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
Foreign Body Infection Ischaemia/infarction Physical/chemical injury Immune reactions
Acute inflammation
Rapid host response - vascular and cellular reaction
Vascular changes to maximise movement of plasma proteins to site of injury:
Vasodilation - increased blood flow to the area of injury, redness and heat (ERYTHEMA). induced by histamine and nitric acid.
Increased permeability follows, - 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 contract
Endothelial injury
Transcytosis
Endothelial cells of vessel wall 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
Together these mechanisms cause leakage of intravascular fluid into the extravascular spaces.
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.
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.
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 -G protein -Opsonin receptors -Cytokine receptors
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
leucocytes - engulfs the cell/particle
leucocyte - 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 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 (1)
Fever Tachycardia Hypotension Raised WCC Raised CRP
Signs and Symptoms (2)
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
Outcomes of acute inflammation
Complete resolution
Healing by fibrosis (scar formation)
Abscess formation
Chronic inflammation
Chronic inflammation
Prolonged (weeks/months) Can develop from acute inflammation but frequently doesn’t: persistent infection prolonged exposure to toxins autoimmune reactions
Can it be harmful? How?
Exaggerated or inappropriate inflammatory response = allergies, hypersensitivity reactions and autoimmune diseases
Poor inflammatory response is the basis for immunodeficiency conditions/diseases; some are acquired and some are hereditary
What can we do about it?
Medications
Non-steroidal anti-inflammatories (NSAIDs)
Anti-histamines
Steroids
Targeted biologics against immune response proteins e.g anti TNF
What happens if there is no inflammatory response?
Defective inflammation →
Increased susceptibility to infection
Delayed healing of wounds
Tissue damage
Eg. hereditary immunodeficiency conditions, post-chemotherapy, medications
Acute appendicitis
Peak age 10-30 years
Central abdominal pain which localises to right iliac fossa; worse on movement; may have nausea/vomiting
Pyrexia, raised HR, raised WCC and CRP
Management – appendicectomy
Complications – perforation leading to peritonitis, abscess formation
Septic Arthritis
Red hot swollen joint
Unable to move joint as limited by pain
Pyrexia, tachycardia, raised WCC and CRP
Risk factors: prosthetic joint, recent surgery/trauma to knee, age, RA, Immunodeficiency
Treatment – Joint aspirate, IV antibiotics, sepsis 6
Minor Injury
Sprained ankle Muscle cells are damaged Leads to swelling pain heat etc Inflammatory response is of no benefit REST – prevent further injury ICE – reverse vasodilation COMPRESS – reduce oedema ELEVATE – prevent blood stasis ANTI- INFLAMMATORY
Rheumatoid Arthritis
Chronic autoimmune inflammatory condition
Leading to warm swollen, stiff and painful joints.
Vessels also can become involved – Vasculitis, leading to circulatory problems.
Immune systems views host cell as foreign, leading to a chronic inflammatory response.
macrophages, lymphocytes (T cell) and plasma attempt to remove foreign agent. Instead healthy joints are destroyed.
Treatment: Steroids, DMARDs, biologics
Peptic Ulcers
Acute inflammatory response e.g. h pylori/excess acid
Necrotic inflammed mucosa falls away and is exposes to stomach acid/ h pylori and does not repair, leading to chronic inflammation
At risk of developing bleed/perforation
Treatment – PPIs / histamine receptor agonist/ antibiotics
