Chapter 3 - Inflammation and Repair Flashcards
0
Q
What three responses are involved in acute inflammation?
A
AI: chemical, vascular, cellular responses
1
Q
Define acute inflammation.
A
AI: transient and early response to injury
2
Q
Rubor, calor, and dolor are mediated by what?
A
Rubor, calor, tumor: histamine-mediated
3
Q
Dolor is mediated by what two compounds?
A
Dolor (pain): mediated by PGE2 and bradykinin
4
Q
What mediates vasodilation of arterioles?
A
Vasodilation of arterioles: histamine, nitric oxide
5
Q
In acute inflammation, what do mast cells release?
A
Mast cells: release preformed histamine
6
Q
How does histamine affect venule endothelial cells resulting in what?
A
Histamine: contracts venule endothelial cells; ↑venular permeability
7
Q
Describe edema fluid.
A
Edema fluid: transudate (low protein and cell levels)
8
Q
What are the primary leukocytes in acute inflammation?
A
Neutrophils: primary leukocytes in AI
9
Q
How does the circulating pool and marginating pool of neutrophils differ between Caucasians and African Americans?
A
Neutrophils: in white people, 50% circulating and 50% marginating; in black people, marginating pool > circulating pool
10
Q
What alters the distribution of neutrophils?
A
Neutrophil distribution: altered by activating/inactivating adhesion molecules
11
Q
What does margination of neutrophils mean?
A
Margination: neutrophils pushed to periphery
12
Q
What are selectins?
A
Selectins: carbohydrate-binding adhesion molecules
13
Q
Where are L-selectin ligands located?
A
L-selectin: selectin ligand on leukocytes
14
Q
Where are E-selectin molecules located?
A
E-selectin: selectin molecule on endothelial cells
15
Q
From where is P-selectin derived?
A
P-selectin: derived from Weibel-Palade bodies in endothelial cells
16
Q
What two cytokines activate selectins?
A
Selectins activated by IL-1 and TNF
17
Q
Describe the process of selectin adhesion.
A
Selectin adhesion: “rolling” (bind−detach) of neutrophils
18
Q
What do β2-Integrins do and what are they activated by?
A
β2-Integrins: firm adhesion of neutrophils; activated by C5a/LTB4
19
Q
How catecholamines and corticosteroids affect the firm adhesion of neutrophils?
A
Catecholamines and corticosteroids inactivate neutrophil β2-integrins: produces neutrophilic leukocytosis
20
Q
How do endotoxins affect β2-integrins producing what?
A
Endotoxins activate neutrophil β2-integrins: produces neutropenia
21
Q
What are ICAM/VCAM and what are they activated by?
A
ICAM/VCAM: endothelial cell integrin adhesion molecules (ligands); activated by IL-1/TNF
22
Q
Name one clinical finding of leukocyte adhesion deficiency due to selectin or CD11a/CD18 deficiency.
A
Delayed separation of umbilical cord: LAD due to selectin or CD11a/CD18 deficiency
23
Q
Describe transmigration (diapedesis).
A
Transmigration (diapedesis): movement of neutrophils from venules into interstitial space
24
What is an exudate?
Exudate: protein- and cell-rich fluid (pus)
25
Name two functions of exudate.
Exudate: dilutes bacterial toxins; provides opsonins
26
What is chemotaxis?
Chemotaxis: directed migration of neutrophils
27
Name four chemotaxis mediators.
Chemotaxis mediators: C5a, LTB4, bacterial products, IL-8
28
Name two opsonins. What do they do?
Opsonins: IgG and C3b; enhance neutrophil ability to ingest bacteria
Opsonins: IgG and C3b; enhance neutrophil recognition and attachment of bacteria
29
In Bruton agammaglobulinemia, there is a defect in what?
Bruton agammaglobulinemia: opsonization defect (lack of IgG)
30
Describe the process of neutrophil ingestion.
Neutrophil ingestion: phagosome → phagolysosome
31
What cannot form in Chédiak-Higashi syndrome?
Chédiak-Higashi syndrome: cannot form phagolysosomes
32
What is myeloperoxidase?
MPO: neutrophil/monocyte lysosomal enzyme
33
What is the most potent microbicidal system available to neutrophils and monocytes?
O2-dependent MPO system: most potent microbicidal system
34
What does the NADPH oxidase complex do?
NADPH oxidase enzyme complex: converts molecular O2 to superoxide FRs
35
What does superoxide dismutase do?
SOD converts superoxide free radicals to H2O2
36
What is the end product of the O2-dependent MPO system?
End-product O2-dependent MPO system: bleach
37
In G6PD deficiency, what is lacking? How does this affect the MPO system?
G6PD deficiency: lack of NADPH interferes with normal function of the O2-dependent MPO system
38
Give two examples of O2-independent microbial systems.
O2-independent systems: lactoferrin (neutrophils), MBP (eosinophils)
39
What is the most important chemical mediator of acute inflammation?
Histamine: most important chemical mediator of AI
40
What is the most common cause of skin abscess?
S. aureus: most common cause of a skin abscess
41
What is fibrinous inflammation?
Fibrinous inflammation: exudate covering serosal surfaces (heart, lungs, peritoneum)
42
What is serous inflammation? Give two examples of serous inflammation.
Serous inflammation: thin watery exudate; blister, viral pleuritis
43
What two microbes may cause pseudomembranous inflammation?
Pseudomembranous inflammation: diphtheria, Clostridium difficile
44
Describe the role of fever in acute inflammation.
Fever is beneficial: OBC right-shifted, ↓bacterial/viral reproduction
45
Describe the half-life of chemical mediators in acute inflammation.
Chemical mediators have a short half-life.
46
What is the role of lipotoxins in acute inflammation?
Lipoxins: inhibit transmigration/chemotaxis; enhance apoptosis
47
What is the role of resolvins in acute inflammation?
Resolvins: inhibit recruitment inflammatory cells
48
How are neutrophils cleared in acute inflammation?
Neutrophils cleared from the inflammatory site by apoptosis
49
List four consequences of acute inflammation.
Consequences: resolution, scar tissue, abscess, progression to chronic inflammation
50
What is the most common cause of chronic inflammation?
Infection: most common cause of chronic inflammation
51
What are the primary leukocytes in chronic inflammation?
Monocytes and/or macrophages: primary leukocytes in chronic inflammation
52
What does granulation tissue consists of?
Granulation tissue: blood vessels, fibroblasts
53
What is a precursor of scar tissue?
Granulation tissue: precursor of scar tissue
54
What is fibronectin and what does it do?
Fibronectin: key adhesion glycoprotein in ECM; chemotactic factor for fibroblasts and endothelial cells
55
What is granulomatous inflammation?
Granulomatous inflammation: specialized type of chronic inflammation
56
Name two types of granulomatous infections.
Granulomatous infections: TB, systemic fungi (e.g., histoplasmosis)
57
Name two examples of noninfectious granulomatous inflammation.
Noninfectious granulomatous inflammation: sarcoidosis, Crohn disease
58
What are the cell types in a tuberculous granuloma?
Cell types in tuberculous granuloma: macrophages and CD4 helper T cells
59
What are epithelioid cells?
Epithelioid cells: macrophages activated by interferon-γ from CD4 TH1 cells
60
How are multinucleated giant cells formed?
Multinucleated giant cells: formed by fusion of epithelioid cells
61
Name two factors involved in tissue repair.
Tissue repair: parenchymal cell regeneration, repair by connective tissue
62
What two cell types can regenerate?
Cell regeneration: only labile and stable cell can regenerate
63
What cell type cannot regenerate?
Cell regeneration: permanent cells cannot regenerate
64
What is G0 phase of the cell cycle?
G0 phase: resting phase of stable cells
65
What is the most variable phase of the cell cycle?
G1 phase: most variable phase in cell cycle
66
What occurs during the G1 phase of the cell cycle?
G1 phase: synthesis of DNA, RNA, protein
67
What occurs during the G2 phase of the cell cycle?
G2 phase: synthesis of tubulin for mitotic spindle
68
What occurs during the a phase of the cell cycle?
M phase: two daughter cells are produced
69
What is the most critical phase in the cell cycle?
G1 to S phase: most critical phase in cell cycle
70
Name two control proteins involved in the regulation of the G1 checkpoint.
Control proteins: Cdk4, cyclin D
71
Describe the role of RB1 in the cell cycle.
RB1 protein phosphorylation by Cdk4: causes the cell to enter S phase
72
Name two genes that control the G1 checkpoint.
Genes controlling G1 to S phase: RB1 and p53 suppressor genes
73
What does the p53 protein product do?
p53 protein product: inhibits Cdk4 (cell arrested in G1 phase)
74
In the event that there is excessive DNA damage, the p53 suppressor gene produces protein products that do what?
Severe DNA damage, p53 protein products: inhibit translation of BCL-2 antiapoptosis genes (initiates apoptosis) and inhibits translation of growth promoting genes (initiates growth arrest)
75
What is required for restoration to normal of a regenerating cell?
Restoration to normal: intact basement membrane; intact ECM
76
What is laminin?
Laminin: key adhesion glycoprotein in basement membrane
77
What is granulation tissue essential for?
Granulation tissue: essential for normal connective tissue repair
78
What is type III collagen? Describe one of its properties.
Type III collagen: initial collagen in wound repair; poor tensile strength
79
Name the cofactor in collagenase.
Zinc: cofactor in collagenase
80
What is the tensile strength of a wound after remodeling?
Tensile strength of the wound ~80% of the original after remodeling
81
Describe three features of scar tissue.
Scar tissue: acellular; lacks inflammatory cells/adnexal structures; surfaced by intact epidermis
82
Describe healing by primary intention.
1° intention: clean wound approximated by suturing
83
Describe healing by secondary intention.
2° intention: contaminated wound left open for reepithelialization
84
Describe healing by tertiary intention.
3° intention: contaminated wound débrided and treated with antibiotics before surgically closing the wound
85
What is the most common cause of impaired wound healing?
Infections: MCC of impaired wound healing
86
What is the most common pathogen causing wound infection?
S. aureus: MC pathogen causing wound infection
87
MRSA is resistant to what type of antibiotics?
MRSA: resistant to β-lactam antibiotics
88
What are the greatest risk factors for wound infection?
Greatest risk factors for wound infection: disruption of skin and malnutrition
89
What percentage of people carry MRSA in the anterior nares?
MRSA carriers: 20%–40% people carry MRSA in anterior nares
90
The majority of CA-MRSA produce what? There may be possible progression to what?
MRSA: majority CA-MRSA produce Panton-Valentine leukocidin (accelerates apoptosis neutrophils); possible progression to necrotizing fasciitis
91
Diabetes mellitus increases the susceptibility to infection by what?
Diabetes mellitus: ↓blood flow, ↑tissue glucose levels
92
List three nutritional deficiencies that impair wound healing.
Nutritional deficiencies: malnutrition, insufficient vitamin C and copper/zinc
93
How do glucocorticoids impair wound healing?
Glucocorticoids: prevent scar formation
94
What are keloids?
Keloids: raised scars extending beyond borders of original wound
95
What is a hypertrophic scar?
Hypertrophic scar: raised scar remaining in confines of original wound
96
How are collagen bundles arrayed in a normal scar?
Normal scar: haphazard collagen bundles
97
How are collagen bundles arrayed in a keloid or hypertrophic scar?
Keloid/hypertrophic scar: collagen bundles in same plane as epidermis
98
If there is severe injury to the liver, what occurs and what is there danger of occurring?
Severe injury liver: regenerative nodules and fibrosis; danger of cirrhosis
99
What is the repair cell in lung injury?
Lung injury: type II pneumocyte is repair cell
100
What occurs in response to a brain injury?
Brain injury: proliferation of astrocytes (gliosis) and microglial cells
101
What is Wallerian degeneration?
Wallerian degeneration: distal degeneration of the axon
102
What is the key to reinnervation in peripheral nerve transection?
Peripheral nerve transection: Schwann cell is key in reinnervation
103
What type of tissue is cardiac muscle? If damaged, how is it repaired?
Cardiac muscle damage: permanent tissue; repair by fibrosis
104
Postexercise, how is skeletal muscle repaired?
Skeletal muscle postexercise: myofiber repair by satellite cells (muscle stem cells)
105
What is neutrophil if leukocytosis?
Neutrophilic leukocytosis: cytokine release of postmitotic neutrophils from the bone marrow
106
What is a left-shifted smear?
Left-shifted smear: ↑band neutrophils (>10%) in peripheral blood
107
What is toxic granulation?
Toxic granulation: dark blue to purple primary granules in neutrophils
108
Toxic granulation is a sign of what?
Toxic granulation: sign of severe inflammatory condition (infectious and noninfectious)
109
What are Döhle bodies?
Döhle bodies: gray-blue inclusions in neutrophils; accompanies toxic granulation
110
What is the predominant immunoglobulin in acute inflammation?
IgM: predominant immunoglobulin in AI
111
List two findings in chronic inflammation.
CI: absolute monocytosis and increased serum IgG
112
What is the effect of corticosteroids in the blood?
Corticosteroid effect in blood: ↑neutrophils; ↓B/T lymphocytes, monocytes, eosinophils by apoptosis
113
Define ESR.
ESR: rate of settling of RBCs in vertical tube in mm/hour
114
What is rouleaux formation? What causes it and how does it affect the ESR?
RBC rouleau (stack of coins appearance): ↑ESR; ↑fibrinogen/immunoglobulins
115
What is CRP a marker of?
CRP: marker of necrosis and disease activity
116
Describe the SPE in AI.
SPE in AI: ↓albumin; no alteration in γ-globulin peak
117
Polyclonal gammopathy is a sign of what?
Polyclonal gammopathy: sign of CI
