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acute inflammation
- adaptive response
- short duration
- fluid & plasma out
- leukocytes (neutraphils) in
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chronic inflammation
- longer duration
- proliferation of blood vessels, tissue necrosis, fibrosis
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endothelial cells in inflammation
- produce antiplatelet antithrombotic agents
- vasodilators & vasoconstrictors
- selective permeable barrier to stimuli
- regulate leukocyte extravasation by expression of adhesion molecules
- synthesis of inflammatory mediators
- cell proliferation through secretion CSF
- production of growth factors stimulate angiogenesis
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platelets in inflammation
- release inflammatory mediators
- increase vascular permeability
- alter chemotactic, adhesive & proteolytic properties of endothelial cells
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leukocytes in inflammation
- granulocytes- cytoplasmic granules, multi-lobed nucleus
- agranulocytes- single nucleus
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neutrophils in inflammation
- first cells to appear
- engulf through phagocytosis
- oxygen-dependent metabolic pathways generate toxic oxygen & nitrogen
- last 24-48 hrs
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eosinophils in inflammation
- appear 2-3 hrs after neutrophil
- contain protein highly toxic to parasitic worms
- interact w/ basophils in allergic reaction
- long life span
- active in chronic
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basophils & mast cells
- allergic reactions mediated by IgE
- triggers release histamine & vasoactive agents
- mucosal surfaces of lung, GI, dermis
- activation of mast cells: release of contents(histamine, proteases, cytokines, IL), synthesis of lipid mediators from cell membrane precursors (prostaglandin, platelet-activating factor), stimulation of cytokine synthesis by other inflammatory cells
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monocyte/macrophage
- single kidnet shaped nucleus
- produce prostaglandins, platelet activating factor, inflammatory cytokines & growth factors
- life span 3-4x longer granulocytes
- destroy causitive agent
- aid in signaling of immunity
- resole inflammatory process
- initiating of healing process
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lymphocytes and plasma cells
- immune-mediated inflammation by infection & injury
- work w/ macrophage to stimulate each other to activation
- activated B-lymphocytes develop plasma cells that produce antibodies against antigens
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selectin CAM
adhesion leukocytes to endothelial wall
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integrin CAM
promote cell-to-cell & cel-to-extracellular matrix interactions
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adhesion molecules
- immuloglobulins
- interact w/ integrins to recruit leukocytes
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cardinal signs of inflammation
- rubor
- tumor (swelling)
- calor (heat)
- dolor (pain)
- loss of function
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vascular stage
- vasoconstriction followed rapidly by vasodliation/ increased vascular permeability w/ leakage of protein-rich fluids into extravascular tissue
- induced by histamine & nitric oxide
- loss of fluid makes blood thicker concentrating blood components, slowing of flow, & clotting
- fluid shift dilates offending agent
- histamine, bradykinin & leukotrienes cause contraction of endothelial cells and separation of intracellular junctions
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patterns of responses
- immediate transient-rapid, reversible, short duration (15-30 min);leakage in venules
- immediate sustained- several days; all levels of microcirculation; direct damage to endothelium
- delayed hemodynamic- increased permeability after delay 2-12 hours; injuries due to radiation (sunburn)
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cellular stage of acute inflammation
- 1. margination & adhesion
- 2. transmigration
- 3. chemotaxis
- 4. activation & phagocytosis
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margination & adhesion
- leukocytes slow migration, adhere to endothelium & move along edge of blood vessel
- cytokines cause endothelial cell lining to express adhesion molecules that bind the carb on leukocytes (tethering)
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transmigration
adhesion causes endothelial cells to seperate allowing leukocyte to extend pseupodia & go through vessel wall & migrate to tissues
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chemotaxis
leukocyte wanders through tissue guided by gradient of chemoattractants (chemokines, debris)
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phagocytosis
recognition, adherence & intracellular killing
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opsonization
enhanced binding of antigen due to antibody
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plasma derived mediators
- made in liver
- acute phase proteins, coag factors, complement factors
- products of coag/fibrinolysis system & protein of complement
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cell-derived mediators
- normally sequestered in intracellular granules (histamine) or
- newly made in response to stimulus (cytokines)
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vasoactive amines-histamine & serotonin
- stored in preformed molecules in mast cells
- H-dilation of arterioles & increases permeability of venules; principal mediator of transient phase
- serotonin- vasoactive mediator in platelet granules
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arachidonic acid metabolites (prostaglandins, leukotrienes)
- corticosteriods block action preventing release
- prostaglandins potentiate mediators
- NSAIDs block prostaglandin pathway
- leukotriene- slow & sustained constriction of bronchioles
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Omega-3 polyunsaturated fatty acids
partial replacement of omega-6 arachidonic acid blocking prosta & leuko production
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platelet activating factor
- stimulates neutrophils, nonocyte, endothelial cell & vascular smooth muscle
- enhances serotonin release
- enhances leukocyte adhesion, chemotaxis, & synthesis of mediators
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cytokines
- low-molecular-weight proteins
- source of TNF & IL-1 by activated phagocytes
- fever, hypotension, high HR, anorexia, release of neutrophils into circulation & increased corticosteriods
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chemokines
- chemoattractants- recruit & direct inflammatory & immune cells
- chemotactic gradient binding proteoglycans on endothelium
- response to bacterial toxin & cytokines
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nitric oxide
- relaxation of vascular smooth muscle
- antagonism of platelet adhesion, aggregation & degranulation
- regulator of leukocyte recruitment
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oxygen-derived free radicals
- increase expression of cytokines & endothelial adhesion
- produces endothelial cell damage- increase of vascular permeability, inactivate antiproteases, produce injury to rbc's
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serous exudate
- watery fluids low in protein
- from plasma
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hemorrhagic exudates
- severe tissue injury
- leakage of rbc from capillaries
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fibrinous exudates
- fibrinogen
- form thick sticky meshwork
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membranous exudates
- mucous membranes
- necrotic cells in fibropurulent exudate
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purolent exudate
degraded white cells, proteins, tissue debris
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abcess
central necrotic core contining purulent exudate surrounded by layer of neutrophils
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ulceration
epithelial surface becomes necrotic & eroded
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resolution
- replacment of injures cells & return of tissues to normal structure & function
- neutralization of inflammatory mediators, normal vascular permeability & stopping of leukocyte infiltration
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chronic inflammation
- infiltration of mononucleur cells & attempted repair by angiogenesis
- low-grade infection/irritants unable to penetrate deeply or spread rapidly
- adipose tissue source of TNF & insulin resistance
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granuloma
- massing of macrophages surrounded by lymphocytes
- foreign bodies
- poorly digested & controlled by inflammatory mechanisms
- coalese (clump) & form giant cell
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acute phase response
- change concentrations plasma proteins
- skeletal muscle catabolism
- negative nitrogen balance
- high sed rate
- high leukocytes
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acute-phase proteins
- stimulated by cytokines
- CRP-binds to & targets cell for destruction
- SAA (serum amyloid A)- starts transfer HDL from liver to macrophage to utilize for energy; rise in fibrinogen causes rbc to form stacks & increase sed rate
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WBC response
- shift to left-increase in immature neutrophils
- bacteria-neutrophilia
- parasitic-eosinophilia
- viral-neutropenia & lymphocytosis
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heat production
- metabolism source of heat production
- epi & norepi-shift metabolism to heat production instead of energy
- shivering-hypothalmus 3-5x increase
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heat loss
- AV shunts-sympathetic nervous system
- radiation- air or vacuum; 60% of loss
- conduction- transfer to molecules (blood cariies from inner core to outer)
- convection-circulation of air currents
- evaporation-sweating
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fever definition
cytokine-induced upward displacement of set point in hypothalmus
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pyrogens
act directly & immediately on hypothalmus to increase set point
-
neurogenic fever
- damage to hypothalmus
- resistant to therapy no sweating
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purpose of fever
- signal infection
- enhance immune function
- inhibit microbial growth
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fever patterns
- intermittent-return to normal once in 24 hrs
- remittent-no return to normal varies few degree in either direction
- sustained- above normal minimal variations
- relapsing-one or more episodes of fever w/ several days between
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prodromal fever
non-specific complaints (fatigue, HA, malaise, aches)
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second-stage (chill) fever
generalized shaking though temp rising
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third stage (flush) fever
vasodilation
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fourth stage fever (defervescense)
sweating
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causes of manifestations of fever
- increase in BMR
- increased need ofr oxygen
- use of body proteins & fat as energy
- HA-vasodilation of cerebral vessels
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