Mediators of Inflammation
Histamine
Prostaglandins
Leukotrienes
Cytokines
Chemokines
Platelet-activating factor
Complement
Kinins
What is inflammation?
Response of vascularised tissue to bring cells of host defence from blood circulation to site of inflammation (where foreign bodies are present) to eliminate these pathogens
Differences between acute and chronic inflammation (4)
- Acute onset is rapid (minutes/hours), chronic onset is slow (days)
- Infiltrate of acute inflammation consists of mostly neutrophils, infiltrate of chronic inflammation consists of macrophages and lymphocytes
- Cellular injury and fibrosis in acute inflammation is mild and self-limiting, in chronic inflammation it is often severe and progressive
- Local and systemic signs of acute inflammation are prominent, in chronic inflammation they are less prominent
Process of acute inflammation (think about the 5 presentations of acute inflammation!)
- Antigen enters the dermis
- Mast cells release histamine and prostaglandins and macrophages release prostaglandins, causing vasodilation of blood vessels, increasing blood flow and causing redness and warmth
- During vasodilation, endothelial cells separate, forming gaps, which causes plasma and protein to leak into the tissues, creating exudate, increasing extravascular fluid and causing swelling
- Kinins enter the gaps and are activated to form bradykinins. Bradykinins and prostaglandins stimulate nerve endings and send pain signals, causing avoidance of touching or moving and hence a loss of function.
- Chemokines are released by inflammatory cells, causing transmigration of neutrophils through endothelial gaps, allowing neutrophils to travel to the site of inflammation to carry out its actions by phagocytosis. Neutrophils have multilobulated nucleus and are comprised of 3 lobes in order to fit through endothelial gaps more easily. Neutrophils are inflammatory cells.
- Cytokines (e.g. IL-1, TNF) are released by macrophages that travel to other parts of the body (e.g. brain, hypothalamus), causing fever
Mediators of vasodilation
Histamine
Prostaglandins
Nitric Oxide
Mediators of increased vascular permeability
Histamine
Serotonin
C3a and C5a
Leukotrienes
Mediators of chemotaxis, leukocyte recruitment and activation
IL-1, TNF
Chemokines
C3a and C5a
Leukotrienes
Mediators of fever
IL-1, TNF
Prostaglandins
Mediators of pain
Prostaglandins
Bradykinins
Mediators of tissue damage
Lysosomal enzymes of leukocytes
Reactive oxygen species
Exudate vs Transudate (6)
- Exudate has higher specific gravity than transudate
- Exudate has higher protein concentration than transudate
- Exudate is cell rich, with many inflammatory cells, transudate is cell poor
- Exudate contains plasma fibrinogen and coagulates easily, transudate does not
- Exudate is not clear, transudate is clear
- Exudate is unilateral, results from increased vascular permeability or decreased lymphatic drainage. Transudate is bilateral, arises from increased capillary hydrostatic pressure or decreased capillary oncotic pressure.
Fluid in pleural cavity/pleural effusion: transudate or exudate?
Can be both!
Transudate: Heart failure
Exudate: Infection in the lungs/pneumonia with possible tumour
Role of lymphatics
Carry away exudate and injurious stimuli, then drain into lymph nodes for further deactivation by immune system
5 cardinal signs of acute inflammation
Heat
Redness
Swelling
Pain
Loss of function
Outcomes of inflammation
Abscess (pus) formation
Chronic inflammation
Resolution
Fibrosis with excessive fibrous layers (scar formation)
Systemic effects of inflammation
Fever, lethargy, nausea, weight loss
Swelling of lymph nodes
Haematological effects:
- increased erythrocyte sedimentation rate (RBCs settle faster because they clump faster)
- increased WBC production
- anemia because bone marrow HSCs are producing more WBCs and less RBCs
Special patterns of acute inflammation
Serous
Fibrinous
Suppurative
Ulcer
Serous acute inflammation
When exudate is cell poor, and not associated with infection
e.g. blister
Fibrinous acute inflammation
When there is a lot of fibrinogen in the exudate, and threads of fibrin are formed
e.g. pericarditis
Suppurative acute inflammation
When there is pus containing neutrophils, necrotic debris, bacteria
When it is localised, an abscess is formed
Ulcer acute inflammation
When there is a defect in the epithelium
e.g. gastric ulcer
What is chronic inflammation?
A response of prolonged duration in which inflammation, injury and attempts at repair can occur simultaneously
Can occur following acute inflammation or insidiously (e.g. in autoimmune disease such as rheumatoid arthritis)
Causes of chronic inflammation
Persistent infections that resist elimination
Hypersensitivity reactions (autoimmune, allergies)
Continuous exposure to toxins (exo, endo)
e.g. Exogenous - silicosis from silica; Endogenous - atheroscleorosi from cholesterol
Granulomatous inflammation: a type of chronic inflammation
Characterised by formation of granulomas aka aggregates of epithelioid histiocytes (macrophages)
Results in formation of multinucleated giant cells
Often with T lymphocytes, sometimes with central necrosis
