Chronic Inflammation Flashcards
How can chronic inflammation occur?
- takes over from acute inflammation if damage is too severe to be resolved in a few days
- occurs de novo with autoimmune conditions e.g. rheumatoid arthritis, chronic infections such as viral hepatitis, low-level irritation such as foreign bodies
- develops alongside acute inflammation with severe, persistent or repeated irritation e.g. chronic cholecystitis (gallstones)
Define chronic inflammation.
Chronic response to injury with associated fibrosis.
What cells are present in chronic inflammation, and what are their respective functions?
Macrophages:
- phagocytosis
- antigen-presenting
- synthesis of cytokines, complement components, blood clotting factors, proteases, interleukins-1, elastase
Lymphocytes (“chronic inflammatory cells”):
- B-lymphocytes: form plasma cells to secrete antibodies (implies considerable chronicity) and memory cells
- T-lymphocytes: CD4+ = activates macrophages & stimulates differentiation of lymphocytes & CD8+ = cytotoxic functions
- Eosinophils: (allergic reactions, parasite infections, some tumours)
- Fibroblasts: produce collagen and are recruited by macrophages
What is a giant cell?
Multinucleate cell made by fusion of macrophages due to frustrated phagocytosis (foreign material/pathogens that cannot be easily phagocytosed)
Describe some of the histological appearances of different types of giant cell.
- Langhans = horseshoe-shaped
- Foreign body = giant cell around foreign body
- Touton = clock-face
Give an example of a condition caused by fibrosis of chronic inflammation.
Chronic cholecystitis (gallstone in cystic duct/common bile duct) = repeated obstruction/mucosal damage by gall stones -> fibrosis of gall bladder wall
note: gastric ulceration caused by defect in mucosal surface due to imbalance in acid production
- acute: alcohol, drugs
- chronic: Heliobacter pylori
Give an example of a disease caused by impaired function due to chronic inflammation.
Chronic inflammatory bowel disease (“cobble-stone ulceration”)
e. g. ulcerative colitis (superficial layers affected) - diarrhoea, bleeding
e. g. Crohn’s disease (transmural: superficial & deep layers affected) - diarrhoea, bleeding, strictures (narrowing), fistulae (abnormal connection between two epithelia-lined organs)
Give an example of a disease caused by atrophy due to chronic inflammation.
Rheumatoid arthritis: joint destruction due to local inflammation of synovial membranes
note: systemic inflammation: amyloidoses
What is a granuloma, and when do they occur?
GRANULOMA = accumulation of lymphocytes and epithelial histiocytes (macrophages in tissue)
Occur due to persistent, low-grade antigenic stimulation/hypersensitivity reactions
e.g. foreign material, TB (caseating necrosis), leprosy, sarcoidosis (non-caseating necrosis; lymph nodes/lungs involved), Wegener’s, Crohn’s (patchy, full-thickness inflammation throughout bowel), beryllium (found in fluorescent lamps)
Describe the pathogenesis of TB.
Usually caused by Mycobacterium tuberculosis (mycoside cell walls difficult to destroy, therefore TB survives within macrophages)
Bacterium does not produce toxins or lytic enzymes; causes disease due to persistence and induction of cell-mediated immunity
- caseating necrosis
- Arrest = immune system localises TB in organ and stops it spreading (but causes fibrosis - scarring) (TB remains latent in macrophages -> granuloma formation until immune response decreases)
- Erosion into bronchus = bronchopneumonia (can spread to GI if swallowed)
- Tuberculous empyema (pleural infection)
- Erosion into bloodstream (miliary TB = multi-organ failure)
Give some examples of connective tissue disorders associated with inflammation.
Polymyositis = idiopathic (unknown cause) inflammatory disease causing muscle weakness, swelling, pain
Dermatopolymyositis = same as above + skin involvement causing a scaly butterfly rash
Systemic lupus erythematous (SLE) = autoantibodies attack anti-neutrophil antibodies causing fatigue, arthralgia (severe joint pain), butterfly rash on face, etc. (varying presentation)
Sjögren’s syndrome = lymphocytes attack exocrine glands (salivary & lacrimal) causing dry mouth and dry eyes
Systemic sclerosis = accumulation of collagen and injuries to smallest arteries
Rhabdomyolysis = muscle breakdown due to exercise, muscle wasting, or crush injury which can cause renal failure
How do macrophages reach areas of inflammation?
- chemoattractants produced by other macrophages
- growth factors and interleukins activate
- diapedesis stimulated by mediators of inflammation e.g. kinins, histamine, prostaglandins
- monocytes stimulated to become macrophages by gamma-interferon
What are the functions of the large intestine? What are the histologically signs of ulcerative colitis?
- absorption of water
- peristalsis
- mucus secretion
- absorption of fat-soluble vitamins
Absent goblet cells (mucin depletion) + damaged mucosal surface (ulceration) + crypt distortion (filled with lymphocytes)
Crohn’s: inflammation is transmural & granulomas are present
What is sarcoidosis? How does it present histologically?
Multi-system inflammation (granulomas in lung/intrathoracic lymph nodes), possibly an immune reaction
Symptoms depend on organs affected e.g. pulmonary (haemoptysis, chest pain), systemic (fever, anorexia)
- non-caseating granulomas
- lymphocytes present (chronic inflammation)
How does TB present histologically?
Caseating necrosis (digested granulomas) Lymphocytes present (chronic inflammation)
Use acid fast (Ziehl-Neelsen) to demonstrate mycobacterium
