Exam 3: Acute Inflammation Flashcards
1
Q
What is inflammation?
A
The response of living tissue of injury
2
Q
What does inflammation involve?
A
A well-organized cascade of fluidic and cellular changes
3
Q
Describe the process of inflammation
A
Process is redundant and complex
Process is continuous over a period of time
4
Q
What is the primary delivery system for inflammatory components?
A
Blood
5
Q
What is acute inflammation?
A
Standardized reaction, early response
Immediate vascular response
6
Q
What is chronic inflammation?
A
Alteration of an inflammatory response
Weeks to years
7
Q
What can both acute and chronic inflammation occur due to?
A
Microbes or non-infectious reasons
8
Q
What is the goal of acute inflammation?
A
Dilute toxins
Isolate
Eliminate
Repair
9
Q
Describe diluting toxins with acute inflammation
A
Biological and chemical
Add fluid to it
10
Q
Describe isolation with acute inflammation
A
Sequester microbes, foreign material, dead tissue
11
Q
Describe elimination with acute inflammation
A
Kill/remove inciting cause
12
Q
Describe repair with acute inflammation
A
Remove necrotic cells, recruit reparative cells and factors
13
Q
Is fibrin acute or chronic?
A
Acute
14
Q
What are harmful effects of inflammation?
A
Persistent cytokine release
Destruction of normal tissue
Swelling
Inappropriate inflammatory response
15
Q
What are systemic effects of inflammation?
A
Leukocytosis
Fever
16
Q
What is leukocytosis?
A
An abnormally high number of circulating white blood cells
17
Q
What do increased neutrophils often indicate?
A
A bacterial infection
18
Q
What are increased lymphocytes associated with?
A
Viral infections
19
Q
Describe fever
A
Coordinated by the hypothalamus and involves a wide range of factors
20
Q
What is fever commonly associated with?
A
An infectious cause
21
Q
What are the cardinal signs of inflammation?
A
Heat Redness Swelling Pain Loss of function
22
Q
What is heat?
A
Increase in temperature due to increased blood flow
23
Q
What causes redness?
A
Dilation of small blood vessels within an area (hyperemia)
24
Q
What is swelling a result of?
A
Edema
25
What is pain due to?
Stretching and distortion of tissues (due to edema and chemical mediators)
26
What is loss of function?
Movement inhibited by pain or swelling
27
What are exogenous stimuli of inflammation?
Microbes
Foreign bodies
Injury: chemical, thermal, heat, ischemia
28
What are endogenous stimuli of inflammation?
Autoreactive- newly developed antigens from degenerate or neoplastic cells
Hypersensitivity reactions
29
What do the stimuli of inflammation cause?
Activation of the innate immune response
30
Describe nonspecific defense of the innate immune response
Physical barriers: epithelial surfaces, ciliated cells, secretion
Molecular products: secreted by epithelial cells
Chemical mediators from effector cells within connective tissue of the barriers
31
What are the characteristics of acute inflammation?
Recognition of injury/pathogen
Send inflammatory cells: microvascular exudation of electrocytes, fluid, and plasma proteins (fluidic phase); leukocyte emigration (cellular phase)
Send effector molecules
Repair and heal (reparative phase)
32
How does the body recognize invaders (microbes and damaged cells)?
Cellular receptors
Cellular sensors
Circulating proteins
33
What are innate immune cells able to do?
Recognize certain components from microbes and from damaged/dead tissue
34
What are the different cellular receptors on immune cells?
Receptors on the plasma membrane
Cyctosolic receptors
Receptors on the endosome
35
What happens when TLRs recognize microbial molecules?
Induction of pro-inflammatory cytokines and type I interferons
36
What does TLR4 do?
Bind to LPS of gram-negative bacteria
37
What are pattern recognition receptors?
PAMPs
| DAMPs
38
Describe PAMPs
Pathogen-associated molecular patterns
| Microbial structures
39
Describe DAMPs
Danger-associated molecular patterns
| Released from necrotic cells
40
What are NOD-like receptors?
Cytosolic receptors that recognize a diverse set of molecules
41
What do NOD-like receptors activate?
The inflammasome
42
Describe the inflammasome
A multiprotein complex
| Induces production of IL-1
43
What does IL-1 do?
Recruit leukocytes
44
Describe C-type lecitn receptors
On the plasma membrane
| Detect fungal glycans and elicit inflammation to fungi
45
Describe Fc
Leukocytes express the receptors for Fc tails of antibodies for complement proteins
Recognize opsonized material
46
Describe circulating proteins
Complement: reacts against microbes and produces mediators of inflammation
47
What are mediators of inflammation?
Substances secreted by cells that initiate and regulate inflammatory reactions
48
What are mediators of inflammation secreted by?
Primarily macrophages, dendritic cells, and mast cells
49
What can happen to mediators of inflammation?
Sequestered in intracellular granules for rapid secretion OR may be synthesized de novo
50
What are mediators of inflammation produced in response to?
Various stimuli
51
What do mediators of inflammation bind to and what do they do?
Bind to receptors on target cells to secrete additional inflammatory mediators
52
What are the checks and balances of mediators of inflammation?
Have short half-lives and quickly decay
Are enzymatically destroyed
Are scavenged by antioxidants
53
Describe inflammatory mediators from plasma proteins
They are constantly being secreteed by the liver as precursors
Activated via proteolytic cleavage in circulatory system
54
Look at inflammatory mediators chart
Look at inflammatory mediators chart
55
What are examples of preformed inflammatory proteins?
Histamine
| Serotonin
56
What produces histamine?
Mast cells
Basophils
Platelets
57
What does histamine do?
Vasodilation
| Increased vascular permeability
58
What produces serotonin?
Mast cells
| Platelets
59
What are the functions of serotonin similar to?
Similar to histamine's functions
60
What are the synthesized mediators?
Cytokines
Chemokines
Arachidonic acid metabolites
61
What are cytokines?
Proteins produced by many cell types (primarily macrophages, lymphocytes, dendritic cells)
62
What stimulates production of cytokines?
Extrinsic and intrinsic factors
63
What is the function of cytokines?
Regulate immune and inflammatory reactions
64
What are the cytokines release with acute inflammation?
TNF, IL-1, IL-6
65
What are the actions of cytokines?
Endothelial activation
Leukocyte recruitment
Leukocyte activation
Systemic acute phase response
66
What are chemokines?
Cytokines that promote leukocyte chemotaxis and migration
67
What is an example of a chemokine?
IL-8
68
What does IL-8 do?
Chemotaxis of neutrophils
69
What are arachidonic acid metabolites?
Lipid mediators, prostaglandins and leukotrienes, produced from arachidohic acid present in membrane phospholipids
70
How are arachidonic acid metabolites released?
Mechanical, chemical, physical stimuli releases AA from the membrane
71
What are arachidonic acid derived mediators?
Prostaglandins
| Leukotrienes and lipoxins
72
What is the function of arachidonic acid metabolites?
Mediate virtually every step of acute inflammation
73
Which arachidonic acid metabolites cause vasodilation?
Prostaglandins
74
Which arachidonic acid metabolites cause vasoconstriction?
Leukotrienes, thromboxane
75
Which arachidonic acid metabolites cause increased vascular permeability?
Leukotrienes
76
Which arachidonic acid metabolites cause chemotaxis and leukocyte adhesion?
Leukotrienes
77
What is the complement system?
Collection of soluble proteins and membrane receptors that function in host defense
78
Where are complement proteins present in their inactive forms?
Plasma
79
What are the functions of the complement system?
Inflammation
Opsonization and phagocytosis
Cell lysis
80
How does the complement system cause inflammation?
C3a and C5a are cleavage products
Stimulate histamine release (anaphylatoxins)
C5a: chemotactic for leukocytes
81
How does the complement system cause opsonization and phagocytosis?
C3b: when fixed to microbial cell wall, acts as opsonin and promotes phagocytosis
82
How does the complement system cause cell lysis?
Deposition of the membrane attack complex
| Kills by making cells permeable to water---> lysis
83
What does activated factor XII do?
Activates the intrinsic coagulation and catalyzes the formation of kallikrein
84
Describe Bradykinin
Short lived
Increased vascular permeability
Vasodilation
Pain
85
What does Kallikrein do?
Acts on plasminogen to form plasmin and cleaves C3
86
What do fibrin polymers do?
Provide a surface or network to facilitate phagocytosis and prevent spread of infectious agents
87
What does excessive fibrin do?
Obstructs the microvasculature resulting in ischemic injury
88
What does excessive activation of the fibrinolytic system do?
Leads to depletion of fibrinogen and possibly hemorrhage
89
What are oxygen-derived free radicals released from?
Neutrophils and macrophages following exposure to chemokines and after phagocytosis
90
What can oxygen-derived free radicals do?
Alter signaling molecules
91
What is nitric oxide synthesized by?
Endothelial cells and macrophages
92
What does nitric oxide do?
Vasodilation
Inhibits platelet aggregation and adhesion
Oxidizes lipids
93
Describe platelet-activating factor
Phospholipid derived mediator
Many cells can elaborate the factor
Vasoconstriction and bronchoconstriction
94
Know role of mediators in different reactions of inflammation
Know role of mediators in different reactions of inflammation
95
What is the function of the fluidic phase?
Dilute and localize the stimulus
96
What is the sequence of vascular events in the fluidic phase?
Increased blood flow:
---Mediators- several but most notably histamine
---Vasodilation of arterioles leads to opening of capillary beds---> increased blood flow
Heat and redness
Increased permebaility of capillaries and postcapillary venules:
---Loss of fluid increased vessel diameter---> slower blood flow, concentration or red cells and increased blood vicosity
Swelling
97
What is the mechanism of increased vascular permeability?
Retraction by contraction of actin/myosin filaments or reorganization of the cytoskeletal microtubule and proteins
Endothelial cell necrosis and detachment
Activates platelets, clotting, and complement
98
Describe serous fluid
Clear watery fluid
| Low concentration of plasma proteins with no or low number of leukocytes
99
What does serous fluid result from?
Increased vascular permeability
100
What does serous fluid suggest about the injury?
That is rather mild or peracute
101
How does serous fluid look histologically?
Affected tissues are spread apart by the watery fluid
102
What is fibrinous inflammation?
Term used to describe a pattern of acute inflammation
103
What is fibrinous inflammation caused by?
Infectious etiologies
104
What happens in fibrinous inflammation?
Accumulation of fluid with a high concentration of plasma protein (exudate)
Leakage of large molecular weight proteins (fibrinogen)
Fibrinogen polymerizes to form fibrin
105
What is seen grossly with fibrinous exudate?
Surface of affected tissue is often red
Early- surface may be granular and dull
Surface covered with a thick, stringy, white-gray to yellow material that can be easily removed
106
What is seen microscopically with fibrinous exudate?
Eosinophilic proteinaceous material- often fibrillary
| In many cases, rapidly becomes infiltrated by neutrophils---> fibrinosupparative exudate
107
What is the consequence of fibrinous inflammation?
May resolve without any sequelae
| If extensive, fibroblasts may migrate in and being organizing exudate---> fibrous adhesions
108
What is the function of cellular phase?
Deliver leukocytes to the site in order to kill and/or digest the stimulus
109
Describe the leukocyte adhesion cascade
Movement of leukocytes from vessel into the connective tissue
Driven by chemokines, cytokines, and chemoattractant substances
110
When is the leukocyte adhesion cascade initiated?
During the fluidic phase
111
What occurs during the cellular phase?
Margination
Rolling
Adhesion to endothelium
Migration
112
What is margination?
Leukocytes move to periphery of the vascular lumen in apposition with endothelial cell
113
What is pavementing?
When the surface of the endothelium becomes line by leukocytes
114
What is rolling?
Leukocytes adhere transiently to endothelium
115
What is adhesion to endothelium?
Firm adhesion
116
What is migration?
Migration through the endothelium and then to the stimulus
117
What is rolling and adhesion mediated by?
Adhesion molecules expressed on leukocytes and endothelial cells
118
What is the expression of rolling and adhesion enhanced by?
Cytokines
119
Where does leukocyte migration through endothelium occur?
Mainly in post-capillary venules
120
What stimulates cells to migrate?
Chemokines
121
What causes cell to migrate towards a stimulus?
Chemical concentration gradient (chemotaxis)
122
What happens during chemotaxis?
Leukocytes move toward the site of injury
| Exogenous and endogenous substances act as chemoattractants
123
What are common exogenous substances?
Bacterial products and some lipids
124
What are common endogenous substances?
Cytokines (IL-8), components of complement system, arachidonic acid metabolits
125
What determines which cells are the first to arrive?
The stimulus
126
When are neutrophils the first cells to arrive?
In bacterial infection
127
When are lymphocytes and plasma cells the first to arrive?
In some hypersensitivity reactions
| Lymphocytes are also the first with viral infections
128
When are eosinophils the first cells to arrive?
In allergic reactions
129
What is purulent inflammation?
Term used to describe a pattern of acute inflammation
130
What does the response of purulent inflammation consist of?
Accumulation of fluid with high concentration of plasma protein and high number of neutrophils
131
What is pus?
An accumulation of dead neutrophils
132
What is plegmon?
Pus distributed in tissue layers or along tissue layers
| Also called cellulitis
133
What dpes purulent inflammation look like grossly?
Surface or connective tissue is hyperemic with thick white to gray to yellow material
134
When is purulent inflammation white?
If neutrophils are the predominant component
135
When is purulent inflammation yellow?
If there is a lot of necrotic debris
136
What is the consistency of purulent inflammation?
May be watery, creamy, or firm depending on the species and the inciting agent
137
What is fibrinopurulent?
When purulent inflammation is mixed with fibrin
138
What is seen microscopically with purulent inflammation?
Large numbers of neutrophils
| May degenerate neutrophils and mixed with necrotic debris, tissue debris, plasma proteins, and fibrin
139
What is the significance of purulent inflammation?
Neutrophils are there to neutralize the offending agent
140
What is the outcome of purulent inflammation?
Neutralize
Form pus---> resorption of pus
May progress to chronic inflammation
141
What is an abscess?
A circumscribed collection of pus surrounded by connective tissue capsule
142
What is a systemic acute phase response with TNF, IL-1, and IL-6?
Fever
| Increase production of leukocytes by the bone marrow
143
What is fever mediated by?
Prostaglandins that are increased int the hypothalamus
144
How does fever occur?
Cytokines increase cyclooxygenases that convert AA to prostaglandins
145
How do NSAIDs reduce fever?
By inhibiting prostaglandin synthesis
146
What does increased production of leukocytes by the bone marrow result from?
Mobilization of neutrophils from storage pools in bone marrow
147
What is the systemic acute phase response with TNF?
Energy balance
148
What is the systemic acute phase response with IL-1 and IL-6?
Stimulate acute phase protein production by the liver
149
What are the acute phase proteins?
C-reactive protein
Serum amyloid A
Fibrinogen
150
What do C-reactive protein and serum amyloid A do?
Bind to microbial cells walls
| Activate complement
151
What is septiciemia?
Clinically significant form of bacteremia complicated by toxemia, fever, malaise, and often shock
152
What results in sepsis or shock?
Systemic interaction of microorganisms and their products with hist cells and chemical mediators
153
What are the clinical manifestations of shock?
DIC
Hypotension and metabolic disturbances
Multiple organ failure and death
154
What are the gross findings with septicemia?
Fluid body cavity, pulmonary edema, petechial hemorrhages, congestion of the liver and intestine
155
What are the histology findings with septicemia?
Acute necrosis of renal tubules, centrolobular hepatocytes and cardiac myocytes
156
What are the 4 types of pneumonia?
Bronchopneumonia
Interstitial pneumonia
Granulomatous pneumonia
Embolic pneumonia
