Cell pathology 2 - Inflammation Flashcards
(34 cards)
1
Q
What is inflammation?
A
- 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
2
Q
What cells are involved in inflammation?
A
- Neutrophils
- Macrophages
- Lymphocytes
- Eosinophils
- Mast cells
3
Q
What soluble factors are involved in inflammation?
A
- Antibodies
- Cytokines
- Complement system
- Coagulation system
4
Q
What is acute inflammation?
A
- Acute inflammation is a rapid non-specific response to cellular injury
- It is orchestrated by mediators released from injured cells
- Leukocyte and vascular response
5
Q
What is chronic inflammation?
A
- 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)
6
Q
How is acute inflammation recognised?
A
- Rubor (Redness)
- Calor (Heat)
- Tumor (Swelling)
- Dolor (Pain)
7
Q
What is the purpose of the acute inflammatory response?
A
Rapid delivery of leukocytes and plasma proteins to the site of injury
8
Q
What are the three main components of acute inflammation?
A
- 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
9
Q
What is vasodilation?
A
- 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
10
Q
What causes vasodilation?
A
- Induced by several mediators including histamine and nitric oxide
- Histamine is a major vasoactive amine, which comes from mast cells
11
Q
What is increased vascular permeability?
A
Endothelial cells contract, resulting in increased interendothelial spacing
12
Q
What are the causes of increased vascular permeability?
A
- Histamine and Nitric Oxide
- Endothelial cell injury (burns, toxins)
- Leukocyte-mediated vascular injury (late stage inflammation)
- Increased transcytosis (VEGF)
13
Q
What is exudate?
A
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)
14
Q
What is transudate?
A
- Ultrafiltrate of blood plasma caused by increased hydrostatic pressure or decreased osmotic pressure
- Low protein content (albumin)
- Low specific gravity
- Low cell content
15
Q
What is the purpose of exudate?
A
- Dilute pathogens
- ‘Wall off’ pathogens
- Permit spread of soluble inflammatory mediators
- Provide substrate for inflammatory cell migration
16
Q
What are the first leukocytes in the intial phase of typical acute inflammation and what do they do?
A
- 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
17
Q
Describe the process of leukocytes exiting the vessel lumen.
A
- 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.
18
Q
What receptors may be activated at the site of injury?
A
- 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)
19
Q
Describe the basic stages of phagocytosis.
A
- Attachment
- Engulfment and formation of phagocytic vacuole
- Degradation by various substances (reactive oxygen species, lysozyme, major basic protein)
20
Q
What are the stages in histology of the acute inflammatory response?
A
Normal lung -> vascular congestion and stasis -> leukocytes infiltrate
21
Q
How/when is the acute inflammatory response terminated
A
- 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
22
Q
What is chronic inflammation?
A
Inflammation of prolonged duration in which inflammation, tissue injury and attempts at tissue repair coexist
23
Q
When does chronic inflammation occur?
A
- 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.
24
Q
How is chronic inflammation characterised?
A
- 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
25
What is the role of macrophages in the chronic inflammatory response?
They persist and cause significant tissue destruction
26
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
27
What cases prominent angiogensis in chronic inflammation?
Vascular endothelial growth factor (VEGF) from macrophages and endothelial cells
28
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
29
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)
30
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
31
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)
32
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)
33
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
34
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
