis, thrombosis, ischemia, infarction, cerebral cortical atrophy, destruction of architecture/deformity - Clinical signs: summer months, unilateral, depression, mild ataxia, seizures, behavioral changes, blindness Vitamin B1 (Thiamine) Deficiency - Polioencephalomalacia (PEM): necrosis/softening of the brain - Cattle & sheep > goats o Cattle 6-18 months, sheep 2-7 months - Three causes: o Decreases in ruminal thiamine o Inactive thiamine analogues o Overgrowth of thiaminase producing microbes - Cattle: carbohydrate-rich, little roughage à acidosis à rumen microflora changes - Rumen microbes synthesize thiamine o Young ruminants, not yet populated by these microbes, are susceptible - Thiaminase-containing plants: Bracken Fern - Salt, lead, sulphur toxicosis: sulfite cleaves thiamine - Histo: laminar cortical necrosis, edema, astrocytic swelling o Neuronal necrosis (ischemic change), cortex preferentially affected - Gross lesions: if present, limited to cerebral cortex (grey matter) o Swollen (cerebral edema) +/- brain displacement, herniation o Auto-fluoresce under UV light § Photo: bilaterally symmetrical laminar pattern of apple-green auto-fluorescence (from mitochondrial derivatives) involving full thickness of cortex indicates areas of grey matter necrosis - Clinical signs: depression, stupor, ataxia, head pressing, cortical blindness, opisthotonos, convulsions, recumbency, paddling, death - In carnivores: o Absolute dietary requirement for vitamin B1 (thiamine) in monogastric carnivores – dogs, cats, minks, fox § Fish diet containing thiaminase, B1 deficient diets (especially during heating) à thiamine deficiency o Gross/histo lesions: necrosis, bilaterally symmetrical focal lesions in thalamus, midbrain, or colliculi o Neuronal vacuolation, degeneration, necrosis, hemorrhage, astrogliosis, gitter cells o Clinical signs: vomiting, wide-based stance, ataxia, spastic paresis, circling, seizures, recumbency, opisthotonos, coma, or death Sodium Chloride Toxicity – Salt Toxicosis - Sodium chloride toxicity – sodium ion toxicosis, water deprivation syndrome, or salt poisoning - Primarily in pigs & poultry, occasionally in ruminants - Overconsumption of sodium chloride complicated by limited drinking water à severe dehydration (water restriction of sufficient duration) - Salt toxicity: hyperosmolarity, hypernatremia from excessive Na+ salts or severe dehydration, followed by rehydration & a rapid hypernatremic to normonatremic or hyponatremic shift o When given access to fresh water, acute hypernatremia to hyponatremia occurs, within minutes, the brain offsets osmotic balance by eliminating Na+, K+, Cl- ions by actively transporting ions into vasculature, early response cannot offset osmotic stress created by increased organic osmolytes in brain, water enters brain à brain swelling § Drink slowly! - Histo: cerebrocortical laminar neuronal necrosis (PEM) o Pigs: perivascular eosinophils with laminar cortical necrosis is indicative of salt toxicity in pigs - Gross lesions: cerebral, leptomeningeal congestion, edema - Clinical signs: inappetence, dehydration, leading to head pressing, incoordination, blindless, circling, paddling, convulsions, often found dead Lead Toxicosis - Cattle & other species - Sources: car batteries, lead paint in barns, farm buildings o Birds: pickled up lead while scavenging animals that were shot, fishing sinkers, gunshot wounds - Peracute (no gross/histo lesions), acute, subacute, or chronic - Affects: CNS, PNS, liver, kidneys, GI, bone marrow, BV, reproductive, endocrine - Gross lesions: contents of rumen – battery pieces, paint flakes resemble PEM of cattle o CNS lesions are usually absent; can represent o Lesions of lead encephalopathy in ruminants must be differentiated from other causes of PEM o Lesions in dogs resemble cattle, but more vascular damage § Necrosis, thrombosis - Clinical signs: o Cattle: down, dead, diarrhea, teeth grinding (bruxism), circling, head pressing, incoordination, blindness o Small animals (dogs): ataxia, tremors, clonic-tonic seizures, blindness, deafness o Horses: cranial neuropathy à laryngeal & facial paralysis Microbial Toxins – Botulism (CNS & PNS) - Clostridium botulinum: Gram (+) anaerobe o Found in the soil, spores germinate in necrotic tissue o Neurotoxin of C. botulinum type A, B or C in North America - Horses (in North America) o Type B is most prevalent in mid-Atlantic states to KY o Type A in western US +/- along mid-Atlantic states o Different forms of botulism affect foals & adult horses § Adult horses: contaminated forage > wound botulism § Foals: toxicoinfectious botulism via ingested clostridial spores  - Pathogenesis: replicate, produce endotoxin à bloodstream à myoneural junctions à binds receptors (presynaptic terminals of peripheral cholinergic synapses) à inhibit Ach release à flaccid paralysis à death (paralysis of diaphragm) - No microscopic or gross lesions - Horses have progressive paralysis of muscles (limbs, pharynx, eyelid, tongue & tail) Microbial Toxins – Edema Disease (Enterotoxemic Colibacillosis) - Strains of E. coli producing a Shiga-like toxin - Affects: rapidly growing, healthy feeder pigs fed a high-energy ration o 4-8 weeks of age, younger & older can be affected - Lesion: angiopathy à vessels become leaky à edematous, hypoxic-ischemic injury - Gross lesions: facial edema (also gastric submucosa, colonic mesentery, lungs, thoracic effusion, pericardial sac) +/- congestion, hemorrhage, pallor, spongiosis of CNS parenchyma - Characteristic gross lesions in the brain: bilaterally symmetrical foci of necrosis in caudal medulla - Inflammation is not a primary process – endothelial cells become swollen & vesicular, but layer remains intact so thrombosis is not a feature - Clinical signs: initially ataxia, then laterally recumbent, paddling limbs, comatose, die within 24 hours o Pigs that survive for several days typically develop CNS lesions PlantToxins – Centaurea spp. Poisoning - Yellow Star Thistle, Russian Knapweed - Nigropallidal encephalomalacia - Histo: necrosis, loss of neurons is the primary lesion o Necrotic axons, glia & blood vessels - Gross lesions: bilateral (or unilateral) sharply demarcated foci of yellow discoloration & malacia in globus pallidus (pallidal), substantia nigra (nigro) - Clinical signs: lip/tongue paralysis, reduced jaw tone early in disorder o Horses: persistent chewing, difficulty with prehension of feed & drinking water o Death due to emaciation & starvation Cholesteatomas (Cholesterol Granulomas) - Form in choroid plexuses of lateral ventricles in horses - Age related - Incidental, but can occlude flow of CSF à acquired hydrocephalus o Space-occupying lesion, may or may not cause problems - Gross lesions: tan to yellow-brown, firm masses with a smooth, often glistening, surface +/- mineral o Result from edema & minor but repeated hemorrhages within choroid plexuses à cholesterol deposits o Elicit a foreign body granuloma - Can be confused with a choroid plexus tumor Lysosomal Storage Diseases (LSDs) - LSDs: substrates can’t be degraded by lysosomes à accumulate à death of affected cells o Death of neurons or myelinating cells which release accumulated substrate into adjacent tissue, macrophages phagocytose & die, released substrate is phagocytosed by additional macrophages recruited from blood § Macrophages have the same genetic defect, also accumulate substrate in their lysosomes - Causes of LSDs: o Reduction of lysosomal enzymes synthesis o Synthesis of catalytically inactive proteins o Defects & post-translational processing of enzyme, misdirected to sites on (extracellular) other than to lysosomes o Lack of enzyme activator o Lack of substrate activator protein required to assist with the hydrolysis of substrate o Lack of transport protein required for elimination of digested material from lysosomes - General principle: cell swelling, cytoplasmic vacuolation o Many lipids & glycolipids are unique to the nervous system o When there is a lysosomal defect, neural cells often accumulate substrate - Gangliosidoses: inherited, autosomal recessive - Age of onset: variable among diseases; different lysosomal enzymes o If gene defect is mutant, the enzyme not synthesized at all à early onset o If there is residual synthesis of deficient enzyme à later onset (milder form) - Histo: neurons – foamy, finely vacuolated, or granular cytoplasm o Specific features of stored material best appreciated by EM - Gross lesions: CNS varies among different types of LSDs o Brain atrophy occurs with: § Globoid cell leukodystrophy – due to loss of myelin § Ceroid-lipofuscinosis LSD: Globoid Cell Leukodystrophy - Principal lesion: primary demyelination of oligodendrocytes (CNS), Schwann cells (PNS) - Autosomal recessive – Cairn terrier, West Highland Terrier o Beagles, Mini Poodles, Bassets, Pomeranians, Blueticks, cats - Animals < 1 year old - Sequence of events: o Early “normal” myelination process o Disruption of normal myelin turnover due to deficient galactosylceramidase activity à accumulation of psychosine à primary demyelination o Recruitment of phagocytes (resident microglia, trafficking blood monocytes) o Infiltration of macrophages, become globoid cells after phagocytosing myelin by-products - Histo: loss of myelin, globoid cells containing galactocerebroside, PAS (+) - Gross lesions: discoloration of white matter, especially cerebral hemispheres, & spinal cord - Clinical signs: ataxia, limb weakness, then paralysis, muscular atrophy, blindness  - PNS LSDs – Globoid Cell Leukodystrophy o Peripheral nerves also affected o Lesions: primary demyelination à axonal degeneration o Diagnosis via biopsy of peripheral nerves o Histo: pronounced loss of myelin, abundant globoid cells (activated blood monocytes) o Gross lesions: not evident Hypomyelinogenesis (Hypomyelination) - Underdevelopment of myelin - Classical swine fever (hog cholera):pestivirus o Teratogenic in fetus o Hypomyelinogenesis – not developing myelin o Cerebellar hypoplasia o Other lesions: microencephaly o PI that results in inhibition of cell division, function of selected tissues proposed - Border disease virus (in lamb & goats)pestivirus o Hypomyelinogenesis § Primarily affecting white matter of cerebrum & cerebellum o Gross lesions: difficult to distinguish between white matter & grey matter of cerebrum & cerebellum § PNS is unaffected o Others in lambs: early inflammation, porencephaly-hydranencephaly. Cerebellar hypoplasia, microencephaly, smaller diameter of spinal cord Intervertebral Disc Disease (IVDD) - Disk herniations, occur dorsally in dogs o Dogs present with different neurologic signs - Hansen Type I: o Chondrodystrophic breeds (Daschund, Pekingese) o Acute, progressive degeneration of discs; trauma o Genetic (chondroid) metaplastic change of nucleus pulposus o 6 months of age, progresses rapidly § Loss of elasticity of nucleus pulposus disc compresses blood vessels & spinal cord segment à ischemia, neuronal endotoxicity, necrosis § Stress on annulus fibrosus (degenerative changes similar to nucleus pulposus; annulus fibrosis is thinnest, weakest at point of contact with spinal cord) à most severe spinal cord damage – no time for collateral circulation to develop – very painful! o Multiple discs can be affected - Hansen Type II: progressive/degenerative o Non-chondrodystrophic breeds (GSD, labs, Doberman, obese dogs) o Slower degeneration à gradual loss of elasticity places mechanical stress forces on annulus fibrosus à protrusion/compression of spinal canal o Less painful than Type I o Older dogs, 8-10 years old Meningiomas - Most common CNS neoplasm of dogs & cats o Rare in horses & ruminants - Dogs: 7-14 years old; cats: > 10 years old  - Location of lesions: o Dogs: brain, spinal cord, retrobulbar (optic nerve sheath) o Cats: uniquely occurs in 3rd ventricle, cerebral hemispheres, along cerebri, cerebellum & tentorium, rarely at base of brain - Compress (pressure atrophy) or invade underlying CNS parenchyma - Gross lesions: o Dogs: solitary, vary in size, well-defined, spherical, lobulated, firm, encapsulated, grey-white +/- soft, areas of hemorrhage & necrosis o Cats: multiple, mm-2cm in diameter; can be incidental, old-age findings - Microscopic patterns subtyped as: (Type 1-4 common in dogs) o Transitional o Meningothelial o Psammomatous o Fibrous o Atypical o Malignant o Almost all meningiomas: features typical of meningothelial or transitional type with psammoma bodies being a common feature Hemangiosarcoma - Most are metastases from other organs (right auricle, spleen) - Dogs > other species - Lesions: solitary, expansile, red to dark red-black mass within the cerebral cortex - DDx: primary or metastatic melanoma Ophthalmic System Aqueous Humor Circulation - Aqueous humor is formed by ciliary epithelium - Travels to posterior chamber to pupil - Circulates within anterior chamber - Exits through iridocorneal angle - To scleral venous plexus Glaucoma - Many diseases lead to glaucoma (acute & chronic) – enlargement of globe - Increased intraocular pressure (decreased drainage of aqueous humor) o Damage to optic nerve & retina à blindness - Painful! Number 1 cause for enucleation - Primary: developmental disorders - Secondary/acquired: neoplasia, lens luxation, inflammation, etc. - Diagnostic histo lesions: o Inner retinal atrophy o Atrophy of nerve fiber layer & ganglion cell layer o Atrophy of inner nuclear layer (dogs) o Collapse of iridocorneal angle o Optic nerve head cupping o Atrophy of ciliary process o Scleral thinning - Gross lesions: ocular enlargement (buphthalmia), corneal edema, pupillary dilation & cupping of the optic disc +/- cataract, lens luxation Exophthalmos - Forward displacement of globe - Pugs, Pekingese - Disease process causing a space-occupying lesion o Carnassial tooth root abscess o Neoplasia o Sialocoele - Hyperthyroidism Diseases of the Cornea & Sclera - Indolent corneal ulcers: superficial ulcers that fail to heal o Non-adhering epithelium - Stromal necrosis: keratomalacia à meting ulcer à fibrosis - Desmetocoele: stromal necrosis, Descemet’s membrane intact, but bulges anteriorly - Perforating ulcer: rupture of Descemet’s membrane à aqueous fluid leakage +/- prolapse of iris Equine Recurrent Uveitis - Most common cause of glaucoma, cataract & blindness in horses - Repeated episodes of uveitis (waxing/waning) – immune-mediated signs? - Pathogenesis is not entirely known, but o Multifactorial immune-mediated disease o Infectious agent has been implicated – Leptospira - +/- amyloid Hypopyon vs. Hyphema - Hypopyon: neutrophils (pus) in anterior chamber - Hyphema: blood in anterior chamber Abnormalities of the Cilia - Trichiasis: misdirection of normal cilia that contact cornea - Distichiasis: ectopic cilia (comes from ducts of Meibomian glands) - Ectopic cilia: abnormally placed cilia within lamina propria of conjunctiva Diabetic Cataracts - Inherited to acquired/secondary - Diabetes related cataract: o Develops due to high levels of glucose within aqueous humor o Hexokinase pathway overloaded with glucose, excess glucose absorbed by lens is shifted to sorbitol pathway & transformed by aldose reductase into sorbitol à accumulation of sorbitol à hyperosmotic effect à influx of fluid à rapid swelling of lens & disruption of architecture - Bilateral o Opacity takes days to weeks o Lens capsule can rupture