Path_2.txt

response to injury by vascularized living tissue

• microbial infection
• physical agents, chemicals, necrotic tissue, immune reaction

• contain and isolate injury
• destroy microorganisms
• inactivate toxins
• prepare tissue for healing and repair

• two main; vascular wall response and inflammatory cell response
• termination when invader is eliminated

• early onset
• short duration
• fluid exudation, edema
• nutrophil migration

• later onset, days
• longer duration, weeks to years
• involves lymphocytes and macrophages
• new blodd vessels
• scaring

• heat
• redness
• edema
• pain

• extravascular fluid of a high protein concentration
• SG above 1.02

pus

• extravascular fluid with little protein
• SG below 1.012

• Dilation; causes increased flow and increased hydrostatic pressure
• increased vascular permeability; causes exudation
• Net fluid outflow
• stasis can occur with a large fluid lose increasing viscosity and slowing blood flow; allows white cells to accumulate and begin to migrate

• venule gaps; endothelial cells contract ( histamine immediate, IL1 and TNF in 4-6 hours)
• Direct endothelial injury; burns, affects arterials capillaries and venues
• delayed prolonged leakage; 2-12 hour delay, ;sat for days, sunburn and X-rays, venules and capillaries
• Leukocyte mediated endothelial injury; release of oxygen species
• increased transendothelial channels; VEGF
• leakage from new vessels; angiogenesis results in leaky vessels until the vessel matures

• margination
• transmigration; diapedesis
• migration; chemotaxis

• sailyl lewis X, GP
• P selectin glicoprotein ligand, PSGL-1

• LFA-1 and MAC-1 / VLA4
• intigrens
• ICAM leukocytes
• VCAM eosinophils, monocytes, lymphosytes

• CD32
• leukocyte migration through endothelium

• redistribution of preformed adhesion molecules to cell surface
• induction of adhesion molecules on endothelium, IL1 and TNF increase endothelial expression of selections and intigrins
• Increased avidity to binding; most imoirtant fo intigrens

• endothelial activation; increase selection expression, IL1 and TNF
• rolling; helped by blood stasis,
• integrin activation and stable binding, cytokines increase integrin avidity
• transmigration, PECAM platelet endothelial cell adhesion molecule

• neutrophile / macrophage
• 6-24h / 24-48h

• G protein coupled
• activates phospholipase c, increase in DAG and IP3, increased calcium, increased GTPase activity, activates movement by pseudopods

involved in leukocyte activation and response to microbes

phagosytosis and enzyme release

C3b, Fc fragment

• recognition
• engulfment
• killing

• H2O2, NADPH oxidase
• HOCl, myloperoxidase

• frustrated phagocytosis
• premature fusion of forming phagosome with lysosome
• damage by ingested material, urate crystals

• leukocyte adhesion deficiency
• defective synthesis of LFA-1 and MAC-1 (Beta1 intigrens)

• loss of silly lewis X
• selectin ligand

Defective lysosome enzyme delivery to phagosome

inherent defect in NADPH oxidase

• Mediators are only produced in quick bursts and have short half lives
• anti-inflammatory cytokines TGF-B

• histomine, seritonin
• Increased vascular permeability
• mast cells, basophils and plts
• Mest cell release by IgE, C3a, C5a, IL1 and IL8
• platelet release by ADP, collogen, thrombin, PAF

• activation of C3
• C3 convertase
• Classical pathway, C1 fixation to antigen
• Alternative pathway, microbial surface endotoxin
• Lectin pathway, C1 is activated by mannose binding

C3b cleaves C5 to C5 a and b, C5b binds to 6-9 forming MAC

• MAC induced cell lysis
• Compliment incduced canges in vascular permability, chemotaxis, opsinization

• anaphalatoxins
• stimulate histamine release from mast cells
• increase vascular permeability and vasodilation

• DAF, decay regulating factor
• C1 inhibitor

• Defercts in DAF
• recurrent compliment mediated red cell lysis and anemia

• C1 inhibitor defect
• life threatening edema

• kininogens are cleaved by kallikreins to generate bradykinin
• causes vasodilation, increased vascular permeability, and pain
• Initiated by factor XIIa
• Also activates factor XII

thrombin causes leukocyte adhesion to endothelium

• cleaves C3
• forms fibrin split products, increased vascular permeability
• activates XII

prostaglandins and thromboxanes

leukotrienes and lipoxins

chemotaxis

• vasoconstrict
• broincospasm
• increase permeability

• vaso dilate
• inhibits neutrophil chemotaxis
• stimulates monocyte adhesion
• regulate leukotriene action

increase sensitivity to pain and metiate fever

• from mast cells and other leukocytes
• pltelet aggregation
• bronchospasm
• vasodilation
• increased vascular permeability
• increased leukocyte adhesion and chemotaxis
• All cardinal features of inflammation

IL1 and TNF, induce enothelial activation

• pathogenic state of weight lose and anorexia
• mediated by TNF and IL1

• CXC; recruit neutrophiles
• CC; monocytes, eosonophiles, bsophiles, lymohocytes
• C; lymphocytes
• G protein receptors

• synthesized in macrophages and endothelium
• IF1
• major pathogenesis of septic shock

• catalase
• superoxide dismutase
• glutathione peroxidase

• Neuropeptide
• mediator of vascular permeability
• transmites pain

• prostoglandin
• NO
• Histamine

• Vasoactive amines
• C3a, C5a
• bradykinin
• leukotriene C, D, E
• PAF
• Substance P

• Leukotriene B
• chemokines
• IL1, TNF
• Endotoxin

• IL1,
• TNF
• Prostoglandins

• Prostglandins
• bradykinin

• neutrophil and macrophage
• lysosomal enzymes
• oxygen metabolites
• NO

• resolve
• healing by scar tissue, fibrosis, when healing occurs in non regenerating tissues
• progression to chronic

• reflected by tissue fluid accumulation
• modest increase in vascular permeability
• burn blisters

• more marked increase in vascular permeability
• exudate containing large amounts of fibrinogen

pus consisting of leukocytes and necrotic cells

localization of purulent inflammation accompanied by liquefaction necrosis (staphylococcal abscess)

Local erosions of epithelial surfaces

When active inflammation, tissue distraction, and healing are all going on at the same time

• Infiltration with mononuclear inflammatory cells; macrophages, lymphocytes, plasma cells
• tissue distruction
• Healing, connective tissue replacement and angiogenesis

macrohphage

endotoxins, IF

• NO,
• reactive oxygen
• proteases

lymphocytes

• cc chemokin
• recroutes eosonphiles

binding IgE

• focal accumulation of macrophages; become enlarged and flattened and called epotheliod macrophages
• macrophages are surrounded by lymphocytes secreting IFN
• may form giant cells
• Can form around inert objects
• In tuberculosis the granuloma has caseous necrosis

inflammed lymphatics

inflammed lymph node

• fever; IL1/TNF stimulate cyclooxygenase to produce prostaglandin's, prostoglandins induce cAMP in the hypothalamus that resets the temp
• Acute phase proteins; c reactive protein, fibrinogen, amyloid a. bind to microbial wall and act as opsonins
• Leukocytosis; increase white cell count,

• increased susceptibility to infection and delayed healing
• Inflammation is essential for clearing damaged tissue

X linked

• allergies
• autoimmune
• fibrosis