Chronic Inflammation Flashcards
What are the dominant cell types in acute and chronic inflammation?
- ACUTE - neutrophil
- CHRONIC - macrophage
How can chronic inflammation arise from injury?
- Prolonged injury where the injurious agent is not removed quickly will cause chronic inflammation after a few hours
- Such agents include microorganisms, necrotic tissue, foreign bodies and antigens produced during an autoimmune disease
In what ways can chronic inflammation arise? (3)
- Takes over from acute inflammation
- Begins without any preceding acute inflammation
- Develops alongside of and is superimposed on acute inflammation
Describe one event where chronic inflammation could develop alongside and superimpose on acute inflammation
Ongoing bacterial infection
State 3 events where chronic inflammation can occur without a preceding acute inflammation
- TUBERCULOSIS
- Rheumatoid arthritis
- Prolonged exposure to some toxic agents e.g. Silica
What are macrophages derived from and where are the derived cells produced?
- BLOOD MONOCYTES
- Produced in the bone marrow and circulate in blood for ~6 days
- Enter tissues and become macrophages (remain dormant until activated and can live for months)
What are the main functions of macrophages?
- Phagocytosis
- Presentation of antigens to T lymphocytes
- Secretion of substances to activate other cells
- Stimulate angiogenesis
- Induce FIBROSIS
Name 3 properties of macrophages that neutrophils do not have
- Can replicate
- Presentation of antigens to immune cells
- Induce fever by producing PYROGENIC CYTOKINES
Name the types cells that are seen in chronic inflammation (5)
- Macrophages
- T and B Lymphocytes
- Myo/fibroblasts
- Giant cells
- Eosinophils
What are the roles of T and B lymphocytes in chronic inflammation?
- Killer cells (cytotoxic T cells and natural killer)
- Processing antigens
- Produce antibodies (B lymphocytes that differentiate into plasma cells)
- Secretion of cytokines to influence other inflammatory cells
Where are eosinophils found and what is their function?
- Normally present scattered throughout tissues
- Attack large parasites and are involved in hypersensitivity immune response (asthma)
What is the role of fibroblasts in chronic inflammation?
- Secrete extracellular matrix consisting of collagen, GAGs and elastin
- Can differentiate into myofibroblasts and contract which is important in wound healing
How are fibroblasts similar to leucocytes?
Both can respond to chemotacic stimuli and move to sites where most needed
What are giant cells and where are they usually seen?
- Under certain circumstances, macrophages fuse together to form large single multinucleate cells
- Seen in granulomatous inflammation
Name the 3 types of giant cells and state where you would find them
- Langhans giant cells - tuberculosis
- Foreign body giant cells - when a hard to digest foreign body is present
- Touton giant cells - fat necrosis or xanthomas
Describe the appearance of a Langhans cell
- Large cell with multiple nuclei arranged in a horseshoe shape at the periphery
- Seen in TUBERCULOSIS
Describe the appearance of a foreign body giant cell and state its function
- Large cell with multiple nuclei randomly arranged
- Phagocytose small foreign bodies and stick to surface of larger foreign bodies
Describe the appearance of touton giant cells and where they are commonly found
- Nuclei arranged in a ring towards the centre of the cell
- Form in LESIONS where there is a high lipid content (fat necrosis)
- Lesions may contain FOAM CELLS where macrophage cytoplasm appears foamy due to phagocytosis of lipids
Which of the 4 signs of acute inflammation persist in chronic inflammation?
- TUMOR (swelling) and DONAR (pain) persist
- Ruber (redness) and Calor (heat) both resolve
What is fibrosis and how does it occur?
- Excess of fibrous tissue
- Fibroblasts stimulated by cytokines to produce excess collagen
- Helpful at first but if excessive this could impair the function of the organ
Describe how fibrosis can lead to impaired function of an organ
- Excessive fibrosis may lead to replacement of parenchymal tissue and impair function
- Myofibroblasts if parent in excess may cause further problems by slowly contracting, which may restrict blood flow to organ
How can the immune system cause chronic inflammation which results in a disease?
- AUTOIMMUNE response
- Immune system begins attacking inappropriate targets such as body’s normal tissues, so resulting inflammation becomes disease process (e.g. Graves’ disease)
What is granulomatous inflammation?
Type of chronic inflammation where granulomas are seen
Describe the appearance of a granuloma
- Large pale stained structure containing free or phagocytised foreign bodies/bacteria at centre
- Eosinophilic cytoplasm, high proportion of macrophages (giant cells) and epithelioid cells
What are the two types of granulomas that are typically seen?
- Foreign body granulomas
- Hypersensitivity or immune type granulomas
How do immune type granulomas differ from foreign body type granulomas microscopically?
- Immune type granulomas contain LYMPHOCYTES
- Have more prominent epithelioid cells
- Form around antigenic insoluble material that cause cell mediated immunity
Describe the contents of a foreign body granuloma
- Develop around NON-ANTIGENIC material e.g. surgical threads
- Cells, including macrophages, foreign body giant cells, epithelioid cells, some fibroblasts at periphery
- NO LYMPHOCYTES
How can immune type granulomas be harmful?
Can impair organ function as they can develop in parenchymal tissue and occupy parenchymal space within the organ
Name 4 diseases where immune type granulomas may be seen
- Tuberculosis
- Crohn’s disease
- Sarcoidosis
- Wegener’s granulomatosis
What cell types are present in immune type granulomas?
- Macrophages
- Langhans type giant cells
- Epithelioid histiocytes
- Lymphocytes
- Some fibroblasts
What are epithelioid histiocytes?
- MODIFIED MACROPHAGES
- Elongated and tightly packed so resemble epithelia
- Contain eosinophilic cytpplasm and are present in granulomas
What are immune type granulomas capable of which doesn’t occur in foreign body granulomas?
- Can undergo CENTRAL NECROSIS
- Particularly seen in granulomas associated with tuberculosis
Name 3 idiopathic diseases associated with chronic inflammation
- Crohn’s disease
- Sarcoidosis
- Wegener’s granulomatosis
What is chronic cholecystitis and how does it occur?
- Chronic inflammatory disease of the gall bladder
- Caused by repeated obstruction of the cystic duct by gall stones, causing repeated acute inflammation which can progress to chronic
- Fibrosis of the gall bladder wall can occur
Name 3 structures that can be affected in sarcoidosis
- Lungs
- Lymph nodes
- Skin
Name 2 entities that may be present in the lungs in milliary tuberculosis
- Ghon lesions
- Ranke complexes
Where can TB commonly spread from the lung?
Lymph nodes
List 3 differences between ulcerative colitis and Crohn’s disease
- UC affects mucosa and submucosa; CD is transmural
- UC affects mainly distal colon and does not affect anus; CD affects the anus and can affect more than one section of bowel
- CD can present with cobblestone mucosa, strictures and/or fistulae
What is a systemic consequence of rheumatoid arthritis?
AMYLOIDOSIS of organs
Describe how atrophy of the gastric mucosa commonly occurs
Accumulation of lymphocytes due to cell mediated immunity leads to destruction of the gastric wall
Explain how gastric ulceration occurs
Imbalance between the production of gastric acid and mucus defence leads to ulceration of the gastric wall
Name one acute and one chronic cause of gastric ulceration
- ACUTE - alcohol/NSAIDS
- CHRONIC - Helicobacter pylori
Describe the appearance of a cirrhotic liver
Hard, shrunken liver with nodules of attempted regeneration surrounded by bands of collagen, where excessive fibrosis has occurred
How does mycobacterium tuberculosis cause disease?
- PERSISTENCE
- Induces cell mediated immunity which can cause damage to normal tissue
Name 8 examples of diseases where granulomas may be present
- TB
- Leprosy
- Crohn’s disease
- Sarcoidosis
- Cat scratch disease
- Wegener’s granulomatosis
- Chronic granulomatous disease
- Syphyllis
What are the two types of granuloma that can form? Give examples of when these may occur
- Hypersensitivity/immune type (develop around insoluble but antigenic material triggering cell mediated immunity e.g. TB)
- Foreign body type (develop around material that is non-antigenic e.g. surgical thread)
Describe the significance of granuloma formation in removal of foreign bodies/tough bacteria
- Granuloma forms around the foreign body and walls it off from the surrounding parenchymal tissue (minimises tissue injury)
- Concentrates mononuclear cells at its centre to destroy the particle
When do granulomas form?
- When the body attempts to deal with particles which are poorly soluble or difficult to eliminate
- May also be idiopathic (have no known cause)
What are epithelioid histiocytes?
- Immobile modified macrophages with eosinophilic granular cytoplasms, usually found within granulomas
- Assist in phagocytosis and destruction of foreign bodies
- Elongated and appear tightly packed (similar to appearance of epithelia)
What is a germinal centre?
Accumulation of B lymphocytes within lymph nodes which are undergoing proliferation, differentiation and maturation of antibodies
What are eosinophils? Describe their appearance and action
- Bright pink granular cytoplasm with a bilobar nucleus
- Attack large parasites and are involved in hypersensitivity reactions
