Acute Inflammation

Question 1

What is acute inflammation?

Answer 1

Acute Inflammation is the response of living tissue to injury.

Question 2

What are the characteristics of acute inflammation?

Answer 2

• Innate,
• immediate and early,
• stereotyped (the same every time),
• short duration -minutes/hours/few days.

Question 3

What is the purpose of acute inflamation?

Answer 3

It is Initiated to limit the tissue damage

Question 4

What are the two types of reaction involved in acute inflammation?

Answer 4

1. Vascular and cellular reactions- accumulation of fluid exudate and neutrophild in tissues.

These reactions are controlled by a variety of chemical mediators derived from plasma or cells.

Acute inflamation is protective but can lead to local complications and systemic effects.

Question 5

What are the causes of acute inflammation?

Answer 5

• Microbial Infections eg pyogenic organisms
• Hypersensitivity reactions (acute phase)
• Physical agents
• Chemicals
• Tissue necrosis

Question 6

What are the clinical features of acute inflamation?

Answer 6

• Rubor (redness)
• Tumor (swelling)
• Calor (heat)
• Dolor (pain)
• Loss of function

Question 7

What changes in tissue occur during acute inflammation?

Answer 7

1. Changes in blood flow
2. Exudation of fluid into tissues
3. Infiltration of inflammatory cells.

There are inflammatory mediators of each step.

Question 8

What are the vascular changes in acute inflammation?

Answer 8

1. Transient vasoconstriction of arterioles (few seconds)
2. Vasodilation of arterioles and then capillaries (increase in blood flow causing heat and redness)
3. Increased permeability of blood cells causing excudation of protein rich fluid into tissues and slowing of circulation (swelling)
4. Concentration of RBCs in small vessels and increased viscosity of blood = stasis

Question 9

What is the first chemical mediator? (first 30 mins)

Answer 9

HISTAMINE

This is released from mast cells, basophils and platelets in response to many stimumi eg:

physical damage, immunological reactions, C3a, C5a, IL-1, factors from neutrophils and platelets.

It causes:

vascular dilation, transient increase in vascular permiability, pain

Question 10

What chemical mediators cause a persistant response?

Answer 10

Many and varied chemical mediators, interlinked and of carrying important.

Incompletely understood eg leukotrienes and bradykinin

Question 11

What is Starling’s law?

Answer 11

Fluid flow across vessel wall is determined by the balance of hydrostatic pressure and colloid osmotic pressure compairing plasma and interstitial fluid.

If there is increased hydrostatic pressure then fluid flows out if vessel.

If there is increased colloid osmotic pressure of interstitium then fluid flows out if the vessel.

Question 12

Define oedema

Answer 12

Increased fluid in tissue space

Question 13

How does fluid exudation occur in acute inflammation?

Answer 13

• Arteriolar dilation leads to an increase in hydrostatic pressure.
• Increased permeability of vessel walls leads to loss of protein into interstitum.

Therefore, net flow of fluid out of vessel which causes oedema.

Question 14

What is transudate oedema?

Answer 14

Fluid loss due to hydrostatic pressure imbalance only. This is when fluid has a low protein content. (eg cardiac failiure of veous outflow obstruction)

Question 15

What is exudate oedema?

Answer 15

Fluid loss in inflammation is an exudate. This is when there is high portein content.

Question 16

What are the mechanisms of vascular leakage?

Answer 16

• Endothelial contraction - gaps
• Histamine, leukotrienes
• Cytoskeleton reorganisation -gaps
• -Cytokines, IL-1 and TNF*
• Direct injury - Toxic burns, chemicals
• Leuleukocyte dependant injury
• -Toxic pxygen species amd enzymes from leucocytes*
• Increased transcytosis -channels across endothelial cytoplasm.
• VEGF

Question 17

What plasma proteins are delivered to site of injury?

Answer 17

Fibrin - Make it a LOCALISED response to tissue.

Question 18

What is a neutrophil leukocyte?

Answer 18

This is primary type of white bood cell in acute inflammation. Neutrophils are a type of granulocyte, also know as a polymorphonuclear leucocyte.

Neutrophil = polymorph

Question 19

Other than neurophils, what other type of cells is involved in acute inflamation?

Answer 19

Macrophages also involved.

They are also involved in chronic inflammation.

Question 20

How does the infiltration of neutrophils occur?

Answer 20

(Before, stasis)

1. Margination - stasis causes neutrophils to line up at the edge of the blood vessels along the endothelium.
2. Rolling - Neutrophils then roll along the endothelium, stiking to it intermittently
3. Adhesion -They then stick to more avidly
4. Emigration. -This is then followed by emigration of neutrophils through the blood vessel walls.

Question 21

How do neutrophils escape from vessels?

Answer 21

• Relaxation of inter-endothelial cell junctions
• Digestion of vascular basement membrane
• Movement.

Question 22

How do neutrophils move once they are in cells?

What does this result in?

Answer 22

• Chemotaxis. (Movement along a concentration gradient of chemoattractants)
• Emigration
• Diapedisis (the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation.)

These result in:

• Receptor-ligand binding
• Rearragment of the cytoskeleton
• Production of pseudopod (a temporary protrusion of the surface of an amoeboid cell for movement and feeding.)

Question 23

What three chemotaxins mediate chemotaxis?

Answer 23

• Bacterial peptides -attracted to areas of bacterial infection
• LTB4 - leukotrienes
• C5a - a complement protein so causes compliment activation.

Neutrophils have receptors on their surface for all of these receptors.

Question 24

What do neutrophils do?

Answer 24

Phagocytosis.

Contact, Recognition, Internalisation -forms a phagosome.

These processes are facilitated by opsonins (Fc and C3b)

Also cause cytoskeletal changes

Phagosome then fuse with lysosomes to produce a secondary lysosomes.

Question 25

What facilitates phagocytosis?

Answer 25

**Opsonins** - attatch to neutrophils and help it undergo phagicytosis. Fc and C3b (compliment cascade) stick to surface of bacteria / tissues to allow them to be recognised or phagocytosed by neutrophils.

Question 26

What are the killing mechanisms of phagolysosomes?

Answer 26

**Oxygen dependant** * Produces superoxide and hydrogen peroxide * H₂O₂ -myeloperoxidases-halide system which produces HOCl- **Oxygen indipendant** * Lysozymes and hydrolases * Bacterial permeability increasing protein (BPI) * Cationic proteins ('defensins')

Question 27

How are neutrophils, chemotaxis and phagocytosis linked?

Answer 27

1. Neutrophils **migrate** to site of injury by **chemotaxis** 2. Neutrophils **phagocytose** microorganisms 3. Activated neutrophils May released **toxic metabolites** and enzymes causing damage to the host tissue.

Question 28

What are the groups of chemical mediators in acute inflammation?

Answer 28

**Proteases** (plasma protiens, produced in the liver) * kinins * Complement system C3a, C5a * Coagulation / fibrinolytic system **Prostaglandins / Leukotrienes** * Metabolites of arachidonic acid **Cytokines / chemokines** (produced by WBCs) * Many and vaired! * Interleukins * TNF alpha

Question 29

What are the chemical mediators in each step of acute inflammation?

Answer 29

**Increased blood flow** * Histamine * Prostaglandins **Vascular Permiability** * Histamine * Leukotrienes **Neutrophil Chemotaxis** * C5a * LTB4 * Bacterial peptides **Phagocytosis** * C3b

Question 30

How does the exudation of fluid combat injury?

Answer 30

* **Delivers plasma proteins to the area of injury** inc. * Immunoglobulins * Inflammatory mediators * Fibrinogen * **Dilutes toxins** * **Increases lympharic drainage** * This delivers micro-organisms to phagocytes and antigens to the immune system

Question 31

How does infiltration of cells combat injury?

Answer 31

It removes pathogenic organisms and necrotic debris

Question 32

How does vasodilation combat injury?

Answer 32

* It increased the delivery of blood (therefore proteins ect...) to the site of injury * It increases temperature

Question 33

How does pain and loss of function combat injury?

Answer 33

It enforces rest and therefore reduces the chance of further traumatic damage

Question 34

What are the local complications of acute inflammation?

Answer 34

* **Swelling** * blocking of tubes and obstruction * eg bile duct, intestine * **Exudate** * compression * eg cardiac tanponade (heart cannot pump because of pressure in pleural space). * Serositis * **Loss of fluid** * eg burns * **Pain and loss of function** * especially if prolonged.

Question 35

What are the systemic effects of acute inflammation?

Answer 35

* **Fever -** * ‘Endogenous pyrogens’ produced interleukin 1 and TNFa - * Prostaglandins: aspirin reduces fever * **Leukocytosis** * IL-1 and TNFa produce an accelerated release from bone marrow * Macrophages and T lymphocytes produce colony-stimulating factors * Bacterial infections -neutrophils, viral - lymphocytes * **Acute phase response** * Decreased apetite, raised pulse rate, altered sleep patters and changes in plasma conc of acute phase proteins inc: * C-reactive protein (CRP), a₁ antitripsin, Haptoglobin, Fibrinogen, Serum amyloid A protein * **Shock (a clinical syndrome of circulatory failure)** * ​Caused by a spread of microorganisms and toxins and by the acute phase response

Question 36

What may happen after the development of acute inflammation?

Answer 36

1. Complete resolution 2. Continued acute inflammation with chronic inflammation = abscess 3. Chronic inflammation and fibrous repair, probably with tissue regenerations 4. Death

Question 37

What does the resolution of acute inflammation look like (morphology)?

Answer 37

**Changes gradually reverse** * Vascular changes stop so: * Neutrophils no longer marginate * Vessel permiability retuns to normal * Vessel calibre returns to normal So... * Exudate drains to lymphatics * Fibrin is degraded by plasmin and other proteases * Neutrophils die, break up and are carried away or phagocytosed * Damaged tissue might be able to regenerate If tissue architecture has been destoyed then complete resolution is NOT possible

Question 38

How does the resolution of acute inflammation work?

Answer 38

* All mediators of acute inflammation have short half-lives. * May be inactivated by degridation * Inhibitors may bind * May be unstable * May be diluted in the exudate * Specific inhibitors of acute inflammatory changes

Question 39

Clinical examples of acute inflammation?

Answer 39

* Bacterial meningitis * Lobar pneumonia * Skin blister * Abscess * Liver absess * Pericarditis * In serous cavities

Question 40

What is bacterial meningitis?

Answer 40

Acute inflammation the the maninges can cause vascular thrombosis and reduce cerebral pefusion. Dangerous in brain! This is because of the increased pressure.

Question 41

What is lobar pneumonia?

Answer 41

Lungs fills with neutrophils / exudate becuase of the infection -They should be filled with air! Caused by bacteria (Streptococcus pneumoniae). Breathlessness, worsening fever, prostation, hypoxaemia over a few days, dry cough. If treated, it can resolve completely.

Question 42

What are skin blisters?

Answer 42

Causes: heat, sunlight, chemical Presents as painfun with profuse exudate The collection of fluid strips pff the overlying epithelium There are relatively few inflammatory cells so the exudate is clear (unless a bacterial infection develops) There is either complete resolution or scarring

Question 43

What is an abscess?

Answer 43

Abscesses occur in solid tissues. It is when the inflamatory exudate forces the tissue apart. There is liquefactive neucrosis in the centre. This may cause high pressure which results in pain It may cause adjacent tissue damage and squash adaject structures.

Question 44

Serous What is acute inflammation in serous cavites?

Answer 44

This is when exudate pours into cavity. It can be ascites (exudate in peritoneal), pleural or a pericardial effusion. It results in respiratory or cardiac imparment There is localied fibrin deposition

Question 45

What are some disorders of acute inflammation?

Answer 45

These are rare diseased (natural selection ensures that). But, they illustrate the importance of apparently small parts of this complex web of mechanisms. For example: * Hereditary angio-oedema * Alpha-1 antitrypsin deficiency * Inherited complement deficiencies * Defects in neutrophil function * Defects in neutrophil numbers.