Ch2: Acute and Chronic Inflammation Flashcards Preview

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Flashcards in Ch2: Acute and Chronic Inflammation Deck (214):
1

Inflammation is fundamentally what type of response?

Protective

2

Two main components of inflammation?

1. Blood vessels
2. Leukocytes

3

What triggers inflammation?

Soluble factors produced by cells or derived from plasma proteins

4

Is inflammation acute or chronic?

Both

5

Acute inflammation is due to what cells?

PMN's

6

Chronic inflammation is due to what cells?

Lymphocytes

7

Subacute inflammation is due to what cells?

Eosinophils

8

When is inflammation terminated?

When offending agent is eliminated

9

What are some harmful effects of inflammatory response? 2

1. Anaphylactic response
2. Chronic disabling diseases

10

Anaphylactic shock can be induced by what?

1. allergies
2. bug bites
3. certain drugs

11

What is the main component of bee venom?

Melittin

12

What does melittin stimulate?

Phospholipase A2

13

Five features of inflammation in latin and english

1. Calor = heat
2. Rubor = redness
3. Tumor = swelling
4. Dolor = pain
5. functio laesa = loss of function

14

3 main components of acute inflammation?

1. Increased blood flow through change in vessel size (heat, redness)
2. Leaky vessels (swelling)
3. Recruitment of leukocytes to injury and their activation (pain, loss of function)

15

What are 4 acute inflammation stimuli?

1. Infections/toxins
2. tissue necrosis
3. Foreign bodies
4. Immune reactions

16

What receptors recognize certain bacteria, viruses, and fungi?

Toll-like receptors

17

Tissue necrosis can be caused by what? 4

1. ischemia
2. trauma
3. physical and chemical injury
4. Hypoxia

18

What is exudation?

Escape of fluids proteins and blood cells from vascular system into the interstitial tissue or body cavities

19

What is exudate?

High protein content (specific gravity greater than 1.020)

20

What is transudate?

Low protien condate (Specific gravity less than 1.012)

21

What is edema?

Excess fluid in interstitial tissue or body cavities

22

What is purulent exudate?

Exudate rich in neutrophils

23

Is edema transudate or exudate?

Transudate

24

What are the changes in pressure in transudate?

1. increased hydrostatic pressure
2. Decreased colloid osmotic pressure

25

Main cause of transudate?

1. increased hydrostatic pressure
2. Decreased colloid osmotic pressure

26

Main cause of exudate?

Inflammation

27

Compare transudate and exudate in terms of appearance?

Transudate: clear
Exudate: cloudy

28

Compare transudate and exudate in terms of fluid protein?

Transudate: less than 0.5
Exudate: greater than 0.5

29

Compare transudate and exudate in terms of fluid LDH?

Transudate: Less than 0.6
Exudate: Greater than 0.6

30

What is the earliest manifestation of acute inflammation?

Vasodilation

31

Vasodilation first involves what vessels?

Arterioles through opening of new capillary beds

32

Vasodilation causes what two things? (2)

1. heat
2. redness

33

Vasodilation is induced by what?
Two examples?

Mediators of vascular smooth muscle

Histamine and NO

34

Vasodilation is followed by what in acute inflammation?

Increased permeability of microvasculature

35

Changes in vascular flow and caliber lead to what? (3)
All these combine for what state of flow?

1. slower blood flow
2. concentration of red blood cells in small vessels
3. Increased viscosity

Stasis

36

Vascular leakage is normally due to what?
What is this called normally?
If it takes too long?

Contraction of endothelial cells resulting in increased interendothelial spaces

Immediate transient response (15-30 minutes)

Delayed prolonged leakage (2-12 hours)

37

Delayed prolonged leakage is seen when ? (3)

1. burns
2. UV
3. bacterial toxins

38

Two other causes of vascular leakage?

1. endothelial injury: loss of endothelial cells
2. Transcytosis

39

What is transcytosis?

Increased transport of fluids and proteins through endothelial cells

40

During inflammation, what changes in lymph flow?

It is increased due to edema

41

What is lymphangitis?

Inflammation of lymphatic vessels

42

What is reactive or inflammatory lymphadenitis?

Lymph node enlargement because of hyperplasia of the lymphoid follicles and increased numbers of lymphocytes and macrophages

43

Streaking near a skin wound follows what?
What is it diagnostic of?

Course of lymphatic channels

Diagnostic of lymphangitis

44

What is lymphadenitis?

Painful enlargement of draining lymph nodes

45

What are the four steps of recruitment of leukocytes to sites of injury and infection?

1. Margination
2. Rolling
3. adhesion
4. Diapedesis

46

In stasis, what do WBC's do?
What is this process called?

WBC's become more peripheral along endothelial surface
Margination

47

Rolling interactions are mediated by what proteins?

Selectins

48

What is rolling regulated by?

Cytokines

49

Selectins in leukocytes are called?

L-selectins

50

Selectins in endothelium are called what?

E-selectin

51

Selectins in platelets are called what?

P-selectin

52

Firm adhesion of leukocytes is mediated by what?

Integrins

53

What two cytokines induce endothelial expression of ligands for integrins?

TNF and IL-1

54

V-CAM is ligand for what?

VLA-4 integrin

55

ICAM1 is ligand for what?

LFA-1 and Mac-1

56

Leukocytes normally express integrins in what state?
What reverses this?

Low affinity
Chemokines

57

What conains P-selectin and vWF in endothelial cells and platelets?

Weibel Palade Bodies

58

What causes a cell to express P-selectin? 2

Histamine and thrombin

59

3 rolling endothelial molecules and their corresponding leukocyte molecule?

1. P-selectin: Sialyl Lewis
2. E-selectin: Sialyl Lewis
3. Glycam-1/CD34: L-selectin

60

2 adhesion endothelial molecules and corresponding leukocyte molecule?

1. ICAM-1: LFA-1, MAC-1
2. VCAM-1: VLA-4

61

LAD-1 is a defect in what?
What is the functional result of this?

Defect in Beta2 chain of LFA-1 and Mac-1 integrins.

Neutrophils can't adhere

62

Clinical manifestation of LAD-1? (3)

1. Skin infections
2. Inflammatory lesions without neutrophils
3. Delayed separation of umbilical cord at birth

63

Treatment of LAD-1?

Granulocyte concentration with functional WBC's.

64

LAD-2 is a defect in what?
What is functional result of this?

Absence of sialyl-lewis for E- and P- selectins
Rolling issue

65

Manifestations of LAD-2? 2

Skin infections
Mental retardation

66

Leukocyte migration across endothelial cells is called what?

Diapedesis or Transmigration

67

Where does diapedesis occur?

Post-capillary venules

68

What mediates diapedesis?

PECAM

69

What do leukocytes make to cross BM?

Collagenases

70

What is the most common exogenous agent for chemotaxis?

Bacterial products

71

endogenous chemoattracts include? 3

1. Cytokines (IL-8)
2. Components of complement (C5a and C3a)
3. Arachidonic acid metabolites (leukotrieneB4)

72

First cell on scene are what?
Why? (2)

neutrophils

1. more present in blood
2. Respond very rapidly to chemokines

73

When do neutrophils dominate the inflammatory infiltrate?

6 to 24 hours

74

Monocytes predominate during when?
Why? 2

24-48 hours

1. last longer
2. proliferate in tissues

75

Exceptions to when cells show up first (so not neutrophils first) 1

1. Viral infections (lymphocytes first)
2. Hypersensitivity (eosinophils)

76

Responses of leukocytes consist of what two sets of events?

1. Recognition of offending agents
2. Activation of leukocytes to ingest and destroy offending agents and amplify the inflammatory reaction

77

Leukocytes have what receptors (4)

1. Toll-like receptors
2. G-coupled receptors
3. Receptors for opsonins
4. Receptors for cytokines

78

G-protein coupled receptors recognize what?

Bacterial peptide containing N-FM residues

79

Leukocyte receptors for cytokines include what main one?

IFN-gamma (macrophage activating cytokine)

80

Three steps of phagocytosis?

1. Recognition and attachment of particle
2. Engulfment that forms a vacuole
3. Killing or degradation of material

81

Receptors for phagocytosis include? (3)

1. mannose receptors
2. scavenger receptors
3. receptors for various opsonins

82

What are the three steps of engulfment?

1. Extensions of cytoplasm (pseudopods) around material
2. Plasma membrane pinches off to form phagosome
3. phagosome fuses with lysosome to make phagolysosome

83

Microbial killing is accomplished by what? (2)

1. ROS
2. reactive nitrogen species

84

Substances in leukocyte granules for phagocytosis include? 7

1. elastase
2. defensins
3. cathelicidins
4. lysozyme
5. lactoferrin
6. major basic protein
7. bactericidal/permeability increasing protein

85

What is the most efficient bactericidal system in neutrophils?

H2O2-MPO halide system

86

What happens in H2O2-MPO-halide system? 3

1. H2O2 generated by NADPH
2. Myeloperoxidase in granules of PMN's converts H2O2 to hypochlorite (bleach)
3. killing by halogenation or lipid peroxidation

87

The growth factors that activated leukocytes produce do what? (3)

1. Stimulate proliferation of endothelial cells
2. promote synthesis of collagen
3. Promote enzymes that remodel CT

88

Classically activated macrophage (M1) does what?

Microbicidal

89

Alternatively activated macrophage is involved in what?

tissue repair and fibrosis

90

Do activated leukocytes secrete mediators or inhibitors of inflammatory response?

Both

91

What are 3 situations in which leukocytes mediate tissue injury?

1. Infection
2. Autoimmune
3. React excessively against environmental substances

92

What is frustrated phagocytosis

Inability of leukocytes to surround and ingest activating substances with release of lysosomal enzymes extracellularly

93

4 defects in leukocyte function

1. leukocyte adhesion defect
2. phagolysosome defect
3. microbicidal activity defect
4. acquired deficiencies

94

The main leukocyte adhesion defect is what?
Clinical problem?
Classic example?

LAD1 and LAD2
recurrent bacterial infections
delayed umbilical cord separation

95

What is main disease of phagolysosome function?

Chediak-Higashi syndrome

96

Manifestations of Chediak-Higashi syndrome?

1. Albinism (melanocyte problem)
2. nerve defects
3. bleeding
4. Defective PMN's
5. Leukocytes with giant granules
6. Delayed killing

97

What is the genetic problem in chediak-higashi?

LYST gene

98

What is the main defect in microbicidal activity in leukocytes?

Chronic granulomatous disease

99

Chronic granulomatous disease is result of what mutation?

Defective genes encoding NADPH-oxidase either X-linked or autosomal recessive

100

The variants of chronic granulomatous disease also differ in terms of location, what are they?

1. X-linked: membrane
2. AR: cytosol

101

Patients with granulomatous disease have what problem?

Recurrent bacterial infection (catalase positive)

102

Test for chronic granulomatouse disease is what?

Nitroblue tetrazolium (yellow = disease)

103

Most frequent cause of leukocyte defects is what?

Bone marrow suppression due to diabetes or steroids

104

Mediators of inflammation are made when?

Long as the stimulus persists (rapid bursts)

105

What are the anti-inflammatory cytokines? (2)

1. TGF-beta
2. IL-10

106

What are the anti-inflammatory lipid mediators called? (2)

1. Resolvins
2. protectins

107

What neural impulse inhibits production of TNF in macrophages?

Cholinergic discharge

108

Mediators are generated from what?

Cells or plasma proteins

109

What is the relative length of life of a mediator of inflammation?

Short

110

What are the two major vasoactive amines?

Histamine
Serotonin

111

When are vasoactive amines released?

First to be released during inflammation

112

Histamine is released by what cells? (3)

1. mast cells
2. basophils
3. platelets

113

Histamine is released to what stimuli? 6

1. Physical injury
2. binding of antibodies to mast cell
3. anaphylatoxins (c3a c5a)
4. histamine-releasing proteins from leukocytes
5. neuropeptides
6. Cytokines (IL-1, IL8)

114

What neuropeptide modulates pain?

Substance P

115

Histamine causes what? 2

Arterior dilation
Increases permeability of venules

116

Histamine is the principal mediator of what?

Immediate phase of increased vascular pemerability

117

Where does histamine bind?

H1 receptors in interendothelial gaps of venules

118

Serotonin has what effects? 2

Arterior dilation
Increases permeability of venules

119

Serotonin is found where?
When is it released?

Platelets

Platelet aggregation

120

What cells have serotonin in GI?

Enterochromaffin

121

Membrane derived arachidonic acid produces what?
Via what enzyme?
What initiates all this?

Prostaglandins and leukotrienes

Phospholipases

inflammatory mediators

122

Steroids have what effects on phospholipases?

Inhibit them.

123

COX converts what to what?

Arachidonic acid into prostaglandins, prostacyclin, and thromboxanes.

124

12-lipoxygenase converts what to what?

5-HPETE into lipoxin

125

Prostacyclin causes what? 2

Vasodilation
Inhibits platelet aggregation

126

Thrombaxane A2 causes what? 2

Causes vasoconstriction
Promotes platelet aggregation

127

PGD2 and PGE2 causes what? 2

Vasodilation
Increased vascular permeability

128

Leukotrienes do what? 3

Vasoconstriction
Bronchospasm
Increased vascular permeability

129

Lipoxins do what? 2

Inhibit neutrophil adhesion and chemotaxis

130

5-lipoxygenase converts what to what?

Arachidonic acid into leukotriene and lipoxin

131

Platelets contain what prostaglandin enzyme?
Which makes what?

Thromboxane synthetase
TxA2

132

What prostglandin enzyme does vascular endothelium have?

Prostacyclin synthetase

133

Aspirin and NSAIDS inhibit what enzymes?

COX-1 and COX-2

134

COX-2 generates prostaglandins involved in what reactions?

Inflammatory reactions

135

COX-1 generates prostaglandins involved in what?

Cytoprotective and inflammatory reactions

136

LTB4 causes what?

Neutrophils to aggregate (chemotactic)

137

LTC4, LTD4, LTE4 cause what? (3)

Vasoconstriction
Bronchospasm
Increased vascular permeability

138

Which is more potent, leukotrienes or histamine?

Leukotrienes

139

Lipoxin LxA4 causes what?

1. vasodilation
2. antagonizes LTC4

140

Lipoxins may have what relationship with leukotrienes?

Negative regulators of leukotriene actions

141

What are the two COX inhibitors?

ASA and NSAIDS

142

What are the two lipoxygenase inhibitors?

Zileuton
Montelukast

143

Montelukast is used in treatment of what?

Asthma

144

Fish oil has what effect on eicosanoids synthesis? 2

Fish oils can be poorly converted into active metabolites by COX and LOX pathways.
Can be used to produce resolvins and protectins

145

Platelet activating factor is generated from what?

Membrane phospholipids

146

What does PAF do? 7

1. leukocyte adhesion
2. chemotaxis
3. degranulation
4. oxidative burst
5. vasoconstriction
6. bronchoconstriction
7. increased vascular permeability

147

Free radicals at low levels do what?

Increase cytokines

148

Free radicals at high levels do what? (2)

1. tissue damage
2. inactivate antiproteases

149

Antioxidant protective mechanisms are include what? 5

1. catalase
2. superoxide dismutase
3. glutathione peroxidase
4. ceruloplasmin
5. transferrin

150

Nitric oxide factor is released from what cells?
Causes what?

Endothelial cells

Relax smooth muscle causing vasodilation

151

NO in macrophages does what?

kills microbes

152

What is NO's role in inflammation? 3

1. vasodilation
2. antagonize platelet aggregation and adhesion
3. Microbicidal agent

153

Cytokines are defined how?

Peptides modulating functions of other cells

154

TNF and IL-1 are produced by what cells?

Activated macrophages

155

TNF and IL-1 have what effects? 2

1. cause endothelial activation
2. Induce acute phase responses

156

Production of IL-1 is called what?

Inflammasome

157

What happens when IL-1 is mutated?

Cause inherited autoinflammatory syndromes (familial Mediterranean fever) (upregulated IL-1 production

158

Sustained release of TNF causes what?

Cachexia

159

C-X-C chemokines use what coreceptor for HIV?

CXCR4

160

C-C chemokines use what coreceptor for HIV?

CCR5

161

What is the main C chemokine (gamma chemokine)

Lymphotactin

162

What is the main CX3C chemokine?

Fractalkine

163

Two main functions of chemokines?

1. Recruit leukocytes
2. Control normal migration of cell through tissues

164

IFN-gamma is released by what cells?

T lymphocytes and NK cells

165

IFN-gamma activates what?

Macrophages

166

What counteracts proteases?
Two examples?

Antiproteases

1. alpha2-macroglobulin
2. alpha1-antitrypsin

167

Neuropeptides are secreted by who?

Sensory nerve fibers and leukocytes

168

Neuropeptides have what role?

Initiate and propagate inflammatory response

169

Nerve fibers containing substance P do what? (3)

1. transmit pain signals
2. regulate vessel tone
3. modulate vascular permeability

170

Is complement system innate or adaptive?

Both

171

What triggers classical complement pathway?

Fixation of C1 to IgM or IgG

172

What triggers alternative pathway?

Microbial surface proteins

173

C3a and C5a are called?
Because they do what?

Anaphylatoxins
Stimulate histamine release

174

c5a acts as what agent as well?
What can it activate also?

Chemotactic for leukocytes
Activate lipoxygenase pathway

175

C3b has what role in phagocytosis?

Act as opsonin

176

MAC makes cells permeable to what?

Water and ions

177

Intrinsic clotting pathway activated by what?

Hageman factor/Factor XII

178

Thrombin promotes what?

Inflammation

179

Describe the steps of Kinin system 2

1. Factor XIIa converts prekallikrein into kallikrein
2. Kallikrein converts HMWK into bradykinin

180

What are the precursors of vasoactive peptides called?

Kininogens

181

Bradykinin has what functions? (3)

1. Increase vascular permeability
2. Smooth muscle contraction
3. Dilation of blood vessels

182

What inactivates bradykinin?

Kininase

183

Factor XIIa, induces what two pathways?

1. fibrin clot formation
2. fibrinolytic system

184

What other thing does kallikrein do besides kinin pathway? 2

Converts plasminogen to plasmin
Convert C5 to C5a

185

Activated Hageman factor (factor XIIa) initiates what four pathways?

Kinin
Clotting
Fibrinolytic
Complement

186

What does plasmin do?

1. Cleaves fibrin
2. Converts C3 to C3a

187

What are possible outcomes of inflammation? (2)

1. Resolution and healing
2. progression to chronic inflammation

188

Morphologic hallmarks of inflammation? (3)

1. Dilation of small blood vessels
2. slowing of blood flow
3. accumulation of leukocytes and fluid in extravascular tissue

189

What is serous inflammation?
Example?

Outpouring of thin fluid (effusion)

Skin blister

190

What is fibrinous inflammation?
When is it seen?

Fibrin is formed and deposited in extracellular spaces. Exudate develops when leaks become large.
Common in lining of body cavities: meninges, pericardium, pleura

191

Suppurative/purulent inflammation/abscess is due to what?

Production of large amounts of pus or purulent exudate.

192

bacteria that cause pus formation are known as what?

Pyogenic

193

What is an ulcer?

Local defect on surface of organ or tissue produced by sloughing or inflamed necrotic tissue

194

What is chronic inflammation?

Inflammation lasting weeks to months

195

Chronic inflammation results from what? (3)

1. persistent microbial infections
2. prolonged exposure to toxic agents
3. autoimmune diseases

196

Silica in lungs leads to what?

Silicosis

197

Plasma lipid toxicity is known as what?

Atherosclerosis

198

Characteristic cells of chronic inflammation?

Macrophages
Lymphocytes
Plasma cells

199

What shows up morphologically in chronic inflammation?

Tissue destruction
Attempts to heal by CT replacement of damaged tissue utilizing angiogenesis and fibrosis

200

What is the dominant player in chronic inflammation?

Macrophages

201

Macrophages in spleen and lymph nodes are known as what?

Sinus histiocytes

202

macrophages in placenta?

Hofbauer cell

203

Half life of blood monocyte?

1 day

204

life span of tissue macrophage?

several months or years

205

Macrophages secrete products to do what?

1. eliminate agents (ROS, NO, enzymes)
2. initiate repair (growth factors)

206

Plasma cells are involved in opsonization how?

Make IgG

207

granules of eosinophils contain what?

Major basic protein

208

Mast cells are found in what tissues mainly?

CT

209

Mast cells upon IgE activation do what?

Release histamines and prostaglandins

210

What is chronic bacterial infection of bone?

Osteomyelitis

211

What are two types of granulomas?

Foreign body
Immune granulomas

212

What initiates a foreign body granuloma?

Inert foreign bodies like sutures

213

What initiates immune granulomas?
Typical one

Something doesn't degrade well.
Myobacterium tuberculosis

214

What does defective inflammation result in?
Why?

Susceptibility to infections
And bad wound healing

Bad inflammation = bad innate immunity