1
Q
Cornelius celsius
A
- calor, rubor, dolor, tumor
- virchow added loss of function
2
Q
Julius cohnheim
A
Revealed basis of inflammatory response
3
Q
Characteristics of acute inflammation
A
- vasc. Changes
- inflammatory edema (plasma proteins & fluid)
- leukocyte emigration ( mostly neutrophils)
4
Q
Subacute inflammation characteristics
A
- decline in vasc. Contrib. (Edema and hyperemia)
- change in leukocytes (neutrophils @ inflamm. site & infiltrate mixed with mononuclear cells)
- lasts few days- few weeks
5
Q
Chronic inflammation characteristics
A
- presence of lymphoc., macrophages
- prolif. of small BV and fibroblasts
6
Q
3 stages of acute inflammation
A
1) hemodynamic changes
2) vasc. Permeability changes
3) leukocytic exudation
(May have overlap)
7
Q
3 types of hemodynamic changes
A
1) vasoconstriction of arterioles
2) vasodilation of arterioles
3) slowing of blood flow
8
Q
Vasoconstriction
A
- part of acute inflamm. response
- inconsistent finding
- usually disappears within 3-5 seconds
9
Q
Vasodilation
A
- believed to be caused by histamine, prostaglandins, and nitric oxide
- initially involves arterioles
- then opening of new capillaries & venule beds
10
Q
Slowing of blood flow
A
- started by increas. permeability of microvasculature
- slowing disrupts laminar flow of blood -> cellular elements to move to periphery of vessels
- pavementing occurs
- leuk. exit BV and enter extravasc. space via emigration
11
Q
3 types of vascular permeability changes
A
- immediate transient perm. resp.
- immediate prolonged perm. resp.
- delayed prolonged perm. resp.
12
Q
Exudation
A
- increas. Vascular perm. W/ escape of plasma fluid and leukocytes
- major & constant feature of acute inflammation rxns
13
Q
Immediate transient permeability response
A
- assc. w/ mild injury
- immediate
- elicited by histamine
- increas. Perm. In venules
- peak @ 5-10 mins
- goes away within 30 mins
14
Q
Immediate prolonged permeability response
A
- assc. w/ severe inj.
- immediate
- lasts several days
- peak @ few hrs
- increas. perm. & vasc. Leakage in venules, arterioles, & capillaries
15
Q
Delayed prolonged permeability response
A
- delayed
- lasts several hrs-days
- mild to mod. Thermal injury, x ray & uv irrad., bact. Toxins, delayed hypersen. Rxns
- increas. Permeability and leakage (MOA unkn.)
-venules & capillaries affected
16
Q
Leukocytic exudation definition
A
Massing of leuk. (Esp. Neutr. & monocytes) @ inflammation sites
17
Q
4 leukocyte exudation steps
A
- margination and pavementing
- emigration
- chemotaxis
- phagocytosis
18
Q
Neutrophils are assc. w/ what type of inflamm?
A
Acute
19
Q
Lymph. & macroph. assc. w/ what type of inflamm?
A
Chronic
20
Q
Margination/pavementation
A
- leuk. -> periphery of bloodstream
- cellular elements fall out central column & roll along vasc. endoth.
- leuk. Adhere to endothelial wall
21
Q
Emigration of leuk. Definition
A
Leuk. Escape bv & enter perivasc. Tissue
22
Q
Diapedesis definition
A
- movement of leuk. between endothelial cells
23
Q
Emigration of leuk.
A
- after stuck to endoth. wall, they insert pseudopods between junctions & escape via gap (diapedesis)
- cross BM & enter perivasc. Tissue
- erythrocytes may leave bv
- neutr. 1st predominant, after 6-24 hrs, monocytes predom.
24
Q
Chemotaxis definition
A
Unidirect. migration of leuk. towards attractant
25
Chemotaxis
- influences may be exogenous or endogenous
- granulocytes, monocytes, & some lymph. Respond to chemoattract.
- primarily respond to bact. products & C5a, LTB4, and IL-8
26
Pathophys. of chemotaxis
- chemotactic agents bind to reansmembrane recept.
- signal from binding -> activation of effector molecules in leuk., i.e.: Phospholipase C and Phosphoinositol-kinase
- enzymes act on membrane lipids -> generate 2nd messengers
- 2nd mess. Increase cytosolic calicum & activate enzymes that cause actin polymeriz.
- actin regulatory proteins interact w/ leuk. cytoplasmic actin & myosin -> cell contract. And movement
27
3 steps of phagocytosis
- recognition
- engulfment
- killing/degrad.
28
2 important opsonins in Recognition phase of phagocyt.
IgG & C3b
29
Engulfment phase of phagocyt.
- pseudopods wrap around particle -> phagosome
- phagosome membrane fuses w/ lysosomal granules of leuk. -> expulsion of granule content into phagolysosome
30
4 intracellular events phagocytosis stimulates
- increased O2 consumpt.
- glycogenolysis
- incre. Glucose oxidation via oxygen monophosphate shunt
- H2O2 prod.
31
2 categories of bactericidal mech. Caused by killing/degrad. Phase
- O2 dependent mech.
- O2 independent mech.
32
O2 dependent bactericidal mech.
- triggered by activation of cytosolic and plasma membr. linked oxidases that -> O2 into H2O2
- toxic byprod. Of rxn -> kill ingest. Bact.
33
H2O2-myeloperoxidase-halide system
- kills bact, fungi, viruses, & mycoplasma
- reduced NADPH oxidase during phagocyt. -> liberation of H2OS from phagolysosome
- H2O2 in presence of myeloperoxidase & halide ion -> hypochlorite
- hypochlorite very effective in killing phagocytized org.
- superoxide anion also toxic
34
O2 independent bactericidal mech.
- H+ ions from lactate or carbonic anhydrase -> decreas. in pH in phagolysosomes
- lysozyme action attacks bact. cell wall via hydrolyzing muramic acid N-acetyl glucosamine bond in glycopeptide coat
- lactoferrin: Fe binding protein in specific granules of neutr. are toxic
- defensins: cationic arginine rich peptides toxic to microbes
35
2 types of chemical mediators of inflamm.
- plasma deriv.
- cell deriv. (Preformed or newly synth.)
36
3 types of preformed mediators
- histamine
- serotonin
- lysosomal enzymes
37
4 Newly synthesized cell mediators
- prostaglandins
- leukotrienes
- platelet activating factors
- cytokines
38
3 plasma mediators
- complement syst.
- kinin syst.
- clotting/fibrinolytic syst.
39
Histamine
- from mast cell
- increase.: arterial dilat. & venule perm.
- early inflamm. resp. (IMMEDIATE TRANSIENT RESP.)
40
6 factors that release histamine
- IgE
- Phys. Agents: trauma or heat, etc
- C3a & C5a frag.
- cationic proteins form neutroph. lysosomes
- substance P (neuroproteins)
- IL-1 & IL-8
41
Serotonin
- pre-formed
- similar to hist. in rodents
- released from mast cell granules & platelets
42
Kinins
- from kininogens
- lysis of cells -> kinin precurs.
- Bradykinin: sust. & enhances histamine effects
- pain mediator & contracts smooth m.
- kallekrein: activates hageman fact.; fibrinolytic path.; and complement syst.
43
C3a & C5a
- vasodilat. via stim. by histamine release
- aka: anaphylatoxins
44
C5a
- chemotactic for eosin., neutr., basoph., & monocytes
45
C5b-9 complex
MAC (lyses bact.)
46
C3b
- opsonin
47
Prostaglandins
- 20 carbon fatty acid
- enhance/reduce effects of biological processes
- stim. by inflamm. stimuli
- causes: vasodil., increas. Perm., fever, & pain
48
Lysosomal enzymes
- from neutr.
- microbicidal
- causes inadvertent tissue damage w/ oxyradicals
- may increase vasc. Perm. & chemotaxis via C3 and C5
49
Cytokines
- proteins that mod. funct. of other cells
- prod. by all cells, mainly lymph. & macroph.
- roles in acute & chronic inflamm.
- TNF & IL-1= Major inflamm. Cytokines (effect on endoth. Cells, leuk., and fibroblasts)
