Cell Events in Acute Inflammation & Outcomes

Question 1

Vasoactive Amines

Answer 1

• Preformed molecs in granules
• Se from platelets
• His from mast cells & other cells
• physical trauma or heat
• IgE on mast cells
• complement C3a, C5a
• leukocyte derived his releasing proteins
• neuro peptides substance P
• IL-1, IL-8

Question 2

Arachidonic Acid metabolites

Answer 2

1. vasodilation- PGI2, PGE1, PGE2, PGD2
2. vasoconstriction- Thromboxane A2, leukotrienes C4,D4,E4
3. increased vascular permeability- leukotrienes C4,D4,E4
4. Chemotaxis, leukocyte adhesion- luekotriene B4

Question 3

PAF

Answer 3

• mem phospholipid derived mediator
• aggregate platelets & cause degranulation
• acetyl glycerol ether phosophrylcholine
• from neutrophils, monocytes, basophils, endoth cells, & platelets
• acts on GPCR
• vasoconstriction & bronchoconstriction
• 100-1000 more potent than his in inducing vasodilation & increase vascular perm
• enhanced leukocyte adhesion, chemotaxis, leukocyte degranulation & ox burst
• stimulates syn of eicosanoids

Question 4

ROS

Answer 4

• NADPH oxidase pathway makes it
• from neutrophils & macrophages when killing microbes, immune omplexes, cytokines & other inflamm stimuli
• ROS are produced w/in lysosomes to destroy microbes & necrotic cells
• Increase chemokine, cytokine & adhesion molec expression= amplify cascade of inflamm mediators

Question 5

ROS

Answer 5

@ higher levels

• endoth damage w/ thrombosis & increased perm
• protease activation & antiprotease inactivation, breakdown of ECM
• direct injury to cells like tumor cells, RBCs, parenchymal cells
• antiox protective mech in place= catalase, SOD, glutathione

Question 6

NO

Answer 6

• regulate NT release in CNS
• macrophage-cytotoxic metabolite against microbes & tumor cells
• endoth cells it causes smooth m. relaxation & vasodilation
• NO syn from L- arg, O2 & NADPH by NOS

Question 7

NO 3 isoforms

Answer 7

1. type I nNOS- constitutively expressed neuronal NOS
2. type II iNOS- inducible enz present in macrophages & endoth cells, induced inflamm cytokines & mediators (IL-1, TNF, IFN-g) & bac endotoxin.
3. Type III eNOS- constitutively syn NOS found w/in endothelium

Question 8

NO

Answer 8

Question 9

Cytokines

Answer 9

• Polypep products of many cell types that f as mediators
• some stim bone marrow precursors to produce more leukocytes
• interleukins b/c mediate b/t leukocytes
• Many act on leukocytes but not call ILs
• TNF, IL- & chemokines= acute inflammation
• IFN-g & IL-2 in **chronic inflammation **

Question 10

TNF

Answer 10

Found in macrophages, mast cells, T lymph

Action:

• stim expression of endoth adhesion molec
• secretion of other cytokines
• systemic effects!
• acute inflamm

Question 11

IL-1

Answer 11

Found in macrophages, endoth cells, epith cells (some)

Action:

• similar to TNF
• greater role in fever
• acute inflamm

Question 12

Chemokines

Answer 12

Found in macrophages, endoth cells, T lymph, mast cells, other cell types

• recruite leukocytes to sites of inflamm
• migration of cells to normal tissues
• acute inflamm

Question 13

IL-6

Answer 13

Found in macrophgaes, other cells

• produce systemic effects
• acute inflamm

Question 14

IL-12

Answer 14

found in dendritic cells, macrophages

Action:

• increae IFN-g production
• chronic inflamm

Question 15

IFN-g

Answer 15

Found in T lymph, NK cells

Action:

• activation of macrophges (increased killing of microbes & tumor cells)
• chronic inflamm

Question 16

IL-17

Answer 16

Found in T lymphocytes

Action:

• recruit of neutrophils & monocytes
• chronic inflamm

Question 17

Chemokines

Answer 17

• small protein- chemo attractant
• leukocyte recruitemnt in inflamm & other cells in lymphoid & other tissues
• activate leukocytes
• produced constitutively in tissues & responsible for T & B lymphocyte segregation in diff areas of LN & spleen
• mediate via GPCR
• CXCR4 & CCR5 are coR for binding & entry of HIV into lymphocytes

Question 18

Lysosomal Enz of Leukocytes

Answer 18

• neutrophils & monocytes lysosomal granules release molecs
• acid protease pH optima limit activity only w/in phagolysosomes
• neutral protease- elastase, collagenase & cathepsin. Active in ECM & degrade matrix proteins
• Neutral Protease cleaves complement proteins directly to generate C3a & C5a & directly generate bradykinin from kininogen

Question 19

Antiprotease check damaging effects of lyssomal enz

Answer 19

• a1 antitrypsin- major I of neutrophil elastase & a2 macroglobulin
• deficiencies of these inhibitors leads to tissue destruction @ sties of luekocyte accumulation
• a1 antitrypsin def in lung can cause sever panacinar emphysema

Question 20

Neuropeptides

Answer 20

• substance P, transmit pain signals, reg vessel tone & modulate vascular perm
• n. fibers secrete neuropeptides prominent in lung & GI

Question 21

Complement Sys

Answer 21

• Found in plasma
• produced in liver

action:

• leukocyte chemotaxis, activation, opsonization
• vasodilation

Question 22

Bradykinin

Answer 22

• found in plasma
• produced in liver

action:

• increased vascular perm
• smooth m. contraction
• vasodilation
• pain

Question 23

Proteases activated during coagulation

Answer 23

• found in plasma
• produced in liver

action

• endoth activation
• leukoyte recruitment

Question 24

Complement

Answer 24

Question 25

Complement

Answer 25

* complement prot present in circulation * classic pathway when Igs are attached * Cascade generates C3b which acts like opsonin or C5a (neutrophil attractant) * C5-9 complex is known as Mem Attack Complex MAC * When MAC attaches, lysis by perforation of cell mem

Question 26

Alternate Pathway

Answer 26

* Generate C3b oR C5a via bacterial products * NOT Ig mediated * Still create MAC & lyse cell mem by perforation

Question 27

Clotting Cascade

Answer 27

Question 28

Phagocytosis & clearance

Answer 28

Question 29

Acute inflammation

Answer 29

* resolution * exudate- serous, fibrinous, purulent * suppurative inflamm * abscess * ulcer \*neutrophils at first

Question 30

Serous exudate

Answer 30

sqamous mucosa separated from dermis 2nd degree burn blister

Question 31

Serous exudate pleural effusion

Answer 31

Question 32

Fibrinous exudate

Answer 32

contains fibrin fibrinous pericarditis w/ strangs of fibrin b/t visceral & pareital pericardiaum Bread & butter pericarditis of uremia

Question 33

Fibrinous exudate

Answer 33

Question 34

fibrinous pericarditis- uremia

Answer 34

Question 35

Purulent Pericardial Effusion

Answer 35

Question 36

Purulent Ascites Abdomen

Answer 36

Question 37

Purulent exidate inflammation

Answer 37

acute bacterial meningitis

Question 38

Acute meningitis

Answer 38

Question 39

Acute bronchopneumonia

Answer 39

Question 40

Acute Bronchopneumonia

Answer 40

Question 41

Bronchopneumonia

Answer 41

productive cough- large amts of purulent sputum suppurative inflamm (w/ pus)

Question 42

G+ cocci in pneumonia gram stain

Answer 42

Question 43

Abscess

Answer 43

localized collection of pus liquefactive necrosis of abascess is apparent b/c purulent contents are draining out to leave a cavity

Question 44

Acute Pneumonia Abscess formation

Answer 44

loss of alveolar spaces & liquefactive necrosis

Question 45

acute inflammation ulcer

Answer 45

local mucosal defect of surface of organ or tissue produced by sloughing of necrotic tissue Found in an ulcer base: * fibrin * neutrophils * active granulation tissue * collagen

Question 46

Gastric ulcer

Answer 46

Question 47

Gastric ulcer micro

Answer 47

Question 48

Skin Ulcer

Answer 48

Question 49

Cardinal Signs of Inflammation

Answer 49

1. red- hyperemia (increase BF) & vasodilation (his, PG, NO) 2. PAIN- swelling from stretch sensory R & inflamm mediators 3. heat- increased BF to body periph 4. swelling- due to his, SE, C3a & 5a, bradykinin, leukotrienes, PAF, SP 5. loss of f- from mech/structural necrosis or healing