Session 3 -> Chronic inflammation Flashcards
What is chronic inflammation?
-The chronic response to injury and process of healing with the production of granulation tissue and fibrosis
What is the predominant cell type in chronic inflammation?
-Macrophage
Give an example of a persisting injurous agent which can cause chronic inflammation
- Foreign body
- Necrotic tissue
- Bacteria
- Autoimmune antigen
When does chronic inflammation occur?
- Alongside acute inflammation
- After acute inflammation
- Begins without any preceeding inflammation
- Autoimmune conditions
- Prolonged exposure to toxic agents
When would chronic inflammation occur alongside acute inflammation?
-During a severe or persistent irritation eg cholecystitis
Give an example of when chronic inflammation would occur without any preceeding acute inflammation
-In some chronic infections such as tuberculosis
Give an example of an autoimmune condition where chronic inflammation occurs
-Rheumatoid arthritis
Name a toxic agen which can cause chronic inflammation after prolonged exposure
-Silica
When do macrophages become activated in tissues?
-Can live and be dormant for many months until they are activated by a local challenge
Which cell type are the best at destroying persistent bacteria such as TB, neutrophils of macrophages?
-Macrophages
What are the functions of macrophages?
- Phagocytosis
- Present antigens to adaptive immune system
- Secrete substances which summon and activate other cellls
- Stimulate angiogenesis (important in wound healing)
- Induce fever, acute phase reaction and fibrosis
What does lymphocyte presence in normally absent tissues indicate?
-Antigenic material is or has been present
Where are lymphocytes normally present?
- Lymph nodes
- Spleen
- Liver
What are the functions of lymphocytes?
- Secrete antibodies (plasma B cells)
- Process antigens
- Secrete cytokines
- Kill cells
How do plamsa cells differ phenotypically from other lymphocytes?
-They have peri-nuclear hof -> pale cytoplasm due to abundance of ER and golgi producing antibody
What is the main function of eosinophils?
-Attack large parasites, eg worms
In what immune responses are eosinophils present in high numbers?
- Asthma (in bronchi)
- Tumours such as hodgkin’s lymphoma
- Allergic reactions
What cell types are principally involved in chronic inflammation?
- Macrophages
- Lymphocytes
- Eosinophils
- Fibroblasts and myofibroblasts
What is the function of fibroblasts?
- Produce connective tissue substances such as collagen, elastin and GAGs
- Differentiate into myofibroblasts
What is a giant cell?
-A single giant multinucleate cell formed by the fusion of many macrophages
In what type of inflammation are giant cells often seen?
-Granulomatous inflammation
What do giant cells do?
-Perform frustrated phagocytosis
Describe Langhan giant cells
When are they often seen?
- Cell nuclei arranged around the periphery in a horse-shoe
- Foamy cytoplasm
- Often, but not exclusively, seen in tuberculosis
Describe foreign-body giant cells
When are they seen?
- Nuclei arranges randomly within the cell
- Often but bot exclusively seen when a hard to digest foreign body is present
How do foreign-body giant cells eradicate foreign bodies?
- Small foreign bodies are phagocytosed
- Giant cells stick to the surface of large foreign bodies
Describe a touton giant cell
When are they often seen?
- Nuclei are arranged in a ring towards the centre of the cell
- Lipid is around the outside
- Often formed in lesions where there is a high lipid content such as fat necrosis and xanthomas
Is there a typical composition of cells within chronic inflammation?
-No, the response is not sterotyped and thus the proportion of cells will vary depending on the cause
eg Rheumatoid arthritis = plasma cells
Chronic gastritic = lymphocytes
Leishmanaisis (protazoal infection)= macrophages
What is the cause of scarring?
-Excessive fibrous tissue deposition
List the possible complications of chronic inflammation
- Fibrosis
- Impaired function
- Atrophy
- Stimulation of immune response
When does excess fibrosis occur?
-When fibroblasts are stimulated by cytokines to produce excess collagen
How is collagen production important in chronic inflammation?
- Walls off infected areas
- Production of a fibrous scar to replace damaged tissue
When does collagen deposition become problematic?
-when it is excessive or inappropriate and replaces normal parenchymal tissue and impairs the function of the organ
Provide an example of when collagen deposition occurs and impairs function?
-Interstitial fibrosis of the lung
How can myofibroblasts be problematic?
-When an area contains excess myofibroblasts there can be excessive contraction of the wound leading to contractures
Provide an example of when myofibroblasts can impair function
-Contraction in the cirrhotic liver will impair the flow of portal blood resulting in ascites
Chronic cholecystitis is an example of fibrosis, describe this process of inflammation
- Gallstones blocking the cystic duct
- Bile is not secreted and accumulates causing multiple repeated episodes of acute inflammation as it is toxic
- Chronic inflammation ensues and the gall bladder becomes increasingly fibrous and thickens over time
Why does the muscular component of the gallbladder thicken in cholecystitis?
-Repeated attempts at extruding gall stones
What is gastric ulceration?
-Necrosis of epithelia on gastric mucosal surface
What is another name for gastric ulceration?
-Peptic ulcer
Why is gastric ulceration seen in chronic gastritis?
- There is a focal imbalance of acid production and mucosal defence leading to erosion of the mucosal surface
- The submucosa becomes washed with HCl
What is often seen at the base of an ulcer?
-White slough
What is inflammatory bowel disease?
-A group of diseases characterised by relapsing and remitting inflammation of the gastrointestinal tract
What are the most common types of inflammatory bowel disease?
- Crohn’s
- Ulcerative colitis
Why are inflammatory bowel diseases described as episodic?
-Repeated episodes of acute inflammation which can be treated occur in addition to the underlying chronic inflammation
What is the most common cause of inflammatory bowel diseases?
-It is most commonly idiopathic
What are the main differences between ulcerative colitis and Crohn’s?
- Ulcerative colitis is inflammation and ulceration of the superficial mucosa, usually effecting the rectum but can involve part of the colon or retreat and effect the whole colon
- Crohn’s disease is transmural inflammation and ulceration which is usually segmental from the mouth to the anus (skip lesions)
What is liver cirrhosis?
-A condition where the liver responds to injury by producing interlacing strands of fibrous tissue between which are nodules of regenerating cells
How do patients with inflammatory bowel disease usually present?
-Diarrhoea, rectal bleeding and varied symptoms
What is a stricture?
-Narrowing of a tube
Do strictures and fistulas form in ulcerative colitis or crohn’s?
-Crohn’s
What is a fistula?
-Abnormal connection between two epithelial lined organs
How does a cirrhotic liver look characteristically?
-Shruken and nobbly
How does cirrhosis occur?
- Chronic inflammation leads to excess collagen deposition and fibrosis
- This causes disorganisation of the architecture, whilst regeneration is attempted inbetween the bands of fibrosis
- This leads to the multinodular liver with impaired function ie cirrhosis
What are the common causes of liver cirrhosis?
- Alcohol
- Infection with HBV/HCV
- Fatty liver disease
- Immunological causes
- Drugs/toxins
What is atrophic gastritis?
-Atrophy of the gastric mucosa, possibly suceeding chronic gastritis but often occurs spontaneously as an autoimmune disease in association with pernicious anaemia
Can the immune response induce inflammation?
-Yes, it uses inflammation as a non-specific weapon
What is rheumatoid arthritis?
-An autoimmune disease where there is chronic inflammation in the synovial membrane of joints due to autoimmune antibodies
What does the localised chronic inflammation in rheumatoid arthritis cause?
-Destruction of joints
What are the systemic effects of chronic inflammation in rheumatoid arthritis?
- Can cause amyloidosis (mis-folding of fibbres into b-sheets which become insoluble and deposit as amyloid fibres)
- Can effect other organs such as skin, liver and lung
What is the overlap between chronic inflammation and immune response?
- Immune diseases cause pathology by chronic inflammation
- Chronic inflammatory processes can stimulate immune responses
What is granulomatous inflammation?
-Chronic inflammation with granulomas
What is a granuloma?
-A localised collection of cells characterised by the presence of epitheloid histiocytes, giant cells and monocytes/lymphocytes
What are epitheliod histiocytes?
-Immobile macrophages which represent epithelial cells as they are elongated, have eosinophilic cytoplasm and are tightly packed
When does granulomatous inflammation occur?
- Persistant, on-going low-grade antigenic stimulation
- Hypersensitivity
How do granulomas form in relation to the target material?
-They form around the particle which can be free or phagocytosed in the centre
What immune cells are often found in the centre of granulomas and why?
-Monocytes as they try to wall the particle off from the environment
How big are granulomas?
-Usually 0.5-1mm
What are the two types of granuloma?
- Foreign body granuloma
- Hypersensitivity/immune-type granuloma
When do foreign-body granulomas occur?
-When there is persistent, ongoing low-grade stimulation
Describe a foreign body granuloma
-Contains macrophages, foreign body giant cells, epitheloid cells and some fibroblasts at periphery. There are very few lymphocytes as the stimulus is non-antigenic
Describe hypersensitivity/immune-type granulomas
- Contain macrophages, giant cell (possible langhans), epitheloid cells, fibroblasts and lymphocytes
- Can undergo central caseous necrosis and develop around insoluble but antigenic particles
What is a granuloma, which has central caseous necrosis, associated with?
-TB
What are the main causes of granulomatous inflammation?
- Mildly irritant foreign material (artificial joint break down, surgical thread etc)
- Persistant Infections (TB, leprosy, syphyllis, cat-scratch disease)
- Unknown causes
What is leprosy?
-Chronic disease caused by mycobacterium leprae that effects skin, mucous membranes and nerves
What is cat-scratch disease?
-An infectious disease which is transmitted to humans by a cat scratch
which can become chronic
What is sarcoidosis?
-A chronic disorder of unknown cause in which the lymph nodes are enlarged and granulomas form in the lungs, liver and spleen, however many other sites can be effected
What is wegener’s granulomatosis?
-An autoimmune disease predominantly effecting the nasal passages, lungs and kidneys, characterised by the formation of necrotising granulomas in addition to pulmonary vasculitis
Do granulomas appear in ulcerative colitis or crohn’s disease?
-Crohn’s disease
How does tuberculosis cause disease?
-Through persistance and induction of cell-mediated immunity
What giant cells are associated with tuberculosis?
-Langhan cells
Describe a granuloma associated with TB
-Granuloma contains langhan cells and has central caseous necrosis (histiologically appears pink)
What are the 4 possible outcomes of TB?
- Arrest, fibrosis and scarring
- Erosion into bronchus leading to bronchopneumonia or TB in the GIT through coughing and then swallowing
- Tuberculosis empyema -> chronic active infection of the pleural space with calcification of the pleura
- Erosion into the bloodstream which can result in focal tb(localised in one organ) or miliary TB (effects everywhere)
Who is sarcoidosis most commonly seen in?
-Young women
What macroscopic features of acute inflammation remain in chronic inflammation?
-Tumor and Dolor (swelling and pain)
