CH 2 - Acute Inflammation Flashcards
1
Q
Thick, yellow fluid draining from a breast fissure is
A
a purulent exudate.
2
Q
Purulent exudates and effusions are associated with
A
pathologic conditions such as pyogenic bacterial infections, in which the predominant cell type is the segmented neutrophil (polymorphonuclear leukocyte).
3
Q
Mast cells are
A
granulated cells that contain receptors for IgE on their cell surface. They are additional cellular sources of vasoactive mediators, particularly in response to allergens.
4
Q
B lymphocytes and plasma cells are
A
mediators of chronic inflammation and provide antigen-specific immunity to infectious diseases.
5
Q
Complement proteins
A
act upon one another in a cascade, generating biologically active fragments (e.g., C5a, C3b) or complexes (e.g., C567).
6
Q
Products of complement activation cause
A
local edema by increasing the permeability of blood vessels. They also promote chemotaxis of leukocytes and lyse cells (membrane attack complex) and act as opsonins by coating bacteria.
7
Q
Kinins
A
are formed following tissue trauma and mediate pain transmission.
8
Q
The most potent chemotactic factors for leukocytes at the site of injury are
A
(1) complement proteins (e.g., C5a); (2) bacterial and mitochondrial products, particularly low molecular weight N-formylated peptides; (3) products of arachidonic acid metabolism (especially LTB4); and (4) chemokines (e.g., interleukin-1 and interferon g
9
Q
Plasmin is
A
a fibrinolytic enzyme generated by activated Hageman factor (clotting factor XII).
10
Q
Histamine is
A
one of the primary mediators of increased vascular permeability.
11
Q
During acute inflammation, neutrophils (PMNs) adhere to
A
the vascular endothelium.
12
Q
What happens to PMNs after they adhere to the vascular endothelium?
A
They flatten and migrate from the vasculature, through the endothelial cell layer, and into the surrounding tissue.
13
Q
About 24 hours after the onset of infarction, PMNs are observed to do what?
A
infiltrate necrotic tissue at the periphery of the infarct.
14
Q
What is the of the PMNs in acute inflammation?
A
function is to clear debris and begin the process of wound healing.
15
Q
Lymphocytes and plasma cells are
A
mediators of chronic inflammation and provide antigen specific immunity to infectious diseases.
16
Q
Fibroblasts and macrophages regulate what?
A
scar tissue formation at the site of infarction.
17
Q
Forces that regulate the balance of vascular and tissue fluids include
A
(1) hydrostatic pressure, (2) oncotic pressure, (3) osmotic pressure, and (4) lymph flow.
18
Q
Inflammatory edema
A
1) an increase in the permeability of the endothelial cell barrier results in local edema. 2) Vasodilation of arterioles exacerbates fluid leakage 3) vasoconstriction of postcapillary venules increases the hydrostatic pressure in the capillary bed potenti
19
Q
Vasodilation of venules
A
decreases capillary hydrostatic pressure and inhibits the movement of fluid into the extravascular spaces.
20
Q
Acute inflammations’ effect on plasma oncotic pressure
A
it is not associated with changes in plasma oncotic pressure
21
Q
Hageman factor
A
(clotting factor XII) provides a key source of vasoactive mediators.
22
Q
Activation of Hageman
A
plasma protein at the site of tissue injury stimulates (1) conversion of plasminogen to plasmin, which induces fibrinolysis; (2) conversion of prekallikrein to kallikrein, which generates vasoactive peptides of low molecular weight referred to as kinins;
23
Q
Septicemia (bacteremia) denotes
A
the clinical condition in which bacteria are found in the circulation. It can be suspected clinically, but the final diagnosis is made by culturing the organisms from the blood.
24
Q
In patients with endotoxic shock
A
lipopolysaccharide released from Gram-negative bacteria stimulates monocytes/macrophages to secrete large quantities of TNF alpha.
25
LPS causes
direct cytotoxic damage to capillary endothelial cells.
26
Suppurative inflammation
describes a condition in which a purulent exudates is accompanied by significant liquefactive necrosis. It is the equivalent of pus.
27
Chronic inflammation
is nonsuppurative.
28
Fibrinoid necrosis is observed in areas of
necrotizing vasculitis.
29
Granulomatous inflammation is seen in patients with
tuberculosis.
30
Reactive gliosis is
a normal response of the brain to injury and infection but is not visible on the cut surface of the brain at autopsy.
31
A transudate denotes
edema fluid with low protein content
32
An exudate denotes
edema fluid with high protein content.
33
A purulent exudate or effusion contains
a prominent cellular component (PMNs).
34
A serous exudate or effusion is characterized
by the absence of a prominent cellular response and has a yellow, strawlike color.
35
Fibrinous exudates does not contain
leukocytes.
36
Serosanguineous exudate contains
RBCs and has a red tinge.
37
Eosinophils are particularly evident during
allergic-type reactions and parasitic infestations.
38
Infections with Trichinella are accompanied by
eosinophilia, and skeletal muscle is typically infiltrated by eosinophils.
39
Patients with muscular dystrophy show
elevated serum levels of creatine kinase, but eosinophils are not seen on muscle biopsy.
40
Bacterial infections are associated with
neutrophilia, and affected tissues are infiltrated with PMNs.
41
Viral infections are associated with
lymphocytosis, and affected tissues are infiltrated with B and T lymphocytes.
42
Polymyositis,
an autoimmune disease, does not feature eosinophils.
43
The importance of oxygen dependent mechanisms in the bacterial killing by phagocytic cells is exemplified in
chronic granulomatous disease of childhood.
44
Children with CGD
suffer from a hereditary deficiency of NADPH oxidase, resulting in a failure to produce superoxide anion and hydrogen peroxide during phagocytosis.
45
Persons with CGD are susceptible to
recurrent bacterial infections.
46
Patients deficient in myeloperoxidase cannot produce
hypochlorous acid (HOCl)
47
Patients deficient in myeloperoxidase experience
an increased susceptibility to infections with the fungal pathogen Candida.
48
Catalase
converts hydrogen peroxide to water and molecular oxygen.
49
Deficiency of C1 inhibitor
with excessive cleavage of C4 and C2 by C1s, is associated with the syndrome of hereditary angioedema.
50
Hereditary angioedema is characterized by
episodic, painless, nonpitting edema of soft tissues.
51
Hereditary angioedema is the result of
chronic complement activation, with the generation of a vasoactive peptide from C2
52
Hereditary angioedema may be life threatening because of
the occurrence of laryngeal edema.
53
Chronic granulomatous disease
is due to a hereditary deficiency of NADPH oxidase.
54
Myeloperoxidase deficiency
increases susceptibility to infections with Candida.
55
Selective IgA deficiency and Wiskott-Aldrich syndrome are
congenital immunodeficiency disorders associated with defects in lymphocyte function.
56
Eosinophils are recruited in
parasitic infestations and would be expected to predominate in the portal tracts of the liver in patients with schistosomiasis.
57
Eosinophils contain
leukotrienes and platelet-activating factor, as well as acid phosphatase and eosinophil major basic protein.
58
Plasma cells
are differentiated B lymphocytes that secrete large amounts of monospecific immunoglobulin.
59
Inflammation has historically been referred to as either acute or chronic, depending on
the persistence of the injury, clinical symptoms, and the nature of the inflammatory response.
60
The cellular components of chronic inflammation are
lymphocytes, antibody producing plasma cells and macrophages.
61
The chronic inflammatory response is often
prolonged and may be associated with aberrant repair (i.e., fibrosis).
62
Neutrophils are featured in
acute inflammation and menstruation
63
patient with viral myocarditis will show an accumulation of
lymphocytes in the affected heart muscle.
64
Naïve lymphocytes encounter
antigen-presenting cells (macrophages and dendritic cells) in the secondary lymphoid organs.
65
Naïve lymphocytets with APCs in the secondary lymphoid organs
In response to this cell-cell interaction, they become activated, circulate in the vascular system, and are recruited to peripheral tissues (e.g., heart).
66
Binding of vasoactive mediators to specific receptors on endothelial cells results in
contraction and gap formation leading to the leakage of intravascular fluid into the extravascular space.
67
Direct injury to endothelial cells also leads to
leakage of intravascular fluid.
68
A fibrinous exudate contains
large amounts of fibrin as a result of activation of the coagulation system.
69
When a fibrinous exudate occurs on a serosal surface, such as the pleura or pericardium, it is referred to as
fibrinous pleuritis or fibrinous pericarditis.
70
Release of exogenous pyrogens by bacteria, viruses, or injured cells stimulates
the production of endogenous pyrogens such as IL-1 alpha, IL-1 beta, and TNF-alpha.
71
IL-1 is
a 15-kDa protein that stimulates prostaglandin synthesis in the hypothalamic thermoregulatory centers, thereby altering the “thermostat” that controls body temperature.
72
Inhibitors of cyclooxygenase
(e.g., aspirin) block the fever response by inhibiting PGE2 synthesis in the hypothalamus. Chills, rigor (profound chills with shivering and piloerection), and sweats (to allow heat dissipation) are symptoms associated with fever.
73
Many inflammatory cells are able to
recognize, internalize, and digest foreign materials, microorganisms, and cellular debris. This process is termed phagocytosis, and the effector cells are known as phagocytes.
74
Phagocytosis of most biologic agents is enhanced by
their coating with specific plasma components (opsonins), particularly immunoglobulins or the C3b fragment of complement.
75
The primary role of neutrophils in inflammation is
host defense and débridement of damaged tissue.
76
However, when the neutrophilic response is extensive or unregulated, the chemical mediators of inflammation may
prolong tissue damage. Thus, the same neutrophil-derived lysosomal enzymes that are beneficial when active intracellularly can be harmful when released to the extracellular environment.
77
Proteolytic enzymes that are released by phagocytic cells during inflammation are regulated by
a family of protease inhibitors, including alpha 1-antitrypsin and alpha 2-macroglobulin.
78
These plasma-derived proteins alpha 1-antitrypsin and alpha 2-macroglobulin do what?
inhibit plasmin-activated fibrinolysis and activation of the complement system and help protect against nonspecific tissue injury during acute inflammation.
79
Lysozyme is
a glycosidase that degrades the peptidoglycans of Gram positive bacterial cell walls.
80
Myeloperoxidase is contained within
neutrophil granules.
81
Selectins are
sugar-binding glycoproteins that mediate the initial adhesion of leukocytes to endothelial cells at sites of inflammation.
82
E-selectins are found on
endothelial cells
83
P-selectins are found on
platelets
84
L-selectins are found on
leukocytes.
85
E-selectins are stored in
Weibel-Palade bodies of resting endothelial cells.
86
Upon activation, E-selectins are
redistributed along the luminal surface of the endothelial cells, where they mediate the initial adhesion (tethering) and rolling of leukocytes.
87
After leukocytes have come to a rest
integrins mediate transendothelial cell migration and chemotaxis.
88
Cadherins
mediate cell-cell adhesion, but they are not involved in neutrophil adhesion to vascular endothelium.
89
Entactin and laminin are
basement membrane proteins.
90
The initial response of arterioles to neurogenic and chemical stimuli is
transient vasoconstriction.
91
Shortly thereafter the initial response in arterioles
vasodilation occurs, with an increase in blood flow to the inflamed area. This process is referred to as active hyperemia.
92
Asthma is
a chronic lung disease caused by increased responsiveness of the airways to a variety of stimuli.
93
Chemical mediators released by chronic inflammatory cells in the lungs of asthma patients stimulate
bronchial mucus production and bronchoconstriction.
94
Among the mediators released by chronic inflammatory cells in the lungs of asthma patients are
leukotrienes, also known as slow-reacting substances of anaphylaxis.
95
Leukotrienes are derived from
arachidonic acid through the lipoxygenase pathway.
96
Leukotrienes stimulate
contraction of smooth muscle and enhance vascular permeability.
97
What are responsible for the development of many of the clinical symptoms associated with asthma and other allergic reactions?
Leukotrienes
98
When IgE-sensitized mast cells are stimulated by antigen what happens?
preformed mediators of inflammation are secreted into the extracellular tissues.
99
Histamine binds to specific H1 receptors in the vascular wall, inducing endothelial cell contraction, gap formation, and edema. Massive release of histamine may cause
circulatory collapse (anaphylactic shock).
100
Bradykinin and Hageman factor are
plasma-derived mediators.
101
Myeloperoxidase catalyzes
the conversion of H2O2, in the presence of a halide (e.g., chloride ion), to form hypochlorous acid.
102
hypochlorous acid
This powerful oxidant is a major bactericidal agent produced by phagocytic cells.
103
Patients deficient in myeloperoxidase
cannot produce hypochlorous acid and have an increased susceptibility to recurrent infections.
104
Catalase
catabolizes H2O2.
105
Cyclooxygenase
mediates the conversion of arachidonic acid to prostaglandins.
106
NADPH oxidase
is involved in oxygen-free radical formation during the neutrophil respiratory burst.
107
Superoxide dismutase
reduces the superoxide radical to H2O2.
108
The macrophage
is the pivotal cell in regulating chronic inflammation.
109
Macrophages are derived from
circulating monocytes,
110
Macrophages regulate
lymphocyte responses to antigens
111
Macrophages secrete
a variety of mediators that modulate the proliferation and function of fibroblasts and endothelial cells.
112
Leukopenia is defined as
an absolute decrease in the circulating WBC count.
113
Leukopenia is
occasionally encountered under conditions of chronic inflammation, especially in patients who are malnourished or who suffer from a chronic debilitating disease.
114
Leukopenia may also be caused by
typhoid fever and certain viral and rickettsial infections.
115
Leukocytosis is defined as
an absolute increase in the circulating WBC count.
116
Neutrophilia is defined as
an absolute increase in the circulating neutrophil count.
117
Pancytopenia
refers to decreased circulating levels of all formed elements in the blood.
118
Vasodilation of precapillary arterioles does what?
increases blood flow at the site of tissue injury. (active hyperemia)
119
active hyperemia is caused by
the release of specific mediators.
120
Vasodilation and hyperemia are primarily responsible for
the redness and warmth (rubor and calor) at sites of injury.
121
Platelet adherence, aggregation, and degranulation occur when
platelets come in contact with fibrillar collagen or thrombin (after activation of the coagulation system).
122
Platelet degranulation is associated with
the release of serotonin, which directly increases vascular permeability.
123
the arachidonic acid metabolite thromboxane A2
plays a key role in the second wave of platelet aggregation and mediates smooth muscle constriction.
124
Prostaglandins E2 and I2
inhibit inflammatory cell functions.
125
Leukotrienes C4 and D4
induce smooth muscle contraction.
126
PGI2
is a derivative of arachidonic acid that is formed in the cyclooxygenase enzyme pathway.
127
PGI2 promotes
vasodilation and bronchodilation and also inhibits platelet aggregation.
128
PGI2 activates
adenylyl cyclase and increases intracellular levels of cAMP.
129
The action of PGI2 is diametrically opposite to that of
thromboxane A2
130
thromboxane A2
activates guanylyl cyclase and increases intracellular levels of cGMP.
131
Plasmin
degrades fibrin.
132
Serotonin is
a vasoactive amine.
133
Thrombin is
a protease that mediates the conversion of fibrinogen to fibrin.
134
Granulomas are
collections of epithelioid cells and multinucleated giant cells that are formed by cytoplasmic fusion of macrophages.
135
The cell is termed a Langhans giant cell when
the nuclei are arranged around the periphery of the cell in a horseshoe pattern
136
The label foreign body giant cell is used when
a foreign pathogenic agent is identified within the cytoplasm of a multinucleated giant cell
137
Activation of the complement cascade by
the classical or alternative pathway
138
Activation of the complement cascade leads to
the cleavage of complement fragments and the formation of biologically active complexes.
139
The C5b fragment
aggregates with complement proteins C6, C7, C8, and C9, resulting in the polymerization of the membrane attack complex (MAC).
140
MAC lyses cells by
inserting into the lipid bilayer, forming a pore, and destroying the permeability barrier of the plasma membrane.
141
Kallikrein and kinins are formed
following tissue trauma and mediate pain transmission.
142
Cellular sources of vasoactive mediators are
(1) derived from the metabolism of arachidonic acid (prostaglandins, thromboxanes, leukotrienes, and platelet-activating factor), (2) preformed and stored in cytoplasmic granules (histamine, serotonin, and lysosomal hydrolases), or (3) generated as normal
143
Free arachidonic acid in the acute inflammatory cells (PMNs) is derived from
membrane phospholipids (primarily phosphatidylcholine) by stimulus-induced activation of phospholipase A2.
144
According to the Starling principle,
the interchange of fluid between vascular and extravascular compartments results from a balance of forces that draw fluid into the vascular space or out into tissues.
145
The starling forces include
(1) hydrostatic pressure, (2) oncotic pressure (reflects plasma protein concentration), (3) osmotic pressure, and (4) lymph flow. When the balance of these forces is altered, the net result is fluid accumulation in the interstitial spaces (i.e., edema).
146
Noninflammatory conditions leading to the formation of edema.
1) obstruction of venous outflow or decreased right ventricular function results in a back pressure in the vasculature, thereby increasing hydrostatic pressure. 2) Loss of albumin (kidney disorders, this case) or decreased synthesis of plasma proteins (li
147
Noninflammatory edema is referred to as
a transudate.
148
A transudate is
edema fluid with a low protein content.
149
An exudate is
edema fluid with a high protein and lipid concentration that frequently contains inflammatory cells.
150
An effusion represents
excess fluid in a body cavity such as the peritoneum or pleura.
151
Lymphedema is
usually associated with obstruction of lymphatic flow (e.g., surgery or infection).
152
Chemokines and other proinflammatory molecules activate
a family of cell adhesion molecules, namely the integrins.
153
Molecules in the integrin family
participate in cell-cell and cell-substrate adhesions and cell signaling
154
Integrins are involved in
leukocyte recruitment to sites of injury in acute inflammation.
155
Arachidonic acid is metabolized by
cyclooxygenases (COX-1, COX-2) and lipoxygenases (5-LOX) to generate prostanoids and leukotrienes, respectively.
156
The early inflammatory prostanoid response is
COX-1 dependent.
157
COX-2
becomes the major source of prostanoids as inflammation progresses.
158
Inhibition of COX
is one mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, indomethacin, and ibuprofen, exert their potent analgesic and anti-inflammatory effects.
159
NSAIDs block COX-2–induced formation of prostaglandins, thereby
mitigating pain and inflammation.
160
Myeloperoxidase
catalyzes the conversion of H2O2, in the presence of a halide (e.g., chloride ion) to form hypochlorous acid.
161
hypochlorous acid
This powerful oxidant is a major bactericidal agent produced by phagocytic cells.
162
Superoxide dismutase
reduces the superoxide radical to H2O2.
163
The importance of protection afforded by acute inflammatory cells is emphasized by
the frequency and severity of infections in persons with defective phagocytic cells.
164
The most common defect of phagocytic cells is
iatrogenic neutropenia secondary to cancer chemotherapy.
165
Chemotherapy would not be expected to deplete serum levels of
complement or alter the respiratory burst within activated neutrophils
166
necrotizing granuloma due to M. tuberculosis appears as
The necrotic center is surrounded by histiocytes, giant cells, and fibrous tissue.
167
Granulomatous inflammation
is elicited by fungal infections, tuberculosis, leprosy, schistosomiasis, and the presence of foreign material.
168
Granulomatous inflammation is characteristically associated with
caseous necrosis produced by M. tuberculosis.
169
The vascular endothelium has the ability to
promote or inhibit tissue perfusion and inflammatory cell influx through multiple mechanisms.
170
Endothelial cells in the vicinity of the thrombus produce
tissue-type plasminogen activators, which activate plasmin and initiate thrombolysis (fibrinolysis).
171
Nitric oxide (NO),
which was previously known as endothelium-derived relaxing factor, leads to relaxation of vascular smooth muscle cells and vasodilation of arterioles.
172
NO also inhibits
platelet aggregation and mediates the killing of bacteria and tumor cells by macrophages.
173
Histamine, leukotrienes, and thromboxane A2 stimulate
the contraction of smooth muscle cells.
174
Coal workers’ pneumoconiosis
reflects the inhalation of carbon particles.
175
The characteristic pulmonary lesions of simple coal worker’s pneumoconiosis include
nonpalpable coal-dust macules and palpable coaldust nodules, both of which are typically multiple and scattered throughout the lung as 1- to 4-mm black foci.
176
Nodules in coal worker’s pneumoconiosis consist of
dust-laden macrophages associated with a fibrotic stroma.
177
Nodules occur when
coal is admixed with fibrogenic dusts such as silica and are more properly classified as anthracosilicosis.
178
Coal-dust macules and nodules appear on a chest radiograph as
small nodular densities.
179
leukemoid reaction
Circulating levels of leukocytes and their precursors may occasionally reach very high levels (>50,000 WBC/microL). Sometimes difficult to differentiate from leukemia.
180
In contrast to bacterial infections, viral infections (including infectious mononucleosis) are characterized by
lymphocytosis, an absolute increase in the number of circulating lymphocytes.
181
Parasitic infestations and certain allergic reactions cause
eosinophilia, an increase in the number of circulating eosinophils.
182
Leukopenia is defined as
an absolute decrease in the circulating WBC count.
183
Myloid metaplasia and myeloproliferative disease are
chronic disorders of the hematopoietic system.
184
neutrophilia
by itself does not demonstrate immature cells (band forms) and usually refers to lower levels of increased neutrophils.
185
Peripheral blood lymphocytosis is defined as
an increase in the absolute peripheral blood lymphocyte count above the normal range (<4,000/microL in children and 9,000/microL in infants).
186
The principal causes of absolute peripheral blood lymphocytosis are
(1) acute viral infections (infectious mononucleosis, whooping cough, and acute infection lymphocytosis), (2) chronic bacterial infections (tuberculosis, brucellosis), and (3) lymphoproliferative diseases.
187
Primary biliary cirrhosis (PBC) is
a chronic progressive cholestatic liver disease characterized by destruction of intrahepatic bile ducts (nonsuppurative destructive cholangitis).
188
PBC occurs principally in
middle-aged women and is an autoimmune disease.
189
Most patients with PBC have
at least one other disease usually classed as autoimmune (e.g., thyroiditis, rheumatoid arthritis, scleroderma, Sjögren syndrome, or systemic lupus erythematosus).
190
More than 95% of patients with PBC have
circulating antimitochondrial antibodies.
191
In PBC, the cells surrounding and infiltrating the sites of bile duct damage are
predominantly suppressor/cytotoxic (CD8+) T lymphocytes, suggesting that they mediate the destruction of the ductal epithelium.
192
In PBC, Macrophages and B lymphocytes are
associated with periductal inflammation but do not mediate epithelial cytotoxicity.
193
Eosinophils and PBC
have no role in primary immune-related mechanisms.
194
Corticosteroids are widely used to
suppress the tissue destruction associated with many chronic inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus.
195
Corticosteroids induce
the synthesis of an inhibitor of phospholipase A2 and block the release of arachidonic acid from the plasma membranes of inflammatory cells.
196
Prolonged corticosteroid use
they are widely used to suppress inflammatory responses, the prolonged administration of these compounds can have deleterious effects, including atrophy of the adrenal glands.
197
Myeloperoxidase
catalyzes the conversion of H2O2, in the presence of a halide (e.g., chloride ion) to form hypochlorous acid.
198
hypochlorous acid
This powerful oxidant is a major bactericidal agent produced by phagocytic cells.
199
Superoxide dismutase
reduces the superoxide radical to H2O2.
200
Acute phase proteins
These proteins are synthesized primarily by the liver and are released into the circulation in response to an acute inflammatory challenge.
201
Changes in the plasma levels of acute phase proteins are mediated primarily by
cytokines (IL-1, IL-6, and TNF- alpha).
202
Increased plasma levels of some acute phase proteins are reflected in
an accelerated erythrocyte sedimentation rate,
203
erythrocyte sedimentation rate is
an index used clinically to monitor the activity of many inflammatory diseases.
