3. Acute and chronic inflammation

Question 1

Inflammation

Answer 1

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.

Question 2

Triggers of Inflammation

Answer 2

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

Question 3

Acute inflammation

Answer 3

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

Question 4

VASCULAR PERMEABILITY

Answer 4

Endothelial cells of vessel wall contract
Endothelial injury
Transcytosis

Question 5

Endothelial cells of vessel wall contract

Answer 5

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

Question 6

Endothelial injury

Answer 6

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

Question 7

Transcytosis

Answer 7

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.

Question 8

Cellular reaction

Answer 8

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.

Question 9

Margination:

Answer 9

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

Question 10

Rolling:

Answer 10

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

Question 11

Adhesion:

Answer 11

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

Question 12

Transmigration:

Answer 12

Leucocyte is then encouraged to pass through endothelium to extravascular space

Question 13

Chemokines

Answer 13

stimulate migration and leucocyte move towards the chemical concentration gradient

Question 14

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

Answer 14

PECAM-1 – platelet endothelial cell adhesion molecule

Question 15

Chemotaxis:

Answer 15

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

Question 16

Neutrophils

Answer 16

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

Question 17

Function of leucocytes

Answer 17

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

Question 18

Toll

Answer 18

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

Question 19

G protein

Answer 19

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

Question 20

Opsonin receptors

Answer 20

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

Question 21

Cytokine receptors

Answer 21

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

Question 22

Phagocytosis

Answer 22

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.

Question 23

Outcomes

Answer 23

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.

Question 24

Chronic inflammation

Answer 24

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

Question 25

Granulomas

Answer 25

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.

Question 26

Clinical signs

Answer 26

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

Question 27

Signs and Symptoms (1)

Answer 27

``` Fever Tachycardia Hypotension Raised WCC Raised CRP ```

Question 28

Signs and Symptoms (2)

Answer 28

Anorexia General malaise Weight loss (chronic inflammation) Sepsis- large amount of toxins stimulate cytokines, can lead to cardiovascular failure (septic shock)

Question 29

Acute Inflammation

Answer 29

Rapid response Short lived NEUTROPHILS predominate Aim is complete resolution

Question 30

Outcomes of acute inflammation

Answer 30

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

Question 31

Chronic inflammation

Answer 31

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

Question 32

Can it be harmful? How?

Answer 32

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

Question 33

What can we do about it?

Answer 33

Medications Non-steroidal anti-inflammatories (NSAIDs) Anti-histamines Steroids Targeted biologics against immune response proteins e.g anti TNF

Question 34

What happens if there is no inflammatory response?

Answer 34

Defective inflammation → Increased susceptibility to infection Delayed healing of wounds Tissue damage Eg. hereditary immunodeficiency conditions, post-chemotherapy, medications

Question 35

Acute appendicitis

Answer 35

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

Question 36

Septic Arthritis

Answer 36

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

Question 37

Minor Injury

Answer 37

``` 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 ```

Question 38

Rheumatoid Arthritis

Answer 38

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

Question 39

Peptic Ulcers

Answer 39

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