MoD - Acute inflammation

Question 0

What is acute inflammation?

Answer 0

This is a rapid response to an agent that aims to deliver mediators to a site of damage/infection. These mediators bring about a series of tissue changes.

Question 1

What are the causes of acute inflammation?

Answer 1

Foreign bodies 
Immune reactions 
Infections
Tissue necrosis 
Trauma 
Physical and chemical agents

Question 2

What are the clinical signs of acute inflammation?

Answer 2

Rubor - redness
Color - heat
Tumour - swelling
Dolor - pain

Question 3

What are the types of chemical mediators and what are their functions?

Answer 3

Vasoactive amines (histamine and serotonin) cause vasodilation + vascular permeability 
Vasoactive peptides (bradykinin) - vascular permeability + pain
Complement - C3a and C5a - chemotaxis and punch holes in bacteria
Cytokines/chemokines- interleukins, TNF

Question 4

What do the mediators cause?

Answer 4

Tissue changes

• changes in blood flow
• fluid loss from vessels
• neutrophil migration

Question 5

What changes in blood flow do mediators bring about?

Answer 5

Initial vasoconstriction of arterioles
Then vasodilation of arterioles and capillaries
Increased permeability of BV
Increased concentration of RBCs in small vessels - increased blood viscosity = STASIS

Question 6

Which specific mediators cause vasodilation and increase vascular permeability?

Answer 6

Histamine - released from mast cells, basophils and platelets in response to physical damage or cytokines (from macrophages, B and T cells)
Serotonin
Bradykinin (also causes pain)

Question 7

How is fluid flow across vessel walls determined?

Answer 7

The balance of hydrostatic pressure and oncotic pressure (colloid osmotic pressure)

Question 8

What is oncotic pressure?

Answer 8

The pressure exerted by proteins (usually albumin) in blood plasma.
Usually tends to pull water in

Question 9

What does arteriolar dilation lead to?

Answer 9

This leads to an increased hydrostatic pressure

Question 10

What does an increase in vascular permeability lead to?

Answer 10

Endothelial cells contract and pull apart leaving gaps for plasma protein. And protein rich fluid moves into the interstitium.

Question 11

What is exudate?

Answer 11

This is the protein rich fluid lost in oedema.

Question 12

What is a transudate?

Answer 12

This is low protein fluid loss due to hydrostatic pressure imbalance.
E,g cardiac failure

Question 13

What is oedema?

Answer 13

Net flow of fluid out of vessels

Question 14

What are neutrophils?

Answer 14

First response to site of inflammation.
They migrate through BVs and tissue space following chemical signals 
Ie. Interleukins, C5a (chemotaxis)
Predominate cells in pus 
They also have a multi-lobed nucleus 
They are phagocytotic cells

Question 15

What are the main proteins found in exudate?

Answer 15

Opsonins - coat foreign material - enhance phagocytosis
Complement - bacteria perforation
Antibodies - act as opsonins by binding to microorganism surface.

Question 16

What are the stages in neutrophils reaches their target?

HINT - getting though BV wall

Answer 16

They are ‘summoned’ to place of injury by chemotaxis
They are activated by sodium and calcium entering the cell (sticky)
They marginate (line up near endothelial wall)
They roll along wall until they adhere (bind firmly)
Then they migrate through BV wall
They crawl though endothelium (diapedesis)

Question 17

How do neutrophils act on their target?

Answer 17

They recognise bacteria via opsonins.
Then they phagocytose the bacteria
The membrane round the phagocyte forms a crater
Degranulation occurs in the phagosome
Killing by free radical injection or proteases occurs.

Question 18

What is the difference between oxygen dependent killing and oxygen independent?

Answer 18

Ox dependent injects free radicals into phagosome

Ox independent uses proteases and phospholipases

Question 19

Name some complications of acute inflammation

Answer 19

Damage to normal tissue from neutrophil substances
Obstruction of rubes from swelling of exudate
Loss of fluid

Question 20

What are the systematic effects of acute inflammation

Answer 20

-Fever- thermostat turned up
-Leucocytosis - no of circulating leukocytes increase (esp neutrophils)
-Acute phase response - change in levels of plasma protein
Liver changes protein synthesis pattern
-Shock

Question 21

How is acute inflammation resolved?

Answer 21

Mediators have a short half life so degrade quickly and are only present as long as the stimulus persists
Exudate is reabsorbed into the vessels or drained to lymphatics
Fibrin is degraded
Neutrophils undergo apoptosis (and are phagocytosed)

Question 22

What is hereditary angio-oedema?

Answer 22

Autosomal dominant
Deficient in C1 esterase inhibiter (component of complement syst)
Patients have attack of rapid oedema of the dermis and intestine.
Gives abdominal pain

Question 23

What is alpha 1 antitrypsin deficiency?

Answer 23

Autosomal recessive
Low level of alpha 1 antitrypsin (a protease inhibitor which deactivates neutrophil enzymes)
Proteases are realised unchecked so patients develop emphysema.
Hepatocytes also produce misfolded version which polymerises in the ER

Question 24

What is chronic granulomatous disease?

Answer 24

This is when phagocytes are unable to produce the superoxide radical.
So they fail to kill bacteria and chronic inflammation occurs