Cell pathology 2 - Inflammation Flashcards
What is inflammation?
- Complex reaction in viable vascularised tissues to sublethal cellular injury
- A protective response geared towards removing the cause and consequences of the injury
- Sets stage for potential healing
- Tightly regulated process consisting mainly of leukocyte and vascular responses
- Triggered by various cell types and soluble mediators
What cells are involved in inflammation?
- Neutrophils
- Macrophages
- Lymphocytes
- Eosinophils
- Mast cells
What soluble factors are involved in inflammation?
- Antibodies
- Cytokines
- Complement system
- Coagulation system
What is acute inflammation?
- Acute inflammation is a rapid non-specific response to cellular injury
- It is orchestrated by mediators released from injured cells
- Leukocyte and vascular response
What is chronic inflammation?
- Chronic inflammation is a persistent inflammatory response
- Ongoing inflammation and repair over weeks to years
- May arise form acute inflammation (Granulomatous inflammation is a specific subtype of chronic inflammation)
How is acute inflammation recognised?
- Rubor (Redness)
- Calor (Heat)
- Tumor (Swelling)
- Dolor (Pain)
What is the purpose of the acute inflammatory response?
Rapid delivery of leukocytes and plasma proteins to the site of injury
What are the three main components of acute inflammation?
- Alteration in the calibre of blood vessels to increase flow
- Structural changes to the microvasculature to allow proteins and leukocytes to leave the circulation
- Emigration, accumulation and activation of leukocytes at the focus of injury
What is vasodilation?
- Increased diameter and loss of fluid slow down flow and lead to stasis
- May be preceded by brief arteriolar constriction
- Causes the heat and redness of acute inflammation
- Quickly followed by increased permeability of microvasculature
What causes vasodilation?
- Induced by several mediators including histamine and nitric oxide
- Histamine is a major vasoactive amine, which comes from mast cells
What is increased vascular permeability?
Endothelial cells contract, resulting in increased interendothelial spacing
What are the causes of increased vascular permeability?
- Histamine and Nitric Oxide
- Endothelial cell injury (burns, toxins)
- Leukocyte-mediated vascular injury (late stage inflammation)
- Increased transcytosis (VEGF)
What is exudate?
A fluid secreted from the cells, as a result of increased vascular permeability.
- High protein content (fibrin and antibodies)
- High specific gravity
- May be purulent (leukocyte-rich)
What is transudate?
- Ultrafiltrate of blood plasma caused by increased hydrostatic pressure or decreased osmotic pressure
- Low protein content (albumin)
- Low specific gravity
- Low cell content
What is the purpose of exudate?
- Dilute pathogens
- ‘Wall off’ pathogens
- Permit spread of soluble inflammatory mediators
- Provide substrate for inflammatory cell migration
What are the first leukocytes in the intial phase of typical acute inflammation and what do they do?
- Nautrophils & Monocytes (capable of phagocytosis)
- Kill bacteria and eliminate foreign and necrotic material
- Produce multiple factors and mediators that interact with other cells
- Overactivation may prove harmful in the long term
Describe the process of leukocytes exiting the vessel lumen.
- Margination (leukocytes are close to the surface)
- Rolling (on the vessel surface)
- Adhesion to activated endothelium
- Transmigration across the vessel wall
- Migration up the chemotactic gradient.
What receptors may be activated at the site of injury?
- Toll-like receptors for certain microbial products such as endotoxin
- G-protein coupled receptors for certain bacterial peptides (N-formylmethionyl residues)
- Opsonin receptors (IgG and C3b especially)
- Cytokine receptors (macrophages: interferon-𝛾)
Describe the basic stages of phagocytosis.
- Attachment
- Engulfment and formation of phagocytic vacuole
- Degradation by various substances (reactive oxygen species, lysozyme, major basic protein)
What are the stages in histology of the acute inflammatory response?
Normal lung -> vascular congestion and stasis -> leukocytes infiltrate
How/when is the acute inflammatory response terminated
- Inflammatory mediators and neutrophils have a short half life
- Macrophages, mast cells and lumphocytes release a number of anti-inflammatory products
- Lipoxins
- The cause of the injury (e.g. bacteria) is removed
- Under normal conditions, process comes to a stop
What is chronic inflammation?
Inflammation of prolonged duration in which inflammation, tissue injury and attempts at tissue repair coexist
When does chronic inflammation occur?
- Can follow from acute inflammation, or rise from a low grade smouldering inflammation
- May include persistant infection, prolonged exposure to toxins, autoimmunity or a foreign body.
How is chronic inflammation characterised?
- Mononuclear cell infiltrate (macrophages, lymphocytes, plasma cells)
- Tissue destruction, induced by persistent inflammatory agent or by the inflammatory cells themselves
- Attempts at healing by replacement of damaged tissue with connective tissue
- Accomplished by fibrosis and accompanied by angiogenesis
What is the role of macrophages in the chronic inflammatory response?
They persist and cause significant tissue destruction
What cell types¬ other than macrophages¬ are involved in chronic inflammation?
- T-Lymphocytes (can be stimulated by macrophages; regulated immune reaction and can be cytotoxic)
- Plasma cells (develop from activated B-lymphocytes and produce antibodies)
- Eosinophils (in response to parasites or IgE mediated inflammation)
- Mast cells
- Neutrophils if co-existing acute inflammation
What cases prominent angiogensis in chronic inflammation?
Vascular endothelial growth factor (VEGF) from macrophages and endothelial cells
What is granulomatous inflammation?
- Chronic inflammation where granulomas form (aggregates of activated macropages), which attempt to eliminate a resistant offending agent.
- Triggered by a strong and specific T lymphocyte reaction
What are the causes of granulomatous inflammation?
- Infections (TB, leprosy, syphilis, fungi)
- Foreign material (foreign body granuloma)
- Tumour reaction
- Granulomatous diseases (Sarcoidosis, Crohn’s disease)
Compare acute and chronic inflammation?
- Acute onset is faster and lasts a few days, chronic inflammation takes longer and lasts a long time.
- Acute is mainly neutrophils, chronic is mainly monocytes or macrophages
- Acute involves necrosis (cell death), chronic involves scarring as repair occurs
What are the long term sequelae of inflammation (outcomes)?
- Removal of offending agent
- Cessation of the inflammatory response
- Healing of tissue damage with preservation of integrity and function (resolution)
- Excessive tissue damage and scarring (may affect adjacent tissue)
- Multiorgan failure (septic shock)
List the possible ways wounds may heal.
- Resolution (involves regeneration of parenchymal cells with restoration of function)
- Scarring (involves angiogenesis, migration and repair of fibroblasts, scar formation and connective tissue remodelling)
When does resolution/scarring in wound repair occur?
Resolution - tissue can regenerate, with little structural damage
Scarring - significant tissue loss, tissue is unable to regenerate so there is loss of function
What factors can impair wound healing?
- Poor nutrition (protein, energy)
- Vitamin deficiency (Vitamin C, Vitamin A)
- Mineral deficiency (Zinc)
- Suppressed inflammation (Steroids, Old Age)
- Poor local blood supply (Peripheral vascular disease)
- Persistent foreign body
- Movement
