inflammation, wound healing, trauma/ICU/Burn Flashcards
phases of inflammation
injury-> exposed collagen-> plt activating factor release and tissue factor release from endothelium-> platelets bind collagen-> release growth factors (ie-ptl-derived GF PDGR)-> PMN and macrophage recruitment
role of macrophages in wound healing- what do they release
dominant role, release PDGF (plt derived GF) and cytokines (IL-1 and TNF-alpha)
Growth and activating factors in inflammation: role of the following
1) PDGF (platelet derived growth factor)
2) EGF (epidermal growth factor)
3) FGF (fibroblastic growth factor)
4) PAF (platelet-activating factor)
1) chemotactic and activates inflammatory cells (PMNs and macrophages) and activates fibroblasts-> ECM proteins and collagen. Imp for angiogenesis and epithelialization. Chemotactic for smooth muscle cells. accelerates wound healing
2, 3) Chemotactic, activates fibroblasts, angiogenesis, epithelialization
4) generated by phospholipase in endothelium (a phospholipid) which is chemotactic for inflam cells and inc adhesion mlqs
1) what are the chemotactic factors for inflammatory cells
2) for fibroblasts
3) angiogenesis factors
4) epithelialization factors
1) PDGF, IL-8, LTB-4, C5a and C3a, PAF
2) PDGF, EGF, FGF
3) PDGF, EGF, FGF, IL-8 and hypoxia
4) PDGF, EGF, FGF
1) How long do PMNs last in tissues and in blood
2) how long do platelets last
3) lymphocyte role in inflammation
1) 1-2 days in tissues, 7 days in blood
2) 7-10 days
3) involved in chronic inflammation (T cells) and Ab production (B cells)
Type 1 hypersensitivity rx:
1) role of eosinophils
2) what type of infections have increased eosinophils
3) role of basophils, where aren’t they found
4) Mast cells role
5) role of histamine
6) role of bradykinin
7) what inactivates bradykinin and where is it found
1) release major basic protien once bound to allergin-> stimulates basophils and mast cells to release histamine
2) parasitic
3) main source of histamine in blood (not in tissue)
4) main source of histamine in tissues, primary cell in type 1 hypersensitivity
5) vasodilation, tissue edema, postcapillary leakage; primary effector type in type I hypersensitivity rxs (allergic rxs)
6) peripheral vasodilation, increased permeability, pain, pulm vasoconstriction
7) Angiotensin-converting enzyme located in lung
Nitric oxide
1) what is its precursor
2) what does it activate and end effect
3) another name for it
4) what has the opposite effect of NO
1) Arginine
2) guanulate cyclase-> inc cGMP-> vascular smooth muscle dilation
3) endothelium-derived relaxing factor
4) Endothelin-> vascular smooth muscle constriction
cytokines
1) main initial cytokine resonse to injury and infection is release of
1) TNF-alpha and IL-1
cytokines
1) largest producer of TNF
2) role of TNF-alpha
3) what can high concentrations of TNF-a cause
4) largest producer of IL-1
5) effects of IL-1 and what does it synergize with
6) which cytokine causes cachexia in CA pts
7) which cytokine is responsible for fever and how?
8) how do NSAIDS reduce fever
9) role of IL-6
1) Macrophages
2) increases adhesion mlqs, procoagulant, activates neutrophils and macs-> more cytokine production and cell recruitment
3) circulatory collapse and multisystem organ failure
4) macs
5) same as TNF-alpha, synergizes with TNF-alpha
6) TNF-alpha
7) IL-1 (how alveolar macs cause fever with atelectasis), PGE2 mediated in hypothalamus
8) reduce PGE2 synthesis
9) increases hepatic acute phase proteins (CRP, amyloid A -> activate complement), decreases albumin, pre-albumin and transferrin
Interferons
1) what are they released by
2) what stimulates release
3) effect of release
1) lymphocytes
2) viral infection or other stimulants
3) activate macs, NK cells and cytotoxic T cells-> inhibit viral replication
Cell adhesion mlqs- where are they located, what they bind and type of adhesion
1) Selectins
2) Beta-2 integrins (CD11/18 molecules)
3) ICAM, VCAM, PECAM, ELAM
1) L-selectins on leukocytes bind E- (endothelial) and P-(platelet) selectins-> rolling adhesion
2) on leukocytes, bind ICAM etc-> anchoring adhesion
3) on endothelial cells, bind beta-2 integrin mlqs located on leukocytes and platelets. Also involved in transendothelial migration
Complement- what activates the following pathways and what factors are only in each one
1) classic pathway
2) alternative pathway
3) what complement factor is common to both pathways
4) what electrolyte is required for both pathways
1) (IgG or IgM) Ag-Ab complex activates. Factors C1, C2, C4
2) endotoxin, bacteria, other stimuli activate. Factors B, D and P (properdin)
3) C3
4) Mg
Complement
1) factors that are anaphylatoxins and actions
2) membrane attack complex factors and actions
3) opsonization factors and action
4) factors involved in chemotaxis for inflammatory cells
1) C3a, C4a, C5a. increase vascular permeability, bronchoconstriction and activate mast cells and basophils
2) C5b-9b-> cell lysis (usually bacteria) by creating hole in the membrane
3) C3b and C4b- targets Ag for immune response
4) C3a and C5a
Prostaglandins
1) precursor
2) LTC4, LTD4, and LTE4 actions
3) LTB4 actions
1) arachidonic precursors
2) slow-reacting substances of anaphylaxis, bronchoconstriction, vasoconstriction followed by increased permeability
3) chemotactic for inflammatory cells
Catecholamines
1) when after injury do they peak
2) where is norepinephrine released?
2) where is epinephrine released?
1) 24-48hours
2) sympathetic postganglionic neurons and adrenal medulla
3) adrenal medulla (neural response to injury)
T/F thyroid hormone plays a major role in injury/inflammation
false
neuroendocrine response to injury
afferent nerves from site of injury stimulate CRF, ACTH, ADH, growth hormone, epi and norepi release
CXC chemokines
1) what are they
2) what is their role
3) what does CXC stand for
1) IL-8 and platelet factor 4
2) chemotaxis, angiogenesis, wound healing
3) C=cysteine, X= another amino acid
1) what oxidants are generated in inflammation
2) what are cellular defenses against oxidative species
1) superoxide anion radical (NADPH oxidase), hydrogen peroxide (xanthine oxidase)
2)superoxide anion radical- defense is superoxide dismutase
hydrogen peroxide- defence is glutathione peroxidase, catalase
primary mediator of reperfusion injury
PMNs
Chronic granulomatous disease:
1) enzyme defect and result
NADPH-oxidase system enzyme defect in PMNs-> decreased superoxide radical formation-> increased infection from bacteria and fungi
stages of wound healing- cells involved, what happens during each and time frame
1) Inflammation
2) proliferation
3) remodeling
1) days 1-10. PMNs, macs. Epithelialization (1-2mm/day)
2) 5days-3wks. fibroblasts. collagen deposition, neovascularization, granulation tissue formation; type III collagen replaced with type 1
3) 3wk to 1 year. decreased vascularity. net amount of collagen unchanged despite sig production and degradation
rate of
1) epithelialization
2) peripheral nerve regeneration
1) 1-2 mm/day
2) 1mm/day
order of cell arrival in wound: PMNs, lymphoctes, macs, fibroblasts, platelets
1) platelets
2) PMNs
3) Macrophages
4) lymphocytes
5) fibroblasts