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Flashcards in Inflammation 1 Deck (45)
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What is fibrosis?

the thickening and scarring of connective tissue, usually as a result of injury. (result of chronic inflammation)


How does inflammation act as a protective function?

Dilutes, destroys or neutralizes harmful agents (bacteria, necrotic tissue)

Sets into motion the process of repair

Main components:
Vascular reaction and Cellular response (intertwined)

Although inflammation helps clear infections and other noxious stimuli and initiates repair, the inflammatory reaction and the subsequent repair process can themselves cause consider- able harm


What are the 5 R's of inflammation

(1) recognition of the injurious agent,
(2) recruitment of leukocytes,
(3) removal of the agent,
(4) regulation (control) of the response, and
(5) resolution (repair)

The external manifestations of inflammation, often called its cardinal signs, are heat (calor), redness (rubor), swelling (tumor), pain (dolor), and loss of function (functio laesa)


What are some of features of acute inflammation?

Fast onset: minutes or hours
Mainly neutrophils
Tissue injury usually mild
Local and systemic signs are often prominent


What are some of features of chronic inflammation?

Monocytes/macrophages and lymphocytes
Tissue injury/fibrosis is often severe and progressive
Local and systemic signs are often less prominent and may be subtle


What are the basic phases of acute inflammation?

Transient Vasoconstriction: (lasting only for seconds)

Vasodilation (primary): leads to greater blood flow to the area of inflammation (floods downstream capillary beds), resulting in redness and heat (erythema and warmth).

Vascular permeability and increased vascular flow (secondary): The microvasculature becomes more permeable, and protein-rich fluid moves into the extravascular tissues. This causes the red cells in the flowing blood to become more concentrated, thereby increasing blood viscosity and slowing the circulation. These changes are reflected microscopically by numerous dilated small vessels packed with red blood cells, called stasis. (histamine mediated)

Exudation: fluid, proteins, red blood cells, and white blood cells escape from the intravascular space as a result of increased osmotic pressure extravascularly and increased hydrostatic pressure intravascularly (i.e. outflow of protein makes water follow)

Vascular stasis: slowing of the blood in the bloodstream with vasodilation and fluid exudation to allow chemical mediators and inflammatory cells to collect and respond to the stimulus

The outcome of acute inflammation is either elimination of the noxious stimulus, followed by decline of the reaction and repair of the damaged tissue, or persistent injury resulting in chronic inflammation.


What is erythema?

Superficial reddening of the skin, usually in patches, as a result of injury or irritation causing dilatation of the blood capillaries.


What are some common stimuli for acute inflammation?

-Tissue necrosis
-Foreign bodies
-Immune/hypersensitivity reactions- Because the stimuli for these inflammatory responses often cannot be eliminated or avoided, such reactions tend to persist, with features of chronic inflam- mation. The term “immune-mediated inflammatory disease” is sometimes used to refer to this group of disorders.


What is margination?

stasis allows leukocytes to accumulate along the endothelial surface for diapedesis

As blood flows from capillaries into postcapillary venules, circulating cells are swept by laminar flow against the vessel wall. Because the smaller red cells tend to move faster than the larger white cells, leukocytes are pushed out of the central axial column and thus have a better opportunity to interact with lining endothelial cells, especially as stasis sets in


How does an Inflammasome work?

Binding of pathogenic bacteria causes activation of caspase-1 which activates IL-1beta. IL-1B then plays a role in leukocyte recruitment (important in type II diabetes and atherosclerosis)

Gain-of-function mutations in genes encoding some components of the inflammasome, one of which is called cryopyrin, are responsible for rare but serious diseases called cryopyrin-associated periodic fever syndromes (CAPSs), which manifest with unrelenting fevers and other signs of inflammation and respond well to treatment with IL-1 antagonists.


What is the difference between exudate and transudate?

Exudate- vascular permeability causes edema characterized by high cell density (may contain white and red cells)- usually with inflammation

Transudate- increased hydrostatic pressure caused by venous outflow obstruction (e..g congestive heart failure) caused edema fluid characterized by low protein content and few cells


Vasodilation and vascular edema usually occurs at what point in a blood system?

postcapillary venules. Caused by contact of exposed collagen


Several mechanisms may contribute to increased vascular permeability in acute inflammatory reactions. What are they?

Endothelial cell contraction leading to intercellular gaps in postcapillary venules 

Endothelial injury 

Increased transcytosis of proteins through channels formed by fusion of intracellular vesicles.

Leakage from new blood vessels, from tissue repair. 


What causes vasodilation?

Release of factors from leukocytes (histamine, kinins, prostaglandins, leukotrienes)


What happens after vasodilation occurs?

leukocyte recruitment occurs


How does leukocyte recruitment occur?

Macrophages send out chemokines to recruit them. Once they approach the site of infection, they begin to roll and attach to surface molecules on the endothelial surface. IL-1 will up regulate the expression of these molecules on the endothelial surface. Integrins cause stable adhesion and then diapedesis occurs via PECAM-1 (CD31)


What is the purpose of alpha-1-antitrypsin?

keep the elastase from leukocytes in the lungs from going out of control and causing emphysema


What is Chediak-Higashi?


Characterized clinically by partial oculocutaneous albinism due to defects in melanin granules and recurrent pyogenic bacterial infections due to abnormalities in granulocytes.

results from disordered intracellular traf- ficking of organelles, ultimately impairing the fusion of lysosomes with phagosomes. The secretion of lytic secretory granules by cytotoxic T lymphocytes is also affected, explaining the severe immunodeficiency typical
of the disorder.

All white blood cells contain abnormally giant granules.

You see normally segmented neutrophils with giant azurophilic granules so cytokines are not released properly


What are the 4 morphologic patterns of acute inflammation?



Serous acute inflammation

characterized by the outpouring of a watery, relatively protein-poor fluid that, depending on the site of injury, derives either from the plasma or from the secretions of mesothelial cells lining the peritoneal, pleural, and pericardial cavities. The skin blister resulting from a burn or viral infection is a good example of the accumulation of a serous effusion either within or immediately beneath the epidermis of the skin


Fibrinous acute inflammation

Fibrinous inflammation occurs as a consequence of more severe injuries, resulting in greater vascular permeability that allows large molecules (such as fibrinogen) to pass the endothelial barrier. Histologically, the accumulated extravascular fibrin appears as an eosinophilic mesh-work of threads or sometimes as an amorphous coagulum. A fibrinous exudate is characteristic of inflam- mation in the lining of body cavities, such as the meninges, pericardium, and pleura.

Such exudates may be degraded by fibrinolysis, and the accumulated debris may be removed by macrophages, resulting in restoration of the normal tissue structure (resolution). However, extensive fibrin-rich exudates may not be completely removed, and are replaced by an ingrowth of fibroblasts and blood vessels (organization), leading ultimately to scarring that may have significant clinical consequences, for example organization of a fibrinous pericardial exudate forms dense fibrous scar tissue that bridges or obliterates the pericardial space and restricts myocardial function.


What is an effusion?

fluid in a cavity


What is an inflammasome?

a multi-protein cytoplasmic complex that recognizes products of dead cells, such as uric acid and extracellular ATP, as well as crystals and some microbial products via a sensor protein (a leucine-rich protein called NLRP3) and an adaptor. Triggering of the inflammasome results in activation of an enzyme called caspase-1, which cleaves precursor forms of the inflammatory cytokine interleukin-1β (IL-1β) into its biologically active form.


In what cases would an inflammasome be activated?

The joint disease, gout, is caused by deposition of urate crystals, which are ingested by phagocytes and activate the inflammasome, resulting in IL-1 production and acute inflammation. IL-1 antagonists are effective treatments in cases of gout that are resistant to conventional anti-inflammatory therapy. Recent studies have shown that cholesterol crystals and free fatty acids also activate the inflammasome, suggest- ing that IL-1 plays a role in common diseases such as atherosclerosis (associated with deposition of cholesterol crystals in vessel walls) and obesity-associated type 2 diabetes. This finding raises the possibility of treating these diseases by blocking IL-1.


What mechanisms may contribute to increased vascular permeability in acute inflammatory reactions?

1) Endothelial cell contraction leading to intercellular gaps in postcapillary venules is the most common cause of increased vascular permeability. Endothelial cell contraction occurs rapidly after binding of histamine, bra- dykinin, leukotrienes, and many other mediators to specific receptors, and is usually short-lived (15 to 30 minutes).

A slower and more prolonged retraction of endothelial cells, resulting from changes in the cytoskeleton, may be induced by cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1). This reaction may take 4 to 6 hours to develop after the initial trigger and persist for 24 hours or more.

2) Endothelial injury results in vascular leakage by causing endothelial cell necrosis and detachment. Endothelial cells are damaged after severe injury such as with burns and some infections. In most cases, leakage begins immediately after the injury and persists for several hours (or days) until the damaged vessels are throm- bosed or repaired. Venules, capillaries, and arterioles can all be affected, depending on the site of the injury.

3) Increased transcytosis of proteins by way of an intracellular vesicular pathway augments venular permeability, especially after exposure to certain mediators such as vascular endothelial growth factor (VEGF). Transcytosis occurs through channels formed by fusion of intracel- lular vesicles.

4) Leakage from new blood vessels. Tissue repair involves new blood vessel formation (angiogen- esis). These vessel sprouts remain leaky until prolifer- ating endothelial cells mature sufficiently to form intercellular junctions. New endothelial cells also have increased expression of receptors for vasoactive media- tors, and some of the factors that stimulate angiogenesis (e.g., VEGF) also directly induce increased vascular permeability.


What happens to lymphatic vessels in response to acute inflammation?

In inflammation, lymph flow is increased and helps drain edema fluid, leukocytes, and cell debris from the extravascular space. In severe inflammatory reactions, especially to microbes, the lymphatics may transport the offending agent, contributing to its dissemination.


T or F. A price that is paid for the defensive potency of leukocytes is that once activated, they may induce tissue damage and prolong inflammation, since the leukocyte products that destroy microbes can also injure normal host tissues.

T. Therefore, host defense mecha- nisms include checks and balances that ensure that leukocytes are recruited and activated only when and where they are needed (i.e., in response to foreign invaders and dead tissues). Systemic activation of leukocytes can, in fact, have detrimental consequences, as in septic shock (Chapter 3).


Where is E-selectin (also called CD62E), expressed?; P-selectin (CD62P)?, L-selectin (CD62L)?

E=on endothelial cells
P=present on platelets and endothelium
L=on the surface of most leukocytes

The endothelial selectins are typically expressed at low levels or are not present at all on unactivated endothelium, and are up-regulated after stimulation by cytokines and other mediators. Therefore, binding of leukocytes is largely restricted to endothelium at sites of infection or tissue injury (where the mediators are produced).


What are Weibel-Palade bodies?

P-selectin is found primarily in intracellular Weibel-Palade bodies in platelets and endothelial cells. These also secrete vMF


What causes up regulation of P-selectin on platelets and endothelial cells?

histamine and thrombin