Peripheral Arterial Disease Flashcards
(40 cards)
define intima
the inner-most layer of a blood vessel, including the endothelial monolayer and the elastic extracellular matrix of connective tissue
define platelets
small megakarocyte cell fragments that contribute to the formation of clots during vascular injury
define stenosis
an abnormal narrowing in a blood vessel or other tubular organ or physiological structure
define foam cell
monocyte-derived macrophages that have absorbed high concentrations of oxidized LDL particles
define embolism
the migration of material, often from an existing thrombus or clot, though the circulation, leading to formation of a new occlusion in another part of the body
define ischemia
a reduction or cessation of blood flow that results in damage to the tissue
blood leaves the heart in (arteries or veins)?
arteries
blood returns to the heart in (arteries or veins)?
veins
this layer of a blood vessel responds to signals from sympathetic nerves to control the circumference of the vessel
media
this is the outer layer of blood vessel and is comprised of connective tissue and collagen-producing fibroblast cells
adventitia
the level of resistance of blood flow can be altered by what properties?
changes in the viscosity of blood, the length of the blood vessels, and the vessel diameter
name two inhibitory factors that are secreted by the vascular endothelial cells that prevent aggregation of platelets in circulating blood
nitric oxide (NO), prostacyclin (PGI2)
what is the leading cause of PAD?
patients over 40 with narrowing or occlusion of the arteries of the limbs due to atherosclerosis
strongest risk factors for PAD
smoking and DM
response-to-injury hypothesis
a mechanism that describes a chronic inflammatory and healing response of arterial vessels to injury and leads to the development of atherosclerosis
how does an atherosclerosis form?
- LDL particles collect in the intima of the arterial vessel and may be retained there by binding to the macromolecules that make up the extracellular matrix (e.g., glycosaminoglycans). This makes up a “fatty streak”
- Oxidized LDL particles recruit white blood cells (leukocytes) through two mechanisms
- they initiate an inflammatory response that recruits lymphocytes to the site of the fatty streak
- they stimulate cells of the vascular wall to secrete cytokines to attract mononuclear phagocytes - phagocytic macrophages absorb the lipoproteins through receptor-mediated endocytosis and may become converted to foam cells
- foam cells secrete growth factors and cytokines which cause smooth muscle cells to migrate into the intima
- smooth muscle cells synthesize collagen, creating a rigid area where is should be elastic
- circulating platelets become activated by exposure to collagen and other components of the ECM that normally makes up the external layer of the vessel and aggregate around the site
- activated platelets stimulate the formation of a blood clot (thrombus) via the molecule thromboxane (TXA2)
what is thromboxane (TXA2) synthesized from?
arachidonic acid
synthesis of TXA2 requires the activity of what enzyme?
cyclooxygenase (COX1)
what are the 3 main components of atherosclerotic plaques?
- cells (smooth muscle cells, macrophages, and T lymphocytes)
- extracellular matrix (collagen, elastic fibers, and proteoglycans)
- intracellular and extracellular lipid
is platelet aggregation dependent on low or high levels of cAMP?
low
what happens when ADP binds to P2Y12 receptors expressed on platelet mebmranes?
G proteins get activated which then inhibit the enzyme responsible for the synthesis of cAMP, called adenylyl cyclase
name the enzyme that synthesizes cAMP
adenylyl cyclase
what happens to cAMP when you inhibit P2Y12 receptors?
cAMP levels would increase inside the cell, thus inhibiting platelet aggregation
what happens to intracellular cAMP levels when PDE isoforms are activated?
intracellular cAMP levels decrease
