Midterm Exam 1: Modules 1-6D

What is hemostasis?

- all vessels, thrombosis (platelet plug and coagulation cascade) - small (capillaries) close by tissue pressure - medium (venules > arterioles) stretching promotes vessel contraciton - large (arteries and veins) require ligation

What is a cicatrix?

- an avascular region of dense fibrous connective tissue - arises by contraction of fibrous tissue laid down to close defects within a wound - typically undergoes some amount of remodeling to form a final scar - composed mainly of type 1

What can been seen in an inflammatory response (what you see depends on time)?

- an inciting cause - damaged tissue: especially necrosis, +/- degeneration - inflammatory cells - altered regional circulation: congestion, thrombosis, etc. - fluid exudation: from both blood and lymphatic vessels - proliferation of various cells (late): fibroblasts (stromal cells) and angioblasts (vascular cells)

What is morphologic diagnosis?

- an orderly, detailed description of a lesion - "what is the lesion composed of?" - common descriptors: affected structure (cell/tissue/organ), process (ex: inflammation), distribution, severity, time course, +/- cause - example: acute, severe, diffuse suppurative encephalitis

What are the types of extrinsic etiologies of disease?

- animate agents (and their products) = "pathogens" - inanimate causes

What are the histologic features of dysplasia?

- anisocytosis (cells of unequal size) - ansiokaryosis (nuclei of unequal size) - hyperchromatism (excessive (usually darker) coloration) - poikilocytosis (cells of abnormal shape)

What are the charcterisitics of necrosis?

- ante mortem - focal or multifocal - selected cells only - induces local tissue reaction: inflammation +/- vascular reaction - living and dead tissue in same section - calcification of dead tissue = dystrophic mineralization - erythrocytes are intact with vessels

What are defining characteristics of necrosis?

- ante mortem - "oncotic" = cell swelling - "apoptotic" = cell suicide

What are some characteristics of necrosis that distinguish it from autolysis?

- ante mortem - focal or multifocal - selected cells only - induces local tissue reaction: inflammation +/- vascular reaction

What is a free radical?

- any molecule with an unpaired election - if control systems are overwhelmed or depleted, free radials contribute to mechanism of cell death- especially mitochondrial damage

What are characteristics of liquefactive necrosis?

- architecture lost --> tissue is dissolved - inflammation prominent (neutrophils)

What is a typical foci for necrosis?

- are well-demarcated from adjacent tissue - have irregular contours - are pale - may be associated with cavitation (fallen in on themselves) - depending on lesion duration and type, foci may have distorted contents and colored rims

What are the driving forces of fluid exchange and homeostasis?

- arterial blood pressure (active, force out ) - colloid osmotic pressure (passive, influences in) - interstitial fluid pressure (passive, influences in)

What is the microscopic appearance of hyperemia?

- arterioles and capillaries dilated and filled with blood - if inflammatory cause, may see inflammatory cells, edema, necrotic cells

What is the microscopic appearance of congestion?

- arterioles and capillaries dilated and filled with blood - note: hyperemia and congestion look similar histologically

What is saponification of fat?

- as adipose dies, fatty acids are released and combined with Ca2+ and K+ ions and deposited as "soaps" on the pancreas surface - these deposits are white, chalky, and firm and can be extensive in the abdominal cavity

What are the different types of processes of cellular adaptation?

- atrophy - hypertrophy - hyperplasia - metaplasia

What is seen for cells with adaptation?

- atrophy - hypertrophy - hyperplasia - metaplasia

Classic granulomas have what structure (center to periphery)?

- central core of macrophages - zone of epithelioid macrophages - zone of MNGC with lymphocytes (CD4 and CD8 T cells), plasma cells and NK cells - peripheral zone of fibrous connective tissue

What does persistence/resistance entail?

- foreign bodies (poorly degradable) - persistent injury or trauma - persistent antigen - persistent infection (intracellular/atypical bacteria, fungi, some viruses, etc.)

There are two different types of MNGC with distinct morphology microscopically. What are they?

- foreign body type: nuclei are arranged haphazardly in center of the cell - Langhan's type: nuclei are arranged in a semi-circle or horseshoe shape at the periphery of the cell

What are the potential causes for eshcar?

- gangrene - ulcer - fungal infection - necrotizing spider bite wound

What are gross morphological internal features of autolysis?

- gas production and putrefaction: crepitus may make visible bubbles in tissues as bacterial fermentation occurs, strong odor usually present, abdominal viscera become pale - post mortem tissue discoloration (imbibition): hemoglobin imbibition, pseudomelanosis, bile imbibition

What is the cell appearance for reversible reactions?

- general swelling of cell and organelles - blebbing of plasma membranes - detachment of ribosomes from ER - clumping of nuclear chromatin

Increased intravascular pressure can cause what kind of edema?

- generalized edema: pulmonary hypertension and heart failure - local edema: venous obstruction from torsion

What is DIC Schwartzman reaction?

- generalized renal cortical necrosis - an organ-specific manifestation of arteriolar microthrombosis (DIC)

What are the susceptible components of the cell?

- generation of ATP by aerobic respiration - integrity of cell membrane - protein synthesis - cytoskeleton - genetic integrity

Cirrhosis of the liver combines multiple processes such as what?

- going inflammation: interstitial & nonsuppurative - scar formatin and remodeling: intersection bands of fibrosis - renewal of functional parenchyma: multifocal nodular proliferation

What helps malignant tumors to be invasive?

- greater cell motility via adhesion loss - increased fluidity of tumor cell membranes (due to reduced or absent expression of multiple membrane proteins - pressure: leading to necrosis/separation of nearby normal tissue -secretion of proteases (which dissolve the basement membrane) and anti-proteases (which block stromal cell-derived protease inhibitors - survival advantage in seeking nutrients/oxygen, especially in deficient environments

What is cellular glycogen accumulation?

- grossly, liver will be slightly pale, slightly enlarged - difficult to distinguish from fatty change or hydropic degeneration

What are examples of hematogenous pigments?

- hemoglobin - methemoglobin - carboxyhemoglobin - hemosiderin - hematin: acid formalin, parasitic - bilirubin - porphyrin

What are the resolutions of hemorrhage?

- hemostasis - removal of extravascular blood - restoration of vascular bed

What causes decreased colloid osmotic pressure?

- high protein loss: burns, chronic gastrointestinal or renal glomerular disease - hypoalbuminemia - decreased protein absorption: chronic gastrointestinal disease - reduced protein production: severe chronic liver disease

What are the characteristics of acute?

- hours to 3-5 days - edema - extensive vascular engorgement with possible thrombosis - fibrin exudation followed by neutrophil influx - lymphatic dilation --> swollen regional lymph node - 5 hallmark signs of inflammation are very evident

What are Russel bodies?

- hyaline bodies present in cytoplasm some plasma cells (Mott cells) - bodies are large, eosinophilic, homogenous and amorphous - accumulated immunoglobin - clinically, may be seen in feline plasma cell pododermatitis

What is seen for cells with degeneration?

- hydropic - fatty change - glycogen - myxomatous

What are the types of cellular degeneration?

- hydropic (acute cell swelling) - fatty change - glycogen accumulation - myxomatous

What are the forces regulating movement of body water?

- hydrostatic pressure on the arterial side pushes water out of vessels - osmotic pressure on the venous side pulls water into blood vessel

What are the later stages of necrosis?

- hypereosinophilia of the cytoplasm - fragmentation of the cell - inflammation

What is the microscopic appearance of catarrhal exudate?

- hyperplasia of goblet cells and epithelial cells forming glands - hyperplasia and hypersecretion due to actions of cytokines of these cells - connective tissue separated by mucins

What are the causes of cellular fatty change?

- hypoxia - starvation - anemia - inhibition of protein synthesis (aflatoxins do this clinically!)

The type of lesion or pattern of lesions allows the pathologist and clinician to do what?

- identify an etiology - define a pathogenesis - establish a diagnosis - make a prognosis

What is granulation tissue?

- immature, highly vascular fibrous connective tissue - angioblasts and fibroblasts - This is NOT granulomatous!

What are the major cell types involved in chronic inflammation?

- immune cells: macrophages, lymphocytes, plasma cells - stromal cells: fibroblasts, angioblasts

What can cause increased vascular permeability?

- immune mediated: many of the same events that accompany inflammation cause an increase in permeability - direct endothelial injury: toxins, chemicals or infectious agents (viruses, bacteria - in cases of systemic hypersensitivity, there can be more widespread fluid loss/edema

What is the pathogenesis of gout?

- impaired excretion of uric acid by kidneys - or over production of uric acid - elevation of plasma uric acid concentration --> precipitation of monosodium urate crystals on many visceral and/or articular surfaces --> chronic inflammation

What is an abscess?

- important term for suppuration - chronic: lots of neutrophils + mononuclear cells (macrophages and lymphocytes) - peripheral fibrosis - central liquefactive necrosis - agent is sometimes present in center - mineralization of necrotic debris can occur

What are the intravascular events for alterations in blood flow?

- increase in volume blood in any tissue - increased flow: hyperemia - decreased flow: congestion

What is the cell appearance for irreversible reactions?

- increased cell swelling - swelling of mitochondria - disruption of lysosomes - additional cell membrane disruption - profound nuclear changes: pyknosis, karyorrhexis, karyolysis

What is physiologic hyperemia?

- increased flow to the skin for heat loss (blushing) - increased GI flow following a meal - physically active muscles

What happens for a transudate to occur?

- increased hydrostatic pressure (venous outflow obstruction e.g. congestive heart failure) - decreased colloid osmotic pressure (decreased protein synthesis, e.g. liver disease, increased protein loss, e.g. kidney disease) - one or the other

What are the four mechanisms of edema?

- increased intravascular hydrostatic pressure - decreased colloid osmotic pressure - increased vascular permeability - obstructed lymphatic drainage

What is hyperplasia?

- increased number of cells - may be normal size and appearance or also be hypertrophied

What are the characteristics of fibrinous exudate?

- increased vascular permeability due to injury of endothelium and basement membrane - leakage of plasma proteins including fibrinogen - once fibrinogen is in tissues, it polymerizes to form fibrin - fibrin may fill space in tissues or form a mat on surfaces - most commonly caused by infectious microbes - common on serosal surfaces

Eosinophilic granulomas are characteristic of what?

- infections in which a parasite migrates as part of its lifecycle - parasitic worms, especially nematodes, may be found in the central core of the granuloma

What is the unwanted sequelae of oncotic necrosis?

- inflammation - fibrosis (scarring) - mineralization - permanent loss of function

What are the etiologies of hemorrhage by diapedesis?

- inflammation (severe) - necrosis or inflammation of endothelium - endotoxemia - infectious agents: canine adenovirus-1

What causes obstructed lymphatic drainage?

- inflammation --> parasites, scarring - neoplasia - iatrogenic occlusion of lymphatics by a bandage or dressing - intestinal lymphangiectasia

What are the characteristics of catarrhal exudate?

- inflammation of mucous membranes or mucosal surfaces - hypersecretion of mucin-containing, thick, gelatinous fluid

What is the mechanism of suffusion?

- inflammation, coagulation factor problems - larger vessel walls are breached - injury is more severe

What are potential causes of fat necrosis?

- inflammation/release of adipose-digestive enzymes (as in pancreatitis) - crushing/other physical trauma - idiopathic (unknown)

Once in extravascular spaces, neutrophils die and contribute to what?

- inflammatory exudate - lots of neutrophils = pus!

What are the characteristics of carbon as an exogenous pigment?

- inhalation - results in anthracnosis (black lung) - most exposed live in environment with air pollution - phagocytosed by macrophages in alveoli then transported to lymph nodes - inert and not metabolized = remains in tissue for life of animal

What is gangrenous necrosis?

- initial necrosis is coagulative and progresses to gangrenous - three types: wet, dry, gas

What is the nomenclature of neoplasms?

- initial part (prefix) that indicates the type of cell (histogenesis) - following part (suffix) indicates the benign or malignant nature of neoplasm - benign tumors have the suffix -oma - malignant tumors originating from epithelial cells carry the suffix carcinoma and mesenchymal cells carry the suffix sarcoma

What is pathologic hyperemia?

- initial stages of inflammation - initial vascular response - neovascularization- repair

What is intrinsic pathway for apoptosis?

- initiated by injury due to toxins, hypoxia, radiation, hormone withdrawal, etc. - important caspase: caspase 9

What is the mechanism of petechiae?

- injury to endothelium - platelet problems (e.g. thrombocytopenia) or mild vascular injury

What are viral inclusion bodies?

- intranuclear and/or intracytoplasmic with some viral infections - accumulations of viral protein, incomplete or complete virions

What are the two types of etiologu?

- intrinsic (inside) - extrinsic (outside)

How does one know that saprophytic intestinal bacteria are post mortem invaders and NOT the cause of disease?

- invasive commensal bacteria are typically Gram + anaerobic rods - there is NO host inflammatory response

What does removal of extravascular blood entail?

- involves a foreign body reaction to erythrocytes (i.e. inflammation) - macrophages remove erythrocytes (to scavenge heme/iron)

What is hemosiderin?

- iron storage pigment - mostly stored in spleen - increased amounts: breakdown of erythrocytes at end of erythrocyte life, hemorrhage, congestion (slow blood flow), hemolysis

What are the types of necrosis nuclear changes? What do they eventually lead to?

- karyolysis, pyknosis, karyorrhexis - eventually nucleus dissolves, leaving an anuclear necrotic cell

Ceroid accumulates where?

- kupffer cells - hepatocytes, skeletal and smooth muscles - neurons in ceroid lipofuscinoses

What are the features of ecchymosis?

- larger foci from 2-10mm, "blotchy" and irregular - indicates injury of capillaries, arterioles and venules (diapedesis) - best appreciated on surfaces, especially skin (i.e. subcutis) - lesions are larger than petechiae (2-10mm), "blotchy" and irregular

What is suffusive?

- larger than ecchymosis, but localized or contiguous area of tissue - "paint-brush" hemorrhage is when suffusive hemorrhage forms streaks

What are the attributes of lesions?

- larger than normal = "something added" - smaller than normal = "something removed/lost" - color: what color is it? - consistency: fluid, soft, firm, hard? - contours: raised, flat or depressed - distribution: spatial arrangement of lesions? - duration: acute or chronic? - extent: how much of the organ or tissue is affected? - locations - margins - shape: do lesions have geometric shape? -size: dimensions of masses, nodules, depressions, etc. - textures: what does the cut surface look like? Amorphous or solid?

What are the features of suffusion?

- larger vessels targeted - best appreciated on surfaces - lesions are fairly large (usually 1 cm or more), and often coalescing - affects larger contiguous areas

What are the characteristics of serous fluid?

- leakage or accumulation of fluid with low plasma protein and low leukocytes - watery material leaks from small gaps in endothelial cells - inflamed serous glands add to fluid via hypersecretion - a transudate results: low specific gravity (SG) - example: burn, acute allergic reactions

What is the gross appearance of chronic inflammation?

- lesions vary depending on composition and presence of prior/ongoing necrosis - color: grey to white (macrophages & lymphocytes + proliferative fibroblasts and fibrous connective tissue) - texture: firm (fibrous connective tissue (fibroblasts + endothelial cells) and consolidation (solidification) of lymphocytes in exudate) - shape: irregular to pitting to nodular

What occurs during the activation & adhesion step of the leukocyte adhesion cascade?

- leukocytes & endothelium activated by interleukin (IL)-1, IL-6, IL-8, TNFα - binding of leukocyte integrins to endothelial ICAM-1

What occurs during the rolling step of the leukocyte adhesion cascade?

- leukocytes express selectins - cause loose & transient binding

What are gross morphological external features of autolysis?

- livor mortis (blue-purple color of the lower tissues and organs due to post mortem congestion --> blood pooling/settling) - rigor mortis: occurs between 1-6 hours after post mortem, gas production and foul odor usually accompany this change - desiccation: the removal of moisture from something, late autolysis of homeotherms

What is ulceration and eorsion?

- local defects or excavations of organs/tissue surfaces - often mucous membranes with resultant sloughing of necrotic tissues

What is the pathologic significance of neoplasms?

- local disease: compression, invasion and disruption of normal structures - distant disease: metastases - functional activity: hormone synthesis - cancer cachexia: loss of body mass - systemic manifestations: paraneoplastic syndromes

What causes localized congestion?

- local obstruction to venous drainage from organ displacement (intestinal volvulus/intussusception/strangulation) - external pressure: inflammatory or neoplastic masses, organ displacement or localized fibrosis

What are the effects of emboli?

- local obstructive effects - dissemination of infection, neoplastic disease

Where does edema occur?

- localized accumulation in soft tissues - generalized accumulation in soft tissues (especially fetus) = anasarca - fluid accumulation in cavities = "hydro" + cavity name

What are the types of edema?

- localized: due to obstruction of venous outflow - generalized: chronic venous congestion or heart failure

What does it mean if a cell is stable?

- long half-lives = renewed by proliferation if needed - low turnover

What is gastrointestinal hemorrhage? What are the types?

- loss occurs inside and out - melena and hematochezia

What are the microscopic features of autolysis?

- loss of tissue architecture - separation of blood: blood clots settled on the "down side" of the animal due to gravity - invasion of saprophytic intestinal bacteria: saprophyte = organism that grows on dead tissues

What are monocytes?

- main source of tissues macrophages in necrosis and inflammation - are "less active" but effectively the same cell in circulation

What is methemoglobin?

- oxide of hemoglobin - ferrous iron of hemoglobin is converted to ferric iron resulting in "chocolate brown" blood - caused by nitrate poisoning - reported with acetaminophen, naphthalene, local anesthetics and chlorates

What is the mechanism for repair by regeneration?

- parenchymal restoration aka regrowth - complete regeneration of functional tissue in a damaged organ - proliferation of residual stem cells or differentiated cells with regenerative ability

What is congestion?

- passively congested tissues are blue or purple - decreased outflow and capillary bed swollen with deoxygenated venous blood -passive accumulation of blood in a vessel usually due to decreased outflow, with normal inflow - often accompanied by edema (swollen, turgid vessels leak) - tissue is dark red to blueish color (stagnant blood), swollen and cool to touch - results in cyanosis (blue ting)

What are characteristics of necrosis and apoptosis?

- pathologic or programmed cell death as opposed to expected decomposition - can affect any tissue or organ but pattern varies with the affected site - distinct morphologic features and sequalae - basic mechanisms: disruption in energy supply and disruption in cell membrane

Chronic inflammation occurs secondary to acute inflammation due to one or more of what?

- persistence/resistance - isolation - unresponsiveness - autoimmunity - unidentified cause

What are conditions and factors that impair wound healing?

- persistent foreign bodies - infection - neoplasm - lack of first intention healing - impaired collagen synthesis - chemotherapy - starvation - malnutrition

What is a sequestrum?

- persistent fragment of necrotic bone - can happen in other tissues, but bone is most common

What can cause chronic inflammation?

- persistent infections - intralesional indigestible material - atypical bacteria - many types of fungi and parasites can cause persistent, chronic infections - foreign material may be made by a pathogen or introduced

What are serous clinical examples?

- photosensitization: link to consumption of certain plants or can be spontaneous - exotic Newcastle disease: serous tracheitis with pulmonary congestion and hemorrhage in a chicken

What is hemorrhage by rhexis?

- physical disruption of the vascular wall (large tear) - usually caused by trans-mural injury (right across the wall) - larger accumulations of blood

What are the etiologies of hemorrhage by rhexis?

- physical trauma: laceration, rupture - vessel weakening (aneurysm and/or excessively high blood pressure)

What are hematogenous pigments?

- pigments ordinating from hemoglobin modification or breakdown - endogenous pigment

Malignant tumors are what?

- pleiotropic (composed of variably differentiated cells) - progressive, over time losing resemblance to normal cells of their lineage (de-differentiation)

What causes increased intravascular hydrostatic pressure?

- portal hypertension (right heart failure. hepatic fibrosis) - iatrogenic fluid overload - pulmonary hypertension (left-side heart failure) - localized venous obstruction (gastric dilation, volvulus)

What are the characteristics of autolysis?

- post mortem - diffuse - affects all cells in a given area - does NOT induce a tissue reaction - no inflammation - only dead tissues in section - pigment: hemoglobin, bile, pseudomelanosis - gas formation & putrefaction - erythrocytes may have hemoglobin leeching - skeletalization

What are defining characteristics of autolysis?

- post mortem - progressive anoxia --> energy --> putrefaction

What are some characteristics of autolysis that distinguish it from necrosis?

- post mortem - diffuse - affects all cells in a given area - does NOT induce a tissue reaction

Where is lipofuscin most common?

- post-mitotic cells: cardiac myocytes, skeletal muscles, and neurons - slowly dividing cells: hepatocytes and glial cells

What is important to know about myxomatosis?

- poxviruses = double stranded, DNA viruses - transmitted by biting arthropods (mosquito, flea) or direct contact - disease severity variable- depends upon viral strain and host species

What is the significance of chronic inflammation nonsuppurative?

- presence in this inflammation type tells you that the lesion is subacute to chronic - typical terms: lymphocytic, lymphoplasmacytic, lymphohistiocytic (note: macrophage = histiocyte)

What can occur if inflammation becomes chronic?

- proliferation of some inflammatory cell populations - proliferation of stromal network including fibroblasts and angioblasts - proliferation of surviving tissues and cells - proliferation only occurs in cell populations that are not terminally-differentiated - neutrophils and platelets cannot proliferate in tissues

What are the most common biopsies?

- punch biopsy - wedge biopsy - excision biopsy

What is Splendore-Heoppli material?

- radiating, eosinophilic to basophilic material that forms around bacteria, fungi and parasites - dense, often stellate aggregate composed of antigen-antibody complexes - usually with pyogranulomatous inflammation

What do sarcoids look like macroscopically?

- raised, firm, nodules or plaques with a broad base - ulcerated +/- encrusted - local reoccurrence common

Explain production of fibrous connective tissue as a physiological response to tumors

- reactive "fibrosis": desmoplasia and scirrhous - carcinomas and adenocarcinomas may stimulate fibrotic response (desmoplasia) - secondary to proliferation of non-neoplastic stroma among (malignant) tumor cells - the response is mediated by growth factors secreted by neoplastic cells or any infiltrating leukocytes

What are the types of amyloid accumulations?

- reactive systemic - amyloid association (AA) - primary amyloid - amyloid light-chain (AL)

Acute inflammation: tissues become what?

- red due to increased blood flow - swollen due to edema

What is metastasis? It can occur by what?

- spread of neoplasm from the primary site (where originally formed) to a distant site (different organ) - can occur by hematogenous spread, lymphatic spread, implantation

What are the categories under special stains?

- standard histochemistry: example is toluidine blue (t-blue) for the metachromatic granules of mast cells - immunohistochemistry (IHC): cell markers

What are the conditions that can result in decreased osmotic pressure?

- starvation: inadequate protein intake - liver disease: decreased protein production - renal disease (protein losing nephropathy): glomerular loss of albumin - gastrointestinal disease: malabsorption, parasitism - severe burns

The cellular and proliferative inflammatory response can be what?

- suppurative - nonsuppurative - granulomatous - or a combination thereof, they are named by the predominant feature of the exudate

What is the gross appearance for fibrinous exudate?

- surfaces are covered in thick, stringy, elastic, white-gray to yellow exudate - can be pulled and removed from underlying tissue

What are simple findings with disseminated intravascular coagulation (DIC)?

- systemic microthrombosis - affects capillary loops - numerous petechiae - poor blood clotting

Define health

- the "normal" condition of the body, in which all cells, tissues, organs and systems are structurally intact and functioning properly - the body, as a whole, is in harmony with its environment

Define etiology

- the cause of a lesion or disease - anything that can disrupt the normal functioning of a cell, tissue, organ or system

What is right sided heart failure?

- the liver and abdominal vasculature are primarily congested - blood backs up in the portal circulation - fluid accumulation in the abdominal cavity (i.e. ascites) - if the problem is primarily in the right side of the heart (pooling right atrium and vena cava), the blood will back up causing congestion throughout the body but especially in the liver

Macrophages are activated by what?

- the process of phagocytosis via autocrine stimulation - bacterial products like lipopolysaccharide )LPS) - cytokines, especially IFNɣ, TNFα, and type 1 IFN from other macrophages

What is left sided heart failure?

- the pulmonary circulation is primarily congested - blood backs up in pulmonary circulation - fluid accumulates in the alveoli of the lung (pulmonary edema) - if the blockage originates due to backup on the left side of the heart, the hydrostatic pressure is first noticeable in the lung (pulmonary congestion)

What is cellular degeneration?

- the result of sub-lethal injury - reversible but no always as readily as adaptation responses - may reverse and result in recovery or may progress to cell death

What is cellular adapatation?

- the result of sub-lethal injury - reversible! Readily returns to original state when inciting cause is removed

What is implantation?

- the spread of tumors over tissues (rather than through blood or lymph) - separation of malignant cells from primary site and implant in the adjacent tissue with migration through blood or lymph

What is a biopsy?

- the surgical removal of a representative sample of tissue from a suspicious lesion for a diagnosis - processed and examined under a micrscope

What is proud flesh in horses?

- this is a term used in equine medicine to describe exuberant overgrowth of granulation tissue - typically occurs on a distal limb

What is the microscopic appearance for fibrinous exudate?

- thread-like eosinophilic meshwork that forms solid masses of material - often appears beaded

What is a hallmark sign of nitrate poisoning?

chocolate brown blood and muscle

What are the types of pathologic calcification?

dystrophic and metastatic

Define friable

easily broken, prone to crumbling when handled

What do benign neoplasms do?

expand and compress surrounding tissues

Define ulcers

full thickness loss through the basement membrane

Define abscessation

formation of abscesses

What does autolysis result from?

from progressive tissue anoxia - energy depletion --> putrefaction or spreading decomposition via microbes which come mostly from the gut

What is anasarca?

generalized edema affecting the entire body

What is the fundamental etiology of cancer?

genetic mutations within dividing or potentially replicating cell population

What are primary intrinsic etiologies of disease?

genome alterations - genetic mutations (germ cell or somatic) - familial/breed predispositions

What is the embryologic origin neuroectodermal?

give rise to CNS

What is an obturating thrombus?

partial vessel occlusion by the floating tail of a thrombus

What is embolism (thromboembolism)?

parts of a thrombus dislodge and form obstruction at distant location

What is the single most important concept for understanding diagnostic pathology (and clinical medicine)

pathogenesis

What is amyloid?

pathologic, extracellular, insoluble, proteinaceous (hyaline) substance resistant to proteolysis and deposited between cells

In the absence of repair, mutations become what?

permanent ("fixed")

What does autoimmunity entail?

persistent antigens that induce immune responses (persistent because antigens are host-origin)

What most often causes caseous necrosis?

persistent pathogens: fungi, protozoa, mycobacteria like the causative agent in bovine tuberculosis

Granulomatous epithelioid macrophages are most common with what?

persistent stimuli such as atypical bacteria, fungi, parasites, foreign material. etc.

Fluid distribution between compartments is controlled by what?

physicals barriers, differences in pressure, and concentration of substances within the fluid

What are secondary intrinsic etiologies of disease?

physiologic abnormalities related to - age - sex - species

What are the types of hyperemia?

physiologic and pathologic

What is petechia?

pinpoint (1-2mm) hemorrhage usually associated with mild injury of capillaries (diapedesis)

What are Mott cells?

plasma cells that contain Russel bodies

What is a clinical example of atrophy?

portosystemic shunt --> liver atrophy - due to decreased blood flow - smaller organs and cells

What is carcioma in situ?

pre-invasive form of carcinoma

What are the pigments in pathology?

pre-mortem and post-mortem color changes

What are the types of intrinsic etiologies of disease?

primary, secondary, idiosyncratic

Define inspissation

process of drying/desiccation of pus

What does familial amyloid mean?

systemic form AA amyloidosis hereditary in some breeds dogs and cats - shar pei dogs and Abyssinian cats

Decreased osmotic pressure can cause what kind of edema?

tends to be generalized - high protein loss: burns, chronic gastrointestinal or renal glomerular disease - decreased protein absorption: chronic gastrointestinal disease - reduced protein production: severe chronic liver disease

What is an example of a mixed tumor?

teratomas: arise from totipotential germ cells, contain tissues from all embryonic germ layers

What is the significance of suppurative inflammation (what does finding a large number of neutrophils and liquefactive necrosis tell us)?

that the agent is typically bacterial

Where does liquefactive necrosis occur?

the CNS is predisposed - malaica = term for liquefactive necrosis in CNS - low amount of protein = less to coagulate - high amount of lipids --> tend to liquefy

What can proliferative chronic inflammation appear like microscopically?

the mucosa is markedly thickened due to hyperplasia of the mucosa

Define intravasation

the process by which tumor cells enter blood and lymphatics

Acute inflammation is classified based on what?

the type of exudate present

What is neoplasia?

the uncontrolled, abnormal growth of cells or tissues in the body

What is an important note about the term "hypertrophy"?

this term is often used to describe gross enlargement of an organ regardless of whether the enlargement is due to hypertrophy and/or hyperplasia

Nodular granulomatous inflammation is also called what?

tuberculoid

What is the microscopic appearance of adenocarcinoma?

tubules and Acini or glandular

Define poorly differentiated

tumor cells do not function like the normal tissue and appear abnormal on microscopy

Define dedifferentiated (anaplasia)

tumor cells have a lack of differentiation and an embryonic phenotype

Define well differentiated

tumor cells look and function like normal cells of the tissue

What is the nature of lesions (the process) for inflammatory?

types of inflammation - purulent/suppurative (full of neutrophils) - granulomatous - hemorrhagic - necrotizing - proliferative - lymphocytic/plasmacytic - catarrhal - ulcerative

What does the necrosis lesion gradient refer to?

typically one can identify a visual gradient of degenerative cells between normal, intact tissue and overtly necrotic tissue

What is the microscopic appearance of articular gout?

urate crystals are seen as acicular clefts and birefringent crystals surrounded by an inflammatory response (macrophages, giant cells and neutrophils)

How is cellular glycogen accumulation identified?

use histology and special stains: - cytoplasm will appear granular - PAS stains glycogen magenta

Which cells are included in the stable cell population?

hepatocytes, osteoblasts, chondroblasts, smooth muscle, skeletal muscle, endothelium, glial cells, adipose cells

What is the gross appearance of wet gangrenous necrosis?

soft, moist, reddish-brown to black

What is a simple granuloma?

solid core of macrophages thus non-caseating

What is proliferative chronic inflammation?

some inflammatory processes result in signaling that causes the remaining tissue to markedly proliferate

What is hemorrhagic diathesis?

systemic bleeding caused by a deficit of clotting factors (hypocoagulation from a coagulopathy)

What is extrinsic pathway for apoptosis?

- activated in response to pro-inflammatory cytokines like tumor necrosis factor (TNF) - important caspase 8

Appearance of the final scar depends on multiple factors like what?

- nature of initial injury - degree of ischemia - amount of wound contamination - method of wound closure - accuracy of margin realignment

What is melena?

- originates in upper alimentary tract, blood is digested by gastric acid - feces is black and tarry

What are potential causes of Zenker's necrosis?

- vitamin E deficiency - ischemic necrosis (myocardial infarction) - bacterial toxins (black leg and other diseases caused by clostridium spp.)

What is the time frame (duration)?

- acute (hours to a day or so) - subacute (one or a few days) - chronic (several days to weeks, months or years) - chronic-active (chronic duration but ongoing inciting stimulus)

What is fibrinous?

- acute adhesion that temporarily bridge structures - may be used by fibroblasts as a highway to make more permanent connective structures aka a scaffold for wound healing - fibrin is made by the coagulation cascade - low strength, acute

What are the subtypes of coagulative necrosis?

fat necrosis and Zenker's necrosis

What is dystrophic calcification?

- affects visibly diseased or necrotic tissue - inflammation: nodules due to indigestible microbes (abscesses, granulomas) and persistent irritants (foreign bodies, migrating parasites)

What is ventral edema?

fluid in dependent (ventral) tissues- typically reflects a primary disease of the heart, lungs and/or liver

What are the factors influencing the quality of restoration?

- cell type - structural integrity: basement membrane, supporting stroma, vascular supply - extent of inflammation

What is hydropericardium?

fluid in the pericardial sac

What are early changes of necrosis?

- celling swelling and/or palor - loss of internal cell detail - characteristic chromatin changes in the nucleus

What are mesenchymal round cell tumors?

- cells are round to oval and discrete - may cluster if in large numbers (sheets)

What is hypertrophy?

- cells larger than normal - may have increase in size of tissue mass - cells otherwise appear normal

What is atrophy?

- cells smaller than normal - may have reduction in size of tissue mass - cells otherwise appear normal - reversible unless prolonged: prolonged atrophy may become irreversible and eventually lead to cell death

What are the attributes of effusion?

- cellularity - color - protein content - specific gravity

How does exudate occur?

- fluid and protein - vasodilation and stasis - increased vascular permeability

What is hydroperitoneum?

- fluid in the peritoneal cavity - aka ascites

What happens for an exudate to occur?

- fluid protein leakage - inflammation: vasodilation and stasis, increased interendothelial spaces

What does restoration of vascular bed entail?

- fluids removed by lymphatic vessels - proteins and cells cleared by histiocytes

What are the "atypical bacteria"?

- mycoplasma, chlamydise, rickettsia - all lack cell wall, apa "incomplete" - all are zoonotic

What are the features of hematoma?

- acute: blood is fresh, usually red or purple - subacute: old blood is degrading ("organizing"), may be multicolored - chronic: blood pool may be walled off by a fibrous capsule, which remains after blood is resorbed

What is hydrothorax?

fluid in thoracic cavity

What is hydrocephalus?

fluid within the ventricular system of the brain

What are vaccination or injection-site sarcomas?

- affected species = cats > ferrets > dogs - arise at vaccination sites neck, thorax, lumbar region, flank and limbs - "culprit" vaccines usually FeLV and rabies

What are the causes of cell injury?

"Double MINT" -malformation: genetics, teratogens - miscellaneous: metabolic, aging, hypoxia - infectious: viruses, bacteria, fungi - immune: autoimmune, hypersensitivity, immune responses - nutritional: protein caloric intake, vitamins, minerals - neoplastic: genetic, viral, chemical, radiation -trauma: mechanical, temperature, radiation - toxicity: inorganic chemicals, drugs, plants

Classic granulomas are also called what?

"simple" and "non-caseating" granulomas

What are macrophages?

- "big eater" - phagocytose debris and agents - present antigens - secrete cytokines and chemokines critical in chronic inflammation and repair/restoration processes

What is hemorrhage by dipedesis?

- "leakage" through minor defects in a grossly vascular wall - usually caused by damage to the endothelium (not functioning properly)

What is used for gross pathology?

- "macroscopic" - with the naked eye

What is used for histopathology?

- "microscopic" - using a light microscope

What are the features of suffusive "paint-brush"?

- "paint-brush" hemorrhage is when suffusive hemorrhage forms streaks (zebra striping) - inflammation, coagulation factor problems - larger vessel walls are breached - injury is more severe

What kind of bacteria are responsible for the infections that cause suppurative inflammation?

- "typical" - bacteria have a cell wall

What are the characteristics of subacute?

- 3-5 days to 7-14 days - minimal edema (+/- any pus reabsorbed) - decreased vascular changes - shift from neutrophils to lymphocytes and plasma

What are the general mechanisms of cell injury?

- ATP depletion - membrane damage - disturbances in cellular metabolism - genetic damage

What are other important tumor markers besides cytokeratin and vitmetin?

- CD31 for endothelial cells - CD3, CD20 for T and B lymphocytes in lymphoma

What occurs in response to persistent stimuli/antigens?

- Granulomatous epithelioid macrophages - granulomatous multinucleated giant cells

What are the histologic changes of amyloids?

- H&E: eosinophilic amorphous substance looks like "Cotton Candy" - Congo red stain: amyloid stains orange to red with this stain - Congo red stain with polarized light: Congo red positive amyloid shows apple green fluorescence with polarized light

What examples of some recognized DNA tumor viruses- double stranded DNA?

- Herpesvirus: α-herpesvirus: Marek's disease (lymphoma, gallid HV-2) - papovaviridae: papillomavirus - poxvirius: myxomatosis ("big head") domestic rabbits (sylvilagus)

What are the characteristics of disseminated intravascular coagulation (DIC)?

- Syndrome: wide-spread endothelial injury or activation results in activation of the coagulation cascade at numerous sites and activation of the fibrinolytic system (dissolves clots as they form) - numerous thrombi forming simultaneously in a widespread manner - net effect = consumption of platelets and coagulation factors with fatal bleeding (often characterized by petechiae)

What is fibrous chronic inflammation?

- a "form" of inflammation dominated by fibroblast proliferation - these lesions are generally chronic-active - represents either a self-perpetuating reaction or an early stage if lesion resolution

What is etiologic diagnosis?

- a diagnosis that names the cause or agent of the disease - common descriptors: agent or cause, location and/or process - e.g. parvoviral enteritis

What is disease diagnosis?

- a diagnosis that states the "name of the disease" - e.g. Johne's disease

Define pathognomonic

- a lesion so distinctive and unique that it can only be caused by a single etiologic agent or disease process - very high specificity

What is the mitotic index?

- a measure of cellular proliferation - percentage of cells undergoing mitosis in a given population of cells

What is prognosis?

- a prediction of a future outcome for the patient - typically expressed in degrees of "optimism" (like excellent, good, fair, guarded or poor) - combines the case history with prior experience - important to fully understand the disease, especially pathogenesis

The meaning of diagnosis is understood from context to be what?

- a set of possibilities: the "differential" list - a procedure: test used to identify a disease - an interpretation: opinion regarding the test outcome

What is a lesion?

- a visible manifestation of disease - a "morphologic" (structural) change in cell, tissue, or organ anatomy that can be visualized as abnormal at some level

Autolysis is typically most extensive in what?

- abdominal viscera due to proximity to gut - lesions associated with bacterial infections - overheated carcasses

What are the steps that lead to chronic inflammtion?

- abscess formation - persisting damaging agent with tissue destruction - organization with continued inflammation

What is fibrinoid necrosis?

- accumulation of pink amorphous masses of fibrin, antibodies and serum proteins in arterial walls - often due to immune injury - neutrophils are often present

What are parenchymal changes due to neoplasia?

- atrophy: directly by pressure from tumor on tissue, or indirectly as tumor presses and occludes ducts (causing fluid buildup and back pressure on the organ) - necrosis/hemorrhage: as tumor destroys normal tissue (pathologic fractures)

What is a mural thrombus?

- attached to a large vessel (aorta) or endocardium of ventricle or atrium wall by a very wide base

What is the etiology of chronic inflammation granulomatous?

- atypical bacteria - fungi - foreign material - etc.

What are animate agents of extrinsic etiologies of disease?

- bacteria - fungi - parasites (protozoa and metazoa) - viruses - weird "microbes" (prions)

What are some types of emboli?

- bacteria: septic emboli - cartilage: fibrocartilaginous emboli - gas/air: chest wall injury, deep sea diving - lipid ("fluid") - neoplasm (cells): neoplastic emboli - parasites: e.g. heartworms

How is normal body fluid maintained?

- balance between hydrostatic and colloid oncotic pressure - proteins keep fluid in vessels

What is the tumor nomenclature of round cell tumors?

- benign: -oma - malignant (circulating): leukemia - malignant (solid): sarcoma

What is hematin?

- black-brown compound from oxidation of hemoglobin, contains ferric iron - black fluke pigment - deposited pigment in migration tract of parasite within liver - hemoglobin ingested & digested by parasites- "Fluke Exhaust"

What are clinical examples of necrohemorrhagic inflammation?

- blackleg in cattle - necrohemorrhagic enteritis

Infarcts are most common in what?

- blockages of arteries > veins - organs with limited collateral blood supply (e.g. brain, kidney)

Expansion (outward growth) for benign and malignant tumors are limited by what?

- blood (nutrient and oxygen supply) - density of tissue - encapsulation (fibrosis) - inflammation/immunity

What is important to know about the tumor vascular supply?

- blood supply matters - tumor cells care less dependent upon adequate vascularization than are their normal cell counterparts - tumors growing under suboptimal growth condition(s) may experience ischemic degeneration and necrosis, with the most viable areas residing near blood vessels

What is pseudomelanosis?

- blue-green to black discoloration due to Iron Sulfide (FeS) - results from putrefactive bacteria (H2S) + iron (Fe) from hemoglobin - 1-2 days post mortem

What are the factors that impact autolysis rate?

- body size - insulation - haircoat - species - temperature - time

What are the factors that accelerate autolysis?

- body size: larger (maintain higher body temp for longer) - insulation: obese (fat means maintenance of body temp for longer) - haircoat: wool or thick (help maintain body temp) - species: herbivore- gut microbes - temperature: higher; febrile animals or homeotherms - time: longer

What are clinical examples of fibrinonecrotizing inflammation?

- calf diphtheria - pseudomembranous colitis

What is transmissible cancer? What are examples?

- cancer cell or cluster that can be transmitted from animal to animal - canine transmissible venereal tumor (TVT) --> round cell lineage - devil facial tumor disease

What are the features of petechiae?

- capillaries targeted (diapedesis) - best appreciated on the surface - lesions are very small (<2mm) - damage is minimal but widespread

What is carboxyhemoglobin?

- carbon monoxide poisoning results in formation of carboxyhemoglobin (carbon monoxide + hemoglobin) - CO --> higher affinity for heme than oxygen - causes blood to be "bright cherry red"

What are the 4 main aspects of disease?

- cause (etiology) - pathogenesis - morphologic changes (structural alterations from normal) - functional consequences

What is fescue foot?

- caused by a fungus producing ergot alkaloids - dry gangrene results from ischemia of the distal limbs - example of gangrenous necrosis

What is venous obstruction?

- caused by blockage of veins leading away from organ - venous infarction are dark red/black because blood cannot leave

What causes generalized congestion?

- caused by decreased flow of blood through heart or lungs - heart failure

What are key characteristics of apoptosis that make it different from necrosis?

- cell completely controls process - no inflammation in dead tissues - often individual cells affected - cells shrunken, membranes intact - uniform nuclear chromatin clumping - mitochondrion is key here also, but here the organelle actually drives the process

What are common etiologies of cell death?

- cell deprivation: glucose and/or oxygen lacking - cell overload: buildup of metabolic byproducts - immunologic: inflammatory reactions - kinetic energy: heat, cold, pressure, trauma, radiation - toxic agents: exogenous (chemicals/drugs) or endogenous (metabolic byproducts) - reactive oxygen species (ROS) or Nitrogen Species (RNS)

What are key characteristics of necrosis that make it different from apoptosis?

- cell loses control of its processes - inflammatory response in dead tissue - typically many cells affected - variable cell appearance: swollen vs shrunken, membrane often not intact, pyknosis vs karyolysis vs karyorrhexis - mitochondrial injury is key

What is the structure of caseating granulomas?

- central core of necrotic debris (caseous necrosis) - often include material: common in cattle, less common in pigs, uncommon in sheep - zone of activated macrophages and MNGC - zone of macrophages and lymphocytes - +/- peripheral zone of fibrous connective tissue

What is the pathogenesis of DIC Schwartzman reaction?

- characteristic of the horse, also rabbit - equine cortex has limited plasmin relative to other species, leading to massive fibrin activation

What are the characteristics of chronic active?

- chronic duration but ongoing inciting stimulus: may see long-term lesion with both macrophages and neutrophils for example

What are the harmful effects of inflammation?

- chronic lesions may become self-perpetuating ("positive feedback") - tissue injury may, over time, lead to autoimmune diseases if inflammation begins targeting normal "self" tissues

What is the pathogenesis of amyloid?

- circulating precursor protein such as SAA or light chains - partial degradation leads to misfolding - misfolded protein is deposited in tissues - misfolded protein aggregates to form amyloid fibrils that displace and compress cells

What do sarcoids look like microscopically?

- circumscribed with widespread invasion of superficial dermis - plump spindle cells arranged in short interlacing bundles, whorls, columns - variable epidermal hyperplasia

What are the characteristics of transudate?

- clear - not inflammatory - watery/thin - low specific gravity - low protein - acellular - no microbes

What is the gross appearance of edema?

- clear, gel-like fluid within tissue - swollen, wet, heavy - expansion of fascial planes by fluid or free fluid - tissue wet on cut surface, readily leaking fluid - fluid is generally clear or slightly yellow - tissue may have a doughy, gel-like consistency ("pitting edema")

What is paraneoplastic syndromes?

- clinical signs that are a side effect of neoplasia - usually caused by secretion of hormones, metabolites, or other mediators that have an action on other organs, but not related to the size, location or metastasis of the tumor - tumors secrete proteins

What are some important things to remember about first intention wound healing?

- closure of a recent (<24 hours) clean wound in a well-vascularized tissue ("clean" = surgical) - wound must be debrided before granulation tissue has had time to form if not "clean", this cleans it up - wound edges must not be under tension

What is second intention wound healing?

- closure of untreated wound by granulation tissue & subsequent re-epithelialization (takes longer and a larger scar forms) - commonly used to manage infected or contaminated wounds - approximation of wound margins occurs by contraction of newly made myofibroblasts - complications include delayed closure & excessive scarring

What are the characteristics of exudate?

- cloudy +/- color - inflammatory - viscous/thick - high specific gravity - high protein - many cell types - may have microbes

What are the characteristics of gangrenous necrosis?

- coagulation + liquefaction + saprophytic bacteria + mummification - necrosis + anaerobic bacteria = emphysema

What are the major different types of necrosis?

- coagulation/coagulative - liquefactive - caseous - grangrenous

What is gas gangrenous necrosis?

- coagulative necrosis + anaerobic bacteria producing a toxin - results in emphysema - commonly caused by clostridium spp.

What is wet gangrenous necrosis?

- coagulative necrosis + liquefaction and saprophytic bacteria - tends to ooze and produce a lot of discharge

What roles do fibroblasts play in inflammation?

- collagen production: increases tissue tensile strength - proliferation: filling space - secretion of cytokines and growth factors

What are the subtle gross changes of hydropic?

- color: paler - consistency: softer - size: slightly larger - weight: heavier

What are the gross changes of cellular fatty change?

- color: paler - size: larger - the surface appears (and would likely feel) greasy

What is the significance of hypertrophy?

- common, often protective response - may be secondary to increased functional demand - may be a compensatory change - can be due to over nutrition (increased adipose size)

Inflammation can also be a potentially harmful process. How?

- components of the inflammatory response capable of destroying microbes can also injure normal host "bystander" tissue - beneficial and detrimental effects both locally and systemically

What is the microscopic appearance of caseous necrosis?

- composed of amorphous and granular debris lacking cell outlines and tissue architecture - inflammation is prominent: granulomatous inflammation consists of macrophages and multinucleated giant cells

What are the characteristics of suppurative/purulent exudate?

- composed of large numbers of neutrophils (live and dead) and dead cells + neutrophilic debris - this forms pus --> exudate of suppurative inflammation

What are mixed tumors?

- contain multiple cell types derived for single to multiple germ layers - thought to rise from pluripotent cells (capable of differentiating into variety of cell types)

Acute vascular response activates targets of many mediators such as what?

- contractile elements in endothelial cells - vascular smooth muscle cells

What are the types of inclusion bodies?

- crystalline protein inclusion bodies - viral inclusion bodies

Malignant neoplasms may be what?

- cystic/friable/hemorrhagic (evidence of necrosis) - surface tumors often are ulcerated - usually not encapsulated and grows deep (invades)

What happens with fibrosis?

- damage to supporting stroma, the connective scaffold of tissue, is common - orderly regeneration is impeded when this damage is significant or severe - an influx of collagen-producing fibroblasts fills defects left by dead cells

What is a necropsy?

- dead + view - traditional term applied to the post mortem dissection of an animal to determine the cause of death - literal meaning = death examination - owners are often not familiar with the term "necropsy" but readily recognize the concept of "autopsy"

Reduction in mass of tissue or organ as an adaptation to altered demands are due to what?

- decreased workload - decreased nutrition - loss of hormonal stimulation - decreased blood supply - loss of innervation

What is hyaline?

- deposited protein material that is homogenous, eosinophilic (pink), amorphous or glassy with H&E - nonspecific for several changes - intracellular and extracellular

What are the beneficial effects of inflammation?

- destroy or neutralize injurious agent - restrict damage due to agent - encourage repair of surviving tissue

What is an embolus?

- detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant - often occlude small vessels, cause complete obstruction which may lead to ischemic necrosis (infarction)

What is a diagnosis?

- determination of the nature or cause of a disease - origin: "dia" = through, "gnosis" = knowledge - requires thought and persistence

What are autolytic changes characterized by?

- diffuse distribution in a tissue - variable degree of severity (worse near gut) - often sharp borders orders between autolytic and "normal" tissue - lack of tissue reaction: no inflammation, no vascular leakage, no host response to bacteria

Granulomatous inflammation can be what?

- diffuse: loose but aggregated and replacing normal stroma - nodular: organized into distinct structures called granulomas

What is feline plasma cell pododermatitis?

- disease of unknown pathogenesis or cause - clinically --> soft and spongy swelling of multiple foot pads - the central metatarsal and metatarsal pads most consistently involved

What is turbulence?

- disrupts laminar blood flow - mixes blood = interaction with coagulation factors - physically injures endothelium, stimulus for platelet adhesion and coagulation

What are the different thrombus resolution?

- dissolution/resolution (no scar): small thrombi via thrombolysis - organization (inelastic scar): larger thrombi via phagocytosis debris, granulation tissue, fibrosis, and regrowth endothelium - recanalization (new channels): organized by fibroblasts and formation new vascular channels

What is the mechanism of ecchymosis?

- e.g. bacterial sepsis - damage is mild but widespread

What is the histogenesis of epithelial tumors?

- ectoderm, endoderm - carcinomas, adenocarcinomas

What is effusion? What is edema?

- effusion: an fluid that is filling space in a body cavity - edema: fluid in tissues

What are the goals of inflammation?

- eliminate the initial cause of injury: dilute, destroy or wall off injurious agents - remove necrotic cells and tissues - initiate the process of repair aka healing

What is melanin?

- endogenous pigment - light brown to black pigment - protects against UV light - produced by melanocytes located in basal layer skin, retina, iris, hair follicles - normal in pia-arachnoid of black animals and oral mucosa of some breeds

What is ceroid?

- endogenous pigment - similar histologically to lipofuscin but secondary to pathologic conditions (not aging associated)- as a result of fat oxidation

What is lipofuscin?

- endogenous pigment - wear-tear pigment or aging pigment (undigested residues within lysosomes) - yellow-brown, granular intracytoplasmic pigment - product of lipid peroxidation and aging - no damage to cells

What are inanimate causes of extrinsic etiologies of disease?

- energy (radiation, thermal) - physical forces (pressure, trauma) - surgical intervention - xenobiotics (chemicals, drugs, metals, toxins)

Neoplasia growth relative to normal tissue is what?

- excessive - unregulated (not subjected to normal growth control processes) - irreversible (persists after removal of the initiating stimulus) - may lead to malignancy: local invasion or systemic metastasis

What is keloid?

- excessive scarring - an overgrown, firm, raised, stellate, often shiny, white to pink plaque that extends beyond the margins of the original wound - some people/animals are prone to these, even in wounds that close by first intention

There are three major pathways via which a cell executes apoptosis. What are they?

- extrinsic - intrinsic - perforin/granzyme - all apoptosis pathways lead to an execution phase mediated by caspase 3

What are the two most common causes of parasite hematin?

- fasciologies magna liver fluke in ruminants - pneumonyssus simicola lung mites in macaques

What are fibrinous clinical examples?

- fibrinous pleuritis: thick mat of fibrin covering the cranioventral portion of lungs - contagious bovine pleuropnemonia: pleural surfaces are covered by a thick, greyish friable exudate composed of fibrin and other plasma proteins - Glasser's disease: acute fibrinous polyserositis (pericarditis and peritonitis)

What are the prefixes for various tissues?

- fibroblasts: fibr- - bone: osteo: - cartilage: chondro- - striated muscle: rhabdo - blood vessel: hemangio- - fat cells: lipa

Extracellular products made by some neoplasms include what?

- fibrosarcoma (collagen) - osteosarcoma (osteoid) - chondrosarcoma (cartilaginous matrix)

How does transudate occur?

- fluid - increased hydrostatic pressure: venous outflow obstruction, example: congestive heart failure - decreased colloid oncotic pressure: decreased protein production, example: functional liver disease

What is statis

- major factor for development of venous thrombi - slow flow rate veins favors accumulation of activated clotting factors & contact of platelets with endothelium - reduced flow systemically via heart failure, or local congestion (vascular obstruction, dilatation) - humans --> inactivity, thrombosis in limbs

What is classification based on behavior for tumors?

- malignant tumors differ from parent tissue morphologically and functionality - malignant tumors characterized by anaplasia or cellular atypia, which refer to lack of differentiated features in cancer cells - abundant mitosis (not always) - invasiveness and metastasis

What are the cells types for fibrous chronic inflammation?

- many dividing fibroblasts - mixed leukocytes, especially mononuclear

What is the significance of carioma in situ?

- marked nuclear and cellular pleomorphism (variation in size and shape) - numerous mitotic figures A preinvasive form of carcinoma - remains within the epithelial structure which it arises from - does not penetrate the basement membrane

What are the clinical effects of benign neoplasms?

- mass effects and swelling - compression of surrounding structures - bleeding, infection, or other complications

What are the types of mesenchymal round cell tumors?

- mast cell tumor - plasma cell tumor - histiocytoma - lymphoma - transmissible ventral tumor

What is the microscopic structure of a remodeling scar?

- maturing scars consist of dense, avascular fibrous connective tissue - the collagen fibers are less organized and the bed of fibrosis is hypercellular

Why does autolysis matter?

- may obscure actual lesions relevant to diagnosis - actual lesions can affect the rate of autolysis

What are body reactions to leukocytes due to neoplasia?

- may promote tumor growth (by secreting pro-proliferative factors) or inhibit it (by participating in an immune response) - commonly in greatest numbers near the edges of the mass - benign neoplasms frequently have a prominent and visible inflammatory response while malignant neoplasms have minimal or none - carcinomas tend to have visible inflammation while sarcomas have minimal or none

What is eccymosis?

- medium size, "blotchy" and irregular (up to 2-10mm) hemorrhage associated with more moderate injury to endothelial cells - indicates injury of capillaries, arterioles and venules (diapedesis)

What are toll-like receptors (TLRs)?

- membrane receptors that recognize bacterial foreign antigens - downstream signaling from here often the initiation of a macrophage response

What is the histogenesis of mesenchymal/stromal tumors?

- mesoderm - round cell tumors (hematopoietic) - spindle cell tumors (sarcoma)

What is the difference between severity of inflammation?

- minimal: barely discernable histologically - mild: little to no tissue destruction & little cellular exudation, grossly detectable only if reddened or swollen - moderate: tissue damage grossly visible, cellular exudation & vascular reaction easily detectable histologically - severe: considerable tissue damage & extensive cellular exudation

What are the characteristics of peracute?

- minutes to 24 hours - edema +/- pus filled - hyperemia (redness) - possible hemorrhage - minimal cellular infiltrate - example: hives

Benign tumors are what compared to normal tissues?

- more cellular than their normal tissues - composed of generally well-differentiated cells

What is reaction system amyloid association?

- most common in animals - secondary to chronic antigen stimulation: chronic infections, neoplasia - precursor protein is serum amyloid associated protein (SAA)

What is primary amyloid- amyloid light chain (AL)?

- most common in humans - plasma cell tumors, myelomas - deposits same organs as reactive - protein is AL (immunoglobulin light chains)

What are the characteristics of venous thrombi?

- most common site - often fully occlusive - seldom yield infarction - many RBCs ("red") - site of stasis - no lamination - readily embolize

What are the characteristics of arterial thrombi?

- most serious site - usually partial occlusion - often yield infarction - few RBCs ("white") - alternating layers of platelets, fibrin, RBC's, and leukocytes = "Lines of Zahn" - often laminated

What is coalescing distribution?

- multiple sites merge together to form multiple foci - many people use "multifocal to coalescing"

What is a complex granuloma? What are the different types?

- multiple types depending on core contents - caseating, eosinophilic, suppurative (pyogranuloma), splendore-hoeppli

What does unidentified cause entail?

- multiple unique histologic patterns - people have hypothesized that everything from autoimmune to cryptic infectious agents

What are the descriptive terms for thrombi?

- mural (walls) - vegetative (on heart, great vessel valves) - occlusive (vascular obstruction) - obturating ("tail" extends in the direction of blood flow) - saddle (occurs at bifurcation of vessels) - septic (incorporates an infectious agent)

What are the characteristics of an ante mortem thrombi?

- mural thrombi attached to vessel walls - dry, dull, laminated - often tail extends downstream

What are the causes of inflammation?

- necrosis: from any cause - pathogens and their products (aka infections): bacteria, fungi, parasites, viruses - physical agents/trauma - toxicants: chemicals , metals, natural poisons or toxins - immune defenses: autoimmune diseases, hypersensitivity reactions

Explain hypoxia and angiogenesis as a physiological response to tumors

- neoplasms, (carcinomas particularly) frequently outgrow their blood supply - carcinomas often exhibit necrosis and hemorrhage at the center - sarcomas live quite will in low oxygen environments, so most cells in the mass remain alive - angiogenesis (the formation of new blood vessels from existing ones): an important process in the growth of malignant tumors, supplies nutrients, O2 and growth factors

All neoplasms are composed of two basic tissue elements. What are they?

- neoplastic cells (epithelial or mesenchymal) in origin - non-neoplastic fibro-vascular stroma (gives framework for growth and blood for nutrients)

What is sarcoid?

- neoplastic change - a locally-aggressive but non metastatic skin neoplasm in horses - arises at an old wound site in animals infected with bovine papilloma virus 1 or 2 - common on legs, eyelids, ears

What are the events in the resolution of inflammation?

- neutralization, decay or enzymatic degeneration of the various chemical mediators - normalization of vascular permeability - cessation of leukocyte emigration and apoptosis of remaining neutrophils in the exudate - the necrotic debris, edema fluid and inflammatory cells are cleared by phagocytes and lymphatic drainage

What occurs during the margination step of the leukocyte adhesion cascade?

- neutrophils out of central flow column - more to periphery next to endothelium

What is stroma?

- non-neoplastic supporting structure composed of extracellular connective tissue - consists of proteins, glycoproteins (collagen), embedded in proteoglycans - contain blood vessels that supply the tumor, fibroblasts, and variety of immune and inflammatory cells (fibrovascular) - produced by surrounding non-neoplastic mesenchymal cells - many mesenchymal tumors produce the extra cellular matrix (ECM) in their stroma

What type of inflammation is seen with subacute inflammation?

- nonsuppurative: exudate includes mainly lymphocytes (fewer/no neutrophils) - lymphoplasmacytic: exudate includes lymphocytes and is accompanied by locally made plasma cells

What type of inflammation is seen with chronic inflammation?

- nonsuppurative: exudate includes mainly lymphocytes (fewer/no neutrophils) - lymphoplasmacytic: exudate includes lymphocytes and is accompanied by locally made plasma cells - granulomatous: exudate is rich with macrophages, possibly activated cells (epithelioid) and multinucleated giant cells - granulation tissue: immature fibrous tissue with variable numbers of intermingled monocellular cells

What are the 3 categories of intracellular accumulations?

- normal cellular components accumulated in excess: water, lipids, glycogen, carbohydrates - abnormal substance: exogenous (mineral, infectious agents) or endogenous (abnormal synthesis during metabolism) - pigments

What is karyolysis?

- nuclear fading - DNAses and RNases dissolve the nucleus

What is karyorrhexis?

- nuclear fragmentation - pyknotic nuclear membranes rupture

What is pyknosis?

- nuclear shrinkage - DNA condenses into basophilic mass

What are the mechanisms for infarcts?

- obstruction (from inside): thrombi, emboli and arterial occlusion - compression (from outside): masses, tourniquets, mechanical twists (torsion/volvulus), traumatic vessel rupture

What are crystalline protein inclusion bodies?

- occur in normal hepatocytes and renal tubular epithelium, especially old dogs - large, eosinophilic, and rhomboid - may distort nucleus but unknown significance

What is local congestion?

- occurs due to acute or chronic occlusion of a vein - local or regional impairment of venous outflow: thrombus, pressure, twisting

Where does gout occur?

- occurs in human, birds and reptiles (all lack uricase)

What is metastatic calcification?

- occurs in normal tissue - hypercalcemia

When does autolysis occur?

- occurs post mortem - cell death in a dead animal

What is first intention wound healing?

- occurs with minimal tissue damage and edges are closely opposed, small tissue gap - epithelial continuity can be restored as early as 48 hours - allows epithelium to migrate across the wound before it fills with granulation tissue

What are functional tumors?

- often endocrine organs: thyroid adenoma, parathyroid adenoma, insulinoma - renal cell carcinoma --> erythropoietin --> high RBC count

What is the gross appearance of benign neoplasm?

- often raised above the tissue - may be wart like, polypoid and papillomatous - may be attached by a narrow stalk

What is the gross appearance of liquefactive necrosis?

- often there is cavitation with thick, creamy, viscous fluid replacing the tissue - the fluid is frequently malodorous (smelling very unpleasant)

What are the classes of regulatory genes that can be affected in the development of abnormal growth, eventually leading in neoplasia?

- oncogenes: growth-promoting regulatory genes - tumor suppressor genes: growth-inhibiting regulatory genes - apoptotic genes: regulate "programmed cell growth" - DNA repair genes; often considered to be another class of tumor suppressor genes

What are vaccine-associated sarcoma features?

- origin fibroblast > other mesodermal lineage - pathogenesis includes aluminum (in the adjuvant) and subcutaneous inflammation (higher if aluminum present - lesions are locally invasive (and highly recurrent) and metastasis has been reported regional lymph nodes, mediastinum, and lungs

What is hematochezia?

- originates in lower alimentary tract, blood is not digested completely - feces are more red and contain more clotted blood

What is included in the classic "triple response" associated with histamine release?

- red spot: due to capillary dilation centrally - flare: in the surrounding area due to arteriolar dilation, which is mediated by axon reflex - wheal: due to exudation of fluid from capillaries and venules aka swelling

What is hemoglobin imbibition?

- red staining due to lysed erythrocytes - especially myocardium, aorta, artery tunica intima - 1-2 days post mortem

What is fibrous?

- refers to connective tissue made by fibroblasts - tough, white, chronic

What is hypercoagulability?

- reflects an increase or decrease in concentration of activated hemostatic proteins (coagulation factors, coagulation or fibrinolytic inhibitors) - increase in prothrombotic factors, decrease inhibitory factors - activity of coagulation factors increase in multiple conditions (inflammation, stress, neoplasia, pregnancy, surgery, renal disease)

What is metaplasia?

- replacement of a fully differentiated cell type with another fully differentiated cell type - usually a "delicate" cell type is replaced with a "sturdy" cell type

What does it mean if a cell is permanent?

- replicative agility is lost when postnatal - no turnover

What are the four major outcomes of acute inflammation?

- resolution - healing by repair - abscess formation - chronic inflammation

What are outcomes of thrombosis?

- resolution: lysis - organization/recanalization - embolism (thromboembolism) - infarction and ischemia - disseminated intravascular coagulation (DIC)

What are intracellular examples of hyaline?

- resorption droplets of protein due to proteinuria - intestinal epithelium of neonatal pigs with ingested colostrum - Russel bodies in plasma cells

After dead tissue is removed, repair options are what?

- restoration: stem cells proliferate to reestablish full or partial structure +/- function - evolution: debris is dehydrated (inspissation) to form a semi-solid core (caseation) - replacement: the defect left by tissue removal is filled by fibrosis (scarring) - tissue loss: when cells on a surface die, the dead cells slough off and one of the other outcomes ensues - death: if the quality of dead tissue is too large for orderly removal, a sequestrum is formed

What are the fundamental characteristics of hypertrophy?

- reversible - cells are larger but NO new cells - not swelling - this involves synthesis of more structural components - often occurs with hyperplasia

What is dysplasia?

- reversible, abnormal cellular proliferation - loss in uniformity of individual cells and a loss in architectural orientation - epithelia most often affected - cancers may be preceded by severe epithelial dysplasia

What is the normal blood flow?

- right side of the heart pumps blood to the lungs, where oxygen is added to he blood and carbon dioxide is removed from it - left side pumps blood to the rest of the body, where oxygen and nutrients are delivered to tissues, and waste products are transferred to the blood for removal by other organs

What is the mechanism of hematoma?

- rupture of a vessel wall (usually of large caliber) - bleeding fills cavities or loose connective tissues - hematoma grows until pressure exerted by extravascular blood matches pressure within vessels OR vessel seals by hemostasis

What is autopsy?

- self + view - traditional term applied to post mortem dissection of a human being to define the cause of death - literal meaning = self examination - competing interpretations: a) "to examine one's own kind" - the traditional veterinary meaning b) "to examine for oneself" - the original meaning of the enlightenment anatomists

What is pathogenesis?

- sequence of events from start to end of a disease - encompasses both mechanism(s) and responses - lesions may require many steps to develop

What are the commonly affect areas for fibrinous exudate?

- serous membranes of body cavities: pleura, pericardium - fibrinous pleuritic, pericarditis, etc.

What type of inflammation is seen with acute inflammation?

- serous: exudate is mainly fluid - fibrinous: exudate is mainly fibrinogen-rich fluid - catarrhal: exudate includes substantial mucus - suppurative (or purulent): exudate includes many PMNs (neutrophils)

Ceroid is found in response to what?

- severe malnutrition - vitamin E deficiency - cancer cachexia - irradiation - inherited ceroid-lipofuscinoses

What does it mean if a cell is labile?

- short half-lives = constantly renewed - high turnover

For epithelial lined ducts, what are common sites for implantation and what are the potential tumor types?

- sites: gastrointestinal, genitourinary, or pulmonary systems - tumor types: usually adenocarcinomas or carcinomas

For serosa-covered surfaces, what are common sites for implantation and what are the potential tumor types?

- sites: linings of abdominal and thoracic cavities - tumor types: carcinomas or sarcomas

What is re-epithelialization?

- skin regrows beneath a scab or eschar - eventually get complete restoration of the epidermis with simultaneous loosening & release of the wound covering

What happens to blood accumulated and clotted outside vessel?

- small hemorrhages: serum absorbed by lymphatics, blood cells and hemoglobin degradation products picked up by macrophages at site of hemorrhage or draining lymph node - larger hemorrhage: clot may organize by fibrous tissue, hematoma, scarring

What is the interstitium?

- space between cells and the microcirculation that is composed of the extravascular matrix (structural, adhesive an absorptive elements) - fluid moves between vessels and the interstitium

When talking about the specific site of a lesion, what two things need to be addressed?

- specific organ involved (kidney, adrenal gland, lung, brain, etc.) - site within the organ (cortex, medulla, bronchi, hippocampus)

What are the characteristics of coagulative necrosis?

- tissue architecture is preserved - inflammation is a minor component - cell outlines remain with loss of cellular detail - microscopic changes are typical: nuclear (pyknosis, karyolysis, karyorrhexois) and cytoplasmic (hypereosinophilia, loss of detail)

What is the appearance of coagulative necrosis grossly?

- tissue retains original form - necrosis is often surrounded by reddened area caused by hemorrhage or hyperemia

What is caseous necrosis?

- tissues have a semi-solid "cheesy" composition - granular and friable - may include mineralization

What are the characteristics of caseous necrosis?

- tissues semi-solid (cheese) - friable +/- dystrophic mineralization - inflammation prominent (macrophages)

What are integrins?

- transmembrane receptors that mediate attachment between a cell & its surroundings - leukocytes express a variety of integrins: Mac-1, CDa11/CD18 - these bind to ICAM-1 on endothelium to initiate activation and adhesion in preparation for transmigration via CD31

What is important to know about canine papillomavirus?

- transmission by direct contact - causes exophytic lesions within the oral mucosa of young dogs - solitary or multiple on lips, tongue, roof of mouth, inside cheeks - affects puppies and young dogs - spontaneously regress over 1-5 months with immune response - DNA virus

What is important to know about rabbit fibroma virus?

- transmission by direct contact and arthropods - enzootic in cottontail rabbits - SQ nodules on head and legs - lesions spontaneously regress - DNA virus

What are the kinds of effusions?

- transudate - modified transudate - exudate

What are the different types of aneurysms?

- true aneurysm, saccular form (partial diameter) - true aneurysm, fusiform variant (full diameter) - false aneurysm, (full rupture, extravascular hematoma) - dissecting aneurysm (intramural hematoma)

What is polioencephalomalacia?

- type of CNS malacia - most commonly due to thiamine deficiency - cattle particularly but can also be dogs - in cattle, this is linked to consumption of a carbohydrate-rich diet that is poor in roughage

What are the characteristics of chronic inflammation suppurative abscesses?

- typically walled in fibrous capsule or bordered by dense parenchyma (progressive from acute suppurative inflammatory lesion) - centers may be inspissated

What are the characteristics of a post mortem clot?

- unattached to vessel walls - shiny, wet - forms a perfect cast of vessel lumina

What are the characteristics of hemorrhagic exudate?

- uncommon - usually causes: septicemia or bacteremia - always peracute - results form serious vascular injury leading to substantial blood loss with the inflammation - exudate contains large amount of free blood - can be difficult to distinguish between hemorrhage and hemorrhagic inflammation

Why are the fundamentals of cellular pathology important?

- understanding disease starts with understanding the cell - cell injury ties normal physiology to disease - there are clinically relevant examples of all of these processes

What is the pathogenesis of cellular myxomatous?

- unknown - frequently associated with cachexia or malnutrition of any cause (malabsorption, chronic infection, parasitism, neoplasia, etc

What is cyanosis?

- unoxygenated hemoglobin = blue color - blue tinged paw pads - secondary to saddle thrombus (partial obstruction iliac artery at aortic bifurcation)

What is perforin/granzyme pathway for apoptosis?

- used by T cells to eliminate virus-infected cells or any cell displaying surface molecules that signal to lymphocytes that they require elimination - does not require a caspase, but uses caspase 10 when this pathway is utilized

What is the purpose of immunohistochemistry (IHC)?

- used to assist in determining histogenesis, prognostic and therapeutic indications - antibodies paired with a marker are used to identify cells & tissues

What is systemic congestion?

- usually due to heart failure - usually associated with cardiac insufficiency (heart failure = generalized slowing of blood everywhere)

What are the characteristics for arterial obstruction?

- usually secondary to emboli - blood supply interrupted - arterial infarction pale because blood cannot enter

What is the pathogenesis of septic thrombi: valvular endocarditis?

- valve endocardium is injuried, expsoing the underlying tissue - a platelet-fibrin mesh covers the damage surface - the mesh becomes colonized by bacteria (or rarely fungi) - plaque fragments may break off, sending septic emboli to capillaries in other organs

What are the characteristics of malignant tumors?

- variable degrees of de-differentiation, expansion, metastasis, invasion, poorly demarcated origins, unencapsulated, fairly rapid growth rate, many abnormal mitoses, relentless progression, inadequate blood vascular supply (usually outgrown), pleomorphism (variation in size of nucleus), multiple nucleoli, many mitotic figures

What causes increased vascular permeability?

- vascular leakage associated with inflammation (infectious agents) - neovascularization (new, leaky vessels) - anaphylaxis (vaccinations, venoms)

At least initially, almost all inflammation is oriented where? Why is that?

- vascular oriented - b/c this is where inflammatory cells enter tissues

What is the morphology of septic thrombi?

- vegetations --> septic thrombi - very high numbers of bacteria - heart valves have "cauliflower" appearance

What occurs during the transmigration step of the leukocyte adhesion cascade?

- via PECAM-1 (CD31 on endothelium) - cells are called to inflammation via chemotaxis

What are the usual etiologies for chronic inflammation nonsuppurative?

- viruses especially - also neoplasms, immune-mediated diseases

What are the characteristics of chronic?

- weeks, months or years - angiogenesis, fibroplasia, regeneration: clear manifestation of host reparative process - inflammatory cells predominantly macrophages: +/- formation of epithelioid cells and multinucleated giant cells - infiltration of lymphocytes and plasma cells

What are the common clinical signs associated with cachexia?

- weight loss and debility (muscle wasting) - anemia - hypoproteinemia - immunosuppresion

What happens with inflammation?

- when cells die, the contents released when membranes break down are pro-inflammatory - neutrophils are attracted most often and arrive first - neutrophils produce heterolytic enzymes to liquefy necrotic material

What is the gross appearance of suppurative exudate?

- white, tan or green - foul odor - liquid (pus) or crumbly, dry (inspissated) exudate

What is the microscopic appearance of edema?

- widening of fascial planes and boundaries - clear spaces between stromal components (cells and fibers) - lymphatic vessels are prominently dilated - fluid may stain pink on H&E due to high protein content - no overt inflammation

What is the embryologic origin mesoderm?

develops in mesenchymal tissues which give rise to bone, bone marrow, connective tissue, muscles, fat and vessels

What is the embryologic origin endoderm?

develops into internal epithelial tissues- gastrointestinal (including liver, pancreas); pulmonary, reproductive and urogenital

Cells respond to injury or stress in 3 ways. What are they?

1) adaptation - cells in a tissue can react to stress such that a new homeostatic state is established, can eventually go back to its original form 2) degeneration - reversible cell injury from which a cell can adapt and recover 3) death - irreversible cell injury results in cell death by definition

What are the 4 types of cellular adapatation?

1) atrophy 2) hypertrophy 3) hyperplasia 4) metaplasia

What are examples of steps of pathogenesis?

1) biochemical change 2) functional alterations 3) morphological lesion 4) clinical signs

What is the pathogenesis of hydropic?

1) cell injury --> hypoxia 2)reduced energy metabolism --> reduced ATP production 3) Altered ionic gradient - Na+, H20 move into the cell - K+ moves out of cell 4) osmotic pressure increases --> accumulation of intracellular water 5) organelle and cell swelling 6) formation of "vacuoles", cytoskeletal disruption, bleb formation 7) Outcome - insult removed --> reversal and recovery - insult remains or is too severe --> cell death

What are the steps for appropriate repair?

1) crusting 2) granulation tissue 3) fibrosis = scar = cicatrix

What are the mechanisms of vascular permeability during inflammation?

1) endothelial reaction - mainly venules - mediated by vasoactive mediators: histamine, nitric oxide, etc. - rapid onset, short-lived (minutes) 2) endothelial injury - arterioles, capillaries, venules - anything that causes injury: burns, toxins, etc. - hours to days 3) leukocyte-mediated vascular injury - venules and capillaries in the lungs (pulmonary capillaries) - late stages of inflammation, long-lived (hours) 4) increased transcytosis - induced by VEGF = vascular endothelial growth factor

How are lipids accumulated in the body

1) free fatty acids (FFA) from adipose or ingested 2) transport to hepatocytes, then - esterified to cholesterol or phospholipids - oxidized to ketones - esterified to triglycerides 3) triglycerides combine with apoproteins 4) lipoproteins transported in blood to tissues

What is the pathogenesis of hyaline droplets?

1) glomerular damage 2) proteinuria 3) protein taken up by proximal tubular epithelial cells

What are the 5 hallmark signs of inflammation?

1) heat 2) redness 3) swelling 4) pain 5) loss of function

Repair starts soon after inflammation and has four temporal phases. What are they?

1) hemostasis 2) acute inflammation 3) proliferation (granulation) 4) remodeling (maturation and contraction)

What is an example of the steps of a diagnosis?

1) history and observations 2) differential diagnosis 3) diagnostic procedures 4) final diagnosis

What are the two consistent characteristics that lead to necrosis?

1) inability to restore mitochondrial function 2) severe cell membrane damage - lysosome leak, leading to breakdown of the nucleus and cytoplasm - cell contents subsequently leak and there is a large influx of calcium

What is the general pathogenesis of cell death?

1) initial injury: hypoxia, ischemia, membrane insult 2) severe cell membrane damage 3) intracellular influx of calcium 4) Ca2+ activates degradative enzymes: phospholipase, ATPases, endonucleases 5) Further membrane breakdown, mitochondrial damage, decreased ATP 6) Outcome - cytochrome C release: apoptosis - loss of membrane potential and ability to generate ATP: necrosis

What are the events in neoplastic progression?

1) initiation: irrevaerbile DNA damage 2) transformation: initiated cells with a new potential for immortality 3) Promotion: habitat allows survival, expansion of initiated cells

What are the steps for malignant cells to metastasize?

1) invasion of the basement membrane underlying the tumor 2) movement through the extracellular matrix 3) penetration of the vascular and lymphatic channel --> intravasation 4) survival and arrest within the blood or lymph 5) exit from circulation into a new site 6) survival and growth into a new site

What are the steps of the leukocyte adhesion cascade?

1) margination 2) rolling 3) activation and adhesion 4) transmigration

What is the pathogenesis of disseminated intravascular coagulation (DIC)?

1) massive endothelial damage 2) simultaneous thrombus formation many capillary beds 3) consumption of clotting factors in plasma 4) widespread petechiae and ecchymoses

What is the process of fibrosis?

1) necrosis 2) removal of dead tissue & inflammatory exudate by macrophages 3) space filled with granulation tissue 4) granulation tissue replaced by immature fibrous connective tissue 5) eventually replaced by mature connective tissue (type 1 collagen) 6) wound heals by formation of a scar (cicatrix)

What are the components of a morphologic diagnosis?

1) organ - noun: lung: pyogranulomas, multifocal - adjective: multifocal pulmonary pyogranulomas - part of process: multifocal pyogranulomatous pneumonia 2) distribution - focal, multifocal, MF to Coalescing, diffuse, etc. 3) Nature of lesion (the process) - e.g. types of inflammation, cancer, developmental abnormalities 4) Duration - peracute, acute, subacute, chronic 5) extent (severity) - minimal, mild, moderate, marked/severe

What are the phases of inflammation?

1) recognition of prom-inflammatory stimulus 2) acute vascular response 3) acute cellular response 4) chronic cellular response 5) resolution/repair

What are the causes of metastatic calcification?

1) renal failure: retention phosphates induce hyperparathyroidism 2) vitamin D toxicosis 3) parathyroid hormone-related protein secondary to canine malignant lymphoma, canine adenocarcinoma of apocrine glands of anal sac 4) destruction bone from primary or metastatic neoplasms

What are the responses of endothelial cells to injury aka activation?

1) swell and retract foot processes in acute inflammation 2) proliferate in chronic inflammation 3) produce/secrete cytokines, prostaglandins and basement membrane proteins

What are the components of inflammatory responses?

1) vascular endothelium & smooth muscle, mast cells: histamine, other mediators 2) polymorphonuclear leukocytes: chompin' microbes, complement mediators & clotting factors, kininogens 3) lymphocytes: adaptive response 4) monocytes/macrophages: clean up crew, more mediators, additional response input 5) fibroblasts, extracellular matric components, etc.: repair, healing

What are the steps for first intention wound healing?

1) wound fills with blood clot 2) acute inflammation 3) proliferation of endothelial cells, fibroblasts, epithelial cells at the periphery 4) epithelium "bridges" 5) granulation tissue matures with collagen underneath

What are the four mechanisms of intracellular accumulation?

1)abnormal metabolism 2) Defect in protein folding, transport 3) lack of enzyme 4) ingestion of indigestible materials

What is the embryologic origin ectoderm?

develops into skin, adnexa, oral cavity, oropharynx or rectum

What is an example of pathognomonic lesion?

diamond-shaped rash on pigs = swine ersipelas

What special stain is used to visualize mucin in goblet cells?

Alcian Blue (AB)

What is benign and malignant for mesenchymal?

B: -oma M: sarcoma

What is benign and malignant for glandular epithelium?

B: adenoma (-oma) M: adenocarcinoma

What is benign and malignant for hematopoietic?

B: histiocytoma (histiocytes) M: lymphoma (lymphocytes )

What is benign and malignant for nonglandular epithelium?

B: papilloma (-oma) M: carincoma

What is benign and malignant for glandular surface epithelium?

B: polyp M: adenocarcinoma

What is hemoperitoneum?

Blood in the peritoneal cavity

What do cytokines and TNFα stimulate?

E-selectin expression

What can occur with acute vascular responses?

In addition to becoming congested, vessel dilation and increased permeability lead to loss of cells, protein and fluid --> edema

What is the acute inflammation cellular response?

Leukocyte adhesion cascade: - migration of leukocytes from the vessel lumina of capillaries and postcapillary venules into interstitial tissues - neutrophils and monocytes (circulating macrophages) crawl along vessels but don't swim

What happens in appropriate repair when you can't make a crust?

eschar: piece of dead tissue that sloughs from a surface over time

What is the pathogenesis of parathyroid hormone-related protein?

PTHrP uses 3 primary mechanisms which induce hypercalemia 1) stimulation of osteoclastic bone resorption 2) increase in calcium reabsorption in the distal convoluted tubules 3) activation of vitamin D precursors, resulting in increased intestinal absorption of calcium

Which stain stains glycogen?

Periodic acid schiff (PAS)

What stain is used to stain hemosiderin (iron) blue?

Prussian blue

The basic causative mechanisms of cell death result in what?

Result in one or more of the following: - ATP decrease - mitochondrial damage - loss of calcium homeostasis - oxidative stress

What is a saddle thrombus?

an embolus that has broken off a left atrial thrombus formed secondarily to hypertrophic cardiomyopathy

What are the causes of thrombosis?

Virchow's Triad of Thrombosis 1) blood vessel endothelial damage - endothelial integrity = most important factor - can affect other two factors 2) alteration of normal blood blow (stasis or turbulence of blood flow) - can cause endothelial injury 3) hypercoagulability of blood

What is cachexia?

a generalized metabolic decline, possibly by nutritional competition with the host or secretion/generation of cachexins (TNF-like substances) - etiology complex: anorexia, nutritional demands tumor tissue, nutrient loss to effusion, etc.

Define abscess

a focus of liquefactive necrosis surrounded by a connective tissue capusle - caused by bacteria and neutrophils --> release proteolytic enzymes --> liquefy tissue

What is hematoma?

a large area of hemorrhage that forms a mass or blood coagulum (3D blood clot) of blood into a focal confined space or cavity - most common: ears of long-eared dogs or pigs and in spleen after trauma

What are infarcts?

a localized area of ischemic necrosis from blockage or occlusion of arterial supply or venous drainage - typically coagulative necrosis - liquefactive ("malacia") in the CNS

What is the significance of neoplasia?

a pathologic response characterized by an uncontrolled, expanding mass of cells that is - "unique" to the patient - generally monoclonal in origin (cells originating from a single neoplastic transformed cell) - commonly a result of genomic mutations - single cells have a genetic mutation leading to unresponsive to genetic control mechanisms controlling normal cell proliferation and differentiation

What are idiosyncratic intrinsic etiologies of disease?

a patient-specific disease - often related to enzymopathy (inherited or acquired) - may be triggered by extrinsic factors (e.g., drug exposure

What is generalized edema?

a reflection of systemic fluid imbalance

What is a wedge biopsy?

a small slice or chunk of tissue is removed from the tumor or mass

What is a punch biopsy?

a small, circular piece of tissue is removed using a biopsy punch

What is a scab?

a temporary hard coat of congealed protein covering a skin wound

What is inflammation?

a) a protective response involving host cells, blood vessels and proteins b) the reaction of living, vascularized tissues to injury - a forceful, evoked defensive reaction - requires a stimulus to be initiated - only occurs in living tissues (and thus autolysis has no inflammation!)

What is hydropic?

a) acute cell swelling results from water accumulation - in organelles and/or the cytosol b) common terms are based on the location of the water - mainly in organelles (especially endoplasmic reticulum) --> cloudy swelling, vacuolar change - mainly in cytosol --> ballooning degeneration, hydropic degeneration q

What is metastatic calcification?

a) affects visibly normal tissue b) system metabolic disease- elevated serum calcium levels --> hypercalcemia - primary hyperparathyroidism: excess parathyroid hormone -->rare - secondary hypercalcemia: vitamin D toxicity, renal failure, paraneoplastic syndrome

What components make up the circulatory system?

a) blood b) heart (central pump) c) blood vessels - arterial (blood distribution) - venous (blood collection) d) lymphatic vessels (drain fluid from extravascular spaces into blood vascular system)

What is significant about metaplasia?

a) can be a normal physiological response - usually a severe or chronic stimulus b) functions as a protective response

What is significant about hyperplasia?

a) can be a normal physiological response to a stimulus - often hormonal - may be secondary to chronic irritation b) occurs to meet increased functional demand

What is a garnuloma?

a) cell debris and inflammatory cells surrounded by a fibrous connective tissue capsule b) Layers: - core of inspissated (semi-dry) necrotic cell material - inner later of degenerative neutrophils - outer layer of "foamy" macrophages +/- multinucleated giant cells - all of this is surrounded by capsule

What are the regeneration requirements for parenchyma restoration?

a) cell type capable of proliferation b) appropriate supporting structures - debris removal: phagocytes - intact basement membrane - source of renewal: stem cells c) proper microenvironment - patent vascular supply - trophic factors: in the matrix or released by leukocytes - absence of pro-inflammatory mediators, achieved most easily in uncontaminated wounds

What is the microscopic structure of granulation tissue?

a) characteristic pattern: "cross-hatch" or "herring bone" b) tissue organization - fibroblasts are parallel to the granulation bed - angioblasts are perpendicular to granulation bed c) early: type III collagen d) late: type I collagen (fibrosis)

What are the etiologies of hemorrhage for conditions affecting blood?

a) coagulation disorders - coagulation cascade deficiencies (selected factors- genetic or induced) - disseminated intravascular coagulation (DIC): run out of clotting factors b) platelet disorders (leading to thrombocytopenia)

How is cancer diagnosised?

a) combination of clinical and pathologic examinations, used for diagnosis and to gauge the success of a treatment regimen b) clinical diagnosis - based on gross features (papilloma, cystic, fibrotic, nodular tumor) - any non-healing growth or lesion and growth of profusely bleeding nature are to be suspected for possible cancer c) radiology - radiological examination of viscera and bone may show primary or secondary lesion d) cytology (exfoliative, needle biopsies, impression smears, hematologic smears) e) biopsy (histopathology) f) special stains (to identify cell types)

What is the nature of lesions (the process) for non-inflammatory?

a) degeneration: hepatic lipidosis b) pigmentation: intestinal lipofuscinosis c) mineralization: pleural mineralization d) disturbances of growth: renal hypoplasia e) neoplasms - name of neoplasm and organ - ex: renal lymphosarcoma f) displacement of viscera: volvulus, torsion

What is the significance of amyloidosis?

a) deposits mechanically interfere with cell (and thus organ) function b) amyloid deposits are indicators of systemic disease - causes: chronic inflammation, neoplasia - consequences: organ failure (espically kidney, also liver), protein-losing "organ-opathy" (intestine, kidney)

Local vascular responses are modulated by what?

a) direct endothelial damage: degeneration and necrosis - the most critical initiating step b) release of vascular mediators from inflammatory cells - leukocytes, mast cells, platelets - activation of plasma proteins to produce vasoactive peptides - autonomic nerves control arterial smooth muscle

Inflammatory responses are always what?

a) dynamic b) redundant - numerous cell types, signals, amplification cascades - many mediators with multiple overlapping functions c) continuous - occur over time as an overlapping continuum of events - duration terms (peracute, acute, subacute, chronic) describe the different stages

What is the pathogenesis for endothelial injury/damage?

a) endothelial cell damage & exposure of subendothelial collagen releases platelet-activating factor (PAF) b) platelet adhesion - aggregation and release reactions (released platelets proteases and tissue thromboplastin from damaged endothelia) c) formation of platelet-fibrin plug attached to the vascular defect and protruding into the vessel lumen - fibrin-platelet clot releases additional thromboplastin to recruit more platelets - circulating erythrocytes and leukocytes become entrapped in the fibrin meshwork, parallel to the direction of blood flow

What are granulomatous epithelioid macrophages?

a) epithelioid macrophages resemble epithelium - abundant cytoplasm, closely packed b) increased cellular metabolism & elevated phagocytic abilities - enhanced cytotoxicity - increased secretion of pro-inflammatory and pro-proliferation cytokines - increased lysosomal enzymes - increased number and "stickiness" of membrane antigen receptors

Vital endogenous anti-neoplastic processes involve DNA repair through which mechanisms?

a) excision repair - primarily occurs in G1 - enzymes identify altered nucleotides, remove them, and rebuild using the sequence from the complementary (intact) DNA strand b) post-replication repair - occurs in G2 immediately after DNA synthesis (S phase) - must happen before mitosis (M phase) c) methylation: reduced gene expression (especially retroviral

What are pre-mortem color changes?

a) exogenous - particles: barium, carbon, silica - xenobiotics: antibiotics b) endogenous - hematogenous: heme ring based - nonhematogenous

What are selectins?

a) expressed by leukocytes, endothelium and platelets b) cell adhesion molecules - endothelium: E-selectin - leukocytes: L-selectin - platelets (and endothelium): P-selectin - bind to carbohydrate groups on leukocyte surface proteins to slow the leukocyte down

What is the difference between fibrinous and fibrous?

a) fibrinous - low strength, acute - those temporary bridges may be invaded by fibroblasts and become permanent fibrous adhesions over time b) fibrin - refers to connective tissue made by fibroblasts - tough, white, CHRONIC - these cannot be easily pulled apart, require cutting

What are the types of lesion distribution?

a) focal: limited to one site - focally extensive b) multifocal: multiple sites - coalescing (merging together of multiple foci) - multifocal to coalescing c) diffuse: involves entire tissue/organ

What is the severity (extent) of lesion(s)?

a) generally on a four or five category scale - minimal (just barely detectable) - slight/mild - moderate - marked/moderately severe - severe (considerable tissue damage)

What are exceptions to the rule in tumor nomenclature?

a) glands that do not have a tubular morphology - sebaceous adenoma/carcinoma adrenocortical adenoma/carcinoma - thyroid adenoma/carcinoma b) non-glandular organs that have a tubular morphology - renal adenoma/carcinoma - pulmonary adenoma/adenocarcinoma - gastrointestinal polyp/adenocarcinoma

What are the types of morphologic changes?

a) gross - visible without a microscope - observed at necropsy b) microscopic (histology) - visible with a light microscope c) ultrastructural (cell organelles) - visible with an electron microscope

What are the characteristics of centrilobular hepatic congestion?

a) hypoxia --> necrosis of centrilobular hepatocytes b) cut surface of congested livers will have a "nutmeg" appearance - red = pooled blood in centrilobular areas - may see necrosis secondary to hypoxia

Foreign bodies infrequently cause neoplasms but how can they cause neoplasms?

a) inciting agents: implants, parasites b) tumor types are site-dependent - bone implants = osteosarcoma - soft tissue implants = fibrosarcoma - surface implants = squamous cell carcinoma c) lesions are locally invasive (and can recur) but rarely metastasize d) pathogenesis involves - chronic stromal activation - implant character like ingredients and texture

What are the causes of endothelial injury/damage?

a) inflammation of vessel wall - bacterial localization generates thrombosis - cytokine release stimulate tissue factor release - immune-mediated b) deposition of mineral - uremia --> endothelial damage - alteration of normal blood flow (stasis or turbulence of blood flow) - hyper-coagulability of blood c) physical trauma - iatrogenic --> repeated venipuncture, injections d) parasite migration

What is apoptosis?

a) irreversible "programmed" cell death b) selective elimination due to physiologic or specific pathologic stimuli c) cells appear shrunken and condensed d) this process is deliberate and therefore localized and tidy - no inflammtion - no gross lesions - no fibrosis (scarring) - variable loss of function depending on cause and degree of apoptosis

What causes coagulative necrosis?

a) local heat b) decreased/disrupted blood flow - ischemia/infarct c) toxin exposure - endogenous or exogenous - toxins produced by bacteria often do this

Hemorrhage can be significant to life-threatening. What are the factors that influence the clinical outcome?

a) location - vital vs. non-vital tissues or organs - often lethal in brain, lung, pericardial b) volume - loss of large blood volumes can lead to shock - 35% to 50% of volume --> death by hypovolemic shock c) rate of loss - slows rates of loss can have come compensation

What can lead to decreased lymphatic drainage?

a) lymphatic obstruction - compression from inflammatory or neoplastic masses - intraluminal obstruction by thrombi or emboli b) lymphatic anomalies - congenital anasarca/lymphedema

What is the microscopic features of chronic inflammation granulomatous?

a) macrophages (histiocytes) and fibroblasts - both of these cell types, plus remaining parenchyma, can proliferate b) activated macrophages +/- multinucleated giant cells - +/- neutrophils, eosinophils, lymphocytes - peripheral fibrosis - central caseous necrosis - agent is often at the center of the lesion

What are the gross features of amyloidosis?

a) organ appear - uniformly firm, pale, tan to yellow ("waxy") - swollen and enlarged b) amyloid deposits stain black in fresh tissue with a Lugol's iodine stain

What are the causes of hepatic lipidosis?

a) physiologic - pregnancy toxemia - ketosis b) nutritional - obesity - starvation - malnutrition c) other - Wilson's disease (a storage disease) - Endocrine Disease: diabetes mellitus - toxicity: aflatoxin, CCL4 d) unknown (idopathic) - feline hepatic lipidosis

What are the differences between post mortem and ante (thrombi) mortem clots?

a) post mortem - unattached to vessel walls - shiny, wet - forms perfect cast of vessel lumina b) ante mortem - mural thrombi attached to vessel walls - dry, dull, laminated - often tail extends downstream

What are the fundamental characteristics of hypreplasia?

a) proliferation: increase in number of normal cells b) cells resemble predecessors in structure and function c) growth relative to normal is: - coordinated: subject to normal regulatory processes - reversible: can regress after removal of a stimulus

What are the characteristics of chronic inflammation suppurative?

a) remember, can be acute or chronic b) etiology: typical bacteria c) microscopic features *abscess - lots of neutrophils + macrophages - peripheral fibrosis + central liquefactive necrosis - +/- inciting agents in the center of the lesion - +/- mineralization of necrotic debris * cellulitis - spreading diffuse suppurative inflammation in soft or connective tissues - +/- a capsule around affected tissue

Repair after injury as several potential outcomes. What are they?

a) repair by regeneration - growth of cell and tissues to replace lost structures b) repair by replacement - tissues that cannot regenerate will repair with scar formation - usually due to loss of structure needed for regeneration or severe tissue framework damage - fibrosis (scar formation) is an expected outcome of healing by replacement that may be more severe with severe damage

What are the fundamental characteristics of metaplasia?

a) replacement of a fully differentiated "delicate" cell type with another fully differentiated "sturdy" cell type b) most common in epithelia, especially surface (mucosa, skin) c) growth relative to normal tissue is: - coordinated: subject to normal regulatory processes - localized to the region of insult - reversible: can regress after removal of stimulus

What is oncotic necrosis? What is it caused by?

a) reversible cell injury caused by - hypoxia - ischemia - membrane damage - often +/- free radical-induced damage, increased intracellular calcium b) "oncotic" b/c cells swell and eventually burst c) this process is uncontrolled and thus very messy

What is the terminology for morphologic diagnoses for inflammaton?

a) severity - minimal, mild, moderate, marked, severe - occasionally we use "equivocal" b) duration - peracute -> acute -> subacute -> chronic - sometimes you will also see "chronic active" to indicate long-standing inflammation with characteristics of acute lesion c) distribution - focal, multifocal, coalescing, diffuse, massive d) type of inflammation e) location: typically organ + "itis" f) optional components - position modifier: central, interstitial, intra-, pan-, peri-, etc. - structure modifier: follicular, lobar, nodular, etc.

What are the general features of cellular degeneration?

a) shifts from normal to abnormal structures b) minimal or no circulatory and inflammatory responses c) morphological features - color: paler than usual - consistency: softer than usual - size: slightly larger than normal (subtle at macroscopic level, more easily seen at the microscopic level) - weight: heavier than normal

What are the characterizations of hemorrhage morphology?

a) surface hemorrhage- skin, mucosa, serosa - petechia - eccymosis - suffusive b) extravasation- larger area

What are the etiologies of hemorrhage for conditions affecting blood vessels?

a) trauma b) infections - bacteria * bacteremia: circulating bacteria * sepsis: systemic inflammatory response * toxemia: circulating bacterial toxins (especially G- endotoxin) - viruses c) vascular disorders - hypertension (primary or secondary) - invasion (inflammation, neoplasia, parasites) - mural weakness: aneurysm (age, collagen, synthesis defects) - necrosis

What are the clinical effects of malignant neoplasia?

a) tumor invasion and metastasis - the major cause of cancer morbidity and mortality b) tumor metastasis can result in major clinical consequences: - loss of tissue function - loss of nervous control - pain and discomfort

What are the components of inflammation?

a) vascular - vasodilation and increased permeability b) cellular - cells move out of the blood vessels and to the target area via chemotaxis - inflammatory cells then become activated - some directly target offending stimulus, some phagocytose agents or materials

What is pathologic calcification (calcium deposits) ?

abnormal deposition of calcium salts in tissue other than bone (soft tissue) - usually calcium with phosphate or carbonate

Removal of the stimulus should abate inflammation. When not removed, what happens?

acute inflammation becomes chronic

What is amyloid fibrils?

abnormally folded proteins (beta sheet)

What is edema?

accumulation of abnormal quantities of fluid (water) in interstitial tissues or body cavities

What is cellular fatty change?

accumulation of fat vacuoles in the cytoplasm of non-adipose cells - results from conditions causing increased mobilization of body fat stores - reversible - a pathologic accumulation in non-adipose cells and NOT obesity

Which cellular injury responses are reversible?

adaptation and degermation

Where does cellular myxomatous occur?

adipose and connective tissue

What are common sites of amyloid deposition?

all species - deposits kidney (glomeruli, medulla, basement membrane), liver (space of Disse), Spleen (germinal centers), lymph nodes (germinal centers), adrenal cortex Species specific sites of predilection - brain: humans, nonhuman primates - pancreatic islets: cats - skin: horses mainly - myocardium: humans, mice - small intestine: mice

What are "lines of Zahn"?

alternating layers of platelets, fibrin, RBC's, and leukocytes

What is hyperemia?

an active, increased flow of blood into the microvascular with normal outflow - engorgement with oxygenated blood - resulting in erythema (redder) - associated with an acute inflammatory process - all capillaries in particular area dilate with markedly increased blood flow (local)

Necrosis and apoptosis occur when?

ante mortem

Where does scar/eschar loosening start?

at the peripheral margins

What occurs during acute inflammation vascular changes?

changes in blood vessel caliber and blood flow - increased flow -> vasodilation -> redness and heat -> active hyperemia - increased permeability -> blood flow through capillaries slows -> leukocyte margination -> emigration through gaps in vessels - formation of exudate: fluid, protein including fibrin, leukocytes

What is cell injury?

any change resulting in loss of the ability to maintain the normal or adapted homeostatic state

Define disease

any detectable deviation from the normal range

What are the two types of repair by replacement?

appropriate and inappropriate repair

What is microcirculation composed of?

arterioles, metarterioles, capillaries, and postcapillary venules

What is hemorrhage arrest?

as hemorrhage occurs, blood pressure drops and clotting occur

What is an example of a classic RNA tumor virus lesions?

avian sarcoma leukosis virus (lymphoblastic)

What is the most common cause of liquefactive necrosis?

bacterial infections, which attract neutrophils

What is a clinical example of hydropic?

ballooning degeneration due to Papular Stomatitis Virus in the oral mucosa of a cow

What may initiate "third intention" healing?

by surgical debridement of a wound that was initially allowed to close by second intention

How are tumors classified?

based on histogenesis (cell of origin) and behavior (benign vs. malignant)

What is hyphema?

bleeding into the anterior chamber of the eye

What is primary delivery system of inflammatory components?

blood

Cells and fluids involved in the inflammatory response are derived from what?

blood and bone marrow

What is hemopericardium?

blood filling the pericardial sac

What is hemarthrosis?

blood in a joint space

What is a hemothorax?

blood in the pleural space

What is external hemorrhage?

blood loss occurs outside the body -lost components cannot be recycled - tolerance for external hemorrhage is less than for internal hemorrhage

Inflammation is a ____________________ response to injury.

blood vessel-centered

What is adhesion as a mechanism of invasion and metastasis?

cells separate by dismantling desmosomes, adherens junctions and break through

What is the gross appearance of articular gout?

chalky, white appearance

What is one of the most common clinical entities where Splendore-Heoppli material is found?

botryomycosis

What is the gross appearance for physiologic hyperemia?

bright red at necropsy will fade as oxygen is quickly transferred from erythrocytes into mucosal tissues

What is the microscopic appearance of pathologic calcification?

calcium deposits are purple/blue color with H&E stain and black with von Kossa stain - dystrophic calcification will also include inflammation and/or necrosis of adjacent tissue

What is a clinical example of hyperplasia?

canine benign prostatic hyperplasia

What is the most common exogenous pigment?

carbon

The appearance of hemorrhage depends on what?

cause, location and severity

What are the two categories of cell injury causes?

causes of cell injury can be extrinsic or intrinsic - extrinsic = external: trauma, infectious agents, toxins, etc. - intrinsic = internal: genetic mutations

What is cytology?

cells from tissue or body fluid fixed and stained for microscopic examination

What is coagulative necrosis?

coagulation of proteins in tissue

What is dry gangrenous necrosis?

coagulative necrosis following infarction - mot commonly distal extremities, ears - mummification of dead tissue - frostbite, fescue or ergot poisoning

What is fat necrosis?

coagulative necrosis of adipose tissue

What is Zenker's necrosis?

coagulative necrosis of striated muscle - skeletal or cardiac muscle

Where does catarrhal exudate commonly occur?

common where goblet and mucus cells are abundant - respiratory tract - GI tract

What is infaraction?

complete obstruction of blood flow so that the tissue dies

What are the causes of disseminated intravascular coagulation (DIC)?

complications of sepsis, endotoxemia, neoplasia, burns, heat stroke, shock, and endotheliotropic viral infections

What is the microscopic appearance of liquefactive necrosis?

contain dead and dying neutrophils mixed with - acellular debris - few remaining parenchymal cells - electrolytes - water - sometimes smeared or smudged nuclear debris from the dead cells (looks like stringy, purple thread-like material)

Explain the significance of Ki67

determination of proliferation indices (Ki67) and gene expressions or mutations may also help predict the behavior of certain tumors

Inflammation is on a _________________ with the healing process

continuum

What is the microscopic appearance of carinoma?

cords, trabeculae

What is eosinophilic granuloma?

core contains eosinophils and these are typically associated with parasite migration tracks

What is a caseating granuloma?

core contains friable material due to caseating necrosis

What is suppurative (pyogranuloma) granuloma?

core contains large numbers of neutrophils

What is hemopytsis?

coughing up blood due to bleeding in airways

What does the antibiotic tetracyclic do to the body?

deciduous teeth or developing teeth and bone may show yellow or brown deposits

What are the etiologies of gout (birds and reptiles)?

dehydration, high protein diets, or renal failure--> anything that disrupts excretion of uric acid

What is gout?

deposition of sodium urate crystals or urates in tissues (viscera and joints)

What are fibroblasts?

dominant cell type during: - chronic inflammation - resolution phase, especially scarring

What is verminous thrombi?

due to parasites or their fragments within cores of thrombi (think heartworm disease)

What is the primary cause of most thrombi?

endothelial injury/damage

What is a capillary bed?

enormous volume site where fluid exudes from circulating blood

What is liquefactive necrosis?

enzyme breakdown of tissues resulting in dissolving or liquefying

What are the types of necrosis cytoplasmic alterations?

eosinophilia - loss of RNA - denatured proteins

What is eosinophilic exudate?

eosinophils

Explain cell marker vitmetin

epithelial cells negative and mesenchymal cells positive

Explain the cell marker cytokeratin

epithelial cells positive and mesenchymal cells negative

What is hemorrhagic exudate?

extravascular erythrocytes + protein, fluid, some cells

What is the optimal specimen for biopsy?

fits in a single or several tissue cassettes, permitting evaluation of almost all the tissue in the sample

What is the pathogenesis of hepatic lipidosis?

five mechanisms that may occur alone or in combination 1) excessive delivery of FFA from fat stores or diet 2) decreased fatty acid oxidation due to toxins like aflatoxin 3) impaired apoprotein synthesis (starvation reduced all protein synthesis) 4) impaired lipoprotein synthesis 5) decreased lipoprotein excretion Insults can become chronic/irreversible, leading to fibrosis, pigment accumulation, nodular hyperplasia, etc.

What is hydroarthrosis?

fluid in a joint

Often, necrosis and inflammation form a what?

granuloma

What does nodular shape mean?

granulomas and pyogranulomas

What is bile imbibition?

green-yellow-brown staining due to bile leaching from ducts and gall bladder

What is the gross appearance of pathologic calcification?

gritty, hard, white appearance

What does irregular/pitting shape mean?

haphazard accumulation of leukocytes and fibrosis with scarring and contraction of tissue

What are the characteristics of chronic inflammation granulomatous?

has a "classic" cell composition that are considered hallmarks of this type of chronic inflammation: - macrophages +/- - multinucleated giant cells (MNGC)

What occurs almost immediately after a wound occurs?

healing

Which cells are included in the labile cell population?

hematopoietic cells, lymphoid cells, surface epithelium, GI mucosal epithelium

A ruptured aneurysm (spontaneous or traumatic) may result in what?

hemoabdomen or hemothorax

What type of inflammation is seen with peracute inflammation?

hemorrhagic- vascular changes -> exudative phase

What is coagulopathy?

hemostasis defect (too little or too much)

What causes endothelial cells to mobilize P-selectin from intracellular stores?

histamine and thrombin

What are the most clinically significant paraneoplastic syndromes in veterinary medicine?

hypercalcemia, hypoglycemia, cachexia and anemia

What is an example of a tumor cell with paraneoplastic syndromes?

hyperestrogenism in a male dog secondary to an estrogen-secreting Sertoli tumor of the testes

What is a clinical example of hypertrophy?

hypertrophy of the right cardiac ventricle of a dog - cardiomyocytes appear normal except for large size

What are the common causes of eosinophilic exudate?

include parasitic infections or autoimmune conditions with an eosinophilic compotent

What is a clinical example of mucopurulent inflammation?

infectious bovine keratoconjunctivitis "pink eye"

What is the most common cause of hypercoagulability?

inflammation

What is the gross appearance for pathologic hyperemia?

inflammation - arteriolar dilation is a response to inflammatory stimuli/mediators - red coloration is a cardinal sign of inflammation - often see associated with edema

What is fibrinonecrotizing inflammation?

inflammation of well-vascularized epithelial surface

What are the sequelae of necrosis?

inflammation, fibrosis (scarring) and loss of function

What are mixed exudates?

inflammatory process often persists long enough to evoke more than one type of exudate, typically all of acute inflammation types

What is the microscopic appearance of anthracosis?

intracellular and extracellular fine, black granules

What are the hallmarks of malignant tumors?

invasion and metastasis

What are the hallmarks of malignancy?

invasiveness and metastatsis

What is diffuse distribution?

involves the entire tissue or organ

What is anaplasia?

irreversible dedifferentiation (reversion to embryonic phenotype) characterized by: - pleomorphism - abnormal nuclear morphology - loss of normal polarity (orientation to other cells)

For hyperemia, as arterioles and capillaries fill with blood, what happens to affected tissue?

is red and warm

Granulation tissue is beneficial unless what?

it occurs in excess

What are the types of inappropriate repair?

keloid and sarcoid

What is the gross appearance of dry gangrenous necrosis?

leathery

Diffuse granulomatous inflammation is also called what?

lepromatous

Tumor viruses carry oncogenes, but some also appear to limit what?

limit activity of tumor suppressor genes

What is focal distribution?

limited to a single site

What does the cell cycle of cancer cells look like?

little time G0 and often no arrest in response to DNA damage or lack of growth signals

Where is coagulative necrosis common in?

liver, kidney and muscles

What are the types of congestion?

local and systemic

What is an anerysm?

localized dilatation or outpouching of thinned or weakened blood vessel - usually large, elastic arteries, but can happen in veins

What is internal hemorrhage?

lost blood stays within body - if slow enough, can be compensated for over a long period of time - blood components can be resorbed and recycled

What is a clinical example of metaplasia?

lung from a chronic smoker - undergoes metaplasia to multiple layers of stratified squamous epithelium, which is less delicate and lacks cilia

What is the gross appearance of anthracosis?

lungs speckled with black foci (1-2mm)

What are the cell types for chronic inflammation nonsuppurative?

lymphocytes and plasma cells admixed with macrophages

What is lymphocytic/lymphoplasmacytic inflammation?

lymphocytes/lymphocytes & plasma cells

What is chronic inflammation granulomatous?

macrophages +/- MNGC - fewer lymphocytes and plasma cells, though these also common with chronicity - aggregation of these cells with replacement of normal stroma

What is granulomatous inflammation?

macrophages +/- multinucleated giant cells

What does hemosiderosis with "heart failure cells" refer to?

macrophages containing intracellular hemosiderin

What is cancer?

malignant neoplasms

What is exasnguination?

marked acute external blood loss causing death

An elevated mitotic index indicates what?

more cells are dividing

What are the sites for chronic inflammation nonsuppurative?

more common in CNS, skin, tissue surfaces, and infiltrating into neoplasms

What is fibrinous exudate?

mostly fibrin protein and fluid

What is serous exudate?

mostly fluid

What is invasion?

movement of neoplasm directly through tissue plans often via enzymes such as type IV collagenase

What is catarrhal exudate?

mucoid + protein and fluid, some cells

What is mucopurulent inflammation?

mucus and pus

What is the gross appearance of eosinophilic exudate?

multiple green foci are scattered throughout the muscle

What is multifocal distribution?

multiple sites

What is the etiology of DIC Schwartzman reaction?

natural --> a sequel to endotoxemia and non-lethal endotoxic shock

Which cellular injury responses are irreversible?

necrosis (cell death) and autolysis (cell dissolving)

What is necrohemorrhagic inflammation?

necrosis and hemorrhage

What is malignant neoplasm?

neoplasm that tends to grow rapidly, is poorly differentiated, often metastasizes, and frequently causes death of the host

What is a benign neoplasm?

neoplasm that tends to grow slowly, is well differentiated, does not metastasize, and is usually non-life threatening

Which cells are included in the permanent cell population?

neurons, cardiac muscle, retinal rods and cones, Sertoli's cells in the testis

What is purulent/suppurative inflammation?

neutrophils

What is the microscopic appearance of suppurative exudate?

neutrophils (viable and dead/degenerate) + liquefactive necrosis

What is suppurative/purulent exudate?

neutrophils + all these other things

What is fibrinopurulent inflammation?

neutrophils and fibrin

What is pyogranulomatous inflammtion?

neutrophils and macrophages

Inflammatory cells arrive into an area of injury and move between what?

normal and abnormal tissue

What is epistaxis?

nose bleed

What are inclusion bodies?

nuclear and cytoplasmic aggregates

What is eosinophilic myositis?

occurs commonly in cattle and can affect any major skeletal muscle: esophagus, heart, other large muscles

When does fibrosis occur?

occurs when loss or necrosis of tissue framework (stromal elements prevent regeneration)

What is local edema?

often associated with trauma or inflammation- soft tissues or body cavities affected

What is a tumor or mass?

often used to describe the actual swelling or other physical appearance of a neoplasm

What special stain is used to stain lipids?

oil red O or sudan black

What is uricase?

or urate oxidase, is an enzyme that catalyzes the oxidation of uric acid to allantoin (more easily excreted)

What does isolation entail?

organisms or foreign bodies become isolated from immune responses and antimicrobials

Chronic inflammation is both what?

productive and proliferative

What is invasion as a mechanism of invasion and metastasis?

proteases (MMP) enable cells to degrade basement membrane and extracellular matrix (ECM)

What is empyema?

pus in a body cavity

What is a chronic inflammation suppurative clinical example?

pyoderma in a dog

What is Splendore-Hoeppli granuloma?

pyogranulomatous inflammation + Splendore-Hoeppli material

What type of inflammation is seen with chronic active inflammation?

pyogranulomatous: exudate includes macrophages and PMNs (neutrophils)

What is ischemia?

reduced blood flow to tissues

What is metastasis?

refers to the transfer of disease manifestations from one organ to another (secondary growth of a malignant neoplasm in an organ or site remote from the primary site)

What is important to know about biopsy?

reliable method by which diagnosis can be made based on characteristics (microscopically: anaplasia, invasion, mitosis, metastasis, loss of polarity) which indicate malignancy (staging and grading)

What does the cell cycle of normal cells look like?

reside in G0 (nonreplicative) and when enter cycle, may rest at checkpoints (G1-S, G2-M) in response to DNA damage, lack of external growth stimuli

What does unresponsiveness entail?

resistant to degradation or antimicrobial killing

What are intrinsic causes of neoplasia?

responsible for 10-15% of neoplasms in humans (and presumably animals) a) inherited - germ cell: present as familial predispositions to a particular kind of cancer, or to developing neoplasia in general, typically inherited as autosomal recessive genes - somatic cell: unique to individual, develops in utero or after birth b) endogenous carcinogens - agents include free radicals and toxic metabolic byproducts - exposure in unavoidable

What are extrinsic causes of neoplasia?

responsible for 85-90% of neoplasms in humans (and presumably animals) - exogenous carcinogens (xenobiotics) - diet (high fat content predisposes to free radial production) - foreign bodies (implants, parasites) - gastrointestinal microbes (Helicobacter sp.) - radiant energy (UV rays, x-rays) - transplantation (direct contact or injection) of intact cancer cells - vaccination-associated (especially cats, ferrets) - viruses (DNA viruses and oncogenic retroviruses)

What is cellular myxomatous?

results in accumulation of mucin-like material - induces conversion of mature proteins to embryonic forms

What is a clinical example of cellular myxomatous?

serous atrophy of fat

What are suppurative clinical examples?

shipping fever in cattle

What is focally/locally extensive distribution?

single site but spreads further than just a "focus"

What do spindle cell tumors look like microscopically?

streams and bundles of spindle shaped cells with variable distinct cell borders

What is disseminated intravascular coagulation (DIC)?

syndrome-widespread endothelial injury or activation resulting in platelets adhering and activation of the coagulation cascade at numerous sites and activation fibrinolytic system (dissolves clots as form)

What is microcirulation?

system for exchange of nutrients and waste between blood and extravascular tissue

Highly cellular neoplasms have very little what?

stroma

What are the sources of angiogenesis factors?

stromal inflammatory cells (macrophages and endothelia) and tumor cells (autocrine stimulation)

Where can intracellular accumulations occur?

substance may be in cytoplasm (especially phagolysosomes) or nucleus, may be produced or stored, transient or permanent, harmless or harmful

Define erosion

superficial loss with intact basement membrane

What bridges acute and chronic inflammation?

supuurative inflammation, particulary when the inciting cause is not cleared

What is the gross appearance of catarrhal exudate?

surface is clear to opaque with thick fluid

What are the evidence of disease?

symptoms, signs, lesions

Making a diagnosis from a biopsy is directly proportional to what?

the amount of tumor tissue evaluated

What are mitotic figures?

the chromosomes are visible as tangled, dark-staining threads

The outcome of acute inflammation depends on what?

the degree of tissue damage and whether the inciting stimulus persists

Define differentiation

the degree to which neoplastic cells resemble their normal counterparts

What is a excision biopsy?

the entire mass is excised or removed

What is thrombosis?

the formation of a blood clot, attached to a vessel wall, during life - fibrin, platelets and other elements of the blood - the clot itself = thrombus, thrombi - usually in veins (low pressure, low flow), but more serious in arteries

What are caspases?

the functional molecule involved in apoptosis

What can proliferative chronic inflammation appear like grossly?

the ileum appears thick with deep folds in the mucosa

What is CD31 (PECAM-1)?

the immunohistochemical marker of choice for endothelium

What is hemorrhage?

the loss of blood from vessels to extravascular sites

What is a neoplasm?

the mass itself

Emboli usually (99%) orginate from where?

thrombi (thromboemboli)

If it increases _______ or _______________, it accelerates autolysis!

time or temperature

What is the gross appearance of congestion?

tissue is dark red to blueish in color (blood is stagnant), slightly swollen, cool to the touch

What is the gross appearance of gas gangrenous necrosis?

tissues are dark red to black with gas bubbles and fluid exudate

What are variants of chronic inflammation?

tissues responses within inflammation - fibrous inflammation - proliferative

What is the function of the fluidic phase of acute inflammation?

to dilute and localize inciting agent

What is the function of the heart?

to pump blood

Tumors are named according to what?

to their cell and tissue or origin (histogenesis), pattern of growth and biological behavior (begin vs malignant)

What is used with ultrastructural pathology?

using an election microscope

Where does cellular fatty change usually occur?

usually occurs in liver, kidney, and muscle - tissues where triglycerides are synthesized or processed for transport (liver) - tissues that depend on triglycerides for energy (myocardium)

Endothelial cells regulate ________ __________________ via response to vasoactive amines, parasympathetic nerve stimulation and direct injury

vascular permeability

Which type of gout is most common in birds and reptiles?

visceral form is most common - affects visceral serosa, especially pericardium and kidneys

What are the two types of gout?

visceral gout and articular gout

What is hematemesis?

vomiting of blood

What are characteristics of benign tumors?

well-differentiated, expansion only, frequently encapsulated, relatively slow, few normal mitoses, slow or dormant growth, no invasiveness, adequate blood vascular supply and nuclear morphology resembles normal

Where does turbulence occur?

where vessels branch, narrowing of vessel or chamber lumen, and sites of venous or lymphatic valves

"Carcinomatosis" and "Sarcomatosis" are other terms for what?

widely dispersed neoplastic disease

What are the characteristics of a modified transudate?

will fall in the middle of transudate and exudate, a little more protein, a few more cells, etc.

What is catarrhal inflammation?

with mucus (and often hemorrhage; frequently mucous membranes)

What is necrotizing inflammation?

with necrosis

What are the morphologic traits of neoplasia?

with no relationship to behavior - core of mass --> cavernous vs. cytic vs. solid - lining of cavity --> papillary - surface --> ulcerative - type of attachment --> pedunculated vs. sessile

What is proliferative inflammation?

with proliferation of tissue cells

What is fibrinous inflammation?

with significant fibrin

What is hemorrhagic inflammation?

with significant hemorrhage

What is ulcerative inflammtion?

with ulceration of an organ surface