Acute inflammation Flashcards
What is the definition of acute inflammation?
It is a transient and early response to injury characterised by the release of numerous chemical mediators.
This leads to sterotypic small vessel and leukocyte response.
What are some of the main causes of an acute inflammation?
Infections (bacterial or viral)
Immune reactions (bee sting)
Other stimuli e.g. tissue necrosis
What are the cardinal signs or acute inflammation?
Rubour (redness) and Calor (heat)
-due to the histamine mediated vasodilation
Tumour (swelling)
-due to histamine mediated increase in vascular permeability
Dolor (pain)
-prostaglandin E2 sensitises the nerve endings to effects of bradykinin and other inflammatory mediators
What is the sequence of vascular events that occurs in acute inflammation?
Initially there is brief vasoconstriction due to a neurogenic reflex
Then vasodilation due to release of histamine, nitric oxide and other vasodilators from the mast cells surrounding the small vessels
Vasodilation also causes increased flow and increased hydrostatic pressure
Increased vessel permeability means that transudate leaves the blood
This causes swelling
This causes reduced blood flow because fluid is leaving into the interstitial fluid
What are the two types of peripheral blood neutrophils?
There is a circulating pool in the central axial stream of blood
There is a marginating pool that is already adhering to endothelial cells
Around 50% in each
Activating or inactivating the neutrophil adhesion molecules changes the number in each pool
what is neutrophil margination?
The aggregation of RBCs in the venules forces the neutrophils out of the axial stream and towards the periphery of the blood stream
Describe the rolling stage of neutrophil migration?
Selectin adhesion molecules on the leukocytes and the endothelial cells begin to bind together
Interleukin-1 (IL-1) and tissue necrosis factor (TNF) stimulate expression of selectins
This binding is weak s causes the to roll along the endothelial wall
Describe the adhesion stage of neutrophil migration?
It is due to neutrophil expression of intergrins
Beta integrins on neutrophils interact with ligands on endothelial cells
How do catecholamines and corticosteroids affect neutrophil adhesion?
They inhibit neutrophil adhesion because they inhibit the activation of the neutrophil adhesion molecules
This increases the circulating neutrophils as there are less in the marginating pool
how do endotoxins affect neutrophil adhesion?
They cause increased activation of intergrins and hence the normal circulating neutropil pool becomes part of the marginating pool
What is LAD and what are the clinical findings?
an autosomal recessive deficiency of b2 integrins
Clinical findings:
First manifestation is usually delayed seperation of the umbilical cord becuase this is done by neutrophils
Poor wound healing
peripheral blood neutrophilic leukocytosis
Describe the transmigration stage of neutrophil migration?
Neutrophils moving along the endothelium dissolve the collgen between the cells and pass through into the interstitual space
What are the two functions of exudate?
Dilutes bacterial toxins Provides opsonins (IgG, C3b) to assist phagocytosis
Describe neutrophil phagocytosis?
Neutrophils are opsonised by IgG and complements
They are then phagocytosed and primary lysosomes empty hydrolytic enzymes into the phaygocytic vacuoles causing formation of phagolysosomes
Neutrophil killing then occurs through the myeloperoxidase (MPO) system
This produces superoxide free radicals, peroxide and bleach
Describe the pathology behind chronic granulomatous disease?
It is an X linked recessive disorder that doesnt code for a protein in the MPO (myeloperoxidase) pathway.
This means that there is no oxidative burst to kill bacteria once they are phagocytosed
Phagocytes then fuse to form giant multinucleated cells
