Session 3 ILOs - Chronic inflammation

Question 1

Describe the common causes (aetiology) of chronic inflammation (e.g. after or alongside acute inflammation; chronic persistent infections; autoimmune conditions, prolonged exposure to toxic agents)

Answer 1

There are 3 main ways chronic inflammation can arise:

1. Takes over from acute inflammation (if a resolution is not possible with acute inflammation)
2. Develops alongside acute inflammation (e.g. from severe or persistent irritation)
3. Can arise de novo aka. by itself without a preceding acute inflammation e.g. an autoimmune disease

Question 2

Explain the action of the cells principally involved in chronic inflammation i.e. macrophages, giant cells, lymphocytes, eosinophils and fibroblasts/myofibroblasts

Answer 2

Macrophages:

• Slipper shaped nucleus, abundant cytoplasm with foamy appearance
• Main role is phagocytosis (have many phagolysosomes responsible for destruction)
• Role in antigen presenting (presenting the products of phagocytosis)
• Role in synthesis and release of inflammatory mediators

Giant cells (many macrophages):

• 3 types
• Formed by fusion of multiple macrophages where a single macrophage can’t destroy it on its own

Lymphocytes:

• Thin rim of cytoplasm and dark staining central nuclei
• 2 main functions
  1. T cells - helper (assists other inflammatory cells) and cytotoxic (destroys pathogens directly)
  2. B cells - mature into plasma cells which produce antibodies and neutralise pathogens

Eosinophils:

• Bi-lobed nucleus and granular, red staining cytoplasm
• Release a variety of mediators
• Responsible for hypersensitivity reactions and parasitic infections

Fibroblasts/myofibroblasts:

• Spindle shaped nucleus and cytoplasmic extensions
• Secrete collagen and elastin to form extracellular matrix (myofibroblasts express intracellular actin and can contract in wound contraction)
• Responsible for regeneration and repair

Question 3

Describe the complications of chronic inflammation and interpret how these might affect organs (structurally and functionally) e.g. tissue destruction, excessive fibrosis, impaired function, atrophy

Answer 3

4 main complications of chronic inflammation:

1. Fibrosis
   - Deposition of collagen e.g. liver cirrhosis
2. Impaired function
   - Generally reduced function
   (very rarely increased function e.g. Graves disease)
3. Atrophy
   - e.g. atrophic gastritis
4. Stimulation of the immune response
   - Results in antigen presentation

Question 4

Describe the features seen in some common clinical examples of chronic inflammation: 
Rheumatoid arthritis
Crohn’s disease
Ulcerative colitis
Chronic cholecystitis
Chronic gastritis
Liver Cirrhosis

Answer 4

Rheumatoid arthritis:
- Mainly see plasma cells

Crohn’s disease:

• See disordered architecture
• Discontinous patches of inflammation that is transmural
• Can sometimes see granulomatoma

Ulcerative colitis:

• See disordered architecture
• Continous patches of inflammation that is only superficial
• No granulomatoma

Chronic cholecystitis:

• See fibrosis (deposition of collagen) as pale pink strands
• See lymphocytes and plasma cells
• Caused by repeated obstruction of bile duct by gall stones
• This can progress into chronic inflammation

Chronic gastritis:
- Mainly see lymphocytes

Liver Cirrhosis:

• Fibrosis and attempted regeneration
• See thick bands of mature fibrous tissue

Question 5

Describe the appearance and explain the action of different types of giant cells (e.g. Langhan, foreign body and Touton) and the conditions in which they might be seen

Answer 5

Foreign body:
Appearance - nuclei are randomly distributed within giant cell
Seen - around tissue where there is a foreign body i.e. suture material

Langhan:
Appearance - nuclei are around the outside of the giant cell
Seen in - mainly tuberculosis infections

Touton:
Appearance - nuclei form in the centre of the giant cell
Seen in - mainly in fat necrosis (where there is damage to fat tissue)

Question 6

Describe a granuloma and granulomatous inflammation

Answer 6

A granuloma is a collection of multiple macrophages (with a distinct appearance - epithelioid histiocytes) with surrounding lymphocytes

Granulomatous inflammation:
- Unclear or not well defined, but can tell that a granuloma has formed

Question 7

Describe the common causes (aetiology) of granulomatous inflammation (e.g. foreign body material, infections and other diseases such as sarcoidosis and Crohn’s disease) and recognise and explain the microscopic appearances

Answer 7

2 types of granuloma:

1. Forgein body - few lymphocytes
2. Immune mediated - many lymphocytes

Causes of granulomatous inflammation:

1. Infections e.g. mycobacterium tuberculosis or mycobacterium leprae (difficult to destroy so induces granulomas) = involves CASEOUS necrosis
2. Crohn’s disease (non-caseating granulomata)
3. Sarcoidosis (non-caseating granulomata)