Acute Inflammation Flashcards
What is inflammation?
A defensive reaction of a macro organism mechanism against injury
How long does acute inflammation take to develop?
Minutes/ hours
How long does acute inflammation last for?
Hours or days
What are the 5 (general) triggers for inflammation?
- Infections Tissue damage due to: - physical agents - Chemical agents - mechanical injury and ischemia - foreign bodies
What are the 5 responses inflammation induces?
- alerts and initiates appropriate immune response
- limits the spread of infection or injury
- protects site from infection
- eliminates dead cells/ tissue
- makes conditions right for healing
Is acute inflammation beneficial?
Yes
Name the 5Rs
Recognition of injury Recruitment of leukocytes Removal of injurious agents Regulation (closure of inflammatory response) Resolution/ repair of affected tissue
What are the 5 signs of acute inflammation?
Heat Redness Swelling Pain Loss of function
Why does the area heat up when inflamed?
Increased blood flow and metabolic activity
Why does the area go red when inflamed?
Increased blood flow to injured area
What is hyperaemia?
Increased blood flow
Why does the area swell up when inflamed?
Fluid accumulation due to permeability of vessels
Why does the area become painful when inflamed?
Release of pain mediators; pressure on nerve ends
Why does the area (sometimes) lose function when inflamed?
Damage to the area
What are the 3 systemic changes that happen when an area is inflamed?
Fever
Neurophilia
Acute phase reactions are released
What does an increase in fibrinogen mean?
Makes the RBCs sticky -> stacking of RBCs -> faster sedimentation rate
Give some examples of acute phase reactants
- C reactive proteins
- fibrinogen
- complement
- serum amyloid A protein
Are there complications of the acute inflammation response?
Very rarely, it causes a severe systemic inflammatory reaction called sepsis or a form of inflammatory response syndromes (SIRS)
What happens to the vasculature in the acute inflammatory response?
Local reaction. Vasodilation, plasma exudation and oedema
What happens to the cells in the acute inflammatory response?
Infiltration of inflammatory cells. Cell recruitment, phagocytosis and NETosis
What happens to the humor in the acute inflammatory response?
Release of inflammatory mediators
What inflammatory mediators are released in the acute inflammatory response (5)?
Complement, plasma factors, clotting cascade, chemokines and cytokines
What happens in the resolution of the acute inflammatory response?
Inflammation is controlled and self-limiting. Healing, regeneration and repair of tissue
What is vasodilation induced by?
Histamine and seratonin released by injured cells, mast cells and macrophages
What does increased vascular permeability lead to?
Leakage of fluids into the tissues (swelling)
What happens as exudate accumulates at the inflamed site?
Pressure increases, and nerve endings are stimulated by the excess fluid and inflammatory mediators (pain)
What does the activation of endothelial cells lead to?
Increasing their expression of adhesion molecules
What is the overall effect of increased vascular permeability?
Leukocytes and plasma proteins exit vessels and enter the inflammation site to deal with infection
What does endothelial cell constriction lead to?
Loss of proteins and cell movement
What happens when the proteins are lost into the tissue in acute inflammation?
Increases the osmotic pressure/ gradient, leading to fluid leakage to the area, causing oedema
What is in inflammatory exudate?
Water, salts, small plasma proteins, inflammatory cells and RBCs
What is transudate?
When the fluid leaks due to altered osmotic/hydrostatic pressure; vessel permeability stays normal
What are the cellular mediators of inflammation (4)?
Macrophages
Neutrophils
Mast cells
Platelets
What do mast cells in the tissues secrete?
Histamine
What is needed for clotting to begin?
Fluid, anti microbial proteins and clotting factors
What do chemokines do?
Attract more phagocyte cells from the blood to the injury site
Why are neutrophils recruited?
To kill pathogens and remove cell debris at the site
What is regulation and tissue repair promoted by?
The release of immunoregulatory factors (TGFbeta)
What are the 5 steps in neutrophil recruitment?
Margination and rolling Integrin activation Firm adhesion to endothelium Cell movement through endothelium into tissue Chemotaxis
What is rolling mediated by?
Selectins
What is arrest and adhesion in inflammation mediated by?
Integrins and cell adhesion molecules
What is margination in neutrophil recruitment of acute inflammation?
Leukocytes and stem cells move towards the edges of the vessels
What molecules are involved in neutrophil recruitment?
Selectins
Integrins
Immunoglobulin superfamily cell adhesion molecules (CAMs)
What are selectins expressed by?
Activated endothelium
What are p-selectins?
Preformed granules
What are e-selectins?
Cytokines produced by macrophages, mast cells and endothelial cells at site of inflammation
What do leukocytes express?
selectin
What do neutrophils express?
Integrins
What configuration are integrins in if there is no binding to ligands?
Low affinity
What do activated endothelial cells produce?
Chemokines
What do integrins bind to?
Ligands on the endothelium
What does integrin binding result in?
Firm adhesion to the neutrophil
Where do neutrophils migrate through?
Interendothelial spaces
What is neutrophil chemotaxis?
Movement of cells towards tissue towards inflamed sites
What is chemotaxis guided by?
Chemoattractants
Where are chemoattractants produced?
At the site of infection/ damage
What mechanisms are involved in pathogen destruction?
- Release of granule content
- Phagocytosis
- generation of reactive oxygen/nitrogen species
- formation of NETs
What are NETs?
Mesh of chromatin that traps microbes
What are the two types of neutrophil granules and which one is small and which is large?
Specific granules (small) Azureophil granules (large)
What can granule content cause?
Healthy tissue damage
What are monocytes recruited to do?
Fight infection and differentiation into macrophages that promote dead cell clearance and tissue repair
What are the short lived cells at inflammation sites?
Neutrophils
What are the longer surviving cells at inflammation sites?
Monocytes
Do inflammatory mediators naturally damage the tissue?
Yes
Why is termination of acute inflammatory reaction important?
To avoid extensive bystander damage
Why do inflammatory mediators degrade?
Short lived or are used up
What does apoptosis of neutrophils and their subsequent clearance drive?
Potent anti-inflammatory and tissue-restoring mechanisms
Why are macrophages so critical?
They secrete anti-inflammatory and reparative mediators and orchestrate the reparative processes
What happens if the inflammatory response doesnt reach a critical threshold?
The mechanisms of regulation are not effectively promoted