Inflammation Flashcards
What is inflammation?
The response of vascularised tissue that brings cells and molecules of host defences from circulation to site where they are needed, to eliminate offending agents.
What are 4 main causes of inflammation?
1) Infection
2) Tissue necrosis (eg. Ischaemia, Trauma, Chemical injury)
3) Foreign bodies
4) Immune rxns (eg. Autoimmunity, Hypersensitivity)
What are the differences between acute and chronic infection?
Acute:
- quick onset: mins - hrs
- mainly neutrophils
- mild and self-limiting injury and fibrosis
- prominent local and systemic signs
Chronic:
- slow onset: days
- monocytes/macrophages, lymphocytes
- severe and progressive injury and fibrosis
- less sever local and systemic signs
What are the 5 cardinal signs of (local) inflammation?
1) Redness
2) Warmth
3) Swelling
4) Pain
5) Loss of function
What are 3 systemic signs of inflammation?
1) Fever (via IL-1, TNF)
2) Loss of appetite
3) Loss of weight
What are the steps of acute inflammation?
1) Foreign Ag detected by mast cells and macrophages
2) Mast cells secrete histamines and prostaglandins → vasodilation → Redness and warmth
3) Exudate containing plasma, cells and proteins (including kinins → bradykinins)
4) Bradykinins + Prostaglandins (from macrophages) → stimulate free nerve endings → Pain
5) INF-α, IL-1ß from macrophages → Fever
6) Slower blood flow + endothelial selectins → margination of neutrophils → roll and adhere with integrins → transmigration into site of injury via chemokine gradient
What is the difference between exudate and transudate?
Exudate is caused by inflammation has a much higher protein and cells.
Transudate is caused by ↑hydrostatic pressure but ↓colloid (proteins) osmotic pressure.
What chemicals do mast cells produce?
Prostaglandins and histamines
What chemicals do Macrophages produce?
Prostaglandins, IL-1ß, TNF-α
Which chemicals cause vasodilation?
Prostaglandins and Histamine
Which chemicals cause pain?
Prostaglandins and Bradykinins (activated kinins from exudate)
Which chemicals cause fever?
IL-1ß and TNF-α → hypothalamus
What causes the loss of function?
Pain and swelling → voluntary loss of function
Tissue injury → involuntary loss of function
What enables the extravasation of neutrophils?
1) Vasodilation → ↓ speed of blood flow
2) Endothelial selectins slow neutrophils
3) Adherence by integrins
4) Transmigration through basal lamina into adventitia down the chemokine gradient
Which chemicals increase vascular permeability?
Histamine, c3a, c5a, Leukotrienes
Where do complements responsible for increased vascular permeability come from?
Blood plasma
What are the consequences of inflammation?
1) Resolution
2) Abscess formation
3) Fibrosis
4) Chronic inflammation
What are some determinants of resolution?
1) Tissue type (labile, stable, permanent)
2) Injury duration
3) Extent of tissue destruction
4) Nature of agent (eg. bacteria → abscess)
What are the 4 general patterns of acute inflammation?
1) Serous
2) Fibrinous (fibrosis)
3) Suppurative (pus → neutrophils, necrotic debris, bacteria)
4) Ulcer (defect in epithelial surface)
What are the components of pus?
Dead neutrophils, necrotic debris, bacteria
What forms when suppuration is localised?
Abscess
What is the difference between systemic inflammation and systemic effects of inflammation?
Systemic effects of inflammation are caused by local release of cytokines into circulation.
Systemic inflammation is associated with Sepsis.
What are 6 systemic effects of infection?
1) Pyrexia
2) Constitutional symptoms (malaise, lethargy, anorexia)
3) Weight loss
4) Reactive hyperplasia of reticuloendothelial system (lymph node swelling)
5) Haematological changes (eg. Anaemia, Leukocytosis, ↑ESR)
6) Amyloidosis (deposition of serum amyloid A in tissues)
What are the benefits and drawbacks of inflammation?
Benefits:
- toxin dilution
- Ab entry
- drug transport
- fibrin formation
- O2 and nutrient delivery
- stimulation of immune response
Drawbacks:
- Digestion of normal tissue
- swelling
- inappropriate response (eg. autoimmunity, atopy)
- can lead to abscess formation, chronic inflammation or fibrosis
