Inflammation 2
Terms
undefined, object
copy deck
- 2 main components of inflammation
- vascular reaction + cellular reaction
- 2 distinct phases of inflammation
-
Acute --> minutes to days --> leukocyte emigration (neutrophils) + edema
Chronic --> months to decades --> lymphocytes + macrophages - 3 main components of acute inflammation
-
1. Increased blood flow
2. Increased vascular permeability - allow protein extravasation, leukocyte movement to interstitium
3. Emigration of leukocytes - accumulation at site of injury, activation to eliminate agent - Exudate
- inflammatory extravascular fluid that has high protein concentration, usually due to increased permeability
- Transudate
- a fluid with low protein concentration (most albumin), permeability not increased
- Edema
- excess interstitial fluid, can be either exudate or transudate
- Pus
- Purulent exudate, leukocytes (neutrophils), debris of dead cells and microbes
- Stimuli for acute inflammation
-
-Infections (bacteria, viral, parasitic) + microbial toxins
-Trauma
-Physical and chemical (burns, frostbite, radiation)
-tissue necrosis
-foreign body
-immune reactions - hypersensitivity - Vascular changes of inflammation
-
Responsible for delivering cellular components (neutrophils, Ab's ) to the site of infection
Blood vessels change to allow movement of plasma proteins from circulation to site of injury - Vasodilation
-
one of earliest changes of acute inflammation
occasionally follows a transient vasoconstriction of arterioles - lasts only seconds
dilates arterioles first
As a result blood flow increases - Increased permeability
- quickly follows vasodilation --> increases protein movement into interstitium
- Stasis
- With fluid movement as result of permeability changes, RBC concentrate in vasculature causing stasis
- Which leukocytes are present in acute inflammation
- Neutrophils
- What is a landmark of acute inflammation
- Increased vascular permebaility - exudate extravasation, decreases plasma oncotic pressure, increases tissue oncotic pressure --> edema formation
- What is the mechanism for endothelial cells to become "leaky" - increasing permeability
-
ENDOTHELIAL GAPS IN VENULES - mediated via histamine, bradykinin, leukotrienes
-occurs rapidly, reversible and short lived
-capillaries and arterioles are not affected - How does histamine affects permeability
- Causes contraction of venular endothelial cells - causes separation of intercellular junctions - increased permeability
- Direct endothelial cell injury
-
Usually associated with platelet cell attachment
-necrotizing injuries
-such as severe burns
-"immediate sustained response"
-all levels of microcrculation are affected - arterioles, venules and capillaries - Delayed prolonged leakage
-
Begins after delay (2-12 hrs)
-venules and capillaries
-late appearing sunburn - 4 steps of journey of leukocytes from vessel lumen to interstitium
-
Margination
Rolling
Adhesion
Transmigration (diapedesis) - Describe normal blood flow through venules
- Axial streaming- RBC at center, plasma and leukocytes toward vessel wall
- Margination of leukocytes
- inflammation induces stasis - causing more leukocytes to gather at blood vessel wall
- Rolling of leukocytes
- Lwukocytes tumble slowly along endothelium and adhere transiently
- Adhesion of leukocytes
- Leukocytes come to rest and adhere to the wall
- Transmigration = diapedesis
- Leukocytes are regulated by adhesion molecules and chemical mediators
- 4 types of adhesion receptors
-
1. Selectins
2. Ig super family - ICAM + PCAM
3. Integrins - expressed on many cell types, bind to ligands
4. Mucin line glycoproteins - heparan sulfate - Leukocyte effects
-
-Increase arachidonic acid metabolites
-Increase lysosomal enzymes and activation of O2 burst
-Increase cytokines
-Leukocyte adhesion modulation - Leukocyte receptors
-
Toll like receptors - activated by microbes
Seven transmembrane
Cytokine receptors - on phagocytes - 3 steps of phagocytosis
-
Recognition and attachment
Engulfment
Killing and degradation - What converts H2O2 to HOCl
- Myeloperoxidase
- Most frequent cause of leukocyte dysfunction
- Bone marrow suppression
- Histamine comes from
- mast cells
- Histamine causes
-
vasodilation
increase vascular permeability
immediate transient phase of inflammation - Serotonin comes from
- Platelets
- Complement mostly located in
- Plasma
- Name anaphylotoxins
- C3a and C5a --> histamine
- C5a
- Chemotaxis
- C3b
- opsonin
- Activated Hageman factor initiates
-
Clotting
Kinin
Fibrinolytic
COmplement