S2L1 - Acute Inflamation Flashcards
What is the purpose of inflamation?
To deal with cell injury or insult by removing the causative agent (microorganisms, foreign particles and necrotic tissue).
What are the cardinal signs of inflammation?
Calor - heat Rubour - redness Dolor - pain Tumor - swelling Loss of function
The acute inflammatory response results in oedema, fibrin and neutrophils accumulating in tissue. What processes do these result from?
Haemodynamic changes
Alterations in permeability of blood vessels
Recruitment and migration of neutrophils
Haemodynamic changes are part of the acute inflammatory response. Through what process does this occur, and what is its consequence?
Vasodilation of arterioles due to mediators such as NO and histamine results in increased blood flow and subsequently hyperaemia. This results in the characteristic redness (rubor) and heat (calor).
Alterations in the permeability of blood vessels are part of the acute inflammatory response. Through what process does this occur, and what is its consequence?
Endothelial cells swell and partially retract (gap formation) so the endothelium becomes permeable.
This allows fluid, salt and proteins to enter the damaged area (oedema).
This process is due to mediators such as platelet activating factor (PAF) and histamine, which increases vascular permeability.
What is oedema? What is exudate, and how does it differ to transudate?
Oedema is the accumulation of exess extravascular fluid, resulting in swelling.
Inflamatory fluid, known as exudate, has a high protein concentration. Conversly, transudate has a low protein content. Exudate is caused by alteration in the hydrostatic or oncotic pressure in the transudate,
What are the different types of exudate arising from oedema?
Fibrinous - large amounts of fibrinogen
Purulent (pus) - pyogenic bacterial infections
Recruitment and migration of neutrophils is part of the acute inflammatory response. What are the four steps in the sequence of events leading to the accumulation of cells at the inflammatory site?
Margination
Adhesion (pavementing)
Emigration
Chemotaxis
Describe the process of margination, the first step in the recruitment and migration of neutrophils.
The arterioles dilate, and stagnation in the microcirculation displaces cells from the central axial flow, moving the white blood cells to the periphery of the vessels. this leads to the next step: adhesion.
Describe leukocyte adhesion, the second step in the recruitment and migration of neutrophils.
Leukocytes bind to endothelial cells due to the expression of complementary adhesion molecules. Inflammatory mediators increase this expression. Genetic deficiency of adhesion molecules results in repeated bacterial infections.
What type of cell increases expression of adhesion molecules on endothelium? Why is p-selectin, ICAM-1 and Beta-2-integrin important?
Cytokines (eg. IL-1, TNF), especially selectins. eg. p-selectin is important as it acts as a tethering molecule, rolling the polymorphonuclear neutrophil along the vessel wall.
Intercellular adhesion molecule-1 (ICAM-1) and Beta-2-integrin promotes adhesion of neutrophils.
Describe leukocyte emigration, the third step in the recruitment and migration of neutrophils.
Adhesion of the polymorphonuclear neutrophil activates the cytoskeletal elements, leading to the extension and contraction of pseudopodia.
Leukocytes then push through the gaps between the endothelial cells in the venules and digest teh basement membrane by releasing proteolytic enzymes.
Describe chemotaxis, the fourth and final step in the recruitment and migration of neutrophils.
Chemotaxis is the directional movement of phagocytic cells towards areas of injury, necrotic tissue, or bacterial invaion.
It is mediated by a series of chemical messengers along a gradient, eg:
- bacterial products
- cytokines (eg. IL-8, C5a, leukotrieneB4)
- denatured proteins
Neutrophilic phagocytosis allows the destruction of foreign material and removal of damaged tissue. How does this happen?
The neutrophils recognise dead tisse/foreign material either directly via mannose receptors, or via opsonins and FC and C3b receptors, then bind to it. They then engulf the material. Phagosomes then fuse with lysosomes, which contain free radicals (aerobic) or enzymes (anaerobic), which destroys the material.
What are the metabolites used in nuetrophilic phagocytosis when the phagosome fuses with lysosomes?
Oxygen dependent system (aerobic - production of oxygen metabolites):
- superoxide ion; hydrogen peroxide; hydroxyl radical
Oxygen indipendent system (anaerobic):
- enzymes; lysozymes and hydrolases
*some bacteria may survive eg. TB
