S2 Flashcards
What is inflammation?
The response of living tissue to injury
What are the characteristics of acute inflammation?
Immediate Short duration Innate Stereotyped- always the same Limits damage
What happens in the vascular phase?
Vasoconstriction of arterioles (for a few seconds).
Vasodilation of arterioles and then capillaries. This increases the blood flow to the affected area, resulting in heat and redness (calor and rubor).
Increased permeability of local blood vessels allows proteins, cells and fluid to leave the blood vessel and enter the interstitial fluid causing swelling (tumor). This is called exudate
The increased concentration of red blood cells in small vessels and increased blood viscosity leads to stasis within the vessel.
What chemical mediators control the vascular phase of acute inflammation?
Within the first 30 minutes the main mediator, histamine, is released from mast cells, basophils, and platelets.
Histamine acts to dilate vasculature, increase vascular permeability and stimulate pain (dolor).
What is the cellular phase?
the migration of neutrophils to the site
What causes inflammation?
Trauma/foreign bodies Microorganisms Tissue necrosis Hypersensitivity Chemical agents or radiation Other illnesses
What are the clinical signs of acute inflammation?
Rubor – Redness Calor – Heat Tumor – Swelling Dolor – Pain Functio laesa – Loss of function This forces the person injured to immobilise the affect area which helps to reduce further damage.
How is the movement of fluid controlled?
Starling’s Law= movement of fluid is controlled by the balance of hydrostatic pressure and oncotic pressure
If there is increased hydrostatic pressure, there is an increased flow of fluid out of the vessel.
If there is increased oncotic pressure within the vessel then there will be a reduction in the flow of fluid out of the vessel.
If there is an increased oncotic pressure in the interstitial fluid, there will be an increased flow of fluid out of the vessel as the oncotic pressure draws fluid out of the capillary.
Pressures exists in the vessels and interstitium
What happens to vessels in acute inflammation?
Vasodilation- increased capillary hydrostatic pressure
Increased vessel permeability =plasma proteins move into interstitium=increased interstitial oncotic pressure
Fluid movement out to vessel into interstitium= oedema
What does movement of fluid out of the vessel affect the blood?
Increased viscosity of blood
Reduced flow through vessel= stasis
Describe exudate interstitial fluid and its functions
a collection of fluid, protein and cells that have left the blood vessel and formed in the interstitium.
Increased vascular permeability
Protein rich fluid
Functions:
To deliver fibrin, inflammatory mediators and immunoglobulins to the site of damage.
Dilutes toxins to reduce the damage to tissues.
Increases lymphatic drainage to deliver antigens and pathogens to lymph nodes to initiate an immune reaction.
Describe transudate interstitial fluid
Vascular permeability unchanged
Fluid movement due to: increased capillary hydrostatic pressure, reduced capillary oncotic pressure
Occurs in heart failure/hepatic failure/ renal failure
How does a vessel wall become permeable?
Retraction of endothelial cells caused by histamine, NO, leukotrienes
Direct injury e.g. burns, toxins, direct trauma
Leukocyte dependant injury- enzymes/toxic oxygen species released by activated inflammatory cells
Cytoskeletal reorganisation forming gaps between cells= Mediated by cytokines, interleukin-1, and TNF (tumour necrosis factor).
Increased transcytosis – production of channels within the endothelial cell to allow movement of proteins and fluid between cells= Mediated by VEGF.
How is the vascular phase effective?
Interstitial fluid dilutes toxins
Exudate- delivers proteins e.g. fibrin mesh limits spread of toxin, Ig from adaptive immune response
Fluid drains to lymph nodes- delivery of antigens stimulates adaptive immune response
How do neutrophils escape vessels?
Chemotaxis – neutrophils are attracted towards the site of injury by chemical attractants.
Activation – neutrophils switch to a higher metabolic level and change shape to help them move towards the chemical attractant.
Margination – neutrophils move towards the endothelial wall where they then roll along it until they become trapped. When they become trapped, they then crawl out of the vessel.
Diapedesis – neutrophils relax the junctions between the endothelial cells so they can move across the endothelium. They also use collagenase to break down the basement membrane.
Which adhesion molecules are involved in neutrophils escaping vessels?
Selections=expressed on activated endothelial cells. Cells activated by chemical mediators =responsible for rolling
Integrins found on neutrophil surface= change from low affinity to high affinity state =responsible for adhesion
How does neutrophils move through the interstitium?
Chemotaxis- movement along an increasing chemical gradient of chemoattractants
=bacterial peptides, inflammatory mediators (C5a, LTB4)
Rearrangement of neutrophil cytoskeleton
What do neutrophils do?
Phagocytosis
Release inflammatory mediators
Describe the process of phagocytosis
The membrane of the phagocyte forms a crater around the particle to be eaten.
The edges then come together and the opposed plasma membranes fuse.
The particle is then in a vacuole known as a phagosome.
Lysosomes fuse with the phagosomes forming a phagolysosome.
Chemicals are released that break down the engulfed particle.
The debris are released by exocytosis.
Engulfed cells can be killed via oxygen in/dependent mechanisms
How do neutrophils recognise what to phagocytose?
Opsonisation
=toxic covered in C3b and Fc (opsonins)
Receptors for C3b and Fc on neutrophil surface
Describe the oxygen depend killing mechanism
release of oxygen-derived free radicals into the phagosome: O. OH. H2O2 = oxidative burst
release reactive nitrogen intermediates: NO, NO2
Describe the oxygen independent killing mechanism
uses enzymes to kill bacteria inside the phagolysosome e.g. proteases, lipases, nucleases
How is the cellular phase effective?
Removal of pathogens, necrotic tissue
Release inflammatory mediators
What are inflammatory mediators?
Chemical messengers
=control and co-ordinate the inflammatory response
Varying chemical structures
Overlapping functions
