Lecture 11 - acute inflammation Flashcards
1
Q
What is Rubor
A
Redness, Vessel dilation and increased blood flow
2
Q
What is Calor
A
Heat, Vessel dilation and increased blood flow
3
Q
What is tumor
A
Tumor (Swelling)
– Accumulation of exudate fluid
4
Q
What is Dolor
A
Dolor (Pain)
– Chemical mediators,
– Pressure on nerve endings
5
Q
What are the cardinal signs of inflammation
A
- Rubor
- Calor
- Tumor
- Dolor
- Functio Laesa
6
Q
Whatis functio Laesa
A
Loss of function
7
Q
What are the inflammatory mediators
A
Autacoids
Eicosanoids
Cytokines
8
Q
What are Autocoid
A
(fast, short-acting, hormone-like factors)
• Histamine
• Bradykinin
• Substance P
9
Q
What is eicosanoid
A
(arachidonic acid metabolites)
• Prostaglandins
• Leukotrienes
10
Q
What is cytokines
A
(cell-signalling molecules)
• Tumour-necrosis factor (TNF)
• IL-1
11
Q
Where is histamine released?
A
Mostly released from mast cells (also basophils)
12
Q
What stimulate histamine release?
A
Wide range of stimuli for release: heat, cold, trauma, IgE
antibodies, cytokines, bacterial components, nerve signalling…
13
Q
What are histamine
A
autocoids
14
Q
What are bradykinin
A
autocoids
15
Q
What substance P
A
autocoids
16
Q
What are prostagladins
A
eicosanoids
17
Q
What are Leukotrienes
A
eicosanoids
18
Q
What are Tumour-necrosis factor (TNF)
A
cytokines
19
Q
What are IL-1
A
cytokines
20
Q
What are the effects of autacoid
A
• Vasodilation (reddening/hyperaemia)
• Increased vascular permeability (swelling/oedema)
• Pain/itching
Other effects:
• Histamine and bradykinin causes bronchoconstriction
• Histamine causes increased mucus secretion
• Substance P activates leukocytes
21
Q
What are effects of eicosanoids
A
Metabolites of arachidonic acid from cell membrane Synthesized on demand, slower action Two major types: • Prostaglandins • Leukotrienes
22
Q
What are prostagladins
A
Eicosanoids
23
Q
What are the inflammtory prostagladins
A
Prostaglandin D2
(PGD2)
Prostaglandin E2
(PGE2)
24
Q
What produce prostagladin D2
A
mast cells
25
What are the effect of prostagladin D2
Causes vasodilation and increased vascular permeability
26
What are the effects of prostagladin E2 (PGE2)
Causes vasodilation and increased vascular permeability
| • Also causes pain and fever
27
What produces prostagladins E2 (PGE2)
Produced by epithelium, fibroblasts and smooth muscle
28
What are the coagulation mediators
– Prostacyclin (PGI2
)
– Thromboxane A2 (TxA2
)
29
What are the effects of prostacyclin (PGI2)
Vasodilation and prevention of coagulation
30
What are the effects of thromboxane A2 (TxA2)
Vasoconstriction and promotion of coagulation
31
What are prostagladins synthesized by
arachidonic acid by cyclooxygenase 2 (COX-2)
32
What does cyclooxygenase 1 regulate
many important physiological effects
| • Renal and gastrointestinal homeostasis
33
What synthesized leukotrienes
arachidonic acid by lipoxygenases (LOX)
34
What are the leukotrienes
Leukotriene B4
Leukotrienes C4
, D4 and E4
35
What produces leukotriene B4
– Produced by neutrophils
36
What are the effects of leukotriene B4
Attracts and activates neutrophils
37
What are the effects of C4, D4, E4
– Cause vasoconstriction and increased vascular permeability
| – Cause bronchoconstriction
38
What produces leukotrienes C4, D4 and E4
mast cells and eosinophils
39
What is does corticosteroids do
inhibits the production of arachidonic acid, blocks phospholipid A
40
What is the function of non-steroidal antiinflammatories
prevents the production of prostagladin H2, blocks cyclooxgenases (COX)
41
What is the function of lipooxygenase
prevent the production of leukotriene A4, blocks LOX
42
What happens during the acute-phase cytokines
Mediators of inflammation secreted by leukocytes
43
What mediators of inflammation are secreted by leukocytes
* Tumour necrosis factor (TNF)
| * Interleukin 1 (IL-1)
44
What are tumour necrosis factor (TNF) produced by
Produced by leukocytes (especially macrophages)
45
What aree interleukin 1 (IL-1) produced by
leukocytes (especially macrophages) and epithelial cells
46
Wjhat are the effects of the Mediators of inflammation secreted by leukocytes
* Increase vascular permeability
* Promote leukocyte release and activation
* Promote leukocyte extravasation
* Increase production of inflammatory mediators (autacoids, eicosanoids)
* Induce fever
* Promote coagulation
47
What are the key response from acute inflammatory
1. Vasodilation
2. Increased vascular permeability
3. Emigration of leukocytes
48
What is vasodilation mediated by
```
• Autacoids (histamine/bradykinin)
• Prostaglandins (PGD2
, PGE2
, PGI2
)
• Nitric oxide
```
49
What are the effects of vasodilation
Perfuses tissue with inflammatory mediators and leukocytes
| • Slows blood flow to allow leukocyte margination
50
What causes Increased vascular permeability during accute inflammation
Leaking due to disruption of endothelial barrie
51
What does vacular permeability do
Allows release of plasma proteins and leukocytes from blood vessels
52
What mechanism does vascular permeability have
Endothelial cell retraction
| Endothelial injury
53
What does endothelial cell retraction do
– Increased intercellular gaps mostly in venules
– Immediate response due to histamine
– Delayed (approx. 2-8 hours) due to eicosanoids, bradykinin,
complement and cytokines
54
What happens when there is endothelial injury
– Damage leads to prolonged leakage until repair
| – Can result from initial injury or damage by leukocytes
55
What are the effects of increased vascular permeability
* Transudate
* Modified transudate
* Exudate
56
What does the fluid produced depend on
degree of
| permeability
57
What is the effect of transudate
– Mild increase in permeability for fluid only
– Low protein, few cells
– Often non-inflammatory (eg. heart failure)
58
What is the effect of modified transudate
– Moderate increase in permeability
– Leakage of fluid and protein
– Higher protein, but still few cells
59
What are the effect of exudate
– Large increase in permeability
– Leakage of fluid and protein with cell migration
– High protein, many cells
– Typically inflammatory
60
What are the steps for emigration of leukocytes
1. Endothelial activation
2. Leukocyte rolling
3. Adhesion
4. Transmigration
61
What is Endothelial activation in emigration of leukocytes
* Expression of adhesion molecules (selectins, integrins)
| * Induced by TNF, IL-1, tissue damage
62
What does leukocyte rolling do
* Allows loose attachment of leukocytes via selectins
| * Gradual slowing of leukocyte
63
What does adhesion of leukocyte do
Firm attachment via integrins
64
What does transmigration do
* Migration (chemotaxis) between endothelial cells into interstitium
* Attracted by chemical signals (chemokines)
65
What in an exudate
Fluid
Plasma proteins
Leukocytes
66
What are in the fluid in an exudate
* Water containing mixture of salts to dilute toxins and pathogens
* Drains via lymphatics and lymph nodes for immune surveillance
67
What plasma proteins are in an exudate
• Inflammatory mediators and antimicrobial molecules
• Antibodies
• Clotting factors
• Fibrin
– Formed from circulating precursor protein, fibrinogen
– Polymerises via blood coagulation cascade
– Forms clot composed of filamentous, insoluble protein
– Meshwork blocks migration of bacteria and aids migration of leukocytes
68
What leukocytes are in an exudate
* Neutrophils
| * Other leukocytes
69
What the role of neutrophil in an exudate
Neutrophils
– First-line immune defence
– Phagocytose and degrade foreign material
– Produce enzymes, free radicals, cytokines and other inflammatory
mediators
70
What is the role of other leukocyte in an exudate
• Other leukocytes
| – Sometimes macrophages and lymphocytes (chronic changes)
71
What is does the classification of acute inflammation, serous mean
– Least severe; mild inflammation
– Only water and low MW solutes pass out of plasma
– Formation of transudate
72
What is does the classification of acute inflammation, catarrhal mean
– Exudate formed on mucosal surfaces
– Hypersecretion of mucus intermixed with serous fluid
plus cell debris and inflammatory cells
73
What is does the classification of acute inflammation, fibrinous mean
Fibrinous
– Leakage of fibrin from vessels
– Fibrinogen converted to fibrin
– Yellow gel which gradually becomes more solid over time
– Typically coats serosal or mucosal surfaces
– ‘Ground glass’ (mild) or ‘bread and butter’ appearance
74
What is does the classification of acute inflammation, suppurative mean
– Purulent exudate (pus)
– Contains
• Large numbers of neutrophils
• Dead cell debris
75
What is does the classification of acute inflammation, Abscess mean
– Localised collection of pus caused by suppurative inflammation
– Response to pyogenic bacteria
– Confined by wall of fibrous tissue when chronic
76
What is does the classification of acute inflammation, phlegmon
– Spreading diffuse suppurative inflammation
– Within loose connective tissue
– Margins poorly defined
– In soft tissue referred to as cellulitis
77
What is does the classification of acute inflammation, Empyema mean
Accumulation of pus within a body cavity
78
What are the other features of inflammation
Pain, itch, Fever (pyrexia; febrile response)
79
What do pain usually caused by?
– Damage/injury to peripheral nerve endings
– Effect of inflammatory mediators on nerve endings (nociceptors)
– Pressure on nerve endings from tissue swelling
80
What caused Heightened pain sensitivity in inflammation
– Hypersensitivity of nerve endings
– Amplification of pain pathways in the spinal cord
– Caused by mediators such as prostaglandin E2
, IL-1b
81
What is neurogenic inflammation
– Inflammatory mediators such as substance P released from
| nerve endings
82
What does itch usually accompanied with?
local skin inflammation
83
What does itch usually caused by
– Effect of inflammatory mediators on nerve endings
(puriceptors)
• e.g. histamine, serotonin, prostaglandins
– Substance P releases histamine from mast cells
84
Where does Unmyelinated nerve fibers for itch and pain originate from
in the skin
85
What is the purpose of Fever (pyrexia; febrile response)
– Increases motility of leukocytes, phagocytosis
– Increases proliferation of T cells
– Impairs growth of temperature-sensitive pathogens
86
What is the mechanism behind Fever (pyrexia; febrile response)
– Induced by pyrogens
• Endogenous: cytokines, such as interleukin 1 (α and β), IL-6, TNF-α
• Exogenous: e.g. bacterial toxin, lipopolysaccharide (endotoxin)
– Pyrogen causes a release of PGE2
– PGE2 acts on the hypothalamus in the brain:
• Increases physiological “thermostat”
• Results in systemic responses to increase temperature
– Shivering
– Peripheral vasoconstriction
87
What is fever pyrexia induced by?
* Endogenous: cytokines, such as interleukin 1 (α and β), IL-6, TNF-α
* Exogenous: e.g. bacterial toxin, lipopolysaccharide (endotoxin)
88
What does pyrogen cause
release of PGE2
89
What does PGE2 do?
```
acts on the hypothalamus in the brain:
• Increases physiological “thermostat”
• Results in systemic responses to increase temperature
– Shivering
– Peripheral vasoconstriction
```
90
What is the resolution of inflammation
• Reduced stimulus for leukocyte migration
• Apoptosis of neutrophils in tissue
• Lipoxins
– Alternative arachidonic acid metabolism
– “Stop signal” to suppress neutrophil activity
• Anti-inflammatory cytokines
– IL-10 from regulatory T cells
– TGF-β from anti-inflammatory macrophages
91
What is the ideal outcome of acute inflammation
Resolution (ideal outcome)
• Damaged area replaced by organised tissue with
normal structure and function
92
What are the outcome of acute inflammation
Resolution
Fibrous repair
Chronic inflammation
93
What is Fibrous repair outcome
Scar tissue, • Tissue architecture destroyed; original cell types
cannot re-grow
• Usual response to substantial tissue damage (nonspecialised)
94
What is a chronic inflammation
* Damaging agent and tissue destruction persists
* Ongoing attempts to heal by fibrous repair
* Ongoing immune responses
95
Which one is mostly responsible for asthma
leukotrienes
96
What is the difference between selectins and integrins
Selectin specialise in sticky and not sticky attachment. Where integrins specialises in firm attachment to the endothelial
97
What causes Septic shock and multiple organ dysfunction from inflammation
Coagulopathies
Haemodynamic disturbances
Tissue damage
98
What Pro-inflammatory
cytokines: IL-1, TNF
Eicosanoids: PGE2
, PGI2 do
Endothelial activation
| Leukocyte activation
99
What is inflammation
The body’s response to infection, irritation or injury
100
What is acute inflammation
* Rapid response to injury, onset in seconds to minutes
| * Non-specific response – innate immune mechanisms
101
What is the function of inflammation
– Delivery of biological mediators and leukocytes to site of inflammation
– Destruction of pathogens
– Breakdown and removal of damaged tissue and debris
