*UNIFINISHED* MOD Session 2

Question 1

What is inflammation?

Answer 1

Response of living tissue to injury to limit the tissue damage

Question 2

Describe acute inflammation.

Answer 2

Innate, immediate, stereotyped, short duration (minutes, hours, days)

Question 3

What are the causes of acute inflammation?

Answer 3

Microbial infections e.g. pyogenic organisms
Hypersensitivity reactions (acute phase)
Physical agents 
Chemicals 
Tissue necrosis
Foreign bodies
Trauma

Question 4

What are the clinical features of A.I?

Answer 4

Rubor = redness
Tumor = swelling
Dolor = pain
Calor = heat

Loss of function

Question 5

Describe the changes in blood flow in tissues undergoing A.I?

Answer 5

1) Transient vasoconstriction of arterioles
2) Vasodilation of arterioles and then capillaries (increase blood flow causing heat and redness)
3) Increase permeability of blood vessels (causes exudation of protein-rich fluid into tissues and slowing of circulation causing swelling
4) Concentration of RBCs in small vessels and increased viscosity of blood

Question 6

Describe the early chemical mediators in A.I (within 30mins)? What does it cause?

Answer 6

1) Histamine released from mast cells, basophils and platelets. (responds to many stimuli e.g. physical damage, C3a, C5a, IL-1 etc.

Causes vascular dilatation, transient increase in vascular permeability and pain

Question 7

What are the three examples of persistant mediators involved in A.I?

Answer 7

Interleukins, bradykinins and prostaglandins and 5-HT

Question 8

What two properties of vessels cause fluid infiltrate into tissues?

Answer 8

1) Increased hydrostatic pressure by vasodilation of vessels

2) Increased colloid osmotic pressure of interstitium leaks plasma proteins into the tissue

Question 9

What is oedema and what does it lead to?

Answer 9

Excess fluid in interstitium which can be exudate or transudate. Leads to increased lymphatic drainage

Question 10

What is the difference between exudate and transudate?

Answer 10

Exudate - fluid loss in inflammation which is protein-rich

Transudate - fluid loss due to hydrostatic pressure with a low protein content e.g. cardiac failure or venous outflow obstruction

Question 11

What molecules/situations contribute to vascular permeability and increasing leakage?

Answer 11

1) Endothelial contraction - histamine, leukotrienes
2) Cytoskeletal reorganisation - cytokines, IL-1 and TNF
3) Injury
4) Leukocyte dependent injury (toxic oxygen species and enzymes from leucocytes
5) Incerased transcytosis - channels across endothelial cytoplasm e.g. VEGF

Question 12

What is the primary WBC involved in acute inflammation?

Answer 12

Neutrophil / Polymorph

Question 13

How do neutrophils migrate and exert its actions at the site of injury?

Answer 13

1) Respond to chemotatic agents from the site of injury e.g. C5a, LTB4, PAMPs. DAMPs,
2) Produce pseudopods and migrate toward site of injury
3) Marginate at edge of venule and produce a rolling interaction
4) Bind to specific selectins and integrins e.g. ICAM-1 and MAdCAM
5) Produce collagenases which digest the basement membrane allowing extravasation into the tissue.

Question 14

What are the two killing mechanisms of neutrophils?

Answer 14

1) Oxygen depandent - (efficient) produces superoxide and hydrogen peroxide radicals
2) Oxygen independent - lysozyme and hydrolases, bactericidal permeability increasing protein and defensins (cationic proteins)

Question 15

What are the metabolites of arachidonic acid?

Answer 15

Prostaglandins / Leukotrienes

Question 16

What molecules contribute to a) increased blood flow, b) vascular permeability, c) neutrophil chemotaxis, d) phagocytosis ?

Answer 16

a) Histamine and PGLs
b) Histamine and Leukotrienes
c) C5a, LTB4 , bacterial peptides
d) C3b

Question 17

What are the two hallmarks of acute inflammation?

Answer 17

Exudate of fluid and infiltrate of inflammatory cells

Question 18

What is the purpose of the exudate in A.I? (3 points)

Answer 18

Delivers plasma proteins to are of injury e.g. Igs, inflammatory mediators and fibrinogen

Dilutes toxins

Increased lymphatic drainage which delivers micro-organisms to phagocytes and antigens to immune system

Question 19

What is the purpose of the infiltrate of cells in A.I?

Answer 19

Removes pathogenic organisms, necrotic debris

Question 20

What is the purpose of vasodilatation in A.I?

Answer 20

Increases delivery, increases temperature

Question 21

What is the purpose of pain and LOF in A.I?

Answer 21

Enforces rest, reduces chance of further traumatic damage

Question 22

What are the local complications of A.I?

Answer 22

Swelling (blockage of tubes e.g. bile duct, intestine)
Exudate (Compression e.g. cardiac tamponade, serositis)
Loss of fluid e.g. burns
Pain & LOF (especially if prolonged)

Question 23

What are the systemic effects of A.I for fever and leukocytosis?

Answer 23

Fever : endogenous pyrogens produced : IL-1 and TNFa, PGL2 (NSAIDS inhibit COO thus reducing swelling and PGL2 production e.g. aspirin)

Leukocytosis
IL-1 and TNFa produce accelerated release from marrow
Macrophages, TLym produces CSFs
Bacterial infections - neutrophils
Viral infections - Lymphocytes

Question 24

What are the systemic effects of A.I for acute phase response and proteins?

Answer 24

APR: Decreased appetite, raised pulse rate, altered sleep patterns and changes in plasma concentrations of:

APP: CRP, a1 AT, Haptoglobin, Fibrinogen, Serum amyloid A protein

Question 25

What is shock?

Answer 25

Clinical syndrome of circulatory failure

Question 26

What are the pathways after the development of A.I?

Answer 26

1) Complete resolution
2) Continued acute inflammation with chronic inflamm = abcess
3) Chronic inflamm and fibrous repair with tissue regenration
4) Death

Question 27

How is complete resolution brought about?

Answer 27

Changes gradually reverse
Vascular changes stop
1) Neutrophils no longer marginate (die!)
2) Vessel permeability returns to normal
3) Vessel calibre returns to normal (exudate drains into lymphatics, fibrin degraded by plasmin + proteases)

Question 28

Give examples of acute inflammation and where it can go wrong.

Answer 28

Bacterial meningitis (vascular thrombosis and reduce cerebral perfusion)
Lobar pneumonia (pneumonia affceting large area of lobe of lung), caused by strep pneumoniae
Skin blister (pain and profuse exudate which is clear unless infection, few inflamm cells)
Abcess (solid tissues, inflamm exudate forces tissue apart, liquefactive necrosis, can cause high pressure = pain, cause tissue damage)

Question 29

Describe A.I in serous cavities?

Answer 29

Exudate pours into cavity e.g. ascites, pleural effusion, pericardial effusion

Resp or CVS impariment
Localised fibrin depostition
Bread and butter pericarditis

Question 30

List 5 hereditary disorders of A.I?

Answer 30

1) Hereditary angio-oedema
2) Alpha -1 AT deficiency
3) Inherited complement disorders
4) Defects in neutrophil numbers
5) Defects in neutrophil function