Chronic Inflammation Flashcards
Chronic compared with acute inflammation
Duration - weeks/months --> years Inflammatory cells mainly mononuclear - lymphocytes, plasma cells, macrophages compared to acute where neutrophils are main Tissue destruction Healing (angiogenesis and fibrosis)
Causes of chronic inflammation
Progression from acute inflammation
- repeated episodes of acute inflammation - chronic cholecystitis, peptic ulcer
- persistence of injurious agent with failure of resolution e.g. Formation of abscess with lack of drainage - empyema, osteomyelitis
Primary chronic inflammation
- micro organisms associated with intracellular infection
E.g. Viral agents hep b,c, bacteria resistant to phagocytosis - mycobacterium TB, leprosy
- foreign body reactions
Exogenous material - silica, asbestos, suture materials
Endogenous substances - lipid material in atherosclerosis
- autoimmune disease
Organ specific - Hashimoto’s thyroiditis
Non organ specific - rheumatoid arthritis
- unknown aetiology
Chronic inflammatory bowel disease
Examples of progression from acute inflammation - repeated episodes
Chronic cholecystitis
Chronic peptic ulceration.
What are the example of acute inflam progress to chronic inflam associated with
Damage to the deeper layers of the wall
- damaged smooth muscle cannot heal by regeneration
- healing by repair results in fibrous scarring
What happens in chronic cholecystitis with gall stones
The gall stones predispose to acute inflammation of the gall bladder
Tendency to develop repeated episodes (may be associated with mild/no clinical symptoms)
Fibrous scarring of the wall results in loss of normal gall bladder function
What happens with a chronic peptic ulcer
Gastric acid normally does not damage the mucosa however due to excess acid the protective mucus covering is no longer protective so the acid begins to erode
Mucosa can become neurosed Each layer of the stomach can be effected - submucosa - muscle layers - peritoneum Deeper the healing response of the body is - acute inflammatory exudate - vascular granulation tissue - fibrovascular granulation tissue - fibrous scar formation Which results in an ulcer
Consequences is chronic inflammation and fibrosis - gall bladder cholecystitis
The gall bladder becomes
- non contractile
- get fatty food intolerance
- right upper quadrant pain
Consequences is chronic inflammation and fibrosis - stomach chronic peptic ulcer
Fibrous scarring of muscle is still present after mucosa has healed
- may be visible in an endoscopy
Fibrous scarring contributes to important complications
- pyloric stenosis is near the pylorus
- gastric haemorrhage
Types of cells involved in chronic inflammation
Lymphocytes
Plasma cells
Macrophages
Lymphocytes involvement
T lymphocytes - cell mediated immune response
CD4 T cell (helped T cells)
- secrete cytokines in response to antigen presentation
– activation of effector cells (CD8, macrophages)
– cooperate with B cells in humoral response
CD8 T cell (cytotoxic T cell)
- involved as effector cells
– direct cell killing by apoptosis (receptor specific)
– production of cytotoxic cytokines (non- specific)
B lymphocytes (humoral immune response)
- respond to stimulation by differentiating into plasma cells
- plasma cells secrete immunoglobulin
Macrophages involvement
Derived from circulating monocytes and are transformed in the tissues
Normal resident population in many tissues -Kupffer cells in the liver, alveolar macrophages: involved with phagocytosis (inhaled particles, senescent RBC) and immune surveillance
May become activated by cytokines and other inflammatory mediators
Activated macrophages increase in size, mobility and phagocytic activity and produce a range of substances promoting tissue injury, angiogenesis and fibrosis
Often seen in the late stages of acute inflammation, where they may be involved in removing dead tissue and initiating the repair process
Substances macrophages produce and their biological effects
Toxic oxygen metabolites
Arachidonic acid metabolites
Proteases –> direct tissue damage
Pro inflam cytokines - IL1, TNF
Chemokines –> activation and recruitment of other inflammatory cells
Growth factors - fibroblast GF, platelet derived GF, transforming GF –> fibrosis and angiogenesis
Collagenases –> remodelling of connective tissue
What is granulomatous inflammation
A granuloma is an aggregate of macrophages
- may have an epithelioid morphology (resemble epithelial cells) - large vesicular nuclei, eosinophilic cytoplasm
- little phagocytic activity
- may fuse to form giant cells
E.g. Langerhans, foreign body and Touton
Causes of granulomatous disease
Infections
- mycobacteria - TB, leprosy
- atypical mycobacterium, fungi, parasites
- syphilis
Foreign bodies
- endogenous e.g. Keratin, necrotic bone, cholesterol crystals
- exogenous - talc, silica, suture materials
Drugs
- hepatic granulomas- phenylbutazone, sulphonamides
Unknown
- Crohn’s disease, sarcoidosis, wegners granulomatosis
Disease associated with granuloma formations - clinical relevance
1) understanding pathogenesis and complications of the disease
- sequelae of granuloma formation in pulmonary TB
2) diagnostic interpretation of biopsy material
- causes of granulomatous hepatitis in a liver biopsy e.g. Sarcoidosis, TB, primary biliary cholangitis, drug toxicity
- differential diagnosis of inflammatory bowel disease in a rectal/colon biopsy
