The classical example to the skin's response to a scratch - a wheal and flare reaction. There is a red line and swelling.
- Bodies response to injury and basis of tissue response
- Occurs over seconds, minutes, hours, and days
- It is the local reaction of living tissue to injurious agents.
- It is the vascular response to injury.
Comparing types of inflammation
- Acute inflammation : Of sudden onset and short duration
- Chronic inflammation: Of gradual onset and long duration
The five classical signs of acute inflammation
- rubor (redness)
- calor (increased heat)
- tumour (swelling)
- dolor (pain),
- functio laesa (loss of function)
The principal causes of acute inflammation are
- Microbial infections, e.g. pyogenic bacteria, viruses
- Hypersensitivity reactions, e.g. parasites, tubercle bacilli
- Physical agents, e.g. trauma, ionising irradiation, heat, cold
- Chemicals, e.g. corrosives, acids, alkalis, reducing agents, bacterial toxins
- Tissue necrosis, e.g. ischaemic infarction.
Events in Acute Inflammation
- FLOW: Initial decrease in flow with vasoconstriction then increased blood flow due to dilation of arterioles, capillaries and postcapillary venules supplying the region: causes warmth and erythema locally.
- PERMEABILITY: Increased permeability of the capillaries, allows fluid and blood proteins to move into the interstitial spaces: causes localised swelling. The increased permeability of the capillaries occurs because the endothelial cells separate from one another at their edges. Endothelial swelling with the widening of intra-endothelial gaps of postcapillary venules. OR ii- Major endothelial damage involving arterioles, capillaries and venules. This results in leakage of proteinaceous fluid (exudate) which causes inflammatory oedema.
- EXUDATE: Due to increased vascular permeability. Rich in protein esp. fibrin - Coagulates on standing. - High specific gravity > 1.018).Contains inflammatory cells. - Occurs late in inflammation. The initial response is often a cell-free transudate due to increased hydrostatic pressure.
- PAIN: only if there are appropriate sensory nerve endings in the inflamed site
- INFLAMMATORY CELLS
- Appear in the first 24 hours of inflammation. They are of short life span. Increased Neutrophils in the peripheral blood. It occurs mainly during pyogenic bacterial infection and in the early phase of infarction.
- Comes from the bone marrow reserve pool. - Usually, this is associated with the appearance of less mature forms ( band or stab neutrophils) (left shift). Migration of neutrophils (and some macrophages) out of the capillaries and venules and into interstitial spaces. Neutrophils contain granules containing H2O2 and HO are the main products produced by neutrophil activation.
- They cause endothelial damage, increased vascular permeability, Inactivation of anti-peptidases as a-1 antitrypsin resulting in the destruction of the extracellular matrix. They injure other cell types e.g parenchymal cells and RBCs.
- They are important for Phagocytosis of bacteria and killing and destruction of engulfed bacteria by releasing enzymes from the cytoplasmic granules (lysosomal enzymes).
Monocytes-Macrophages replace neutrophils after 2-3 days in the course of inflammation and persist in chronic inflammation. They have a longer life span than neutrophils and can divide and proliferate within the inflamed tissue. Monocytosis:- Increased number of peripheral monocytes - Occurs in tuberculosis, salmonella infection, typhus and brucellosis.
Types of acute inflammatory exudate
- Serous:- Clear fluid with few cells and fibrin e.g in burns and the common cold.
- Serofibrinous Fluid rich in fibrin mainly in serous sacs (pleura and pericardium).
- Pus Thick, fluid rich in cells (living and dead neutrophils). Occurs in suppurative inflammations.
Cell Adhesion Molecules
- The classical acute inflammatory cell is the neutrophil which in acute inflammation move from blood vessels into the tissues. They bind to the endothelium using cell adhesion molecules (CAMs), found on the surfaces of neutrophils and on endothelial cells in injured tissue. The binding occurs in two steps.
- Selectins: In the first, adhesion molecules called selectins lightly tether the neutrophil to the endothelium, so that it begins rolling along the surface.
- ICAMS: a much tighter binding occurs through the interaction of ICAMs on the endothelial cells with integrins on the neutrophil.
- The neutrophils then squeeze through gaps between adjacent endothelial cells into the interstitial fluid, a process called diapedesis. They are attracted by chemotactic factors released by local tissue.
- The initial step is margination whereby neutrophils move close to the endothelium. There is then Rolling which is mediated by the action of E-selectins which bind endothelial cells loosely to leucocytes (Through sialyl-Lewis X modified glycoprotein) producing a characteristic rolling movement of leucocytes along the endothelial surface.
- Adhesion:- Leucocytes adhere to the endothelial surface through the interaction of integines (leucocytes) and the immunoglobulin -family adhesion proteins (endothelium) and then
- Transmigration: is the movement of leucocytes across the endothelium. -It is mediated by platelet-endothelial cell adhesion molecule-1 (PECAM-1) expressed on both the endothelium and the leucocytes
- Once outside the blood vessel, the neutrophil follows various diffusing chemotactic factors. Examples include the chemokines and the complement peptide C5a, which is released when the complement system is activated either via specific immunity or innate immunity.
- Chemotaxis is mediated by diffusible chemical agents, movements of leucocytes occur along a chemical gradient. Chemotactic agents act by stimulating the contractile elements within leucocytes.