An Introduction to Inflammation


Introduction

Inflammation can be characterised by 5 main features (names in brackets are the Latin), these are:

  • Swelling (tumour)
  • Heat (calor)
  • Redness (rubor)
  • Pain (dolor)
  • Loss of function (functio laesa)

Inflammation is a protective response by the body towards cell injury. Cell injury may be due to; necrotic cells or tissue, the introduction of microbes (such as viruses or bacteria), toxins, hypoxia, etc. Inflammation is therefore the body’s way of attempting to remove the primary cause of inflammation and any damage that may have occurred as a result (Healing and repair). However if inflammation did not occur, then the body would be unable to deal with wounds and infections letting them go unchecked and progressively destroy the tissue. All injured organs would therefore be unable to regain function, eventually leading to mortality.

Inflammation is a complicated series of biological reactions, only taking place in vascularised tissue, simply however it works by attempting to remove, dilute or barricade the injurious/pathogenic agent or tissue. Its secondary role is to induce the healing and the repair of the damaged tissue. The result of this is an accumulation of leukocytes and fluid in the vascularised tissue.

It is also important to remember that chronic inflammation may pose problems to the body; these may be hypersensitivity reactions, autoimmune reactions or organ dysfunction due to the formation of scars/obstructions caused by fibrosis e.g. hay fever (hypersensitivity) or arthritis (autoimmune response).

The Inflammatory Response

As said before, an inflammatory response will only occur in vascularised connective tissue. A typical inflammatory response will involve the utilisation of plasma, circulating cells (leukocytes), blood vessels (endothelial cells) and other cells/extracellular matrix in the connective tissue.

The inflammatory response is mediated by chemical factors which are derived from the plasma or from the cells. The chemical mediators are triggered by an inflammatory stimulus which could include anything from a splinter (foreign material) to necrotic cells. Necrotic tissue/cells are able to contribute to inflammation (as opposed to triggering the inflammatory system) by producing their own inflammatory mediators. The chemical factors involved in the whole process both amplify the inflammatory response and impact on its progression.

The inflammatory response will only stop when the initial stimulus is removed and all the chemical mediators which arose as a result are inhibited (or dissipated).

Components of Inflammation

Some of the main components of inflammation include:

Connective tissue layer:

  • Mast cells – Resident cells of tissues which contain many granules rich in histamine and heparin. They play an important protective role as well, being intimately involved in wound healing and defence against pathogens.
  • Fibroblasts – A type of cell which synthesizes the extracellular matrix and collagen and also plays a critical role in wound healing.
  • Macrophages – Resident large phagocytes (Some also circulate in the blood stream)

The Circulating Cells:

  • Polymorphonuclear Leukocytes (Neutrophils)
  • Lymphocytes
  • Monocytes
  • Eosinophils
  • Basophils
  • Platelets

The Extracellular Matrix:

  • Collagen and Elastin fibres – These are structural fibrous proteins
  • Proteoglycans
  • Adhesive glycoproteins (Fibronectin, laminin, non-fibrillar collagen, tenascin and others)

The Extracellular Matrix (ECM)

The ECM is a network of locally secreted and assembled proteins, such as collagen and elastin. It forms in the spaces surrounding cells and linkage occurs between cells and the ECM by adhesive glycoproteins (such as Fibronectin, laminin, non-fibrillar collagen, tenascin and others). It also consists of proteoglycans which are usually attached to the proteins. They have a net negative charge that attracts water molecules, keeping the ECM and resident cells hydrated. Proteoglycans may also help to trap and store growth factors within the ECM.

The function of the ECM is to sequester molecules such as water (using the mechanism described above), it also acts as a reservoir for growth factors and a substratum for cells to adhere, migrate and proliferate.

Terms Associated With Inflammation

The inflammatory response can be classified as either:

  • Acute inflammation – Typically these are of relatively short duration, from a few minutes to a few days. The main characteristics of acute inflammation are; exudation (see below) of fluid and plasma proteins (oedema) and the emigration of leukocytes (predominantly neutrophils)
  • Chronic inflammation – Chronic inflammation is of longer duration and is associated with:
    • The presence of lymphocytes and macrophages
    • Proliferation of blood vessels
    • Fibrosis
    • Tissue necrosis

Definitions:

  • Exudation – The escape of fluid, proteins and blood cells from the vascular system into the interstitial tissue or body cavities
  • Exudate – Inflammatory extravascular fluid which contains; a high protein concentration, much cellular debris and a specific gravity (density in relation to water) of >1.012. The specific gravity of >1.012 is due to the increased permeability of small blood vessels in the area of injury.
  • Transudate – This is fluid with a low protein content (of which the main constituent is albumin) and it has a specific gravity of <1.012 due to the ultrafiltrate of blood plasma which results in a hydrostatic imbalance across the vascular endothelium. Permeability of the endothelium is not altered.
  • Oedema – Excess fluid in the interstitial or serous cavities (The fluid can be either transudate or exudate)
  • Pus – Inflammatory exudate rich in leukocytes (predominantly neutrophils) and cell debris.
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