INFLAMMATION

INTRODUCTION: inflammation is the local physiological response to tissue injury. It is protective endeavor
by the body to remove the injurious stimuli as well as to initiate the process of healing and repair. In the absence
of an inflammatory response, wounds and infections would fail to heal and progressive destruction of the tissue
would ensue, thereby compromising the survival of the organism.

Inflammation follows two basic patterns are acute and chronic.

Acute inflammation: is short lived and may last for a few minutes to a few days only, and involves infiltration
by neutrophils and exudation of fluid and plasma proteins.

Chronic inflammation: is of longer duration and is associated with lymphocytes, macrophages, proliferation of
blood vessels and fibrosis.

Inflammation is terminated when the injurious stimulus is removed or once the mediators of inflammation have
degenerated or inhibited.

ACUTE INFLAMMATION

Acute inflammation is the initial reaction of tissue to injury. There are three major components of acute
inflammation:

1. Changes in the caliber of blood vessels, resulting in an increase in the blood flow.

2. Structural changes in microvasculature that allow leakage of plasma proteins and leukocytes.

3. Emigration of neutrophils and their accumulation at the site of injury.

Causes of Acute Inflammation:

 Bacterial, viral, parasites and other infections.

 Physical injuries due to trauma, and exposure to ionizing radiation, heat and cold.

 Injury caused due to exposure with chemicals such as corrosives agents, acids, alkalis, reducing agents
and bacterial toxins, etc. due to tissue necrosis caused due to ischemia or infarction.

Cardinal signs of Acute Inflammation:

 Swelling (tumor)

 Redness (rubor)

 Pain (dolor)

 Heat (calor)

 Loss of function (function laesa)

Pathological changes in Acute Inflammation:

Vascular Events:

The sequence of the hemodynamic changes in acute inflammation is as follows:

1. Vasodilation: There is a dilation of the blood vessels, which begins with the arterioles, followed by the
capillaries and venules. This leads to a local increase in vascular flow, which manifests as redness and
warmth.

2. Increase permeability of the microvasculature: Leads to escape of protein rich fluid (exudates) into
the interstitium. The accumulation of fluid in the interstitial space is called edema, which gives rise to
the local swelling. The mechanisms contributing to increased vascular permeability are contraction of
endothelial cells moving intracellular junctions apart, endothelial retraction, direct endothelial cells
moving intracellular junctions apart, endothelial retraction, direct endothelial injury caused by
leukocytes and excessively leaky newly formed blood vessels (neoangiogenesis).

3. Loss of fluid results in concentration of blood cells and hence increases the viscosity of blood, leading
to slowing of the flow in the microvasculature (stasis).

4. Vascular stasis leads to sticking of leukocytes (predominantly neutrophils) to the vascular endothelium-
leucocytic margination.

Cellular Events

The main function of inflammation is the delivery of leukocytes to the site of injury. Leukocytes ingest the
offending agent, kill microbes and degrade foreign antigens and necrotic tissue. Cellular events of acute
inflammation can be divided into two phases are extravasation and phagocytosis.

Extravascation of neutrophils:

The migration of neutrophils from the vascular lumen to the interstitial tissue is called extravasation and
involves the following sequence of events:

1. Margination: Vascular stasis leads to a peripheral orientation of the leukocytes, i.e leukocytes, which
normally flow in the central column of the bloodstream, accumulate towards the endothelial surface of
the vascular lumen. This process is called margination.

2. Rolling and adhesion: The accumulated leukocytes roll over the endothelial cells lining the vessel wall,
and adhere transiently to the endothelial cells (adhesion). The main adhesion molecules are selectins,
integrins, immunoglobulins and mucus-like glycoproteins.

3. Diapedesis: Transmigration of leukocytes from the vascular lumen to the interstitial tissue, across the
endothelium is called diapedesis. Leukocyte diapedesis occurs predominantly in the venules.

4. Chemotaxis: It is defined as movement oriented along a chemical gradient. After extravasation into the
interstitial space, leukocytes migrate towards the site of injury by chemotaxis.

Neutrophils are the predominant cells in the inflammatory infiltrate during the initial 24 hours of acute
inflammation and are then replaced by monocytes in the next 24-48hours.

Phagocytosis
Phagocytosis a process of engulfment of solid particulate material by the cells. There are two types of
phagocytic cells-polymorphonuclear neutrophils, also known asmicrophagesand monocytes, also known as
macrophages. Phagocytosis involvesthree distict steps are recognition and attachment, engulfment and killing.

Recogonition and attachment of the particle/microbe to be ingested by the leukocyte. Many microbes are coated
with naturally occurring factor in the serum called opsonins, which facilitate recognition by the phagocytic
cells. Opsonins are recognized by receptors on theleukocytes, and opsonization of the particles markedly
enhances the efficiency of phagocytosis.

Engulfment: The leukocytes/phagocytic cells extend pseudopods around the particle to be engulfed, and
subsequently form a phagocytic vacuole or phagosome. This is followed by fusion of the membrane of the
phagosome with that of the lysosome, leading to formation of a phagolysosome. The contents of the granules of
the polymorphonuclear cells are secreted into the phagolysosome.

Killing or degradation: This stage involves the killingof bacteria by a number of bactericidal mechanisms, like
oxygen dependent bactericidal mechanism, oxygen independent bactericidal mechanism and nitric oxide
mechanism. In all these processes there in production of reactive oxygen species, which can kill the bacteria
directly. The killed organisms are eventually degraded by hydrolases and other lysosomal enzyme.

Chemical mediators of inflammation:

The chemical mediators of the inflammation are either derived from the cells(cell derived) or from the plasma
(plasma derived).

Effects of acute inflammation:

Acute inflammation has local and systemic effects, which may be both beneficial and harmful.

Beneficial effects of inflammation:

 Dilution of toxins, such as those produced by bacteria and allows them to be carried away by lymphatics
thereby stimulating immune response.

 Entry of antibodies, due to increased vascular permeability.

 Transport of drugs such as antibiotics to the site where bacteria are multiplying.

 Fibrin formation from exuded fibrinogen, which serves as a matrix for granulation tissue formation.

 Delivery of nutrients and oxygen, which are essential for repair and healing, byincreased blood flow
through the area.

Harmful effects of inflammation:

 Digestion of normal tissues: Enzymes such as collagenases and proteases may digest normal tissues,
resulting in their destruction; for example, in type III hypersensitivity reactions, in some types of
glomerulonephritis and in abscess cavities.

 Swelling: The swelling of acutely inflamed tissues maybe harmful; for example the swelling of
epiglottis due to hemophilus influenza in children may obstruct the airway resulting in death. Acute
 meningitis or cerebral abscess may raise the intracranial pressure to the point where blood flow in the
brain is impaired, resulting in ischemic damage to the brain.

 Inappropriate inflammatory response: Such as those which occur in type I hypersensitivity reactions
where the provoking environmental antigen otherwise poses no threat to the individual. Such allergic
inflammatory responses may be life-threatening, for example, extrinsic asthma.

Morphological forms of acute inflammation:

Acute inflammation may manifest in varied morphological forms. An inflamed organ is referred to by adding
the suffix ‘itis’ to its name; for example, acute appendicitis, acute salpingitis and acute pancreatitis. Few
morphological varieties of acute inflammation are as listed below;

1. Ulcer: It is a localized breach in the surface epithelium of an organ due to inflammation. Common sites
of ulceration are skin and mucosa of gastrointestinal tract. Initially there is vasodilation and infiltration
by polymorphs, which is later replaced by lymphocytes, plasma cells and macrophages and subsequently
heals by scarring.

2. Abscess formation: An abscess is formed when there is tissue necrosis due to intense neutrophilic
infiltration in the inflamed tissue. A cavity is formed, which is called abscess and contains purulent
exudates. This process of abscess formation is called suppuration.

3. Bacterial infection of blood: There are mainly three conditions-bacteremia wherein there is presence of
small number of bacteria in the blood, which do not multiply significantly, septicemia means presence
of highly pathogenic, rapidly multiplying bacteria in the blood stream, and pyemia refers to circulation
of minute septic thrombi in the blood, which lodge at distant sites and lead to development of septic
infarcts and pyemic abscesses.

4. Celllulitis: It is an inflammation of soft tissues caused by the release of substances like hyaluronidases
by the bacteria.

5. Pseudomembranous inflammation: It is an inflammatory response of mucosal surfaces. Due to

denudation of the epithelium, plasma usually exudes on the surface where it coagulates and forms a false
membrane together with the necrosed epithelium.