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What are vascular events of acute inflammation?

Vascular Phase – In the vascular phase, small blood vessels adjacent to the injury dilate ( vasodilatation ) and blood flow to the area increases. The endothelial cells initially swell, then contract to increase the space between them, thereby increasing the permeability of the vascular barrier.

1. This process is regulated by chemical mediators (see Appendix).
2. Exudation of fluid leads to a net loss of fluid from the vascular space into the interstitial space, resulting in oedema (tumour).
3. The fluid present is termed an ” exudate “, and characteristically is high in protein contents due to the increased vascular permeability The formation of increased tissue fluid acts as a medium for which inflammatory proteins (such as complement and immunoglobulins) can migrate through.

It may also help to remove pathogens and cell debris in the area through lymphatic drainage.

What are the vascular responses to inflammation?

5.4: Inflammatory Response I: Vascular and Cellular – The inflammatory response is the body’s defense against infection, injury, or irritation from bacteria, trauma, toxins, or heat. Inflammation helps locate and destroy pathogens and remove damaged tissue elements to heal the body.

During this initial phase, fluid, blood products, and nutrients migrate to the injured area, resulting in redness, heat, swelling, ache, and loss of function. Moreover, signs of systemic inflammation include fever, increased WBC count, malaise, anorexia, nausea, vomiting, lymph node enlargement, or organ failure.

The crucial components of the inflammatory process are the vascular and cellular stages. At the vascular stage, small blood vessels constrict initially; then, the arterioles and venules that supply the area dilate, increasing the blood flow and causing redness and heat.

1. In addition, the release of cell mediators, such as histamine, increases vascular permeability and allows protein-rich fluids to flow into the area, which can cause swelling, pain, and loss of function.
2. During the cellular stage, white blood cells rush into the area.
3. Neutrophils and monocytes engulf pathogens through phagocytosis and ingest cell debris and foreign material.

This leads to the phagocytic release of pyrogens from bacterial cells, causing fever.

What are the major events in acute inflammation?

INTRODUCTION – Inflammation is the immune system’s response to harmful stimuli, such as pathogens, damaged cells, toxic compounds, or irradiation, and acts by removing injurious stimuli and initiating the healing process, Inflammation is therefore a defense mechanism that is vital to health,

Usually, during acute inflammatory responses, cellular and molecular events and interactions efficiently minimize impending injury or infection. This mitigation process contributes to restoration of tissue homeostasis and resolution of the acute inflammation. However, uncontrolled acute inflammation may become chronic, contributing to a variety of chronic inflammatory diseases,

At the tissue level, inflammation is characterized by redness, swelling, heat, pain, and loss of tissue function, which result from local immune, vascular and inflammatory cell responses to infection or injury, Important microcirculatory events that occur during the inflammatory process include vascular permeability changes, leukocyte recruitment and accumulation, and inflammatory mediator release,

Various pathogenic factors, such as infection, tissue injury, or cardiac infarction, can induce inflammation by causing tissue damage. The etiologies of inflammation can be infectious or non-infectious (Table ​ 1 ). In response to tissue injury, the body initiates a chemical signaling cascade that stimulates responses aimed at healing affected tissues.

These signals activate leukocyte chemotaxis from the general circulation to sites of damage. These activated leukocytes produce cytokines that induce inflammatory responses,

Why does inflammation cause vasodilation?

Inflammation – Inflammation can occur due to a variety of injuries, diseases, or conditions. Vasodilation happens during the inflammatory process in order to allow increased blood flow to the affected area. This is what causes the heat and redness associated with inflammation.

Are there 5 cardinal signs of acute inflammation?

Introduction – Based on visual observation, the ancients characterised inflammation by five cardinal signs, namely redness ( rubor ), swelling ( tumour ), heat ( calor ; only applicable to the body’ extremities), pain ( dolor ) and loss of function ( functio laesa ).

The first four of these signs were named by Celsus in ancient Rome (30–38 B.C.) and the last by Galen (A.D 130–200), More recently, inflammation was described as “the succession of changes which occurs in a living tissue when it is injured provided that the injury is not of such a degree as to at once destroy its structure and vitality”, or “the reaction to injury of the living microcirculation and related tissues,

Although, in ancient times inflammation was recognised as being part of the healing process, up to the end of the 19 th century, inflammation was viewed as being an undesirable response that was harmful to the host. However, beginning with the work of Metchnikoff and others in the 19 th century, the contribution of inflammation to the body’s defensive and healing process was recognised,

Furthermore, inflammation is considered the cornerstone of pathology in that the changes observed are indicative of injury and disease. The classical description of inflammation accounts for the visual changes seen. Thus, the sensation of heat is caused by the increased movement of blood through dilated vessels into the environmentally cooled extremities, also resulting on the increased redness (due to the additional number of erythrocytes passing through the area).

The swelling (oedema) is the result of increased passage of fluid from dilated and permeable blood vessels into the surrounding tissues, infiltration of cells into the damaged area, and in prolonged inflammatory responses deposition of connective tissue.

Pain is due to the direct effects of mediators, either from initial damage or that resulting from the inflammatory response itself, and the stretching of sensory nerves due to oedema. The loss of function refers to either simple loss of mobility in a joint, due to the oedema and pain, or to the replacement of functional cells with scar tissue.

Today it is recognised that inflammation is far more complex than might first appear from the simple description given above and is a major response of the immune system to tissue damage and infection, although not all infection gives rise to inflammation.

• Inflammation is also diverse, ranging from the acute inflammation associated with S.
• Aureus infection of the skin (the humble boil), through to chronic inflammatory processes resulting in remodeling of the artery wall in atherosclerosis; the bronchial wall in asthma and chronic bronchitis, and the debilitating destruction of the joints associated with rheumatoid arthritis.

These processes involve the major cells of the immune system, including neutrophils, basophils, mast cells, T-cells, B-cells, etc. However, examination of a range of inflammatory lesions demonstrates the presence of specific leukocytes in any given lesion.

That is, the inflammatory process is regulated in such a way as to ensure the appropriate leukocytes are recruited. These events are controlled by a host of extracellular mediators and regulators, including cytokines, growth factors, eicosanoids (prostaglandins, leukotrines, etc), complement and peptides.

In fact, it is the discovery of many of these mediators over the past 20 years that has increased our understanding of the regulation of the inflammatory process whilst, at the same time, revealing its complexity. These extracellular events are matched by equally complex intracellular signalling control mechanisms, with the ability of cells to assemble and disassemble an almost bewildering array of signalling pathways as they move from inactive to dedicated roles within the inflammatory response and site.

Which cells and mediators come into play depends on wide range of factors. These include: what stage the process of inflation is at; the initiating event, i.e. type of pathogen, auto-immune, chemical or physical injury, etc.; the tissue or organ involved; whether the inflammation is of an acute, resolving form or chronic, non resolving or long-lasting type; whether formation of granuloma is involved, or whether scarring results.

The role of inflammation as a healing, restorative process, as well as its aggressive role, is also more widely recognised today. Inflammation is now considered as the full circle of events, from initiation of a response, through the development of the cardinal signs above, to healing and restoration of normal appearance and function of the tissue or organ.

However, in certain conditions there appears to be no resolution and a chronic state of inflammation develops that may last the life of the individual. Such conditions include the inflammatory disorders rheumatoid arthritis, osteoarthritis, inflammatory bowel diseases, retinitis, multiple sclerosis, psoriasis and atherosclerosis.

In order to study inflammation a multidisciplinary approach is necessary. Classically, it has required the study of the immune system, in order to understand the events involved in initiating and maintaining inflammatory conditions. Today it is recognised that the underlying genetics and molecular biology basis to cellular responses are also important in order to identify genetic predisposition to inflammatory diseases, while pharmacological studies are necessary to identify targets and develop novel treatments to bring relief from chronic life-threatening inflammatory conditions.

1. Thus research into inflammation includes not only the study of immunological and cellular responses involved but also the pharmacological process involved in drug development.
2. Many of the drugs used in the treatment of inflammatory conditions, predate our current understanding of the biochemical processes involved in the disease.

Traditionally, the standard treatments for rheumatoid arthritis has been to use a non-steroidal anti-inflammatory drug (NSAID), such as aspirin, for pain relief and to use corticosteroids or even disease-modifying anti-rheumatic drugs in an attempt to reduce other symptoms of the disease.

For many years the pharmaceutical industry attempted to develop NSAIDs which shared the therapeutic action of aspirin but which did not cause the main adverse event, namely gastric ulceration. This research led to the development of indomethacin, the fenamates, ibuprofen and many others. However, while all these drugs had clinical utility they also eroded the gastric mucosa.

In addition, this research also led to the development of some of the animal models still used in arthritis research today, such as carrageenin oedema and adjuvant arthritis ). The development of NSAIDs, with reduced potential to cause gastric ulcers, was finally realised with the demonstration that clinically useful NSAIDs inhibited the enzyme cyclo-oxygenase, which was also present in the gastric mucosa.

1. The finding that cyclo-oxygenase present in inflammatory lesions (COX2) was distinct from that found in the stomach (COX1) led to the development of selective COX2 inhibitors, such as celecoxib.
2. These drugs provide relief from many of the symptoms of arthritis but have a reduced potential to cause gastric ulceration,

The differential responsiveness to these, and other, therapeutic agents and, indeed, the induction of the inflammatory response in some patients with asthma by aspirin, has led to the concept of pharmacogenomics to understand individual drug sensitivities with a view to producing therapy tailored to the individual.

1. Similarly, glucocorticoids are widely used in the treatment of inflammation.
2. Unlike the NSAIDs these agents do not relieve pain but reduce inflammation by inhibiting leukocyte function.
3. The active ingredient responsible for the anti-inflammatory activity of adrenal cortex extracts was discovered in the 1940s.

This led to the use of cortisol as an anti-inflammatory and the development of potent synthetic agents typified by dexamethasone. However, because cortisol, and synthetic glucocorticoids, produce their therapeutic action at supra-physiological concentrations, adverse effects, such as suppression of the HPA-axis and Cushingoid changes are inevitable.

Many of these adverse effects can be avoided by giving glucocorticoids topically. This has led to the development of inhaled glucocorticoids for the treatment of inflammatory diseases of the respiratory tract and steroid containing creams for the treatment of skin inflammation. However, applying this approach to the treatment of rheumatoid arthritis necessitates the use of intra-articular injection.

Thus, there is a clear unmet medical need for a drug that provides relief from the symptoms of inflammation but can be given systemically. The fact that a large number of patients with severe chronic inflammatory disease fail to respond to conventional systemic or topical therapy resulting in a huge clinical and socio-economic burdon underlies the need to develop novel therapies.

• Thus, modern research has used molecular techniques to identify which genes are regulated by glucocorticoid receptors in an attempt to identify novel therapeutic targets.
• This work has attempted to fine tune the immune system through use of agents that inhibit specific pathways and mediators rather than to suppress immune cell activity.

Examples of such approaches include the development of anti-TNFa therapies, anti adhesion molecule therapies and inhibitors of cytokines believed to be pivotal in a given pathology, Furthermore, inhibitors of selective pro-inflammatory intracellular signalling pathways are currently in use e.g.

• Cyclsporin or under development e.g.
• NF-κB, p38 MAPK and PDE4 inhibitors,
• As we understand more about the complexity of the inflammatory response and the actions of the currently available drugs the value of particular clusters of targets becomes apparent.
• However, the success of anti-TNFα therapy in RA underlines the importance of understanding/discovering the initial driver(s) of the inflammatory response in individual diseases and patients.

While research into inflammation has resulted in great progress in the latter half of the 20th century, we recognise that the rate of progress is accelerating. Furthermore, it is our perception that there is a need for a vehicle through which this very diverse research can readily be made available to the scientific community.

What is considered a vascular event?

Care from a recognized leader in blood vessel diseases Any condition that affects your blood’s circulation is considered vascular disease. Slowed, interrupted, or decreased blood flow can lead to a host of problems, including: Heart attack. Kidney failure. Limb loss.

Is acute inflammation vasodilation or vasoconstriction?

Acute Inflammation – An early, if not immediate, response to tissue injury is acute inflammation. Immediately following an injury, vasoconstriction of blood vessels will occur to minimize blood loss. The amount of vasoconstriction is related to the amount of vascular injury, but it is usually brief.

Vasoconstriction is followed by vasodilation and increased vascular permeability, as a direct result of the release of histamine from resident mast cells. Increased blood flow and vascular permeability can dilute toxins and bacterial products at the site of injury or infection. They also contribute to the five observable signs associated with the inflammatory response: erythema (redness), edema (swelling), heat, pain, and altered function.

Vasodilation and increased vascular permeability are also associated with an influx of phagocytes at the site of injury and/or infection. This can enhance the inflammatory response because phagocytes may release proinflammatory chemicals when they are activated by cellular distress signals released from damaged cells, by PAMPs, or by opsonins on the surface of pathogens. Figure \(\PageIndex \): (a) Mast cells detect injury to nearby cells and release histamine, initiating an inflammatory response. (b) Histamine increases blood flow to the wound site, and increased vascular permeability allows fluid, proteins, phagocytes, and other immune cells to enter infected tissue.

These events result in the swelling and reddening of the injured site, and the increased blood flow to the injured site causes it to feel warm. Inflammation is also associated with pain due to these events stimulating nerve pain receptors in the tissue. The interaction of phagocyte PRRs with cellular distress signals and PAMPs and opsonins on the surface of pathogens leads to the release of more proinflammatory chemicals, enhancing the inflammatory response.

During the period of inflammation, the release of bradykinin causes capillaries to remain dilated, flooding tissues with fluids and leading to edema. Increasing numbers of neutrophils are recruited to the area to fight pathogens. As the fight rages on, pus forms from the accumulation of neutrophils, dead cells, tissue fluids, and lymph.