Pathology - Inflammation and repair 1 Flashcards
what is inflammation?
a responsive process to perceived aggression: infection, tissue damage, non-self recognition
What happens to the concentration of cells and molecules during inflammation?
Concentration of cells and molecules of immunity increase to the sites where the trigger of inflammation happens
Why is inflammation is important?
Inflammation is important to fight infection, to heal wounds, to repair injury
What are the changes in vascular flow during inflammation?
- Arteriolar dilatations (vascular ectasia/dilation) and opening of capillary bed
- Localized increased blood flow: increased pressure (heat and redness)
What happens to vascular permeability during inflammation ?
Increased vascular permeability (vascular leakage) (leakage of palsma proteins that creates edema)
- Endothelial gaps
- Endothelial injury (endothelial cell death)
Describe a normal vascular environment
hydrostatic pressure = colloid osmotic pressur, plasma protein stays in the lumen. No net fluid or protein leakage
Describe the formation of exudate
Increased interendothelial space, along with vasodilation and stasis leads to fluid and protein leakage
describe the formation or transudate
Increased (++) pressure (venous outflow obstruction, like in congestive heart failure)
+
Decreased colloid osmotic pressure (decresed protein synthesis; increased protein loss; protein malnutrition) leads to fluid leakage
What is exudate
High protein content and may contain some white and red cells
What is transudate
Low protein content, few cells.
Consequences of the vascular leakage
- Outpouring of protein-rich fluid in the extravascular tissues: exsudative edema (tumor)
- Localized increased viscosity: blood stasis
- Leukocyte migration
Process of leukocyte migration
- Rolling along the endothelium
- Adhesion to the endothelium
- Transmigration across the endothelium (diapedesis)
- Piercement of the basement membrane
- Migration and cell-matrix interactions
Caracteristics of a neutrophil (4)
- Innate immune system
- Nucleus divided in 2-5 lobes
Type of phagocytes - Migrate through interstitial tissue
- Predominate during the first 6-24 hrs
Caracteristics of a monocyte (5)
- Innate immune system
- Bean-shaped nucleus, unilobar
- Change into macrophages after entering the tissue spaces
- Phagocytosis
- Replace neutrophils in 24-48 hrs
Phases of phagocytosis
- Recognition and attachement of the particle to be ingested by the leukocyte: mannose receptors
- Engulfment: phagocyte membrane zips up around particle
- Killing and degradation within neutrophils and macrophage.
Process of killing and degradation within neutrophils and macrophages
- Fusion of phagosome with lysosomes
- Killing by lysosomial enzymes
- Killing by ROIs and NO (oxygen compounds)
What happens after phagocytosis
Neutrophils undergo apoptosis and are ingested by macrophages
Why are toll-like receptors (TLRs) are important players in leukocyte activation
They recognize pathogen-associated signatures and initiate the inflammatory response of the innate immune system
What are TLRs
receptors expressed at the surface of leukocytes involved in their activation (i.e., TLR3, ligand: viral double-strand RNA)
Name some chemical mediators of inflammation
- Vasoactive amines (i.e., histamine, serotonine)
- Complement and kinin systems
- Clotting system (i.e., FXII, FX, fibrin, plasmin)
- Arachidonic acid metabolites.
- IFN-gamma by NK cells and T lymphocytes
- Reactive Oxygen Intermediates (ROIs), Nitric Oxyde (NO), Lysozymes, O2 free radicles
How is the acute inflammatory response is terminated
- Many chemical mediators have a short half-life: rapid decline
- Stop signals:
Switch in the production of pro-inflammatory to anti-inflammatory products from arachidonic acid
Secretion of TGF beta
Inhibition of TNF - Tissue macrophages half-life is prolonged (months or years)
What is the outcome of acute inflammation?
- Resolution
- Fibrosis after healing (i.e., hypertrophic scar)
- Progression to chronic inflammation:
Angiogenesis
Mononuclear cell infiltrate
Fibrosis
Example of a serous inflammation
Skin blister
Example of fibrinous inflammation
fibrin (large molecule) extravasation needs severe vascular modification; more often associated with secondary fibrosis
example of Suppurative inflammation
Suppurative acute appendicitis
Morphologic patterns of acute inflammation
- Serous inflammation
- Fibrinous inflammation
- Suppurative inflammation
- Ulcer
What di you have instead of vasodilation in chronic inflammation?
angiogenesis and then fibrosis
Players in chronic inflammation
- macrophage
- Lymphocytes
- Plasma cells
- Antigen presenting cells
- eosinophils: rarely.
- mast cells
What is a macrophage
Component of the mononuclear phagocyte system
What does a macrophage secretes?
Mediators of inflammation (TNF)
What antigens do macrophage display?
Displays antigens to T lymphocytes
(HY) What is the difference between clasically activated macrophage (M1) vs alternatively activated macrophage (M2)
M1 leads to microbicidal actions, phagocytosis and killing bacteria and fungi
M2 leads to anti-inflammatory effects, wound repair, fibrosis
Where do B and T lymphocytes migrate
Into inflammatory sutes
How can B cell (lymphocyte) can differentiate?
into plasma cells which secrete antibodies
What CD4+ T produces?
cytokines
Physical characteristic of a lymphocyte
Large dark-staining nucleus, little cytoplasm
What is the distinctive pattern of chronic inflammation
Granulomatous inflammation
what is a granulomatous inflammation
It is a distinctive pattern of chronic inflammation: Activated macrophages acquiring an epitheloid appearance
In what diseases granulomatous inflammation is present?
- tuberculosis, sacoidosis, inflammatory bowel diseases
Is there necrosis when there is granulomatous inflammation?
Sometimes yes: necrotizing granuloma
What do lymphocytes and plasma cells look like when there is granulomatous inflammation?
Peripheral rim of lymphocytes and plasma cells
4 systemic effects of inflammation
- Fever
- production of acute-phase proteins
- leukocytosis
5 in severe situations: septic shock, disseminated intravascular coagulation (DIVC)
Process of fever
central process, production of prostaglandins in hypothalamus, under the control of TNF and IL-1. Antipyretics can act in reducing the production of PGs.
What protein can we test to measure inflammation?
C-reactive protein produced by the liver
Two essential characteristics of stem cells in regeneration
- Self-renewal capacity
- Asymmetric replication: one daughter cell differentiates, the other retains self-renewal capacity
What are the 2 kind of stem cells
- ES (embryonic stem cells): stable
- Adult stem cells: admixed with differentiated cells, specialized (i.e., can differentiate in one type). Involved in chemoresistance?
What is the mechanical support in the extra-cellular matrix ? (for regeneration)
- collagen and elastin
how much of the liver can be removed and why?
up to 40-60% for primary tumor or metastasis, transplantation
By what is initiated the regeneration of the liver?
By TNF and IL6
Steps of a scar formation
- Hemostatic plug
- Inflammation (acute and chronic) and macrophages are central
- Cell proliferation
- Remodeling
What can delay tissue repair? (5)
-Infection
-Protein deficiency
-Treatments: glucocorticoids
-Poor perfusion: diabetes
-Increased ECM production in keloids
