Term
| Acute Inflammation: Vascular (fluid) Phase |
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Definition
Inflammation causes increased amounts of:
1.blood flowing through the vessels (BV dilation)
2.the amount of fluid leaking from the vessels into the interstitial fluid.
*these 2 things lead to slower blood flow and hemoconcentration.
1. Vascular changes leading to increased blood flow:
a.biochemical mediator release from bacteria or damaged tissue causes vasodilation
b.Histamine and nitric oxide cause relaxation of arteriolar smooth muscle and arteriolar dilation -->opening of new capillary beds and thus increased blood flow to the area.
c.Venuoles dilate to accommodate
*all these changes account for heat and redness (erythema)to the area.
2. Vascular changes that increase leakyness:
a.endothelial cell contraction in response to histamine, nitric oxide and other mediators = fast and short lived
b.TGJ enlargement due to this process causes fluid and protein leakage
c.increased hydrostatic pressure and osmotic pressure occur following step b, causing further edema.
*these processes account for the swelling in acute inflammation |
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Term
| Acute Inflammation: benefits to the vascular phase |
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Definition
1.dilution of toxic substances
2.delivery of Ab's
3.delivery of nutrients to leukocytes
4.delivery of fibrinogen (-->fibrin)
*fibrin's roles:
a.stick opposing surfaces together
b.confine bacteria
c.scaffold for phagocytosis
d.scaffold for capillaries and fibroblasts during repair. |
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Term
| Acute Inflammation: Cellular Phase |
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Definition
The body must make it easy for the leukocytes to identify the injured area and travel to it--->"vascular stickiness" where WBC's and platelets stick to the endothelium. This allows for leukocyte recruitment to the injured area. There are 6 steps:
1.margination
2.Rolling
3.Adhesion
4.Emigration
5.Migration
6.phagocytosis |
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Term
Acute Inflammation: Cellular Phase
Margination |
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Definition
| Occurs due to the slowing of blood and increased vascular stickiness. Leukocytes move to the periphery of the vascular lumen and contact the BV walls. Seen within 30 minutes of injury. |
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Term
Acute Inflammation: Cellular Phase
Rolling |
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Definition
| Occurs on the endothelial surface and is mediated by adhesion molecules called SELECTINS, which are regulated by cytokines. Selectins form low-affinity bonds between WBC and endothelium. |
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Term
Acute Inflammation: Cellular Phase
Adhesion |
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Definition
| Occurs on the endothelium. Cytokines produced by the damaged tissue activate the WBC's and endothelial cells. This allows a new set of adhesion molecules, INTEGRINS(high-affinity bonds), to be expressed by the WBC's. Adhesion also involves the rearrangement of the WBC cytoskeleton resulting in flattening of the cells to the endothelial surface. |
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Term
Acute Inflammation: Cellular Phase
Emigration (diapedesis) |
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Definition
| Movement of the WBC from the BV lumen out into a fluid exudate in the tissues. The WBC squeezes out through the TGJ of two endothelial cells. Also mediated by adhesion molecules. |
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Term
Acute Inflammation: Cellular Phase
Migration |
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Definition
Through the tissues via chemotaxis. Chemoattractants include:
1.bacterial products
2.cytokines
3.chemokines
which all are members of the compliment system and leukotrienes. Migration is usually well advanced by 2-3 hours after injury. |
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Term
Acute Inflammation: Cellular Phase
Phagocytosis |
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Definition
Neutrophils and macrophages are the most common types. Once phagocytosed, the bacteria are killed and digested (usually). Steps involved:
1.recognition and attachment (opsonization): Opsonins are particles that coat the bacteria or material and increase phagocytosis. These can be Ab's or certain complement components.Phagocytic cells recognize opsonins via surface cell receptors.
2.ingestion or engulfment: occurs by the formation of pseudopodia -->produces a phagosome-->further becomes a phagolysosome.
3.killing and degradation: lysosome release of oxygen species to lyse the bacterial cell. |
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Term
Acute inflammation: Biochemical Mediators
General |
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Definition
-3 major categories:
1.plasma-borne (source = liver)
a.Kinin system
b.coagulation system
c.fibrinolytic system
d.complement system
2.Pre-formed:
a.histamine (mast cells, platelets, Bo)
b.Serotonin (platelets)
c.lysosomal enzymes (No, Mo)
3.synthesized during inflammation
a.prostaglandins (WBC's, platelets and endothelial cells)
b.Leukotrienes (WBC's)
c.platelet activating factor (WBC's, platelets and endothelial cells)
d.Activated oxygen spp (WBC's)
e.nitric oxide (Mo)
f.cytokines (lymphocytes, Mo and endothelial cells) |
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Term
Acute inflammation: Biochemical Mediators
plasma-borne mediators- kinin system |
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Definition
*fibrinolytic and coagulative systems - see hemostasis notes
1.Kinin System:
-kinins are polypeptides activated via the cascade system (hemostasis notes)
-kallikreins (enzymes) form active products from the precursor high- molecular weight kininogen (HMWK).
-the most important kinin is brady kinin which does:
1.contract non-vascular smooth muscle
2.vasodilation
3.increased vascular permeability in the delayed or secnod phase
4.cause pain
**Factor XII (Hageman factor) links all 4 cascades together. It is present in plasma and is activated when it comes into contact with collagen on the surface of endothelial cells (most injuries) |
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Term
Acute inflammation: Biochemical Mediators
Plasma-borne mediators- complement system |
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Definition
A cascade where inactive proteins (C1, C2, C3...) are cleaved to become active compliment factrs (C3a, C3b...).
-it is important because is causes a large systemic reaction, important to both inflammation and immunity.
-the important compliment factor is C3 and thus C3a and C3b (opsonin) which are activated by one of 3 pathways:
1.classical pathway- initiated by Ab binding to Ag
-C1 binds to the Ab/Ag complex which causes C3 to bind and become activated...and so on
2.alternative pathway- initiated by bacterial products , bacterial or fungal cell walls and foreign material to the blood stream (i.e. collagen)
3.lectin pathway (less important)
-major functions and outcomes:
1.Opsonization and phagocytosis
-C3b
2.chemotaxis and leukocyte activation
-C5a and C3a activate macrophages
3.microbial cell wall lysis
-various activated complement factors (C9) combine to form memebrane attack complex (MAC)
4.increased vascular permeablility
-C3a and C5a stimulate histamine release from mast cells
5.clearance of immune complexes and apopttic cells
-C3 and C4 fragments |
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Term
Acute inflammation: Biochemical Mediators
Cell-produced mediators- general |
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Definition
They may be pre-formed (histamine) or synthesized during inflammation (prostaglandins and cytokines). Inflammatory mediators work together to initiate, control and modulate:
1.increasing BV permeability
2.increasing endothelial cell "stickiness" for margination and diapedesis
3.promoting chemotaxis
4.clotting fibrinogen in exudate
5.activating macrophages
6.promoting proliferation of cells in repair and regeneration
7.killing microbes and parasites
-the lifespan of these mediators is very short (seconds) and/or are rapidly inactivated by lysosomal enzymes (=cascade control mechanism).
-4 major types:
1.histamine: is pre-formed and released from mast cells, Bo and platelets when triggered by verious stimuli including IgE binding and trauma. It is one of the earliest responses and results in rapid vasodilation and increase permeability
2.Arachidonic acid metabolites (Eicosanoids)
3.Cytokines
4.lysosomal enzymes (in leukocyte lysosomes) |
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Term
Acute inflammation: Biochemical Mediators
cell-produced mediators- Eicosanoids |
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Definition
Arachidonic acid is released from the internal cell membrane phospholipids by activation of phospholipases. It is then converted into different eicosanoids, such as prostaglandins and thromboxanes (cyclooxygenase pathway)and leukotrienes and lipoxines (lipoxygenase pathway), which are potent local signaling molecules.
1.Prostaglandins (PG):
-cause:
a.vasdilation (except TBA2)
b.edema
c.fever and pain (PGE2)
d.modulation of inflammatory cell function (PGE1 and PGE2)
2.Leukotrienes:
-causes:
a.No chemotaxis, aggregation and margination
b.smooth muscle contraction and vascular leakage during inflammation |
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Term
Acute inflammation: Biochemical Mediators
cell-produced mediators- Cytokines |
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Definition
-Primary role: modulate the functional expression of verious cells during inflammatory and immune responses.
-produced by many cells but mainly Mo and lymphocytes.
-can be broadly grouped by function:
1.hematopoiesis stimulators
2.inflammatory and immune mediators
3.chemotactic cytokines
4.regulators of lymphocyte function
-examples:
Tumor necrsis fector (TNF) and interleukin-1 (IL-1) mediate inflammation by:
a.inducing changes in the endothelium to increase WBC adhesion and clotting
b.increasing synthesis of other biochemical mediators
c.induction of the systemic acute phase response |
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Term
Acute inflammation: Biochemical Mediators
Control of inflammatory reactions |
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Definition
Uncontrolled can prduce injury more severe than the initial insult (usually by proteolytic enzymes or proteases) therefore this cascade must be kept under control.
-Inflammatory mediators are produced on site and short lived,therefore continuation of acute inflammtion depends on continued synthesis and release of these mediators.
1. Protease inhibitors:
-highly selective
-made by the liver and naturally found in the serum (and thus exudate)
-acute phase proteins
-types:
a.antithrombin III- anticoagulant
b.antiplasmin- prevents fibrin breakdown
c.C1 inhibitor- control over classical pathway of complement cascade
d.macroglobulin- inhibits most proteases.
** like all systems, this system also has a control mechanism which involves albumin systhesis reduction in plasma in order to compensate for the overproduction of acute phase proteins by the liver. |
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Term
| Acute inflammation: Sequelae of acute inflammation |
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Definition
-4 general outcomes:
1.complete resolution: when injury is limited and short lived or when there is little tissue damage.
-involves:
a. neutralization of chemical mediators
b.normal vascular permeability
c.cessation of WBC infiltration
d.removal of inflammation products (fluid, WBC's, proteins, debris...etc)
2.Healing: Scar formation occurs following substancial tissue damage, damage in non-regenerative tissues (CNS, heart), or when there is too much fibrin for macrophages to handle.
3.abcess formation: occurs with pyogenic bacteria and may persist for a long time.
4.chronic inflammation |
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