Acute Inflammation 1 Flashcards
Triple response
- Reddening = vasodilation
- Flare (red halo) = hyperaemia
- Wheal (swelling)= oedema
Vascular Response: Key Processes
1.Transient vasoconstriction –neurogenic – occurs within seconds 2.Arteriolar dilation –axon reflex arc capillary beds open: red & hot –histamine, nitric oxide 3.Increased blood viscosity –blood stasis –impedes outflow 4.Increased vascular permeability –fluid enters interstitial space (transudate) –hallmark feature of AI
Increased vascular permeability: transudate vs exudate
Transudate: low protein ( albumin) less than 30g/L, low cells ( less than 1500 cells per micro/L) NON- INFLAMMATORY RESPONSE
Exudate: high protein ( greater than 30g/L), high cells ( greater than 5000 per micro/L) INFLAMMATORY EFFUSION
Oedema
Increase in interstitial fluid
Usually classifies as a transudate ( NON- INFLAMMATORY)
Increased Vascular Permeability
- Gaps between endothelial cells
•Vasoactive mediators (histamine, leukotrienes)
•VEGF-induced channels - Direct endothelial injury
•Toxins, burns, chemicals - Leukocyte-mediated injury to endothelium
•Leukocyte products (ROS, enzymes) - Angiogenesis
•Leakage from new vessels - Radiation damage
•Sunburn, x-rays, UV radiation damage to endothelial cells
Inducers of Acute Inflammation
- Infections
- Trauma (+/- sterile)
- Physical and chemical agents
- Foreign bodies
- Tissue necrosis (“bad death”)
- Hypersensitivity reaction
Components of Acute Inflammation
•Vascular Response
–Changes to blood flow and vessel permeability
•Cellular Response
–Recruitment of leukocytes
•Soluble mediators
–Co-ordinators of the tissue response
•Molecular “sensors”
–Control the type of inflammation
Acute Inflammation
•Immediate response to tissue damage
•Primarily an innate response
–Cells and molecules of the innate immune system: non-specific
•Local response to limit tissue damage
•Characterised by:
–Leakage of blood proteins (fibrinogen > fibrin)
–Recruitment of leukocytes from the blood
•Inflammatory exudate
–hallmark feature of AI
Cardinal Signs of Acute inflammation
- Heat (calor)
- Pain (dolor)
- Redness (rubor)
- Swelling (tumor)
- Loss of function (functio laesa)
Leukocyte activation
People sometimes say money counts
Production of arachidonic acid metabolites
Secretion/ degranulation of lysosomal enzymes
Secretion of cytokines
Modulation of leukocyte
Cell division induction
What are the three types of soluble mediators
Vasoactive amines
Cytokines
Arachidonic acid metabolites
What is the arachidonic acid metabolites pathway
Phospholipase forms 5-lipoxygenase and cyclooxygenase
5-lipoxygenase forms 12-lipoxygenase
What are cytokines
Activate leukocyte
IL-1, IL-2, TNF-a
Induce acute phase response
Tissue necrotic factor are produced by what type of cells?
Macrophages
What are interleukins?
Produced by leukocytes
Act of leukocytes
Activate T-cells and neutrophils ( phagocytic cells)
What are chemokines?
Activators and chemoattractants for leukocytes
Two branches of CHEMOTAXIS
Exogenous- bacterial
Endogenous- chemokines, cytokines
Process of phagocytosis
- Recognition and attachment
- Engulfment- forming a phagosome
- Killing and degradation- lysosomes secrete into phagosome
Oxygen dependent and oxygen independent
What do mast cells and basophils produce when they degranulation?
Heparin: prevents thrombosis
Histamine: increases vascular permeability
Leukotrienes: increases vascular permeability
Difference between mast cells and basophils
Basophils are short lives, mast cells are long lives
What do eosinophils produce when they degranulate?
Enzymes Toxic proteins Cytokines Chemokines Leukotrienes
Leukocytes extravasation
1. Extravasation Leukocytes move from blood to injury 2. Margination Leukocytes adhere to endothelial wall 3. Transmigration Leukocytes move through endothelium 4. Migration Leukocytes move into interstitial fluid
Types of plasma proteins in exudates
Albumin: Ca, Cu, Zn Interferrin: Fe Heptoglobin: haemoglobin Ceruloplasmin: Fe mechanism Immunoglobulins: binding antigens
Neutrophils produce
Bacteriocidal and oxygen free radicals
What is a modified transudate?
High proteins
Low cells
Triple response
Redness- vasodilation
Flare- hyperaemia
Wheal- oedema
Increased vascular permeability: mechanisms
- Gaps between endothelial cells
- Direct endothelial injury
- Leukocyte- mediated injury to endothelial wall
- Angiogenesis- leakage from new vessel
- Radiation
Vascular changes to acute inflammation
Transient vasoconstriction: neurogenic
Arteriolar dilation: histamine and nitric oxide
Increased vascular permeability: fluid enters interstitial fluid
Increased blood viscosity: blood stasis, impedes outflow
