Ch. 2&3 Inflammation and Repair Flashcards
1
Q
What is inflammation?
A
The reaction of BVs, leading to accumulation of fluid and leukocytes in extravascular tissues
2
Q
What are the components of inflammation (WBCs) in order of %?
A
Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils (Never Let Monkeys Eat Bananas)
3
Q
What is the function of a neutrophil?
A
First responder, used in ACUTE inflammation. Bacterial or fungal infections. Increased activity and death => PUS
4
Q
When are lymphocytes more common?
A
Chronic inflammation
5
Q
What are lymphocytes?
A
T cells and B cells
6
Q
What are monocytes and what is their function?
A
Long-lived phagocytes, present pathogen parts to T cells
7
Q
What do monocytes become in tissues?
A
Macrophages
8
Q
When are eosinophils used?
A
Parasite and allergic responses
9
Q
When are basophils used?
A
Allergic and antigen responses - release HISTAMINE
10
Q
What do basophils become in tissues?
A
Mast cells
11
Q
What is the life span of an RBC?
A
120 days
12
Q
What is the life span of a WBC?
A
days - years
13
Q
What is the life span of a platelet?
A
8 days
14
Q
What does a lymphocyte become in tissues?
A
Plasma cell
15
Q
Onset of acute vs chronic inflammation?
A
Acute = Rapid onset Chronic = Slower onset
16
Q
Duration of acute vs chronic inf.?
A
Acute = short duration Chronic = Longer duration
17
Q
Which type of inflammation has edema?
A
Acute
18
Q
What is the predominant WBC involved in acute inf.?
A
Neutrophils
19
Q
Which type of inflammation has new blood vessels, fibrosis, and tissue necrosis?
A
Chronic inflammation
20
Q
What are the predominant WBCs involved in chronic inf.?
A
macrophages and lymphocytes
21
Q
What is fibrosis?
A
Space occupying lesion (SOL) on cellular/molecular level
22
Q
What are the signs/symptoms of acute inflammation?
A
Redness (rubor), Heat (calor), Swelling (tumor), Pain (dolor), Loss of function (functio laesa)
23
Q
What are the 3 main vascular changes in acute inflammation?
A
- Vascular dilation and increased blood flow 2. Extravasation and deposition of plasma fluid and proteins (edema) 3. Leukocyte emigration and accumulation in the site of injury
24
Q
What is the normal avg. colloid osmotic pressure in a capillary?
A
25 mmHg
25
What is the avg. colloidal osmotic pressure in a capillary during acute inflammation?
20 mmHg
26
Why does colloidal osmotic pressure drop during acute inflammation?
Protein leakage across venule
27
What is the net result of decresed colloidal osmotic pressure?
Excess of extravasated fluid
28
What causes oncotic pressure?
Concentration of proteins increases in capillaries, pushing fluid out. Increased concentration of proteins in venules "suck" proteins back in
29
What controls arteriole pressure?
Precapillary sphincters
30
What happens when precapillary sphincters relax in acute inflammation?
Hyperemia
31
What is a Rouleaux?
Stacking of RBCs
32
What is neutrophil margination?
Pushed to outside of bloodstream due to RBC rouleaux
33
What is the process of Leukocyte extravasation?
1. Margination 2. Pavementing (Rolling -> Tight binding -> Diapedesis) 3. Extravascular migration
34
What is the relation of Rouleaux to ESR?
Directly correlated - increased rouleaux = increased ESR
35
What initiates Leukocyte rolling?
P-Selectin and E-Selectin on endothelial cells
36
What causes Leukocyte binding?
Expression of endothelial adhesion molecules like ICAM-1 (by TNF and IL-1) and increased aviditiy of integrins on Leukocytes (by chemokines)
37
What causes leukocyte migration after diapedesis?
Chemokines
38
How are microbes destroyed by macrophages?
1. Recognition and attachment 2. Engulfment 3. Microbe ingested in phagosome 4. Fusion of phagosome with lysosome => phagolysosome 5. Killing of microbes by lysosomal enzymes (ROIs and NO)
39
How are microbicidal reactive Oxygen intermediates produced within phagocytic vesicles?
Cytoplasmic oxidases, membrane oxidases, and myeloperoxidase
40
What are the 2 groups of mediators of inflammation?
Plasma derived and cell derived
41
What type of inflammation mediator is histamine?
Cell derived - biogenic amine
42
What is histamine released from?
Platelets and mast cells
43
What does histamine induce in endothelial cells?
Retraction - creates gaps => increased permeability
44
Why does histamine have short action (immediate transient reaction)?
Inactivated by histaminase
45
What Vitamin stabilizes mast cells?
Vitamin C (acute bolus of ascorbic acid when having a reaction)
46
What is bradykinin?
Plasma protein derived from kininogen
47
What enzyme is used to make bradykinin?
Kallikrein
48
What is kallikrein activated by?
Hageman factor
49
What does Hageman factor act on besides kallikrein?
Clotting and fibrinolytic systems of blood
50
What does bradykinin do?
Similar actions to histamine - also induces pain.
51
What are the preformed chemical mediators in secretory granules?
Histamine, serotonin, lysosomal enzymes
52
What are the newly synthesized chemical mediators of inf.?
PGs, Leukotrienes, Platelet-activating factors, Activated oxygen species, Nitric oxide, cytokines
53
What are the chemical mediators that are activated by Hageman factor?
Bradykinin, coagulation/fibrinolysis system
54
What are the chemical mediators that are activated by complement?
C3a, C3b, C5a, C5b (MAC attack)
55
What is the complement system?
Group of plasma proteins produced by liver, circulating in inactive form
56
How is complement activated?
Classical or alternative pathways
57
What does complement activation lead to?
formation of biologically active fragments, intermediate complexes, and MAC attack complex
58
What are the 4 main functions of activated complement derivatives?
1. Opsonization 2. Anaphylaxis 3. Chemotaxis 4. Cell lysis
59
What is opsonization?
Flagging of antigens for macrophages to recognize
60
What is anaphylaxis?
Histamine release with increased vessel wall permeability
61
What is chemotaxis?
migration of leukocytes
62
How does complement cause cell lysis?
Through action of MAC - makes cell membranes "leaky"
63
3 steps of phagocytosis of bacteria?
1. Attachment of opsonized bacterium to PMN 2. Engulfment of bacterium 3. Formation of phagocytic vacuole
64
How is arachidonic acid derived?
From phospholipids through the action of phospholipases
65
Two pathways which further metabolize arachidonic acid?
Lipoxygenase pway, Cyclooxygenase pway
66
5 types of arachidonic acid derivatives?
Leukotrienes, Lipoxins, Thromboxane, Prostacyclin, Prostaglandins
67
What do leukotrienes control?
chemotaxis, vascular permeability, bronchospasms
68
What do lipoxins control?
vasodilation, inhibition of neutrophil chemotaxis, monocyte adhesion
69
What does thromboxane control?
platelet aggregation, thrombosis
70
What does prostacyclin control?
Opposes the effects of thromboxane - antagonist to clot formation
71
What does prostaglandin control?
smooth muscle contraction
72
Acute-phase inflammation effects of TNF/IL-1?
Fever, increase sleep, decrease appetite, increase acute-phase proteins, hemodynamic effects, neutrophilia
73
Long term endothelial effects of TNF/IL-1?
Increased leukocyte adherence, Increased PGI synthesis, increased procoagulant activity, decreased anticoagulant activity, increased IL-1, IL-6, IL-8, PDGF
74
Fibroblast effects of TNF/IL-1?
Increased proliferation, Increased collagen synthesis (=> FIBROSIS), Increased collagenase, Increased protease, Increased PGE synthesis
75
Leukocyte effects of TNF/IL-1?
Increased cytokine secretion (IL-1, IL-6)
76
What is the pathogenesis of fever?
IL-1/TNF change the basal body temp to a higher set point
77
What is eNOS?
endothelial Nitric Oxide Synthase
78
What is iNOS?
Inducible Nitric Oxide Synthase
79
What effect does eNOS have on endothelial cells of BVs?
Local effect - relaxes smooth muscle => vasodilation (increased blood flow => more WBCs)
80
What does long-term TNF production cause?
Cachexia
81
When is iNOS activated?
When need to initiate microbial destruction - iNOS makes Nitric Oxide in macrophages
82
What type of granule is lactoferrin?
Specific granule
83
What type of granule is lysozyme?
Specific granule
84
What type of granule is Alkaline phosphatase?
Specific granule
85
What type of granule is type IV collagenase?
Specific granule
86
What type of granule is Leukocyte adhesion molecule?
Specific granule
87
What type of granule is plasminogen activation?
Specific granule
88
What type of granule is phospolipase A2?
Specific granule OR azurophil granule
89
What type of granule is myeloperoxidase?
Azurophil granule
90
What type of granule is lysozyme - bactericidal factors?
Azurophil granule
91
What type of granule is cationic protein?
Azurophil granule
92
What type of granule is acid hydrolase?
Azurophil granule
93
What type of granule is elastase?
Azurophil granule
94
What type of granule is nonspecific collagenase?
Azurophil granule
95
What type of granule is BPI?
Azurophil granule
96
What type of granule is defensin?
Azurophil granule
97
What type of granule is cathepsin G?
Azurophil granule
98
Events in resolution of inflammation?
1. return to normal vascular permeability 2. drainage of edema and proteins into lymphatics or by pinocytosis into macrophages 3. phagocytosis of apoptotic neutrophils and necrotic debris 4. disposal of macrophages
99
What cell type has a central role in resolution of inflammation?
Macrophage
100
What do macrophages produce to initiate process of repair?
Growth factors
101
What is serous inflammation?
Early stage of most inflammations. Clear, non-viscous fluid
102
Examples of serous inflammation?
Viral infection of skin vesicles (eg Herpesvirus), joint swelling in RA, eczema, skin burn (blister)
103
What is effusion?
Fluid secreted from lining of peritoneal, pleural, or pericardial cavities - trapped in compartment
104
What is fibrinous pericarditis?
deposits of fibrin on pericardium
105
What is purulent inflammation?
Pus from dead/dying neutrophils
106
What is an abscess?
Purulent inflammation encapsulated beneath tissue
107
What is a sinus (in inflammation)?
Purulent inflammation can escape to surface
108
What is a fistula?
Connection from one place to another
109
What is a granuloma?
Lymphocytes, epithelioid cells, and multinucleated giant cells
110
What are epithelioid cells?
Macrophages that resemble epithelial cells - line up around area of inflammation and wall it off
111
What is granulomatous inflammation characteristic of?
tuberculosis (caseous necrosis)
112
At what point does a monocyte become a macrophage?
When it leaves bloodstream/enters tissues
113
When does a macrophage become activated?
In tissues
114
What cytokine secreted by T cells activates macrophages?
Interferon(IFN)-gamma
115
Non-immune activators of macrophages?
endotoxin, fibronectin, chemical mediators
116
What are microglia and where are they located?
Macrophages in the CNS
117
What are Kupffer cells and where aer they located?
Macrophages in liver
118
Where are alveolar macrophages located?
Lungs
119
What are osteoclasts and where are they located?
Macrophages in bone
120
What are sinus histocytes and where are they located?
Macrophages in spleen and lymph nodes
121
Products made by macrophages that cause tissue injury/destruction?
Toxic oxygen metabolites, proteases, neutrophil chemotactics, coagulation factors, AA metabolites, Nitric Oxide
122
Products made by macrophages that cause fibrosis?
Growth factors (PDGF, FGF, TGF-beta), Fibrogenic cytokines, angiogenesis factors, "remodeling" collagenesis
123
3 characteristic histologic features of chronic lung inflammation?
1. collection of chronic inflammatory cells 2. destruction of parenchyma 3. replacement by connective tissue (FIBROSIS)
124
3 steps of macrophage amplification?
1. recruitment 2. division 3. immobilization
125
Chronic inflammation effects?
*SLIDE 67* activated lymphocytes and macrophages influence each other, and release inflammatory mediators that affect other cells
126
Wound healing vs regeneration?
Healing = wound healing or fibrosis Regeneration = renewing tissues (epidermis, GI epithelium) or compensatory growth (liver/kidney)
127
What is the cell cycle?
G1 -> S -> G2 -> M -> cell division -> permanent cells OR quiescent cells (G0)
128
What are quiescent cells?
Stable cells, focus on normal functions instead of generation but are capable of reentering cell cycle. In G0 phase
129
Can permanent cells (neurons, cardiac myocytes) reenter the cell cycle?
NO
130
What are the differentiation factors for pluripotent bone marrow stromal cells?
Myo D, myogenin, VEGF, FGF2, Sox9, CBFA1, PPAR-gamma
131
What does myo D or myogenin cause pluripotent cell to differentiate into?
Myotube
132
What does VEGF or FGF2 cause pluripotent stromal cells to differentiate into?
endothelial cells
133
What does Sox9 cause pluripotent stromal cells to differentiate into?
Chondroblasts
134
What does CBFA1 cause pluripotent stromal cells to differentiate into?
Osteoblasts
135
What does PPAR-gamma cause pluripotent stromal cells to differentiate into?
Fat cell
136
What is autocrine signaling?
Target sites on same cell
137
What is paracrine signaling?
Target sites on adjacent cells
138
What is endocrine signaling?
Target sites on distant cells - signals enter bloodstream
139
What is the general signaling pathway used in tissue regeneration?
Ligand binds to target cells, causes cascade of enzymes ->->-> turn on transcription/translation processes for repair
140
What does binding of growth factor to tyrosine kinase receptors cause?
Receptor dimerization and autophosphorylation of tyrosine residues
141
How does liver regenerate after partial hepatectomy?
Enlargement of remaining lobe without regrowth of removed lobe
142
Cytokines that prime quiescent hepatocytes?
TNF, IL-6
143
Growth factors that act on primed hepatocytes to make them progress through cell cycle?
HGF, TGF-alpha
144
Adjuvants for liver regeneration?
Norephinephrine, insulin, thyroid hormone, growth hormone
145
Major components of basement membrane?
Type IV collagen, laminin, proteoglycans
146
Components of Interstitial Matrix?
Fibrillar collagens, elastin, proteoglycan and hyaluronan
147
What vitamin is needed for HO-ization in collagen synthesis?
Vitamin C
148
What reaction needs to happen for collagen to twist properly while being synthesized?
Hydroxylation
149
What are focal adhesion complexes?
protein aggregates that include vinculin, paxillin, and talin
150
What do focal adhesion complexes bind to?
ECM components (fibronectin and laminin)
151
Process of angiogenesis from bone marrow?
endothelial precursor cells (EPCs) mobilized from bone marrow and migrate to site of injury/tumor growth. Once there, EPCs differentiate and form mature network by linking w/ existing vessels
152
Process of angiogenesis from pre-existing vessels?
endothelial cells become motile and proliferate to form capillary sprouts.
153
What stimulates matrix metalloproteinases?
PDGF, EGF, TNF/IL-1
154
What inhibits metalloproteinases?
TGF-beta, steroids
155
How are metalloproteinases activated?
Plasmin
156
What do metalloproteinases do?
Break down collagen/debris
157
What do TIMPs do?
block metalloproteinases with specific tissue inhibitors
158
What mineral are MMPs dependent on?
Zinc
159
What are the phases of wound healing?
Inflammation, granulation tissue, wound contraction, remodeling
160
What are the three intentions of wound healing?
Primary, Secondary, Tertiary
161
When is wound healing considered primary intention?
wound edges directly next to each other (eg surgical incisions)
162
When is wound healing considered secondary?
Wider, not clean edges
163
Does scarring occur with primary intention healing?
Minimal
164
Does scarring occur with secondary intention healing?
Yes - granulation
165
What is delayed primary closure?
tertiary intention - wound is purposely left open
166
What is a keloid?
excess collagen deposition in the skin forming a raised scar
167
What causes "cauliflower ear"?
Chronic tissue damage to ears
168
What does persistent stimulus (chronic inflammation) cause?
Activation of macrophages/lymphocytes => Growth factors, cytokines, decreased metalloproteinase activity => increased collagen synthesis/decreased collagen degradation => FIBROSIS *diagram slide 98*
169
What is tissue regeneration?
Restitution of normal structure
170
What is tissue healing?
Scar formation, organization of exudate
171
What is tissue fibrosis?
Tissue scar
