Response to Injury II: Acute Inflammation

• What is inflammation?

  The complex, biological response of tissues to harmful stimuli & is a protective response involving blood vessels, immune cells & molecular mediators
• What is acute inflammation?

  Early and immediate response to injury lasting for a short duration
• What is chronic inflammation?

  Inflammation of prolonged duration
• What are the purposes of acute inflammation?

  To destroy/contain noxious stimuli:

  This is brought about by dilution of toxins & entry of leukocytes

  
  

  To initiate repair & return to function:

  This is brought about by fibrin formation, transport of nutrients & transport of drugs

  
• Give a broad overview of the sequence of events in acute inflammation.

  1. Stimulus is recognised

  2.vascular events

  3.Cellular events

  4.Exudate which acts as a framework for healing to occur

  
• What are the 2 key vascular events in inflammation?

  Vasodilation & increased vascular permeability

  
• What is the earliest event in acute inflammation?

  Increase in capillary vasculature size (vasodilation)
• Why does vasodilation occur in acute inflammation?

  It results from the direct action on the capillary smooth muscle cells & endothelial cells by certain chemical mediators of inflammation that are released as a result of tissue damage.

  
  

  These include histamine (primarily), prostaglandins, platelet activating factor, kinins
• What does vasodilation lead to?

  A decrease in flow rate of blood through the vessel & vascular congestion
• What happens after vasodilation?

  Increased vascular permeability which is a result of the gaps between endothelial cells opening up

  
  

  Therefore, this leads to a leakage of fluid & plasma proteins into the extravascular space

  
• What is 'increase in gaps between endothelial cells' a direct action of?

  Chemical mediators of inflammation, including:

  
  

  Histamine

  Leukatriene

  Platelet activating factor

  Kinins
• What is exudation?

  The escape of fluid, proteins, and blood cells from the vascular system into the extravascular space

  
  

  The fluid that collects in the extravascular space is called the fluid exudate
• How does the fluid exudate form?

  In normal condition, the osmotic pressure is high within the blood vessel so fluid flows out but in the venous end the increased hydrostatic pressure in the extra vascular space forces fluid back in.

  
  

  However in inflammation, due to increased vascular permeability, at the venous end fluid flows out into the extra vascular space

  
• What does the cellular events in inflammation centre around?

  Neutrophils
• What is margination?

  Neutrophils cling to the walls of capillaries in the injured area
• What are neutrophils able to do as they marginate?

  Able to detect ligands expressed on endothelial cells

  
  

  Likewise, various receptors on endothelial cells are able to detect receptors or neutrophils

  
• What is a particularly important group of receptors when it comes to inflammation?

  Selectins:

  
  

  P-selectin being expressed on endothelial cells

  
  

  L-selectins being expressed on neutrophils

  
• What are the selectins regulated by?

  Cytokines, which are expressed as a result of tissue damage
• What is rolling?

  When the neutrophil rolls along the endothelial surface through attachment & detachment because the bond between neutrophil & endothelial cells via selectins is weak
• When does rolling stop?

  When the neutrophil firmly attaches to an endothelial cell, brought about by the expression of receptors on the neutrophil surface known as integrins.

  
  

  The ligand for integrins expressed on the endothelial cells are called ICAM-1

  
• What can the neutrophil now do after it has developed a firm attachment to the endothelial cell?

  It can squeeze between the endothelial cells to exit the vessel lumen & to become part of the inflammatory exudate

  
  

  These neutrophils now act as the cellular component of the exudate

  
• Does the process of transmigration damage the basal lamina of the vessel wall?

  No
• What happens once the neutrophil has exited the vessel?

  It migrates to the site it's needed at the most (chemotaxis)

  It does this by attraction from chemotactic factors

  
• What are some chemotactic factors?

  Bacterial products

  Chemokines

  C5a

  Leukotriene B4
• What is serous exudate?

  Watery exudate: indicates early inflammation

  
  

  Can be feature of certain viral infections like herpes virus infection

  
• What is fibrinous exudate?

  Thick, clotted exudate: indicates more advanced inflammation

  
  

  E.g. extraction of teeth

  
• What is purulent exudate?

  Exudate with microbe and WBC involvement (ie. infection or pus)

  
  

  It is usually thick, cloudy, and white/yellow/green coloured depending on the microbe involved

  
• What do the neutrophils do once they've migrated to where they're needed?

  They act to remove bacteria as well as necrotic debris via phagocytosis
• What are the steps of phagocytosis?

  1. Adherence & ingestion of the bacterium by the neutrophil

  
  

  2. Phagosome formation

  
  

  3. Phagolysosome formation (lysosome contains potent enzymes for digestion/bacterial killing)

  
  

  4. Digestion

  
  

  5. Residual body formation

  
  

  6. Digested debris discharged

  
• What happens within a phagolysosome?

  1. NADPH is reduced to NADP+

  2.Reactive oxygen species is formed

  3.This is converted to hydrogen peroxide which has some killing activities

  4.Hydrogen peroxide is more potent when combined with MPO

  5.Hydrogen peroxide and MPO in presence of Cl- Forms hypocholride OCL which has stronger killing activity

  
• What are the cardinal signs of inflammation?

  Heat, redness, swelling, pain, loss of function
• How does the cell & tissue response explain the cardinal signs of inflammation?

  
• What are the effects of acute inflammation?

  Pyrexia - fever

  
• What are the possible outcomes of acute inflammation?

  Resolution - return to normal function and structure

  
  

  Repair - Tissues heal through scar tissue

  
  

  Chronic inflammation