Inflammation II Flashcards
What are three mediators in vasodilation?
Prostaglandins, nitric oxide, and histamine
C3a and C5a function to increase
Vascular permiability
What three mediators function to induce fevers?
IL-1, TNF, and prostaglandins
Chronic inflammation can be described by the predominant type of inflammatory cell, i.e
Mononuclear inflammatory cells
Parenchymal cell death and tissue destruction that result in growth of new blood vessels and production of connective tissues are examples of
Irreversible tissue damage
A dying cell release soluble mediators of inflammation that initiate a response similar to that seen in
Acute inflammation
Then, mononuclear emigration replaces neutrophilic emigration. Two new things occur. These are:
Angiogenesis and fibroblast migration
As chronic inflammation progresses, we see the development of a transient
Granular tissue
A precursor to scar formation
Granulation
The process by which new blood vessels are created from preexisting ones
Angiogenesis
Occurs at the level of capillaries that consist of a vascular endothelium resting on a basement membrane with an overlay of pericytes
Angiogenesis
Angiogenesis is stimulated by
Inflammation and hypoxia
Regulate angiogenesis through their receptors leading to the formation of new blood vessels
Chemokines
Chemokines indirectly influence endothelial cell behaviors by attracting chemokine receptor-expressing
Leukocytes
These subsequently secrete pro-angiogenic factors, such as
-Act on endothelial cells and initate angiogenesis
Vascular Endothelial Growth Factor (VEGF)
The coordinated arrangement of endothelial cells in three dimensions to form and maintain a vascular tube requires endothelial cell proliferation, migration, survival, and permeability. These biological responses are mediated mainly by
BEGFA-activated VEGFR2
On VEGFA-binding to extracellular Ig-like domains 2 and 3 of VEGFR2, signaling molecules bind to respective
Phosphorylation sites
Ultimately, the granulation field becomes relatively accellular, with dense fibrous connective tissue (scar tissue) replacing the
Original architecture
The persistent stimulus of chronic inflammation activates macrophages and lymphocytes, leading to the production of growth factors and cytokines, which increase the synthesis of
Collagen
Deposition of collagen is enhanced by decreased activity of
Metalloproteinases
The principal cells producing the ECM of fibrosis are the myofibroblasts, defined as fibroblasticlike cells that express
Alpha-smooth muscle actin
These cells derive from tissue resident mesenchymal cells (fibroblasts and pericytes) following stimulation by various
Cytokines
In an MI, the initial infiltrate is replaced by a monocytic response that peaks
One day later
Reaches its peak at two weeks of age whereas a full dense scar appears only by several months
Granulation
Inflammation of the gallbladder, a condition that can result from gallstones that block the common bile duct
Cholecystisis
Gross examination reveals variable thickening of the gallbladder wall. Microscopic exam can reveal chronic inflammation with
Rokitansky-Aschoff sinuses
Periportaland receives blood with the highest oxygen concentration
-closer to bile duct and hepatic artery
Zone 1 of hepatocyte
In micronodular cirrhosis, the regenerative nodules average 3 mm or less in size. The yellow-brown appearance of these nodules is caused by concomitant
Hepatic Steatosis
The most common cause of micronodular cirrhosis and steatosis is
Chronic Alcohol abuse
A fine reticulin network of type IV collagen is normally present in the liver, but with cirrhosis there is extensive deposition of type
I and III collagen
The increased hepatocyte proliferation from nodular regeneration increases the risk for
Hepatocellular cholangiolar carcinoma
Liver injury leads to Kupffer cell activation with release of cytokines, such as
-stimulate stellate cells in the space of Disse to proliferate into myofibroblasticcells that contribute to the fibrogenesis
Platelet-derived growth factor and TNF
In cirrhosis, the flow of blood over hepatocytes from portal triad to central vein is impeded due to the architectural changes resulting from
Fibrosis
Achronic inflammatory infiltrate is typically seen in viral pneumonias such as those resulting from
Influenza
The final common pathway for various severe lung injuries
Diffuse Alveolar Damage (DAD)
In early DAD, hyaline membranes, as seen here, line the alveoli. Later in the first week after lung injury, the hyaline membranes resolve, and we see proliferation of
Macrophages
Fibroblasts migrate into the alveolar exudates through defects in the epithelial basement membrane to lay down collagen within the hyaline membranes in the
Organization phase of DAD
As epithelial cells grow over the newly formed connective tissue, a new basement membrane is formed, thereby incorporating the collagen into the interstitium, a process known as
Fibrosis by accretion
Involvement of the alveolar ducts results in these structures being lined by a ring of
Granulation tissue
Less frequently, the organized exudates retain a predominantly intra-alveolar position, resulting in loose buds of granulation tissue similar to those seen in
Pneumonia
It is claimed that this intra-alveolar pattern of repair is particularly found when the initial damage is caused by
Generalized sepsis
However, interstitial fibrosis is more characteristic of injury caused by
Cytotoxic drugs
Fibrotic disease that is often reversible with steroid treatment. Thus there remains a potential of reversibility with fibrosis
BOOP
Its appearance within air spaces rather than the interstitium, and likely the better preservation of the alveolar cells themselves, that predisposes to recovery
Boop
An example of extensive and irreversible fibrosis
UIP
Require stabilizing linkages that extend from the stroma through basement membrane to receptors to cytoskeleton
Skeletal muscle fibers
The thin extracellular matrix, consisting largely of basement membrane, is important for maintaining theadjacent
Myofiber
A loss of anyone of the linkage proteins can result in a
Muscular dystrophy
The most common of these result from X-linked mutations of the gene coding for
Dystrophin
Caused by a defective dystrophin gene on the X chromosome that leads to an inability to produce the striated muscle sarcolemmal membrane structural protein dystrophin
Duchenne Muscular Dystrophy (DMD)
What is the inheritance pattern of DMD?
X-linked recessive
About one third of cases of DMD arise from
Spontaneous new mutations
While they can be considered as forms of chronic inflammation, retain the leukocyte characteristics seen in acute inflammation
Abscesses
Encapsulated accumulation of pus (usually neutrophils)
Abscess
It can be a complication of pneumonia, is seen in aspiration, bronchiectasis, and airway obstruction
Pulmonary Abscess
Accumulation of pus in an existing body cavity
Empyema
A circumscribed form of chronic inflammation that occurs in response to a localized inciting agent such as a foreign body or certain bacteria that can be sequestered by inflammatory tissue but that cannot be easily removed from the tissue
Granuloma
A special type of chronic inflammation characterized by a circumsized collection of macrophages
Granuloma
The initiating event of granuloma growth is the growth of
Myobacterium
The initial response is that seen in acute inflammation, in which there is
Vasodilation and neutrophilic and mononuclear diapedesis
Mononuclear cells surround site of injury and both fuse to form giant cells and adhere to produce
Epithelioid macrophages
Then, fibroblasts surround the inflammatory cells and we see the walled-off formation of a
Granuloma
One of the most well-studied cases of granulomas is
Tuberculosis
The causative organism for tuberculosis stains red with the
Acid fast stain
Non-caseating and of uncertain cause and need to be distinguished from those of TB and other infectious diseases
Sarcoid granulomas
The most important factors in determining the extent of the inflammatory reaction are (a) whether there is significant amount of cell death and (b) whether there is destruction of the underlying
Basement membrane
If the parenchymal cell can rapidly migrate on its basement membrane substrate and re-epithelialize the injured surface, we will see
No irreversible changes
On the other hand, if this migration and regeneration is impeded, either because the cells can’t divide, or because the underlying basement membrane and stromal architecture is destroyed, then we will see
Irreversible angiogenesis and fibrosis
Serves as a good example of a severe and yet self-limiting inflammation reaction
Gout
Unlike gout, results in the development of permanent sequelae
Silicosis
The result of silicosis is extensive scarring of the
Lung
One mechanism by which this may operate is that injured macrophages release the cytokines IL-1 and TNF which initiate angiogenesis, recruit fibroblasts and induce
Collagen and fibronectin synthesis
