Week 3 - Chronic Inflammation Flashcards
What is chronic inflammation?
Chronic response to injury with associated fibrosis
- Characterised by the microscopic appearances which are much more variable than in acute inflammation
- The most important characteristic is the type of cell present
Which cells are present in chronic inflammation?
- Macrophages (important in acute and chronic inflammation)
- Lymphocytes (B produce antibodies)
- Plasma cells
- Eosinophils (allergic reactions, parasite infestations, some tumours)
- Fibroblasts/myofibroblasts (recruited by macrophages, make collagen)
What are myofibroblasts?
Differentiated fibroblasts that can contract
What are giant cells?
Multinucleate cells made by the fusion of macrophages
- Caused by frustrated phagocytosis (the macrophages can’t deal with how much they have to phagocytose, so join together to deal with it)
What are the different types of giant cells?
- Langhan (seen in TB, nuclei arranged around the periphery)
- Foreign body type (seen with foreign material, nuclei are arranged randomly)
- Touton (seen in lesions with high lipid content: fat necrosis, nuclei are arranged in a ring towards the centre of the cell)
In what situations can chronic inflammation occur?
- May ‘take over’ from acute inflammation (if damage is too severe to be resolved within a few days; most common)
- Begins without any preceding acute inflammation (e.g. in some chronic infections, in some autoimmune conditions)
- Develops alongside acute inflammation and superimposes on it (e.g. in ongoing bacterial infection; in severe, persistent or repeated inflammation)
What are some possible complications of chronic inflammation?
- Fibrosis and impaired function
- Involvement in inappropriate immune responses
- Atrophy
What is atrophy?
Cell shrinkage/loss
What is fibrosis?
An excess of fibrous tissue
- It occurs when fibroblasts are stimulated by cytokines to produce excess collagen
- Typically seen during chronic inflammation
How is collagen useful in chronic inflammation?
- Collagen production can help to wall off infected areas
- The production of a fibrous scar to replace damaged tissue is essential in wound healing
What happens if collagen is excessive/inappropriate? (In chronic inflammation)
It can replace normal parenchymal tissue
- This will impair the function of the organ
- If the area of fibrosis contains enough myofibroblasts, it can slowly contract and cause further problems
How can chronic inflammation cause inappropriate immune responses?
The immune system uses inflammation as a non-specific weapon to destroy its specific targets
- But it doesn’t always get right
- It can attack innocuous targets such as pollen, or inappropriate targets such as the body’s normal tissue (resulting in autoimmune disease)
What is a granuloma?
An aggregate of activated macrophages
- The body’s way of dealing with particles that are poorly soluble or difficult to eliminate for some reason
- E.g. foreign bodies, tough bacteria (e.g. mycobacterium TB)
- Usually about 0.5-1mm in diameter
What does a granuloma do?
It forms around the particle, which can be free or phagocytised in the centre of the granuloma
- It walls it off whilst concentrating mononuclear cells within its centre, with which it hopes to destroy the particle
What do granulomas contain?
Epithelioid cells
- Macrophages which have been modified to be elongated
- They have eosinophilic cytoplasm
- They appear tightly packed together
- Like epithelial cells
What are the 2 types of granuloma?
- Foreign body
- Hypersensitivity/immune type
What do foreign body granulomas do?
Develop around material that is not antigenic
What do foreign body granulomas contain?
- Macrophages
- Foreign body giant cells
- Epithelioid cells
- Some fibroblasts
- Very few lymphocytes
What do hypersensitivity granulomas do?
Develop around insoluble but antigenic particles that cause cell-mediated immunity
- Can undergo central necrosis
- Can be harmful because they occupy parenchymal space within an organ
What do hypersensitivity granulomas contain?
- Macrophages
- Giant cells
- Epithelioid cells
- Some fibroblasts
- Lymphocytes
When can hypersensitivity granulomas be seen?
- Sarcoidosis
- Wegener’s
- Granulomatosis
- Crohn’s disease
- Chronic inflammation
What is rheumatoid arthritis?
- Autoimmune disease
- Localised chronic inflammation leads to joint destruction (chronic inflammation in the synovium of joints)
- Systemic immune response (can affect other organs and cause amyloidosis)
What are the key symptoms of rheumatoid arthritis?
- Pain
- Fatigue
- Warm, swollen joints
What is ulcerative colitis?
A type of inflammatory bowel disease
- Disrupted and thinned mucosa, reduced density of gastric glands
How do patients present in ulcerative colitis?
- Diarrhoea
- Rectal bleeding
- Weight loss
- Other symptoms
What are the features of ulcerative colitis?
- Inflammation is limited to mucosa and submucosa
- Crypt accesses are common
- Distorted crypt architecture is very common
- Gives a significant risk of colon cancer
- Often most severe in distal colon
- Colectomy often indicated
- Lots of neutrophils and lymphocytes (so both acute and chronic inflammation are present)
- It is superficial
What is Crohn’s disease?
A type of inflammatory bowel disease
- Causes strictures and fistulae (abnormal connections between 2 epithelium-lined organs)
- It is transmural
- Patients present similar to ulcerative colitis
What are the features of Crohn’s disease?
- Discontinuous distribution
- Affects any part of the GI system (mouth to anus)
- ‘Cobblestone’ appearance of bowel mucosa is classically seen
- Anal lesions are common
- Bowel fistulae are likely
- Granulomas are often present
What is chronic cholecystitis?
- Gallstones develop in the gall bladder due to cholesterol/bilirubin pigment/etc.
- Causes irritation to gall bladder
- Repeatedly obstructs cystic ducts
- Repeated acute inflammation leads to chronic inflammation
- Causes fibrosis of gallbladder wall
What is chronic gastritis?
Inflammation of the stomach lining
- Causes a gastric ulcer
- Because of an imbalance in acid production and mucosal defence
- Lose part of the mucosal wall
- Usually caused by helicobacter pylori
What are the symptoms of chronic gastritis?
- Gnawing/burning stomach pain
- Nausea and vomiting
- Feeling full after eating
What is cirrhosis?
Chronic inflammation in the liver with fibrosis
- Disorganisation of architecture, attempted regeneration
- Usually caused by alcohol abuse
What are the symptoms of cirrhosis?
- Pain in the abdomen
- Loss of appetite
- Nausea
- Itchy skin
Later on: - Jaundice
- Vomiting blood
- Dark stools
- Build up of fluid in legs
