Inflammation

Definition- Inflammation is a response of vascularized tissues that delivers leukocytes and

molecules of host defense from the circulation to the sites of infection and cell damage in order
to eliminate the offending agents.

 It is a responseden of vascular connective tissue towards injury regardless whatever

cause.
 Inflammation is defined as the reaction of the host tissue to injury.
Historical Highlights

 Clinical features of inflammation were described in an Egyptian papyredus dated around

3000 BC, Celus a Roman writer of the first century AD, first listed the four cardinal signs
of Inflammation
 Rubor (Redness)
 Tumor (Swelling)
 Calor (Heat)
 Dolor (Pain)
Purpose of Inflammation-

 Remove the cause of injury

 Neutralize the cause of injury
 To remove the dead cell when injury occurred
Causes of Inflammation-

1. Infections-
Bacterial, viral, fungal, parasitic and microbial toxins are among the most common and medically
important causes of inflammation.
Different infectious pathogens elicit varied inflammatory responses, from mild acute
inflammation that causes little or no lasting damage and successfully eradicates the infection to
severe systemic reactions that can be fatal, to prolonged chronic reactions that cause extensive
tissue injury.

2. Tissue Necrosis-
Tissue Necrosis elicits inflammation regardless of the cause of cell death.
Cells may die because of ischemia (reduced blood flow, the cause of myocardial infarction),
trauma and physical and chemical injury (e.g., thermal injury as in burns)
Several molecules released from necrotic cells are known to trigger inflammation.
 3. Immune Responses/Reactions-
It also called hypersensitivity
These are the reactions in which the normally protective immune system damages the individual
own tissues. The injurious immune responses may be inappropriately directed against self-
antigens, causing auto immune diseases or may be reactions against environmental substances,
as in allergies, or against microbes.
4. Foreign Bodies-
Splinters, dirt, sutures may elicit inflammation by themselves or because they cause traumatic
tissue injury or carry microbes .
Physical agents like heat, cold, radiation, mechanical trauma.

1. Recognition-

 Recognition of the noxious agent that is the initiating stimulus for inflammation.
 The cells involved in inflammation on (tissue-resident sentinel cells, phagocytes and
others) are equipped with receptors that recognize microbial products and substances
released from damaged cells.
2. Recruitment-
Recruitment of leukocytes and plasma proteins into the tissues. Since blood perfuses every
tissue, leukocytes and proteins such as complement can be delivered to any site of microbial
invasion or tissue ivyury.
When pathology microbes invade the tissues or tissue cell die, leukocytes (fruit mainly
neutrophils, later monocytes and lymphocytes) and plasma proteins are rapidly recruited from
the circulation to the extravascular site.
3. Removal-
Removal of the stimulus for inflammation is accomplished mainly by phagocytic cells, which
ingest and destroy microbes and dead cells.

4. Regulation-
Regulation of the response is important for terminating the reaction when it has accomplished
its purpose.
 5. Repair-
Repair consists of a series of events that heat damaged tissue. In the process the injured tissue
replaced through regeneration of surviving cells and filling of residual defects with connective
tissue.
Recognition of Microbes and Damaged Cells-
Recognition of microbial components or substances released from damaged cells is the initiating
step in inflammatory reactions.
The cells and receptors that perform this function evolved to protect multicellular organism from
microbes in environment.
Several cellular receptors and circulating proteins are capable of recognizing microbes.

Cellular receptors for microbes-

Cells express receptors in the plasma membrane (for extracellular microbes). The endosomes and
cytosol that enable the cells to sense the presence of foreign invaders.
The best defined of these receptors belong to the family of toll-like receptors
The receptors are expressed on many cell types including epithelial cells, dendritic cells,
macrophages and other leukocytes.
Receptors produced triggers production of molecules.
Sensors of Cell damage-

All cells have cytosolic receptors, such as NOD like receptors such as NOD like receptors that
recognize diverse molecules that are liberated of cell damage.

These receptors activate a multiprotein cytosolic complex called inflammasome which induces
the production of cytokine interleukin IL-1, IL-1 recreates leukocytes and thus induce
inflammation.

Circulating proteins-
The complement system reacts against microbes and produces mediators of inflammation.
A circulating protein called mannose binding lectin recognizes microbial sugars and promotes
ingestion of the microbes and the activation of the complement system.
Types of Inflammation
1. Acute Inflammation-
 Acute Inflammation is rapidly developing inflammatory response which is short duration.
Ouset-fast minutes or hours
Cellular- Mainly neutrophils infiltrate
Tissue injury- usually mild
Local and systemic signs- prominent
Chronic Inflammation-

 Inflammation response last very long ouset-slow-days.

 Cellular - Monocytes/macrophages and lymphocyte infiltrate
 Tissue injury – often severe and progressive fibrous
 Local and syntenic signs – less
Acute Inflammation has three major components
1. Dilation of small vessels to an increase in blood flow.
2. Increased permeability of the microvasculature enabling plasma proteins and leukocytes
to leave the circulation.
3. Immigration of leukocytes from the micro-circulation their accumulation is the focus of
injury and their activation to eliminate the offending agent.
Causes of Acute Inflammation

 Microbial infection e.g., Bacteria, virus.

 Mechanical trauma cutting, bruising and crushing.
 Hypersensitivity reaction. This is an altered state of immunological response.
 Irritant and corrosive agents.
 Radiation injury.
 Tissue nerveius – Infarction
 Injury due to cold and heat
Inflammatory cells in acute inflammation-
 Neutrophils
 Macrophages
Reactions of Blood vessels in Acute Inflammation
The vascular reactions of acute inflammation consist of changes in the flow of blood and the
permeability of vessels, both designed to maximize the movement of plasma proteins and
leukocytes out of the circulation annnd into the site of infection or injury.
The escape of fluid, proteins and blood cells from the vascular system into the intersitial tissue
or body cavities is known as exudaaation.
A transudate is fluid with low protein context (most of which is albumin), little or no cellulose
material and low specific gravity.
Changes in acute inflammation-
1. Vascular changes
2. Cellular changes
3. Chemotaxis
Changes in vessels-

The earliest charges following an injury or trauma cureww described by Lewis in 1927.
These changes are known the triple response

 Flush
 Flare
 Weal
When a trauma such as a stroke or a scratch occurs on the skin, there is almost an immediate
white line formation.
This is due to a momentary vasoconstriction; a persistent vasodilation follows. First the arterioles
and then the capillaries dilate.
This type of vascular response causes formation of red lines called flush. This is followed by flare.
This appears 15 to 30 seconds after the appearance of the red lines called flush.
Features of Chronic inflammation-

Chronic Inflammation is presence of chronic inflammatory cells and macrophages, granulation

tissue formation, lymphocytes, plasma cells.
Vascular events-
Flow different vessels
Reaction of changes of vascular system/blood vessel
1. Hemodynamic changes
2. Increased vascular permeability
Hemodynamic changes

 The earliest feature of inflammatory response result from change in vascular flo.
1. Transient vasoconstriction-
 For short duration
 First event
 Vessels willldl narrow.
2. Vasodilation-
 Arterioles dilated
 Increased blood supply
 Slow flow of blood
 Due to increased blood supply redress or warm at the site of inflammation
 After vasodilation, the local hydrostatic pressure resulting in transudation of fluid in to
the extracellular space.
 This is responsible for swelling at the local site of acute inflammation.
3. Slowing or staris-
Slowing or staris of microcirculation follows which causes increased concentration of red cells
and thus raised blood viscosity.
4. Leucocytic marigination
(2) Increased vascular permeability
1. Contraction of endothelial cells

 It occurs mainly in vacoules.

 In vacoules endothelium cells develop temprary gaps.
 It is mediated release by the release of histamin bodykinin.
2. Contraction or mild endothelilal damage

 Leukocytes (W.B.C)
 Direct damage.
 In this there is structural reorganization of the cytoskeleton of endothelial cells that
causes reversible retraction at the intercellular function or mild form of endothelial
damage.
 3. Direct injury to endothelial cells-
 Direct injury causes cell necrosis and appearance of gaps at the site of detached endo
cells.
 Process of thrombosis (blood clot) involving platelets of fibrin is initiated at damaged
endo cells.
4. Endothelial injury by leucocytes-
Adherence of leucocytes to endothelium at the site of inflammation may result in activation of
leucocytes
Newly formed capillaries under the influence of vascular endothelial growth factor during the
process of repair and in tumours are excessively leaky.
Cellular events-

1. Exudation of W.B.C.
2. Phagocytosis

1. Exudation of W.B.C.
Escape of leucocytes from the lumen of microvascular to the interstial tissue.
Margination

 Normally central stream of cell comprised by W.B.C + R.B.C and peripheral cell layer of
plasma close to vessel wall.
 Due to slowing and staris W.B.C come to margin and have to leak out from endo gap.
 Neutrophils of central column close to the vessel wall, this is known as pavementing.
2. Rolling-
Peripherally marginated and pavemented neutrophils slowly roll over the endothelial cells linig
the vessel wall.
Mediators- Cell Adhesion molecule (CAM)

Selectins- There are the cell adhesion molecules and present on endothelium cells.

3. Adhesion- Permanent bond of W.B.C with endo cells.

Integrins- firm.

 On the W.B.C and ligards on endotherlium cells.

4. Transmigration / Diapedsis-
 Cell movement from blood vessels to intestitium
1) Neutrophils
2) Monocytes
5. Chemotaxis- Movement of W.B.C toward the direction of chemical molecule or damaged
cells with the help of chemoattractants
6. Phagocytes-
 Killing of bacteria.
 Neutrophils of macrophages are phagocytic cells
1) Recognition of attachement
2) Engulment
3) Killing and degradation
Chronic Inflammation-

 Inflammation of prolonged duration (weeks to years) is labelled as chronic inflammation

 Chronic inflammation is associated with asymptomatic response.
 This is red, irregular and blotchy zone, which the surrounds the red lines and is due to
arteriolar dilation. The flush and flare give the red colour (rubor) to the inflamed area.
The dilation of the vessels increases the blood flow raising the temperature (calor) and
also the hydrostatic pressure which along with increased permeability.
Morphologic patterns of Acute Inflammation-
The morphologic hall marks of acute inflammatory reactions are dilation of small blood vessels
and accumulation of leukocytes and fluid in the extravascular tissue.
Serous inflammation-
Serous inflammation is marked by the exudation of cell poor fluid into spaces created by cell
injury or into the body cavities lined by the peritoneum pleweaaa or pericardium.
Fibrous Inflammation-
A fibrous exudate develops when the vascular leaks are large or there is local procoagulant
stimulus. A fibrous exudate is characteristics of inflammation in the living of body cavities, such
the meninges, pericardium and pleurea.