Chronic inflammation Flashcards
What is chronic inflammation compared to acute?
prolonged duration - wks/months - years
inflammatory cells = mononuclear- lymphocytes, plasma cells, macrophages
tissue destruction
healing involves angiogenesis and fibrosis
How does acute inflammation progress to chronic inflammation?
repeated episodes e.g. peptic ulcer
persistence of injurious agents with failure of resolution e.g. osteomyelitis
What are the different causes of primary chronic inflammation?
1) micro-organism associated with intracellular infection e.g. viral agents (hep B) or bacteria resistant to phagocytosis
2) Foreign body reactions - e.g. exogenous materials (silica, asbestos), endogenous substances (lipid material in atherosclerosis)
3) autoimmune diseases e.g. Hashimoto’s thyroiditis, RA
4) Unknown aetiology - chronic inflammatory bowel disease , sarcoidosis
Give 2 examples of progression from acute inflammation to chronic due to repeated episodes
Chronic cholecystitis and chronic 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- this affects contractility of tissue
What predisposes acute inflammation of the gallbladder?
gallstones
Why do peptic ulcers form?
imbalance between damaging and protective factors of the mucosa - too much HCl released and a lack of protective mucus - leads to flattening and loss of normal mucosal folds
What are the consequences of chronic cholecystitis?
Gallbladder is non-contractile due to scar tissue, fatty food intolerance, RUQ pain
What are the consequences of chronic peptic ulcers?
Fibrous scarring of stomach muscle which can lead to:
- pyloric stenosis = tend to suffer projective vomiting as stomach can’t process food
- gastric haemorrhage = fibrous tissue holds artery in place, preventing contraction
What is the role of CD4+ T cells?
secrete cytokines in response to antigen presentation = activates CD8+ cells and macrophages
cooperate with B cells in humoral response
What is the role of CD8+ T cells?
Effector cells
- direct cell killing by apoptosis
- produce cytotoxic cytokines
What is the role of B cells?
Respond to stimulation by differentiating into plasma cells
Plasma cells secrete antibodies
How can you distinguish plasma cells from lymphocytes?
Plasma cells have a much more abundant cytoplasm
What are the key roles of resident macrophages e.g. kupffer cells?
phagocytosis and immune surveillance
What happens to macrophages once they are activated by cytokines?
increase in size, mobility and phagocytic activity and produce a range of substances promoting tissue injury, angiogenesis and fibrosis
When are macrophages commonly seen?
late stages of acute inflammation as they are involved in removing dead tissue and initiating tissue repair
What effect does the production of toxic oxygen metabolites and arachidonic acid metabolites and proteases by macrophages have?
causes direct tissue damage
What effect does the production of pro-inflammatory cytokines and chemokines by macrophages have?
activation and recruitment of other inflammatory cells
What effect does the production of growth factors by macrophages have?
fibrosis and angiogenesis
What effect does the production of collagenases by macrophages have?
remodelling of connective tissue
What is a granuloma?
aggregate of macrophages
- may have epithelioid morphology
- little phagocytic activity once granulomas formed
- may fuse to form giant cells like langhan’s, foreign body and touton
What are the causes of granulomatous disease (subtype of chronic inflammation)?
infections - mycobacteria (TB), syphilis
foreign bodies - endogenous (cholesterol crystals, necrotic bone), exogenous (silica, oils)
drugs - hepatic granulomas (sulphonamides)
unknown - CD, sarcoidosis, wegner’s granulamatosis
What causes TB and what is the immune response?
mycobacterium TB
Mainly T cell mediated (delayed hypersensitivity), macrophages recruited with granuloma formation
What occurs in the primary infection of the lungs in TB?
subpleural location (ghon focus), centre undergoes caseation necrosis (TNF-mediated) and bacilli are carried to regional lymph nodes (ghon complex)
What is the sequelae of primary TB infection?
Heal by scarring, may undergo calification - CXR shows calcification
progressive pulmonary TB - local tissue destruction
Haematogenous spread - erosion of pulmonary vein or artery =miliary TB
If an inadequate immune response then the pathogen replicates- lung progressively gets destroyed= consumption
What are the 2 types of miliary TB?
Pulmonary artery stenosis - lung infection
Pulmonary vein erosion - systemic infection - brain, liver, kidney = very high mortality
What are the characteristic features of CD?
transmural (full thickness) of bowel wall
damage to smooth muscle heals by fibrosis - lose contractile component
stenosis may lead to bowel obstruction
What are the characteristic features of UC?
Chronic inflammation with ulceration
mucosa heals by regeneration
repeated cycles of ulceration/regeneration
may progress to invasive carcinoma
