06-10-21 - Chronic Inflammation Flashcards
What are the usual sequelae of acute information?
What can cause it to take difference routes?
- Acute inflammation typically ends in resolution
- If there is excess exudate, this can lead to suppuration, which can cause the discharge of pus, and eventually leads to repair and resolution
- If there is excessive necrosis (dead tissue), this can lead to repair and organisation, which can cause fibrosis (thickening or scarring of the tissue)
- If the causal agent Is persistent, this can cause chronic inflammation, which can lead to fibrosis)
What are the 4 factors that favour resolution from acute inflammation?
- Minimal cell death and tissue damage
- Occurrence in an organ or tissue with regenerative capability, such as the liver
- Rapid destruction of the causal agent
- Rapid removal of fluid and debris by good local vascular drainage
What is organisation?
What is fibrous tissue made from?
What are the 3 factors that favour organisation?
What are indications of organisation on a diagram?
- Organisation is the replacement of destroyed tissue by granulation tissue, which leads to fibrosis (thickening/scarring) (fibrous tissue is composed of parallel bundles of collagen)
- Factors that favour organisation:
- Large amounts of fibrin (protein involved in wound healing)
- Substantial necrosis
- Exudate and debris can not be removed or discharged
- Indications of organisation on a diagram:
- Formation of sprouting capillaries
- Infiltration of inflammatory cells e.g macrophages
- Proliferation of fibroblasts – fibroblasts are the most common cell type in connective tissue.
- Fibroblasts secret collagen which is used to maintain a structural framework in tissues. They are also involved in healing in wounds.
What happens during healing of a severe burn?
What does granulation appear like in a severe burn?
What is the inflammatory exudate replaced by during organisation?
- In a severe burn, much of the skin is destroyed, and the underlying tissue will be undergoing repair.
- The damaged area is being replaced by vascular granulation tissue
- The burn is red and has a moist, bumpy appearance due to the new sprouting capillary beds in the granulation tissue.
Why is inflammatory exudate replaced during organisation?
What is it replaced by?
What are the growth factors that regulate this process?
- When inflammatory exudate cannot be cleared away properly, it is replaced by granulation tissue containing:
- Capillaries
- Macrophages
- Fibroblasts
- Collagen
- This is regulated by growth factors: EGF, FGF, TNF
What are the 3 ways in which chronic inflammation develops?
- Primary Chronic Inflammation – occurs without previous episode
- Progression from acute inflammation
- Recurrent episodes of acute inflammation
What are 6 ways Primary Chronic inflammation develops?
What are example diseases of each?
- Resistance of infectious agent to phagocytosis and intracellular killing e.g tuberculosis, leprosy, brucellosis, viral infections
- Foreign body reactions to endogenous materials (from inside of the body) ) (might be acute or chronic) e.g gout which is caused by accumulation of urate crystals in the joint
- Foreign body reactions to exogenous materials (from outside of the body) e.g asbestos
- Some autoimmune disease e.g rheumatoid arthritis, which is the body’s immune system destroying cartilage in the joints
- Specific diseases of unknown aetiology (cause) e.g ulcerative colitis
- Primary granulomatous diseases e.g TB and sarcoidosis, which is the accumulation of inflammatory like cells which form granulomas
What are 3 factors that favour the progression from acute inflammation to chronic inflammation?
What are examples of this?
• Persistence of substances that can cause acute inflammation at the start, then long term chronic inflammation e.g indigestible substances like glass, suture material
- Deep seated suppurative inflammation where abscess draining is delayed or inadequate
- This can be due to:
- Thick abscess wall
- Fibrous/granulation tissue
- Pus in access becomes organised
- Formation of fibrous tissue
- An example of this is osteomyelitis, which is a chronic abscess in the bone that is extremely difficult to eradicate
- Recurrent episodes of acute inflammation and healing may result in chronic inflammation
- An example of this is chronic cholecystitis, which is the replacement of the wall in the gallbladder with fibrous tissue.
What are 5 examples of what Chronic Inflammation can look like?
- Chronic ulcer
- This is a breach in the mucosal surface (GI or respiratory tract)
- The breach of chronic ulcers is lined by granulation tissue
- Chronic ulcers can form fibrous tissue throughout muscle layers, which is what is seen in peptic ulcers.
- Chronic abscess cavity e.g osteomyelitis, empyema thoracis (collection of pus in pleural space)
- Thickening of the wall of a hollow viscus
- Granulomatous inflammation - chronic inflammation in which a compact collection of immune cells (chiefly macrophages and cells derived from them) are present e.g TB and Sarcoidosis
- Fibrosis
What are the primary cells associated with chronic inflammation?
What is this usually accompanied by?
• Chronic inflammation is an inflammatory process in which lymphocytes, plasma cells (activated differenciated B-lymphocyte WBCs) and macrophages predominate.
• Macrophages can also fuse to produce mutli-nucleate giant cells, which are very characteristic of some immune responses.
• This is usually accompanied by the formation of granulation tissue, resulting in fibrosis.
Macrophages are the major cells associated with chronic inflammation.
What are indications of chronic inflammation on a diagram?
- Plasma cells, which consist of differentiated B-lymphocytes
- Lymphocytes around the vessel
- Multinucleate cell formed by the fusion of macrophages
- Macrophages
- Fibroblasts (secrete collagen and used in structure of tissues and wound healing)
How are macrophages related to chronic inflammatory response?
What are their capabilities?
How big are they?
What do they produce?
How are they activated and deactivated?
What can be a potential issue with macrophages?
- Macrophages are the most common cell associated with chronic inflammatory response.
- They have considerable phagocytic capabilities, and can ingest a wide range of materials
- They are relatively larger cells (larger than lymphocytes)
- They produce a range of important cytokines, which activated and inhibit other cells.
- The are activated on migration to an area of inflammation by macrophage activation factor (MAF)
- They are inhibited by migration inhibition factor (MIF)
- A problem with macrophages, is they can harbour viable organisms’ resistance to lysosomal enzymes, which gives them protection from immune responses. e.g mycobacterium TB
What are the macrophages derived from?
What is the name for macrophages in the blood?
Why do macrophages get new names?
- Macrophages are derived from haematopoietic stem cells
- Monocytes are macrophages in the blood
- Macrophages then slightly differentiate depending what tissue/organ they end up in, so they are all referred to by a different name, despite being very similar.
What is a granuloma?
Where might granulomas be found?
What does a granuloma look like?
- A granuloma is an aggregate of epithelioid histiocytes (macrophages in connective tissue) into giant cells that have very little phagocytic activity, but maintain their secretory function
- Granulomas can be found in sarcoidosis of the liver (accumulation of inflammatory cells) and TB
What are 5 causes of Granulomatous disease?
How do many causative agents get in the body?
- Specific infections
- Foreign bodies reactions (endogenous/exogenous)
- Specific chemicals
- Drugs
- Unknown.
- Many caustaive agents are ingestible (foreign bodies and speicifc infections)
What are the 2 forms of histiocytic giant cells?
- Langerhans giant cell
* Foreign body giant cell
