Chronic Inflammation Flashcards
How is chronic inflammation different from acute inflammation?
- prolonged duration (weeks/months -years)
- inflammatory cells mainly mononuclear (lymphocytes, plasma cells, macrophages)
- tissue destruction
- healing (angiogenesis and fibrosis)
How can chronic inflammation be categorised?
Progression from acute inflammation
- reported episodes of acute inflammation e.g. chronic cholecystitis, peptic ulcer
- persistence of injurious agent with failure of resolution –> formation of abscess with lack of drainage (e.g. osteomyelitis, empyema)
Primary chronic inflammaton
Give examples of types of primary chronic inflammation
- Micro-organisms associated with intracellular infection
- viral agents e.g. hep B and C - Foreign body reactions
- exogenous materials e.g. silica, asbestos fibres, suture materials
- endogenous substances e.g. lipid material in atherosclerosis - Autoimmune disaeses
- organ specific e.g. Hashimoto’s thyroiditis
- non-organ specific e.g. rheumatoid arthritis - Unknown aetiology
- chronic inflammatory bowel disease, sarcoidosis
Describe the pathogenesis of chronic inflammation as a progression from acute inflammation
e.g. chronic cholecystitis or peptic ulceration
Both are associated with damage to deeper layers of the wall
- damaged smooth muscle cannot heal by regeneration
- healing by repair results in fibrous scarring
GALLSTONES cause acute inflammation, repeated episodes leads to scarring, loss of gallbladder function, this is when a patient presents
What are the consequences of chronic inflammation and fibrosis in the gallbladder?
non-contractile
fatty food intolerance
RUQ pain
What are the consequences of chronic inflammation and fibrosis in chronic peptic ulcer?
- fibrous scarring of muscle still present after mucosa has healed (may be visible at endoscopy)
- can lead to pyloric stenosis and/or gastric haemorrhage
What are the chronic inflammatory cells?
CD4+ helper cells
- secrete cytokines in response to antigen presentation
- activation of effector cells (CD8+ and macrophages)
- cooperate with Cells in humeral response
CD8+ cytotoxic cells
- involved as effector cells
- direct killing by apoptosis (receptor specific)
- production of cytotoxic cytokines (non-specific)
B lymphocytes
- respond to stimulation by differentiating into plasma cells
- plasma cells secrete Ig
Macrophages
- from monocytes
- normal resists population in many tissues
- may become activated by cytokines
- increase in size, mobility and phagocytic activity, product tissue injuring substances
- seen in late stages of acute inflammation for removal of dead tissue
What substances do macrophages produce and what are their effects?
Direct tissue damage via - oxgen metabolites - arachadonic acid metabolites - proteases Activation and recruitment - pro-inflammatory cytokines (IL-1, TNF) - chemokines Fibrosis and angiogenesis - GF's (FGF, PDGF, TGFbeta) Remodelling of connecting tissue - collagenases
Define granuloma
Describe it
an aggregate of macrophages
- may have epithelioid morphology - large vesicular nuclei, eosinophilic cytoplasm
- little phagocytic activity
- may fuse to from giant cells (e.g. Langhans, forget body and Touton)
What are the causes of granulomatous disease?
- Infections
- mycobacteria e.g. TB and leprosy
- atypical mycobacteria, fungi, parasiets
- syphilis - Foreign bodies
- endogenous e.g. keratin, necrotic bone, cholesterol crystals
- exogenous e.g. talc, silica, suture materials, oils - Drugs
- hepatic granulomas e.g. phenylbutazone, sulphonamides - Unknown
- Crohn’s disease, sarcoidosis, Wegener’s granulomatosis
What is the clinical relevance of disease associated with granuloma formation?
- understanding pathogenesis and complications of dies e.g, sequelae of granuloma formation in TB
- diagnostic interpretation of biopsy material
- causes of granulomatous hepatic in a liver biopsy (sarcoidosis, TB, primary biliary cholangitis. drug toxicity)
- differential diagnosis of IBD in a rectal/colonic biopsy
How can UC and Crohn’s be distinguished on biopsy in terms of granulomas?
Crohn’s = granuloma formation
not in UC
What is the causative agent of TB?
What is the immune response to TB?
Causative agent = mycobacterium TB
Immune response
- mainly Tell mediated (delayed hypersensitivity)
- macrophages recruited with granuloma formation
What are the pathological features of primary TB infection in lung?
- subpleural location (Ghon focus)
- centre undergoes caseation necrosis (TNF mediated)
- bacilli carried by macrophages to regional lymph nodes at hilum (Gohn complex)
Describe the layers of a TB granuloma
SUPERFICIAL –> DEEP
- fibroblast layer
- lymphocytes
- activated macrophages and giant cells
- caseous necrosis in centre
