S2: acute inflammation Flashcards
Define inflammation
The response of living tissue to injury
Name the common causes of acute inflammation
Foreign bodies Immune reactions Infections Tissue necrosis Trauma Physical and chemical agents
What are the 5 clinical signs of inflammation?
Rubor = redness Calor = heat Tumor = swelling Dolor = pain Loss of function
Explain the vascular phase
Brief moment of vasoconstriction
Swiftly followed by vasodilation (brought about by vasoactive mediators) = increase the delivery of fluid and leucocytes to the area of injury
Increased permeability = results in an increased haematocrit within the venules and increased resistance to blood flow within them (increased pressure within the vessels results in greater exudation of fluid into the tissue spaces thus delivering plasma proteins to the site of injury)
What is the cellular phase?
Delivery of neutrophils
What happens to the different pressures in acute inflammation?
Main force driving the fluid out of the vessels is increased (arterioles dilate increasing capillary pressure)
The main force driving fluid back into the blood is reduced as plasma proteins escape into the tissue spaces raising the osmotic pressure there so that it roughly equals that of blood
Net flow of fluid out of the vessels into the tissue space
What is the difference between exudate and transudate?
Exudate = increased vascular permeability, protein rich fluid & occurs in inflammation Transudate = vascular permeability unchanged, occurs in heart failure, hepatic failure & renal failure
What are the three types of defensive proteins in exudate?
Opsonins = which coat foreign materials and make them easy to phagocytose Complement = a group of proteins that are assembled locally to produce a bacteria-perforating structure Antibodies = bind to the surface of micro-organisms and also act as opsonins
What is the primary type of leucocyte involved in acute inflammation?
Neutrophils
They escape from blood vessels into tissue spaces in response to chemical ‘calls’ originating from bacteria, injured cells or other inflammatory cells.
What are the 3 ways by which a vessel wall can become permeable?
Retraction of endothelial cells
Direct injury
Leucocyte dependent injury
How do neutrophils leave blood vessels?
Margination = movement of the neutrophil from middle of the vessel to the edge
Rolling = brought about by weak intermittent bonds between the neutrophil & endothelial cell
Adhesion = brought about by tight strong bonds between the neutrophil & endothelial cell -> tethered to each other
Emigration (diapedesis) = movement of neutrophil out of the blood vessel into the interstitial space (produce collagenase which digests the basement membrane)
What is chemotaxis?
Chemotaxis is the directional movement towards a chemical attractant (chemotaxin)
What do opsonins do? Name the two main examples
Opsonins are substances which make it easier for phagocytes to recognise targets, attach to them and then phagocytise them
IgG antibody – this is the most important opsonin but it will not be present when a bacterium is encountered for the first time
C3b fragment of complement – this is released when complement is activated
Describe the process of phagocytosis
During phagocytosis the membrane of the phagocyte forms a crater shape around the particle that is to be phagocytised.
This crater then develops into a cup which surrounds the particle.
The edges of the cup come together and the apposed plasma membranes fuse.
The particle is then within an intracellular vacuole which is called a phagosome.
The phagosome then proceeds to digest the particle. The cell’s granules move towards the phagosome, fuse with it and inject their bactericidal substances into it. This process is called degranulation.
What are main two phagocytic killing mechanisms?
Oxygen-dependent = using oxygen derived free radicles which are released into the phagosome
Called respiratory burst
Oxygen-independent = using enzymes
What are the main roles and main sources of inflammatory mediators?
- Vasodilatation – histamine and serotonin (from mast cells and platelets), prostaglandins (from many cells).
- Increased vascular permeability – histamine and serotonin (from mast cells and platelets), bradykinin (from the plasma precursor kininogen).
- Chemotaxis – leukotriene B4 (from leucocytes), C5a and C3a (from complement plasma precursors), chemokines (from leucocytes and other cells), bacterial products (from bacterial metabolism).
- Phagocytosis – C3b (from complement plasma precursor).
- Pain – bradykinin (from the plasma precursor kininogen), prostaglandins (from many cells)
What are local complications of acute inflammation?
Damage to normal tissue
Obstruction of tubes and compression of vital structures
Loss of fluid
Pain and loss of function
What are systemic effects of acute inflammation?
Fever
Leucocytosis
Acute phase response
Shock
What are the 4 types of exudate?
1) pus/abscess = exudate is creamy/white as it is rich in neutrophils
2) haemorrhagic exudate = appears bloody to the naked eye -> indicates that as well as inflammation significant vascular damage has occurred
3) serous exudate = contain plasma proteins but few leucocytes suggesting that there is no infection by microorganisms eg. blisters
4) fibrinous exudate = significant deposition of fibrin -> can result in friction between serosal surfaces which can be heard as a rubbing sound
Describe hereditary angio-oedema
Autosomal dominant
Inherited deficiency of C1-esterase inhibitor
Experience recurrent abdominal pain, non-itchy cutaneous angio-oedema
Often have a family history of sudden death (laryngeal involvement)
Describe alpha-1 antitrypsin deficiency
Autosomal recessive disorder
Low levels of alpha-1 antitrypsin (protease inhibitor which deactivates enzymes released from neutrophils at the site of inflammation)
Develop emphysema and liver disease
Describe chronic granulomatous disease
Phagocytes are unable to generate the free radical superoxide
Bacteria are phagocytised but the phagocytes cannot kill them as they can’t generate an oxygen burst
Results in many chronic infections in the first year of life
