3 Acute and chronic inflammation Flashcards
Inflammation
The host response to tissue damage
Protective response
– to remove/ contain cause, initiate repair and reinstate useful function
Stops when injurious agent is eliminated
Essential for healing.
Triggers of Inflammation
Inflammatory response Foreign Body Infection Ischaemia/infarction Physical/chemical injury Immune reactions
Acute inflammation
Rapid host response triggering vascular and cellular reaction
Vascular changes to maximise movement of plasma proteins to site of injury:
Vasodilation leads to increased blood flow to the area of injury, clinically causing redness and heat (ERYTHEMA). This is induced by histamine and nitric acid.
Increased permeability follows, which leads to fluid leaking into the extravascular tissue. This leads to swelling (OEDEMA)
Together this creates blood stasis, pooling the blood at site of inflammation
VASCULAR PERMEABILITY
Endothelial cells of vessel wall triggered to contract increasing inter-endothelial spaces, triggered by histamine, bradykinin, leukotriens, substance P etc. It is the Immediate transient response
Endothelial injury leading to endothelial cell death, vessel wall is damaged and there is immediate extravascular leakage
Transcytosis leading to increased transport of fluids/proteins through cell channels. Promoted by specific factors triggered by inflammation eg VEGF
Cellular reaction
Main aim of inflammation is to recruit leucocytes to area of damage. by adhering them to vessel wall
Neutrophils and macrophages ingest and kill bacteria and necrotic cells, as well as promoting repair.
These white blood cells
need to be recruited from
the vessel lumens.
Cellular reaction
Margination:
Red blood cells flow in centre of vessel lumen and WBCs flow peripherally. In stasis, more wcc fall into peripheral flow.
Rolling:
This leads to an increased amount of leucocytes to roll along then edge of the damaged endotehlium. Mediated by selectins.
Adhesion: The leucocytes finally stop and adhere to the endothelium. Cytokines secreted by by injured cells encourage the adhesion of the leucocytes.
Cellular reaction
Transmigration: Leucocyte is then encouraged to pass through endothelium to extravascular space
Chemokines stimulate migration and leucocyte move towards the chemical concentration gradient
(towards site of injury where the chemokines are being produced)
PECAM-1 – platelet endothelial cell adhesion molecule
Chemotaxis: Exogenous (bacteria ) and endogenous (cytokines/complement) substances attract the leucocytes towards the area of injury.
Neutrophils appear at 6-24 hours, monocytes appear at 24-48hours. Neutrophils are more common in circating blood and respond to chemokines.
Function of leucocytes
Receptors on the leucocytes recognise foreign microbes
These include:
-Toll like receptors present on cell surface of leucocytes and attach to bacteria products
-G protein coupled receptors recognise N-formymethionyl of bacteria as well as chemokine breakdown
-Opsonin receptors recognoze microbes that have been coated with proteins ( antibodies/complement) or opsonins, thus called opsonization. This targets them for phagocytosis
-Cytokine receptors are present on leucocytes respond to the cytokines produced in response to microbes.
Phagocytosis
Through these receptors the leucocyte recognises and attaches itself to bacteria or damaged cell
The leucocytes then engulfs the cell/particle
The leucocyte then kills and degrades the offending agent, removing its harmful effects.
This continues until all foreign and damaged products are removed, so healthy cells remain and healing and repair can begin
Outcomes
Complete resolution
Healing with connective tissue replacement (fibrosis)
Following substantial tissue destruction, some cells cannot regenerate. Connective tissue replaces area or damage.
Progression to chronic inflammation
- Acute problem is not resolved due to persistent injury or interference with healing.
Chronic inflammation
Caused by:
Persistent infection: microorganisms that are difficult to remove e.g. parasite, mycobacteria.
Immune mediated inflammation: reaction against host tissue leading to auto-immune diseases.
Prolonged exposure to toxic agent : silica, asbestos, lipids (atherosclerosis)
Predominantly show infiltration of mononuclear cells: macrophages, lymphocytes and plasma cells.
( Macrophages destroy damaged cells and promote repair)
Tissue destruction following prolonged inflammatroy reaction
Signs of attempts at healing: connective tissue repair, increased growth of small blood vessels and fibrosis
Granulomas
Cellular attempt to contain offending agent it cannot eradicate
Strong activation of macrophages and T lymphocytes, leading to injury of normal tissues.
e.g Tuberculosis which leads to caseating lesions in the lungs.
Clinical signs
Redness (rubor) Heat (calor) Swelling (tumor) Pain (dolor) Loss of function
Signs and Symptoms
Fever
Tachycardia
Hypotension
Raised WCC
Raised CRP
Anorexia
General malaise
Weight loss (chronic inflammation)
Sepsis- large amount of toxins stimulate cytokines, can lead to cardiovascular failure (septic shock)
Acute Inflammation
Rapid response
Short lived
NEUTROPHILS predominate
Aim is complete resolution
