Path Cal Review

Merkel Cells, langerhans cells, melanocytes, keratinocytes

1. Lipid-laden lamellar granules migrate from the stratum spinosum to the junction of the stratum granulosum and stratum corneum. 2. Granules are released into the intercellular space, creating a hydrophobic seal. 3. Proteases, DNAases, and RNAases are released, which denature the keratinocyte nucleus and organelles4. Filaggrin causes the polymerization of intermediate filaments forming a keratin core of the corneocyte. Transglutaminase converts the plasma membrane into a hard protein shell5. Desquamation

persistence of the nuclei of keratinocytes as they rise into the stratum corneum of the epidermis.

Improper cell maturation can occur with an increased epithelial cell turnover. The decreased transepidermal migration time does not allow for nuclear degredation.

Zinc-responsive dermatosis, good prognosis with zinc supplementation

Necrolytic Migratory Erythema (Hepatocutaneous Syndrome), poor prognosis

Lethal acrodermatitis of Bull Terriers, poor prognosis

Acanthosis is hyperplasia of the stratum spinosum while acantholysis is the loss of cohesion between keratinocytes (loss of desmosomes) resulting in the formation of clefts, vesicles, and bullae.

Acantholytic cells can commonly be seen in pemphigus foliaceus, superficial bacterial infections (due to proteolytic enzyme release), ballooning degeneration in viral diseases, and severe spongiosis.

1. desmoglein 3 (a cadherin) 2.Intraepidermal vesicular dermatitis 3. Between S. basale and S. spinosum. 4. mucous membranes & mucocutaneous junctions

1.Desmogelin 1 ( a cadherin) 2.Intraepidermal pustular dermatitis 3. All but S. basale (Suprabasilar)4. Haired skin

1. Hemidesmosomes2. Subepidermal vesicular 3.No layers affected. (Subbasilar bulla) 4.mucous membranes & mucocutaneous junction

Bacterial: staphylococcus intermedius Fungal: dermatphytosis (Ringworm) Parasitic: demodecosis (Demodectic Mange)

stage of active growth. Thyroid hormone, androgens

transitional stage

Resting stage/no growth. Glucocorticoids, estrogen.

Coronavirus

Cats can be infected by exposure to exogenous virus, probably by the oro-nasal route, or infection may arise from mutation of an endogenous enteric coronavirus.

Viral infection → no cell-mediated immune response → antibody production → macrophages producing virus accumulate around vessels and in the interstitium of the serous surfaces and tissues throughout the body → virus enters these tissues → virus complexes with antibodies → complexes deposit on vessel walls and attract complement → damage to vessel walls → leakage of protein rich fluid into body cavities → effusive or wet form of FIP which may lead to dyspnea and/or cardiac tamponade.

Viral infection → Weak or ineffective cell-mediated immune response → less florid macrophage response in tissue and poorer virus production → The noneffusive or dry form of FIP ensues.

Rupture of the gastrointestinal tract is common in horses, cattle, and rabbits. When seen on post mortem exam it is important to determine whether the rupture occured antemortem or postmortem. If this occured postmortem the margins of the defect of the gastrointestinal wall are not hemorrhagic, and the peritoneal surfaces show no indication of inflammation.

A group of diseases characterized by a persistent increase in intraoccular pressure, which causes pathological changes in the eye.

Physical or functional obstruction of the filtration angle → decreased outflow of aqueous humor → increased intraocular pressure

Optic disc cupping, Corneal edema- striate keratopathy, BuphthalmosCataract (lens malnutrition),Exposure keratitis secondary to buphthalmos, Iris and ciliary body atrophy, Retinal atrophy (inner layers first), Retinal separation following buphthalmos,Scleral thinning

The iris, ciliary body, and choroid (all structures within the sclera) are inflammed in panuveitis, a combination of anterior and posterior uveitis

Corneal opacity (edema, inflammation, fibrosis)Anterior and/or posterior synechiaeGlaucomaRetinal degeneration or separation, Cataracts, Preiridial fibrovascular membrane (PIFMs) with intraocular hemorrhage (also caused by retinal separation/detachment), Phthisis bulbi

herniation of Descemet's membrane (usually outward through the corneal stroma and epithelium).

adhesion of the iris to the cornea.

Corneal Injury (chemical, physical trauma, microbial, immune mediated, glaucoma, or genetic)→ Erosion: loss of epithelium→ Edema: due to increased stromal fluid from the aqueous humor via damaged endothelium and from tears through damaged epithelium→ Inflammation: keratitis (The eye can return to normal if successful healing occurs at this point)→ Ulceration: loss of epithelium through the basement membrane→ Neovascularization→ Deep corneal stromal ulcer → Descemetocele→ Corneal rupture

Blood glucose >90mg/dl → hexokinase saturated in glycolysis pathway in lens fibers → glucose is shunted to sorbital pathway → sorbital accumulates → sorbital osmotically attracts water → hydropic degeneration (vacuolization) and rupture of lens fibers → opacification

• Diabetes mellitus
• Trauma
• Inflammation
• Glaucoma
• Interferences with lens nutrition

Gross findings: The mucosa is reddened, possibly bleeding.Histologic findings: Erosions and ulcers accompanied by a neutrophil infiltrate and edema of the lamina propria.Urinalysis findings: Blood, abundant sloughed epithelial cells and leukocytes.

Prolonged cystitis results in proliferative changes such as urothelial hyperplasia, urothelial metaplasia to squamous cells, and abundant inflammatory cells that include lymphocytes, plasma cells, and probably macrophages and eosinophils. These inflammatory cell aggregates might be grossly visisble as gray or red foci. A chronic, yet active cystitis will still have numerous neutrophils.

alimentary tract ulcersuremic mineralization of various tissuesfibrous osteodystrophyanemiaedema

specific gravity: isosthenuric (1.008 to 1.012)sediment cellularity: variable; cellular and hyaline castsdip stick findings: albumin +++

creatinine: elevated; usually well above 2.0 mg/dLphosphorus: elevated, usually above 7mg/dL for nonruminantsprotein: diminshed total protein due to low albumin fraction <2g/dL

convoluted tubules of the cortex

Acute tubular necrosis results in shedding of tubular epithelial cells, which occludes the lumen of the tubule and form casts.

his is the death by "poison" or death by "suffocation" story. There are numerous causes.

• disuse
• denervation
• malnutrition/starvation/cachexia/metabolic

1. Synthesis of contractile proteins is reduced 2. Expression of muscle regulatory proteins is increased (MyoD, Myogenin) 3. Acetylcholine receptors increase in number and become extrajunctional spreading over the surface of the muscle 4. Neural cell adhesion molecule (NCAM) expression increases and NCAMs spread over the entire surface of the denervated muscle

Schwann cell proliferation at the motor end plate of the denervated fiber cause collateral sprouting of neighboring neurons. With increased numbers of NCAMs on their processes, the Schwann cells guide the new branch of the axon to the motor end plate of the atrophied muscle fiber.

Normally, motor unit types (nerve and associated muscle fiber) are intermingled, giving the muscle bundle a checkerboard appearance of both fast and slow muscle fibers. With renervation a single neuron may innervate more adjacent myofibers, changing their phenotype, producing the histological appearance of type grouping.

Insult (trauma) Loss of muscle striation and cytoplasm becomes hypereosinophilic Influx of macrophages and inflammatory cells, which begin to clear necrotic debris Cell nuclei move from the periphery to the center of the myofiber, and the necrotic area is walled off from the rest of the intact muscle Satellite cells within the injured area begin to proliferate and join, forming a syncitium in the basal lamina of the damaged fiber. The muscle fiber is regenerated.

Immune-mediated, infectious agents (bacteria, such as Clostridium spp. and protozoa, such as Sarcocystis spp, Neospora.)

hypothyroidism, hyperadrenocorticism (iatrogenic and spontaneous)

vitamin E and/or selenium deficiency

Deficiency in vitamin E and/or Selenium → peroxidation of membrane lipids (sometimes exacerbated by stress) → Ca 2+ enters cytoplasm and mitochondria, damaging respiratory mechanisms → cell death → symmetrical necrosis of the most active skeletal muscle (like postural muscles)

• location of lesion
• size of lesion
• rate of growth
• secondary vascular lesions (edema and hemorrhage)

Localization or distribution of function.Unique anatomic and physiological features

1. The nervous system is vulnerable to focal lesions, which is compounded by the limited ability of the nervous system to regenerate following inury.2. Because there is localization of function in the nervous system, the same pathologic process can present clinically different when a different part of the system is affected. Conversely, different diseases affecting the same area of the nervous system will present clinically similar. A meningioma at the base of the brain may compress the optic nerve and lead to blindness.Yet, a meningioma in the lateral cortex may lead to seizures and a meningioma in the medulla may cause a head tilt.A choroid plexus tumor, infarct, or inflammation affecting the medulla may also lead to a head tilt.3. Groups of neurons are selectively vulnerable to different diseases.Because the nervous system is comprised of different types of cells, different toxins will affect different groups of neurons, which results in a specific pattern of pathologic changes.4. The response of the nervous system to injury is limited and non-specific, so the diagnosis often depends on the location of the injury rather than the microscopic appearance of the lesion.

focal lesion → secondary edema and hemorrhage → occupies space due to limited and fixed volume of the calvaria → increased intracranial pressure → herniation of the brain caudally → compression of medullary respiratory and cardiocascular centers → death

Herniation of the nucleus pulposus = extrusion of the nucleus pulposus through a tear in the annulus fibrosis(a.k.a. Hansen's Type I)Protrusion of the annulus fibrosis = bulging of the annulus fibrosis - usually into the spinal canal(a.k.a. Hansen's Type II)

degeneration of the nucleous pulposus (earliest lesion in chondrodystrophic dogs)protrusion or herniation through the damaged annulus fibrosus (earliest lesion in non-chondrodystrophic dogs)direct compression of the spinal cord and/or nerve roots and spinal vessels when disc material hits spinal corddemyelination (least severe)leukomyelomalacia (more severe)edema and hemorrhage (more severe)poliomyelomalacia (most severe)occasionally ascending myelomalacia occurs following severe disc disease due to an unknown pathogenesis

• blood (most common route)
• local extension (occurs from established infections)
• direct penetration
• retrograde axonal flow

a. leukoencephalitisb. myelomalaciac. polioencephalomalaciad. meningoencephalitis

Inhibition of cell mitosis examples: microencephaly, cerebellar agenesis or hypoplasia, optic nerve hypoplasiadestruction of cells before complete maturationexamples: porencephaly/hydraencephaly, cerebellar hypoplasia/degeneration, like from feline panleukopenia viruscell migration disordersexamples: lissencephaly, microgyri, macrogyri, porencephaly

axonal injury (transection of an axon leading to Wallerian degeneration) segmental demyelination (destruction of the myelin sheath, composed of Schwann cells in the PNS and oligodendrocytes in the CNS, leaving bare axon) axonal degeneration (axonodystrophy)

After transection of the axon with separation of the distal and proximal portions, the adjacent axonal membranes self-sealAnterograde and retrograde axonal flow are both halted and there is swelling of the severed ends due to accumulation of neurofilaments, mitochondria, and debris within 24 hours of the injuryThe distal segments undergoes Wallerian degeneration (axon and myelin sheath degenerates and is removed by macrophages and glial or Schwann cells)Chromatolysis of cell body occurs (cell body swells, cytoplasm becomes homogenous & glassy, nucleus moves to eccentric position)Presynaptic terminals move out of synaptic contact while affected neuron is attempting to repairIf the site of axonal injury is close to the cell body, the neuron may die.Anterograde and retrograde transneuronal atrophy may occur because of the trophic relationship between the neurons of assemblies. Schwann cell proliferation occurs distally inside the tubes of the basement membrane of the original Schwann cells.Axonal sprouts appear proximally at the site of transection.Axonal sprouts follow Schwann cells to the site of the former synapse.Schwann cells remylinate the axon.

Destruction of myelin sheaths leaving intact axon bare (internode or segment of myelin is lost)Conduction block or slowing of nerve impulseSchwann cells proliferate and remyelination is often complete

Distal portion of the axon dies back and the myelin sheath breaks down at the same time.Axonal regeneration is very poor, and there is little Schwann cell proliferation.

Oligodendroglial cells do not proliferate readily and therefore there is very poor remyelination in the CNS.Loss of myelin sheath is detected by a lack of staining using stains specific for myelin (ex., Luxol-blue).