Session 2 - Acute inflammation

Question 1

How does acute inflammation evolve?

Answer 1

It is something that occurs over a matter of hours or days

Question 2

What is a leukocyte?

Answer 2

This is another term for a white blood cell. You have many different types including lymphocytes, granulocytes and monocytes.

Question 3

Provide some examples of causes of acute inflammation?

Answer 3

• Foreign bodies (splinters, dirt, sutures)
• Immune reactions
• Infections (bacterial, viral, parasitic) and microbial toxins
• Tissue necrosis
• Trauma
• Physical agents
• Chemical agents

Question 4

What are the classical signs of acute inflammation?

Answer 4

• Rubor = redness
• Calor = heat
• Tumour = swelling
• Dolor = pain
• Loss of function = this enforces rest and reduces the chance of further damage.

Question 5

The first thing that happens in acute inflammation is a period of brief vasoconstriction followed by vasodilation of the arterioles. What is the main inflammatory mediator that brings about this vasodilation?

Answer 5

Histamine.

Question 6

What is the role of leukotrienes?

Answer 6

They stimulate bronchoconstriction and this is one of the leading pathologies in asthma.

They stimulate the production of cytokines (such as histamine) from mast cells and therefore play a role in vasodilation - “leakytrienes”.

Question 7

Vasodilation ensures that fluid containing plasma proteins will be delivered to the site of injury. By what other mechanisms does it ensure this (other than the venules becoming leaky due to the vasodilation of the arterioles)

Answer 7

This changes results in an increased haematocrit and therefore increased total peripheral resistance. Blood outflow from the area is hampered and this causes an increased pressure upstream which will cause further vasodilation and further delivery of plasma proteins to the site of injury.

Question 8

Where is histamine found?

Answer 8

It is stored within the granules of mast cells, basophils and platelets.

Question 9

What is the role of histamine?

Answer 9

• Histamine causes endothelial cells to contract and pull apart and therefore causes:
• vasodilation of arterioles
• venular leakage
• pain

Question 10

What is the role of prostaglandins?

Answer 10

• Makes the skin more sensitive to pain
• Vasodilation
• Causes fever

Question 11

What are the main forces that drive fluid out of the vessels and back into the blood vessels?

Answer 11

• Out of the blood vessels = hydrostatic pressure
• Into the blood vessels = colloidal osmotic pressure

Question 12

Describe the process of swelling - what causes fluid to leak into the interstitium and stay there for an ‘acute’ period of time?

Answer 12

• The semipermeable membrane becomes leaky.
• Arterioles dilate increasing capillary pressure - therefore the force driving fluid out of the vessels is increased
• Colloid oncotic pressure gradient is lost due to the loss of plasma proteins into the tissue spaces (the osmotic pressure is roughly equivalent to that of the blood).

Question 13

What is the name of fluids in the tissues that are:

protein rich?

protein poor?

Answer 13

Protein rich fluid is called exudate

Protein poor fluid is called transudate (note that there is no endothelial cell contraction in this meaning that there aren’t increased gaps for proteins to leak out of).

Question 14

Name some chemical mediators that induce vascular leakage?

Answer 14

• Histamine
• Serotonin
• Bradykinin
• Complement (c3a, c4a and c5a)

Question 15

What is the lifespan of a neutrophil?

Answer 15

12-20 hours

Question 16

What are the different stages of neutrophil migration? Describe each term.

Answer 16

1. chemotaxis = where the neutrophil is summoned to the site of injury by chemical mediators
2. activation = switches to a higher metabolic level
3. margination = neutrophil sticks to the endothelial surface
4. Diapedesis = the neutrophil crawls through the endothelium
5. recognition attachment = neutrophil recognises the bacterium and attaches.
6. Phagocytosis

Question 17

What is chemotaxis?

Answer 17

This is the directional movement towards a chemotaxin. Examples of chemotaxins including endotoxins, clotted blood (as fibrin degradation products and thrombin are chemoattractants), C3, C4, and C5.

Question 18

What is margination? What are the two processes found in margination?

Answer 18

Rolling and adhesion. When the neutrophil is rolling along the endothelium it is binding to selectins. When it undergoes adhesion it binds to integrins such as ICAM-1. The number of selectins and the activation of integrins is done via chemotaxins and mediators.

Question 19

Discuss the process of diapedesis.

Answer 19

Leucocytes produce collagenase which digests the basement membrane. This will take around 3-9 minutes.

Question 20

Provide some examples of opsonins.

Answer 20

1. Mannose binding lectin
2. C3b
3. IgG antibody - this is an important opsonin but wont be there the first time that a bacteria is encountered.

Question 21

What is the name of the enzyme that produces prostaglandins or thromboxanes from arachidonic acid?

Answer 21

cyclo-oxygenase

Question 22

What is the name of the enzyme that produces leukotrienes from arachidonic acid?

Answer 22

lipoxygenase.

Question 23

What are some examples of pyrogenic cytokines? How do they cause fever?

Answer 23

Tumour necrosis factor and interleukin-1. They cause an increase in the production of prostaglandin E2 within the anterior hypothalamus.

Question 24

what cells produce colony stimulating factors?

Answer 24

macrophages and endothelial cells.

Question 25

What is the acute phase response?

Answer 25

This is where the liver will change the levels of some plasma proteins in response to inflammatory mediators. It will make lower levels of albumin and increased amounts of fibrinogen, ceruoloplasmin, C3 and alpha 1 antitrypsin, and CRP.

Question 26

What causes the acute phase response?

Answer 26

The release of cytokines during inflammation.

Question 27

What symptoms does a patient have during the acute phase response?

Answer 27

Sleepiness and a lack of appetite.

Question 28

What are the four systemic complications of inflammation?

Answer 28

1. Fever
2. Leucocytosis
3. Acute phase response
4. Shock

Question 29

What is the name of the type of shock that is caused by sepsis/anaphylaxis?

Answer 29

Redistributive shock - this means that the circulation volume doesn’t change however the volume of the vasculature its self does.

Question 30

What are the four different types of exudate?

Answer 30

Pus/abscess - thick and creamy due to the high concentration of neutrophils

haemorrhagic exudate - this is where it is red to the naked eye due to infiltration of red blood cells. This is seen in malignant tumours

Serous exudate - this is where the fluid is protein rich but it is clear due to the presence of few leucocytes.

Fibrinous exudate - This is where the exudate has a high concentration of fibrin. This happens quite often in visceral membranes and in the pericardium this can produce a rubbing sound.

Question 31

What is hereditary angio-oedema?

Answer 31

A rare autosomal dominant condition in which sufferers have an inherited deficiency of C1-esterase inhibitor (a component of the compliment system).

Patients will have attacks of non-itchy cutaneous angio-oedema. This is due to rapid oedema of the dermis, subcutaneous tissue, mucosal surfaces, etc. There is often a family history of sudden death.

Question 32

What is alpha1-antitrypsin deficiency? What chronic condition can this condition cause?

Answer 32

This is an autosomal recessive disorder with varying levels of severity in which there are low levels of alpha-1 antitrypsin - a protease inhibitor which deactivates enzymes released from neutrophils at the site of inflammation.

This genetic condition can cause emphysema. This is because the proteases released from the neutrophils will destroy lung parenchymal tissue.

Question 33

What is chronic granulomatous disease?

Answer 33

This is a genetic condition that causes a deficiency in NADPH oxidase. This means that phagocytes are unable to generate the superoxide radical meaning that phagocytes cannot undergo an oxygen burst.

Patients will have numerous granulomas and abscesses affecting the skin, lymph nodes, lung, liver and bones. However the granulomas are INEFFECTIVE at eliminating the infectious agents.

Question 34

What is bradykinin?

Answer 34

This is a chemical mediator that causes vasodilation and increases sensitivity to pain.

Side note: ACE inhibitors inhibit the breakdown of bradykinin into peptide fragments, and bradykinin causes bronchial constriction and this is why a side effect of ACE inhibitors is a dry cough.