Chronic Inflammation

Question 1

Define chronic inflammation [3]

Answer 1

Inflammation is defined as chronic when…

1. it is persistent and lacks resolution when the inflamed tissue is unable to overcome the effects of the injurious agent
2. it persists for weeks, months, or years
3. it is characterised by infiltrates of lymphocytes, plasma cells, and macrophages

Question 2

What are the 3 types of cells involved in chronic inflammation? [3]

Answer 2

1. macrophages
2. plasma cells
3. lymphocytes

Question 3

Granulomatous Inflammation

1. what is a granuloma? [1]
2. causes of granulomatous inflammation? [5]
3. predominant cell types involved? [3]
4. what is sarcoidosis? [1]
5. what are epithelioid macrophages? [2]
6. pathogenesis of granuloma formation? [2]

Answer 3

1. a localised aggregation of epithelioid histiocytes (macrophages) that is produced in response to an infectious process
   
   • monocytes, giant cells and lymphocytes may also be present
2. Causes:
   
   • infectious agents: TB, leprosy, toxoplasmosis
   • foreign material (e.g. talc)
   • sarcoidosis
   • Crohn’s disease
   • response to tumour e.g. Hodgkin lymphoma.
3. Predominant cell types:
   
   • epithelioid macrophages & giant cells
   • CD4 lymphocytes
   • CD8 lymphocytes
4. sacroidosis = disease involving abnormal collections of inflammatory cells that form lumps known as granulomas
5. epithelioid macrophages:
   
   • modified macrophages arranged in small nodules or clusters that have a mainly secretory role and fuse to form multinucleated giant cells
6. pathogenesis:
   
   • formation of granulomas is a manifestation of T cell mediated immune reaction (delayed type hypersensitivity)
   • the antigen is presented to CD4+ T Cells which in turn produce IFN gamma and other cytokines resulting in macrophage activation

Question 4

Describe the clinical features of rheumatoid arthritis [7]

Answer 4

1. chronic inflammatory disease affecting the skin, blood vessels, heart, lungs, muscles and joints
2. caused by non-suppurative, proliferative synovitis which leads to destruction of articular cartilage
3. inflammatory infiltrate includes:
   
   • lymphocytes
   • plasma cells
   • dendritic cells
   • macrophages
4. increased vascularity due to vasodilatation and angiogenesis
5. aggregation of fibrin
6. pannus formation leading to erosion of cartilage and bone
7. neutrophils in synovial fluid

Question 5

Describe the clinical features/pathogenesis of atherosclerosis [4]

Answer 5

1. the macrophage plays a key role in atherogenesis
2. endothelial injury (sheer stress, smoking etc)
3. recruitment of macrophages, become foam cells
4. lymphocytes release chemical mediators

Question 6

Chronic Granulomatous Inflammation

1. Cause?
2. Consequences? [3]

Answer 6

1. defect in NADPH oxidase system within phagocytes (including macrophages)
2. consequences:
   
   • inability to kill intracellular organisms by respiratory burst
   • patients have repeated and recurrent infections
   • patients develop granulomata of lymph nodes, skin, lungs, liver and Gl tract

Question 7

Wound Healing

1. What is healing by primary intention?
2. What is healing by secondary intention?

Answer 7

1. primary intention = simple incision
2. secondary intention = dirty/infected wound

Question 8

What are the 7 phases of wound healing? [7]

Answer 8

1. Formation of blood clot
2. Formation of granulation tissue
3. Cell proliferation and collagen deposition
4. Scar formation
5. Wound contraction
6. Connective tissue remodelling
7. Recovery of tensile strength

Question 9

List the local factors influencing wound healing [8]

Answer 9

1. type of wound
2. size of wound
3. location of wound
4. movement within wound
5. infection
6. presence of foreign/necrotic material
7. irradiation
8. poor blood supply

Question 10

List the systemic factors influencing wound healing [5]

Answer 10

1. age
2. nutrition (vitamin C, zinc)
3. systemic disease (e.g. renal failure)
4. drugs (esp. steroids)
5. smoking

Question 11

Describe the 3 Phases of Fracture Healing

1. Inflammatory Phase? [4]
2. Repair Phase? [4]
3. Remodelling Phase? [3]

Answer 11

1. Inflammatory Phase:
   
   • haematoma forms at the site of fracture
   • prostaglandins recruit neutrophil polymorphs, macrophages, lymphocytes and fibroblasts to the site of injury
   • granulation tissue, ingrowth of vessels, migration of mesenchymal cells occurs
   • nutrients and oxygen are supplied by the exposed bone and muscle
2. Repair Phase:
   
   • fibroblasts lay down stroma to support ingrowing vessels
   • collagen matrix is laid down
   • osteoid is secreted and mineralised leading to soft callus formation
   • callus ossifies after 4-6 weeks by forming bridge of woven bone between fracture fragments
3. Remodelling Phase:
   
   • occurs slowly over months and years
   • returns bone to its original shape, structure and mechanical strength
   • facilitated by mechanical stress