Session 2: Acute Inflammation

Question 1

Define inflammation.

Answer 1

The response of living tissue to injury.

Question 2

Give some features of acute inflammation.

Answer 2

Immediate
Short duration
Innate
Stereotyped (The same regardless of toxic stimulus)
Limits damage

Question 3

Give some features of inflammation in general.

Answer 3

It is vascular and cellular:
There is an accumulation of exudate or transudate as well as neutrophils in tissue.
It is controlled by a variety of chemical mediators that are derived from plasma or cells.
It is induced for protective purposes but can cause local and systemic complications.

Question 4

What are the clinical signs of inflammation?

Answer 4

Can Tubby Don Lose Rugby
Calor (heat)
Tumor (swelling)
Dolor (pain)
Loss of function
Rubor (redness)

Question 5

As an inflammation is induced what happens to changes in blood flow? Give four steps.

Answer 5

1. Vasoconstriction shortly after onset and only lasts for seconds
2. Vasodilation which will follow and lasts for minutes. This also accounts for the rubor and calor.
3. The permeability of the blood vessels will increase and because of this oedema will form as there will be more fluid in the surrounding tissue (interstitium)
4. Lastly due to the increase in permeability and fluid being moved into the interstitium the remaining substance in the vessels will be a thicker fluid. This is called red cell stasis and means that the fluid inside the vessels will move slower.

Question 6

What is Starling’s law?

Answer 6

Describes the movement of fluid into tissue by controlling factors.

Question 7

What controlling factors of movement of fluid between vessels and interstitium are there?

Answer 7

Hydrostatic pressure and oncotic pressure.

Question 8

Explain hydrostatic pressure.

Answer 8

Pressure exerted on vessel wall by fluid. This means a high hydrostatic pressure pushes fluid away.

Question 9

Explain oncotic pressure.

Answer 9

Essentially the opposite of hydrostatic pressure in the sense that instead of pushing it is pulling fluid towards it.
It is pressure exerted by plasma protein which pulls fluid towards it. A high oncotic pressure means a lot of proteins and fluid will follow.

Question 10

Where will fluid flow in increased hydrostatic capillary pressure?

Answer 10

Increased flow of fluid out of the vessel into interstitium.

Question 11

What will happen if there is an increased oncotic pressure in the interstitium?

Answer 11

An increased amount of fluid will move from the vessel to the interstitium.
Both pressures are found in both vessels and interstitium!

Question 12

Explain what happens to the movement of fluid between vessels and interstitium/tissue in acute inflammation.

Answer 12

Vasodilation
Increased hydrostatic pressure in capillaries.
Increased oncotic pressure in interstitium.
Net flow out of vessel causing oedema.

Vasodilation occurs slightly after onset which will increase the capillary hydrostatic pressure. This increases vessel permeability and there will also be leakage of plasma proteins into the interstitium as the endothelium gets somewhat ‘fragmented’.
This increased oncotic pressure in the interstitium causing a net flow of fluid into interstitium. This causes oedema.

Question 13

What is a consequence other than oedema as a result of the net flow being increased into interstitium.

Answer 13

It increases the viscosity of the blood which means the blood will be thicker and there will be a reduced flow through vessels called red cell stasis.

Question 14

What types of interstitial fluid are there? Two main types.

Answer 14

Exudate and transudate.

Question 15

What are the major differences between exudate and transudate?

Answer 15

Exudate:

• occurs in inflammation
• there is an increase in vascular permeability which means that exudate arises due to a leaky vascular wall
• it is protein rich because of the leaky vascular wall.

Transudate:

• there is fluid loss due to increased vascular hydrostatic pressure OR reduced capillary oncotic pressure.
• there is no change of vascular permeability so the vessel walls stay the same
• because of no change in vascular permeability there will be no leakage of proteins into the interstitium which means that transudate is NOT protein rich.
• This does not occur in inflammation.

Question 16

Give causes of transudate.

Answer 16

Heart failure which results in increased hydrostatic pressure.
Hepatic failure which results in a reduced oncotic pressure. (Low protein levels means less oncotic pressure which leads to oedema.)
Renal failure results in a reduced oncotic pressure.

Question 17

Give some mechanisms of increased vascular permeability.

Answer 17

Histamine and leuktrienes which acts on endothelial contraction (gaps between endothelial cells)
Cytokines IL-1 and TNF involved in the reorganisation of endothelial cytoskeleton.
Direct injury resulting in leakage.
Leucocyte dependent injury of the endothelial such as enzymes of free radicals from the white blood cells.

Question 18

What is the primary leucocyte involved in acute inflammation?

Answer 18

Neutrophils (Type of granulocyte)

Also called neutrophil polymorph or just polymorph.

Question 19

What do neutrophils look like in histology?

Answer 19

The colour is a mix of an eosinophil and a basophil. It is stained fairly neutral and blueish. It has a trilobed nucleus that can resemble a horseshoe.

Question 20

Give the stages of how neutrophils move from vessels to interstitium.

Answer 20

1. Margination
2. Rolling
3. Adhesion
4. Emigration

Question 21

Explain margination.

Answer 21

When stasis is induced due to the thick blood as a result of the increased vascular permeability the neutrophils will line up at the edges of the blood vessels along the endothelium.

Question 22

Explain rolling.

Answer 22

The neutrophils will roll along the endothelium and sticking to it intermittently.

Question 23

Explain adhesion.

Answer 23

The neutrophils will now bind with a higher affinity and get ‘stuck’.

Question 24

Explain emigration (diapedesis).

Answer 24

Neutrophils enter the interstitium via gaps in the endothelial wall.

Question 25

What are the main adhesion molecules of which neutrophils stick to the endothelium?

Answer 25

Selectins | Integrins

Question 26

Where can selectins be found? What happens to them during inflammation?

Answer 26

They can be found on the endothelial cell surface. They are upregulated (increased expression) by chemical mediators.

Question 27

Where can intergrins be found? What is the main difference between integrins and selectins?

Answer 27

They are found on the neutrophil’s surface. They have a higher affinity than the selectins.

Question 28

What roles do selectins and integrins have in rolling and adhesion?

Answer 28

In rolling, glycoproteins from the neutrophils will bind to E-selectins and P-selectins on the endothelial wall. This is not high affinity and the neutrophils will roll. In adhesion stage the integrin from the neutrophil will bind to ICAM-1 which is a high affinity binding and will stick more intensely than the glycoprotein-selectin binding.

Question 29

How do neutrophils move through the interstitium?

Answer 29

By a mechanism called chemotaxis. | Chemotaxis is the movement along a chemical gradient of chemoattractants.

Question 30

Give actions of neutrophils.

Answer 30

Phagocytosis | Opsonisation

Question 31

How can neutrophils kill organisms? (Two ways)

Answer 31

Oxygen dependent | Oxygen independent

Question 32

Explain how neutrophils kill organisms via oxygen dependent mechanism.

Answer 32

By oxidative burst with free radicals like O*, OH* and H2O2. | Also reactive nitrogen intermediates like NO and NO2

Question 33

Explain how neutrophils kill organisms via oxygen independent mechanism.

Answer 33

Lysozyme with hydrolytic enzymes break down organisms with help of defensins.

Question 34

Why is acute inflammation so effective?

Answer 34

The vascular phase with exudation of fluid into interstitial causes oedema. The cellular phase with infiltration of neutrophils kills pathogen.

Question 35

Why is oedema beneficial?

Answer 35

Because it dilutes the toxins. It delivers plasma proteins to area of injury like fibrin, inflammatory mediators and immunoglobulins. Fibrin creates a mesh which limits the spread of the toxin to other sites. It also increases lymphatic draining from the area of the injury so the antigens will end up in the lymph nodes inducing an adaptive immune response.

Question 36

How do inflammatory cells limit damage?

Answer 36

Removal of toxins and pathogenic organisms. Removal of necrotic tissue. Release of chemical mediators which stimulate and regulate further inflammation. Stimulates pain.

Question 37

Why is it beneficial to stimulate pain?

Answer 37

To encourage rest and limits risk of further damage.

Question 38

What are chemical mediators released by?

Answer 38

Activated inflammatory cells Platelets Endothelial cells Exotoxins

Question 39

3 stages of inflammation.

Answer 39

Changes in blood flow Movement of fluid into tissue Infiltration of inflammatory cells into tissue.

Question 40

Say there are 5 steps instead of inflammation: Vasodilation Increased vascular permeability Chemotaxis Fever Pain. What chemical mediators can be found at each step? (Follow up flashcards)

Answer 40

-

Question 41

Chemical mediators at vasodilation.

Answer 41

Histamine, serotonin, prostaglandins and NO

Question 42

Chemical mediators at increased vascular permeability.

Answer 42

Histamine, bradykinin, leukotrienes, C3a and C5a

Question 43

Chemical mediators at chemotaxis.

Answer 43

C5a, LTB4, TNF-a, IL-1, Bacterial peptides

Question 44

Chemical mediators at fever.

Answer 44

Prostaglandins, IL-1, TNF-a, IL-6.

Question 45

Chemical mediators at pain.

Answer 45

Bradykinin, substance P, prostaglandins.

Question 46

Two main complications of acute inflammation. (Very general)

Answer 46

Local or systemic.

Question 47

Local complications of acute inflammation.

Answer 47

Swelling which can cause blockage of nearby ducts and tubes like bile duct and intestines. Exudate which can cause compression of organs like in cardiac tamponade. Loss of fluid like in burns leading to dehydration. Pain and loss of function of muscle (atrophy) or psycho-social consequences of chronic pain.

Question 48

Give examples of systemic complications.

Answer 48

``` Fever NSAIDS Leucocytosis Acute phase proteins -> acute phase response Septic shock ```

Question 49

Explain how a fever arises generally.

Answer 49

Endogenous pyrogens like prostaglandin, IL-1 and TNF-a released in inflammation act on hypothalamus to alter baseline temperature control. NSAIDs are common drugs to treat inflammation and fever.

Question 50

How do NSAIDs work?

Answer 50

By blocking cycle-oxygenase enzymes involved in the production of prostaglandins.

Question 51

How can leucocytosis happen in acute inflammation?

Answer 51

IL-1 and TNF act on bone marrow to increase production of white blood cells.

Question 52

How can you by blood test differ between bacterial infection and viral infection?

Answer 52

By looking at white blood cells. | Bacterial infections have more neutrophils and viral infections have more lymphocytes.

Question 53

Symptoms of acute phase response.

Answer 53

Malaise Reduced appetite Altered sleep Tachycardia

Question 54

How does acute phase response happen?

Answer 54

Due to acute phase proteins in acute inflammation. Release of proteins from inflammatory cells like CRP, alpha1 antitrypsin, haptoglobin, fibrinogen and serum amyloid A protein.

Question 55

Complications of septic shock.

Answer 55

Overwhelming infection with huge release of chemical mediators causing widespread vasodilation, hypotension and tachycardia. Multiorgan failure as perfusion stops working and ultimate death.

Question 56

Give 4 fates of acute inflammation.

Answer 56

Complete resolution Continued acute inflammation leading to chronic inflammation. Can also lead to abscess Chronic inflammation and fibrous repair leading to scar tissue formation. Death

Question 57

Explain what happens in complete resolution.

Answer 57

All changes will gradually reverse meaning neutrophils no longer marginate, vascular permeability returns to normal and vessel calibre returns to normal as well. Exudate drains away via lymphatics Fibrin is degraded Neutrophils die, break up and get phagocytosed Architecture is preserved Mediators are eventually degraded

Question 58

Give common causes of acute inflammation.

Answer 58

Appendicitis Pneumonia Bacterial meningitis Abscess Inflammation of serous cavities Hereditary angio-oedema Alpha-1 antitrypsin deficiency Chronic granulomatous disease

Question 59

Common causative organisms of pneumonia.

Answer 59

Streptococcus pneumoniae or haemophilus influenzae

Question 60

Signs and symptoms of pneumonia.

Answer 60

``` Shortness of breath Fever Cough Sputum production Chest pain ```

Question 61

Causative organisms of bacterial meningitis.

Answer 61

Group B Streptococcus E. coli N. meningitidis

Question 62

Clinical signs of bacterial meningitis.

Answer 62

``` Neck stiffness Fever Photophobia Altered mental state Non-blanching rash ```

Question 63

What is an abscess?

Answer 63

Accumulation of dead and dying neutrophils Associated with liquefactive necrosis Causes compression of surrounding structures and nerves leading to pain and blockage of ducts.

Question 64

Causes of inflammation of serous cavities.

Answer 64

Variety of causes but it's essentially exudate which pours into a serious cavity like in ascites, pleural effusion and pericardial effusion.