Lecture 3 - Inflammation Flashcards
what is the clinical evidence of inflammation in terms of vascular changes?
heat (calor)
redness (rubor)
swelling (tumor)
what is clinical evidence of inflammation in terms of chemical mediators and leukocytes?
pain (dolor) and loss of function
how long does acute inflammation last and how is it characterized?
- from hours to days
- exudation and neutrophil infiltration
how long does chronic inflammation last and how is it charcterized?
- spans days to years
- mononuclear inflammatory cell (lymphocytes, macrophages, plasma cells) infiltration with vascular proliferation and fibrosis in later stages
does acute or chronic inflammation cause additional tissue injury
trick questionnnn
*BOTH acute and chronic inflammation may cause additional tissue injury
what factors is fever mediated by?
IL-1, TNF, PGE2
role of vasodilation
- begins in the precapillary arterioles and results in engorgement of capillary beds
- account for the redness and localized heat
- mediated by endothelial cell derived NO that induces vascular smooth muscle relaxation, and mast cell release of histamine
- it is maintained by prostaglandins (PGI2, PGD2, PGE2, and PGF2)
increased vascular permeability results in:
- movement of fluid outside of the microvasculature, transudate or exudate
- blood becomes more concentrated and flow slows (stasis)
- movement of inflammatory cells out of the vessels (diapedesis) occurs at level of post- capillary venules
accumulation of fluid in the extravascular tissue leads to..
swelling (edema)
what are some characteristic of transudate?
- low protein content
- low specific gravity (<1.012)
- clear and yellow
- Noninflammatory - endothelium is intact, fluid accumulates due to increase hydrostatic pressure and/ or decreased serum oncotic pressure
- Inflammatory - early endotheial cell contraction
what are some characteristics of exudate?
- indicative of tissue and endothelial cell damage
- high protein content
- high specific gravity (> 1.020)
- often contains inflammatory cells
what kind of exudate has the following characteristics: high protein (fibrin), few cells, cloudy?
fibrinous exudate
what kind of exudate has the following characteristics: contains cells (neutrophils), opaque
purulent exudate (pus)
what kind of exudate has the following characteristics: pink to red due to blood
sanguineous
increased vascular permeability may be due to..
inflammatory mediators or direct injury to the endothelial cells
what happens as a result of endothelial cell contraction
forms intracellular gaps (mainly in post capillary venules) due to reversible contraction
- occurs rapidly and lasts for 15-30 mins
- it is mediated by histamine and bradykinin early, and later by leukotrienes and PAF
- C3a and C5a induce vasoactive amine release that leads to edema
what happens as a result of endothelial cell retraction?
due to restructuring of cytoskeletal proteins is mediated by IL-1, TNF, and IFN-gamma
- takes 4-6 hours to develop and lasts for 24 hours or more
increased vascular permeability due to direct endothelial injury may….
start immediately (immediate-sustained) or be delayed (delayed - prolonged) and persists for hours to days
direct venule endothelial injury may occur from what?
neutrophilic release of ROS and lysosomal enzymes (e.g. proteases) during the inflammatory response
various factors will activate endothelial cells, these include:
histamine thrombin complement factors cytokines (IL-1 and TNF) bacterial products hypoxia viruses PAF
activated endothelial cells are characterized by:
- production of PGI2 and NO that induce vasodilation
- contraction
- rearrangement of cytoskeletal proteins leading to retraction
- increased expression and affinity of surface cell adhesion molecules
- synthesis and release of inflammatory mediators (PGI2, PAF, IL-1, IL-6, and chemokines)
leukocyte extravasation and accumulation at the site of injury proceeds in an orderly coordinated sequence of events, what are they?
- leukocyte migration
- leukocyte rolling
- leukocyte adhesion
- emigration
- chemotaxis
cell adhesion molecules mediate the processes involved in the movement of leukocytes from the blood stream to the
extravascular tissue
margination definition
mechanical process due to slowing of blood flow
rolling definition
selectins mediate a weak, transient, sticking that slows the cells forward progression
adhesion definition
mediate by integrins through the vessel wall (diapedesis) - mediated by PECAM-1
what is chemotaxis
it is a non-randomized movement of leukocytes to the site of injury along a concentration gradient of chemotactic factors
- the factors bind to the cell surface receptors
- chemotactic factors also stimulate leukocyte activation
what are examples of chemotactic factors? (6 of them)
PAF (potent) LTB4 (potent) C5a chemokines bacterial lipids and peptides fibrin degradation products
Several different factor activate leukocytes during an inflammatory response, these include:
bacterial products cellular debris Ab-Ag complexes cytokines and chemokines chemotactic factors
activation of leukocytes is characterized by:
- production of leukotrienes and prostaglandins from arachidonic acid
- degranulation and release of lysosomal enzymes
- production of ROS
- synthesis and secretion of cytokines
- altered expression of cell adhesion molecules
what is phagocytosis?
- attachment mediated by opsonins (IgG, C3B, collectins) on targets and specific leukocyte receptors (Fc receptor for IgG, complement receptors)
- engulfment into a phagocytic vacule
- lysosomal degranulation by fusion with the phagosome
- oxidative burst releasing ROS (superoxide, hydrogen peroxide, hypochlorous radical)
- other mechanisms of intracellular killing; lysozyme, major basic protein, defensins and bactericidal permeability- increasing protein
what is the morphologic hallmark for acute inflammation and begin to accumulate within 6-24 hours?
neutrophils (PMNs)
what is the cell described below:
- infiltrate tissue in response to tissue necrosis (e.g. myocardial infarction) and bacterial and some fungal infections
- undergo apoptosis after phagocytosis and digestion
- release ROS and lysososomal enzymes
neutrophils (PMNs)
what cell replaces PMNs, usually beginning within 48 hours
monocytes (Macrophages/ histiocytes)
monocytes are called histiocytes or macrophages after…
entering into tissue
what is the half life for circulating monocytes
half life is months compared to one day
activated macrophages have several functions including:
- Phagocytize and digest cellular debris
- take up and metabolize antigens and present membrane bound antigen to immunocompetent T cells
what are various factors that monocytes elaborate?
- enzymes (proteases)
- complement and coagulation factors
- cytokines (e.g. IL-1, TNF)
- ROS and NO
- prostaglandins
- growth factors
what are other cells of inflammation under monocytes:
- lymphocytes, plasma cells
- eosinophils (allergic reactions, parasitic infections)
- mast cells - surface IgE (release hsitamine)
definition of cellulitis
diffuse, permeative infiltration of neutrophils with edema
definition of abscess
localized area of liquefactive necrosis
definition of ulcer
erosion of an epithelial surface exposing underlying connective tissue
how does acute inflammation differ from chronic inflammation in terms of time?
acute inflammation - 10-14 days
chronic - months to years
acute inflammation is innate whereas chronic inflammation relies upon …
specific, adaptive immune system
T/F.
Acute inflammation may be reversible or fatal.
Chronic inflammation may be reversible or fatal.
Both are true
causes for chronic inflammation include:
- persistant infections
- prolonged exposure to a toxic agent
- immune mediated inflammatory disease
non specific chronic inflammation is often associated with tissue ____
repair (granulation tissue/ fibrosis
in regards to non-specific chronic inflammation, the cellular infiltrate may contain….
macrophages, lymphocytes, plasma cells, and/or eosinophils
*few neutrophils my also be present
which type of inflammation is linked to the delayed type IV hypersensitivity immune reaction
granulomatous inflammation
morphology of granulomatous inflammation includes:
epithelioid (activated) histiocytes - granular pink cytoplasm with indistinct borders
- Central caseous necrosis often present
- epithelioid histiocytes coalesce to form multinucleated giant cells Langerhans or foreign body type
- a collar of mononuclear cells often surrounds the aggregated epithelioid histiocytes, older granulomas develop a rim of fibroblasts and CT
how does granulomatous inflammation heal?
heals by fibrosis
Diseases characterized by granulomatous inflammation include:
- bacterial infection - TB, cat scratch fever
- parasitic infection - schistosomiasis, toxoplasmsis
- fungal infection - coccidioidomycosis, histoplasmosis
- inorganic matter - silicosis, inert foreign material
- unknown - sarcoidoss, Crohn’s disease
What is the source and function of histamine?
source: mast cell
function: vasodilation, increase vascular permeability
What is the source and function of bradykinin
source: plasma protein
function: increase vascular permeability, pain
What is the source and function of nitric oxide?
source: endothelial cells and other cells
function: vasodilation, tissue damage
What is the source and function of prostaglandins?
source: membrane phospholipids
function: vasodilation, pain, fever, potentiate, other mediators
What is the source and function of leukotrienes C4, D4, E4?
source: membrane phospholipids
function: increase vascular permeability, vasoconstriction, bronchoconstriction
What is the source and function of leukotriene B4?
source: leukocytes
function: leukocyte activation, chemotaxis
What is the source and function of PAF?
source: leukocytes, endothelial cells
function: increase vascular permeability, chemotactic
What is the source and function of cytokines (IL-1 and TNF)
source: macrophages, endothelial cells
function: endothelial cell and leukocyte activation, fever
What is the source and function of C5a and C3a?
source: plasma protein
function: chemotaxis (C5a), phagocytosis (C3b), increase vascular permeability (C3a and C5a)
histamines are release by physical injury, antigen binding to…
IgE, C3a, C5a, cytokines
prostaglandins and leukotrienes are derived from arachidonic acid through the action of…
cyclo-oxygenase (prostaglandins) or lipo-oxygenase (leukotrienes)
aspirin and non-steroidal anti-inflammatory drugs reduce inflammation by blocking…
cyclo-oxygenase activity
steroids inhibit release of arachidonic acid from…
cell membrane phospholipids
while prostaglandins generally cause _____, thromboxane A2 causes _______
vasodilation; vasoconstriction
thromboxane A2 promotes _____ _____ and prostacyclin inhibits _____ _______
platelet aggregation
what are examples of the intrinsic capacity for proliferation forL continuously dividing cells
- continuously dividing: hematopoietic cells, surface epithelium
what are examples of the intrinsic capacity for proliferation for: stable cells
stable: minimal replication in normal conditions, capable of proliferation in response to injury, parenchymal calls of most solid organs, smooth muscle cells, fibroblasts
what are examples of the intrinsic capacity for proliferation for: permanent cells
Permanent: no capacity for proliferation, neurons, cardiac muscles
what are the 7 steps for healing by first (primary) intention
- blood clot (minutes)
- neutrophils (within 24 hours)
- early proliferation/ migration of epithelial cells (24-48 hours)
- Macrophages replace neutrophils; early granulation tissue (day 3)
- Peak neovascularization (day 5)
- Progressive collagen deposition (during 2nd week)
- increasing wound strength during next 4 months
what are the 2 steps in healing by second intention?
- more inflammation; more granulation tissue
2. wound contraction due to myofibroblasts
growth factors and cytokines have a role in…
wound healing (he says look up on page 62, table 2-9 - aint nobody have time or money for that)
factors that affect wound healing (6 of them)
- infection
- nutrition (protein, vitamins)
- steroids
- mechanical factors
- poor perfusion
- diabetes mellitus
