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Flashcards in 3. Acute and chronic inflammation Deck (39)
1

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.

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Triggers of Inflammation

Foreign Body
Infection
Ischaemia/infarction
Physical/chemical injury
Immune reactions

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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

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VASCULAR PERMEABILITY

Endothelial cells of vessel wall contract
Endothelial injury
Transcytosis

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Endothelial cells of vessel wall contract

increasing inter-endothelial spaces, triggered by histamine, bradykinin, leukotriens, substance P etc. It is the Immediate transient response

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Endothelial injury

leading to endothelial cell death, vessel wall is damaged and there is immediate extravascular leakage

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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.

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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.

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Margination:

Red blood cells flow in centre of vessel lumen and WBCs flow peripherally. In stasis, more wcc fall into peripheral flow.

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Rolling:

This leads to an increased amount of leucocytes to roll along then edge of the damaged endotehlium. Mediated by selectins.

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Adhesion:

The leucocytes finally stop and adhere to the endothelium. Cytokines secreted by by injured cells encourage the adhesion of the leucocytes.

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Transmigration:

Leucocyte is then encouraged to pass through endothelium to extravascular space

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Chemokines

stimulate migration and leucocyte move towards the chemical concentration gradient

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(towards site of injury where the chemokines are being produced)

PECAM-1 – platelet endothelial cell adhesion molecule

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Chemotaxis:

Exogenous (bacteria ) and endogenous (cytokines/complement) substances attract the leucocytes towards the area of injury.

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Neutrophils

appear at 6-24 hours, monocytes appear at 24-48hours. Neutrophils are more common in circating blood and respond to chemokines.

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Function of leucocytes

Receptors on the leucocytes recognise foreign microbes
These include:
-Toll
-G protein
-Opsonin receptors
-Cytokine receptors

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Toll

like receptors present on cell surface of leucocytes and attach to bacteria products

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G protein

coupled receptors recognise N-formymethionyl of bacteria as well as chemokine breakdown

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Opsonin receptors

recognoze microbes that have been coated with proteins ( antibodies/complement) or opsonins, thus called opsonization. This targets them for phagocytosis

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Cytokine receptors

are present on leucocytes respond to the cytokines produced in response to microbes.

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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.

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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.

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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

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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.

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Clinical signs

Redness (rubor)
Heat (calor)
Swelling (tumor)
Pain (dolor)
Loss of function

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Signs and Symptoms (1)

Fever
Tachycardia
Hypotension
Raised WCC
Raised CRP

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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)

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Acute Inflammation

Rapid response
Short lived
NEUTROPHILS predominate
Aim is complete resolution

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Outcomes of acute inflammation

Complete resolution
Healing by fibrosis (scar formation)
Abscess formation
Chronic inflammation

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Chronic inflammation

Prolonged (weeks/months)
Can develop from acute inflammation but frequently doesn’t:
persistent infection
prolonged exposure to toxins
autoimmune reactions

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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

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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

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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

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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

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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

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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

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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

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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