inflammation and healing Flashcards
what is inflammation
- complex response of vascularized tissues to cell damage in order to eliminate offening agents
- protective mechanism to remove injurious stimuli and to initiate the healing process
inflammation develops through a series of steps:
5 R’s
- recognition
- recruitment
- removal
- regulation
- repair
what does inflammation look like
- rubor (redness)
- calor (warmth)
- tumor (swelling)
- dolor (pain)
- functio laesa (loss of function)
what is acute inflammation
- takes several hours to several days
- many endogenous and exogenous triggers
- if acute inflammation fails to clear the stimulus -> chronic inflammation
what are the 3 sequential phases of acute inflammation
- fluidic
- cellular
- reparative
fluid phase of acute inflammation
vasodilation
- hisamine, nitric oxide (NO)
- hyperemia -> increased blood flow (calor, rubor)
fluid phase of acute inflammation
endothelial cell activation
- increased vascular permeability -> fluid, protein, fibrinogen exudation -> edema (tumor)
- fibrinogen = important plasma protein normally floating around in blood -> fibrin in tissues
fluid phase of acute inflammation
increased blood viscosity
slower blood flow -> allows leukocytes to accumulate along endothelium
what are the 4 stages of the cellular phase in acute inflammation
- margination
- rolling
- stable adhesion
- transendothelial cell migration
step 1
margination
- bridge between fluidic and cellular phases
- vasodilation (reduced blood flow, increased blood viscosity, leukocytes line up along endothelial surface)
step 2
rolling
- transient, WEAK binding between endothelial cell and leukocyte
- selectins (some on endothelial cells, some on leukocytes)
step 3
stable adhesion
- leukocytes STRONGLY adhere to endothelium
- requires leukocyte and endothelial cell activation (cytokines - IL-1, IL-6, IL-8, TNF; complement factors)
- integrins (beta-integrains on leukocyte surface)
step 4
transendothelial cell migration
- leukocytes move across endothelial cell layer into tissue
- PECAM-1 (CD31)
what are 4 variations of acute inflammation
- serous inflammation
- catarrhal inflammation
- fibrinous inflammation
- suppurative inflammation
what is serous inflammation
- low plasma protein, little or no leukocytes
- thermal injury to skin (burns) -> blister
- acute allergic responses -> watery eyes and runny nose
what is catarrhal inflammation
- thick gelatenous fluid containing abundant mucus
- chronic inflammation of airways of the respiratory system -> chronic asthma
what is fibrinous inflammation
- due to endothelial cell activation/injury -> leakage of fibrinogen -> formation of fibrin
- body cavities
- synovial membranes of joints
- meninges
what is suppurative inflammation
- inflammation with high plasma protein and high numbers of leukocytes, predominantly neutrophils -> pus
- due to pyogenic bacteria (pyometra ex)
kinetics of neutrophils in inflammation
6-24 hrs
kinetics of monocytes (macrophages) in inflammation
24 hrs and beyond
kinetics of lymphocytes and plasma cells in inflammation
greater than 48 hrs and beyond
what are the main histologic and pathologic features of acute inflammation
- neutrophils first, then macrophages
- plasma/fluid leakage -> edema +/- fibrin
what are outcomes of acute inflammation
- progression to chronic inflammation
- complete resolution
- healing by fibrosis
progression of chronic inflammation occurs when:
- acute response is unresolved/inciting cause is not cleared
- repeated episodes of acute inflammation w/ extensive injury and necrosis
- establishment of an autoimmune reaction
there is a shift of cellular elements from neutrophils to: ____, ____, ____, etc. when acute inflammation progresses to chronic inflammation
lymphocytes, monocytes, plasma cells
a hallmark for chronic inflammation
tissue destruction
lymphocytes
in chronic inflammation
antibody- and cell-mediated immune reactions
plasma cells
in chronic inflammation
develop from activated B lymphocytes, produce antibody against antigens or altered tissue components
macrophages
in chronic inflammation
- responsible for much of the tissue injury in chronic inflammation (ROS, ECM proteases)
- important role in healing -> induce fibroblast activation and proliferation -> collagen deposition, and antiogenesis
what are the 3 special types of chronic inflammation
- granulomatous inflammation
- pyogranulomatous inflammation
- abcess formation
what is granulomatous inflammation
- epithelioid macrophages, multinucleated giant cells, variable # of lymphocytes and plasma cells, surrounding an indigestible organism, particle, or central necrotic area
- surrounded by fibrosis
- implies certain etiologic agents
- granuloma = one of more isolated foci of granulomatous inflammation
what is pyogranulomatous inflammation
- epitheliod macrophages forming granulomas with admixed neutrophils and necrosis
- implies certain etiologic agents
what is abcess formation
- occurs when the acute inflammatory response fails to rapidly eliminate inciting stimulus
- enzymes and inflammatory mediators from neutrophils -> liquefy tissue to form pus
- a collection of pus circumscribed by a fibrous capsule that is visible grossly
main points of acute inflammation
- rapid onset (seconds to minutes), short duration (minutes to days)
- fluid and plasma proteins leak into tissues (edema)
- fibrinogen -> fibrin
- leukocytes (neutrophils) migrate into tissues
- if unresolved, leads to chronic inflammation
main points of chronic inflammation
- long time frame (days, weeks, years)
- lymphocytes, plasma cells, and macrophages
- fibrous connective tissue deposition
- tissue necrosis
what are the 4 phases of wound repair
- hemostasis
- acute inflammation
- proliferation
- remodeling
what is complete resolution of acute inflammation
- typical outcome to limited injury (mosquito bite)
- mediators decay quickly
- vascular permeability returns to normal
- leukocytes die, edema and proteins removed by macrophages
tissue regeneration is ____% normal when resolved
100
what is regeneration
- replacement by cells of the same type
- requires intact framework
- occurs by compensatory growth -> organ becomes functional due to cell hyperplasia and hypertrophy
what determines whether a tissue will undergo regeneration or healing
- type of tissue damaged
- damage to the extracellular matrix
- extent of the wound
- blood supply, nutrition
regeneration
continuously dividing (labile) tissues=
cells proliferate throughout life (gut epithelium)
regeneration
quiescent (stable) tissues=
low level of replication; may undergo division in response to stimuli (e.g. parenchymal cells of liver, kidneys, and pancreas)
regeneration
post-mitotic(permanent/terminally differentiated) tissues=
cannot undergo mitotic division in postnatal life (neurons, cardiac muscle cells)
cannot undergo renegeration
what is healing
- restoration of integrity to injured tissue
- typically involves collagen deposition and scar formation
wound healing
what is the inflammation phase
- 24hrs after injury; lasts up to 96 hrs
- macrophages = necessary for tissue repair (remove cell debris, degrade ECM, release growth factors necessary for proliferation phase)
- fibrin = loose gel-like matrix to serve as the scaffold for granulation tissue
wound healing
what is the proliferation phase
- lasts up to 3-4 weeks
- granulation tissue = proliferation of new blood vessels, fibroblasts, and deposition of early collagen (necessary for re-epithelialization, sometimes called the “wound bed”
wound healing
remodeling/maturation phase
- begins ~3-4 weeks after injury, but only after the other phases are successfully completed (can last years)
- granulation tissue (blood vessels and immature CT) converted to mature CT (fibrosis)
- mediated by TGF-B -> pro-fibrosis, anti-inflammatory
- extracellular collagen formation -> ECM reestablished
- contraction of tissue
- fibroblasts, myofibroblasts
does tissue return to 100% normal structure and function with wound healing
no
what are disruptors of wound repair
- bacterial infections
- poor nutriton
- glucocorticoid therapy
- mechanical factors
- poor apposition/dehiscence
- poor perfusion
- amount of tissue injured
- tissue type
abnormalities in tissue repair
- inadequate granulation tissue formation
- ecessive formation
- aberrations of cell growth and ECM production
- contraction
