PATH Flashcards
(33 cards)
What mediates transmigration in acute inflammation?
PECAM-1 on endothelial cells and CD31 on leukocytes (homotypic like like interactions)
What does activation of toll like receptors lead to?
Up regulation of NF-kB
How is the acute inflammatory response terminated?
Mediators only produced transiently
- and regulated by stop signals such as:
Switch of leukotrienes to lipoxins (anti-inflammatory form)
Production of anti-inflammatory cytokines such as TFG-B and IL-10
Neural impulses that inhibit macrophage TNF production
Examples of chemical mediators of inflammation?
Vasoactive amine Plasma proteases Phospholipid derived products Cytokines Nitric oxide Lysosomal enzymes oxygen derived free radicals
Beneficial effects of inflammation?
Dilution of toxins Arrival of antibodies to site of inflammation Drug transport Delivery of nutrients and oxygen Fibrinogen converted to fibrin Destruction of microbial agent Removal of tissue debris Stimulation of immune response
Pyrogens stimulate which cells to release what?
Macrophages to release IL-1 and TNF
What is platelet activating factor?
Increases vascular permeability
Lipid mediator that allows aggregation of platelets and mediator of leucocyte functions
Harmful effects on inflammation?
Mechanical effect such as epiglottitis
Impaired flow e.g. acute meningitis
Impaired function
Tissue destruction
Outcomes of inflammation?
- Resolution
Complete resolution with regeneration of native cells - Healing and repair
Healing by connective tissue replacement (fibrosis) occurs:
- after substantial tissue destruction
- setting of abundant fibrin exudation (organization) - Progression to chronic inflammation
- where injurious agents cant effectively be eliminated - Abscess formation
Abscess is a walled off collection of pus
Morphological features of inflammation?
Infiltration with mononuclear inflammatory cells such as macrophages, lymphocytes and plasma cells.
As well as tissue destruction due to persistent injury or inflammation.
Repair granulation tissue due to angiogenesis and fibrosis.
What activates macrophages to become larger?
Cytokines and bacterial endotoxins
How do macrophages evolve from type M1 to M2?
By IL13 and IL-4
Convert to M2 for wound repair
What are substances released by macrophages that cause tissue destruction?
Proteases and other enzymes Aa metabolites Toxic oxygen metabolites NO Coagulation factors Neutrophil chemotactic factors
What are substances released by macrophages that cause vascular proliferation?
Growth factors
Cytokines
Remodeling collagenases and metalloproteinases
What induces formation of classical macrophages, M1?
Microbial products
IFN-g
Causes of granulomatous inflammation?
Infection (specific types) Foreign body Response to tumors Metal/dust (silicosis/berylliosis) Unknown etiology (sarcoidosis/ crohns disease)
When does a foreign body granuloma occur? Types?
It occurs in response to poorly digestible foreign material,
- exogenous such as splinter, suture, graft material
- endogenous due to keratin or pilonidal sinus
Examples of type four delayed hypersensitivity
Langerhaans giant cells
TB caseous necrosis
What distinguishes ulcers from erosions?
Extent of tissue loss
What is a sinus?
Examples?
A tract lined by granulation tissue leading from a chronically inflamed cavity to a surface.
Examples include:
- sinuses associated with osteomyelitis (inflammation of bone)
- pilonidal sinus (nest of hairs)
Mechanisms associated with cell injury?
Inhibition of aerobic respiration causes ATP depletion
Generation of oxygen species (free radicals)
Defects in membrane permeability
Disruption of calcium homeostasis (calcium influx)
Describe reversible injury
Increased anaerobic glycolysis
Reduced activity of sodium pump causing accumulation of sodium and water.
Reduced activity of calcium pump increases cytosolic free calcium and activates enzymes:
- ATPase causing decreased ATP
- phospholipase decreasing phospholipids
- endonuclease causing nuclear chromatin damage
- protease causing disruption of membrane and cytoskeletal proteins
What are factors that affect the healing process?
Ability to remove the causative agent Ability to clear the inflammatory debris Degree of architectural damage Ability of cell to proliferate Extent of damage to ECM
What are polypeptide growth factors?
They are the most important mediators affwcting cell growth:
- present in serum or produced locally
- exert pleiotropic effects such as proliferation, cell migration, differentiation and tissue remodeling
- regulate growth of cells by controlling expression of genes that regulate cell proliferation
