CHAPTER 3 (Inflammation & Repair) Flashcards
1
Q
Response of vascularized tissues to infections and damaged tissues that brings cells and molecules of host defense from the circulation to the sites where they are needed, in order to eliminate the offending agents
A
Inflammation
2
Q
Mediators of Defense
A
- Phagocytic leukocytes
- Antibodies
- Complement proteins
2
Q
The major participants in the inflammatory reaction in tissues
A
blood vessels and leukocytes
2
Q
Mediators of inflammation
A
- Soluble factors
- Microbes
- Necrotic cells
- Hypoxia
3
Q
Identify: Its local and systemic signs are less
A
Chronic Inflammation
3
Q
Main Characteristics: Edema and Emigration of Leukocytes
(Polymorphonuclear Cells)
A
Acute Inflammation
4
Q
Identify: More Destruction, Lymphocytes, Macrophages, Tissue And, Adaptive Immunity
A
Chronic Inflammation
5
Q
Identify: Its local and systemic signs are prominent
A
Acute Inflammation
6
Q
First listed the 4 cardinal signs of inflammation
A
Celsus (1 century AD) - Roman writer
7
Q
Discovered the hallmarks of acute inflammation
A
Celsus (1 century AD) - Roman writer
8
Q
What are the 5 Cardinal signs of Inflammation?
A
- Heat (Calor)
- Pain (dolor)
- Redness (Rubor)
- Swelling (Tumor)
- Loss of function (function laesa)
9
Q
According to him, inflammation is not a disease but a stereotypic response that has a salutary effect on its host
A
John Hunter (1793) - Scottish surgeon
10
Q
Discovered the process of phagocytosis (ingestion of rose thorns by amebocytes of starfish larvae and of bacteria by mammalian leukocytes.)
A
Elle Metchnikoff (1800s) - Russian biologist
11
Q
The concept (Process of phagocytosis by E.M) was satirized in his play “The Doctor’s Dilemma,” in which one physician’s cure-all is to “stimulate the phagocytes!
A
George Bernard Shaw
12
Q
Discovered the 5th clinical sign of inflammation, loss of function (function laesa)
A
Rudolf Virchow (19th century) - Father of Modern Pathology
13
Q
Studied the inflammatory response in the skin; established chemical substances such as histamine mediate the vascular changes of epithelium
A
Sir Thomas Lewis
14
Q
Causes of Inflammation
A
- Infections (bacterial, viral, fungal, parasitic)
- Tissue Necrosis
- Foreign bodies (splinters, dirt, sutures)
- Immune reactions (hypersensitivity)
14
Q
Its presence implies that there is an increase in the permeability of small blood vessels triggered by some sort of tissue injury and an ongoing inflammatory reaction
A
Exudate
14
Q
Three Major Components of Acute inflammation
A
- Dilation of small vessels
- Increased permeability of the microvasculature
- Emigration of the leukocytes from the microcirculation
15
Q
Extravascular fluid that has a high protein concentration and contains cellular debris.
A
Exudate
16
Q
Fluid with low protein content (albumin), little or no cellular material, and low specific gravity.
A
Transudate
17
Q
It is essentially an ultrafiltrate of blood plasma that is produced as a result of osmotic or hydrostatic imbalance across the vessel wall without an increase in vascular permeability
A
Transudate
18
Q
Escape of fluid, proteins, and blood cells from the vascular system into the interstitial tissue or body cavities
A
Exudation
19
Q
Denotes an excess of fluid in the interstitial tissue or serous cavities; it can be either an exudate or a transudate
A
Edema
19
A purulent exudate, is an inflammatory exudate rich in leukocytes (mostly neutrophils), the debris of dead cells and, in many cases, microbes
Pus
20
Vasodilation is induced by the action of several mediators, notably _______, on vascular smooth muscle.
histamine
21
It is one of the earliest
manifestations of acute inflammation.
Vasodilation
22
First involves the arterioles and then leads to opening of new capillary beds in the area. The result is increased blood flow, which is the cause of heat and redness (erythema) at the site of inflammation.
Vasodilation
23
Vasodilation is quickly followed by?
Increased permeability of the microvasculature
24
A condition of which there is an engorgement of small vessels with slowly moving red cells
stasis (vascular congestion)
25
Process where blood leukocytes, principally neutrophils, accumulate along the vascular endothelium
Migration
26
A hallmark of acute
inflammation
increased permeability of postcapillary venules
27
Resulting in increased inter-endothelial spaces are the most common mechanisms of vascular leakage
Contraction of endothelial cells
27
Resulting in endothelial cell necrosis and detachment
Endothelial injury
27
Increased transport of fluids and proteins, through the endothelial cell.
transcytosis
27
Steps in the Recruitment of Leukocytes to Sites of Inflammation
1) Margination
2) Rolling
3) Adhesion
4) Transmigration (Diapedesis)
5) Migration in the tissues towards the chemotactic stimulus
28
Like blood vessels, _______ proliferate during
inflammatory reactions to handle the increased load.
lymphatic vessels
29
Drain the small amount of extravascular fluid that has seeped out of capillaries.
Lymphatics
30
The journey of leukocytes from the vessel lumen to the tissue is a multistep process that is
mediated and controlled by adhesion molecules and cytokines called
Chemokines
31
The most important mediators of acute inflammation
- Vasoactive amines
- Lipid products (prostaglandins & leukotrienes)
- Cytokines (inc. chemokines)
- Products of complement activation
32
Mediators are either secreted by _____ or generated from
__________.
cells; plasma proteins
33
Cell-derived mediators are normally sequestered in intracellular granules and can rapidly secreted by _______ or are ___________ in response to a stimulus.
exocytosis; synthesized de novo
34
The major cell types that produce
mediators of acute inflammation
macrophages, dendritic cells, and mast cells,
but platelets, neutrophils, endothelial cells, and most epithelia can also be induced to elaborate some of the mediators
35
Produced mainly in the liver and are present in the circulation as inactive precursors that must be activated, usually by a series of proteolytic cleavages, to acquire their biologic properties
Plasma-derived mediators
36
T/F: Most of the mediators are short-lived
TRUE
37
Sources of Histamine
Mast cells (richest source), basophils, and platelets
38
Considered to be the principal mediator of the immediate transient phase of increased vascular permeability
Histamine
39
Sources of Serotonin
Platelets and neurodocrine cells (GIT)
40
Function of serotonin
Vasoconstrictor
41
Preformed vasoactive mediator present in platelets and certain neuroendocrine cells, such as in the gastrointestinal
tract, and in mast cells in rodents but not humans.
Serotonin
(5-hydroxytryptamine)
42
Its primary function is as a neurotransmitter in the gastrointestinal tract
Serotonin
(5-hydroxytryptamine)
43
The lipid mediators’ prostaglandins and leukotrienes are produced
from?
Arachnoid Acid (AA)
44
AA-derived mediators are synthesized by two major classes of enzymes such as
- Cyclooxygenase (generate prostaglandins)
- Lipoxygenases (produce leukotrienes & lipoxins)
44
AA-derived mediators are also called?
Eicosanoids (because
they are derived from 20-carbon fatty acids;)
45
Prostaglandins are produced by?
mast cells, macrophages, and endothelial cells
46
Leukotrienes are produced by?
leukocytes and mast cells
47
Involved in the vascular
and systemic reactions of inflammation
Prostaglandins
48
Involved in vascular and smooth muscle reactions and leukocyte recruitment
Leukotrienes
49
Suppress inflammation by inhibiting the recruitment of the leukocytes
Lipoxins
49
Cytokines are produced by?
- activated lymphocytes
- macrophages
- dendritic cells
and also by:
- endothelial
-epithelial
- connective tissue cells
49
By convention, ________ that act on epithelial and mesenchymal cells are not grouped under cytokines.
Growth factors
49
Serve critical roles in leukocyte recruitment by promoting adhesion of leukocytes to endothelium and their migration through vessels.
Tumor Necrosis Factor (TNF) & Interleukin-1 (IL-1)
50
Tumor Necrosis Factor (TNF) and Interleukin-1 (IL-1) are mainly produced by?
activated macrophages & dendritic cells
51
TNF is also produced by?
T lymphocytes and mast cells
52
IL-1 is also produced by
some epithelial cells
53
A family of small (8 to 10 kD) proteins that act primarily as chemo attractants for specific types of leukocytes.
Chemokines
54
Collection of soluble proteins and membrane receptors that function mainly in host defense against microbes and in pathologic inflammatory reactions
Complement system
55
The critical step in
complement
activation is the
proteolysis of?
Complement 3 (C3)
55
Cleavage of C3 can occur by one of three pathways, namely:
- Classical Pathway
- Alternative Pathway
- Lectin Pathway
55
Triggered by microbial surface molecules (e.g., endotoxin, or LPS), complex polysaccharides, cobra venom, and other substances, in the absence of antibody
Alternative Pathway
55
Triggered by fixation of C1 to antibody (IgM or IgG) that has combined with antigen
Classical Pathway
56
All three pathways of complement activation led to the formation of an active enzyme called
C3 Convertase
56
Plasma mannose-binding lectin
binds to carbohydrates on microbes and directly activates C1
Lectin Pathway
57
These have effects similar to those of mast cell mediators that are involved in the reaction called Anaphylaxis
Anaphylatoxins
58
Also a chemotactic agent for neutrophils, monocytes, eosinophils, and basophils.
C5a
59
Activates the lipoxygenase pathway of AA metabolism in neutrophils and monocytes, causing further release of inflammatory mediators.
C5a
60
Act as opsonins and promote phagocytosis by neutrophils and macrophages, which bear cell surface receptors for the complement fragments.
C3b and its cleavage
product iC3b (inactive C3b)
61
A phospholipid-derived mediator that was discovered as a factor that caused platelet aggregation
Platelet-activating Factor (PAF)
62
Causes vasoconstriction and bronchoconstriction, and at low concentrations, it induces vasodilation and increased venular permeability.
Platelet-activating Factor (PAF)
62
Inhibiting coagulation reduced the inflammatory reaction to some microbes
Products of coagulation
63
Vasoactive peptides derived from plasma proteins, called kininogens
Kinins
64
Secreted by sensory nerves and various leukocytes, and may play a role in the **initiation and regulation of inflammatory responses**
Neuropeptides
64
Increases vascular permeability and causes contraction of smooth muscle, dilation of blood vessels, and pain when injected into the skin.
Bradykinin
65
Small peptides such as substance P and neurokinin A are produced in?
central and peripheral nervous systems
66
Marked by the exudation of cell poor fluid into spaces created by cell injury or into body cavities lined by the peritoneum, pleura, or pericardium
Serous inflammation
67
Hallmark of the Morphologic patterns of Acute Inflammation
Dilatation of small blood vessels and accumulation of leukocytes and fluid in the extravascular tissue.
68
Not infected by destructive organisms and does not contain large numbers of leukocytes
Serous inflammation
69
May be derived from plasma as a result of increased vascular permeability
Serous inflammation
70
Secretions of mesothelial cells as a result of local irritation
Serous inflammation
71
EFFUSION: accumulation in body cavities (skin blister resulting from a burn or viral infection)
Serous inflammation
72
Exudation of fibrinogen and fibrin deposition in extracellular space
Fibrinous inflammation
73
Develops when the vascular leaks
are large or there is a local procoagulant stimulus (e.g., cancer cells)
Fibrinous inflammation
74
Characteristic of inflammation in the lining of body cavities, such as the meninges, pericardiumm and pleura
Fibrinous inflammation
75
Are localized collections of purulent inflammatory tissue caused by suppuration buried in a tissue, an organ, or a confined space
Abscesses
75
Production of pus consisting of neutrophils, liquified necrotic debris, and edema fluid
Purulent (Suppurative) Inflammation, Abscess
75
The most frequent cause of purulent inflammation is?
infection with bacteria that cause liquefactive tissue necrosis (staphyylococci)
76
Occur only when tissue necrosis and inflammation exist on or near a surface.
Ulcer
76
Local defect or excavation of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflamed necrotic tissue
Ulcer
76
A common example of an acute suppurative inflammation is
Acute appendicitis
77
It is most commonly encountered in
(1) the mucosa of the mouth, stomach, intestines, or genitourinary tract, and
(2) the skin and subcutaneous tissue of the lower extremities in older persons who have circulatory disturbances
Ulcer
78
Patterns of Acute Inflammation
- Serous inflammation
- Fibrinous inflammation
- Purulent (Suppurative) Inflammation
- Ulcer
79
Involves removal of cellular debris and microbes by macrophages and resorption of edema fluid by lymphatics
Complete Resolution
79
Outcomes of Acute Inflammation
- Complete Resolution
- Healing by connective tissue replacement (scarring fibrosis)
- Progression to chronic inflammation
80
The usual outcome when the injury is limited or short-lived or when there has been little tissue destruction and the damaged parenchymal cells
can regenerate.
Complete Resolution
81
Occurs after substantial tissue destruction, when the inflammatory injury involves tissues that are incapable of
regeneration, or when there is abundant fibrin exudation in tissue or in serous cavities (pleura, peritoneum) that cannot be adequately cleared
Healing by connective tissue replacement (scarring fibrosis)
82
Acute to chronic transition occurs when the acute inflammatory response cannot be resolved, as a result of either the persistence of the injurious agent or some interference with the normal process of healing.
Progression to chronic inflammation
82
Dominant cells in most chronic inflammatory reactions
macrophages
83
Response of prolonged duration (weeks or months) in which inflammation, tissue injury, and attempts at repair coexist, in
varying combination
Chronic Inflammation
84
Causes of Chronic Inflammation
- Persistent infections
- Hypersensitivity diseases
- Prolonged exposure to potentially toxic agents either exogenous or endogenous
85
Morphologic features of Chronic Inflammation
- Infiltration with mononuclear cells (macrophages, lymphocytes, plasma cells)
- Tissue destruction
- Attempts at healing
86
Lymphocytes that are often present at sites of chronic inflammation
Activated B lymphocytes
and antibody-producing plasma cells
86
Have granules that contain major basic protein, a highly cationic protein that is toxic to parasites but also causes lysis of mammalian epithelial cells.
Eosinophils
87
Abundant in immune reactions mediated by IgE and in parasitic infections.
Eosinophils
88
Are characteristic of acute inflammation, many forms of chronic inflammation, lasting for months,
Neutrophils
89
Form of chronic inflammation characterized by collection of activated macrophages often T lymphocytes and sometimes associated with central necrosis
Granulomatous inflammation
90
Activated macrophages that may develop abundant cytoplasm and begin to resemble epithelial cells
Epithelioid cells
90
A cellular attempt to contain an offending agent that is difficult to eradicate
Granuloma formation
91
Activated macrophages that fuse
Multinucleated giant cells
92
Incited by relatively inert foreign bodies, in the absence of T cell-mediated immune responses
Foreign Body granulomas
92
Caused by a variety of agents that are capable of inducing a persistent T-cell mediated immune response.
Immune granuloma
93
Prototype of a granulomatous disease caused by infection and **should always be excluded** as the cause when granulomas are identified
Tuberculosis
94
Important mediators of the acute-phase reaction
TNF, IL-1, IL-6, Interferon
95
One of the most prominent manifestations of the acute-phase response, especially when inflammation is associated with infection
Fever
(elevated Body temp usually by 1° to 4°C)
96
Best known Acute-phase proteins
C-reactive protein, Fibrinogen, and Serum Amyloid A (SAA) protein
96
Plasma proteins, mostly synthesized in the liver, whose plasma concentrations may increase several hundred-fold as part of the response to inflammatory stimuli.
Acute-phase proteins
96
The increase in body temperature is caused by __________ that are produced in the vascular and perivascular cells of the hypothalamus
Prostaglandins
97
Rise in the number of more immature neutrophils in the blood
Shift to the left
98
Increased pulse and BP, decreased sweating, rigors (shivering), chills. anorexia, somnolence, and malaise
Leukocytosis
99
If the injured tissues are incapable of complete restitution, or if the supporting structures of the tissue is severely damaged
Deposition of connective tissue to form a scar (scar formation)
99
Clinical triad and known as SEPTIC SHOCK
Disseminated intravascular coagulation (DIC), hypotensive shock, and metabolic disturbances (including insulin resistance and hyperglycemia)
100
Some tissues are able to replace the damaged components and essentially return to a normal state
Regeneration
101
Constitute parenchyma of most solid tissues (liver, kidney, and pancreas) endothelial cells, fibroblasts, and smooth muscle cells
Stable tissues
101
Continuously being lost and replaced by maturation from tissue stem cells and by proliferation of mature
cells
Labile tissues
102
Steps in Scar Formation
1. Angiogenesis
2. Formation of granulation tissue
3. Remodeling of connective tissue
102
Considered to be terminally differentiated and non-proliferative in postnatal life. Neurons and cardiac muscle cells belong here
Permanent tissues
102
Limited capacity to regenerate after an injury (aside from liver)
Stable tissues
103
Produce the stable fibrous scar
remodeling
104
Factors that influence tissue repair
- infection
- diabetes
- nutritional status
- glucocorticoids (steroids)
- mechanical factors
- poor perfusion
- foreign bodies
- type and extent of tissue injury
- -location of the injury
105
Clinically one of the most important causes of delay in healing
infection
106
Inhibits collagen synthesis and retards healing
Vit. c deficiency
106
One of the most important systemic causes of abnormal wound healing
diabetes
107
Abnormalities in Tissue Repair
- Dehiscence or ulceration
- Hypertrophic scars or keloids
- Proud flesh/ Exuberant granulation
- Contraction
107
Due either to arteriosclerosis and diabetes or to obstructed
venous drainage (e.g., in varicose veins), also impairs healing.
Poor perfusion
108
Inadequate formation of granulation tissue or formation of scar
Dehiscence or ulceration
109
Although not common, occurs most frequently after abdominal surgery and is due to increased abdominal pressure.
Dehiscence or rupture
110
Excessive formation of the components
of the repair process
Hypertrophic scars or keloids
111
The accumulation of excessive amounts of collagen may give rise to a raised scar known as a
Hypertrophic scars
112
If the scar tissue grows beyond the boundaries of the original wound and does not regress, it is called
Keloid
112
Formation of excessive amounts of granulation tissue.
Exuberant granulation
113
Protrudes above the level of the surrounding skin and
blocks re-epithelialization
Proud flesh
114
An exaggeration of this process gives rise to the contracture and results in the deformities of the wound and the surrounding tissues.
Contraction
115
These are particularly prone to develop on the palms, the soles, and the anterior aspect of the thorax
Contractures
115
It is commonly seen after serious burns and can compromise the movement of joints
Contractures
