Inflammation

Question 1

what does inflammation aim to do?

Answer 1

• get rid of damaged or necrotic tissue
• remove microorganisms or other foreign material
• sets the scene for regeneration to repair of tissues

Question 2

how can inflammation be harmful?

Answer 2

• hypersensitivity’s
• autoimmune reactions
• prolonged inflammation

Question 3

what are the cardinal signs of inflammation?

Answer 3

• Rubor (redness)
• Tumor (swelling)
• Calor (heat)
• Dolor (pain)
• Functio laesa (loss of function)

Question 4

is acute inflammation a rapid or slow response to stimuli?

Answer 4

rapid

Question 5

what 3 things happen in the rapid response to stimuli in acute inflammation?

Answer 5

• increased blood flow
• increased vascular permeability
• leukocyte emigration

Question 6

what stimuli can result in acute inflammation

Answer 6

• microorganisms e.g parasitres or bacteria
• Necrosis - ischaemia, trauma etc
• hypoxia
• Foreign bodies
• Hypersensitivity reactions / autoimmune disease

Question 7

How do blood vessels react to acute inflammation?

Answer 7

they change to allow plasma proteins and cells out of the circulation into the site of stimulus. They:
- release excess fluid into tissue or body cavities = called OEDEMA
- release of fluid and cells from the circulation is called = EXUDATION

Question 8

define oedema

Answer 8

release excess fluid into tissue or body cavities

Question 9

define exudation

Answer 9

release of fluid and cells from the circulation

Question 10

what is an exudate?

Answer 10

extracellular fluid, rich in protein and contains cells

Question 11

what is pus (purulent exudate) rich in?

Answer 11

leukocytes and debris of dead cell

Question 12

ultrafiltrates of plasma are caused by what?

Answer 12

loss of osmotic pressure or high hydrostatic pressure

Question 13

what is a transudate?

Answer 13

fluid with low protein content and little or no cellular material.

Question 14

when there is loss of hydrostatic pressure in a vessel what is the result

Answer 14

forms transudate fluid, fluid leakage into extracellular fluid

Question 15

when tissue gets damaged the vessels vasoconstrict and then what and what does it allow for?

Answer 15

vasodilation, the arterioles dilate opening new capillary beds in the region
- allows increased blood from to the tissue
causes erythema at the site

Question 16

what is erythema?

Answer 16

heat and redness

Question 17

what is vasodilation induced by?

Answer 17

histamine and nitric oxide acting on the sooth muscles of the vessels

Question 18

with vasodilation there is increased vascular permeability, what does this allow for?

Answer 18

allows escape of protein rich exudate into the tissue (oedema)

Question 19

Name the 3 mechanisms that promote the increase in vascular permeability

Answer 19

1. contraction of endothelial cells (increased inter endothelial spaces)
2. endothelial injury (necrosis and detachment)
3. Increased transport through endothelial cells (transcytosis)

Question 20

How does contraction of endothelial cells increase vascular permeability

Answer 20

• increased spaces between the endothelial cells
• typically immediate and transient response, mediated by chemical mediators like histamine
• sometimes delayed with prolonged leakage

Question 21

how does endothelial injury increase vascular permeability?

Answer 21

• direct damage to endothelial cells leading to necrosis and detachment from basement membrane
• starts immediately after injury is sustained for several hours until damaged vessels thrombosed or repaired

Question 22

how does transcytosis increase vascular permeability?

Answer 22

• fluids and proteins can be transported through endothelial cells (trasncytosis)
  channels created and vesiculovacuolar organelle allow this transport

Question 23

with increased vascular permeability what happens to proteins? specifically fibrin

Answer 23

• plasma leaving the vessels acts to dilute the stimulus of acute inflammation
• fibrinogen is one of the proteins which leaves the vessels in exudates
• fibrinogen polymerise to form fibrin
• this fibrin stops the stimulus spreading to nearby tissue and allows leukocytes to target cause of inflammation

Question 24

what is stasis?

Answer 24

slower blood flow and increased viscosity

Question 25

what is happening for stasis to occur

Answer 25

fluid loss and increased vessel diameter results in the slower blood flow increased concentration of red cells results in increased viscosity of blood

Question 26

stasis is observed as what?

Answer 26

vascular congestion

Question 27

how does stasis help with inflammation

Answer 27

allows leukocytes to accumulate and adhere on the vascular endothelium and migrate through the vessel wall to the stimulus

Question 28

how do lymphatic vessels react to inflammation?

Answer 28

- lymph flow increased draining oedema fluid - proliferate during inflammation - can result in other issues: lymphangitis, lymphadenitis

Question 29

what is lymphangitis?

Answer 29

secondary inflammation of lymphatic vessels

Question 30

what is lymphadenitis?

Answer 30

draining lymph nodes become inflamed

Question 31

what is reactive/inflammatory lymphadenitis

Answer 31

lymph nodes increase in size due to hyperplasia of lymphoid follicles

Question 32

describe how leukocytes adhere to the endothelium

Answer 32

- adhesion to endothelium: when stasis occurs there leukocytes make contact with the endothelial surface = margination. these cells start rolling along the endothelium before adhering with it. This adhesion is by complementary adhesion molecules. Cytokines enhance expression of the adhesion molecules how - SELECTINS are proteins that mediate rolling: L-selectin E-selectin P-selectin - the selections bind to ligands - these selectins and ligands are expressed in response CYTOKINES - interactions beween these two is LOW-AFFINITY, so that the leukocytes can bind, detach and re-attach quickly so they can ROLL along the endothelium

Question 33

where are these different selections expressed: L-selectin E-selectin P-selectin

Answer 33

L selectin = expressed on leukocytes E selectin = expressed on endothelial cells P selectin expressed on platelets and endothelial cells

Question 34

Rolling slows down the luekocyte allowing stronger adhesions. What is this mediated by and how?

Answer 34

mediated by integrins ICAM-1 on endothelial cells binds to B2 integrins VCAM-1 on endothelial cells binds to B1 integrins this stops the rolling, reorganises the cytoskeleton so that the leukocyte spreads out on the endothelial surface

Question 35

describe how leukocytes migrate across the vessel

Answer 35

- once leukocytes have adhered they need to move through endothelium = diapedesis (or transmigration) - migration down a chemokine concentration gradient - PECAM-1, JAM A, JAM C mediate (receptors) transmigration - The leukocyte gets through basement membrane due toSECRETING COLLAGENASES - leukocytes adhere to extracellular matrix using intwgrins and CD44

Question 36

what are leukocyte adhesion deficiencies characterised by?

Answer 36

recurrent bacterial infections due to the inability of leukocytes to perform the steps

Question 37

what is chemotaxis?

Answer 37

migration of cells along a chemical gradient

Question 38

describe how leukocytes migrate to the stimulus?

Answer 38

- chemotaxis, used by leukocytes migrating towards sites of injury - exogenous: bacterial products, such as lipids and peptides - endogenous: cytokines, complement system, arachidonic acid metabolites all of these chemotactic agents bond to receptors on the surface of leukocytes Downstream signalling alters the cytoskeleton of leukocytes, causing filopodia to move the cell in the direction of the stimulus, along the chemical gradient.

Question 39

Anne and describe the four types of receptors in the recognition of foreign organisms and dead tissue

Answer 39

- G protein-coupled receptors found on leukocytes they recognise short bacterial peptides - Toll-like receptors (TLRs) Recognise components of different microbes - Cytokine Receptors Leukocytes express these in response to microbes -Opsonin Receptors proteins that can be used to kill organisms. The act of coating is called opsonisation. These receptors are present on leukocytes.