MoD S4 - Chronic Inflammation Flashcards
What is chronic inflammation?
Chronic response to injury with associated fibrosis
How does chronic inflammation arise?
Give examples for each ‘mechanism’
May take over from acute inflammation:
- If damage is too severe to be resolved quickly
May arise de novo:
- Some autoimmune conditions (Rheumatoid arthritis)
- Some chronic infections (Viral hepatitis)
- Chronic low level irritation
May develop alongside acute inflammation:
- If severe persistent or repeated irritation
How is chronic inflammation characterised?
What is the most important characteristic?
Characterised by the microscopic appearance (which is much more variable then acute inflammation)
Most important characteristic is the cell type present
What cell types might be involved with chronic inflammation?
Macrophages Lymphocytes Plasma cells Eosinophils Fibroblasts/myofibroblasts
What is frustrated phagocytosis?
When macrophages encounter a large foreign body that they cannot internalise (E.g. an implant) they experience frustrated phagocytosis where they attach to the foreign body and secrete superoxides, free radicals and lysosomal contents to damage it.
Inability to internalise foreign body may also result in giant cell formation
What is a giant cell?
A multinucleate cell made by fusion of macrophages
What types of giant cells are there?
Langhans
Foreign body type
Touton
Give a few examples of chronic inflammation and the major inflammatory cell type present in these conditions
Rheumatoid arthritis - Plasma cells
Chronic gastritis - Lymphocytes
Leishmaniasis - Macrophages
Langhans Giant cells appear in what conditions?
Granulomatous conditions (E.g. Tuberculosis)
Touton giant cells appear in what conditions?
Appear during fat necrosis
When do foreign body type giant cells appear?
When the body is exposed to foreign substances (E.g. Sutures, implants or bone fragments)
Why is looking at giant cell type useful?
Can aid diagnoses (Different types appear in different conditions)
List the major effects of chronic inflammation
Fibrosis
Impaired or increased function
Atrophy
Stimulation of immune response
What causes chronic cholecystitis?
What is the major effect of chronic inflammation on the gallbladder?
Repeated obstruction of the cystic duct by gall stones from the gall bladder
Repeated acute inflammation leads to chronic inflammation
Leads to fibrosis of the gallbladder wall
How does gastric ulceration occur?
What is the end result?
Acute gastritis - Alcohol, drugs
Chronic gastritis - Helicobacter pylori
Ulceration occurs due to the imbalance between acid production and mucosal defence that these condition result in
The affected gastric wall will become fibrotic
What is inflammatory bowel disease?
How does it present?
Idiopathic chronic inflammatory disease affecting large and small bowel, comes in two forms:
Ulcerative colitis:
- Superficial
- Diarrhoea, bleeding
Crohn’s Disease:
- Transmural (across the entire wall)
- Diarrhoea, bleeding
- Strictures (narrowing of bowel)
- Fistulae (abnormal connection between the bowel and another epithelium lined organ)
- Cobblestone ulceration
Acute inflammation appears in the mucosa/crypts
What is the result of Inflammatory bowel disease?
Impaired function (causing diarrhoea)
What is cirrhosis?
What are the common causes of cirrhosis?
Chronic inflammatory process of the liver
Alcohol Hepatitis A, B, C viruses Immunological Fatty liver disease (associated with diabetes and obesity) Drugs and toxins
What does cirrhosis lead to?
Fibrosis causing increasingly disorganised architecture
Impairment of function
Normal liver tissue replaced with ‘nodules’
Cholestasis (bile cannot flow out of the liver)
When can chronic inflammation cause increased function?
In Thyrotoxicosis (Grave’s Disease)
When can chronic inflammation cause atrophy?
What are the consequences in this case?
Atrophic gastritis
Auto-antibodies destroy parietal cells (Secrete gastric acid) and cause atrophy of gastric mucosa and impairment of function
What is rheumatoid arthritis?
How is chronic inflammation involved?
Autoimmune disease that results in loalised and systemic immune response
Systemic immune response can affect organs apart from joints and can cause amyloidosis
Localised chronic inflammation leads to joint destruction
What is meant when you say ‘There is overlap between chronic inflammation and the immune response’
Immune diseases can cause pathology by chronic inflammation
Also, chronic inflammatory processes can stimulate immune responses
What is granulomatous inflammation?
What is a granuloma?
Chronic inflammation with granulomas
An accumulation of epitheloid histiocytes (modified, immobile macrophages) surrounded by lymphocytes
How do granulomas arise?
Persistent, low grade antigenic stimulation
OR
Hypersensitivity
What are the main causes of granulomatous inflammation?
Mildly irritant foreign material
Infections:
- Mycobacteria (tuberculosis, leprosy)
- Other infections (Some fungi)
Unknown causes:
- Sarcoid
- Wegeners’ granulomatosis
- Crohns’ Disease
What causes tuberculosis and how does that cause disease?
Caused by mycobacterium (especially M. tuberculosis)
Causes disease by persistence and induction of cell mediated immunity (no toxins or lytic enzymes)
Describe a tuberculosis granuloma
Has the same general structure as a granuloma however:
- Area of caseous necrosis in the centre (surrounded by epitheloid histiocytes)
Giant cells (Langhans’ type) present
What are the outcome of tuberculosis?
Arrest (stops the TB and localises it - Dormant TB)
Fibrosis
Scarring
Erodes into the bronchus and causes acute inflam.
Tuberculous empyema (collection of pus in the pleura)
Erosion into the bloodstream
What can happen if tuberculosis erodes into the bloodstream?
Many bugs:
- Miliary (systemic) tuberculosis
Few bugs:
- Single organ tuberculosis
What are the similarities in morphology between tuberculosis and BCG?
Both result in the formation of granulomas
List some granulomatous infections and idiopathic granulomatous diseases
Infections:
- Tuberculosis
- Syphilis
- Leprosy
- Chronic fungal infections
- Cat scratch disease
Idiopathic:
- Sarcoidosis
- Crohns’
