S3) Chronic Inflammation Flashcards
What is chronic inflammation?
- Chronic inflammation refers to the prolonged inflammatory response that involves a progressive change in the type of cells present at the site of inflammation
- It is characterised by the simultaneous destruction and repair of the tissue from the inflammatory process
Why does chronic inflammation occur?
Chronic inflammation takes over acute inflammation in a few hours if the injurious agent is not quickly removed (hence, persists)
How does chronic inflammation present?
With regards to the four clinical signs of acute inflammation, redness and heat resolve but swelling but pain persists in chronic inflammation
What is the dominant cell in chronic inflammation?
The dominant cell in this type of inflammation is the macrophage and the process is more sophisticated than that seen in acute inflammation
What are the possible injurious agents causing chronic inflammation?
- Micro-organism
- Necrotic tissue
- Foreign body
- Crystalline substance
- Antigen
Draw a comparison between chronic and acute inflammation in terms of the following:
- Cells involved
- Chemical mediators involved
- Lesion formed
- Clinical examples
How can chronic inflammation arise?
- Takes over from acute inflammation (most common)
- Begins without preceding acute inflammation, e.g. tuberculosis, RA
- Develops alongside and superimposed on acute inflammation e.g on-going bacterial infection
Describe the microscopic appearance of chronic inflammation
- Macrophages and lymphocytes are present
- Granulation tissue begins to form
Identify the cells principally involved in chronic inflammation
- Macrophages
- T and B lymphocytes
- Eosinophils
- Fibroblasts
- Myofibroblasts
In the context of chronic inflammation, what are macrophages?
Macrophages are derivatives of blood monocytes and migrate into tissue spaces at the site of inflammation, after neutrophils, to take over from them
What are the functions of macrophages?
- Phagocytosis
- Antigen presentation
- Activate other cells (secrete substances)
- Stimulate angiogenesis
- Induce fibrosis
- Induce fever, acute phase reaction and cachexia
In the context of chronic inflammation, what are lymphocytes?
Lymphocytes are cells of the immune system which are present in tissues where there is antigenic material
What are the functions of lymphoctes?
- Process antigens
- Secrete antibodies (B lymphocytes)
- Secrete cytokines (T lymphocytes)
- Kill tumour / virus-infected cells (natural killer cells)
What are eosinophils and what do they do?
Eosinophils are immune cells which attack large parasites such as worms and they are present in high numbers in some immune responses e.g. in the bronchi in asthma, Hodgkin’s lymphoma
What do fibroblasts do?
- Respond to chemotactic stimuli and move to sites where they are needed
- Produce connective tissue substances e.g. collagen, elastin and GAGs
- Differentiate into myofibroblasts (can contract)
What are giant cells?
- Giant cells are cells formed when macrophages fuse with each other in circumstances when foreign bodies / certain bacterial infections are present
- These cells can be very large, contain dozens to hundreds of nuclei and are seen in granulomatous inflammation
What are the three types of giant cell?
- Touton giant cells
- Langhans giant cells
- Foreign body giant cells
Describe the structure of Langhans giant cells.
Where are they often seen?
- Nuclei are arranged around the periphery of the giant cell
- Often seen in tuberculosis (not exclusively)
Describe the structure of foreign body giant cells.
Where are they often seen?
- Nuclei are arranged randomly in the giant cell
- Often seen when an indigestible foreign body is present (not exclusively)
- Large foreign bodies stick to cell surface, small foreign bodies are phagocytosed
Describe the structure of touton giant cells.
Where are they often seen?
- Nuclei are arranged in a ring towards the centre of the giant cell
- Form in lesions where there is a high lipid content e.g. fat necrosis and xanthomas
What are possible complications of chronic inflammation?
- Fibrosis and impaired function
- Involvement in inappropriate immune responses
What is the role of collagen production in chronic inflammation?
- Collagen production is initially helpful as it walls off infected areas produces a fibrous scar to replace damaged tissue
- This is essential in wound healing
What is fibrosis and how does it lead to impaired function in chronic inflammation?
- Fibrosis is the excess production of fibrous tissue, occurring when fibroblasts are stimulated by cytokines to produce excess collagen
- This replaces normal parenchymal tissue and impairs organ function e.g. interstitial fibrosis of the lung
Provide six clinical examples of chronic inflammation
- Rheumatoid arthritis
- Ulcerative colitis
- Crohn’s disease
- Chronic cholecystitis
- Chronic gastritis
- Cirrhosis
What is rheumatoid arthritis?
- Rheumatoid arthritis is a long-term condition that causes pain, swelling and stiffness in the joints
- The symptoms usually affect the hands, feet and wrists
What is ulcerative colitis?
- Ulcerative colitis is a long-term condition, where the colon and rectum become inflamed
- Small ulcers can develop on the colon’s lining, and can bleed and produce pus
What is Crohn’s disease?
- Crohn’s disease is a long-term condition that causes inflammation of the lining of the digestive system
- Inflammation can affect any part of the digestive system, but most commonly occurs in the ileum / large intestine
What is chronic cholecystitis?
- Chronic cholecystitis involves repeated episodes of acute inflammation of the gallbladder
- It usually occurs when a gallstone blocks the cystic duct
What is chronic gastritis?
- Chronic gastritis occurs when the stomach lining becomes inflamed, often due to bacterial infection by Helicobacter pylori
- It can be painless or cause dull, persistent stomach pain
What is an ulcer?
An ulcer is breach in the mucosa to the level of submucosal layer/deeper
How does Helicobacter pylori cause gastritis?
Helicobacter pylori stimulates the production of pro-inflammatory cytokines, directly injures epithelial cells and increases acid secretion
What changes can be seen microscopically in chronic gastritis caused by Helicobacter pylori?
- Helicobacter pylori organisms
- Chronic inflammation (lamina propria, superficial epithelium)
- Lamina propria fibrosis
- Mucosal atrophy
- Intestinal metaplasia
Which malignancies are associated with Helicobacter pylori gastritis?
- Gastric adenocarcinoma
- MALT (mucosa associated lymphoid tissue) lymphoma
What is cirrhosis?
- Cirrhosis is the scarring of the liver caused by continuous long-term liver damage
- Scar tissue replaces healthy tissue irreversibly in the liver and if extensive, impairs liver function (liver failure)
What are granulomas and when do they form?
- A granuloma is a mass of granulation tissue, formed in response to infection, inflammation or due to the presence of a foreign substance
- They wall off substances the body perceives as foreign and unable to eliminate e.g. foreign bodies (thorns), bacteria like Mycobacterium tuberculosis
What do granulomas do?
- The granuloma forms around the particle which is free/phagocytosed within its centre
- It walls the particle off whilst concentrating mononuclear cells within its centre hoping to destroy the particle
What is granulomatous inflammation?
Granulomatous inflammation is a type of chronic inflammation in which granulomas are seen
What do foreign body granulomas do and what do they contain?
- Contain: macrophages, foreign body giant cells, epithelioid cells, some fibroblasts (at periphery), very few lymphocytes
- Function: develop around non-antigenic material e.g. surgical thread
What do hypersensitivity / immune type granulomas do and what do they contain?
- Contain: macrophages, Langhans giant cells, epithelioid cells (more prominent), some fibroblasts (at the periphery), lymphocytes
- Function: develop around insoluble antigenic particles that cause cell-mediated immunity e.g. in tuberculosis, syphillis
Besides TB and syphillis, where else are hypersensitivity granulomas seen?
- Sarcoidosis
- Wegener’s granulomatosis
- Crohn’s disease
What is a key process occuring in immune type granulomas?
Immune type granulomas undergo central necrosis
What is sarcoidosis?
- Sarcoidosis is a rare condition of unknown cause which causes granulomas to develop in the organs of the body
- It usually affects the lungs and skin
In 7 steps, describe what happens when a person inhales Mycobacterium tuberculosis
⇒ MTB enters macrophages by endocytosis
⇒ MTB replicates within phagosome
⇒ MTB proliferates in alveolar macrophages and air spaces
⇒ Bacteraemia develops + seeding of multiple sites
⇒ 3 weeks later, T helper cell response activates macrophages
⇒ Activated macrophages produce TNF
⇒ Monocytes differentiate into epithelioid histiocytes, forming granulomas
⇒ Contains illness in many
Describe what is meant by the following terms:
- Mantoux test
- BCG
- Mantoux test – a screening test for tuberculosis
- -* BCG – a vaccine against tuberculosis that is prepared from a strain of the attenuated (virulence-reduced) live bovine tuberculosis bacillus
What is a primary complex?
A primary complex consists of local reaction in the lung parenchyma where the organisms lodge and the inflammatory reaction of the associated lymph nodes
Describe what is meant by the following terms:
- Ghon focus
- Ghon complex
- Ranke complex
- Ghon focus – a calcified tuberculous granuloma in the lung
- Ghon complex – a calcified tuberculous granuloma in the lung & hilar lymph node
- Ranke complex – composed of a ghon focus and an ipsilateral calcified hilar node (seen in healed TB)
Describe what is meant by the following terms:
- Miliary tuberculosis
- Pott’s disease
- Scrofula
- Miliary tuberculosis – disseminated tuberculosis throughout the body resulting in tiny lesions seen on a chest X-ray
- Pott’s disease – TB in the vertebrae
- Scrofula – TB nodes in cervical region
Compare and contrast Ulcerative Colitis and Crohn’s Disease in terms of:
- Location
- Pathology
- Rectum involvement
- Mucosal inflammation
- Fistula formation
