Acute Inflammation

Question 1

Inflammation

1. definition? [1]
2. purpose of inflammation? [3]
3. describe the cycle of inflammation [5]

Answer 1

1. universal response to tissue damage caused by infection, necrosis, trauma
2. purpose:
   
   • to destroy or control the harmful stimulus,
   • to initiate repair
   • to restore function
3. cycle of inflammation:
   
   • vascular changes → formation of exudate → cellular factors and release of mediators → removal of damaged tissue → repair and resolution, suppuration, organisation or ongoing chronic inflammation cont.

Question 2

Vascular Changes

1. describe the process of vasodilatation in inflammation, including how it is mediated and what it leads to [6]
2. describe the process of endothelial activation in inflammation, including how it is mediated and what it leads to [4]

Answer 2

1. Vasodilatation
   
   • transient vasoconstriction then vasodilatation
   • mediated by:
     
     • histamine (produced by mast cells),
     • prostaglandins
     • nitric oxide (NO)
   • ​starts in arterioles and leads to increased blood flow
   • increased blood flow leads to vascular congestion/stasis (slower flow leads to increased concentration)
2. Endothelial Activation:
   
   • serotonin, histamine, bradykinin, leukotrienes and substance P activates vascular endothelium, leading to contraction of endothelial cells
   • increased vascular permeability permits escape of protein-rich fluid exudate into extravascular tissue (swelling)
   • increased interendothelial spaces
   • increased levels of adhesion molcules

Question 3

Describe the role of neutrophil polymorphs in acute inflammation [4]

Answer 3

1. opsonisation
2. phagocytosis
3. intracellular killing of micro-organisms
   
   • (which can be oxygen dependent or oxygen independent)
4. release lysosomal products, propagating the response

Question 4

Describe the role of macrophages in acute inflammation [4]

Answer 4

1. chemotaxis
2. synthesis of TNF, IL-I, IL-6
3. phagocytosis
4. they are antigen presenting cells, so act as a link between innate and adaptive immune response

Question 5

Describe the role of mast cells in acute inflammation [4]

Answer 5

1. contain histamine and heparin in preformed granules
2. stimulated to release contents by injury, complement and lgE
3. plays a role in allergy/anaphylaxis
4. also make eicosanoids to propagate immune response

Question 6

Describe the role of lymphocytes in acute inflammation [3]

Answer 6

1. antigen presentation
2. antibody production
3. production of cytokines

Question 7

Describe the role of plasma cells in acute inflammation [1]

Answer 7

antibody production

Question 8

Describe the cellular changes (of WBCs) in acute inflammation under the following headings:

1. Margination [1]
2. Rolling [4]
3. Adhesion [3]
4. Migration/Diapedesis [1]
5. Chemotaxis [2]

Answer 8

1. Margination:
   
   • white blood cells situated peripherally due to stasis
2. Rolling:
   
   • white blood cells stick and detach from wall
   • mediated by selectins
   • upregulated by IL-I and TNF (from macrophages/PMNs)
     
     • histamine, thrombin, PAF
     • binds L-Selectin on leucocytes
3. Adhesion:
   
   • mediated by Integrins
   • stimulated by IL-I and TNF
   • chemokines also facilitate binding
4. Migration/diapedesis:
   
   • chemokines act on leucocytes to stimulate to migration across endothelium
5. Chemotaxis:
   
   • travel along a chemical gradient, attracted by:
     
     • bacterial products
     • cytokines IL-8
     • complement
     • leukotriene B (from arachidonic acid)

Question 9

Describe the 4 types of receptors that recognise microbes at the site of inflammation and result in leucocyte activation, including where each of the receptors are found (location) and the function of each [12]

Answer 9

1. Toll-like receptors
   
   • ​​receptors for microbial products on surface of leucocytes
   • stimulate microbe killing and cytokine production
2. G-protein coupled receptors on PMNs and macrophages
   
   • recognise products of short bacterial peptides, complement, prostaglandins
   • induce migration of cells and production of respiratory burst
3. Receptors for opsonins on surface of leucocytes
   
   • coating a particle to target for ingestion
   • coating includes antibodies and complement
4. Receptors for cytokines on surface of leucocytes
   
   • e.g. IFN-gamma activates macrophages

Question 10

What are the 5 stages of phagocytosis? [5]

Answer 10

1. Opsonisation
2. Engulfment using pseudopodia
3. Formation of phagosomes
4. Fusion with lysosomes containing enzymes to form phagolysosomes
5. Material destroyed and removed from cell by pinocytosis

Question 11

What are the clinical signs of acute inflammation and the cause of each specific sign? [5]

Answer 11

1. Redness → caused by hyperaemia
2. Swelling → caused by fluid exudate and hyperaemia
3. Heat → caused by hyperaemia
4. Pain → caused by release of bradykinin and PGE2
5. Loss of function → caused by combination of above

Question 12

What is the Light’s criteria? [2]

Answer 12

1. differentiates exudate from transudate
2. Exudate = extracellular fluid with a HIGH protein and cellular content
3. Transudate = extracellular fluid with a LOW protein and cellular content

Question 13

Describe the different types of exudate [7]

Answer 13

1. Serous:
   
   • usually a transudate
   • found in pleural, pericardial, peritoneal spaces
2. Fibrinous exudate:
   
   • fluid rich in fibrin, an exudate due to high protein content
   • often on serosal surface, meninges
3. Suppurative exudate
   
   • pus forming
   • an exudate rich in neutrophil polymorphs (abscess)
4. Haemorrhagic
   
   • severe vascular injury or depletion of coagulatory factors
5. Membranous
   
   • the epithelium becomes coated in membrane formed by fibrin, epithelial cells and inflammatory cells
6. Pseudomembranous (ulceration)
   
   • surface exudate on mucosal/epithelial sites
   • e.g. C diff. colitis
7. Necrotising (gangrenous)
   
   • high tissue pressure leading to vascular occlusion and thrombosis
     
     • necrosis and bacterial putrefaction leads to gangrene