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89 Cards in this Set
- Front
- Back
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what is inflammation for?
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protective cell response to rid organism of initial cause of cell injury & consequences of same
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when does inflammation cause tissue injury?
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when it is inappropriately triggered or poorly controlled
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what are the body's principle defenders against foreign invaders? (3)
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plasma proteins
circulating leukocytes phagocytes (derived) |
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what characterises acute inflammation? (2)
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oedema
emigration of leucocytes (neutrophils) |
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what characterises chronic inflmaation? (4)
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presence of lymphocytes & macrophages
proliferation of blood vessels fibrosis tissue destruction |
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what are the two main processes of repair in inflammation? which is the most common?
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regeneration ofnative parenchyma
filling of defect w fibrous tissue (scarring) MOST common - combo of both |
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what would be the characteristic of an ideal anti inflammatory drug?
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control harmful sequelae of infection without interfering with beneficial effects
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what are the three major components of acute inflammation?
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1. alterations in vascular caliber, leading to increased blood flow
2. structural changes of microvasculature, permitting plasma proteins & leucocytes to leave circulation 3. emigration of leucocytes from microcirculation; their accumulation in focus of injury & activation to eliminate offending agent |
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draw the difference between local manifestions of acute inflammation & the normal vascular bed
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robbins fig 2-1
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what are the 4 main categories of stimuli for acute inflammation?
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infection
tissue necrosis from any cause foreign body immune (hypersensitivity) reaction |
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what are the important receptors for detecting microbial products?
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toll like receptors
cytoplasmic receptors which can detect bacteria/viruses/fungi |
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give 5 examples of molecules released from necrotic cells that elicit inflammation
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uric acid
ATP HMGB-1 (DNA binding protein of unknown origin) DNA loose of nuclei hypoxia induced factor 1-alpha (produced by cells deprived of origin) |
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how do foreign bodies elicit inflammation?
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carry microes
cause traumatic tissue injury |
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what are the two main categories of immune reactions leading to acute inflammation
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autoimmune disease
excessive reactions to environmental substances/microbes |
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draw a diagram to distinguish transudate from exudate
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robbins fig 2-2
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what are the causes of transudate vs exudate
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exudate - inflammation (permeable blood vessels)
transudate - osmotic/hydrostatic imabalance across vessel wall without permeability |
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is oedema a transudate or exudate?
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either
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what makes up pus?
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leucocytes (mostly neutrophils)
dead cell debris microbes (often) |
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what mediates vasodilation?
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histamine & NO on vascular smooth muscle
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draw the principal mechanisms of increased vascular permeability in inflammation, their features & underlying causes
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robbins fig 2-3
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what is the most common mechanism of vascular leakage?
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contraction of endothelial cells resulting in increased interendothelial space
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what constitutes reactive lymphadenitis?
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hyperplasia of lymphoid follicles & increased numbers of lymphocytes/macrophages
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what clinical signs are diagnostic of lymphangitis?
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red streaks near a skin wound
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what is the most important characteric of a leukocyte in inflammation? which leucocytes can do this?
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phagocytosis
neutrophils & macrophages |
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??? HOW MUCH DETAIL DO WE NEED TO KNOW ABOUT LEUCOCYTE EXTRAVASATION??
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..
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what are the 3 main steps of leucocyte extravasation?
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1. lumen - margination, rolling & adhesion to endothelium (which doesn't normally bind cells)
2. migration across endothelium/vessel wall 3. migration in tissues towards chemotactic stimulus |
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what does the term margination refer to wrt leucocytes in inflammation?
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blood flow slows early in inflammation; haemodynamic conditions change (decreased wall shear stress) & white cells are redistributed more peripherally along the endothelium
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how does rolling occur wrt leucocytes in inflammation?
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rows of leucocytes attach transiently to endothelium, then bind again
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what are selectins?
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a family of proteins that mediate the initial rolling interactions of leucocytes to endothelium
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what induces leucocytes to migrate through intraendothelial spaces?
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chemokines which pull the leucocytes by an attractive concentration gradient
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how do genetic deficiencies in leucocyte adhesion molecules manifest?
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recurrent bacterial infections
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what is chemotaxis?
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locomotion oriented along a chemical gradient
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what are the main endogenous and exogenous chemoattractants for leucocytes?
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1. exogenous - bacterial products
2. endogenous - cytokines eg IL8 , complement system eg C5a, arachidonic acid metabolites |
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what kind of leucocyte receptors do chemotactic agents bind to?
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specific seven-transmembrane G protein coupled receptors on the leucocyte surface
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how does a leucocyte move?
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extending filopodia that pull the back of cell in direction of extension (like the front wheels of a car pull the car along)
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what type of leucocyte predominates in the first 6-24 hours & are replaced by what in 24-48 hours?
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neutrophils
monocytes in 24-48hrs |
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why would neutrophils appear early in the inflammatory response? (3)
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- more numerous in blood
- respond more rapidly to chemokines - attach more firmly to adhesion molecules on endothelium |
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why do monocytes become the dominant population in chronic inflammation (vs neutrophils)? (2)
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survive longer
can proliferate in tissues |
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what are the two sequential sets of events in leucocyte response once they are at the site of infection/cell death?
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1.recognition of offending agent which delivers signal that
2. activate leucocytes to ingest/destroy offending agents & amplify inflamm reaction |
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what are toll like receptors and where are they found?
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receptors for different components of different types of microbes
on cell surface & endosomal vesicles of leucocytes so can recognise products of both extracellular & ingested microbes |
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draw the different receptors and responses of leucocytes to acute inflam stimuli
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robbins fig 2-8
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what is opsonisation?
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process of coating a microbe to target it for phagocytosis
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give some examples of opsonins
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complement protein C3
antibodies esp IgG |
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what are the functional responses most important for destruction of microbes in acute inflam?
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phagocytosis and intracellular killing
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what are the 3 steps of phagocytosis?
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microbe binds to phagocytic receptor
microbe ingulfed microbe destroyed |
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what increases the efficiency of phagocytosis?
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opsonisation
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what is a phagosome? lysosome? phagolysosome?
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phagosome - pinched off vesicle with plasma membrane & engulfed microbe
lysosome - granule containing enzymes phagolysosome - fusion of above, resulting of mixing of contents |
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how are microbes destroyed once engulfed in the phagolysosome? (2)
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lysosomal enzymes kill microbe
or reactive oxygen species / NO kills microbe |
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how are activated leucocytes involved in tissue repair?
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stimulate proliferation endothelium, fibroblasts & collagen synthesis
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what compounds released by leucocytes can inadvertantly cause cell damage?
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lysosomal enzymes
reactive oxygen species/ NO |
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give 5 clinical examples of leucocyte induced injury
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ARDS - neutrophils
septic shock - cytokines asthma - eosinophils/IgE acute transplant rejection - lymphocyte, antibodies, complement glomerulonephritis - neutrophils, monocytes, antibodies, complement |
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what are the "sentinel" white cells for sensing injury?
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mast cells - eg physical trauma
macrophages - microbial products; responsible for cytokines important in acute inflamm |
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how is acute inflammation terminated?
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short half lives of mediators
degraded after release mediators produced in rapid bursts, only as long as stimulus persits some stop signals produced |
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what are the two major vasoactive inflammatory mediators & what is their source?
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histamine (mast cells)
serotonin (platelets) both cause vasodilation & increased vascular permeability |
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what is arachidonic acid? what are its derived mediators called?
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omega 6 fatty acid, normally found in membrane phospholipids
mediators called eicosanoids |
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what two major classes of enzymes synthesise eicosanoids & what do they generate?
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cyclooxygenases -> prostaglandins
lipoxygenases -> leukotrienes & lipoxins |
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where do eicosanoids bind & what steps of inflammation are they involved in?
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bind G protein receptors on many cell types
can mediate virtually all steps of inflamation |
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at what points do anti inflammtory drugs inhibit inflammatory mediators
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steroids inhibit phospholipases which convert cell membrane phospholipids to arachidonic acid
COX1/2 inhibitors, indomethacin & aspirin inhibit cyclooxygenases which convert arachidonic acid to prostaglandin |
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what are the anti leukotriene drugs and how do they fit into the arachidonic acid pathway?
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montelukast & zafirlukast inhibit the non COX pathway of arachidonic acid metabolism, the 5 lipooxygenase pathway which inevitably results in leukotriene production, which mediates bronchospasm, vasoconstriction & increased vascular permeability
their regular use is no more effective that inhaled beclamethasone but useful in those who don't tolerate this |
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what role does NO have in inflammation?
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dual roles - releases vascular smooth muscle & promotes vasodilatation (contributes to vascular reaction) also inhibits cellular component of inflammatory response
also microbicidal |
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which cells principally produce cytokines?
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activated lymphocytes (CD4 helpers) & macrophages
but can be produced by many cell types |
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what are the two primary cytokines in the acute inflammatory response? produced by what kind of cell?
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TNF
IL-1 (used to be known as endogenous pyrogen because could induce fevers) produced by activated macrophages |
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what is the critical step in complement activation in the acute inflammatory response?
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proteolysis of C3
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?? do we need to know activation and function of complement system??
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robbins 2-14
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how does inflammation and blood clotting relate?
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often intertwined with each promoting the other
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name 3 mediators of vasodilation in inflammation
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histamine
NO prostaglandins |
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name 5 mediators for increased vascular permeability in actue inflammation
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histamine
serotonin C3a/C5a bradykinin leukotrienes PAF |
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name 5 mediators in chemotaxis, leukocyte recruitment & activation in acute inflammation
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TNF
IL1 chemokines C3a C5a leukotriene B4 |
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name 3 mediators in fever in acute inflammation
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TNF
IL1 prostaglandins |
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name 2 mediators of pain in acute inflammation
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prostaglandins
bradykinin |
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name 3 mediators of tissue damage in acute inflammation
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lysosomal enzymes of leucocytes
reactive oxygen species nitric oxide |
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what are the morphologic hallmarks of all acute inflammatory reactions? (3)
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dilation of small blood vessels
slowing of blood flow accumulation of fluid & leucocytes in extravascular space |
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what is serous inflammation?
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outpouring of thin fluid derived from plasma or secreted by cells eg blister from burn/viral infection
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what is fibrinous inflammation?
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vascular permeability becomes so large that fibrinogen passes through the vasculature, fibrin is formed & deposited in extracellular space.
characteristic of inflammation in lining of cavities - meninges, pericardium, pleura |
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what can happen to fibrinous exudate?
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it can be ORGANIZED (converted to scar tissue) which can cause probs eg in pericardium can obliterate pericardial space
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what is suppurative acute inflammation?
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pus, abscess caused by deep seeding of pyogenic (pus causing) bacteria into a tissue
eg acute appendicitis |
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what is an ulcer?
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a local defect or excavation of the surface of an organ or tissue that is produced by sloughing of inflamed necrotic tissue
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what are the only conditions that support an ulcer (2)
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tissue necrosis & resultant inflammation on or near a surface
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summarise acute inflammation
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host encounters injurious stimulus
phagocytes try to eliminate stimulus phagocytes & host cells also liberate cytokines, lipid messengers & other inflammatory mediators small blood vessels affected by mediators -> plasma & circulating leukocytes recruited to the site activated leukocytes try to phagocytose if injurious agent eliminated, process subsides & normal health resumes otherwise may progress to chronic inflammation |
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what causes the redness, heat and swelling of acute inflammation?
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increased blood flow and oedemaw
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what causes pain in acute inflammation?
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prostaglandins, neuropeptides & cytokines
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what is the acute phase response?
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systemic changes associated w acute inflammation
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what are the components of the acute phase response (3 major)
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fever
acute phase proteins ie CRP, fibrinogen leucocytosis |
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what causes fever in acute phase response?
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IL1 & TNF increase cyclooxygenases which convert AA into prostaglandins
prostaglandins, esp PGE2 stimulate neurotransmitters to reset temperature set point upwards |
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how do NSAIDs reduce fever?
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by inhibiting prostaglandin synthesis
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what are the three best known acute phase proteins & where are they made?
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CRP, fibrinogen, serum amyloid A
made mostly in the liver |
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what does ESR measure?
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fibrinogen binding to RBCs causing them to form stacks which sediment more rapidly than individual cells
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which infections are associated w decreased WCC?
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typhoid fever
rickettsiae some protozoa some viruses those in patients otherwise debilitated (eg severe EtOH, TB) |
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when do we see raised eosinophils?
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allergy
bronchial asthma parasites |
