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Flashcards in Inflammation Deck (123):
1

What are Halsted's Principles?

Gentle tissue handling
Meticulous Hemostasis
Preservation of blood supply
Strict aseptic technique
Minimum tension
Accurate tissue apposition
Obliteration of dead space

2

What is the basic principle behind inflammation?

Protective immunovascular response of tissues to harmful stimuli to remove the initial cause of injury

3

What are the three most basic things involved in inflammation?

Immune cells + Blood vessels + Molecular mediators

4

What are the four physical signs of acute inflammation?

Rubor - Calor - Dolor - Tumor

5

What is the result of rubor, color, dolor, and tumor?

Loss of function

6

What are the four major acute vascular responses in inflammation?

Vasodilation
Increased vascular permeability
Stasis
Leukocyte extravasation

7

What is the behavior of the blood vessels at the beginning of an insult?

Immediate vasoconstriction followed by vasodilation

8

What are the stimulators for the initial vasocontriction with inflammation? (Four things)

Catcholamines + Serotonin + Prostaglandins + NE

9

How long does it take vasodilation to occur with acute inflammation?

Minutes

10

What happens with vasodilation in acute inflammation?

Capillary beds open = Increased blood flow = Local delivery of inflammatory mediators

11

What are two major factors that increase vascular permeability?

Histamine + Serotonin

12

What is the behavior of serum protein with acute inflammation?

Loss of serum protein
Decreased osmotic pressure
Increased blood viscosity

13

What occurs with edema in interstitial space?

Delivery of soluble factors
Localized pain + Loss of Function

14

What are the three major steps in leukocyte extravasation?

Margination + Adherence + Diapedesis/Transmigration

15

What is occurring during margination of leukocytes?

Weak cell to leukocyte interaction
Rolling along endothelium = to BF velocity

16

What is responsible for adherence of leukocytes to endothelium?

Integrins

17

What occurs during recruitment of a leukocyte?

Halts progression of leukocyte within circulation

18

What are the four major cellular components to inflammation?

Neutrophils + Mast cells + Macrophages + Lymphocytes

19

Which are the first migratory cells to arrive?

Neutrophils

20

What do neutrophils play a predominant role in?

Acute inflammation

21

What is it that neutrophils do?

Local killing + Degradation of bacterial macromolecules

22

How do neutrophils kill/degrade bacteria?

Phagocytosis + Superoxide radicals

23

Are neutrophils pro or anti inflammatory?

Pro

24

What pro-inflammatory cytokines do neutrophils produce?

IL-1 + IL-6 + TNF-a

25

How long do neutrophils last?

24 to 48 hours

26

What ends neutrophils?

Macrophages

27

What are the three big things macrophages play a role in?

Inflammatory response + Wound debridement + Tissue Repair

28

How do macrophages carry out debridement?

Phagocytosis

29

What do macrophages secrete that dissolve damaged tissue?

Collagenase + Elastase

30

Are macrophages pro or anti inflammatory?

Pro

31

What pro-inflammatory cytokines do macrophages secrete?

IL-1 + IL-6 + TNF-a

32

What cell type do macrophages stimulate to produce collagen?

Fibroblasts

33

What type of immunity are lymphocytes?

Acquired/Cell-mediated

34

What are two paths lymphocytes can take?

Cytotoxic + Helper

35

What is another name for helper T cells?

CD4

36

What is another name for cytotoxic T cells?

CD8

37

What are the two types of helper T cells?

TH-1 + TH-2

38

What is it that TH-1 cells do?

Maximize bacterial killing potential of macrophages

39

What is it that TH-2 cells do?

Helminth infections + Allergic reactions

40

What three basic things can stimulate mast cell degranulation?

Physical trauma
Completment factors
Microbial products

41

What is the major thing mast cells secrete?

Histamine

42

When is histamine released from mast cell? (physiological process)

Acute inflammation

43

Are mast cells pro or anti inflammatory?

Pro

44

What pro-inflammatory mediators do mast cells secrete?

Serotonin + Leukotrines + Heparin + Cytokines

45

What are the six categories of inflammatory mediators?

Vasoactive amines
Cytokines
Lipid/cell membrane derived
ROS
Gaseous mediators
Acute phase proteins

46

What are the two vasoactive amines?

Histamine + Serotonin

47

What are the important pro-inflammatory cytokines?

TNF-a + IL-1/6 + Chemokines

48

What are the important anti-inflammatory cytokines?

IL-10

49

What are the two major lipid membrane derived inflammatory mediators?

Eicosanoids + PAF

50

What are the two types of eicosanoids?

Prostaglandins + Leukotrienes

51

What are the two ROS?

Hydroxyl radical + Superoxide anion

52

What are the three gaseous mediators?

Nitric oxide + Carbon monoxide + Hydrogen sulfide

53

What are negative APP?

Albulmin

54

What are the positive APP?

C-reactive protein
Serum amyloid A
Complement proteins
Coagulation factors

55

What releases Histamine?

Mast cells

56

What does histamine do?

Arteriolar vasodilation
Increased venule permeability
Constriction of large arteries

57

What cells does histamine attract?

Eosinophils

58

What does histamine stimulate receptor wise?

Pruritic nociceptors

59

What are two Anti-inflammatory mediators?

IL-10 + IL-1ra

60

What is the major initiator of acute inflammation?

TNF-a

61

What are the major structural characteristics of TNF-a?

Membrane-bound surface proteins
Anti-tumor activity

62

What is TNF-a associated with in chronic diseases?

Cachexia

63

What cytokine does TNF-a stimulate production of?

IL-6

64

What is a inflammatory process that TNF-a initiates?

Cell invasion at site of inflammation

65

What, besides the cytokine, does TNF-a initiate?

ROS + Endothieal adhesion molecules

66

What can inhibit the production of TNF-a?

Steroids

67

What is IL-1 produced by?

Macrophages (and others)

68

What basic job does IL-1 have?

Mediates increases in other pro-inflammatory cytokines + prostaglandins + NO

69

What four pathologies does IL-1 cause?

Hypotension
Leukopenia
Hemorrhage
Pulmonary Edema

70

What is the counter regulatory function to IL-1?

IL-1ra

71

What does IL-1ra do?

Compete for space at the receptor site with IL-1

72

What does IL-6 in the most basic sense?

Increase all inflammatory conditions

73

What is IL-6 produced by?

Macrophages + T cells + Epithelial cells + Enterocytes

74

What is important about IL-6 clinically?

Mediator + Diagnostic/Prognostic biomarker of inflammation, levels proportional to duration/severity of condition

75

What is IL-10 in the most basic sense?

Anti-inflammatory cytokine

76

What is IL-10 produced by?

TH-2 cells + Monocytes + B cells

77

What does IL-10 depress the production of?

TNF-a + IL-1 + IL-6

78

In a normal immune response what would the levels of IL-10 be in acute phase inflammation?

Low, will increase over time

79

What category of disease is there commonly an IL-10 deficiency?

Chronic autoimmune diseases

80

What is the fatty acid precursor to all eicosanoids?

Arachidonic acid

81

Where is arachidonic acid stored?

Cells membranes of endothelial cells + Leukocytes + etc. k

82

When is arachidonic acid released?

Stimulation but Phospholipase A2

83

What are two things that arachidonic acid can be metabolized by?

Cyclooxygenase + Lipoxygenase

84

What medication can decrease PLA2 production?

Corticosteriods

85

What are the functions of prostaglandin?

Leukocyte recruitment
Vasodilation
Pain
Fever

86

What are the functions of Leukotrienes?

Activate neutrophils

87

What does activation of neutrophils entail?

Extravasation + Degranulation + Free-radical production

88

What are the two cyclooxygenase pathways?

COX-1 and COX-2

89

What medication works on the COX pathways?

NSAIDS

90

What is the major characteristic of COX-1?

Constitutively expressed

91

What is the major characteristic of COX-2?

Inducible

92

What is important medically for control the LOX pathway?

Asthma

93

What are leukotrienes secreted by?

Leukocytes + Platlets + Endothelial cells

94

What is platelet-activating factor metabolized by?

PLA2

95

What is PAF produced by?

Endothelial cells + Neutrophils + Platelets + Macrophages + Eosinophils

96

What does PAF do?

Stimulate Aracodonic Acid release
Pro-inflammatory effects on neutrophils
Platelet aggregation
Degranulation + ROS production in EOS
Vascular effects

97

What are the vascular effects of PAF?

Vascular permeability
Bronchoconstriction
Pulmonary Vasoconstriction

98

What are the PAF effects on neutrophils?

Enhanced Adhesion + Motility + Degranulation

99

What are ROS?

Unstable molecules with unpaired electrons

100

What are three important affects of ROS?

Antibacterial + Intercellular signaling + Tissue damage

101

What are two examples of free radicals?

Hydroxyl radical + Superoxide anion

102

What is an example of a non-free radical?

Hydrogen peroxide

103

What is myeloperoxidase? Where is it found?

ROS generating enzyme found in NEU
Catalyzes Hypochlorous acid from H2O2

104

What is NO synthesized from?

L-arginine by NO synthase

105

What are the three forms of NO?

Endothelial-derived + Neuronal Derived + Inducible

106

What cell types produce the inducible type of NO?

Hepatocytes + Keratinocytes + Macrophages + Neutrophils

107

What conditions will upregulate NO?

Inflammatory

108

What does NO do?

Regulation of vascular tone via smooth muscle relaxation = vasodilation

109

How is CO produced in the body?

Enzymatic break down of heme to bilirubin by heme oxygenase

110

When is heme oxygenase upregulated?

Inflammation

111

When is hydrogen sulfide produced in the body?

Cysteine metabolism

112

What is the function of hydrogen sulfide?

Regulates BP + Visceral analgesia

113

Where do acute phase proteins come from?

Liver

114

What are the cytokines that stimulate the production of ACP?

IL-6 + IL-1 + TNF-a

115

What is the most basic function of positive ACP?

Minimize tissue damage and enhance repair processes after infection/trauma/stress

116

What are the outcomes of inflammation?

Resolution
Systemic Inflammation
Multiple Organ Failure
Immunosupression
Chronic Inflammation

117

What is occurring during resolution?

Decreased NEU recruitment
Increased mononuclear cell infiltration
Macrophages undergo apoptosis
Pro to anti inflammatory factors

118

What is systemic inflammatory response syndrome?

Imbalance of inflammatory mediators = inflammation throughout the body

119

What are some of the signs of SIRS?

Changes in Temp + HR + BP + RR + WBC

120

What else needs to occur with SIRS for it to be considered sepsis?

Infection

121

When can inflammation lead to immunosuppression?

Overwhelming anti-inflammatory response

122

What cell change occurs with chronic inflammation?

Fibroblasts --> Myofibroblasts

123

What are the basic characteristics of myofibroblasts?

Increased collagen production + Fibrosis