Acute inflammation

Question 1

what is inflammation?

Answer 1

the response of living tissue to injury

Question 2

what is acute inflammation?

Answer 2

• immediate
• short duration
• innate response
• stereotyped - the same for all injuries
• limits chronic inflammation

Question 3

what are the 2 phases of acute inflammation?

Answer 3

Vascular phase:
* changes in blood flow
* accumulation of exudate

Cellular phase:
* delivery of neutrophils

Question 4

how is acute inflammation controlled?

Answer 4

chemical mediators

Question 5

what causes acute inflammation?

Answer 5

• trauma
• micro organisms
• hypersensitivity reactions
• other illness (e.g. necrosis)

Question 6

what are the clinical signs of acute inflammation?

Answer 6

The 5 cardinal signs:
1. rubor
2. tumor
3. dolor
4. calor
5. loss of function

Question 7

what happens in the vascular phase in the acute inflammatory response?

Answer 7

1. blood vessels undergo vasoconstriction (few seconds)
2. then blood vessels undergo vasodilation and this causes rubo and dolor (lasts a few minutes)
3. blood vessels become more permeable
4. exudate forms and the blood in vessels becomes viscous and stasis
5. fluid drains into lymph nodes and presents antigens to antigen presenting cells triggering an immune response

Question 8

what is Starling’s law?

Answer 8

fluid movement is based on 2 pressure:
1. hydrostatic pressure - pressure exerted on vessel walls by fluid (forces fluid out of vessels)
2. oncotic pressure - pressure exerted by proteins (draws fluid back into vessels)

Question 9

what are the impacts of acute inflammation on Starling’s law?

Answer 9

• vasodilation - increases hydrostatic pressure
• increased vessel permeability - plasma proteins move into interstitial space which decreases oncotic pressure
  net movement of water out of vessels causes oedema which gives rise to tumor

Question 10

what happens to the blood after fluid moves out?

Answer 10

blood becomes more viscous (sticky)
this results in stasis of blood

Question 11

what are the 2 types of interstitial fluid?

Answer 11

Exudate:
* increased vascular permability
* protein rich fluid
* occurs in inflammation

Transudate:
* vascular permeability unchanged
* fluid movement is due to - increased capillary hydrostatic pressure and reduced capillary oncotic pressure
* occurs in heart failure

Question 12

how do vessel walls become leaky?

Answer 12

1. endothelial cells shrink so spaces between endothelial cells increases
2. injury to endothelial cells as a result of trauma
3. WBC release enzymes and free radicals which damage endothelial cells

Question 13

how is the vascular phase effective?

Answer 13

• interstitial fluid dilutes toxins
• exudate delivers proteions and immunoglobulins
• fluid drains into lymph nodes - when this occurs antigens are delivered to antigen presenting cells (triggers immune response)

Question 14

what happens in the cellular phase of the acute inflammatory response?

Answer 14

neutrophils are the main cells involved in the cellular phase:
* WBC’s involved in acute inflammation
* trilobed nucleus

Question 15

how do neutrophils escape blood vessels?

Answer 15

1. margination - neutrophils move to periphary of vessels
2. rolling - weak intermitent bonds (selectins) form between the neutrophils and endothelial cells
3. adhesion - strong bonds (integrins) formbetween neutrophils and endothelial cells
4. emigration - neutrophils move out of vessels into interstitial space

Question 16

what are the different adhesion molecules?

Answer 16

selectins:
* involved in forming weak intermitent bonds between endothelial cells and neutrophils allowing rolling

Integrins:
* when selectins bind then integrins enter a high affinity state which allows for the formation of stronger bonds between the endothelial cells and neutrophils allowing adhesion

Question 17

how do neutrophils move through interstitial space to area of injury?

Answer 17

Chemotaxis - movement along an increasing electrochemicla gradient of chemoattractants

neutrophils move towards the bacterial peptides, inflammatory mediators etc.

Question 18

what do neutrophils do?

Answer 18

Phagocytosis:
* neutrophils rearrange cytoskeleton to form around a pathogen forming a phagosome
* phagosomes fuse with lysosme to form phagolysosome

Neutrophils also release inflammatory mediators

Question 19

how do neutrophils recognise pathogens?

Answer 19

Opsonisation:
* toxin is covered in C3b + Fc (opsonins on the surface of pathogens)
* neutrophils have receptors specific to these opsonins so can bind to them

Question 19

how do neutrophils actually kill pathogens?

Answer 19

2 proccesses occur in the phagolysosome

Oxygen dependent:
* uses free radicals
* hydrogen peroxide
* nitric oxide

Oxygen independent:
* enzymes in the lysosomes
* defensins

Question 20

how is the cellular phase effective?

Answer 20

• removes pathogens + necrotic tissue
• neutrophils release inflammatory mediators which can stimulate or inhibit inflammation

Question 21

what are the different inflammatory mediators?

Answer 21

chemical messangers which control + co-ordinate the inflammatory response

originate from:
* activated inflammatory cells
* platelets
* endothelial cells
* toxins

Question 22

which chemical mediators cause vasodilation?

Answer 22

histamine
serotonin
prostaglandins
nitric oxide

Question 23

which chemical mediators cause increased vessel permeability?

Answer 23

histamine
bradykinin
leukotrienes
C3a + C5a

Question 24

which chemical mediators cause chemotaxis?

Answer 24

C5a
TNF-a
IL-1
bacterial peptides

Question 25

which chemical mediators cause a systemic response?

Answer 25

prostoglandins
IL-1
IL-6
TNF-a

Question 26

which chemical mediators cause pain?

Answer 26

bradykinin
substance P
prostoglandins

Question 27

what are the local complications associated with acute inflammation?

Answer 27

swelling / tumor causes:
* compression of tubes (airways, bile duct)
* compression of organs (pericarditis)
* severe dehydration (after burns)
* pain

Question 28

what are the systemic complications associated wth acute inflammation?

Answer 28

Fever:
* inflammatory mediators are pyrogenes (e.g. prostoglandins, IL-1, IL-6) which make us feel warmer

Leucocytosis:
* increased production of WBC
* fights infection
* can measure WBC levels and determine what is causing infection

Acute phase response: lethargy, sleep, tachycardia
* stimulates rest and sleep
* occurs as a result of acute phase proteins (CRP) - measuring CRP can be used to determine if treatment is working since levels should drop

Septic shock:
* huge release of chemical mediators
* widespread vasodilation
* hypotension + tachycardia
* multi-organ failure
* can be fatal

Question 29

what are NSAID’s?

Answer 29

drugs which block enzymes involved in the production of prostaglandins
reduces fever + act as pain relief associated with acute inflammation

Question 30

what happens after acute inflammation?

Answer 30

Complete resolution:
* mediators have short half life
* vessles return to normal state
* neutrophils undergo apoptosis
* exudate is drained via lymphatics
* if tissue architecture is preserved then can undergo regeneration

Repair with connective tissue:
* extensive tissue damage

Progression to chronic inflammation:
* prolonged inflammation with repair