Inflammation Flashcards
Purpose of inflammation
-Isolate, dilute, neutralize, confine, and remove offending agent
-Clear area of debris
-Initiate healing and repair
Outcomes of inflammation
-Eliminate agent and return to normal
-Stalemate: ongoing
-Death of host
Cardinal sings of inflammation
-Rubor(redness)
-Tumor (swelling)
-Calor (heat)
-Dolor (pain)
-Function laesa (loss of function)
Vascular events in inflammation (7)
- Transient arteriolar vasoconstriction
- Arteriolar vasodilation
- Capillary congestion
- Increased vascular permeability
- Slowing blood flow
- Redistribution of blood cell elements
- Blood flow stasis
Transient arteriolar vasoconstriction
Caused by stimulus on smooth muscle regulated by local mediators. Doesn’t occur with all stimuli. Can last several seconds up to 5 minutes
Arteriolar vasodilation
A wave starting at arteriole to venule. Causes hypermia. Mediators include: histamine, bradykinin, Prostacyclin, NO etc
Increased vascular permeability
Endothelial junctions become leaky resulting in fluid loss. Mediators from immediate transient response and delayed sustained response (TNF, IL1 etc). Results in edema
Edema from vascular permeability
Fluid in ECM contains proteins involved in inflammation and helps dilute inciting stimulus Starts as a transudate(basically water) to an exudate
Slowing of blood flow
-Large vascular diameter and increased number of blood cells (congestion)
-Increased blood viscosity due to plasma loss
-Increased adhesiveness of erythrocytes
Redistribution of blood cell elements
-Laminar flow is disrupted due to vasodilation and congestion
-Erythrocytes centrally located
-Leukocytes move to periphery along endothelial
End goal
-Dilution of inflammatory stimulus
-Movement and concentration of plasma mediators at inflammation
-Intravascular leukocytes are poised to leave vessel
Cellular events major steps
- Margination and adhesion to endothelium
- Emigration
- Chemotaxis
- Accumulation
Margination
Leukoctes move to periphery of vessels generally post capillary venules
-Roll along endothelium by binding to selectins then firmly bind through ICAM and VCAM and B-2 integrins
Emigration
Leukocytes move from endothelial surface into the ECM
-Go through endothelial pores
-More receptors within the interendothelial junction (PECAM-1 and JAMs)
-Leukocytes exert pseudopods (Ca mediated) into junction and pulls them through to the outside
Order of emigration
-Neutrophils
-Monocytes
-Lymphocytes
Chemotaxis
Leukocytes directed to site of inflammatory stimulus.
-Occurs in response to a concentration gradient of a chemical attractant
Chemotactic factors
-Complement components
-Bacterial products
-Arachidonic acid metabolites
-Kinins
-Collagen and fibrin breakdown products
-Cytokines
-Chemokines
Mechanism of chemotaxis
-Chemotactic factors interact with specific leukocytes membrane receptors
-Phospholipase C activated and get localized release of cytoplasm Ca that causes assembly and disassembly of microtubules
-B1-integrins bind to ECM components and pull to stimulus
Accumulation
-Neutrophils accumulate first byt they are short-lived
-Macrophages more numerous after 24-48hrs but are long lived
-Lymphocytes may persist later in persistent stimuli
Events of phagocytosis
-Opsonization
-Attachment
-Ingestion
-Killing and degradation
-Oxygen independent killing
-Oxygen dependent killing
Most important phagocytes in inflammation
Neutrophils and macrophages
Opsonization
Coat foreign material with opsonin to enhance phagocytosis (C3b, IgG, collectins)
Attachment
Phagocyte attaches to foreign material thanks to opsonins
-Can attach to unopsonized material but less efficiently
Ingestion
Cell membrane pseudopods extend around material and internalize it into an intra-cytoplasmic vacuole (phagosome)
-Ca fluces regulate cytoskeletal changes
Killing and degredation
A lysosome fuses to phagosome to form phagolysosome enzymes released (degranulation)
-Then kill with either oxygen dependent or independent killing
-Degrade and digest material
O2 independent killing
Acid hydrolases
-Bactericidal permeability increasing protein
-Lysozyme
-Lactoferrin
-Defensins
etc
O2 dependent killing
Use Oxygen metabolites that are highly reactive 2 paths: myeloperoxidase independent and dependent pathway
Myeloperoxidase independent path
-Superoxide anion, hydrogen peroxide, and hydroxyl radical
-Form NADPH oxidase during respiratory burst initiates process
Myeloperxidase dependent
Make hypochlorous acid (bleach)
-Most potent killing mechanisms
-In neutrophils
