Inflammation Flashcards
4 cardinal signs of inflammation
Redness (rubor) – secondary to vasodilatation and increased blood flow
Heat (calor) – localised increase in temperature, also due to increased blood flow
Swelling (tumour) – results from increased vessel permeability, allowing fluid loss into the interstitial space
Pain (dolor) – caused by stimulation of the local nerve endings, from mechanical and chemical mediators
2 phases of acute inflammation
Vascular Phase
- small blood vessels adjacent to the injury dilate and blood flow to the area increases. The endothelial cells initially swell, then contract to increase the space between them, thereby increasing the permeability
- Exudation of fluid leads to a net loss of fluid from the vascular space into the interstitial space, resulting in oedema. The fluid present is termed an “exudate“, and characteristically is high in protein
- The formation of increased tissue fluid acts as a medium for which inflammatory proteins (such as complement and immunoglobulins) can migrate through. It may also help to remove pathogens and cell debris in the area through lymphatic drainage.
Cellular phase
- The predominant cell of acute inflammation is the neutrophil. They are attracted to the site of injury by the presence of chemotaxins.
The migration of neutrophils occurs in four stages:
Margination – cells line up against the endothelium
Rolling – close contact with and roll along the endothelium
Adhesion – connecting to the endothelial wall
Emigration – cells move through the vessel wall to the affected area
Once in the region, neutrophils recognise the foreign body and begin phagocytosis. The phagosome is then destroyed via oxygen-independent (e.g. lysozymes) or oxygen-dependent (e.g. free radical formation) mechanisms.
Outcomes of acute inflammation
Complete resolution – with total repair and destruction of the insult
Fibrosis and scar formation – occurs in cases of significant inflammation
Chronic inflammation – from a persisting insult
Formation of an abscess
Abscess formation
An abscess is a localised collection of pus surrounded by granulation tissue.
Pus contains necrotic tissue with suspended dead and viable neutrophils and dead pathogens.
It forms when the primary insult is a pyogenic bacterium and extensive tissue necrosis occurs.
The initial inflammatory exudate forces the tissue apart, leaving a centre of necrotic tissue with the neutrophils and pathogens. Over time, the acute inflammation will cease and, if not surgically drained, the abscess will be replaced by scar tissue.
An abscess can be a source for systemic dissemination of a pathogen, with the abscess acting as a harbour for the infection. It can also cause continually rising pressures within the tissue, resulting in pain and destruction of local structures.
Chronic inflammation
In response to ongoing, unresolved insult.
Either from acute inflammation or arising denovo
Vasodilators
Histamine, Bradykinin, Complement (C3a, C5a), Leukotrienes (LTC4, LTD4), Prostaglandins (PGI2, PGE2, PGD2, PGF2)
Mast cell degranulation
Complement (C3a, C5a)
Chemotaxis
Interleukins (IL-8), PAF, Complement (C5a), Histamine
Lysozymal granule release
Complement (C5a), Interleukins (IL-8), PAF
Phagocytosis
Complement 3b
Pain
Prostaglandins (PGE2), Bradykinin, Histamine
Fever
Interleukins (IL-1, IL-6), TNF-α, Prostaglandins (PGE2)
Inflammatory cells chronic inflammation
Predominant cell for phagocytosis - macrophages. APCs derived from monocytes. Coordinated/targetted response. Release growth factors and cytokines.
Macrophages fuse and form multi-nucleated giant cells in chronic inflammation. They are produced in response to certain stimuli, such as a foreign body (foreign-body giant cell), mycobacterium tuberculosis (Langhans giant cell), or fat necrosis (Touton giant cell).
Lymphocytes work in conjunction with APCs to process antigens.
- B lymphocytes differentiate into plasma cells. Plasma cells are essential for antibody production, which are used for: Neutralising microbes and toxins (binding to and blocking the harmful effects of the antigen), to prevent infective and toxic effects of the antigen
Promote natural killer cells to destroy targeted and tagged pathogens (termed antibody dependant cellular cytotoxicity, or ADCC)
Facilitate easier phagocytosis by the innate immune cells (termed opsonisation)
- T helper lymphocytes (CD4+ cells) act to co-ordinate further targeted inflammatory responses, from both innate and adaptive immune cells. T killer lymphocytes (CD8+ cells) act to co-ordinate the targeted destruction of infected cells.
A granuloma contains a collection of elongated macrophages, termed epithelioid cells, surrounding a core of lymphocytes and giant cells attempting to break down the particles.
As granulomatous inflammation progresses, fibroblasts begin to lay down scar tissue, whilst the central core can become necrotic due to the release of enzymes (particularly seen in tuberculosis).
Granulomatous conditions
tuberculosis, sarcoidosis, Crohn’s disease, Rheumatoid arthritis, and Granulomatosis with polyangiitis (GPA)
