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Pathology 1st LE > Inflammation and Repair - part 1 (Kumar Ch. 3) > Flashcards

Inflammation and Repair - part 1 (Kumar Ch. 3) Flashcards

1
Q

A 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

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2
Q

REMEMBER

The major participants in the inflammatory reaction in tissues are blood vessels and leukocytes

A

blood vessels dilate to slow down blood flow, and by increasing their permeability, they enable selected circulating proteins to enter the site of infection or tissue damage

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3
Q

In rare situations, such as some disseminated bacterial infections, the inflammatory reaction is systemic and causes widespread pathologic abnormalities. This reaction has been called?

A

Sepsis

  • *one form of the sytematic inflammatory response syndorme
  • *Inflammatory reaction is largely confined to the site of infection or damage
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4
Q

Cells and molecules involved in diseases caused by inflammatory reaction

Acute respiratory distress syndrome:

A

Acute respiratory distress syndrome: Neutrophils

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5
Q

Cells and molecules involved in diseases caused by inflammatory reaction

Asthma (ACUTE):

A

Asthma (ACUTE): Eosinophils; IgE antibodies

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6
Q

Cells and molecules involved in diseases caused by inflammatory reaction

Glomerulonephritis (ACUTE):

A

Glomerulonephritis (ACUTE): Antibodies and complement; neutrophils, monocytes

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7
Q

Cells and molecules involved in diseases caused by inflammatory reaction

Septic shock (ACUTE):

A

Septic shock (ACUTE): Cytokines

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8
Q

Cells and molecules involved in diseases caused by inflammatory reaction

Arthritis (CHRONIC):

A

Arthritis (CHRONIC): Lymphocytes, macrophages

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9
Q

Cells and molecules involved in diseases caused by inflammatory reaction

Asthma (CHRONIC):

A

Asthma (CHRONIC): Eosinophils; IgE antibodies

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10
Q

Cells and molecules involved in diseases caused by inflammatory reaction

Atherosclerosis (CHRONIC):

A

Atherosclerosis (CHRONIC): Macrophages; lymphocytes

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11
Q

Cells and molecules involved in diseases caused by inflammatory reaction

Pulmonary fibrosis (CHRONIC):

A

Pulmonary fibrosis (CHRONIC): Macrophages; fibroblasts

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12
Q

REMEMBER

The initial, rapid response to infections and tissue damage is called acute inflammation

A
  • typically develops within minutes or hours and is of short duration, lasting for several hours or a few days
  • its main characteristics are the exudation of fluid and plasma proteins (edema) and the emigration of leukocytes, predominantly neutrophils
  • innate immunity
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13
Q

REMEMBER
When acute inflammation achieves its desired goal of eliminating the offenders, the reaction subsides, but if the response fails to clear the stimulus, the reaction can progress to a protracted phase that is called chronic inflammation

A
  • longer duration and is associated with more tissue destruction
  • presence of lymphocytes and macrophages, proliferation of blood vessels, and the deposition of connective tissue
  • adaptive immunity
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14
Q

Four cardinal signs of inflammation

A

Rubor (redness), tumor (swelling), calor (heat), and dolor (pain)

  • *these signs are hallmarks of acute inflammation
  • *A fifth clinical sign, loss of function (functio esa), was added by Rudolf Virchow in the 19th century
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15
Q

Causes of inflammation

A
  1. infections
  2. Tissue necrosis
  3. Foreign bodies
  4. Immune reactions
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16
Q

REMEMBER

Cellular receptors for microbes

A

Plasma membrane - for extracellular microbes
endosomes - for ingested microbes
cytosol - for intracellular microbes

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17
Q

What are the sensors of cell damage

A
  1. uric acid
  2. ATP (released from damaged mitochondria)
  3. reduced intracellular K+ concentration (refelcting loss of ions because of plasma membrane injury)
    * *These receptors activate a multiprotein cytosolic complex called the inflammasome which induces the production of cytokine interleukin-1
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18
Q

The steps of the inflammatory response can be remembered as the five Rs

A
  1. recognition of the injurious agent
  2. recruitment of leukocytes
  3. removal of the agent
  4. regulation of the response
  5. resolution
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19
Q

What are the three major components of acute inflammation

A
  1. dilation of SMALL VESSELS leading to INCREASE blood flow
  2. increased permeability of the microvasculature enabling plasma proteins and leukocytes to leave the circulation
  3. emigration of the leukocytes from the microcirculation, their accumulation in the focus of injury, and their activation to eliminate the offending agent
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20
Q

REMEMBER
Normal hydrostatic pressure (pushing force towards the extravascular space) is about 32 mm Hg at the arterial end of a capillary bed and 12 mm Hg at the venous end; the mean colloid osmotic pressure (pulling force towards the intravascular space) of tissues is approximately 25 mm Hg which is equal to mean capillary pressure. Thus net flow of fluid is at equilibrium

A

An exudate is formed in inflammation, because vascular permeability increases as a result of increased interendothelial spaces
**an exudate is an extravascular fluid that has high proteins concentration and cellular debris

A transudate is formed when fluid leaks out because of increased hydrostatic pressure or decreased osmotic pressure.
**transudate is a fluid with low protein contnet, little or no cellular material and low specific gravity.

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21
Q

Changes in vascular flow and caliber during acute inflammation:

A
  1. vasodilation - induced by the action of several mediators (notably histamine) - INCREASED blood flow which is the cause of heat and redness at site of inflammation
  2. increased permeability of the microvasculature, with the outpouring of
    protein-rich fluid into the extravascular tissues
  3. The loss of fluid and increased vessel diameter lead to
    SLOWER blood flow, concentration of red cells in small vessels, and increased viscosity of the blood (STASIS)
  4. As stasis develops, blood leukocytes, principally neutrophils, accumulate along the vascular endothelium
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22
Q

Principal mechanisms of increased vascular permeability in inflammation:

  1. Retraction of endothelial cells
  2. Endothelial injury
  3. Transcytosis
A
  1. Retraction of endothelial cells
    - It is elicited by histamine, bradykinin, leukotrienes, and other chemical mediators
    - It is called the immediate transient response because it occurs rapidly after exposure to the mediator and is usually short-lived (15 to 30 minutes).
  2. Endothelial injury
    - Caused by burns, some microbial toxins
    - Rapid; may be long-lived (hours to days)
  3. Transcytosis
    - This process may involve intracellular channels that may be stimulated by certain factors, such as vascular endothelial growth factor (VEGF), that promote vascular leakage
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23
Q

The changes in blood flow and vascular permeability are quickly followed by an influx of leukocytes into the tissue. These leukocytes perform the key function of eliminating the offending agents.

A

The most important leukocytes in typical inflammatory reactions are the ones capable of phagocytosis, namely neutrophils and macrophages

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24
Q

The journey of leukocytes from the vessel lumen to the tissue is a multistep process that is mediated and controlled by what molecules?

A

Adhesion molecules and cytokines called chemokines

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25
Q

The process of leukocytes migration can be divided into sequential phases:

A
  1. In the lumen: margination, rolling, and adhesion to endothelium.
  2. Migration across the endothelium and vessel wall
  3. Migration in the tissues toward a chemotactic stimulus
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26
Q

Because blood flow slows early in inflammation (stasis), hemodynamic conditions change (wall shear stress decreases), and more white cells
assume a peripheral position along the endothelial surface. This process of leukocyte redistribution is called?

A

margination

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27
Q

What are the two major families of molecules involved in leukocyte adhesion and migration?

A

selectins and integrins

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28
Q

Leukocytes adhere transiently to the endothelium, detach and bind again, thus rolling on the vessel wall. The initial rolling interactions are mediated by a family of proteins called?

A

selectins

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29
Q

What are the 3 types of selectins?

A
  1. L-selectin - expressed on leukocytes
  2. E-selectin - expressed on endothelium
  3. P-selectin - expressed on platelets and endothelium
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30
Q

What are the ligands for selectins?

A

sialylated oligosaccharides bound to mucin-like glycoprotein backbones

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31
Q

The expression of selectins and their ligands is regulated by cytokines produced in response to infection and injury. Tissue macrophages, mast cells, and endothelial cells that encounter
microbes and dead tissues respond by secreting several cytokines, including?

A

tumor necrosis factor (TNF), IL-1, and chemokines (chemoattractant cytokines)

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32
Q

These cytokines act on the endothelial cells of postcapillary venules adjacent to the infection and induce the coordinate expression of numerous adhesion molecules

A

TNF and IL-1

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33
Q

Intracellular stores of P-selectin in endothelial cell granules are called?

A

Weibel-Palade bodies

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34
Q

Firm adhesion of leukocytes is mediated by a family of heterodimeric leukocyte surface proteins called?

A

Integrins

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35
Q

REMEMBER
TNF and IL-1 induce endothelial expression of ligands for integrins, mainly vascular cell adhesion molecule 1 (VCAM-1, the ligand for the β1 integrin VLA-4) and intercellular adhesion molecule-1 (ICAM-1, the ligand for the β2 integrins LFA-1 and Mac-1)

A

Leukocytes normally express integrins in a low-affinity state. Chemokines that were produced at the site of injury bind to endothelial cell proteoglycans. These chemokines bind to and activate the rolling leukocytes. One of the consequences of activation is the conversion of VLA-4 and LFA-1 integrins on the leukocytes to a high-affinity state, this result to firm integrin-mediated binding of the leukocytes to the endothelium at the site of inflammation.

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36
Q

The term used for leukocyte migration through the endothelium is?

A

transmigration or diapedesis

**Transmigration of leukocytes occurs mainly in postcapillary venules

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37
Q

After exiting the circulation, leukocytes move in the tissues toward the site of injury by a process called?

A

Chemotaxis

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38
Q

In chemotaxis of leukocytes, Both exogenous and endogenous substances can act as chemoattractants.

A

The most common exogenous agents are bacterial products, including peptides that possess
an N-formylmethionine terminal amino acid and some lipids

Endogenous chemoattractants include several chemical mediators:

  1. cytokines, particularly those of the chemokine family
  2. components of the complement system, particularly C5a
  3. Arachidonic acid (AA) metabolites, mainly leukotriene B4 (LTB4)
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39
Q

All the chemotactic agents bind to what kind of receptor?

A

G protein-coupled receptors on the surface of leukocytes
**Signals initiated from these receptors result in activation of second messengers that increase cytosolic calcium and activate small guanosine triphosphatases of the Rac/Rho/cdc42 family as well as numerous kinases

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40
Q

REMEMBER
The macrophage mannose receptor is a lectin that binds terminal mannose and fucose residues of glycoproteins and glycolipids

A

These sugars are typically part of molecules found on microbial cell walls, whereas mammalian glycoproteins and glycolipids contain terminal sialic acid or N-acetylgalactosamine. Therefore, the mannose receptor recognizes microbes and not host cells

41
Q

After the phagocytes have engulf the microbes, intracellular destruction of microbes and debris takes place. This is done by:

A

ROS and reactive nitrogen species mainly derived from NO

42
Q

ROS are produced by the rapid assembly and activation of this multicomponent oxidase:

A

NADPH oxidase (also called phagocyte oxidase), which oxidizes NADPH (reduced nicotinamide-adenine dinucleotide phosphate) and, in the process, reduces oxygen to superoxide anion (O2 • ).

43
Q

A potent antimicrobial agent that destroys

microbes by halogenation

A

Hypochlorite

  • *H2O2 is converted to hypochlorite in the presence of a halide by the enzyme myeloperoxidase (azuriphilic granules of neutrophils)
  • *The H2O2-MPO-halide system is the most efficient bactericidal system of neutrophils
44
Q

What are the 3 different types of Nitric Oxide?

A

endothelial (eNOS), neuronal (nNOS), and inducible (iNOS)

  • *eNOS and nNOS are constitutively expressed at low levels and the NO they generate functions to maintain vascular tone and as a neurotransmitter, respectively
  • *iNOS, the type that is involved in microbial killing, is induced when macrophages and neutrophils are activated by cytokines
45
Q

REMEMBER
Neutrophil granules:
Specific/secondary granules (smaller) - lysozyme, collagenase, gelatinase, lactoferrin, plasminogen activator, histaminase, and alkaline phosphatase. These mediators induce various components of the inflammatory response typically by distinct mechanisms, which is why inhibiting each has been therapeutically beneficial.

A

Neutrophil granules:
Azurohil/primary (larger) - myeloperoxidase, bactericidal factors (lysozyme, defensins), acid hydrolases, and a variety of neutral proteases (elastase, cathepsin G, nonspecific collagenases, proteinase 3)

46
Q

REMEMBER
The most important mediators of acute inflammation are vasoactive amines, lipid products (prostaglandins
and leukotrienes), cytokines (including chemokines), and products of complement activation

A

These mediators induce various components of the inflammatory response typically by distinct mechanisms, which is why inhibiting each has been therapeutically beneficial.

47
Q

what are the major cell types that produce mediators of acute inflammation?

A

Sentinels that detect invaders and damage tissues (macrophages, dendritic cells and mast cells)

48
Q

Histamine
Source:
Action:

A

HIstamine
Source: Mast cells, basophils, platelets
Action: Vasodilation, increased vascular permeability, endothelial activation

49
Q

Prostaglandins
Source:
Action:

A

Prostaglandins
Source: Mast cells, leukocytes
Action: Vasodilation, pain, fever

50
Q

Leukotrienes
Source:
Action:

A

Leukotrienes
Source: Mast cells, leukocytes
Action: Increased vascular permeability, chemotaxis, leukocyte adhesion, and activation

51
Q

Cytokines (TNF, IL-1, IL-6)
Source:
Action:

A

Cytokines (TNF, IL-1, IL-6)
Source: Macrophages, endothelial cells,
mast cells
Action: Local: endothelial activation (expression of adhesion molecules). Systemic: fever, metabolic abnormalities, hypotension (shock)

52
Q

Chemokines
Source:
Action:

A

Chemokines
Source: Leukocytes, activated macrophages
Action: Chemotaxis, leukocyte activation

53
Q

Platelet-activating factor
Source:
Action:

A

Platelet-activating factor
Source: Leukocytes, mast cells
Action: Vasodilation, increased vascular permeability, leukocyte adhesion, chemotaxis, degranulation,
oxidative burst

54
Q

Complement
Source:
Action:

A

Complement
Source: Plasma (produced in liver)
Action: Leukocyte chemotaxis and activation, direct target killing (membrane attack complex),
vasodilation (mast cell stimulation)

55
Q

Kinins
Source:
Action:

A

Kinins
Source: Plasma (produced in liver)
Action: Increased vascular permeability, smooth muscle contraction, vasodilation, pain

56
Q

REMEMBER

  1. Mediators are either secreted by cells or generated from plasma proteins
  2. Active mediators are produced only in response to various stimuli
A
  1. Most of the mediators are short-lived

4. One mediator can stimulate the release of other mediators.

57
Q

What are the two mediators of acute inflammation that are vasoactive amines?

A

Histamine and serotonin
**They are stored as preformed molecules in cells and are therefore among the first mediators to be released during inflammation.

58
Q

Histamine is released by what stimuli?

A
  1. physical injury
  2. binding of antibodies to mast cells (allergic reactions)
  3. products of complement called anaphylatoxins (C3a and C5a)
59
Q

REMEMBER
Histamine is considered to be the principal mediator of the immediate transient phase of increased vascular permeability, producing interendothelial gaps in venules

A

Its vasoactive effects are mediated mainly via binding to receptors, called H1 receptors, on microvascular endothelial cells

60
Q

REMEMBER
The lipid mediators prostaglandins and leukotrienes are produced from arachidonic acid (AA) present in membrane phospholipids, and stimulate vascular and cellular reactions in acute inflammation

A

AA is a 20-carbon polyunsaturated fatty acid (5,8,11,14-eicosatetraenoic acid) that is derived from dietary sources or by conversion from the essential fatty acid linoleic acid
**It does not occur free in the cell but is normally esterified in membrane phospholipids

61
Q 
Mechanical, chemical, and physical stimuli or
other mediators (e.g., C5a) release AA from membrane
phospholipids through the action of what enzyme?
A

Phospholipase A2

62
Q

REMEMBER

Eicosanoids are AA-derived mediators synthesized by 2 major classes of enymes

A
  1. Cyclooxygenases = prostaglandins

2. Lipoxygensases = leukotrienes and lipoxins

63
Q 
Eicosanoid:
Prostaglandins PGI2 (prostacyclin), PGE1, PGE2, PGD2 - vasodilation
Thromboxane A2, leukotrienes C4, D4, E4 - vasoconstriction
A

Leukotrienes C4, D4, E4 - Increased vascular permeability

Leukotrienes B4, HETE - Chemotaxis, leukocyte adhesion

64
Q

REMEMBER

COX-1 and COX-2 generate prostaglandins

A
  • *COX-1 is produced in response to inflammatory stimuli and is also constitutively expressed in most tissues, where it may serve a homeostatic function
  • *COX-2 is induced by inflammatory stimuli and thus generates the prostaglandins that are involved in inflammatory reactions, but it is low or absent in most normal tissues
65
Q

REMEMBER
platelets contain the enzyme thromboxane synthase, and hence TxA2 is the major product in these cells. TxA2, a potent platelet-aggregating agent and vasoconstrictor, is itself unstable and rapidly converted to its inactive form TxB2

A

Vascular endothelium lacks thromboxane synthase but possesses prostacyclin synthase, which is responsible for the formation of prostacyclin (PGI2) and its stable end product PGF1a. Prostacyclin is a vasodilator and a potent inhibitor of platelet aggregation.

66
Q

PGD2 and PGE2 are major prostaglandin made by mast cells (PGE2 are more widely distributed)

A

it causes vasodilation and increases the permeability of postcapillary venules, thus potentiating edema formation.

67
Q

PGF2a stimulates the contraction of uterine and bronchial smooth muscle and small arterioles

A

PGD2 is a chemoattractant for neutrophils.

68
Q

This enzyme converts AA to 5-hydroxyeicosatetraenoic acid, which is chemotactic for neutrophils, and is the precursor of the leukotrienes.

A

5-lipoxygenase

69
Q

AA => 5-HPETE (enzyme: 5-lipoxygenase) => 5-HETE

5-HPETE => Leukotriene A4 => Leukotriene B4

Leukotriene C4 => Leukotriene D4 => Leukotriene E4

A

**LTB4 is a potent chemotactic agent and activator of neutrophils, causing aggregation and adhesion of the cells to venular endothelium, generation of ROS, and release of lysosomal enzymes
**cysteinyl-containing leukotrienes LTC4, LTD4, and LTE4 cause intense vasoconstriction, bronchospasm and increased permeability of venules
NOTE: Leukotrienes are more potent than is histamine in increasing vascular permeability and causing bronchospasm.

70
Q

Lipoxins (12-lipoxygenase) - inhibit inflammation

A 
Lipoxin A4 (LXA4)
Lipoxin B4 (LXB4)
**They inhibit neutrophil chemotaxis and adhesion to endothelium
**Leukocytes, particularly neutrophils, produce intermediates in lipoxin synthesis, and these are converted to lipoxins by platelets interacting with the leukocytes.
71
Q

REMEMBER
Cyclooxygenase inhibitors include aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen. They inhibit both COX-1 and COX-2 and thus inhibit prostaglandin synthesis (hence their efficacy in treating pain and fever)

A
  1. Aspirin - irreversibly acetylating and inactivating cyclooxygenases
  2. Selective COX-2 inhibitors
72
Q

COX-1 is responsible for the production of prostaglandins that are involved in both inflammation and homeostatic functions

A

COX-2 generates prostaglandins that are involved only in inflammatory reactions
**COX-2 inhibitors may increase the risk of cardiovascular and cerebrovascular events - impair endothelial cell production of prostacyclin (PGI2), a vasodilator and inhibitor of platelet
aggregation; and leaave intact the COX-1-mediated production
by platelets of thromboxane A2 (TxA2), an important mediator of platelet aggregation and vasoconstriction.

73
Q

REMEMBER

5-lipoxygenase is not affected by NSAIDs

A

Pharmacologic agents that inhibit leukotriene production (e.g., Zileuton) are
useful in the treatment of asthma.

74
Q

Serve critical roles in leukocyte recruitment by promoting adhesion of leukocytes to endothelium and their migration through vessels.

A

Tumor Necrosis Factor (TNF) and Interleukin-1 (IL-1)

  • *produced by activated macrophages and dendritic cells
  • *TNF is also produced by T lymphocytes and mast cells
  • *IL-1 is produced by some epithelial cells as well
75
Q

The secretion of TNF and IL-1 can be stimulated by?

A

microbial products, immune complexes, foreign bodies, physical injury, and a variety of other inflammatory stimuli

76
Q

CYTOKINES
TNF (Acute)
Principal sources:
Principal actions:

A

CYTOKINES
TNF (Acute)
Principal sources: Macrophages, mast cells, T lymphocytes
Principal actions: Stimulates expression of endothelial adhesion molecules and secretion of other cytokines; systemic effects

77
Q

CYTOKINES
IL-1 (Acute)
Principal sources:
Principal actions:

A

CYTOKINES
IL-1 (Acute)
Principal sources: Macrophages, endothelial cells, some epithelial cells
Principal actions: Similar to TNF; greater role in fever

78
Q

CYTOKINES
IL-6 (Acute)
Principal sources:
Principal actions:

A

CYTOKINES
IL-6 (Acute)
Principal sources: Macrophages, other cells
Principal actions: Systemic effects (acute phase response)

79
Q

CYTOKINES
Chemokines (Acute)
Principal sources:
Principal actions:

A

CYTOKINES
Chemokines (Acute)
Principal sources: Macrophages, endothelial cells,
T lymphocytes, mast cells, other
cell types
Principal actions: Recruitment of leukocytes to sites of inflammation; migration of cells in normal tissues

80
Q

CYTOKINES
IL-17 (Acute and chronic)
Principal sources:
Principal actions:

A

IL-17 (Acute and chronic)
Principal sources: T lymphocytes
Principal actions: Recruitment of neutrophils and monocytes

81
Q

CYTOKINES
IL-12 (chronic)
Principal sources:
Principal actions:

A

CYTOKINES
IL-12 (chronic)
Principal sources: Dendritic cells, macrophages
Principal actions: Increased production of IFN-γ

82
Q

CYTOKINES
IFN-Y (chronic)
Principal sources:
Principal actions:

A

CYTOKINES
IFN-Y (chronic)
Principal sources: T lymphocytes, NK cells
Principal actions: Activation of macrophages (increased ability to kill microbes and tumor cells)

83
Q

Sustained production of TNF contributes to a pathologic state characterized by weight loss and anorexia that accompanies some chronic infections and neoplastic diseases.

A

Cachexia

84
Q

Chemokine

family of small (8 to 10 kD) proteins that act primarily as chemoattractants for specific types of leukocytes.

A

Cytokines
proteins produced by many cell types (principally activated lymphocytes, macrophages, and dendritic cells, but also endothelial, epithelial, and connective tissue cells) that mediate and regulate immune and inflammatory reactions.

85
Q

Complement system
a collection of soluble proteins and membrane receptors that function mainly in host defense against microbes and in pathologic inflammatory reactions.

A
  • functions in BOTH innate and adaptive immunity for defense against microbial pathogens.
  • consists of more than 20 proteins
  • several cleavage products cause increased vascular permeability, chemotaxis, and opsonization
86
Q

Cleavage of C3 can occur by one of three pathways:

A
  1. Classical pathway - which is triggered by fixation of C1 to antibody (IgM or IgG) that has combined with antigen
  2. alternative pathway - can be triggered by microbial surface molecules (e.g., endotoxin, or LPS), complex polysaccharides, cobra venom, and other substances, in the absence of antibody
  3. Lectin pathway - plasma mannose-binding lectin binds to carbohydrates on microbes and directly activates C1.
87
Q

All three pathways of complement activation lead to

the formation what enzyme which splits C3 into two functionally distinct fragments, C3a and C3b.

A

C3 convertase

  • *C3a is released, and C3b becomes covalently attached to the cell or molecule where complement is being activated.
  • *More C3b then binds to the previously generated fragments to form C5 convertase, which cleaves C5 to release C5a and leave C5b attached to the cell surface
  • *C5b binds the late components (C6-C9), culminating in the formation of the membrane attack complex
88
Q

What are the three main functions of the complement system?

A
  1. Inflammation
    - C3a, C5a and C4a (anaphylatoxins) stimulate histamine release from mast cells
    - C5a is also a chemotactic agent for neutrophils, monocytes, eosinophils, and basophils; activates the lipoxygenase pathway
  2. Opsonization and phagocytosis - C3b
  3. Cell lysis - MAC
89
Q

REMEMBER
The morphologic hallmarks of acute inflammatory reactions are dilation of small blood vessels and accumulation of leukocytes and fluid in the extravascular tissue.

A

However other special morphologic patterns are often superimposed on these general features:

  1. Serous inflammation
  2. Fibrinous inflammation
  3. Purulent (Suppurative) Inflammation, Abscess
  4. Ulcers
90
Q

Serous inflammation is 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

A

the fluid in serous inflammation is not infected by destructive organisms and does not contain large numbers of leukocytes

91
Q

Characterized by the production of pus, an exudate consisting of neutrophils, the liquefied debris of necrotic cells, and edema fluid

A

Purulent (Suppurative) Inflammation, Abscess

**different from serous inflammation

92
Q

Because of the destructive effects of lysosomal enzymes, the initial leukocytic infiltration, if unchecked, can potentiate further inflammation by damaging tissues.

A

These harmful proteases, however, are normally controlled by a system of antiproteases in the serum and tissue fluids. Foremost among these is α1-antitrypsin, which is the major inhibitor of neutrophil elastase. α2-Macroglobulin is another antiprotease. found in serum and various secretions.

93
Q

microbicidal granule contents include:

A

defensins, cationic arginine-rich granule peptides that are toxic to microbes; cathelicidins, antimicrobial proteins found in neutrophils and other cells; lysozyme, which hydrolyzes the muramic acid-N-acetylglucosamine bond, found in the glycopeptide coat of all bacteria; lactoferrin, an iron-binding protein present in specific granules; and major basic protein, a cationic protein of eosinophils, which has limited bactericidal activity but is cytotoxic to many parasites.

94
Q

Histamine and serotonin
are stored as preformed molecules in cells and are therefore among the first mediators to be released during inflammation. The richest sources of histamine are the mast cells that are normally present in the connective tissue adjacent to blood vessels. It is also found in blood basophils and platelets.

A

Histamine is stored in mast cell granules and is released by mast cell degranulation in response to a variety of stimuli, including (1) physical injury, such as trauma, cold, or heat, by unknown mechanisms; (2) binding of antibodies to mast cells, which underlies immediate hypersensitivity (allergic) reactions; and (3) products of complement called anaphylatoxins (C3a and C5a). In addition, leukocytes are thought to secrete some histamine-releasing proteins but these have not been characterized. Neuropeptides (e.g., substance P) and cytokines (IL-1, IL-8) may also trigger release of histamine.

95
Q

Platelets contain the enzyme thromboxane synthase, and hence TxA2 is the major product in these cells. TxA2, a potent platelet-aggregating agent and vasoconstrictor, is itself unstable and rapidly converted to its inactive form TxB2

A

Vascular endothelium lacks thromboxane synthase but possesses prostacyclin synthase, which is responsible for the formation of prostacyclin (PGI2) and its stable end product PGF1a. Prostacyclin is a vasodilator and a potent inhibitor of platelet aggregation, and also markedly potentiates the permeability-increasing and chemotactic effects of other mediators.

96
Q

PGD2 is the major prostaglandin made by mast cells; along with PGE2 (which is more widely distributed), it causes vasodilation and increases the permeability of postcapillary venules, thus potentiating edema formation. PGF2a stimulates the contraction of uterine and bronchial smooth muscle and small arterioles, and PGD2 is a chemoattractant for neutrophils.

A

In addition to their local effects, the prostaglandins are involved in the pathogenesis of pain and fever in inflammation. PGE2 is hyperalgesic and makes the skin hypersensitive to painful stimuli, such as intradermal injection of suboptimal concentrations of histamine and bradykinin. It is involved in cytokine induced fever during infections

97
Q

Leukotrienes are produced by leukocytes and mast cells by the action of lipoxygenase. There are three different lipoxygenases, 5-lipoxygenase being the predominant one in neutrophils. This enzyme converts AA to 5-hydroxyeicosatetraenoic acid, which is chemotactic for neutrophils, and is the precursor of the leukotrienes.

A

LTB4 is a potent chemotactic agent and activator of neutrophils, causing aggregation and adhesion of the cells to venular endothelium, generation of ROS, and release of lysosomal enzymes. The cysteinyl-containing leukotrienes LTC4, LTD4, and LTE4 cause intense vasoconstriction, bronchospasm (important in asthma), and increased permeability of venules.
Leukotrienes are more potent than is histamine in increasing vascular permeability and causing bronchospasm.

98
Q

blocks the activation of C1, the first protein of the classical complement pathway. Inherited deficiency of this inhibitor is the cause of hereditary angioedema.

A

C1 inhibitor (C1 INH)

99
Q

Decay accelerating factor (DAF) and CD59 are two proteins that are linked to plasma membranes by a glycophosphatidyl (GPI) anchor. DAF prevents formation of C3 convertases and CD59 inhibits formation of the membrane attack complex.

A

An acquired deficiency of the enzyme that creates GPI anchors leads to deficiency of these regulators and excessive complement activation and lysis of red cells (which are sensitive to complement-mediated cell lysis) in the disease called paroxysmal nocturna hemoglobinuria (PNH)

Pathology 1st LE (12 decks)

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