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718 Cards in this Set
- Front
- Back
Bone
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-Tissue and an organ
-Site of active construction and demolition -Tuned in to physiologic homeostatic regulatory processes -Changes over time are documented |
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Homeostatic regulatory processes of Bone
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-Mineral balance
--Ca and PO4 -Hematopoetic system -Endocrine system -Adaptation to stress and external environment |
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Appendicular skeleton
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-Long bones
-Proximal and distal limbs -Cuboidal bones are short versions of long bones |
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Axial skeleton
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-Flat bones
-Calvaria (bones of skull) -Hyoid apparatus -Ossicles -Scapulae -Pelvis -mandibles -Ribs -Sternum -Vertebrae -Some portion forms like flat bones, some portions can form like long bones |
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Long bones
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-Predominantly mesenchymal tissue, formed from mesoderm
-Bone, cartilage, and connective tissue -Has adipose elements, blood vessels, hematopoetic elements, and nerves |
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Long bone Structure
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1. Epiphysis: articular cartilage and subchondral bone
-articulates with other bones -Grows with development circumferentially 2. Physis: growth plate 3. Metaphysis: narrowing zone just below metaphyseal growth plate -Trabeculae divert stress down into compact bone 4. Diaphysis: shaft -cortical bone with large medullary cavity |
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Cartilage
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-Specialized connective tissue
-3 types: --Hyaline --fibrocartilage --elastic cartilage |
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Hyaline cartilage
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-Lines articular surfaces of synovial joints
-Undergoes endochondral ossification during bone development -Acts as center for growth during development |
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Fibrocartilage
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-Forms strong connections between connective tissues
-Menisci, intervertebral discs, tendons, and ligament insertions |
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Cartilage basic components
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-Chondroblasts: immature and developmental cells
-Chondrocytes: mature cells within lacunae -Extracellular matrix: mostly collagen fibers type II -Hydrophilic ground substance acts as a "sponge" --proteoglycans attract water --glycosaminoglycans --hyaluronic acid -Has to be able to move and squish, move material in and out of matrix to provide cushion -Water is an important part of cartilage |
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Bone
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-Specialized form of connective tissue
-ECM is mineralized to very hard cement-like tissue -Provides structure and protection for vital organs -Allows for ambulation and frame for muscles -Homeostatic organ --contains hematopoietic elements --controls mineral electrolyte balance --Tuned in and connected to many different organ systems |
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Bone cellular components
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-Pleuripotent stem cells, can be induced to form blood cells and inflammatory cells
-Osteoblast progenitors -Osteoblasts -Osteocytes -Osteoclasts |
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Osteoblasts
Osteocytes Osteoclasts |
-Osteoblats: immature cells that build bone
-Osteocytes: mature cells that maintain bone -Osteoclasts: macrophage/monocyte lineage cells that breakdown/resorb bone |
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Bone ECM components
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-Organic component of Osteoid
-Inorganic component of hydroxyapatite |
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Osteoprogenitor cells
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-Bone stem cells
-Only bone cell capable of undergoing mitosis -Pluripotent, are able to differeniate into osteoblasts, chondroblasts, fibroblasts, adipose tissue -Line periosteal and endosteal surfaces of bone -Connected via connective tissue structure -Flattened, spindle-shaped cells with elongated nuclei |
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Periosteum
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-Lines outer surface of bones
--except at ends and at tendon/ligament insertion sites -Tough outer fibrous layer -Inner cellular cambium layer --contributes to bone progenitor cells for new bone formation |
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Endosteum
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-Lines inner surfaces of bone
-Lines compact and trabecular bone -Thin layer of osteogenic cells -Interface between hematopoietic marrow and bone |
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Periosteal reaction
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-Forms healing callus on injured bone
-Periosteal reaction tends to be more exuberant than endosteal reaction -Used in radiology to give diagnosis of processes |
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Osteoblasts
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-Big, plump cells with big golgi
-Pump out protein -Secrete large amounts of bone matrix -Line bone-forming surfaces -Make new bone |
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Osteocytes
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-Bone maintenance cells
-"Grown up" osteoblasts -"old ladies in rent controlled apartments" -Maintain bone matrix -Embedded within matrix lacunae -Are able to synthesize small amounts of bone matrix for bone maintenance -Are also able to resorb small amounts of bone matrix --osteolytic osteolysis to maintain blood calcium homeostasis -Communicate with external environment and each other via canaliculi --thin cytoplasmic processes extend to periosteal/endosteal surface through canaliculi -Detect stress, strain, microfractures -Sense pressure changes in fluids |
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Osteoclasts
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-Bone resorption cells
-Multi-nucleate cells -Monocyte/macrophage lineage -Eat large amounts of bone, dissolve bone -Give bone a scalloped margin appearance |
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RANK-Ligand
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-Produced by osteoblasts
-Osteoclast differentiation factor -Promotes resporption and inflammatory cytokines --TNF-b, IL-1, IL-6 |
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Factors contributing to proliferation and activation of osteoclasts
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-RANK-Ligand
-Osteoprotegerin -Calcitonin -Parathyroid hormone |
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Osteoprotegerin
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-Produced by osteoblasts
-Acts as a decoy receptor for RANK-ligand and inhibits osteoclast activation -Latch onto RANKL |
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Calcitonin
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-Produced in C-cells of the thyroid gland
-Directly inhibits osteoclast resorption -Causes osteoclast apoptosis |
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Parathyroid Hormone
PTH |
-Produced in parathyroid glands
-Indirectly stimulates bone resorption -DEcreases osteoblast osteoid production -Increases collagenase secretion -Leads to decrease in unmineralized osteoid, allows osteoclasts to make contact with mineralized matrix -Osteoclasts secrete HCl and cause bone resorption |
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Hydroxyapatite
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-inorganic component of bone
-Mostly Ca and PO4 with some other stuff -Osteoblast secretion is biphasic, allows for lag time between organic and inorganic matrix secretion -Organic osteoid is produced first |
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Bone matrix mineralization
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1. Degradation of inhibitors of type I collagen mineralization
2. Osteoblast production of molecules that promote mineralization --osteocalcin, osteopontin, osteonectin -Mineralization occurs 5-10 days after osteoid is deposited 3. Seams of unmineralized osteoid covers surfaces where bone is being deposited |
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Types of Osteogenesis
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1. Intramembranous ossification
-forms membranous bone 2. Endochondral ossification -forms endochondral bone |
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Intramembranous ossification
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-Forms membranous bone
-Bone is formed directly from mesenchymal cells -No cartilage precursor or template -Mesenchymal stem cells migrate from neural crest -Condensation of connective tissue cells → osteoblast differentiation → osteoid production → mineralization → anastomosing trabeculae of woven bone -Centers of ossificaiton expand and condense to form bony plates separated by connective tissue sutures -End of growth leads to bony union -Matures to lamellar bone |
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Endochondral ossification
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-Forms endochondral bone
-Bone is formed from cartilage plate --Fetal hyaline cartilage differentiates from primitive mesenchyme -Majority of bones in appendicular skeleton is formed via endochondral ossification -fetal hyaline cartilage model → cartilage calcifies, bone collar forms around diaphysis → primary ossification center forms in diaphysis -Primary ossification center in diaphysis --lengthens bone from ends -Secondary ossification center at epiphysis -Blood supply encourages mineralization and calcification |
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Endochondral ossification
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-Chondrocytes develop from the perichondrium
-Vascular in-growth at diaphysis -Promotes differentiation to bone -Gives rise to primary ossification center |
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Zones of Endochondral ossification
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1. Resting zone
2. Zone of proliferation 3. Zone of hypertrophy 4. Zone of ossification |
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Endochondral ossification: Resting Zone
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-Cartilage precursors
-Reserve cartilage |
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Endochondral ossification: Zone of Proliferation
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-Chondrocytes proliferate into regular cords
-Extend towards metaphysis -Divisions push older chondrocytes down the line towards zone of hypertrophy |
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Endochondral ossification: Zone of hypertrophy
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-Cartilage cells degenerate and undergo apoptosis
-Secrete pro-minerlization molecules -Leads to cartilage matrix mineralization and capillary ingrowth |
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Endochondral ossification: zone of ossification
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-Mineralization
-Vessels bring in osteoclasts and osteoblasts -Additional capillary ingrowth occurs with delivery of osteoprogenitor cells -Leads to osteoid production and additional mineralization |
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Bone classification by architecture
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1. Osteonal bone
-compact bone, cortical bone -Occurs at ends, outside of bone 2. Trabecular bone -Cancellous bone, apongy bone -Occurs on the inside of bones |
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Osteonal bone
Compact bone Cortical bone |
-Lamellae form concentric layers of bone matrix
-Osteocytes hang out in lacunae -Canaliculi contain communicating cytoplasmic processes of osteocytes -Central canal contains central blood vessels, nerves, and mesenchyme -Further out from central canal osteocytes die off --results in remodeling --no inflammation, inert process |
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Osteonal canal
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-haversian canal, central canal
-Contains arteriole, vein, nerve fiber, and lymphatic -Communicates directly with osteocyte canaliculi |
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Trabecular bone
Cancellous bone Spongy bone |
-intercnnecting plates of bone matrix with intervening marrow spaces
-Forms "honeycomb" -Present in ends of bone at metaphysis and epiphysis -forms anastomosing spicules of lamellar bone -Gives large surface area -Lined by osteoprogenitor cells -Surrounded by hematopoietic marrow |
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Bone classification by maturity
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1. Woven bone (immature)
2. Lamellar bone (mature) |
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Woven bone
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-Primary bone, immature bone, reactive bone
-Highly cellular -Haphazard organization of bone matrix -Forms during rapid growth or in response to disease -Laid down quickly during period of rapid growth or in response to disease -Can heal fracture sites, inflammation/infection, invasive neoplasms -not well mineralized |
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Lamellar bone
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-Mature bone
-Can be osteonal or trabecular bone -Organized parallel lamellae with regular linear cement lines -Can be osteonal or trabecular bone -MUCH stronger than woven bone -Forms over time, takes time to organize -Maximizes distance between lacunae and nutrient supply |
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Osteonal lamellar bone
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-Collagen fibers are laid down in parallel arches around central osteonal canal
-Maximizes density and strength per unit of bone -Maximum distance for nutrients/waste products to diffuse from central vessels through canaliculi |
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Trabecular lamellar bone
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-Collagen fibers deposited parallel to flat surface (endosteal surface)
-Fibers are linear and aligned -Width of one trabecula is one osteon radius |
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Lamellar vs. Woven bone
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-Difference is rate of formation and TIME
-Slow formation: procollagen fibers have time to line up and mineralize into lamellae -Fast formation, procollagen is haphazard in arrangement --fracture healing --Eventually collagen is remodeled into lamellar bone over time Ex: duct tape and tarp fix vs. actual roof |
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Bone as a plastic organ
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-Rigid, yet flexible
-Adapts to change while maintaining strength, rigidity, and flexibility -Able to sense biomechanical, hormonal, and metabolic changes in body and respond -Able to break down and reset along lines of force -Can increase or decrease bone mass based on pressure -Changes shape based on modeling and remodeling --couples bone absorption and resorption |
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Bone modeling
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-Mostly occurs in young bone
-Adaptive process -Results in architectural change in bone --size, structural orientation, contour -Occurs during growth (increases in bone length and diameter -Occurs during pathologic states --architecture needs to change --fracture healing, infection, neoplasia -Strength is transferred from trabecular bone to osteonal bone --trabeculae become fewer and thinner |
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Bone Remodeling
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-Physiologic replacement of old bone tissue by new bone tissue
-3 month cycle -mainly occurs in the adult skeleton -Maintains bone mass -Repairs microfractures from altered mechanical use, stress, or strain -Responds to metabolic disease states --altered Ca, PO4, PTH, calcitonin -Occurs locally, coordinated efforts of osteoblasts and osteoclasts in 5 phases -Systemic and local coordination |
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Stages of Bone remodeling
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1. Activation: stimulation of preosteoclasts by cytokines and growth factors
--leads to mature osteoclasts 2. Resorption: Osteoclasts digest mineral matrix of old bone 3. Reversal: end of resorption, cement line 4. Formation: Osteoblasts synthesize new bone 5. Quiescence: Osteoblasts become resting bone lining cells on newly formed bone |
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Cement line
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-End of resorption, marks "reversal" stage of bone remodeling
-Gravel that dissipates forces -Prevent continuation of micro-cracks in bone |
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Osteonal bone remodeling
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-Initiated from embedded vascular channels (osteons)
-Osteoclasts excavate a tunnel, form cutting (resorption) cone -Basophilic cement lines delineate reversal zone at periphery of remodeling units -Osteoblasts fill in the cone behind osteoclasts with concentric lamellae, centered on a haversian canal -Interstitial lamellae are remnants of older Haversian systems that have been partially excavated or remodeled |
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Trabecular Bone Remodeling
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-Remodeling occurs along the surfaces of trabeculae
-No cutting cone of osteoclasts |
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Blood supply to Bone
Adults |
-Nutrient artery mid-diaphysis is the primary blood supply to medullary cavity cortex
--Centrifugal blood flow -Periosteal arteries supply 25% of outer cortex --proliferate with fractures -Metaphyseal arteries anastomose with branches of nutrient arteries -Epiphyseal arteries supply subchondral bone and chondrocytes --enter bone at joint capsule insertion points |
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Blood Supply to Bone
Growing Animals |
-Nutrient arteries supply diaphyseal marrow and most of central area of the metaphysis
-Metaphyseal arteries form tight hair-pin like loops --low flow rate, can trap bacteria --supply peripheral regions -Epiphyseal arteries supply epiphysis and secondary centers of ossification -Transphyseal blood vessels exist in newborn animals --Allow infections to cross physis --so not exist in small animals, mostly in horses and cattle |
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Synovial joints
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-Diarthroses
-Allow movement of appendicular bones with minimal friction -Stifle, hock, fetlock, elbow |
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Synarthroses
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-Minimize movement
-Fibrous sutures of the skull |
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Classifications of synovial joints
Range of Motion |
-Unaxial: range of motion in one plane
--hinge joint, elbow and hock -Biaxial: motion in 2 planes --condyloid joints, stifle -Triaxial: motion in 3 planes --ball and socket joints, shoulder, hip --Planar joints, carpus |
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Synovial joint structure
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-Articulation of 2 bones with ends covered by articular cartilage (hyaline) and subchondral bone plate
-Supported by fibrous joint capsule -capsule is lined by synovial membrane that secretes synovial fluid |
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Synovial joint capsule
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-Fibrous joint capsule
-Contains blood vessels and nerves -Provides additional support to joint capsule via focal thickenings of the capsule with ligaments or menisci -Lined by synovial membrane that secretes synovial fluid --provides lubrication and nutrients for articular cartilage |
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Articular cartilage
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-Provides articular surface
-Provides growth zone of epiphyseal ossification center in young animals -Maintains structural integrity of the joint -Defects in cartilage or junction with subchondral bone will lead to degenerative changes and joint instability --fissures, ulcers, subchondral bone bruising, retained cartilage cores, etc. |
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Hyaline Articular Cartilage
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-Covers articular surfaces of joints
-Withstands compressive forces of weight bearing -Withstands shear forces during motion -Utilizes lubricating synovial fluid and cartilage organization -No nerves, blood vessels, lymphatics --Capsule has nerves, not cartilage itself -Synovial fluid and subchondral vessels allow for nutrient acquisition and waste removal --requires motion, joints need to move and "squish" to get stuff to flow |
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Chondrocytes
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-Cellular component of cartilage
-Create and maintain proteoglycan component of extra-cellular matrix -Undergoes minimal mitotic activity --damage is not repaired easily, no cell division -Number decreases with age, undergoes atrophy |
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Cartilage extracellular matrix
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-Very important
-Very hydrophilic, attracts water -Acts as a shock absorber -Composed of proteoglycans and type II collagen -Proteoglycans: hyaluronic acid, glycoproteins, glycosaminoglycans |
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Structure of Hyaline Articular Cartilage
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1. Superficial/gliding zone:
--small, flattened chondrocytes --more type I collagen fibers resist shear forces 2. Intermediate/transitional zone --Round chondrocytes 3. Radial zone: --Large, round chondrocytes lined up vertically in short columns 4. Articular Epiphyseal Complex --Mineralized zone --separated from radial zone by tidemark --Anchors cartilage to subcondral bone |
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Articular Epiphyseal Complex
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-Mineralized zone of Hyaline articular cartilage
-Separated from radial zone of large chondrocytes by basophilic line --tidemark -Acts to anchor hyaline cartilage to subchondral bone |
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Synovial membrane
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-Produced by Synoviocytes
-Line the inner surface of the joint capsule -1-4 cell layers thick -Multi-layered array of synoviocytes -Inner fibrovascular stroma subtends the synoviocytes --contains loose collagenous stroma, nerves, blood vessels, and inflammatory cells -Outer fibrous capsule is made of dense collagen --thickens with chronic injury and limits motion |
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Synovial fluid
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-Dialysate of plasma
-Contains proteoglycans (hyaluronic acid and glycoproteins) -Clear to straw-colored -Very Viscous -Increased amounts of protein will give yellow color -Hemorrhage leads to pink-brown color due to clotted blood in joints -Supprative inflammation leads to increased turbidity |
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Subchondral bone
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-Provides support for overlying articular cartilage
-Dissipates concussive forces to peripheral cortical bone -Thickness varies with degree of weight bearing and/or compressive forces -In larger animals, can be composed of osteonal bone |
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Factors determining reaction of bone to Injury
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-Depends on etiology, inciting cause
-Depends on when injury occurs --during development --in mature adult |
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Disruption of Endochondral ossification
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-Modeling response to structural damage or abnormal use
-Involves osteoblast and osteoclast activation -Remodeling in response to abnormal use or systemic disease -Woven bone formation |
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Abnormal Endochondral Ossificaion
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-Young, growing animals
-in Cartilage plate: --chondrodystrophy --osteochondrosis --trauma or infectious physitis -In trabecular bone: --growth arrest lines --growth retardation lattice |
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Chondrodystrophy
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-Type of abnormal endochondral ossification
-Occurs in cartilage plate -Generalized defect in endochondral template |
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Growth Arrest Lines
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-Due to disruption of endochondral ossification in trabecular bone
-Transverse trabeculation -Formation of mineralized trabeculae oriented perpindicular to the long axis of the bone --parallel to the physis -Caused by nutrient deficiencies, general malnutrition, or debilitating disease -Slowed or temporary disruption of endochondral ossification during development |
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Growth Retardation Lattice
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-Osteoclastic activity is imparied and results in abnormal osteoclastic modeling of primary trabeculae
-No osteoclasts, no proper remodeling -Form of skeletal dysplasia, metaphyseal dysplasia -Cartilagenous growth plate is normal -Proximal metaphysis of newly formed bone is not normal -Results in retention of primary trabeculae, trabeculae contain mineralized cartilage template -Caused by osteoporosis -Can also be caused by BVD, Canine Distemper Virus -Toxic-induced osteoclast damage can also be cause --lead poisoning |
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Physeal Lead Line
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-Type of growth retardation lattice
-Osteoclasts are defective, do not remodel bone appropriately -Will have a highly mineralized area that extends further into the growth plate -Can be due to BVD, Parvo, Lead toxicity |
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Normal primary Trabeculae
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-Will have inner mineralized cartilage spicules
-Newly deposited outer layers of woven bone -Is rapidly remodeled into secondary trabeculae --mineralized cartilage is removed, replaced with bone -Trabeculae should become thinner and fewer in number |
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Primary trabeculae in Growth Retardation lattice
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-Defect in osteoclasts and resorption
-No normal modeling of primary spongiosa -Retained mineralized cartilage cores with thick bands of vertically oriented trabecular bone |
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Premature physeal closure
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-Weakening or destruction of physeal chondrocytes or ECM
-Leads to primary closure of the growth plates (Physes) --"Squashage" -Local inflammation or trauma leads to focal closure of the growth plate and secondary angular limb deformities -Nutrient deficiencies can lead to complete closure of the growth plate with shortening of the limb |
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Traumatic Physis
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-Disruption in endochondral ossification
-Will not get ossification, cartilage core will remain and will continue to divide -Vessels under cartilage core are destroyed |
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Infectious physitis and epiphysitis
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-Infection that crosses the physes
-Abscess obliterates the growth plate, damages metaphyseal growth plate -Will get necrosis in the bone -May result in angular limb deformity |
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Bone Modeling
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-Alterations to size and shape of bone in response to altered mechanical stress or structural damage
-Compressive forces favor bone formation, forms more bone -Tensile forces favor bone resorption, bone disappears -Bone trabeculae align along lines of stress --osteoblasts sense currents, stretch receptors, stress forces |
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Altered forced detected by Osteoblasts
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-Piezoelectric currents from crystal matrix deformation
-Streaming potentials generated from differentials in canalicular fluid flow rates -Stretch receptors on osteoblasts |
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Bone Remodeling
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-Occurs in response to abnormal use or systemic disease
-Leads to alterations in bone mass -Activation-resorption/Formation-release cycle is activated -Obvious changes occur in spongy/trabecular bone |
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Bone Remodeling details
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-Increased mechanical use favors bone formation
-Decreased mechanical use decreases suppression of bone resorption -Inflammation or infection of bone leads to increased oosteoblast bone resorption --pro-osteoclast factors are induced, cytokines turn on osteoclasts --M-CSF and RANK-L |
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Bone Repair
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-Rapidly deposited bone, woven bone
-Formation of bone vs. cartilage callus vs. fibrous matrix production depends on O2 tension (vascularization) and instability factors |
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Woven Bone and Rapid Bone Deposition
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-Rapidly deposited when repair is needed
-Formed by reactive periosteum, leads to woven bone "callus" formation that bridges fracture -Low oxygen tension leads to chondroid differentiation within callus -High motion leads to fibrous differentiation and non-union -Woven bone is later modeled by osteoclastic resorption into lamellar bone |
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Fracture callus on radiograph
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-Radiolucent due to low oxygen tension and chondrocyte differentiation
-Increased motion leads to fibroblast deposition and radiolucency |
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Periosteal Reactions
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-Stimulated by instability, direct trauma, inflammation, infection
-Results in nodular woven bone proliferation --Osteophytes --Enthesiophytes |
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Osteophytes
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-Discrete nodules of periosteal new bone
-Often forms near joints in response to Degenerative Joint Disease -Periosteal reaction |
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Enthesiophytes
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-Periosteal new bone
-Forms at insertion of a tendon or ligament -Periosteal reaction |
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Joint Injury
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-Response from all anatomic structures
-Cartilage, synovial membrane, joint capsule, subchondral bone -ALL respond to injury |
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Cartilage response to Injury
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-Cartilage has poor repair response
-No blood vessels or nerves, no pain and no nutrient supply -Erosions, ulcers, and atrophy all occur |
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Cartilage erosion due to injury
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-Partial thickness loss of articular cartilage
-Can persist for long periods of time -Usually no progression until subchondral bone sclerosis, new bone built -Matrix will fill in defect, fill in space -Adjacent chondrocytes proliferate, form reactive clones --clusters of chondrocytes stuck in matrix, cannot get out to heal erosion |
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Cartilage ulceration due to injury
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-Loss of articular cartilage that extends to subchondral bone
-Extends to a vascularized surface -Will fill with granulation tissue -Metaplasia of cartilage to fibrocartilage --fibrocartilage does not have shock-absorbing capacity --will be a weak, friction point in the joint -Signals to other structures in the joint |
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Cartilage atrophy due to Injury
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-Thinning of articular cartilage
-Cartilage is "sick" -Matrix degrades and thins, chondrocytes die off -Can result from constant or excessive compression -Can also result from a lack of weight-bearing --need compressive forces to have nutrient delivery and waste product removal |
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Intraarticular inflammation
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-Can occur in synovium, subchondral bone, or are aof immature vascularized growth
-Cell mediators or degenerating chondrocytes activate gelatinases, collagenases, stromolysins --degrade molecules of hyaline cartilage --Cartilage matrix is digested -Net loss of chondrocytes and cartilage on the whole -Inflammatory mediators prostaglandin and NO inhibit proteoglycan synthesis, lead to additional matrix degradation -Hyaluronic acid and joint lubrication decreases -Surface injury to superficial collagen layer occurs --lose frictionless gliding surface |
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Results of intraarticular inflammation
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-Yellow discoloration of cartilage due to ECM degeneration
-Cartilage will become fibrillar, will have fissures -Can have focal or multi-focal erosions and ulcerations -Cartilage and chondrocyte necrosis with reactive clone formation |
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Supprative arthritis
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-Neutrophic inflammatory mediators are BAD for cartilage
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Reactions of Synovial Membrane to injury
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-Villous hypertrohy and hyperplasia of synovial membrane
--surface will not be smooth anymore -Inflammatory cell infiltrates --neutrophils and fibrin lead to lymphocytes, plasma cells, and macrophages -Joint capsule thickening/fibrosis -Pannus formation with additional distruction of articular cartilage |
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Bone response to chronic joint inflammation
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-Subchondral bone sclerosis due to direct transfer of compressive forces from joint to subchondral bone
-Bone modeling --"lipping" of the joint margin and periarticular osteophytosis -Once articular cartilage is lost, will get joint instability -Nodular proliferation of bone at joints |
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Normal endochondral ossification
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-Chondrocytes proliferate to form columns
-Chondrocytes hypertrophy, alter ECM and promote ECM mineralization -Hypertrophied chondrocytes are "bricked in" and cannot access nutrients, start to die --release factors that promote capillary in-growth at Zone of Calcification -Capillaries penetrate the zone of ossification, bring in osteoclasts -Osteoclasts eat away at dying chondrocytes -Osteoprogenitors become osteoblasts and deposit osteoid seams on mineralized cartilage spicules -Eventually mineralixed cartilage cores are removed and modeled out to form more mature, stronger bone |
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Types of Disorders of Bone Formation
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-Congenital/heritable
-Idiopathic -Nutritional/metabolic/toxic (acquired) -Infectious (acquired) -Sometimes toxic/nutritional/metabolic diseases can resemble congenital disease and vice versa |
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Types of disorders of osteoclast resorption
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-Congenital/heritable
-Infectious (acquired) -Nutritional/metabolic/toxic (acquired) -Sometimes toxic/nutritional/metabolic diseases can resemble congenital disease and vice versa |
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Disorders of bone formation and endochondral ossification
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-Osteogenesis imperfecta
-Osteo chondrodystrophies -Osteochondrosis -Osteochondritis dissecans -Epipihyseolysis |
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Osteogenesis Imperfecta
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-Abnormality of bone formation
-Poor collagen synthesis -Osteopenic disease, decreased bone production and decreased bone density -Affects calves, lambs, puppies, humans -Mutation in type I collagen synthesis -Affects osteoblasts and odontoblasts, bone and dentine forming cells -Will get blue sclera |
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Osteogenesis Imperfecta clinical signs
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-Weak or decreased collagen fiber network
-Weak bone formation and increased bone fragility -Pathological fractures with normal forces -Joint laxity, joint capsule is thin -Scleral thinning, results in blue sclera -Defective dentin and abnormal tooth formation -Decreased and thinned secondary spongiosa bone with pathological trabecular fractures -Abrupt failure of secondary spongiosa formation -No evidence of increased osteoclast activity or fibrous connective tissue -Thinned cortical bone without compaction -Thinned, abnormal tooth dentin and sclera |
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Osteochondrodysplasia
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-Disorder of Endochondral ossification
-Primary defects in growth plate cartilage -Results in disorders of bone growth -Cartilage template is "wonky" -Disease can be generalized or regional --some bones or sites might be more predisposed than others -Occurs in cattle, sheep, pigs, dogs, cats |
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Disproportionate/chondrodystrophic dwarfs
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-Shortened malformed limbs and normal skull
-Standard for basset hounds -Lethal bulldog calves -Spider lamb syndrome -Metaphyseal chondrodysplasia of norweigan elkhounds |
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Primary osteo chondrodystrophy
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-Defective osteochondrogenesis in basset hounds
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Secondary osteo chondrodystrophy
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-Lysosomal storage disease (MPS VI)
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Osteochondrosis and Osteochondritis dissecans (OCD)
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-Heterogenous lesions in growth cartilage
-Occurs in young animals -Species-specific sites of OCD development -Focal defect of endochondral ossification --delay or failure -Necrosis of cartilage vessels within canals -Inadequate capillary vascular ingrowth -Damage to vasculature within growth cartilage -Focal or multifocal sites affected -Many lesions are bilaterally symmetric --50% |
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Epiphysiolysis
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-Separation of the epiphyseal plate from the metaphysis
-Due to formation of a horizontal fissure through the growth pate |
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Factors leading to Osteochondrosis and OCD
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-Damage to vasculature within growth cartilage
-Excessive compressive forces leading to conformational defect or focal trauma -Genetics -Hemodynamic disorders -Nutrition |
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Osteochondrosis Histology
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-Chondrocytes are clonal and stuck in matrix trying to proliferate
-May have dissecting cartilage flaps --will irritate joint -Cartilage necrosis -Cartilage extends into the bone, forms a weak point -Vascular channels extend into growth cartilage plate |
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Osteochondrosis pathology
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-Focal interruption of endochondral vascular invasion or ischemic necrosis → failure of endochondral ossification → retention of cartilage core → pressure induced fissure → OCD
-Growth cartilage retention or growth plate defect → resolved -Defect → retained and heal, may leave weak point in bone -Defect → retained → dissecting cartilage flap → OCD → secondary degenerative joint disease |
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Causes of Epiphysiolysis
|
-Separation of epiphysis from metaphysis
-Developmental -Traumatic: Salter-Harris fractures |
|
Salter-Harris fractures
|
-Fractures through growth plates
-Can result in premature partial or complete physeal closure --results in angular limb deformities |
|
Common Developmental epiphysiolysis
|
-Dog: ununited anconeal process on proximal ulna
--creates joint instability, leads to pain and lameness -Cats: capital femoral epiphyseal slipping -Pigs: femoral head or ischeal tuberosity |
|
Wobbler's syndrome
|
-Form of OCD
-Cervical vertebral dysplasia and compressive myelopathy -Neurological condition in young growing horses and dogs -Common in large breed dogs and horses, fast-growing -Vertebral malformation leads to irregularly shaped bones with multiple centers of ossification -Static or dynamic compression of the cervical spinal cord -Portions ossify with endochondral formation, others with membranous ossification -Malformation closes down on the spinal cord and compresses cord |
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Cervical Vertebral Myelopathy Vertebral malformations
|
-Articular facet OCD or body/lamina
-Malarticulation with joint instability -Stenosis of the spinal cord -Spinal cord compression and secondary facet degenerative joint disease -Wallerian degeneration of the spinal cord -Neurological disease can be intermittent |
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Equine Wommbler's
|
-Cervical vertebral stenosis with compressive myelopathy
-Joint is enlarged, DJD in cassette joint -Does not heal well -White matter tracts degenerate |
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Metabolic Bone Disease
|
-Represents skeletal disease
-Nutritional -Endocrine/hormonal -Toxic origin -GI, renal, hepatobiliary system dysfunction can affect vitamin/mineral absorption, excretion, or hormone production -Vitamens A,D,E,K are lipid soluble |
|
Metabolic bone Disease age
|
-Can affect skeletally immature animals during growth or immature/adults during remodeling processes
-Many osteodystrophies imply specidic morphological changes but NOT specific causes -Different types of osteodystrophy can be present in the same animal --due to different hormones |
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Metabolic Osteodystrophies
|
1. Osteopenia, osteoporosis
--too few or too weak trabeculae 2. Rickets (immature individuals), Osteomalacia (mature individuals) 3. Fibrous osteodystrophies -primary hyperparathyrpodism -Secondary hyperparathyroidism --renal or nutritional deficiencies |
|
Osteopenia
|
-Decreased bone density or mass
|
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Osteoporosis
|
-Clinical syndrome of reduced bone mass manifested by bone pain and pathological fractures
-Bone structure is normal, reduced amount of trabecular and cortical bone --trabecular bone has most surface area exposed to osteoclasts -Quantity not quality of bone is reduced -Eventual compromise in bone strength leads to pathological fractures |
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Nutritional cause of osteoporosis/osteopenia
|
1. Starvation directly leads to decreased bone formation
--no proteins, no collagen 2. Calcium deficiency stimulates PTH release, leads to resorption via osteoclasts --tips balance towards bone resorption 3. Copper deficiency decreases osteoblast activation and collagen strength 4. Severe GI parasitism or IBD leads to malabsorption of vitamin D and release of inflammatory mediators leads to osteoclast activation --TNF, IL-1, IL-6 |
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Physical inactivity as cause of osteoporosis/osteopenia
|
-Disuse atrophy of bone
-Decreased bone formation and increased bone resorption |
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Chronic glucocorticoid excess as source of osteoporosis/osteopenia
|
-Increased osteoclast activity and decreased osteoblasts and pre-collagen synthesis
-Decreased calcium absorption in intestine and increased calcium excretion in the kidneys |
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Hormonal loss as cause of osteoporosis/osteopenia
|
-Not an issue in most domestic animals
-Menopause -Estrogen increases TGF-beta. decreases IL-1, IL-6, TNF-a --osteoclast promoting cytokines -Decreases bone formation and increases bone resorption |
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Trabecular bone lesions associated with Osteoporosis and Oteopenia
|
-Trabecular bone is more affected than lamellar bone
-Ends up with reduced amount of trabeculae -Thinner/fewer trabeculae with perforating holes in bony plates leads to conversion of trabecular bone to rods/struts --get perforating holes --bone and trabeculae change -Infarctions can lead to compression fractures with reduction in bone length --especially in vertebrae of women |
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Compact bone lesions associated with Osteoporosis and Osteopenia
|
-Thinning from osteoclast resorption on endosteal surface, leads to medullary cavity widening
-increased Porosity from osteoclast resorption in vascular space and haversian canals -Decreased osteoblast activity -Brittle bones with fractures |
|
Growth plate lesions associated with Osteoporosis and osteopenia
|
-Occurs in younger animals
-Protein malnutrition may cause thinning |
|
Rickets
|
-Metabolic bone disease that results in defective bone and cartilage mineralization
-Softening of bones and growth cartilage --especially at sites of endochondral ossification -Issue with mineral deposition phase of bone reodeling -In young growing animals -"Softening of bones" -Bone pain -Bone deformities --kyphosis, scoliosis, rachitic rosary of ribs -Fractures |
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Osteomalacia
|
-Metabolic bone disease that results in defective bone mineralization
-Softening of bones only -Syndrome of adult animals, cartilage is not affected -Issue with mineral deposition phase of bone remodeling |
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Causes of Rickets and Osteomalacia
|
-Vitamin D Deficiency
-Phosphorous deficiency -Fluoride toxicity (rare) -Hereditary -Paraneoplastic syndrome -GI malabsorption Calcium deficiency does not result in rickets or osteomalacia except in birds |
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Vitamin D Deficiency and Rickets/Osteomalacia
|
-Uncommon in animals fed commercial pet foods with balanced nutrients
-Regular sunlight prevents -Defective kidneys, do not make 1,25 OH-vitamin D3 --active vitamin D3 |
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Phosphorous Deficiency and RIckets/Osteomalacia
|
-Herbivores on a phosphorous deficient diet
-Usually become unthrifty and anorexic -Decreased reproductive performance |
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Hereditary Rickets/Osteomalacia
|
-Inborn errors in vitamin D metabolism
-Type 1: vitamin D dependent --deficient 1-alpha hydroxylase enzyme --gene is deficient, animal cannot make vitamin D on own --Can give vitamin D and animal will be fine -Type 2: vitamin D resistant --defect in vitamin D receptor --cannot treat --common in marmosets |
|
Paraneoplastic Syndrome
|
-Hypophoshatemic vitamin D resistant rickets
-Humoral substance that reduces phosphorous absorption -Only in humans so far |
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GI malabsorption and Rickets/Osteomalacia
|
-Hepatobiliary disease that reduces vitamin D absorption
-Excessive minerals inhibits PO4 absorption --Fe, Ca, Al |
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Rickets and Osteomalacia Error
|
-Mineralization of osteoid does not occur
-Reduction in mineralization results in deposition of large seams of osteoid along endosteal bone surfaces and osteonal canals --thick seams, strong to support weak squishy bone -Decreased osteoclast resorption --inability of osteoclasts to bind and resorb old bone -Growth plate deformities in young animals due to un-mineralized growth cartilage --leads to decreased formation of primary trabeculae |
|
Lesions of Rickets
|
-Physes are thickened and nodular
-Flared metaphyses with retained cartilage cores --Rachitic rosary of ribs --Normal resorption allows for tapered neck, no resorption flaring occurs -Lesions occur due to failure of mineralization -Failure of normal metaphyseal modeling -Decreased numbers of chondrocytes in proliferative zone with fewer vascular channels -Grossly deformed or bowed endosteal surfaces lined by thick seams of osteoid |
|
Fibrous osteodystrophies
|
-Bones resorbed and replaced with fibrous tissue
-Disease caused by increased osteoclast activity and bone resorption -Fibrous proliferation -Relative decrease in bone formation with production of poorly mineralized, immature bone -Loss of bone leads to bone weakening with pathologic fractures and deformities -Caused by persistent high levels of PTH (hyperparathyroidism) |
|
Hyperparathyroidism Primary cause
|
-Functional parathyroid gland tumors
--produces more PTH than body needs -Idiopathic parathyroid gland hyperplasia --hereditary disease -Pseudohyperparathyroidism and hypercalcemia of malignancy --paraneoplastic syndrome due to PTHrp, LSA, and anal sac adenocarcinoma |
|
Hyperparathyroidism Secondary cause
|
-More common
-Chronic renal insufficiency or failure -Dietary imbalance in Ca, P, or Vitamin D3 (uncommon) --Can be achieved with cereal grains to pigs or all meat dishes to carnivores, excessive bran to horses |
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Mechaisms of PTH-induced bone resorption
|
1. Renal Secondary hyperparathyroidism
2. Nutritional secondary hyperparathyroidism |
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Renal Secondary Hyperparathyroidism
|
-Decreased GFR and PO4 excretion results in disturbances in electrolyte balances
-Ionized Ca is pulled out og the blood -Decreased vitamin D3 production with decreased Ca absorption from GI and kidneys -Stimulates PTH release -Decreased bone formation -Increased osteoclast differentation and activation, LOTS of osteoclasts --increased osteoclast bone resorption with replacement fibrosis -Increased fibroblast differentiation from bone marrow stromal cells Take home: Decreased bone formation, increased osteoclasts and osteoclast activity, increased conversion of osteoblasts into fibrosis |
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Nutritional secondary hyperparathyroidism
|
-Relative increase in PO4 results in PTH release
-Similar pathways activated as in chronic renal failure |
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Cortical bone lesions of Fibrous Osteodystrophy
|
-Excessive bone resorption with replacement fibrosis and pliability
-"Rubber jaw" in dogs --teeth are loose in the jaw -Osteoclast resorption begins on endosteal surface and progresses to include haversian canals -Replacement fibrosis -Results in increased dimension of bone -"Big head" in horses |
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Trabecular bone lesions of Fibrous Osteodystrophy
|
-Osteopenia and thinning of the trabeculae
-May or may not ahve intramedullay fibrosis -Growth plate does not have any primary lesions |
|
Osteopetrosis
|
-Disorder of bone resorption
-Extreme form of growth retardation lattice -Defect in osteoclasts -Autosomal recessive mutation, lethal mutation with cranifascial development defects --brachygnathia inferior, impacted molar teeth, deformed cranial vaults with secondary brain compression -Mutation results in osteoclast defect -Unable to resorb and remodel primary trabeculae formed during development --Entire medullary cavity is filled with trabecular bone |
|
Growth Retardation Lattice
|
-Osteosclerotic disease
-Increase in bone density due to retained primary trabeculae -Acquired defect in osteoclast resorption -Infectious cause --BVD, CDV, Toxic cause (Pb) -Width of lattice indicates time and duration of impaired osteoclastic activity -As osteoclast activity resumes, zone advances towards diaphysis with normal endochondral ossification and osteoclast modeling |
|
Physeal "Lead Line"
|
-Acquired from retained primary trabeculae
-Broad radiodense line at the physis |
|
Transgenic KO osteopetrosis mice
|
-Defect in RANK-L
--osteoclast differentiation factor missing, defect in osteoclast activity |
|
Nutritional imbalances and toxins affecting Skeletal growth
|
-Mn and Co deficiencies
-Zn, Mb, F, Pb toxicity -Vitamin A deficiency and toxicity -Vitamin D deficiency and toxicity -Vitamin C deficiency (scurvy) -Toxic plants --lupine, hemlock, tobacco |
|
Congenital Cortical Hyperostosis
|
-Disorder of bone Modeling
-Diaphyseal dysplasia -Autosomal recessive trait in neonatal pigs -Causes new bone formation on the diaphyses -Histologically will see extreme radiating periosteal reaction |
|
Craniomandibular Osteopathy
|
-"Lion jaw"
-Autosomal recessive diseases in WHWTs -Idiopathic condition in other dog breeds -Hyperpstoses of the jaw and skull bones -Can be quite painful for the dog -Periosteal and endosteal new bone formation with disorganized modeling and remodeling -Growth plates are normal -Bilaterally symmetrical abnormal proliferation of trabecular and cortical bone --mandibles, occipital, and temporal bone proliferation -May have Temporomandibular muscle atrophy and painful mastication |
|
Bacterial Infectious Inflammation of Bone
Septic Osteomyelitis |
-Most common
-"Septic osteomyelitis" -Arcanobacterium pyrogenes, Staph aureus, Strep zooepidemicus, Strep intermedius, Salmonella, E. coli -Coliform bacteria -Will get supprative inflammation -May or may not get pyogranulomatous inflammation |
|
Viral Infectious Inflammation of Bone
|
-Canine distemper, BVD, Canine hepatitis, Feline Leukemia Virus
-has variable effects on bone --growth retardation lattice --Endothelial necrosis with medullary hemorrhage -Myelosclerosis -Oteoclasts are affected, retain primary trabeculae |
|
Fungal Infectious Inflammation of Bone
|
-Pyogranulomatous or granulomatous inflammation
-Stimulates bone lysis -Can look like an aggressive bone neoplasm |
|
Routes of Bone Infection
|
1. Direct inoculation or Direct extension
-Cutaneous wound, open fracture, puncture, or speptic joint -More common in older animals 2. Hematogenous (through blood) -Most common in neonates, immunocompromised, or debilitated animals -Can originate from umbilicus, respiratory tract, or GI tract -Infections on exposed orifices can become septic, bacteria lodges in bone |
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Septic Physitis
Septic Epiphysitis |
-Occurs in young, growing animals
-Bacteria lodge in tight-looped vessels of metaphyseal plates -Leads to septic physitis/epiphysitis with or without abscessation -Increased intramedullary vascular pressure can result in thrombus and infarcts of fat, marrow, or bone --Sequestrum formation with involucrum, will be radiolucent around the sequestrum --Cortical bone periosteal reaction --Can extend through epiphyseal vessels into joint with secondary arthritis |
|
Osteomyelitis on Radiograph
|
-Wedge-shaped sequestrum with involucrum
--will have periosteal reaction -Can look like an osteosarcoma -Osteomyelitis can cross the joint, osteosarcoma usually does not -May see soft-tissue swelling opacity around the injury -Lytic areas of bone are visible |
|
Septic physitis
|
-Growth plate is bridged by infection and fibrosis
-Trabeculae will become thinner and necrotic -Will see lots of supprative inflammation within the epiphysis |
|
Non-infectious inflammation of Bone
-Metaphyseal osteopathy |
-Common in young, growing large-breed dogs
-Signs: lameness, fever, swollen/painful metaphyses in multiple long bones -Metaphyseal necrosis and inflammation with pathological infractions and secondary periosteal new bone formation -Idiopathic] -Will see microfractures in trabeculae |
|
Non-infectious inflammation of Bone on Radiograph
|
-Trabecular bone will have bilaterally symmetrical alternating zones of radiolucency and increased radiodensity in metaphyses
--adjacent and parallel to physis -Radiopacities= necrosis with fibrinosuppurative inflammation -Cortical bone will have metaphyseal periosteal new bone formation -Growth plate will not have any lesions |
|
Eosinophilic Panosteitis
|
-Non-infectious inflammation of bone
-Enostoses-like lesion -Not eosinophilic OR inflammatory (misnomer) -Self-limiting infection in young growing large breed dogs -Proliferations of well-differentiated woven bone and fibrosis -Inflammation is not present -Pain can come and go -Also seen in horses and 1 camel -Areas of increased radiopacity in medullary cavity --radiopacities correspond to osteosclerosis of trabecular bone --Patchy white opacities on radiographs |
|
Enostoses
|
-Osteosclerosis of trabecular bone
|
|
Aseptic necrosis of Bone in Humans
|
-Many causes
-Occlusive vascular disease (infarct) -Hyperadrenocorticism -Fat emboli -Nitrogenous emboli (the bends) -Sickle cell anemia -Intramedullary neoplasms |
|
Aseptic Necrosis of Bones in Animals
|
-Uncommon with few causes
-Intramedullary neoplasms, osteosarcoma -Ischemic infarction --thromboembolic disease --Venous outflow reduction/vascular compression -Increased medullary pressure -Can be idiopathic, Legg Calve Perthes disease |
|
Possible Sequelae of Bone necrosis
|
-Incomplete necrotic bone resorption can lead to a sequestrum
-Impingement on the Physis can lead to premature physeal closure and angular limb deformities --An infarct in the femoral head can lead to premature physeal closure -May have a periosteal new bone response |
|
Histology of Bone necrosis
|
-Will have areas of empty lacunae and viable bone
-Necrotic bone will have increased palor of the matrix |
|
Legg-Calve-Perthes Disease
|
-Possible Sequelae of bone necrosis
-Idiopathic condition --may be due to epiphyseal vascular occlusion? -Necrosis of epiphyseal bone marrow and subchondral bone -Collapse of overlying articular cartilage -Treat with femoral head ostectomy (Remove!) -Occurs in young dogs, esp. small breeds (pug) -Subchondral infarct with continued weight-bearing leads to fracture and collapse of necrotic trabecular bone, which leads to flattening of the femoral head |
|
Legg-Calve-Perthes Disease Pathology
|
Subcondral infarct, continued weight-bearing → fracture and collapse of necrotic trabecular bone → flattening of the femoral head
|
|
Bone fracture classifications
|
1. Traumatic: bone broken by excessive force
2. Pathologic: abnormal bone broken by minimal trauma or during normal weight-bearing forces Cause directly informs treatment and prognosis |
|
Predisposing conditions for pathologic Fractures of Bone
|
-Metabolic bone disease
--Rickets, osteomalacia, osteoporosis -Primary or metastatic neoplasia -Osteomyelitis (bone infection) -Congenital disease Cause directly informs treatment and prognosis |
|
Salter-Harris Fracture
|
-Fracture that involves the growth plates
-Type I and II: hypertrophied cartilage or primary trabeculae --heals well -Type III and IV: cross the physis -Type V and VI: crush growth plate -Types III-VI can heal with growth deformities |
|
Cortical Bone fractures
|
-Simple or Comminuted
-Closed or Open -Transverse, oblique, spiral -Sagittal or parasagittal -Avulsions occur where tendon/ligaments insert --bone is pulled off with tendon or ligament -Greenstick: one side of cortical bone is fractured and other is not, just bent --occurs in young animals |
|
Bone Fracture Healing
|
-Bone heals through series of specific phases or events
-Involves coordination and communication between cytokines, growth factors, and cells -Stable fracture repair needs immobilization of fracture ends and clinical stability |
|
Fracture repair #1
Soft tissue injuries associated with Bone fractures |
-Tearing of periosteum, displacement of fracture ends gives adjacent soft-tissue trauma
-Will get hemorrhage with clot formation -Local tissue trauma → hemorrhage → hematoma → clot with fibrin |
|
Fracture repair #2
|
-Impaired blood flow leads to necrosis of the fractured bone ends
--results in bone lysis and matrix acidifcation -Cytokines are released, growth factors from platelets and macrophages within the blood clot -Proliferation of undifferentiated mesenchymal cells and granulation tissue --new capillaries will be embedded within a loose structural network of fibrous tissue --granulation tissue forms with mesenchymal precursors |
|
Fracture repair #3
|
-Differentiation of mesenchymal stem cells into Osteoblasts
-Metaplasia of granulation tissue into cartilage and bone -Formation of woven bone and primary fracture callus --Primary callus formation can take 4-6 weeks -Extensive periosteal and endosteal woven bone with periosteal vessels -Low O2 tension results in hyaline cartilage formation --eventually hyaline cartilage undergoes endochondral ossification |
|
Primary Fracture Callus
|
-Provides some stability to allow some limb function during healing process
-Degree of motion between the fracture ends determines the size of the fracture callus -Also determines type of tissue produced --bone --fibrous non-union -Callus will shrink down with time as woven bone is converted into lamellar bone --lamellar bone is stronger than woven bone, need less of it |
|
Fracture Repair #4
|
-Modeling and remodeling of primary callus into secondary callus
-Replacement of weaker woven bone by stronger lamellar bone -Bone is restored to its original shape |
|
Complications of Fracture Healing
|
1. Inadequate blood supply
2. Infection (osteomyelitis) 3. Sequestrum at fracture ends 4. Non-union --fibrous or cartilagenous |
|
Inadequate blood supply as a complication of Fracture Healing
|
-Usually due to extensive soft-tissue trauma and disruption of vasculature to site
-Problem in distal limb fractures of horses -Can result in bone necrosis and secondary osteomyelitis or sequestrum |
|
Infection as a complication of fracture healing
|
-Osteomyelitis
-Can be introduced at the time of injury or by direct inoculation or extension -Can be secondary to inadequate blood supply and tissue necrosis |
|
Instability with fibrous non-union in fractures
|
-Leads to "fake joint" or pseudoarthritis
-Fracture instability favors production of fibrous connective tissue instead of chondro-osseous tissue |
|
Excessive wear as a complication of fracture healing
|
-Debris is produced with macrophage response
-Cytokines produced by macrophages stimulate osteoclastic resorption -Osteoclast resorption leads to delayed union of fracture ends -Usually a result of excessive motion or fracture instability |
|
Sequestrum as a fracture complication
|
-Fracture fragments may be too large for osteoclastic resorption
-Inadequate blood supply and necrosis of bone |
|
Rigid Fracture Repair
|
-maintains fracture ends in close proximity
-Can use metallic surgical implants -Complete rigid fixation results in accelerated healing --direct osteonal bridging of the fracture site --No formation of a callus -Gap less than 1mm results in lamellar bone at right angles to fracture --fastest healing -Gap more than 1mm results in woven bone formation first, later remodeled to lamellar bone --slower healing |
|
Joint classifications
|
Classified by degree of mobility and type of connection between adjacent bones
1. Synarthroses: fibrous joints with very little movement 2. Amphiarthroses: cartilagenous joints with limited movement 3. Diarthroses: synovial joints that facilitate motion |
|
Arthrogryposis
|
-Congenital joint contracture
-"Funky angled limbs" -Can be sporadic or idopathic, genetic -Viral infections that damage fetal CNS can lead to abnormal innervation and stimulation of fetal muscles --leads to muscle atrophy and contracture of limbs -Anything that affects skeletal muscle innervation will affect joints -Toxic agents -Malformations at joint surface |
|
Canine Hip Dysplasia
|
-Common in large and giant breed dogs
-Can be genetically predisposed -Can be due to obesity or excessive exercise in growing animals -Shallow acetabular cup and increased joint laxity are primary/predisposing lesions -Can have DJD as a secondary lesion |
|
Canine Hip Dysplasia pathogenesis
|
-Excessive joint laxity due to shallow acetabular cup
-Leads to instability and chronic subluxation of coxofemoral joint -Leads to DJD with modeling of the femoral head and acetabular cup |
|
Secondary lesions of Canine Hip Dysplasia
|
-Erosion and ulceration of the articular cartilage on the femoral head and acetabulum
-Thickening and stretching of the joint capsule --Will also have osseous/cartilage metaplasia, may lead to rupture of the round ligament of the femur -Synovium will be thickened, non-supprative inflammation, and villous proliferation -Subchondral bone of acetabulum will become flattened --acetabulum becomes shallow and wide --femoral head is flattened --May heave eburnation and periarticular osteophyte formation |
|
Eburnation
|
-Bone on Bone contact
-Results in grinding and erosion of bone -Polishing of bone surface due to bone-on-bone frictional forces |
|
Lesions with Canine Hip Dysplasia
|
-Cartilage loss
-Flattening of femoral head, misshapen -Osteophyte formation -Acetabular cup becomes shallower |
|
Arthritis
Arthrosynovitis |
-Inflammatory lesion of the joint
-Can be an inflammatory or infective cause -Exudates are fibrinous, suppurative, serous, or lymphoplasmacytic -Persistent inflammation eventually leads to DJD, even if inciting agent is removed |
|
Arthritis causes
|
-Infection (bacterial, viral, fungal)
-Immune-mediated -Urate precipitates (gout) |
|
Damage to Joint Structures
|
-Direct damage from inciting agent or joint instability
-Liberated inflammatory mediators --prostaglandins, cytokines, leukotrienes, lysosomal enzymes, free radicals, NO, neuropeptides, products of complement and fibrinolytic systems -Activation of proteolytic enzymes --collagenases, proteases, MMPs All lead to degeneration of articular cartilage matrix and degeneration/necrosis of chondrocytes |
|
Infectious Arthritis
|
-Very common in Domestic Animals
-Causes: --neonatal septicemia, bacterial entry from orifices --direct penetration due to trauma, iatrogenic joint injection, surgery --Extension of Osteomyelitis through transphyseal vessels or cortex, shared blood supply |
|
Manifestations of Infectious Arthritis
Articular Cartilage |
-Lysis, erosion, thinning of surface cartilage
-Collapse from chondrocyte degeneration and necrosis -Ulceration from chronic suppurative process -Pannus formation, macrophage and fibroblast proliferation |
|
Manifestations of Infectious Arthritis
Joint Capsule/Synovium/Synovial Fluid Acute Changes |
-decreased viscosity of synovial fluid
--due to enzymatic digestion of GAGs and dilution by edema --cartilage matrix breaks down -Increased turbidity from neutrophils and fibrin exudates -Red/brown discoloration from hemorrhage -Hyperemic synovium, thickened from Edema |
|
Manifestations of Infectious Arthritis
Joint Capsule/Synovium/Synovial Fluid Chronic changes |
-Lymphoplasmacytic inflammation
-Granulation tissue proliferation leading to villous hyperplasia and hypertrophy of the synovium -Joint capsule fibrosis with or without intraarticular adhesions -Subchondral bone sclerosis or disuse osteopenia |
|
Agents in Infectious Arthritis
|
1. Bacteria:
-Gram- leads to fibrinous inflammation -Gram+ leads to suppurative inflammation 2. Mycoplasma: 3. Viruses 4. Reoviruses in Chickens |
|
Mycoplasma and infectious arthritis
|
-Very important in large animals
-Mycoplasma myorhinus: fibrinous arthritis in weanling pigs -Mycoplasma bovis: fibrinous to pyogranulomatous arthritis in feedlot cattle --hematogenous dissemination from pneumonia or mastitis -Mycoplasma capri: chronic arthritis in goats |
|
Viruses and infectious arthritis
|
-Lentiviruses
--Caprine Arthritis Encephalitis (CAE) --Ovine Progressive Pleuropneumonia (OPP) -Very important in goats and sheep -Chronic fibrinous and lymphoplasmacytic arthrosynovitis with syynovial villous hyperplasia --pannus formation --Joint distension and secondary carpal hygromas |
|
Immune-mediated Arthritis
|
-Non-infectious inflammatory arthritis
-Rheumatoid arthritis --common in small and toy breeds of dogs --chronic proliferative inflammatory arthritis -Polyarthritis of greyhounds -Feline chronic progressive polyarthritis --associated with viral infection? -Lupus |
|
Degenerative Joint Disease
|
-Osteoarthritis, osteoarthrosis
-Mono or polyarticular process -Mature or immature animals -Clinically silent or symptomatic -Final endpoint of joint disease regardless of inciting agent -Once started progresses -Can try to prevent with surgery |
|
Degenerative Joint Disease pathogenesis
|
-Release of inflammatory mediators by degenerating/dying chondrovytes and synovial macrophages
--have phagocytosed cartilage breakdown products -Leads to edema and reduced synovial viscosity -Proteoglycan content is reduced, less water binds, and chondromalacia results -Will get: --chondroerosion --Fibrillation --ulceration of cartilage --Eburnation --Subchondral osteosclerosis --Joint capsule fibrosis and periarticular osteophytosis --Subchondral bone cyst formation |
|
Non-supprative synovitis
|
-Edema and reduced synovial viscosity
-Lymphocytes, macrophages, plasma cells -Reduction in proteoglycan content, decreased water binding and chondromalacia -Manifests as linear grooves or score lines |
|
Chondroerosion
|
-Loss of articular cartilage layers
-Grossly apparent thinning and exposure of subchondral vascular channels -Surface layers have "melted" appearance |
|
Fibrillation
|
-Fraying of superficial cartilage layers
--can see grossly and histologically -Matrix is split along the vertical axis --perpendicular to the joint surface |
|
Ulceration of Cartilage
|
-Loss of articular cartilage to the subchondral bone
-DEEP loss of cartilage, all the way down to bone! |
|
Subchondral osteosclerosis and DJD pathogenesis
|
-Subchondral osteosclerosis is due to increased compressive forces from loss of shock-absorbing cartilage surface
-Reduction in osteoclastic bone remodeling |
|
Joint capsule Fibrosis and Periarticular Osteophytosis in DJD
|
-Marked thickening of the joint capsule
--decreases articular range of motion --eventually causes fibrous ankylosis -Extensive periarticular osteophytosis can eventually lead to bony ankylosis |
|
Subchondral bone cyst formation in DJD
|
-Occurs from fissures in the cartilage and synovial herniation into subchondral bone
|
|
Diskospondylitis
|
-Inflammation of the vertebral bone and/or intervertebral discs
-Often associated with prostatitis in dogs --Erysipelas infection in pigs --Enterococcus infection in chickens --Streptococcus infection in farmed mink -Can result in compressive myelopathy or myelitis |
|
Exostosis
Osteophyte |
-Proliferative, non-neoplastic lesion of bone
-Nodular benign proliferation -Projects outward from the surface -Commonly periarticular with DJD |
|
Enostosis
|
-Proliferative, non-neoplastic bone lesion
-Sclerotic bone growth -Originates from the endosteal surface within medullary cavity |
|
Enthesiophyte
|
-Proliferative, non-neoplastic bone lesion
-Similar to Osteophyte -Arises at site of tendon/ligament insertion |
|
Hyperostosis
|
-Proliferative, non-neoplastic bone lesion
-Indicates increased diameter of bone -Implies a uniform thickening of the periosteal surface |
|
Hypertrophic Osteopathy
|
-Periosteal bone formation (progressive and bilateral) at diaphysis of distal limbs
-Dog: Associated with mediastinal or thoracic disease --dirofilariasis --rhabdomyosarcoma of young, large breed dogs -Horse: ovarian neoplasms and intrathoracic disease -Unknown pathogenesis --changes in blood flow results in woven bone formation? --Reflex vasomotor changes via vagus nerve, induced by thoracic disease? -May regress if primary lesion or vagotomy is performed |
|
Osteochondroma
Osteochondromatosis |
-Caused by defect in perichodral ring during skeletal development
-Results in displaced focus of growth cartilage --eventually cartilage undergoes endochondral ossification -Can have one or many masses projecting from bone surfaces of long bones --masses communicate with medullary cavity at the base -Cure by surgical excision |
|
Osteochondroma Clinical Signs
|
-Depends on location
-Can interfere with tendon or other musculoskeletal structures -Space occupying mass that can protrude into the vertebral canal -May undergo malignant transformation to chondrosarcoma -In cats can be viral in origin (FeLV-like virus) --occurs in flatbones and adult animals |
|
Osteochondroma Lesion
|
-Outer cap of hyaline cartilage undergoes orderly endochondral ossification
|
|
Bone Cysts
|
-Well-circumscribed radiolucent areas that are not aggressively growing
-Can be simple, subchondral, or aneurysmal |
|
Simple Bone Cyst
|
-Clear, colorless fluid-filled central cavity
-Surrounded by fibrous connective tissue and woven or lamellar bone |
|
Subchondral bone Cyst
|
-Secondary to OCD or DJD
|
|
Aneurysmal Bone Cyst
|
-Spaces filled with blood of serosanguineous fluid
-Fluid has hemosiderosis -Surrounded by well-differentiated fibro-osseous tissue --mixed with mesenchymal cells/osteoblasts/multinucleate cells -Can be congenital lesions in foals --often occur in mandible |
|
Bone neoplasms
|
-Primary tumors of bones
-Common in dogs, not as much in cats, rarely in other animals -May arise from any mesenchymal tissues present in bone --Bone (Osteoma, Osteosarcoma) --Cartilage (Chondroma, Chondrosarcoma) --Fibrous tissue (Fibroma, Fibrosarcoma) --Adipose tissue (Lipoma, Liposarcoma) --Vascular tissue (Hemangioma, Hemangiosarcoma) -Tumors of bone and cartilage-forming cells are most common -In dogs malignant tumors are more common than benign neoplasms |
|
Bone Neoplasms by Species
|
-IN dogs, most tumors are malignant
-In cats, benign and malignant are equally common -Other domestic animals, benign tumors are much more common than malignant tumors -Secondary tumors of bone are rarely diagnosed in animals --surveillance issue |
|
Primary Neoplasms of Bone
|
-Osteoma/Osteosarcoma
-Chondroma/Chondrosarcoma -Fibrosarcoma -Histiocytic sarcoma -Poorly differentiated sarcomas -Giant Call tumors -Multilobular tumor of bone -Liposarcoma -Hemangiosarcoma -Lymphosarcoma -Multiple Myeloma -Ossifying fibroma (benign) |
|
Secondary processes occuring with bone tumors
|
-Periosteal response
-Osteolysis -Necrosis -Osteomyelitis -Pathologic fractures Bone remodels and responds to neoplastic injury |
|
Osteosarcoma
|
-Most common neoplasm of bone
-Malignant neoplasm of osteoblasts -Produces variable amounts of osteoid and bone -Histological morphology is extremely variable -Radiographic appearance can be an aggressive lesion, lytic, sclerotic, or mixed types |
|
Osteosarcoma locations
|
-80% of all primary neoplasms in dogs
-75% occur on appendicular skeleton --65% occur in forelimbs --30% occur in hindlimbs |
|
Osteosarcoma metastasis
|
-Aggressive neoplasm with extremely poor prognosis
-Arises in the medullary cavity of bones --has easy access to metaphyseal blood vessels -Rapidly metastasizes to lungs, other organs and other bones -Can "skip metastasis" to adjacent bones -Will not cross cartilage plates or joint surfaces -Usually has already metastasized by the time is has been identified |
|
3 features of Osteosarcoma
|
1. Destruction of bone architecture
--no organization 2. Production of reactive periosteal and endosteal new bone 3. Production of osteoid and tumor bone |
|
Chondroma
|
-benign neoplasm of hyaline cartilage
-Rare -Occurs in dogs, cats, and sheep -Tends to arise from flat bones of the head --NOT articular cartilage -Multiple lobules of slow-growing, well-differentiated hyaline cartilage -May or may not have endochondral ossification -Can metastasize and be invasive, but not overwhelmingly |
|
Chondrosarcoma
|
-Malignant Neoplasm of hyaline cartilage
-Predilection site in flat bones --nasal cavity, ribs, pelvis, cartilagenous exostoses -Slow-growing multilobular mass of hyaline cartilage --well-differentiated, anaplastic -Tends to invade -Slow to metastasize -Often has areas of endochondral ossification -Will look like blue-white multilobular islands of hyaline cartilage separated by thin, fibrous trabeculae --often have foci of hemorrhage or necrosis -Ddx: osteosarcoma |
|
Chondrosarcoma Histology
|
-Cell morphology varies
-Can have undifferentiated mesenchymal cells (Myxosarcomatous) to chondroid cells that produce abundant ECM -Clinical history and radiographs give diagnosis, not histology |
|
Fibroma/Fibrosarcoma
|
-Originate from intramedullary fibroblasts or periosteal connective tissue
-Produce abundant collagenous connective tissue --no cartilage or bone is produced -Tumor can invade between fascial planes -Can be difficult to remove surgically -Recurrence is frequent if removed -In cats, can be associated with vaccination --Rabies Vaccine |
|
Maxillary Fibrosarcoma in Dogs
|
-Specific type of fibrosarcoma
-Occurs in maxillae of large-breed dogs -Histologically low grade, looks benign --low mitotic index --can look like scar tissue -Biologically high-grade, invasive behavior |
|
Osteoma
|
-Benign neoplasm
-Uncommon -Arise from the bones of the head -Single, dense protruding mass that projects from bone surface -Slowly progressive growth of trabecular bone --trabeculae will be lined by well-differentiated osteoblasts --covered by layer of periosteum -Does not invade or destroy parent bone |
|
Multilobular tumor of Bone
|
-Locally aggressive and invasive
-Skull predilection site --Causes brain compression and herniation -50% post-surgical recurrence -Metastasis is rare -Well-defined lobules of neoplastic mesenchymal tissue |
|
Multiple Myeloma
|
-Plasma cell Myeloma
-Produces monoclonal IgM --Bence Jones proteins -Produces lytic bone lesions -Neoplastic Plasma cells replace marrow cells |
|
Ossifying Fibroma
|
-Benign, no metastasis
-Commonly found on mandible or maxilla of horses and cattle -Slowly expansile mass -begins as intramedullary neoplasm, progressive destruction of trabeculae and overlying cortical bone -Histologically can see well-differentiated proliferation of cellular fibrous tissue --will be mixed with woven and lamellar bone lined by osteoblasts with osteocytes in lacunae |
|
Metastatic tumors to Bone
|
-Typically occur on rib shafts, vertebral bodies, or humeral/femoral metaphyses
-Can be associated with pain, pathologic fractures, hypercalcemia of malignancy, osteolysis, reactive new bone formation |
|
Common metastatic neplasms to bone
|
-Cats: Pulmonary carconima to the digits
-Dogs: Subungual SCC, prostatic carcinoma, thyroid carcinoma -Horses and dogs: hemangiosarcoma, malignant melanoma |
|
Synovial Neoplasms
|
-Somewhat rare
-Typically malignant behavior -Occur in large joints of extremities -most often in horses and middle-aged, large breed dogs -Arise from fibrocytes of synovial membrane, within joints or tendon sheaths? -May have myxoid component -Negative for histiocytic IHC markers -Locally invasive -Metastasis is uncommon -32 month average survival time |
|
Synovial Myxoma
|
-Occurs in dobermans and horses
-Affects stifle and small joints -30.7 months average survival time |
|
Histiocytic Sercoma
|
-Often associated with joints
-Also has other primary sites --bone marrow, lymph nodes, spleen -Rottweiler dogs predisposed -Stifle and elbow are frequently affected sites -Occasionally classified as synovial sarcomas -Large, bizarre histiocytic morphology with single or multiple nucleoli and bizarre mitoses -One type has erythrophagocytosis and can result in aneima -Poor prognosis, 5.3 month survival time -Metastasizes to liver, lung, regional lymph nodes |
|
Function of Skeletal Muscle
|
-Most energy demanding tissue in the body
-Function is related to function of peripheral nervous system -Myofibers are innervated by axons -Changes in muscle fibers can be neuropathic or myopathic |
|
Neuropathic muscle disease
|
-Determined by effect or absence of nerve supply
-Denervation |
|
Myopathic disease
|
-Primary change takes place in skeletal muscle
|
|
Motor unit
|
-Myofibers all innervated by one motor neuron
-Territory innervated by 1 motor neuron -Myofibers contract simultaneously -Gives checkerboard pattern of innervation to skeletal muscle |
|
Skeletal Muscle Fiber Types
|
-Type I: slow, oxidative, small fibers
--Fatigue resistant --Small diameter -Type IIa: Fast, oxidative, glycolytic --Fatigue resistant --Medium diameter -Type IIb: Fast, glycolytic --Large motor units --Maximal force --Fatigues rapidly Type I and II fibers are arranged in mosaic pattern |
|
Clinical Signs of Muscle Disease
|
-Weakness
-Exercise intolerance -Fatigue -Muscle atrophy or hypertrophy -Pain -Lymphadenopathy -Stiff gait |
|
Clinical Pathology of Muscle Disease
|
-Muscle necrosis may lead to elevations in:
--Creatine Kinase --Lactate Dehydrogenase --Aspartate aminotransferase --Alanine aminotransferase -Myoglobinuria: released after muscle injury and ends up in urine |
|
Skeletal muscle reactions to injury
|
-Atrophy
-Hypertrophy -Degeneration -Necrosis -regeneration -Fibrosis -Mineralization/ossification -Inflammation |
|
Muscle Atrophy
|
-Reaction to muscle injury
-Decreases in size -Loss of myofilaments causes myofibers to decrease in size -Decrease in the diameter of the entire muscle or decrease in diameters of individual myofibers or decrease in both -Can be due to denervation, disuse, malnutrition |
|
Denervation as a cause of muscle atrophy
|
-Loss of connection with peripheral nerves
-Leads to Atrophy, NOT necrosis (decrease in cell size only) -Can be caused by wallerian degeneration, axonal degeneration, or demyelination -Laryngeal hemiplegia in horses --axonal degeneration of left recurrent laryngeal nerve --Brachial paralysis in dogs due to trauma |
|
Wallerian degeneration
|
-Muscle atrophy and denervation secondary to trauma in a peripheral nerve
|
|
Muslce denervation
|
-Atrophy with loss of myofibrils
-Reduced synthesis of contractile proteins -Increased expression of muscle regulatory proteins -No signs of muscle regeneration, muscle just gets smaller |
|
Laryngeal Hemiplegia
|
-Denervation atrophy of the cricoaretynoideus dorsalis muscle
-Due to denervation from recurrent laryngeal nerve -Common in horses -Causes "roaring" |
|
Muscle Reinervation
|
-Schwann cells proliferate at the motor end plate of denervated fiber
-Collateral sprouting of neighboring neurons or axonal regrowth -Will get hypertrophy with increase in myofibrils -May have fiber type grouping --May lead to a single neuron innervating more adjacent myofibers --changes phenotype of myofibers |
|
Fiber Type Grouping
|
-Hallmark of reinnervation
-Damage to certain neurons can result in adjacent neurons innervating denervated myofibrils -A single neuron may innervate more adjacent myofibers -Changes phenotype of myofibers -Produces histological appearance of type grouping -Homogenous area of fiber types -Loss of checkerboard pattern -Usually only part of the muscle is affected |
|
Hypertrophy of skeletal muscle
|
-Increase in diameter of entire muscle or increase in diameter of individual myofibers or both
-Cannot get hyperplastic, cannot increase in cell number -Can be a reaction to injury -Can be due to increased workload --physiologic hypertrophy and exercise --Compensatory hypertrophy from loss of other myofibers |
|
Muscle degeneration as a reaction to injury
|
-Reversible injury
-May or may not lead to cell death -Causes hydropic swelling and fatty change |
|
Muscle necrosis as a reaction to injury
|
-Generally necrosis is segmental, only a portion of the myofiber is involved
-Loss of striations and hypereosinophilic cytoplasm -Can look like autolysis -Inflammatory cells enter myofibrils to clean up debris within 24-48 hours -Will get swelling of myofibrils and fragmentation with neutrophils -May even get mineralization |
|
Possible outcomes of skeletal muscle necrosis
|
1. Regeneration
-Occurs if basal lamina is intact 2. Fibrosis -Occurs if basal lamina is destroyed |
|
Muscle regeneration as a reaction to skeletal muscle injury
|
-Only happens if basal lamina is intact
--basal lamina serves as a scaffold -Depends on satellite cell proliferation, myofiber nuclei cannot synthesize DNA or replicate -Removal of debris by macrophages -Seal off injured areas -Satellite cell proliferation in basal lamina tube --look like flat cells -Regenerating cells will have central nuclei -Fusion of satellite cell processes -If basal lamina is destroyed, fibrosis occurs --cannot have regeneration with fibrosis |
|
Fibrosis as a reaction to skeletal muscle injury
|
-If muscle is damaged down to basal lamina, fibrosis occurs
--No regeneration is possible -May follow any non-fatal injury -Will see firm tan/white foci or streaks in the muscle, collagen deposition -Often associated with atrophy |
|
Mineralization as a reaction to skeletal muscle injury
|
-Appears as chalky white areas
-Histologically will see blue-purple granular material -Causes: --necrosis --primary myopathies --Vitamin D toxicity |
|
Ossification as a reaction to skeletal muscle injury
|
-Rare form of metaplasia
-Inherited in pigs --fibrodysplasia ossificans progressiva -Also seen in other species |
|
Inflammation as a reaction to skeletal muscle injury
|
-Myositis
-Follows necrosis -Associated with trauma, infectious agents, and infarcts -Commonly idiopathic, some are thought to be immune-mediated |
|
Disorders of Skeletal Muscle
|
-Congenital/inherited
-Trauma -Metabolic -Nutritional -Denervation -Circulatory -Inflammatory -Infectious -Toxic -Neoplastic |
|
Congenital/Genetic disorders of skeletal muscle
|
-Ion channel disorders: ion channels have to be working for skeletal muscle to be working
--Hyperkalemic periodic paralysis --Malignant hyperthermia --Myotonia -Myasthenia gravis -Muscular dystrophy -Carbohydrate metabolism defects |
|
Skeletal Muscle Action
|
1. Myofiber receives AP signal from pre-synaptic neuron
2. Na channels open, myofiber floods with Na and is depolarized 3. Ca is released from sarcoplasmic reticulum 4. Na channels are inactivated, K leaves the cell 5. Cl- comes into cell and repolarizes myofiber --Ca is resequestered in SR --Muscle relaxes |
|
Hyperkalemic Periodic Paralysis
|
-In quarter horses
-Autosomal dominant point Mutation in Na channel, -Causes muscle hypertrophy, stiffness, and weakness -Most common hereditary muscle disease in the horse -Due to "Impressive," horse that had huge muscles --offspring were bred to have big muscles also, genetic mutation was also passed on -May have hyperkalemia, but issue is in the Na channel |
|
Na channels in Hyperkalemic Periodic paralysis
|
-Na channel closure is delayed
-with constant contraction (due to Na channel being open), muscle runs out of Ca for contraction --Needs period of relaxation to appropriately contact -Point mutation of Na channel -May appear as if K is high, but issue is in the Na channel |
|
Malignant Hyperthermia
Porcine Stress Syndrome |
-"Excessive contractions"
-Brought on by stress, halothane, and depolarizing muscle relaxants -High incidence in breeds with increased lean muscle mass --Pietrain, Landrace, Yorkshire, Poland China, Duroc -Defect in ryanodine receptor of Ca channel results in muscle rigidity and hyperthermia --channel open time is prolonged --Ca is released from SR into cytoplasm in greater amounts than normal, results in excessive contractions -Acute muscle necrosis is end result -Muscles appear pale, moist, and swollen |
|
Myotonia
|
-Defect in Cl channel in goat breeds
-Causes stiffness, muscle rigidity, and muscle hypertrophy --Cl channel does not open, Ca stays bound and causes continual contractions -Similar conditions occur in other species |
|
Myasthenia Gravis
|
-NMJ disorder
-Can be congenital or acquired --Both involve ACh and ACh receptor |
|
Congenital Myasthenia Gravis
|
-Severe disease
-Deficiency of ACh receptors, fewer ACh receptors present on post-synaptic neuron -No circulating antibodies to ACh receptors -Responds to anti-acetylcholinesterase therapy --decrease in AChase activity leads to more available ACh at synapse and allows for more muscle contraction -Symptoms generally begin 6-8 weeks of age -Common in Jack Russel terriers, springer spaniels, smooth haired fox terriers -Weakness, exercise intolerance |
|
Acquired Myasthenia Gravis
|
-Body produces auto-antibodies to ACh receptors
-Have reduced number of functional ACh receptors -Responds to anti-AChase therapy -Causes megaesophagus, voice changes, generalized or local muscle weakness -Associated with thymoma (neoplasm in thymus) -Often self-limiting disease -Functional deficiency, receptors have antibodies bound to them |
|
X-linked muscular dystrophy
|
-Due to mutation of dystrophin gene
-Dystrophin links ACh to ECM in skeletal and cardiac muscle --Deficiency decreases stability of the plasma membrane, becomes friable and prone to damage -Causes weakness, diffuse muscle atrophy, splaying of limbs (wide base stance) -Leads to muscle necrosis, macrophage infiltration, regeneration, atrophy, and fibrosis -Homologous to Duchenne's dystrophy in human males -Occurs in canine, feline, and mice |
|
X-linked Muscular Dystrophy pathology
|
-Lack of Dystrophin makes plasma membrane unstable, becomes friable and prone to damage
-Animal is weak, has muscle atrophy -Eventually leads to muscle necrosis, macrophage infiltration, regeneration, atrophy, and fibrosis -Continuous cycles of muscle damage and attempts of regeneration results in fibrosis and decreased regeneration -Type IIb fibers are most susceptible to plasma membrane damage --large volume to surface area, greatest force per unit area of membrane |
|
Histology of Skeletal Muscle Regeneration
|
-Will get variation in muscle size
-Central nuclei (instead of on periphery) -May see fibrosis and myofiber loss |
|
Equine Polysaccharide Storage Mrauma to yopathy
|
-Carbohydrate metabolism defect
-Inherited disease of horses -Leads to recurrent rhabdomyolysis and pelvic limb weakness -Abnormal aggregates of acid-schiff positive material --stored polysaccharide |
|
Trauma to Skeletal Muscle
|
-Regeneration can occur
-Extensive trauma is usually followed by fibrosis -Often trauma ends with hemorrhage and damage to other systems |
|
Equine Exertional Rhabdomyolysis
|
-Chronic intermittent rhabdomuolysis, exertional myopathy, Monday Morning Disease
-have mild and severe forms -Triggered by exercise, leads to acute muscle necrosis -May see myoglobinuria due to myoglobin released after muscle necrosis -Sudden onset of stiff gait, reluctance to move, swelling of affected muscles, pain, discomfort -Will have skeletal muscle necrosis, swollen muscles, and yellow streaking of muscles -Unknown pathogenesis --underlying myopathy? --Affected horses may have polysaccharide storage myopathy |
|
Circulatory disorders of Skeletal Muscle
|
-Not common
-Infarcts and ischemia are due to thrombi and emboli -External pressure due to prolonged recumbency --downer cows, animals during surgery |
|
Inflammatory and Infectious disorders of skeletal muscles
|
-Infectious: bacterial, protozoal, metazoan, fungal, immune-mediated, viral
-Idiopathic: masticatory myositis, polymyositis, dermatomyositis -Any infectious agent can cause myositis --Most often bacterial agents |
|
Clostridial Myositis
|
-"Malignant Edema"
-"Blackleg" |
|
Malignant Edema
|
-Clostridial myositis
-Caused by a variety of Clostridium -Wound promotes growth of anaerobic bacteria --necrotic tissue is anaerobic -Results in necrosis/hemorrhage -Occurs in horses -Secondary to a penetrating wound |
|
Blackleg
|
-Clostridium Chauvoei
-Spores are present in the tissue, waiting for anaerobic conditions (tissue necrosis) -Results in necrosis/hemorrhage -Occurs in cattle, sheep, goats -Ingested spores lay dormant in skeletal muscle until localized trauma to muscle results in anaerobic conditions --allows bacterial to proliferate and produce toxins |
|
Botulism
|
-NMJ disorder
-Botulism toxin blocks ACh released in skeletal muscle -Causes generalized flaccid paralysis -Horses are most sensitive to toxin |
|
Parasites encysting in skeletal muscle
|
-Trichinella spiralis
-Tapeworm cysts |
|
Idiopathic myositis
|
-Polymyositis
-Masticatory myositis -Dermatomyositis -Immune-mediated? unknown cause |
|
Polymyositis
|
-Acute or chronic immune-mediated inflammation of multiple muscles
-Occurs in dogs -Unknown cause -Presents as white streaks in muscles, bands of fibrosis |
|
Canine Masticatory Myositis
|
-Bilateral atrophy of temporalis muscle
-Really only in dogs -Animal cannot open mouth to eat -Will have swollen, necrotic skeletal muscle -MASSIVE necrosis of skeletal muscle -Muscle cannot regenerate |
|
Toxic disorders of skeletal muscle
|
-Plants: cause acute muscle necrosis
--glossypol, cofee senna, coyotillo -Feed additives (ionophore toxicity) -Drugs -Mycotoxins |
|
Metabolic Disorders of Skeletal Muscle
|
-Endocrine
--Hypothyroidism --Iatrogenic and spontaneous hyperadrenocorticism -Electrolyte abnormalities --Hypokalemia --Hypernatremia --Hypocalcemia --Hypophosphatemia -Causes dysfunction and weakness |
|
Nutritional disorders of Skeletal Muscle
|
-Vitamin E and Selenium deficiency
-Vitamin E and Selenium act as antioxidants --if missing, will get oxidative damage -Grossly appears as white/tan streaks in the muscle --"White muscle disease" -Histologically consists of necrosis with or without mineralization and later regeneration |
|
Vitamin E/ Selenium deficiency Pathogenesis
|
-Deficiency in Vitamin E/Selenium leads to peroxidation of membrane lipids
--Can be exacerbated by stress -Ca enters cytoplasm and mitochondria, damages respiratory mechanisms -Cell dies without respiration, may get symmetrical necrosis of the most active skeletal muscle -Grossly muscles are white, have white streaks --may also get mineralization -Occurs in cardiac AND skeletal muscle |
|
Neoplastic disease in Skeletal Muscle
|
-Rare
-Primary neoplasms: --rhabdomyoma/rhabdomyosarcoma -Metastatic neoplasms: --lymphosarcoma --Hemangiosarcoma --Malignant melanoma --Carnimomas --sarcomas -Infiltrative lipoma, can form between skeletal muscle layers |
|
Laryngeal rhabdomyoma
|
-Benign neoplasm, not invasive or destructive
-Can cause severe respiratory distress -Requires a wide surgical excision area -Are difficult to remove -Occurs in dogs |
|
Rhabdomyosarcoma
|
-Malignant neoplasm within skeletal muscle, subcutaneous tissue, or urogenital tract
-Locally invasive |
|
Urinary bladder rhabdomyosarcoma
|
-RARE
-Occurs in the trigone of the urinary bladder -Occurs in young, large breed dogs -Can look like transitional cell carcinoma |
|
Skeletal Muscle Disease Principles
|
-Skeletal muscle is one of the largest organ systems in the body
-Active, also has big energy demands -Disease is commonly associated with weakness and fatigue -Function is related to function of the PNS |
|
Type I muscle fibers
|
-Slow fibers
-Postural muscles -Most continuously active muscles in body -Depend on oxidative metabolism for ATP --have lots of mitochondria -Resist fatigue with use -Do not generate a lot of force -Express type I myosin --long contractile cycle, force is maintained while myosin is bound to actin |
|
Type II muscle fibers
|
-Tension is maintained by more rapidly repeating the contraction cycle
-More ATP is used -Fatigue faster than type I fibers -Have large cross dimensions -Generate high force -Glycolytic instead of oxidative metabolism -Less efficient system than OxPhos --generates lactic acid |
|
Type IIb fiibers
|
-Fast contracting
-High Oxidative enzymme activity -Have lots of mitochondria -Fatigue resistant -Small diameter -Do not generate high force |
|
Diseases unique to the nervous system
|
-Diseases of myelin
-Diseases of neurons -Tumors of neuroglia (astrocytes, oligodendrocytes) |
|
Diseases that affect the Nervous system AND other systems
|
-Infections
--CDV, CAEV, bacteria, fungi -Trauma -Neoplasms |
|
Anencephaly
|
-Brain is absent
-Due to neural tube closure failure |
|
Chromatolysis
|
-Loss of normal staining characteristics of cytoplasmic RER in neuronal cell bodies
-Caused by degranulation of rough ER --cell has switched protein synthesis to structural proteins from NT -Cell body swells -Cytoplasm becomes homogenous and glassy -Nucleus moves to an eccentric position -Will see Nissl substance (degranulation of rough ER) as damaged axon tries to fix |
|
Cranium bifidum
|
-Failure of the sutures of the calvaria to close
|
|
Demyelination
|
-Degeneration or loss of myelin without axonal degeneration
|
|
Encephalitis
|
-Inflammation of the brain
|
|
Exencephaly
|
-Location of a large portion of the brain outside the cranial cavity or exposed by failure of development of the calvaria
-Abnormal brain tissue exposed through an incomplete calvaria |
|
Gemistocyte
|
-Hypertrophied astrocyte reacting to non-specific central nervous tissue injury by sweling of its cytoplasm that stains it with eosin
|
|
Gitter cell
|
Mononuclear phagocyte Cell in the nervous system laden with myelin debris
|
|
Gliosis
|
-Astrocytosis: increase in number and size of astrocytes
-recognized by nuclei -Astrocytic sclerosis: increase in size and number of astrocyte fibers |
|
Hepatoencephalopathy
|
-Metabolic disorder of the CNS caused by imparied liver function
-Portosystemic shunts or cirrhosis decrease liver function -Animal presents with seizures or blindness -Toxic metabolites (NH3) not filtered by the liver cause CNS damage -Vacuolization, spongiosis is present in brainstem nuclei -Edema of the white matter tracts -Astrocyte hyperplasia and hypertrophy in the gray matter --prominent in horses |
|
Hydranencephaly
|
-Absence of a large portion of the cerebrum
-Leaves a fluid-filled membranous sac instead of cerebrum -No identifiable cortex remains |
|
Hydrocephalus
|
-Increased volume of CSF in the ventricular system
-Obstructive hydrocephalus produces dilated lateral ventricles and thin cerebral mantle -Leads to dilation of the ventricles -Lateral ventricles are most vulnerable -Cortex and white matter are still recognizable, although atrophic -Externally looks like doming of the skin above the braincase -Primary hydrocephalus: usually in young animals --usually idiopathic -Secondary hydrocephalus: occurs in older animals --usually secondary to other diseases |
|
Leukoencephalitis
|
-Inflammation of brain white matter
|
|
Lissencephaly
|
-Smooth-surfaced cerebrum that lacks gyral development
-On transverse section cortex is usually thicker than normal (Pachygyria) |
|
Malacia
|
-Softening
-Gross manifestation of necrosis in the CNS with softening is palpable |
|
Meningitis
|
-Inflammation of the meninges
|
|
Meningoencephalitis
|
-Inflammation of the meninges, brain, and spinal cord
|
|
Meningoencephalocele
|
-Extension of the meninges and spinal cord outside of the vertebral canal
-Usually through spinal bifida -Smetimes with development of a fluid-filled cavity |
|
Myelitis
|
-Inflammation of the spinal cord
|
|
Myelodysplasia
|
-Abnormal spinal cord development
|
|
Myeloschisis
|
-Failure of closure of the neural folds
|
|
Neuronophagia
|
-Accumulation of mononuclear cells
-Occasionally neutrophils or glia accumulate -Accumulate around or at the site of a neuronal cell body that is undergoing dissolution or has disappeared -Process of neuronal phagocytosis -Monocytes eat up neuron -Leads to neuronal loss |
|
Polioencephalomalacia
|
-Necrosis of brain gray matter
-Usually used in reference to the cerebral cortex |
|
Polioencephalomyelitis
|
-Inflammation of gray matter of the brain and spinal cord
|
|
Poliomyelitis
|
-Inflammation of gray matter of the spinal cord
|
|
Polymicrogyria
|
-Development of small gyri in larger numbers than normal
-Cerebrum is covered in many small gyri |
|
Porencephaly
|
-Cavities in the brain, usually cerebrum
|
|
Satellitosis
|
-Accumulation of glial cells around neuronal cell body
-Usually oligodendrocytes |
|
Spinal bifida
|
-Failure of the vertebral arch to develop
|
|
Spinal Dysraphism
|
-Abnormal spinal cord development with improper union between two contiguous structures
|
|
Syringomyelia
|
-Cavity in the spinal cord parenchyma, usually in white matter
|
|
Wallerian degeneration
|
-Combination of degenerative changes that occur in an axon and its myelin distal to an injury of the axon or its cell body
-Faster in PNS -Slower in CNS -Results from transection of axons by trauma, inflammation, tumor, etc. -Ends self-seal and swell -Myelin and axons degenerate in segment distal to the transection -Chromatolysis can occur in cell body |
|
Nervous system and Focal lesions
|
-Nervous system is very vulnerable to focal lesions
-Specific nuclei control very specific functions -Location is KEY for impact of a lesion --focal lesion in an important area can be VERY detrimental -Focal lesions are compounded by the exceptionally limited ability of the nervous system to regenerate after injury --no regeneration, injury is very detrimental |
|
Location and distribution of function in the nervous system
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-Location, Location, Location
-Clinical signs are based on LOCATION, not type of lesion or disease -Different diseases affecting the same area of the nervous system will show same clinical signs -Same disease at a different location in the nervous system will show different clinical signs -Clinical signs are based on LOCATION |
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Groups of neurons are selectively vulnerable to different diseases
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-Toxins
-Hereditary abiotrophies -Metabolic diseases -Nutritional deficiencies -Specific diseases Affect specific groups of neurons |
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Response of the Nervous System to Injury
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-Limited and non-specific
-Diagnosis may depend on location or distribution of the lesion instead of microscopic appearance of the lesion -Only so many ways the nervous system can respond to injury |
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Nervous system lesion location
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-Focal
-Multifocal -Diffuse -Involve systems of neurons |
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Unique anatomic and physiologic features of the nervous system
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-Blood-brain barrier
-CSF -Meninges -Skull and vertebral column -Peripheral nervous system -Unique cells of the nervous system |
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Blood-Brain Barrier
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-Maintains homeostasis of the CNS
-Endothelial cells regulate transport, form tight junctions -Epithelial cells of choroid plexus produce CSF -Arachnoid barrier cells -Astrocytes send processes out to areas of Blood Brain Barrier --Recycle neurotransmitters --maintain K concentrations --Modify CNS endothelial cells --Protect neurons from injury |
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Cerebrospinal Fluid
CSF |
-Produced by Choroid plexus
-Circulates in ventricles and subarachnoid space -Functions as a shock absorber -Transports nutrients, wastes, hormones -Does job of lymphatics in rest of the body (no lymphatics in the CNS) -Produced in lateral ventricles and 3rd ventricles, flows into 4th ventricle and spinal cord |
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Meninges
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1. Dura mater: outer tough layer
2. Arachnoid mater: middle lyaer 3. Pia mater: thin, right on top of the brain Arachnoid and pia make leptomeninges |
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Skull and vertebral column
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-Bony structures that protect CNS from trauma
-Impose a limited and fixed volume on the brain case and vertebral canal -Swelling of the CNS due to injury can compress vital centers and blood vessels in CNS --leads to coma and death -Injury → swelling → compression of important centers → death |
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Pathology of focal lesions in the CNS
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-Focal lesion (neoplasm, hemorrhage, inflammation) occupies space with ongoing edema/hemorrhage
-Increases volume of the brain, brain swells --Brain cannot really swell all that much in the limited space of the calvaria -Swelling results in increased intracranial pressure -Only place brain material can go, only hole is the Foramen Magnum --Caudal herniation of the brain through the foramen magnum -Cardiovascular and respiratory centers in the medulla are compressed --important centers for life! -Results in coma and death |
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Biochemical lesions on neurons
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-Will not leave a histological mark
-Specific membrane proteins may be affected -Creates a functional disease without obvious histological structural changes |
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Axonal Injury
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-After trauma, ends of axon self-seal
--lipid bi-layer allows sealing --Ends transport along axon -Anterograde and retrograde axonal flow is halted -Severed ends swell due to accumulations of neurofilaments, mitochondria, and debris -Distal segment undergoes Wallerian degeneration, is removed by macrophages and glial/schwann cells |
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Steps in Axonal Injury
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1. Injury to axon
2. Segments self-seal, transport stops, swelling occurs 3. Distal segment degenerates and is removed |
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Axonal Injury Sequelae
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-Presynaptic terminals move out of synaptic contact while affected neuron is attempting repair
-If site of injury is close to axonal cell body, neuron may die --Regeneration is very limited in CNS --re-growth and reinnervation rarely occur -Anterograde and retrograde transneuronal atrophy may occur |
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Ischemic Nerve cell Change
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-Will result in cell death/necrosis
-Shrunken neurons |
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Axonal degeneration
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-Axonodystrophy, neuroaxonal dystrophy
-Metabolic derangement of the entire neuron -Distal portion of the axon dies back, leads to axonal swellings (spheroids) -Myelin sheath breaks down at same time -Toxin, inherited, nutritional, or metabolic diseases -Metabolism changes the entire neuron -Can see pink spheroids in gray matter histologically |
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Neuronal Loss
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-Irreversible end-stage of pathological process involving neurons
-Can be caused by a variety of insults -Difficult to evaluate if mild, hard to know what was there before -Number of astrocytic nuclei is usually increased |
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Vacuolated neurons
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-Occurs with prion diseases
-BIG vacuoles |
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Neuronal storage diseases
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-Inherited due to deficient activity of lysosomal enzyme
-Progressive disease -Usually occurs in young animals -Accumulation of enzyme substrate leads to loss of neuronal or glial function -Small vacuoles |
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Neuronal Inclusion Bodies
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-Seen in some viral infection
-Canine distemper virus |
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Lipofuscin accumulation
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-Neuronal injury
-Common change in aging brains -Rare in storage diseases -Causes neurological clinical signs |
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Astrocytic Lesions
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-Can undergo hypertrophy, hyperplasia, or degeneration
-Response to neuronal cell death, demyelination, ischemia, edema, inflammation, metabolic and toxic diseases |
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Astrocytic hypertrophy
Astrocytic Hyperplasia |
Hypertrophy
-Manifests as swelling of the cytoplasm -Increase in astrocytic fibers, astrocytic sclerosis -Looks like fibrosis, but is really just astrocytes Hyperplasia -Increase in the number of astrocytes |
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Myelin-producing cells
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-Oligodendroglia in CNS
-Schwann cells in PNS |
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Oligodendroglial Injury
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-Die in response to most insults resulting in the loss of myelin
--demyelination -Will increase around neurons in response to aging or neurophagia --satellitosis |
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Ependymal Lesions
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-Ependymal cells line ventricles in the brain
-Loss or desquamation of ependymal cells can occur with hydrocephalus or ventriculitis -May become hyperplastic in response to inflamamtion |
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Choroid Plexus Lesions
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-Fibrosis of connective tissue stroma
--Occurs with age -Focal masses of cholesterol and inflammatory cells --cholesterol granulomas --occurs in older horses |
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Microglia
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-Antigen-presenting cells in the CNS
-react to injury via hypertrophy and hyperplasia -Macrophages from the blood also enter brain with injury and act as phagocytes --will look like foamy, lipid-laiden macrophages |
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Atropy in the CNS
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-Decrease in size
-Best seen as gross lesions in cerebrum or cerebellum -Can be secondary to hydrocephalus or slowly growing tumors -Histologically looks like loss of neurons and myelin --may or may not have astrocytosis and astrocytic sclerosis also |
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Ventricular dilation in the CNS
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-Hydrocephalus
-Increased volume of CSF in the ventricles -Usually unknown cause --over-production of CSF --Obstruction of CSF flow (most common) --Decreased reabsorption of CSF -With focal or diffuse loss of parenchyma ventricles expand and CSF is formed to fill dilated spaces |
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Asymmetry in the Brain
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-Indicates lesion of some sort!!
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Hemorrhage in the CNS
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-Can occur epidurally, within the dura, subdural, arachnoid, intraparenchymal, or intraventricular
-Trauma, issues with vascular system, inflammation, toxic causes, some sort of deficiency, metabolic disorders, neoplasm -May lead to increased ICP, can lead to death |
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Necrosis of the CNS
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-Malacia (softening)
-Can be liquefactive or coagulative -Acute lesions are grossly discolored and soft -Chronic lesions may be cystic if large -Encephalomalacia is necrosis in the brain -Polioencephalomalacia is necrosis of the grey matter of the brain -Leukoencephalomalacia is necrosis of the white matter of the brain -Myelomalacia is necrosis of the spinal cord --leukomyelomalacia --poliomyelomalacia |
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Edema in the CNS
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-Common with brain issues
-Compresses tissues, causes increased ICP and herniation -Compression looks like clear vacuoles -Vasogenic: increased permeability of CNS capillaries --trauma, hemorrhage, infarcts, inflammation, toxic and metabolic diseases, tumors of CNS -Cytotoxic: cellular swelling --failure of the Na/K pump -Interstitial: obstructive hydrocephalus |
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Tissue lesions in the CNS
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-Spongiosis
-Demyelination -Inflammation -Non-specific vascular lesions -Meningeal lesions |
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Spongiosis
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-Tissue lesion in the CNS
-Vacuoles in the grey matter are Spongiform encephalopathies -Vacuoles in the white matter are between myelin lamellae --toxic and metabolic diseases -Can look similar to edema |
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Demyelination
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-Tissue lesion in CNS
-Loss of myelin can be detected by lack of staining using luxol-blue myelin stain -Caused by damage to oligodendrocytes in CNS or schwann cells in PNS --myelin producing cells are damaged -Remyelination is very poor in CNS, usually successful in PNS --schwann cells can regenerate and remyelinate, each cell only interacts with one internode on a single axon --Oligodendrocytes myelinate 1-50 internodes on 1 or many axons |
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Inflammation in the CNS
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-Local or disseminated infiltrates of inflammatory cells with perivascular cuffs, vascular dilation, and edema
-Often due to infectious agents -Can also occur after trauma, infarcts, or secondary to neoplasms -Is often idiopathic -Pachymeningitis, FIP, toxoplasma gondii |
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Pachymeningitis
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-Inflammation involves the dura mater
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Feline Infectious Peritonitis in the CNS
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-Causes inflammation in the brain
-Damages blood vessels to cause inflammation -Monocytes are brought into tissues -Causes unique lesions in the brain, type of damage is indicative of the virus -No inclusion bodies |
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Non-specific vascular lesions in the CNS
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-Ischemia
-Hypoxia -Metabolic disorders -Inflammatory disorders -Result in capillary proliferation with endothelial cell hypertrophy |
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Cellular Lesions of the PNS
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-Wallerian degeneration (usually after traumatic injury)
--axon is transected -Segmental demyelination --axon remains intact --schwann cells can regenerate -Axonal degeneration --Swelling of axon, loss of axon and myelin sheath --axonodystrophy --neuroaxonaldystrophy |
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Wallerian degeneration in PNS
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-Schwann cell proliferation occurs distally inside tubes of schwann cell basement membrane
-Axonal sprouts appear proximally at site of transection -Axonal sprouts follow Schwann cells to former synapse -Muscle undergoes denervation atrophy if motor nerves are severeed -If muscle is reinervated, enlargement of motor units may occur --fiber type grouping |
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Wallerian Degeneration Steps
PNS |
1. Injury and initial reaction (24 hours)
2. Macrophages are recruited, Wallerian degeneration starts (1 week) 3. Schwann cells are aligned and axons are regenerated (weeks to months) --schwann cells proliferate and guide axon back to the muscle 4. Successful target reinnervation (weeks to years) |
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Wallerian Degeneration Outcome
PNS |
-Successful regeneration in PNS depends on 3 factors
1. Site of injury: more distal lesions have better recovery 2. Distance between severed ends: closer is better recovery 3. Amount of damage and debris at the injury site: less injury and debris leads to better recovery If regeneration is unsuccessful, neuroma may develop --small painful nodule of axons and Schwann cells |
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Segmental Demyelination
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-Destruction of Myelin sheaths, leaving intact bare neuron
-Internode or segment is lost -Results in conduction block or slowing of nerve impulse -Schwann cells can proliferate, remyelination is usually complete -Usually associated with inflammatory or toxic diseases |
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Axonal Degeneration
Axonodystrophy |
-Metabolic derangement of the entire neuron
-Leads to dying back of the distal portion of the axon -Myelin sheath breaks down at the same time -regeneration is poor -Associated with toxic, inherited, and metabolic diseases -Inherent issue with a neuron |
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Congenital Malformations of the Nervous System
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-Genetic or environmental factors
-Can be individual factors or interacting factors -Most spontaneous malformations are idiopathic -Nervous system has numerous precisely-timed developmental steps --Critical part of determining the type and severity of a malformation is time of gestation when destructive agent acts on nervous system |
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Neurulation
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-Formation of the neural tube
-Neural plate is formed first -Neural groove forms from the neural plate -Neural tube closes in middle of tube and extends cranially and caudally --Rostral neural tube develops into the brain --Rest of neural tube becomes the spinal cord |
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Meningocele
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-Limited failure of neural tube closure with meninges under the skin
-Section of neural tube fails to close, meninges also fail to close |
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Mechanisms of Hydrocephalus
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1. Oversecretion of CSF (rare)
2. Obstruction of CSF flow (common) -can be congenital or acquired -Congenital blockages can be due to malformations of the mesencephalic aqueduct -Acquired blockages are due to neoplasms, inflammation, astrocytic sclerosis 3. Impaired absorption of CSF (rare) |
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Traumatic diseases of the Nervous System
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-Fractures
-Hemorrhage -Edema -Contusion (bruising) -Concussion -Luxation and ssubluxation of vertebrae -Infarction secondary to vascular compression, occlusion, or rupture |
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Consequences of Trauma to the Nervous system
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-Increased ICP
--leads to cerebellar herniation and compression of the medullary respiratory and cardiovascular centers, leads to death -Infection of open injuries -Scar formation --leads to post-traumatic seizures --glial scars cause abnormal electrical function in brain -Wallerian degeneration of severed axons --can have regeneration depending on severity and location |
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Intervertebral Disks
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-Discs are composed of Nucleus pulposus (gelatinous watery substance)
-Nucleus pulposus is surrounded by Annulus fibrosus (concentric fibrous lamellae) |
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Types of Intervertebral disk disease
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1. Herniation: extrusion of the nucleus pulposus through a tear in the annulus fibrosus
-Hansen's Type I 2. Protrusion: annulus fibrosus bulges into the spinal canal -Hansen's type II |
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Intervertebral Disc Disease
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-Occur in Cervical or thoracolumbar area
--T13-L1 are especially vulnerable -Clinical signs and lesions depend on: --direction (dorsal, ventral, lateral, etc.) --Size or volume, determines degree of compression --Speed (slow vs. explosive) --Spinal cord location --duration until recovery from edema or hemorrhage (shorter duration is better) |
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Pathogenesis of Intervertebral Disc Disease
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1. Nucleus pulposus degenerates with age
--earliest lesion in chondrodystrophic dogs 2. Degeneration leads to protrusion or herniation of nucleus pulposus through damaged annulus fibrosus --earliest lesion in non-chondrodystrophic dogs --annulus fibrosus is damaged 1st 3. Direct compression of the spinal cord and/or nerve roots and spinal vessels --causes hemorrhage and necrosis |
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Sequelae of intervertebral Disc disease
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-Demyelination is least severe
--damage to schwann cells, can regenerate -Leukomyelomalacia is more severe -Edema and hemorrhage is more severe -Poliomyelomalacia is MOST severe --necrosis of gray matter on inside of the spinal cord -Occasionally a syndrome of ascending myelomalacia occurs following severe disc disease |
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Ascending Myelomalacia
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-Huge area of necrosis that ascends
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Vertebral Malformations
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-Lead to compression of the spinal cord
-Due to narrowing of the spinal canal (stenosis) -Hemivertebrae: wedge-shaped vertebrae -Cervical vertebral malformation and malarticulation in large dogs -Cervical stenotic myelopathy (wobbler horses) -Lumbosacral stenosis (cauda equina syndrome) |
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Neurovascular Disease
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-Hypoxia: deprivation of Oxygen, blood flow is maintained
--issue is with O2, not delivery --Usually respiratory disease -Ischemia: blood flow is severely reduced or completely obstructed --directly related to blood flow -Hemorrhage -Infarct: focal brain necrosis that follows obstruction of blood flow --associated with cuterebra larva migration in cats --Septic neoplastic emboli in dogs (bacteria and tumors) --Fibrocartilagenous emboli -Early infarcts may just be hemorrhage, chronicity will lead to loss of tissue |
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Diagnosing Neural Disease
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-Need a FULL history!
-Same gross appearance of clinical signs can be caused by different processes |
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Fibrcartilagenous Emboli in the Neural System
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-Unknown pathogenesis
--Intervertebral disc material? -Occurs in dogs and pigs -Often a history of excessive exercise -Acute onset of clinical signs -Clinical signs depend on site of embolization -Myelomalacia results -Disc emboli can be identified with toluidine blue stains --in veins and arteries |
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Pathogenesis of Fibrocartilagenous Emboli in the Nervous system
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-Intervertebral disc emboli leads to occlusion of small blood vessels
-Infarct occurs, causes necrosis -Macrophages from the blood are recruited to remove necrotic debris |
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Infectious Organism entry into the Nervous System
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1. Blood: crosses blood brain barrier
--most common route --can enter within macrophages or on own if small enough 2. Local extension: areas near the brain get infected and infection spreads --frontal sinusitis, discospondylitis, otitis interna --usually bacterial and suppurative 3. Direct penetration: usually due to trauma --fractures, bite wounds, surgical procedures 4. Retrograde axonal flow: from peripheral infection into the CNS --rabies virus, herpesvirus, listeria monocytogenes --tetanus neurotoxin |
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Viral disease in Nervous System
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-Destruction of nerve cell bodies with or without neuronophagia
--Kills neurons -Locally disseminated perivascular cuffs --usually lumphocytes and plasma cells -Inclusion bodies, intranuclear or intracytoplasmic -Microglial proliferation -Inflammation in the ventricles is atypical with viral diseases |
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Rabies virus in the Nervous system
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-Will see inclusion bodies in neurons
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Canine Distemper Virus in the Nervous System
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-Will see inflammation and necrosis
-May have encephalitis -Nuclear and cytoplasmic inclusion bodies |
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Bacterial infection in the Nervous System
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-Rarely primary infection, usually there is another focus of infection
-Usually suppurative exudate --many neutrophils and macrophages -Often will get extensive necrosis with or without abscesses -Young animals are likely to have bacterial meningoencephalitis secondary to bacteremia/septicemia -Space-occupying abscesses will increase ICP and lead to compression of the medulla --Will have TONS of neutrophils |
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Suppurative Ventriculitis
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-Pus in the ventricles
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Suppurative meningitis
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-Pus in the meninges
-May have pockets of pus in the leptomeninges |
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Parasitic Infections of the Nervous System
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-Usually necrotizing with secondary inflammation
-Need to look for underlying agent |
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Neospora caninum in CNS
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-Will get blood vessels with perivascular cuffs
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Fungal infections in the Nervous System
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-Usually granulomatous inflammation
-Usually in multiple sites in the brain and other tissues --can occur throughout the body |
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Cryptococcus neoformans in the brain
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-Soap bubble exudate in the parenchyma
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Prions
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-Cause spongiform encephalopathies in the brain
-Bovine, sheep, and mink encephalopathies -Cause neuronal vacuolation |
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Necrotizing Encephalitis
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-Big areas of edema
-No distinction between white and gray matter -Loss of symmetry in the brain -Looks similar to an inflammatory disease |
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Granulomatous meningoencephalitis
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-Big areas with lots of macrophages
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Demyelination
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1. direct effect on oligodendrocytes or Schwann cells and myelin
-Damage to myelin-producing cells -Can be viral or toxins 2. Following Wallerian degeneration or axonodystrophy -Axon is injured, myelin is injured with the axon Remyelination may be complete in the PNS Limited remyelination can occur in the CNS |
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Leukodystrophies
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-Abnormal myelin formation, maintenance, or destruction
-Loss of white matter -Histologically white matter can be darker or lighter than it should be -Most are inherited disorders due to enzyme deficiencies -Macrophages eat/digest myelin |
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Fusarium and the CNS
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-From moldy corn
-Can lead to huge cavities in the white matter of the brain -Leukoencephalomalacia |
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Penetren
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-Moldy yogurt
-Lead to polioencephalomalacia -Targets basal ganglia |
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Polioencephalomalacia in Ruminants
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-Can be caused by a thiamine deficiency
-Thiaminase producing bacteria in the rumen destroy thiamine -Will have a think amount of grey matter over the corona radiata in the cerebrum -Pseudolaminar necrosis of the cerebral cortex -Distribution helps with the diagnosis -Metabolites fluoresce with UV light |
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Copper deficiency and Leukoencephalomalacia
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-Occurs in sheep, deer, goats, pigs, elk
-degeneration of white matter involving specific tracts -Molybdenum excess often leads to a relative copper deficiency -Cavities are left where the white matter should be, looks like an "empty brain" |
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Acute Neuronal Necrosis
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-Caused by hypocalcemia or ischemia, toxins, infections
-May also be due to a metabolic disease -Neurons appear angular, surrounded by white space --nuclei are lost --"Kite-shaped" angular neurons |
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Neuronal Storage Diseases
Gangliosidosis |
-Accumulations of uncatabolized material within neurons or glia
-Material may be exogenous, due to plant poisoning -Endogenous, due to lysosomal enzyme deficiency -Named by the substance that accumulates --gangliosides --sphingomyelin --glucocerebrosides -Usually due to an enzyme deficiency and buildup within the neuron -Histologically may see vacuoles accumulating within the neuron --impair function |
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Neuronal Degenerative Diseases
Cerebellum |
-Cerebellar degeneration/atrophy/abiotrophy
-May result in dysfunction of voluntary movement and posture -Can have Purkinje cell loss --astrocytes proliferate to fill in space -May also have loss of granular layer cells and astrogliosis -Have normal development, then degeneration and atrophy occurs -Cerebellum will look small |
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Neuronal Degenerative Diseases
Spinal Cord |
-Loss of myelin and then axons from specific zones or tracts
--White matter tracts -Eventually lose axons, over time -Ex: canine degenerative myelopathy, equine degenerative myelopathy -Looks like dilated myelin sheaths -Swollen axons |
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Lower Motor Neuron Diseases
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Neuronal Degenerative Disease
-canines will have degeneration of ventral horn cells -equine lower motor neuron disease -Glassy material accumulates in the neuron --change in protein production in the neuron |
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Neoplasms in the Nervous System
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-Neoplasms originating in the nervous system are common
-Neoplasms of embryonal remnants are rare -Neoplasms of the skull and vertebral column are common --do not arise in the CNS but compress the CNS -Metastatic/secondary neoplasms in the CNS are common -Neoplasia displaces normal parenchyma --leads to ischemia, necrosis, gliosis, secondary inflammation -Causes increase in ICP -Can also cause hydrocephalus by blocking flow of CSF -Eventually space-occupying masses lead to herniation of the cerebellum and medulla and death -Are non-specific lesions |
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Clinical signs of Neural system Neoplasia
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-Depends on localization, size, rate of growth, and secondary vascular lesions
-Can cause many different clinical signs, depending on location -Loss of function of specific tracts and nuclei --blindness (optic nerves) --Head tilt (vestibular areas) --endocrine abnormalities (pituitary area up into thalamus) --Ataxia (ascending proprioceptive tracts in spinal cord, cerebellum) --Weakness (descending motor tracts) -Seizures (hippocampus or cerebral cortex) -Coma and death (medulla) |
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Suprasellar germ cell tumor
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-Compresses the optic tract and leads to blindness
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Pituitary carcinoma
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-2 different tumors can occur in same location that will have same clinical signs
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Types of Primary Neoplasms in the CNS
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1. Glial tumors
--astrocytoma, oligodendroglioma, ependymomas, glioblasstoma multiforme, glioma, mixed gliomas, gliomatosis cerebri --COMMON, most common type of neural neoplasm 2. Choroid plexus timors --Adenoma, carcinoma --common 3. Primitive neuroectodermal tumors 4. Meningiomas --common but easy to get rid of because they are on the surface 5. Nerve sheath tumors --in spinal cord, common 6. Pituitary tumors --adenoma, carcinoma --common |
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Glial Tumors
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-Astrocytoma
-Oligodendrogliomas -Glioblastoma multiforme |
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Astrocytoma
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-Glial tumor
-Very destructive space-occupying mass -Diffusely infiltrative -Destroy the normal architecture of the site -Can involve the cerebral hemisphere, brainstem, or spinal cord |
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Oligodendrogliomas
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-Glial tumor
-Most frequently involve a cerebral hemisphere, especially in the periventricular site -Can cause extensive compression -Soft, mucinous consistency -May be hemorrhagic -IN the dog, prominent endothelial proliferations create glomerular-like formations |
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Glioblastoma multiforme
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-Glial tumor
-Common in humans -Anaplastic glial tumors -Typically found as palisades of neoplastic cells surrounding necrotic foci -Vascular proliferations are common |
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Meningiomas
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-Originate from the cells of the arachnoid
-Can occur in spinal column -In the Dog can cause variety of clinical signs depending on location --frequently infiltrates the adjacent brain parenchyma, sends tendrils into parenchyma --Infiltration makes complete surgical removal difficult -In Cats can produce clinical signs and can also be silent --3rd ventricle is a common site without any signs --Usually do not infiltrate brain parenchyma |
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Classification of Meningiomas
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-Classifications have little biological significance
-Meningotheliomatous (syncytial) -Fibrous (fibroblastic) -Transitional (mixed) -Psammomatous -Angiomatous (angioblastic) -Papillary -Granular cell -Microcystic -Myxoid (choroid) -Atypical -Anaplastic (malignant) |
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Choroid Plexus Tumors
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-Papillary mass within the ventricles
-Commonly infiltrates into the subarachnoid space --causes extensive meningeal metastasis, especially in the spinal cord -Infiltrates adjacent parenchyma |
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Other primary tumors and cysts of the nervous system
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-Vascular hamartoma
-Epidermoid cyst, lined by stratified squamous epithelium -Pituitary cyst |
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Vascular hamartoma in the Nervous System
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-Need to look histologically to know what it is
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Metastatic tumors to the Nervous System
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-Hemangiosarcoma (dog)
-Carcinomas (dogs and cats) -Lymphosarcoma (dog and cat) --sometimes only occurs in the nervous system -Histiocytic sarcoma --sometimes only occurs in the nervous system -Many others are less common |
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Neoplasms of the skull and vertebral column
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-Osteosarcoma, osteoma
-Chondrosarcoma, chondroma -Multilobular tumor of bone -Synovial myxoma -Multiple myeloma -Nasal carcinoma -Olfactory neuroblastoma -Metastatic prostatic carcinomas All cause clinical signs of nervous system disease |
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Tumors of the PNS
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-Nerve sheath tumor
--Schwannoma, neurofiibroma (benign) --Malignant Schwannoma, neurofibrosarcoma (malignant) -Ganglioneuroma -Peripheral neuroblastoma -Paraganglioma |
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Malignant Nerve Sheath Tumors
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-Common in the dog
-Nodular masses or varicose thickenings of the cranial and spinal roots, peripheral nerve trunks, or nerves -Poor prognosis -Highly invasive, often extend up the nerves to the spinal roots and spinal cord -recur often -Often involve different nerve roots |
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Upper Airway Anatomy
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-Nasal passages, nares, turbinates, ethmoid
-Nasopharynx and auditory tube -Larynx, covered by squamous mucosa -Sinuses and paranasal recesses (outpouchings of nasal cavity) -Lymphoid tissue --increases with caudal progression in the head --abundant in young animals --Occasionally misinterpreted as pathological findings |
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Upper Airway Layout
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-Nares → turbinates → (Paranasal sinuses) → Ethmoid → Nasopharynx → (epiglottis) → laryngopharynx → larynx
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Particulates in the Larynx
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-Material below the larynx is swallowed
-Material above the larynx is coughed up into the nares |
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Lower Airway Anatomy
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-Trachea and Lungs
-Primary, secondary, tertiary bronchi |
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Carina
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-Bifurcation of the primary bronchi
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Accessory Bronchus
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-On right side
-Cranial to tracheal bifurcation -Only exists in ruminants and pigs |
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BALT
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-Bronchus-associated Lymphoid Tissue
-Secretes IgA |
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Bronchi
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-Have full or partial ring of cartilage for support
-Smooth muscle -Glands and BALT |
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Clara cells
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-Cuboidal, non-ciliated cells in the respiratory tract
-Transform xenobiotics -Have rich oxidative enzyme system -Produce P450 enzyme --can create toxic metabolites in certain circumstances |
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Bronchial gland Secretions
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-Mixture of serous and mucous cells
-Create sol-gel blanket of the mucociliary escalator |
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Upper Airway Passages
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-Large surface area
-Humidify and equilibrate temperature of inhaled air -Stop and clear particulates more than 10 microns --filter out particulate matter -Serous and mucous secretions -Neutralizes pathogens via abundant lymphoid tissue --location, size, and quantity of lymphoid tissue varies by species -Pseudostratified ciliated columnar epithelium |
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Bronchioli
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-Smooth muscle only, no cartilage
-Clara cells with metabolic and progenitor activity -No goblet cells |
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Secretions of Lower Airway
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-Bronchial gland secretions
-Serous and mucoid secretions -Serous layer on cilia and within cilia layer -Mucus layer above forms solid gel layer -Cilia move and bend in a unified direction -Lactoferrin binds available iron and prevents bacteria from using iron -Secretory IgA from BALT |
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Cells in the Alveoli
|
-Type I pneumocytes
-Type II pneumocytes -Type III pneumocytes -Alveolar macrophages -Alveolar septum: capillary, basement membrane, and type I pneumocyte on both sides |
|
Alveolar septum
|
-Capillary
--mostly made up of capillary -Basement membrane collagen matrix -Thin wall is critical for gas exchange -Type I pneumocytes on both sides |
|
Type I pneumocytes
|
-Membranous cells
-Make up 97% of the acinar surface -Line both sides of the alveolar septum -0.2 microns thick, not visible to light microscope -Barrier function only -Few organelles in the cytoplasm -Few defense mechanisms |
|
Type II pneumocytes
|
-Granular cells
-Produce phospholipid surfactants -Progenitor cells, Can replace type I pneumocytes -Hard to find on microscopy |
|
Alveolar macrophages
|
-Prowl the alveolar lumen
-AKA Pulmonary Alveolar Macrophage (PAM) |
|
Lower Airway
|
-Non-collapsing unit
-Allows for uniform distribution of air -Lumen diameter is controlled via smooth muscle -Ciliated columnar epithelium predominates -Stops particulates and noxious gasses -Gel-sol matrix has fluid motion towards the larynx --effluent is expelled by swallowing |
|
Antiprotease
|
-Alpha-1-antitrypsin
-Protects airway epithelium from action of neutrophils and body's immune response |
|
Lactoferrin
|
-Airway secretion
-Binds to free iron -Prevents bacteria from using free iron |
|
Avian respiratory tract
|
-Mucosa makes pockets of mucus and serous secreting glands
|
|
Surfactant
|
-Bilayer of plasma filtrate and phospholipid
-Phosphatidylcholine and Phosphatidylglycerol predominate -Surfactant proteins A-D opsonize pathogens -Decreases surface tension -Decreases capillary leakiness -Keeps alveoli from sticking to each other --"anti-cling" material -Layers of phosphatidylcholine |
|
Pulmonary Vasculature
|
-Dual blood supply
-Receives 100% of deoxygenated cardiac output --pulmonary -Receives basically 100% cardiac output from bronchial artery from Aorta -Upper airway is extremely rich with blood vessels -Lymphatic vessels run along airways --Do not extend to alveolar septa -Intravascular macrophages |
|
Pulmonary Intravascular Macrophages
|
-Lung equivalent of the Kupffer cell
-Pinocytosis, phagocytosis, and toxin neutralization -Important Antigen-presenting Cell -Mobile, move around in the lungs -Ruminants, pigs, and cats all have PIMs |
|
Particulates in the Airway
|
-Nasal turbinates create turbulence, particulates impact the seromucus secretions
-Larger particles are arrested in upper airway --expelled with seromucinous secretions -Smaller particles trapped in lower airways --Sol-gel of mucociliary escalator --particles are deposited at the larynx and swallowed -Deposition of particles is a function of size, shape, density, electrical charge, and air velocity -Particulates 0.5-2 microns have potential for impacting alveolus -Air velocity decreases as airway gets smaller --increases effect of gravity on particulate matter |
|
Fetal Lungs
|
-Lungs are non-functional in-utero
--need to be ready to go right at birth, need initial expansion and surfactant on the surface -Blood is shunted from the right side to the left side of the heart via ductus arteriosus -Alveoli are fully collapsed (atelectatic) -Fetal lungs are diffusely purple, rubbery and moist -Sink in water |
|
Squames
|
-Shed squamous epithelial particles in fetal lungs
-Normal finding -Not dangerous to the neonate |
|
Fetal Pneumonia
|
-Occurs from bacterial placentitis or viral infection in the placenta
-Usually results in Abortion -Bacteria can cross fetal membranes, gets into lungs -Will have lots of PMNs |
|
Meconium aspiration
|
-Due to hypoxia in fetus leading to stress
-Hypoxia stimulates fetal gasping and intestinal hypermotility --anal sphincter relaxes -Fetus has bowl movement, meconium is in amnion --can aspirate meconium during parturition -Will turn lung yellow, especially with slow release of meconium -Meconium itself is sterlile and does not cause pneumonia -Predisposes animal to post-natal micro-ciliary diseases |
|
Atelectasis
|
-Non-formed lumen that would normally be formed
-Fetal lungs are atelectatic -NOT the same thing as normal lung recoil -If fetal lung is partially inflated at birth can tell histologically |
|
Fetal Surfactant
|
-Needs to be present and ready to function as soon as animal takes first breath
-Premature neonates have surfactant deficiency -Deficiency leads to atelectasis and hyaline membrane disease -Neonatal respiratory Distress Sydrome |
|
Neonatal Respiratory Distress Syndrome
|
-No surfactant or not enough surfactant at birth
|
|
Avian Respiratory Tract
|
-Highly efficient system, most efficient among air-breathing vertebrates
-2 chambered system -Unidirectional air flow -Minimal lung excursion, do not move around a lot -Lung volume is static -Air sacs function like bellows --covered by squamous epithelium and ciliated cells --common site for bacterial and fungal infections -Secondary bronchi → Tertiary bronchi (parabronchi) → air capillaries (alveoli) -Tertiary distribute air to air capillary for gas exchange |
|
Air Capillaries
|
-Avian equivalent of alveoli
-5-15 micron diameter lumen |
|
Reptilian lungs
|
-Anatomically and functionally similar to avian lungs
|
|
Upper Airway Structural Pathology
|
-Nasofacial deformities:
--cleft palate (Palatoschisis --wry nose --Brachygnathia superior -Brachycephalic airway syndrome -Choanal atresia -Hypoplastic epiglottis |
|
Brachycephalic Airway Syndrome
|
-Stenotic nares
-Elongated palate -Laryngeal deformation, saccule eversion -Cartilage defects to the larynx |
|
Choanal Atresia
|
-Choanal membrane is not fully open
-Bony plate Membrane remains between nasopharynx and oropharynx --should rupture and be fully open at birth -Birth defect -Fatal if complete atresia -Bony plate separates oropharynx from nasopharynx -Occurs mostly in camelids and horses |
|
Hypoplastic Epiglottis
|
-Leads to soft palate displacement
-Frequent in horses |
|
Palatoschisis
|
-Cleft Palate
-Predisposes animal to aspiration pneumonia -Variable midline defect of hard and/or soft palate -LOTS of variation --can be superficial, multifocal |
|
Acute Inflammatory Response of the Lungs
|
-get secretions
-Serous secretion: triggered by cold weather -Mucoid secretion: increase in goblet cells -Fibrinous exudate: indicative of vascular injury -Purulent/suppurative exudate -Diphtheritic membrane formation |
|
Diphtheritic Membrane
|
-Mixture of dead tissue and exudate
-Dead membrane tissue and fibrinous purulent exudate -Semi-rigid scab-like material -Sloughed mucosa mixed with fibrin and neutrophils -Indicative of tissue necrosis and sever mucosal injury |
|
Serous Exudate
|
-Watery fluid
-Indicative of mild injury -Consists of plasma filtrates and increased serous cell secretions -Low concentration of leukocytes |
|
Fibrinous Exudate
|
-White granular to yellow spongy material
-Indicative of vascular injury -Fibrinogen polymerized to fibrin -Chemoattractant for Neutrophils |
|
Catarrhal Exudate
|
-Mucoid material
-Due to incresed secretions by serous and mucus cells -Will be slightly cloudy due to small amounts of fibrin and neutrophils |
|
Purulent/Suppurative exudate
|
-Thick, tan, yellow, green fluid
-Due to large numbers of neutrophils -Indicative of significant injury from released neutrophil enzymes |
|
Sinus Empyema
|
-Pus-filled cavity
|
|
Otitis Media
|
-ear is an Extension of respiratory system via eustacian tube
-infections ascend up the tube to the middle ear |
|
Signs of Chronic Inflammation in the Respiratory System
|
-Goblet cell hyperplasia, leads to increased mucus production
-Squamous metaplasia, increased in undifferentiated cells --decrease in ciliated cells -Ulcer formation -Granulation tissue, can mature to fibrous connective tissue -Lymphoid Hyperplasia -Polyp formation |
|
Polyp formation in the Respiratory tract
|
-Loos construction of granulation tissue
-Result of chronic inflammation -May result from small ulcers -Occlude the nasal passage -Animal will not be able to breathe well -Most often seen in horses and cats -Sometimes originates in the auditory tube of the cat |
|
Granulation tissue in the Respiratory System
|
-Sign of chronic inflammation
-Granulation tissue matures to fibrous connective tissue -Occurs with chronic ulceration of the mucosa -Can seal openings to sinuses, exacerbating the problem |
|
Causes of Rhinitis, sinusitis, laryngitis
|
-Particulates: feed, soil, dust
-Microorganisms: bacteria, fungi, yeast, viruses --Fungal and yeast microorganisms can cause granulomatous inflammation -Trauma: balling gun, endotracheal tube irritation, nasogastric tube irritation -Dental Disease |
|
Atrophic Rhinitis of Pigs
|
-Pasturella multocida (A and D)
-Impair osteoblast function -Causes deformed and atrophic turbinates -Results in too much space between nasal turbinates -Larger material can get down deep into respiratory tract -Predisposes animal to respiratory infections -Will have increased frequency with confinement --CAFOs |
|
Causes of Chronic Irritation in the respiratory System
|
-Persistent infections
-Mechanical irritation --dust --increased load on mucociliary elevator -Direct injury -Dental disease |
|
Dental Disease and Respiratory Issues
|
-Can lead to inflammatory processes in sinuses or nasal cavity
-Lost teeth can result in oronasal fistula --space becomes impacted with feed material --"Old animal thing" |
|
Common Upper Respiratory system Neoplasms
|
-Squamous Cell Carcinoma
-Nasal carcinomas and adenomas --can be disguised due to desmoplastic tissue -Sarcomas -Ethmoid hematoma of horses |
|
Ethmoid Hematoma in Horses
|
-Common upper respiratory quasi-neoplasm
-Will have a foul odor -Horse will bleed out of the nose -Uneven air flow -May result in bone deformation also -May originate in the sinus, not ethmoid -Can tell vs. polyp because it will have multi-nucleated giant cells |
|
Epistaxis
|
-Nose bleed, hemorrhage from the nares
-ALWAYS needs to be investigated -Can be due to trauma -Erosive infections -Necrotic neoplasms -Clotting disorders --thrombocytopenia --DIC --anticoagulant poisoning -Have to identify if bleeding is from pulmonary origin vs. nares |
|
Laryngeal Pathology
|
-Edema
-Trauma --should heal rapidly --also allows exposure to bacteria -Infection -Hemiplegia |
|
Laryngeal Hemiplegia
|
-Neurogenic atrophy of the cricoarytenoideus muscles
-Very common incidental finding -Inability to abduct the corniculate process -Usually injury to left recurrent laryngeal nerve -Causes denervation atrophy of the cricoarytenoideus dorsalis muscle -Leads to "roaring" in horses --almost always on the left side -Can also happen in old large-breed dogs (idiopathic) -Genetic in juvenile dogs -Animal cannot get full gas exchange in lungs |
|
Hypoplastic Epiglottis
|
-Epiglottis is too small
-Leads to ventral displacement and membranous entrapment |
|
Tracheal Conditions
|
-Froth and Foam
-Infectious Diseases -Trauma -Hypoplasia |
|
Tracheal Dysplasia
|
-Dorsoventral flattening with widening of the tracheal ligament
--Lumen area is reduced -Tracheal ligament is elongated -Results in abnormal cartilage matrix -Tracheal ring cartilage is weak and abnormal in shape and composition -Common in small toy dogs -Universal in miniature horses -Will have recurring episodes of honking, tracheal irritation, and hypoxia -Can sometimes initiate tracheal collapse via palpation |
|
Froth and Foam
|
-Post-mortem finding
-Small volume is normal, due to gentle collapse of the lungs -Large volume is due to pulmonary edema |
|
Tracheal Infectious Diseases
|
-Laryngotracheitis of chickens
-May result in diphtheritic membranes or fungal plaques |
|
Tracheal Trauma
|
-Dog fights and bites can result in tracheal cartilagenous injury
-Inflammatory process in trachea runs along the dascial plane, can cause pneumothorax -Will get healing with fibrocartilage -Angular deformity -Iatrogenic trauma with inflating endotracheal cuff that isn't the right size -Tracheal tubes are direct conduits for large particles and bacteria --Easily clogged with stuff from muco-ciliary elevator -Cartilage will not really repair fully |
|
Tracheal Hypoplasia
|
-English bulldogs
|
|
Tracheal Dysplasia in Ruminants
|
-Scabbard trachea
|
|
Antemortem inspection techniques for the lungs
|
-Ascultation
-Radiograph -Ultrasound -Cytology -Biopsy --dangerous, causes bleeding -Tracheal Lavage/wash |
|
Postmortem Inspection of the Lungs
|
1. Look for pleural Vacuum
-remove abdominal viscera first 2. Collapse of pulmonary parenchyma 3. Coloration 4. Texture (depends on species) --Collect samples before palpating! 5. Parenchymal sectioning |
|
Pneumonia Patterns
|
1. Focal: spots uniform size in all lung lobes
2. Lobular: 3. Lobar: specific pattern of foci, may affect whole lobes 4. Diffuse: entire lung is affected |
|
Bronchopneumonia
|
-Most common pattern of pneumonia in animals
-Caused by inhalation of aerosols that deposit bacterial particulates in airways -Inflammation centers on bronchi and bronchioles -Inflammatory exudates spill into alveoli -Typically cranioventral pattern of lung injury --easy to diagnose on gross examination --"Line of Life" -Affected portions are firm due to alveoli consolidation -Discoloration -Lung sections will sink in water -May have an odor due to infectious stuff |
|
Lobar bronchopneumonia
|
-Pneumonia affecting entire lung lobes
-Will look like a bloody, meaty, firm lung or may look juicy -Spillover fibrin and neutrophils from alveoli -Airway is FILLED with neutrophils -Will be able to see exudate in bronchiole lumen |
|
Categories of Pneumonia
|
1. Bronchopneumonia: airway-oriented pattern
-most common pattern 2. Interstitial pneumonia: hematogenous delivery at alveolus level 3. Embolic pneumonia: focal patterns 4. Granulomatous pneumonia: pus -consider possibility of neoplasms and metastatic disease 5. Bronchointerstitial penumonia |
|
Common bacteria causing bronchopneumonia
|
-Rhodococcus equi
-Foal bronchopneumonia -Pasteurellacea -Mannheimia, Pasteurella, Actinobacillus, histophilus |
|
Bovine Mycoplasmosis
|
-Cranioventral pattern of white nodules
-Bronchopneumonia -Re-emerging bug |
|
Actinobacillus pleuropneumonia
|
-Occurs in pigs
-Important in market-weight pigs -Will see patches of affected tissue in all lung fields |
|
Interstitial Pneumonia
|
-All lung fields are affected (diffuse pattern)
-Lung fails to fully collapse -Lung will have rib impressions after release of pleural vacuum -Spotty to uniform discoloration in lung -Nonhomogemous or diffusely rubbery feel to lung -Etiologic agents enter via blood -Injury is focused on the alveolus -Type I pneumocytes are destroyed -Repair occurs by type II pneumocyte proliferation --may see many type II pneumocytes histologically -Will not cause inflammatory exudates to fill airways -Microscopic evaluation is needed to confirm Dx |
|
Embolic Pneumonia
|
-Caused by hematogenous dissemination of bacteria, protozoa, fungi, or septic emboli
-Widespread pattern of nodules, usually of UNIFORM SIZE --Dispersed foci -Microscopically will see acute to chronic abscesses or granulomas -Most examples are grossly obvious -May appear hemorrhagic, necrotic, suppurative, or have thrombosis |
|
Streptococcus Equi
|
-Causes embolic pneumonia
|
|
Duck embolic pneumonia
|
-Usually due to fungal embolism
-Establishes in air sacs -Can see fungi on histology |
|
Bronchointerstitial Pneumonia
|
-Injury to airway epithelium and injury to alveolus
-Requires microscopic Dx -Cannot speculate Dx based on gross appearance -Gross pattern is variable --Often lobular -Associated with systemic viral infections --paramyxoviruses |
|
Granulomatous Pneumonia
|
-Caused by aerogenous or hematogenous distribution of etiologic agent
-Can be caused by fungi, mycobacteria, foreign body, etc. -Nodular pattern -Chronic process -Composed of macrophages, giant cells, lymphocytes, neutrophils -Neoplasms can minic granulomas, differential Dx -Microscopic evalulation is needed to confirm Dx |
|
Lung response to Chronic Injury
|
-Abscesses and fibrosis, leading to scarring
--Destruction of native tissue --Evacuation and replacement -Interstitial leukocytic infiltrates -Type II pneumocyte proliferation --indication of interstitial pneumonia -Epithelial metaplasia -Bronchioalveolar cell hyperplasia --can look like type II pneumocytes -Bronchiectasis and bronchiolitis obliterans --atelectasis of surrounding parenchyma -repair process can collapse airway or expand airway |
|
Chronic Responses to Lung Injury
|
-Fibrosis
-BALT hyperplasia with follicle formation -Type II pneumocyte hyperplasia --interstitial and bronchopneumonia -Bronchiolar epithelium hyperplasia -Bronchiectasis (expansion of bronchiole lumen) -Bronchiolitis obliterans (fibrous occlusion of the bronchiole lumen) -Atelectasis due to obstructed airway |
|
Bronchiolitis Obliterans
|
-Chronic Bronchiopneumonia
-Lung parenchyma is collapsing -Bronchiole is occluded -Granulation tissue starts to obliterate lumen |
|
Synergistic Effects of Bacteria in the lungs
|
-Primary lung injury leads to secondary agents of infection
-Mild respiratory viruses set the sage for pathogenic bacteria -Viruses throw off immunologic balance, bacteria can go rampant - |
|
Lymphadenitis
|
-Mediastinal and tracheobronchial lymph nodes enlarge greatly
-receive pleural and lung lymphatics, infectious agents from pleura and lungs |
|
Lung Injury of Vascular Origin
|
-Trauma
--contusions and lacerations -Infarcts -Edema -Nonseptic thromboses -Exercise-induced pulmonary hemorrhage --alveolar bleeding, unique to the horse |
|
Infarcts in the Lung
|
-Uncommon
-requires a combination of events --heart failure --right-sided endocarditis --Thrombus formation -Lead to a big dead zone of pulmonary parenchyma -Lung lobe torsions facilitated by pleural effusion -Infarct in the lung takes more than just a thrombus --needs to be a large or wide-spread vascular thrombi |
|
Injury to lung due to Trauma
|
-Contusions
-Lacerations -Broke Ribs -Common in Hit-By-Car cases |
|
Causes of Pulmonary Edema
|
1. increased capillary permeability
-due to inflammation and endothelial injury 2. Left sided heart failure -Increases pulmonary hydrostatic pressure, leasd to pulmonary hypertension 3. Reduced oncotic pressure due to decreased plasma protein concentration -nephrotic syndrome (protein loss through glomeruli) -Protein-losing enteropathy (ostertagiases) -IV fluid overload |
|
Signs of Pulmonary Edema
|
-Pleura may be elevated off of the lung
-RBCs end up in alveolus -PAMs respond to RBCs in alveolus, will be present in alveoli and septum --leads to hemosiderin buildup within PAMs --goes up mucociliary elevator |
|
Non-septic Pulmonary Thromboses
|
-Common cause of embolic pneumonia
-Common cause of death in hospitalized human patients -Due to excessive cortisol levels --promotes thrombus formation --Can be exogenous or endogenous steroids -Marrow emboli from fractured bones -Debris from contaminated intravenous injections |
|
Exercise Induced Pulmonary hemorrhage
EIPH |
-Occurs in almost all race horses while racing
-Diapedesis of RBCs into alveoli during peak capillary pressure -Lethal if enough blood floods alveoli and airways (rare) --horse drowns in its own blood at the end of the race -Due to high pressure gradient in alveolar capillaries --Unique pressure gradient in horse lungs -Will see bloody froth coming out of nostrils -Bulk of the bleeding is caudally and dorsally |
|
Pulmonary barotrauma
|
-Tissue injury that is the result of elevated pressure during mechanical ventilation
-Type I pneumocytes die --leads to ruptured alveoli, interstitial emphysema, and pneumothorax -Air gets into lymphatics and interstitium |
|
Aspiration Pneumonia
|
-Bronchopneumonia due to inhalation of gastric contents or chemical substances
-Brings bacteria and foreign material into the lungs --gastric acid (caustic) --medications --mineral oil (interstitial fibrosis) -Common condition! -Gross pattern of pneumonia depends on position of animal when inhalation occurs --normally a cranioventral pattern unless animal itself is in an abnormal position -Numerous causes, in many situations --Sedation, anesthesia, moribund state --stomach tube accidents, misplaced gastric tube |
|
Mineral Oil Aspiration in Equine
|
-Due to misplaced nasogastric tube
-Alveoli are flooded with mineral oil -Mineral oil is a bland substance, not highly antigenic --will result in consolidation of sections of the lung -Leads to interstitial fibrosis |
|
Acute Respiratory Distress Syndrome
ARDS |
-"Shock Lung"
-Capillary injury combined with type I pneumocyte necrosis -Extreme case of interstitial pneumonia --hard to distinguish from interstitial pneumonia -Hyaline membranes form -Protein-rich edema, RBCs, and necrotic cells in alveoli -Fibrin thrombi present in capillaries -Massive chemokine and reactive metabolite attack on the lung --Toxic substances are created by mixed function oxidases -Can be due to gram- sepsis -Recovery leads to type II pneumocytes and fibrosis -Body "pulls out all of the stops" |
|
Ingestion of Petroleum products by Ruminants
|
-Leads to aspiration penumonia
-Unknown how this occcurs |
|
Systemic Inflammatory Response Syndrome
SIRS |
-Can be due to Acute Respiratory Distress Syndrome
|
|
Causes of ARDS
|
-Diverse disease states
-Sepsis (most common in animals) -Aspiration Pneumonia -Generalized trauma or burns -Pancreatitis -Peritonitis -Barotrauma -Toxic gas inhalation -Chemokine warfare --C5a complement system, reactive metabolites, free radicals, etc. -SIRS -Multi-organ failure |
|
Injured Alveolus during Acute Phase Injury
|
-Protein-rich edema
-Increased fibrin exudate -Sloughing of bronchial epithelium -Necrotic or apoptotic type I pneumocytes -Cell debris in the lumen(RBCs, inactivated surfactant, cellular debris) -Denuded basement membrane on alveolar septum -Hyaline membrane formation -Neutrophils migrate into interstitium -widened, edematous interstitium -Big fenestrations in capillaries for diapedesis -Swollen, injured endothelial cells |
|
Pneumotoxicity
|
-AKA acute Bovine Edema and emphysema
-Reactive metabolites from feedstuffs -Can go unrecognized for a while -Atypical interstitial penumonia of cattle -Type I pneumocytes are killed off, type II are induced -Occurs with feedstuffs rich in tryptophan --L-tryptophan is converted into 3 methylindole --pneumotoxic substance leading to death of type I pneumocytes -3 Methylindole gas is eructated and inhaled --inhaled gas causes lesions -Cows do not die -Purple mint, rapeseed, kale |
|
Fusarium solani fermentation and Pneumotoxicity
|
-Fusarium solani fermets on sweet potato vines
-Produces ipomeanol, pneumotoxin -Fumonisin in pig grain feed causes severe lung edema |
|
Toxic gasses causing Pneumotoxicity
|
-100% oxygen leads to free radical formation
-NH3: paralyzes cilia (ciliostasis) and causes cilia to fall off of the cell (ciliocytophthoria) -NO2: silo gas, directly toxic to type I pneumocytes --produced by silage fermentation -H2S: Manure pit gas, derived from bacterial growth on urine and manure -O3: ozone, irritant gas -SO2: irritant gas -Volatile fluoropolymers: overheated teflon -CO: not a pneumotoxin, causes hypoxia |
|
Ammonia NH3 causing pneumotoxicity
|
-Derived from bacterial growth on urine and manure
-Causes ciliostasis and ciliocytophthoria (loss of cilia) -Predisposing factor for pneumonia in swine and poultry production |
|
Nitrogen Dioxide pneumotoxicity
NO2 |
-Soli gas, formed by fermenting silage
-Directly toxic to type I pneumocytes |
|
Hydrogen Sulfide Pneumotoxicity
H2S |
-Manure pit gas
-Produced by bacteria growing on urine and feces -Airway irritant -With increased concentration, paralyzes respiration |
|
Volatile Fluoropolymer Toxicity
|
-Burned teflon
-VERY pneumotoxic to birds -Causes fetal pulmonary hemorrhage in birds -Sudden, unexpected bird deaths with blood-filled lung |
|
Extrinsic Allergic Alveolitis
|
-Allergic Pulmonary Disease, alveolar allergy
-Rare in all animals, no good animal examples -Very important for humans -Type III hypersensitivity, immune complex deposition in alveolar septum -Causes type II pneumocyte hyperplasia -Alveolar fibrosis and interstitial inflammatory cell infiltrates |
|
Chronic Obstructive Pulmonary Disease
COPD |
-Chronic bronchitis
-Due to combined effects of immune-complex deposits, eosinophils, mast cells, IgE, histamine, etc. -Airway allergy -Physiological phenomenon -Have epithelial cell hyperplasia -Excessive mucus production and retention -Smooth muscle hyperplasia and hyper-reactivity -Airway constriction, narrowing of the airway --causes wheezes, stridor, and "air hunger" -Expiratory effort is required, have to work to breathe out --can result in muscle hypertrophy |
|
COPD treatment
|
-Leukotrienes
-Antihistamines -Corticosteroids |
|
Alveolar Emphysema
|
-Destruction of alveolar septa
-Due to elastase induction, increased activity -Bullae form that look like bubble wrap -Pneumothorax can develop if bullae rupture through pleura -Uncommon in animals -Common in humans, due to chronic smoking and elastase induction |
|
Interstitial Emphysema
|
-Gas distention of interlobular lymphatics, lymphatics between lobules
-Common response to respiratory distress in cattle --cattle cannot equilibrate pressure in adjacent alveoli --no pores of Kohn -Common agonal change in cattle from gasping as cow dies -Can be a result or related to respiratory disease and pneumonia |
|
Endogenous Alveolar Lipid
|
-Lipid pneumonia
-Insignificant and incidental finding in cats, ferrets, camelids, wildlife, lab rodents -Subpleural alveoli are affected -Looks like white subpleural spots -Microscopically will see foamy macrophages and cholesterol crystals in alveoli -Mixture of surfact and cell debris -Lipid is derived from surfactant -Usually alveoli on dorsal aspects of the lungs -Looks like sawdust on the lung |
|
Pneumoconiosis
|
-Excessive and prolonged exposure to Inhaled inorganic particulates
--particles accumulate in the lungs -particualtes are eaten by PAMs, some particulates are transported to the interstitium -Often occurs at intersection of bronchioles and alveoli -Inorganic material is retained by macrophages in interstitium, macrophages build up -Never causes clinical signs in animals, can cause signs in humans -Commonly found in older, urban animals -Microscopically looks like refractile and/or pigmented debris within macrophages --carbonaceous particles (anthracosis) --refractile minerals (silicosis) |
|
Idiopathic Pulmonary Fibrosis
|
-Progressive fibrosis of the pulmonary septa
-Mechanism is unclear --in horses has a viral correlation with equine herpesvirus type V -Looks like flesy mounds of tan tissue throughout the lung -Effaces pulmonary parenchyma, decreases space -Insidious process, presents as decreased exercise tolerance -Initially looks like pneumonia -Dx via multi-modes is needed! --imaging techniques coupled with biopsies --Often misdiagnosed as interstitial pneumonia -Irreversible damage, ultimately fatal |
|
Neoplasia in the Lung
|
-Can look identical grossly to granulomas
-Lung is GREAT at receiving neoplasms from other places --mammary carcnimoa --hemangiosarcoma --metastatic melanoma -Primary malignant neoplasms of the lung are rare and benign --Usually come from other places |
|
Smoke Inhalation
|
-Death due to hypoxia, thermal injury, and/or toxic gasses
-Animals will have burns in the upper airway and soot in the airways -Survivors will develop pneumonia to some degree -ARDS is possible in survivors |
|
Drowning
|
-Water is usually inhaled during drowning
-Not an easy post-mortem diagnosis --water is readily absorbed from alveoli while animal is still alive -Waterborne substances will remain in the lungs --algae, diatoms, sand, etc. |
|
Primary Neoplasms of the Lungs
|
-Bronchioalveolar adenoma
--often multicentric --gives false impression of metastasis and malignancy -Carcnimoa --variously sized epithelial cells in arrayed diverse tissue patterns -Carcinoid: neuroendocrine cells origin -Pulmonary adenomatosis of sheep |
|
Metastatic neoplasms in Lungs
|
-Lungs are a "fertile soil" for metastatic carcinomas and sarcomas
-Osteosarcoma -Mammary carcinoma -Hemangiosarcoma |
|
Feline Pulmonary Carcinoma
|
-Desseminates to digits
-Can identify on digital biopsies |
|
Ovine adenomatosis
|
-Retroviral carcinoma
-Incites pulmonary neoplasms |
|
Bronchioloalveolar Adenoma
|
-Floral-looking proliferation
|
|
Upper Airway Parasites
|
-Oestrus Ovi: nasal myiasis of sheep
-Cephenemyia: nasal myiasis of deer and camelids -Nasal mites -Capillaria aerophila: catarrhal inflammation in carnivores |
|
Lung Parasites of dogs and cats
|
-Oslerus osleri: trachea and main bronchi of dogs
-Filaroides hirthi: alveoli and bronchi of dogs -Toxoplasma gondii: pneumonia in dogs and cats -Crenosoma vulpis: bronchioles of dogs -Aleurostrongylus abstrusus: bronchioles of cats -Pargonimus kellicotti: lung fluke of dogs and cats |
|
Lung parasites of other animals
|
-Pneumocystis carinii: yeast in immunocompromised dogs, pigs, foals
-Dictyocaulus: verminous bronchopneumonis in various domestic species -Metastrongylus apri: verminous bronchopneumonia in swine -Meullerius capillaris: bronchiolitis in sheep and goats -Protostrongylus rufescens: bronchiolitis in sheep and goats -Pnemonyssus simicola: lung mite of macaques, leads to cavitating lung lesions -Parafilaroides: common in seals |
|
Roundworm migration in lungs
|
-Leads to minimal lung lesions
|
|
Pulmonary Cytology
|
-Analysis of pulmonary fluid is useful diagnostic technique
-Sterile saline is flushed into larger airways, then aspirated -Lavage recovers mucus, cells, and debris from trachea and bronchi -Fluid returned is centrifuged, sediment is smeared onto a slide and examined -Fluid can be submitted for bacterial culture |
|
Bronchoalveolar lavage
|
-Refined technique
-Samples a targeted region deep in lung -Cell population differs from cells recovered from larger airways |
|
Mucus on Pulmonary Cytology
|
-Blue whispy material is normal and expected
-Curshmann's spiral indicates poor alveolar ventilation -Granular mucus indicates mucus has been altered by neutrophil enzymes |
|
Epithelial cells on Pulmonary Cytology
|
-Some sloughed cells are normal and expected
-Continual turnover of airway epithelium -Bacteria-coated squamous epithelium is from oropharynx |
|
Leukocytes on Pulmonary Cytology
|
-Activated macrophages (PAM) are normal and expected
-Neutrophils should be less than 20% of cell differential count -Neutrophils with intracellular bacteria indicate sepsis -Eosinophils, lymphocytes, and multinucleated giant cells indicate pathology -Macrophages with hemosiderin are result of pulmonary hemorrhage |
|
Debris on Pulmonary Cytology
|
-Should be a minimal component in normal lungs
-Some disintegrating cells are normal and expected -Low level inhaled pollen, spores, fungi, insect parts, plant fragments is normal -Excessive debris can be correlated with aspiration pneumonia |
|
Pleural Anatomy
|
-Mesothelium: covers pleural, pericardial, and peritoneal surfaces
|
|
Mesothelium
|
-Covers pleural, pericardial, and peritoneal surfaces
-Visceral mesothelium covers lungs -Parietal mesothelium covers chest wall, diaphragm, and mediastinum -Mesothelial cells are flattened cells with microvilli -Produce ECM -Phagocytose particles -Pinocytose fluids -Readily proliferate -Generate cytokines |
|
Pleural Compartment
|
-Little amount of serous lubricant present
-Fluid enters from stroma between mesothelial cells on chest wall -Fluid exits through stoma on visceral pleura and other parietal surfaces |
|
Pleuritis
|
-Inflammation of the pleural compartment
-A few small microorganisms can lead to widespread inflammation -Most commonly due to extension of bacterial pneumonia -Acute: Will have fibrin, pyothorax, fibrinosuppurate exudate -Chronic: mixture of fibrosis and exudates -Pleural adhesions represent healed foci of pleuritis |
|
Examples of Infectious Pleuritis
|
-Cat: Feline Infectious Peritonitis
--wet and dry forms -Horse: Fibrinous pleuritis, commonly associated with anaerobic bacteria -Swine: glasser's disease, haemophilus parasuis -Dog: nocardioform pleuritis --chronic infection that generates "tomato soup" -Numerous species can have pleuritis due to mycobacteriosis, pyogranulomas due to mycobacterium |
|
Non-infectious pleural fluids
|
-Hemothorax: due to trauma, neoplasia, anticoagulant poisoning
-Chylothorax: rupture of thoracic lymphatic duct --seen in cats, and dogs a little --white opaque fluid due to triglyceride component -Hydrothorax: increased venous pressure, low oncotic pressure, lymphatic obstruction |
|
Pleural Neoplasia
|
-Pleural carcinomatosis is uncommon in comparison to peritoneal carcinomatosis
-Mesothelioma is rare in animals --reactive mesothelial cells result from peritonitis can mimic neoplastic cells |
|
Infectious Pleuritis
|
-Most examples are extensions of pneumonia
-Dx: percutaneous aspiration of fluid --bacterial culture --cytologic analysis |
|
Pasteurella Multocida in rabbits
|
-Can lead to pleuritis
-Smelly due to anaerobic bacteria -Polymicrobial with anaerobe component -Associated with transportation |
|
Common congenital Cardiovascular Defects
|
-Anomalies of derivatives of the Aortic Arches
-Outflow tract obstructions -Septal defects |
|
Anomalies of Derivatives of Aortic Arches
|
-Congenital cardiovascular defect
-Patend ductus arteriosus -Persistent right aortic arch |
|
Outflow Tract Obstructions in the heart
|
-Common congenital cardiovascular defect
-Aortic stenosis -Pulmonic stenosis -Coarctation of the Aorta |
|
Cardiovascular Septal Defects
|
-Common congenital cardiovascular defects
-Some are functional, some are non-functional -Atrial septal defects -Ventricular septal defect -Peritoneopericardial diaphragmatic hernia -Tetralogy of Fallot -Mitral valve dysplasia -Mitral stenosis -Tricuspid Dysplasia -Ectopic heart |
|
Pericardium
|
-2 layers: parietal and visceral
|
|
Parietal Pericardium
|
-Serous membrane lined by mesothelial cell lyaer on both sides
-NOT endothelium, mesodermally derived -Outer lining is continuous with mesothelium lining the thoracic cavity -Inner lining is continuous with mesothelium that lines visceral layer of the pericardium -Very high tensile strength, able to accomodate stretch due to fluid accumulation or severely enlarged heart -Thick with lots of collagenous tissue -Lots of fibroblasts to make collagen -Structure is important for heart to adapt to pethological conditions --allows stretch |
|
Visceral Pericardium
|
-Reflected over the heart and attaches to myocardium
-AKA epicardium -One layer of mesothelium -Continuous with the inner mesothelial lining of the parietal layer -Lies underneath the mesothelium -Connective tissue continuous with the interstitial connective tissue of the myocardium -Formed from elastin and fibroblasts |
|
Layers above the heart
|
Mesothelial lining (epicardium
Elastic tissue Myocardium |
|
Layers in the heart
|
1. Parietal Pericardium
Dense fibrous layer Loose connective tissue Mesothelium ----------------------------------- 2. Epicardium mesothelium Loose connective tissue ------------------------------------ 3. Myocardium ----------------------------------- 4. Endocardium Loose connetive tissue Smooth endothelium |
|
Pericardial Sac
|
-Space between the pericardium and epicardium
-Has a few ml of fluid to prevent friction -Protects heart from attach by exogenous pathogens -Protects heart from too much exogenous heat -Limits heart motion -Modulates right atrial mechanics |
|
Hydropericardium
|
-Increase volume of fluid in the pericardial sac
-Usually secondary to a disease elsewhere -Tissue reaction to injury of pericardium -Acute: inflammatory conditions --fluid accumulation contains protein (exudate) and inflammatory cells -Chronic: fluid accumulates gradually --Pericardium stretches and accommodates the increased volume --circulatory failure --Low protein, transudate |
|
Hemopericardium
|
-Blood in the pericardial sac
-Accumulates rapidly -Parietal layer of pericardium has no time to stretch and adapt -Interferes with proper ventricular dilation and diastolic filling --"Cardiac Tamponade" -Occurs with rupture of the atrium --usually left --caused by long-standing atrial dilation --congenital right AV valve defect --endocardiosis |
|
Hemangiosarcoma in the Heart
|
-Has predilection site in right auricle
-Will bleed into pericardial sac - |
|
Cardiac Tamponade
|
-Pressure on the heart muscle
-Occurs when the pericardial sac fills up with fluid faster than the pericardial sac can stretch -Causes interference with proper dilation of the ventricle during diastole |
|
Pericardial Effusion
|
-Buildup of fluid inside the pericardium
-Usually inflammation secondary to infection |
|
Pericarditis
|
-Associated with infection in the body
-Usually involves both layers -Non-specific pericarditis in dogs |
|
Acute fibrinous pericarditis
|
-Part of a generalized infection, bacterial or viral
-Associated with hog cholera, bovine pleuropneumonia -Can hear pericardial friction sounds on ascultation -Will see clinical signs of venous stasis and edema -Can also see on radiograph |
|
Route in infection of Pericarditis
|
1. Blood or lymph
-pasteurellosis -Neonatal coliform infection via umbilical vein -Bovine pleuropneumonia 2. Direct extension -tramuatic pericarditis, Hardware disease -Will see swelling in the sternal region 3. Injury and spread of infection -fistulous tract with inflammatory exudate |
|
Pathogenesis of Pericarditis
Acute phase |
-Pain inflammation
-Activer hyperemia -Damage to endothelial lining of the capillaries in pericardium --parietal and visceral damage --increases capillary permeability and leads to edema -Edema (inflammatory exudate) -Inflitration of inflammatory cells (macrophages and neutrophils) -Attempt to clear the necrotic cells and exudate -Will have fibrinous exudate in the pericardium |
|
Pathogenesis of Pericarditis
Chronic Phase |
-Organizing fibrin, if not cleared will organize into fibrosis
-Fibrosis when fibrolasts migrate into region, proliferate and make collagen -Can cause adhesion between visceral and parietal layers of pericardium -Adhesive pericarditis= chronic pericarditis, healed pericarditis -Interferes with diastolic filling of the heart |
|
Focal pericarditis
|
-Non-specific
-Inflammatory cells are present |
|
Ways heart muscle compensates for increased circulatory demand
|
1. Tachycardia: incresed HR
2. Dilation: chamber size increases -cardiac cells are normal or thin 3. Hypertrophy: increase in size of myocardial cells -Increased weight of the heart -As cell size increases, mass increases |
|
Cardiac Dilation
|
-Best method of acute-need compensation
-Increases size of the heart chamber -With increased chamber size, get increased venous return -Muscle fiber length increases, muscle contracts with more strength -Condition of myocardium determines effectiveness --with lots of damage and fibrosis, dilation will not occur |
|
Conditions that lead to Cardiac Dilation
|
-Pulmonary Embolism
--requires acute circulatory demand --Right ventricle dilates to push more blood around -Embolism at the bifurcation of the aorta --left ventricular dilation -General dilation --heart muscle is weak and cannot produce enough force --occurs in acute septicemia or toxemia |
|
Annulus Fibrosus in the Heart
|
-Fibrous rings of the heart
-Surround the right and left AV valves -Atrial and ventricular muscle fibers attach to annulus fibrosus -Valves are also attached to Annulus fibrosus |
|
Process of Dilation followed by Hypertrophy
|
-Eccentric hypertrophy: dilation followed by hypertrophy
-If hypertrophy cannot keep up with increase in circulatory demand, leads to cardiac decompensation -Severe dilation of the ventricles causes chamber size to increase, leads to dilation of the annulus fibrosus --Valve dilation follows AF dilation, causes secondary valvular incompetence -Leads to regurgitation of blood during systeole -Decreases cardiac output -Will be able to hear a heart murmur -Grossly: --increase in chamber size --thinning of chamber wall --flattening of trabeculae carnae and papillary muscles |
|
Pathogenesis of Cardiac Dilation
|
-Response to decreased perfusion to cardiac muscle
--caused by decreased CO -Not enough blood gets to vital organs, including cardiac muscle -Myocardial tissue recognizes low O2 tension -Myocardial ground substance undergoes changes, muscle fibers separate and allow for dilation of the chamber -Dilation is due to separation of muscle cells -Separated fibers stabilize |
|
Cardiac Hypertrophy
|
-Can be physiologic, animals in training
-Can be pathologic, disease process |
|
Intrinsic Cardiac Hypertrophy
|
-Due to something within the ehart
-Valvular stenosis or insufficiencies |
|
Extrinsic Cardiac Hypertrophy
|
-Due to something outside of the heart
-Chronic venous congestion and lung disease can lead to hypertrophy of the right heart --Chronic Obstructive Pulmonary Disease (COPD) -Hypertension and chronic interstitial nephritis leads to hypertrophy of the left heart |
|
Gross Changes in the heart due to Hypertrophy
|
-Increase in mass of myocardium
-Increase in wall thickness -Increased size of papillary muscles and trabeculae carnae -Dilation can come first OR hypertrophy can come first --depends on demand put on the heart |
|
Structural and Biochemical Changes associated with Cardiac Hypertrophy
|
-Increase in the size of muscle cells
-Increase in RNA, protein, and contractile filamine synthesis --more myosin and actin -More sarcomeres form, increases sarcomeres and myosin filaments -Increased myofibrils in muscle cells |
|
Hoe does cardiac Hypertrophy cause more strength?
|
-Hypertrophied muscles produce less force per unit of muscle compared to normal muscle
-More muscle mass leads to more force produced by the muscle -About muscle MASS, not force per unit of muscle |
|
Changes in Cardiac muscle myosin heavy chain isoforms
|
-V1: aa-heavy chains
--adult myosin -V2: ab -V3: bb-fastest chains --fetal myosin With muscle hypertrophy, myosin concerts to V3 form (fetal myosin) -Low ATPase activity, less ATP is hydrolyzed -Changes contractile performance and efficiency of cardiac muscle -Hypertrophic muscles have better utilization of high-energy phosphate (ATP) -Hypertrophied muscles can maintain force at lower O2 tension --better economy for force generation |
|
Myocardial cell Anatomy
|
-1 nucleus per cell
-Striated cells -Intercalated discs are present |
|
Purkinje cells in the heart
|
-Conduct electrical impulses
|
|
Double apexed heart
|
-Hypertrophy of left and right ventricles
|
|
Myocarditis
|
-Inflammation of the myocardium
-Occurs in a wide variety of systemic diseases |
|
Viral myocarditis
|
-Canine parvovirus
-Canine distemper virus -Encephalomyocarditis in swine -Foot and Mouth diseases |
|
Bacterial Myocarditis
|
-Septicemia
-Clostridial infection in cattle (blackleg) -Listeriosis in sheep -Organisms invade myocardium via coronary vessels -Invade myocardium by direct extension of the endocardium or pericardium -Inflammatory reaction is focal |
|
Protozoal Myocarditis
|
-Toxoplasma gondii in cats
--contact with cat feces during pregnancy -Trypanosoma cruzi in young dogs |
|
Parasitic Myocarditis
|
-Usually focal myocarditis
-Trichinella spiralis -Cysticercus cellulosa |
|
Histologic changes in Myocarditis
|
-Interstitial and perivascular connective tissue show edema and infliltration of inflammatory cells
--Type of cells depends on stage of inflammation -Myocardial fibers undergo degenerative changes --Loss of striations --vacuolization and increased eosinophilia --Homogenous appearances -Myocardial cells cannot regenerate --dead cells are removed by macrophages -After healing, fibrosis develops -No vascular changes in the area, can conclude that inflammation was cause of fibrosis -Fibrosis leads to weakness of the myocardium |
|
Myocardial Cell Death
|
-Caused by bacteria, toxins, chemicals, hypoxia
-Treatment is focused on preventing breakdown of cardiac muscle cells --have short timeframe for reversal! -Ca is released into cytoplasm during breakdown --leads to activation of proteases and breakdown of myofibrils -Need to stabilize the membrane and prevent Ca release |
|
Treatment for Myocardial Cell Death
|
-Drugs to stabilize cell membranes
-Cortisol -Stabilize lysosomes containing lytic enzymes -Start treatment as early as possible! |
|
Myocardial Cell Breakdown
|
-Myofibrils are broken down, leads toprotein structures liberating myosin light chains
-Cytoplasmic enzymes are released with cell destruction --Glutamine oxaloacetate transaminase --Glutamine pyruvate transaminase --Creatine phosphokinase --Dehydrogenase -Release of enzymes leads to destruction of cells -Elevated levels of enzymes in the serum indicates myocardial damage -healing leads to myocardial fibrosis |
|
Myocardial infarction
|
-Seen more in humans that in animals
-Obstruction of blood supply, leads to myocardial necrosis -Becomes red due to hemorrhage -Arteries in infarcted area have no tone, rupture, leading to hemorrhage and red infarct -With time and healing, get a pale central area of necrosis and peripheral red zone with increased vascularity |
|
Cardiac Myopathy
|
-Disease within the myocardium
-Common in large-breed dogs -Seen in young animals, need to rule out congental defects -Cardiac muscle has decreased ability to contract --leads to congestive heart failure --whole muscle is affected -Extremely dilated hearts, sometimes with attempt to hypertrophy -Heart muscle cannot contract, dilated to compensate but could not compensate -Cardiac enlargement can be seen on radiographs -No changes histologically -Defect in Excitation/contraction coupling, reduced Ca uptake and release -Changes in the SR lead to decreased Ca uptake and release |
|
Hereditary Cardiac Myopathy
|
-In humans, autosomal dominant familial disease
-Missense mutation of myosin heacy chain, tropomyosin or troponin gene. -Primarily affects skeletal muscle -Cardiac lesions are associated with most muscular dystrophies |
|
Hereditary Cardiac Myopathy in Hamsters
|
-Affects mostly heart muscle
|
|
Heart lesions in Muscular Dystrophy
|
-Dystrophic involvement of the heart
-Myocardial reserve is significant -Cardiac disorder may advance to congestive failure |
|
Canine X-linked Muscular dystrophy
|
-Heart muscle lesions develop and cause death
-Common in golden retrievers -Also exists in Samoyeds, brittany spaniels, irish terriers, etc. -Breakdown of myofibers -Eosinophilia -Edema, fibrosis |
|
Changes causing decreased ability of cardiac muscle contractility
|
-Extremely dilated hearts lead to valvular incompetence
--ventricular wall will be thin relative to chambers -Possible attempt at hypertrophy -Breakdown of Myofibrils -Broadening of the Z-bands -Degenerative changes in the mitochondria, aggregation of mitochondria -Defect in the E-C coupling -Changes in the SR --leads to decreased Ca uptake and release --affects excitation/contraction coupling |
|
Cardiomyopathy in Cats
|
1. Congestive: extremely dilated heart
-caused by taurine deficiency -rare 2. Hypertrophic: hypertrophy of the left ventricle -prominent in interventricular septum -Leads to myocardial ischemia and gradual fibrosis 3. Restrictive cardiomyopathy: scarring of the myocardium In some cases, may see 2 forms |
|
Pathology of Cardiomyopathy in Cats
|
-Endomyocarditis causes formation of thrombus, leads to ball thrombus
-Ball thrombus released from left atrium causes saddle embolus at bifurcation of the aorta |
|
Thyrotoxic Cardiomyopathy
|
-Associated with hyperthyroidism
|
|
Cardiomyopathy Diagnosis
|
-Clinical signs of heart failure
-Dx based on clinical signs, chest radiographs, and ECG -Specific diagnosis is made with cardiac ultrasound or echocardiography |
|
Endocardium
|
-Inner layer of the heart chamber
-Mural endocardium lines the chambers -Valvular endocardium lines the valves -Papillary endocardium lines the papillary muscles -Chordal endocardium lines the chordae tendinae -Need smooth endothelial lining to prevent sticking of platelets or RBCs |
|
Structure of the Endocardium
|
-Lined by a single layer of endothelial cells
-Continuous with endothelial lining of vessels -Interstitial Cells underlie the endothelial lining: --muscle cells, fibroblasts, undifferentiated mesenchymal cells --Connective tissue fibers (collagen and elastin) --Made by smooth muscle cells and fibroblasts -Connective tissue is continuous with connective tissue interstitium of the myocardium |
|
Blood Supply to the Endocardium
|
-From the heart chamber and vi arteries in sub-endocardial region
--from blood in chamber of the heart -Valves are avascular, no blood supply --blood supply to valves comes entirely from the blood in the chambers of the heart --presence of arteries in the valves is abnormal |
|
Non-inflammatory Reactions to Endocardial Injury
|
-Degenerative and proliferative changes
-Valvular endocardiosis -Jet lesion -Rupture of the Atrium -Degenerative changes= elastin breakdown --alteration from the normal architeture, composition, and synthesis -Change in the composition of collagen -Proteoglycans from Hyaluronic Acid become chondroitin sulfate |
|
Lesions associated with degenerative and proliferative changes in Hearts of Dogs
|
1. Endocardiosis: affects valve
2. Jet lesion in the atrium: results from regurgitation during systole due to incompetent valve --blood is going back into atrium like a jet, hits endocardium in atrium 3. Rupture of the atrium: seen in long-standing atrial dilation --due to valvular insufficiency in the mitral valve |
|
Normal Heart Valves
|
-Thin and translucent
-Valve surfaces are smooth and glistening, lined by endothelial cells -Composed of a few cells of smooth muscle and fibroblasts -Have proteoglycans and collagen |
|
Endocardiosis
|
-AKA chronic valvular fibrosis or disease
-Gross thickening of the endocardium without erosion of the endothelial lining -Valvular endocardiosis is common in older dogs -Unknown etiology -Most frequent and important cardiovascular lesion of clinical signifiance -Mitral valve (left AV) is more commonly affected -Tricuspid and semilunar valves may also manifest the change |
|
Histoligcal Changes with Endocardiosis
|
-Smooth, glistening, knob-like thickening of the valve leaflets
-Increase in number of smooth muscle cells and fibroblasts within the valves -Cells begin to synthesize large amounts of synthetic products (collagen, elastin, protepoglycan) -Valve becomes opaque and thicker -Endothelium is intact -Chordae tendinae are thickened by fibrous and elastic connective tissue proliferation --becomes shorter --fails to close during systole -Somtimes have mucinous, myxomatous degeneration -May have chondreogenic metaplasia -May have capillary growth leading to hematoma |
|
Broken Chordae tendinae in Endocardiosis
|
-Results in jet of blood back into atrium
-Rugal thickening -Mechanical effects of abnormal jets of blood and turbulance produces endocardial proliferative reaction under the endothelial lining -Endothelial lining is intact, no embolism |
|
Pathophysiology of Valvular Endocardiosis
|
-Chordae tendinae rupture → valve leaflet curves up during systole → valvular incompetence
-Regurgitation of blood into left atrium during systole → cardiac murmur -Decreased cardiac output → congestive heart failure |
|
Endocardosis vs. Endocartitis
|
-Absence of inflammatory cells in EndocardiOSIS
-EndocardITIS will have neutrophils and macrophages in valve, inflammatory cells present -EndocardiOSIS Endothelium is intact -EndocardiTIS has eroded endothelium --thrombi attached to surface of the valve makes valve thickened |
|
Cracked Atrium
|
-breakdown of connective tissue fibers
-Can have interrupted endothelial lining and thrombosis |
|
Endocardial response to Inflammation
|
-Endocarditis!
-Valvular endocarditis -Mural endocarditis -Chordal endocarditis -Papillary endocarditis |
|
Endocarditis in Domestic Animals
|
-Usually bacterial
-Occasional cases of Myocotic endocarditis -parasitic |
|
Endocarditis in Cowsz
|
-Corynebacterium pyrogenes
-Streptococcus equi (associated with mastitis) |
|
Endocarditis in Horses
|
-Streptococcus Equi
-Pasteurella -Actinobacillus -Associated with primary infection elsewhere in the body |
|
Endocarditis in Pigs
|
-Erysipelothrix rhusiopathiae
-Associated with skin infection |
|
Endocarditis in Dogs
|
-Streptococcus endocarditis
-Associated with pharyngitis and periodontitis -Can be caused by a variety of organisms |
|
Response of Endocardium to Inflammation
|
-Different predilection sites for bacteria in cows, dogs, and swine
-Cows and Horses: 1. tricuspid 2. pulmonic 3. mitral 4. aortic -Dogs and pigs: 1. mitral 2. aortic 3. tricuspid 4. pulmonic |
|
Endocarditis Pathogenesis
|
-Not all animals develop endocarditis
-Always associated with some MILD initial injury and recurrent or persistent bacteremia -Bacteremia is the result of an infection elsewhere in the body |
|
Mild Injury and Endocarditis development
|
-Mild damages may occur to endothelial lining in any animal
-In a normal animal, injury is not significant and will not cause issues -Lesion develops at line of closure of the valve -Surface of the valve that faces the forward flow of the blood may be initial sites of injury -Experimental infection with bacteria alone is not enough to produce endocarditis -Have increased incidence in animals with congenital cardiac defect and animals that are exercised |
|
Recurrent Bacteremia and Endocarditis
|
-Initial site of infection is mastitis in cows
-Skin infection in pigs -Abscesses in oral cavity or prostatitis/prostatic abscesses in dogs |
|
Development of Endocarditis Lesion on Valve
Injury causes a break in the Endothelium |
-Injury is covered by endothelial cells in animals with bacteremia
-Bacteria stick to the site of injury -Bacteria release toxins and produce more damage to the endothelium -Platelets attach to endothelium, fibrinogen is converted to fibrin and thrombus develops -As thrombus develops, more damage occurs --bacteria are resistant to animal's defense systems, bacteria proliferate |
|
Development of Endocarditis Lesion on Valve
Attempt at Repair |
-Macrophages and Neutrophils remove neurotic cells
-Capillaries flow into the area -Fibroblasts migrate and organize the thrombus -Endocarditis is ALWAYS associated with thrombus formation on the surface --organization at the base of the lesion -Bacterial colonies are always present in the lesion |
|
Vegetative endocarditis
|
-Thrombus is Growing on the valve
|
|
Endocarditis vs. Endocardiosis
|
-Inflammatory cells present vs. not present
-Endothelium is eroded vs. endothelium is intact -Thrombi attached to the surface of the valve cause thickening vs. increased number of cells and connective tissue matrix cause thickening |
|
Gross Appearance of Endocarditis
|
-Glistening valve surface does not exist, endothelial lining is not intact
-Erosion on the valve surface where thrombus is not present -Thrombus is attached to the surface of the valve -Mural thrombosis is often present -Thrombus has been organized at the base and is difficult to dislodge -Valve is thickened due to organization of the thrombus |
|
Sequels of Endocarditis
|
-Organization at the base occurs, thombus grows faster than the tissue is able to cover
-Fatal disease because thrombus can breakdown and lead to: --embolism --infarction --Abscesses at emboli site due to bacteria in emboli -Infection can be spread to other sites in the body --Cows get embolism and infarction in the lungs --Dogs get renal, cerebral, etc. |
|
Cardiovascular Lesions associated with uremia
|
-Starts as degenerative change
-With time may see inflammatory cells in lesion -Not a true inflammatory lesion -Mucoarteritis, lesion of the large elastic arteries -Mural endocardial lesion because it is seen in the wall of the heart chamber --result of a totally different process, not true inflammation |
|
Uremic endocardiosis/endocarditis in Dogs
|
-Only in left atrial endocardium
-Caused by uremic waste products -Initially lesion starts as increased amount of proteoglycans are made by smooth muscle cells and fibroblasts in the endocardium -Some edema leads to mucinous change -Endocardial surface has white raised areas -Endothelium is still intact -Over time there is some breakdown of connective tissue fibers --serves as chemotactic stimulus, causes inflammatory cells to migrate |
|
Sequels of Uremic Mural Endocardiosis/Endocarditis
|
-Breakdown causes tissue necrosis, chalky white dystrophic calcification
--deposition of Ca on necrotic cells -Calcification and degeneration leads to endothelial damage and thrombus formation -No associated bacteria, thrombus can break down and get into circulation --causes saddle embolism in dogs |
|
Heart Base Tumor
|
-Neoplastic disease of the heart
-Originates from chemoreceptor cells in the aortic body -Tumor forms at the base of the heart, attached to origin of the aorta -Well-encapsulated, highly vascular, rarely metastatic neoplasm -If large, exerts pressure on the wall of the vena cava, interferes with venous return to the heart --leads to chronic passive congestion and congestive heart failure -Can be surgically removed -More common in brachycephalic dogs |
|
Hemangiosarcoma in the Heart
|
-Predilection site in the tip of the right auricle
-Heart may be a metastatic site also -Rupture leads to hemopericardium and cardiac tamponade |
|
Lymphosarcoma in the Heart
|
-Common in cows
-Usually heart is secondary site |
|
Arteritis
|
-Inflammation of the Arteries
-Associated with viral diseases -Polyarteritis: many small arteries involved -Periarteritis: localized inflammation on the outer tunics of the arterial wall -Panarteritis: all tunics of artery are involved -Endarteritis: begins in the inner layer (intima) of the artery - |
|
Sequence of Pathological Changes in Arteries
|
-Inflammation associated with viral diseases
-Autoimmune disease component -Initial arterial response is fibrinoid degeneration followed by phase of cellular reaction and a stage of healing |
|
Fibrinoid Degeneration/Necrosis
|
-Initial swelling and breakdown of the connective tissue fibers in the media
-Specific necrotic response only in the arterial wall -Smooth muscle cells lose integrity and appear as a homogenous eosinophilic mass -Cellular outlines are no longer apparent -Eosinophilic material looks like fibrin but is not, hence fibrinoid necrosis -Can be associated with immune-complex associated disease -Involves deposition of immune complexes in areas such as the glomerulus and capillaries -Endothelial cells are still lining the lumen, have not been diisrupted |
|
Fibrinoid degeneration repair and healing
|
-Cellular infiltration of macrophages
-Lymphocytes line up around adventitia -Macrophages remove necrotic tissue -Fibroblasts migrate from the adventitia -Synthesize and deposit collagen, produce a less elastic/more fibrotic arterial wall |
|
Sequelae to Fibrinoid degeneration
|
-Fibroid necrosis weakens the artery wall, can lead to rupture and hemorrhage
--hemorrhage is usually a result when several arteries are involved -Thrombosis of the ruptured arteries can lead to multiple infarcts -Healing results in occlusion of the arterial lumen, eventual ischemia |
|
Diseases associated with Fibrinoid degeneration
|
-Equine Viral arteritis
-Malignant catarrhal fever -Aleutian mink disease |
|
Arteriosclerosis
|
-Most prevalent and chemically significant primary vascular disease of humans
-Group of cellular and tissue reactions -Causes thickening, narrowing of the lumen, and loss of elasticity of the arterial walls |
|
Morphologic variants of Arteriosclerosis
|
1. Atherosclerosis
2. Monckberg's Medial Calcific Sclerosis 3. Arteriolosclerosis |
|
Atherosclerosis
|
-Formation of atheromas containing focal lipid deposits
--fat and cholesterol -Lipid deposition in the lesion -Causes degenerative or proliferative changes in the intima and inner third of the media -Hypothyroidism leads to hypercholesterolism and hyperlipidemia --may lead to atherosclerosis |
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Monckberg's Medial Calcific Sclerosis
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-Calcification of the media of muscular arteries
-Seen in humans |
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Arteriolosclerosis
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-Degenerative or proliferative changes in the walls of arterioles
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Arteriosclerosis in Domestic Animals
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-All vertebrate animals including avian species
-Not common in dogs --can occur associated with hypothyroidism |
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Narrowing of the arterial lumen
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-Fragmentation of the internal elastic lamina leads to migration of smooth muscle cells into the intima
-results in fibromuscular proliferation and intimal thickening -Intimal thickening leads to narrowing of the lumen -Fat-laden SM cells (foam cells) can also thicken |
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Atherosclerotic Plaque
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-Foam cells and degeneration of foam cells causes release of lipids outside of the cells
-Calcification of atherosclerotic plaque occurs |
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Intramural coronary atheriosclerosis
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-Leads to narrowing of the lumen
-Narrow lumen, decreased coronary perfusion in tissues -Causes myocardial ischemia and decreased ability of body to respond to increased circulatory demand |
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Intramural Arteriosclerosis Sequels
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-Decreased coronary perfusion, leading to myocardial ischemia
-Multiple microinfarcts and myocardial fibrosis -Fibrosis leads to decreased force during contraction and inability to compensate for decreased cardiac output in older dogs |
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Heart worm and Arterial lesions
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-Inflammatory lesion that leads to arteriosclerotic lesion
-Hang out in pulmonary artery and sometimes left ventricle -Can travel retrograde into lungs |
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Healed arteritis
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-Causes fibromuscular proliferation and a narrower arterial lumen
-Results in increased resistance to the pulmonary circulation |
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Pathogenesis of Arteriosclerotic lesions due to parasitism
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-Arteriosclerotic lesions results in increased resistance to pulmonary circulation
-Right ventricle hypertrophies to compensate, results in eventual right heart failure |
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Cor Pulmonale
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-Right heart failure secondary to lesions in the lung
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Medial Hyperplasia in Cats
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-Secondary to Aleurostrongylus abstrussus infection
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