Term
| Which organs are directly involved in the exchange between the blood compartment and the outside environment? |
|
Definition
|
|
Term
| What defines the pulmonary circulation? |
|
Definition
| the passage of blood from the right ventricle through the arteries, capillaries, and veins of the general system, from the left ventricle to the right atrium |
|
|
Term
| What definies the systemic circulation? |
|
Definition
| the circulation of blood through the arteries, capillaries, and veins of the general system, from the left ventricle to the right atrium |
|
|
Term
| Why is it important that the circulation of most organ systems are in parallel? |
|
Definition
| it prevents blood flow changes in one organ from significantly affecting blood flow in other organs |
|
|
Term
| Which ventricle is a high pressure pump and which is a low pressure pump? |
|
Definition
high: left ventricle low: right ventricle |
|
|
Term
| What is the formula for cardiac output? |
|
Definition
| stroke volume x heart rate |
|
|
Term
| What is the definition of cardiac output? |
|
Definition
| the amount of blood ejected by the heart in a unit of time usually expressed in liters per minute |
|
|
Term
| What is the definition of stroke volume? |
|
Definition
| the volume pumped out of one ventricle of the heart in a single beat |
|
|
Term
| What is vascular resistance? |
|
Definition
| the resistance to flow that must be overcome to push blood through the circulatory system |
|
|
Term
| What substances do the endothelial lining of the blood vessels produce and what is their function? |
|
Definition
| nitric oxide and prostacyclin modulate vascular function, hemostasis, and inflammatory responses |
|
|
Term
| What is the definition of viscosity? |
|
Definition
| the degree of slipperiness between two layers of flued |
|
|
Term
| What does the viscosity of blood have an effect on? |
|
Definition
| the resistance to blood flow and the velocity of blood flow |
|
|
Term
| What are some factors that affect blood viscosity? |
|
Definition
| hematocrit, vessel radius, linear velocity of the blood, temperature |
|
|
Term
| What happens to red blood cells in very large vessels? |
|
Definition
|
|
Term
| What is the difference between laminar and turbulent flow? |
|
Definition
| laminar flow is streamlined, each layer of blood fflowing through the vessel stays in its place and is moving parallel to the blood in the next layer. turbulent flow occurs when the layers are moving so quickly that the layers start mixing with one another and energy is lost |
|
|
Term
| What is the formula for Reynolds number and what does it describe? |
|
Definition
= diameter of the vessels times average velocity of blood times the density of the blood divided by the visocosity it describes whether blood is laminar (<2000) or turbulent (>a critical point between 2000 and 3000) |
|
|
Term
| What is the formula for the total hydraulic energy of the cardiovascular system? |
|
Definition
| = potential energy + kinetic energy (1/2 mv^2) + force due to gravity (pgh) |
|
|
Term
| What is intraluminal blood pressure? |
|
Definition
| that energy that can be measured at any single point within a vessel |
|
|
Term
| What is extraluminal or interstitial fluid pressure? |
|
Definition
| pressure that exerts a force on the outside of the vessel |
|
|
Term
| What is the transluminal pressure? |
|
Definition
| the difference between the intraluminal blood pressure and the extraluminal blood pressure |
|
|
Term
| What is the formula for compliance and what does it measure? |
|
Definition
= change in volume divided by change in transmural pressure the degree to which the vessel can expand |
|
|
Term
| What is the formula for tension on the wall of a blood vessel? |
|
Definition
| = transmural pressure times the radius of the vessel |
|
|
Term
| What is the law of laplace? |
|
Definition
| the larger the radius of a vessel, the higher must be the wall tension to withstand the same transmural pressure so that it does not rupture |
|
|
Term
| What is the formula for flow? |
|
Definition
| difference in pressure divided by resistance |
|
|
Term
| What is the formula for vascular resistance? |
|
Definition
| R= 8 times vessel length times blood viscosity divided by pi times radius ^4 |
|
|
Term
| What dimension has the greatest affect on vascular resistance? |
|
Definition
|
|
Term
| How do you calculate resistances in series? in parallel? |
|
Definition
series resistance is additive in parallel, add conductances (1/R) |
|
|
Term
| How are the valves of the heart anchored? |
|
Definition
| anchored to the fibrous rings of the heart by chorda tendineae and papillary muscles |
|
|
Term
| When and how do the AV valves shut? |
|
Definition
| when the electrical activity of the heart activates the cardiac muscle and IV pressure rises and exceeds the atrial pressure, the av valves are pushed shut by the blood trying to flow back into the atria |
|
|
Term
| What is the shape of the lumen of the left ventricle and how does it expel its blood? |
|
Definition
| cylindrical, it compresses its contents from all sides as the apex shortens |
|
|
Term
| What is the shape of the lumen of the right ventricle and how does it eject its blood? |
|
Definition
bellows arrangement ejection effected by the outer wall contracting inward against the wall of the septum and by traction on the right ventricular wall as the left ventricle changes its shape |
|
|
Term
| In which ventricle is it theoretically easier to eject the full contents? |
|
Definition
|
|
Term
| Which ventricle can produce higher pressures? |
|
Definition
|
|
Term
| How long does each cardiac cycle take? |
|
Definition
|
|
Term
|
Definition
| contraction/ejection segment |
|
|
Term
|
Definition
|
|
Term
| What happens during ventricular systole? |
|
Definition
| there is a period of isovulumetric contraction wherein pressure is generated but no flow of blood occurs. this is followed by a period of rapid ejection of blood and then by a period of reduced filling |
|
|
Term
| What are the states of the aortic and mitral valve before systole? |
|
Definition
| aortic valve remains closed while the mitral valve is open |
|
|
Term
| Why does the aortic pressure fall during diastole? |
|
Definition
| no blood is being added to the aorta because the aortic valve is closed |
|
|
Term
| When does the mitral valve close? |
|
Definition
| with activation of the ventricle, tension increases within the ventricle and the mitral valve closes |
|
|
Term
| What generates the first heart sound and what does it signal? |
|
Definition
vibration of the ventricular wall and acceleration of blood within the ventricle it signals the beginning of systole |
|
|
Term
| What happens during the period of isovolumetric contraction? |
|
Definition
| the entrance and exit valves are both closed at the begining of systole; it is the time required until the intraventricular pressure exceeds the aortic pressure |
|
|
Term
| What are the states of the mitral and aortic valves at the beginning of systole? |
|
Definition
|
|
Term
| When does the aortic valve open? |
|
Definition
| when the intraventricular pressure exceeds the aortic pressure |
|
|
Term
| What causes the second heart sound? |
|
Definition
| blood in the aorta recoils against the closed valve and vibrates the columns of blood in the aorta |
|
|
Term
| What initiates the period of isovolumetric relaxation? |
|
Definition
| closure of the aortic valve at the beginning of diastole which the mitral valve being closed throughout systole. during this period the ventricle is relaxing but it requires time for the intraventricular pressure to fall below the atrial pressure to permit opening of the mitral valve |
|
|
Term
| What generates the third heart sound? |
|
Definition
| the rapid movement of blood from atria to ventricle during the initial filling of the ventricle |
|
|
Term
| What generates the fourth heart sound? |
|
Definition
| the rapid movement of blood into the ventricle with atrial systole |
|
|
Term
| What does the p wave indicate? |
|
Definition
|
|
Term
| What does the a wave indicate? |
|
Definition
|
|
Term
| What does the t wave indicate? |
|
Definition
| completion of the repolarization of the ventricles |
|
|
Term
| What does the c wave indicate? |
|
Definition
| the increase in the atrial pressure with isovolumetric contraction |
|
|
Term
| What does the x descent indicate? |
|
Definition
| the decrease in the atrial pressure during the rapid ejection phase of systole. the nadir of the x descent is associated with the peak ejection of blood from ventricle to aorta |
|
|
Term
| What does the v wave indicate? |
|
Definition
| the increase in the atrial pressure as the atria fill with blood during ventricular systole |
|
|
Term
| What does the y descent indicate? |
|
Definition
| the decrease in the atrial pressure as blood moves from atria to ventricles during rapid filling |
|
|
Term
| What are the five major properties of the heart which regulate its coordinated activity? |
|
Definition
automaticity rhythmicity excitability conductivity contractility |
|
|
Term
| Where is the sinoatrial node located? |
|
Definition
| posterior wall of the right atrium close to the points of entry for the venae cavae |
|
|
Term
| What is the order of electrical propagation from the sinoatrial node? |
|
Definition
| atria, AV node, then to both ventricles via Purkinje fibers |
|
|
Term
| What is the action potential generated by pacemaker cells called? |
|
Definition
|
|
Term
| How do slow response type action potentials differ from the fast type action potential? |
|
Definition
| rate of volatge change during depolarization |
|
|
Term
| What is the primary reason that pacemaker cells can fire action potentials spontaneously? |
|
Definition
| pacemaker cells have an unstable resting potential |
|
|
Term
| What happens during phase 0 of the cardiac membrane potential in atrial and ventricular myocytes and Purkinje fibers? |
|
Definition
| rapid membrane depolarization due to rapid opening of voltage-gated Na+ channels and influx of Na+ions |
|
|
Term
| What is long QT syndrome and what defects are responsible for one form of it? |
|
Definition
a disease associated with abnormal repolarization and ventricular tachycardia a defect in the structural region of the Na+ channel protein implicated in control of channel inactivation, or a defect in a gene that appears to encode a K+channel |
|
|
Term
| What happens during phase 4 of the cardiac membrane potential in atrial and ventricular myocytes? |
|
Definition
| the resting membrane potential, results from K+ efflux through K+channels, typically close to the equilibrium potential for K (-90 mV) |
|
|
Term
What happens during phase 0 of the cardiac membrane potential in cells in the SA and AV nodes? How does the speed of this compare to venticular myocytes? |
|
Definition
Ca++ influx through L-type Ca++ channels (lack functional voltage gated Na+ channels) much slower |
|
|
Term
| What happens during phase 1 of the cardiac membrane potential? |
|
Definition
| notch, or partial repolarization due primarily to inactivation of the Na+ current and to a much lesser extent activation of K+channels |
|
|
Term
| What happens during phase 2 of the cardiac membrane potential? |
|
Definition
| plateau phase, an inward depolarizing Ca++ current primarily through Ca++ channels maintains the cell depolarized during this phase |
|
|
Term
| Where is phase 2 particularly prominent? |
|
Definition
| ventricular myocytes where Ca++ influx triggers muscle contraction |
|
|
Term
| What happens during phase 3 of the cardiac membrane potential? |
|
Definition
| repolarization of cardiac cells due to K+ efflux through K+ channels and to a lesser extent inactivation of the Ca++ current |
|
|
Term
| What happens during phase 4 in pacemaker cells in the SA node and AV node? |
|
Definition
| display progressive depolarization due to opening of pacemaker channels which are permeable to Na, K and Ca ions as well as closing of K channels |
|
|
Term
| Where are fast response type action potentials found? |
|
Definition
| atrial muscle, atrial internodal tracts, Purkinje fibers, ventricular muscle |
|
|
Term
| What are fast response type action potentials characterized by? |
|
Definition
a stable resting potential (-90) an action potential of about 120 mV (-90 -> 30) rapid depolarization phase due to rapid Na channel opening |
|
|
Term
| Where are slow response type action potentials found? |
|
Definition
| SA node, AV node, juntional tissue, abnormally anywhere |
|
|
Term
| What are slow action potentials characterized by? |
|
Definition
less negative resting potential (-50ish) less magnitude of action potential little overshoot less depolarization needed to threshold slower depolarization due to opening of L-type Ca channels shorter action potential duration |
|
|
Term
What is responsible for maintaining the proper balance of K and Na and how does it work? During which phase is it most active? |
|
Definition
Na-K pump extrudes 3 Na for every 2 K in phase 4 |
|
|
Term
| What happens if the Na/K pump fails? |
|
Definition
| membrane depolarization as a consequence of collapse of the ionic gradient across the membrane |
|
|
Term
| What are two methods for extruding Ca++? |
|
Definition
ATP dependent Ca++ pump electrogenic Na+-Ca++ exhange (3 Na in for one Ca out) |
|
|
Term
| What causes the generation of slow action potentials on a regular basis in the SA node? |
|
Definition
| activation of pacemaker channels (increase in Ca and Na influs) coupled to a progressive decrease in K conductance |
|
|
Term
| Other than the SA node, what other cells have pacemaker ability? What establishes the hierarchy? |
|
Definition
Av node and Purkinje fibers 1 intrinsic rate (Sa node fastest then AV then Purkinje) 2 time required for phase 4 depolarization to reach threshold (diastolic potential is -50 for SA, -60 for AV, and -90 for Purkinje) 3 the refractory period |
|
|
Term
| What happens if the primary pacemaker fails? |
|
Definition
| another can take over, AV node next in line |
|
|
Term
| WHen would an electronic pacemaker be needed? |
|
Definition
| When the overall ventricular myocardium depolarization rate is too slow to permit normal physical activity |
|
|
Term
| What accounts for the delay between atrial and ventricular contractions? |
|
Definition
| the slow conduction velocity through the AV node |
|
|
Term
| What is the delay in the AV node? |
|
Definition
| allows the atria to contract and empty their contents into the ventricles |
|
|
Term
| How does the action potential spread from the AV node? |
|
Definition
| exits via the bundle of His which bifurcates into right and left bundle branches, the left divides into anterior and posterior fascicles. the bundle branches descend on the endocardial surface and give off large-diameter Purkinje fibers |
|
|
Term
| What happens if some Purkinje fibers develop spontaneous depolarization? |
|
Definition
|
|
Term
| What factors can modify spontaneous depolarization? |
|
Definition
autonomic stimulation elevated body temperature elevated plasma levels of thyroxin (hyperthyroidism) |
|
|
Term
| What are some consequences of increased extracellular K? |
|
Definition
| partial membrance depolarization, reduced resting potential, slower phase 0 depolarization, reduced AP amplitute, and shortened AP duration |
|
|
Term
| What are consequences of reduced pH in the heart? |
|
Definition
| will shut down the gap junction channels and impede or even block propagation of APs through the ischemic region |
|
|
Term
| What information can an ECG provide? |
|
Definition
orientation of the heart in the thorax mass of cardiac muscle conduction disturbances presence of ischemic damage electrical effects of durgs and electrolytes |
|
|
Term
| When do the ECG electrodes register a positive signal? |
|
Definition
| when the depolarization wave is coming toward it |
|
|
Term
| What type of movement will give rise to a positive wave of depolarization? |
|
Definition
| a wave of depolarization moving toward a recording positive electrode and away from a reference negative electrode |
|
|
Term
| What happens to the ECG stylus if current flows in the same direction as axis of lead? |
|
Definition
| deflected strongly upward from baseline |
|
|
Term
| WHat heppens to the stylus if current flows obliquely to axis of lead? |
|
Definition
| deflected less strongly upward, its height varying with angle that vector of current makes with axis |
|
|
Term
| What happens to the stylus if current flow is perpendicular either toward or away from axis of lead? |
|
Definition
|
|
Term
| What happens to the stylus if current flow is in opposite direction to axis of lead? |
|
Definition
| deflected strongly downward |
|
|
Term
| What happens to the stylus if current flows obliquely in opposite direction to axis of lead? |
|
Definition
| deflected less strongly downward, its depth varying with angle that vector of current makes with axis of lead |
|
|
Term
| What happens to the stylus if there is no current flow? |
|
Definition
|
|
Term
|
Definition
| depolarization of the atria |
|
|
Term
| What causes the QRS complex? |
|
Definition
| depolarization of the ventricles |
|
|
Term
| When do the atria repolartize? |
|
Definition
| while the QRS is occuring, so no wave is evident |
|
|
Term
|
Definition
| repolarization of the ventricles |
|
|
Term
| What does the PR interval tell you? |
|
Definition
| the time required for depolarization to travel from the SA through the AV node |
|
|
Term
| What is the QRS interval? |
|
Definition
| the time it takes for ventricles to depolarize |
|
|
Term
|
Definition
| the interval when the ventricles are depolarized |
|
|
Term
|
Definition
| the interval from the beginning of ventricular depolarization to the end of ventricular repolarization |
|
|
Term
| What are the three primary independent determinants of force of contraction and stroke volume? |
|
Definition
| preload, afterload, contractility |
|
|
Term
| What is the definition of preload? |
|
Definition
| the amount of passive tension or stretch exerted on the walls by the volume of blood in the chamber just prior to the onset of contraction at the end of ventricular diastole and after atrial contraction has just ended |
|
|
Term
| What is the determinant of preload reserve? |
|
Definition
|
|
Term
| What are the major determinants of central venous pressure? |
|
Definition
| venous tone, blood volume, body position |
|
|
Term
| What directly determines stroke volume? |
|
Definition
|
|
Term
| What is the cellular mechanism of preload? |
|
Definition
| altered number of cross-bridges per sarcomere |
|
|
Term
| What is the definition of afterload? |
|
Definition
| the load the ventricle is working against after the onset of contraction |
|
|
Term
| What are the determinants of the afterload? |
|
Definition
| diastolic arterial pressure, aortic compliance, aortic stenosis |
|
|
Term
| What is the relationship between stroke volume and afterload? |
|
Definition
|
|
Term
| What is the cellular mechanism of the afterload? |
|
Definition
| rate of cross-bridge cycling |
|
|
Term
| What is the definition of contractility? |
|
Definition
| the contractile force developed by the ventricle at a given preload and afterload |
|
|
Term
| What are the determinants of contractility? |
|
Definition
| NE/EPI, thyroid hormone, digitalis, hypoxia, acidosis, drug depressants, loss of sarcomeres, intrinsic depression |
|
|
Term
| What is the cellular basis of contractility? |
|
Definition
| Ca++ kinetics, myosin ATPase activity, ATP levels, number of sarcomeres |
|
|
Term
| What is the formula for cardiac output? |
|
Definition
| = heart rate x stroke volume |
|
|
Term
| What is the normal value of cardiac output? |
|
Definition
|
|
Term
| What is the formula for cardiac index and why is it used? |
|
Definition
= cardiac output/ body surface area used to normalize the cardiac output in relation to body size |
|
|
Term
| How much oxygen is in arterial blood? |
|
Definition
|
|
Term
| At rest, how much oxygen do tissues extract? |
|
Definition
|
|
Term
| How does the delivery of oxygen increase with exercise? |
|
Definition
| cardiac output increases 6x and oxygen extraction increases 3x (so 18 fold increase overall) |
|
|
Term
| What is the formula for cardiac output using Fick's principle? |
|
Definition
| = (oxygen uptake in ml/min) / ( oxygen content of pulmonary venous blood - the oxygen content of pulmonary arterial blood) |
|
|
Term
| Name some techniques used to measure cardiac output? |
|
Definition
thermodilution echocardiography gated radionuclide imaging |
|
|
Term
| What is the primary determinant of cardiac output? |
|
Definition
|
|
Term
| What happens with an increase in preload? |
|
Definition
| the force and velocity of contraction increase |
|
|
Term
| What is a measure of preload on the normal left ventricle? |
|
Definition
| the left ventricular end-diastolic pressure, which represents the passive pressure on the walls just prior to the onset of contracton |
|
|
Term
| What directly determines stroke volume? |
|
Definition
|
|
Term
| What is preload most dependent on for each ventricle? Why? |
|
Definition
right: central venous pressure left: pulmonary vein pressure becasue these pressures are the driving forces that determine how much volume the ventricles receive during the diastole |
|
|
Term
| What is left ventricular end diastolic volume - left ventricular end systolic volume? |
|
Definition
|
|
Term
| What is the formula for ejection fraction? |
|
Definition
|
|
Term
| What is the formula for stroke work? |
|
Definition
| stroke volume x mean arterial pressure |
|
|
Term
| Name 6 physiological determinants of central venous pressure? |
|
Definition
venous smooth muscle tone blood volume body position intrathoracic pressure skeletal muscle pump arteriolar dilation |
|
|
Term
| What is the relationship between afterload and stroke volume? |
|
Definition
| an increase in aferload will decrease stroke volume |
|
|
Term
| What does mean arterial blood pressure depend on? |
|
Definition
| cardiac output and vascular resistance |
|
|
Term
| What is the pulse pressure? |
|
Definition
| difference between systolic and diastolic pressure |
|
|
Term
| What is the definition of mean arterial blood pressure and how can it be estimated? |
|
Definition
the pressure that would exist in the artery if there were a steady flow of blood from the ventricle = diastolic pressure + 1/3 pulse pressure (at rest the heart spends 1/3 in systole and 2/3 in diastole) |
|
|
Term
| What is the only limitation to net movement across the capillary wall for small molecules? |
|
Definition
| the rate at which blood flow transports the molecules to the capillary (flow limited) |
|
|
Term
| What is the limiting factor for transport across the capillary for large lipid-insoluble molecules? |
|
Definition
|
|
Term
| What does Starling's hypothesis of capillary transfer state? |
|
Definition
| fluid movement is the result of the net hydrostatic and osmotic forces across the capillary wall |
|
|
Term
| What is the most important factor promoting filtration of fluid in the capillary? |
|
Definition
| capillary hydrostatic pressure |
|
|
Term
| What is the most important factor promoting the absorption to or retention of fluid within the vascular space? |
|
Definition
| oncotic pressure of the plasma proteins |
|
|
Term
| What is the formula for fluid movement according to Starling's hypothesis? |
|
Definition
= forces promoting flitration of fluid from plasma to interstitium - forces promoting absorption of fluid from the interstitium to the plasma = k(capillary hydrostatic P + oncotic P of intertitial fluid) - (oncotic P of plasma + interstitial fluid hydrostatic pressure) k = the filtration constant of the capillary membrane |
|
|
Term
| How did Starling's original hypothesis need to be modified and why? |
|
Definition
needed to include an osmotic reflection coefficient Starling's formula assumed all proteins were impermeable, while in reality not all proteins are impermeable |
|
|
Term
| What is Starling's modified hypothesis? |
|
Definition
fluid movement = k(hydrostatic capillary P - interstitial fluid hydrostatic P) - o (oncotic P of plasma - oncotic P of interstitial fluid) o = osmotic reflection coefficient |
|
|
Term
| What is the difference between hemostasis and thrombosis? |
|
Definition
| hemostasis is normal plugging of vascular injury, thrombosis is pathological formation of clots in inappropriate sites |
|
|
Term
| What are the three basic components of thrombogenesis? |
|
Definition
| endothelium, platelets, coagulation cascade |
|
|
Term
| What roles does the endothelium play in thrombogenesis? |
|
Definition
barrier function - protects platelets from exposure to ecm secretes inhibitors of platelet aggregation secretes inhibitors of coagulation modulates fibrinolysis secretes factors to regulate vascular tone |
|
|
Term
| What are inhibitors of platelet aggregation secreted by the endothelium? |
|
Definition
|
|
Term
| What are the inhibitors of coagulation secreted by the endothelium? |
|
Definition
| thrombomudulin and heparan sulfate |
|
|
Term
| What factors secreted by the endothelium regulate vascular tone? |
|
Definition
|
|
Term
| What factors produced by the endothelium modulate fibrinolysis? |
|
Definition
|
|
Term
| What are the two roles of platelets? |
|
Definition
| responsible for platelet or hemostatic plug formation, site for thrombin generation |
|
|
Term
| What is the function of the coagulation cascade? |
|
Definition
| responsible for thrombin generation and fibrin clot formation |
|
|
Term
| Where are platelets derived from? |
|
Definition
|
|
Term
| Which diseases do platelets contribute to? |
|
Definition
| heart attack, stroke, pulmonary emboli |
|
|
Term
| How long do platelets last? Where are they destroyed? |
|
Definition
10 days primarily in the spleen |
|
|
Term
| How do platelets accelerate coagulation? |
|
Definition
| induces phosphatidylserine exposure on the platelet surface |
|
|
Term
| What are the four steps in platelet plug formation? |
|
Definition
1 exposure of matrix components in basement membrane 2 adhesion and initial activation 3 recruitment of additional platelets, fibrinogen binding to alpha II b beta 3 integrin 4 stabilization of aggregate |
|
|
Term
| What components in the basement membrane do platelets adhere to? |
|
Definition
| collagen, von Willebrand factor |
|
|
Term
| What do platelets release to recruit addtional platelets? |
|
Definition
|
|
Term
| What allows for stabilization of the platelet aggregate? |
|
Definition
| alpha IIb beta 3 signaling and fibrin crosslinking |
|
|
Term
| What is the most potent platelet activating agent? |
|
Definition
|
|
Term
| What cleaves fibrinogen to stabilize the fibrinogen strands intercalated among the aggregated platelets? |
|
Definition
| transglutaminase factor XIII |
|
|
Term
| What impairs PGI2 synthesis by endothelial cells? |
|
Definition
|
|
Term
| What inhibits platelet activation? |
|
Definition
| intracellular cAMP and cGMP |
|
|
Term
| How do PGI2's help to inhibit platelet activation? |
|
Definition
| bind to a G protein-coupled receptor on the platelet surface which is coupled to the heterotrimeric G protein Gs which stimulates adenylyul cyclase to produce cAMP |
|
|
Term
What cleaves von Willebrand factor? What can a defect in this protein cause? |
|
Definition
the metalloprotease ADAMTS13 von willebrand disease, sufferers bleed more easily than the rest of the population |
|
|
Term
Which receptors on the platelet surface bind collagen? Which bind von Willebrand factor? |
|
Definition
alpha 2 beta 1 and GPVI GPIb/V/IX and alpha IIb beta 3 |
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Term
| What does GPVI signaling result in? |
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Definition
| the release of intracellular calcium and the activation of protein kinase C |
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Term
| What results from the release of calcium and the activation of protein kinase C? |
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Definition
| production of thromboxane A2 and the release of ADP from platelet dense granules |
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Term
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Definition
| inhibits COX 1 and thus suppresses thromboxane A2 production |
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Term
| How is thromboxane A2 synthesized by activation of phospholipase A2? |
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Definition
| liberates arachidonic acid from phospholipids in the plasma membrane, then ararchidonic acid is converted to the prostaglandin precursors of thromboxane A2 by COX-1 |
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Term
| What does the binding of thromboxane A2, ADP and thrombin to a G protein coupled receptor trigger? |
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Definition
| a cascade of signaling events within the platelet that ultimately results in the activation of platelet integrin alpha IIb beta 3 such that it becomes competent to bind circulating fibrinogen |
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Term
| What does thrombin mediated activation of PAR1 and PAR4 enable the platelet to do? |
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Definition
1 change its shape from a smooth disc to a more spiny form 2 to release calcium from intracellular stores 3 to activate protein kinase C |
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Term
| What effect does ADP have on clot formation? |
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Definition
| binds to P2Y1 and P2Y12, results in activation of PKC and Ca release and inhibits cAMP formation; also helps integrin alpha IIb beta3 to bind fibrinogen |
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Term
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Definition
| targets P2Y12, reduces the incidence of acute MI, stroke, and vascular death in high risk patients |
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Term
| Which drugs are integrin alpha IIb beta 3 blockers? |
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Definition
| ReoPro, integrilin, tirofiban |
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Term
| What is phosphatidylserine required for? |
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Definition
| factors VIIIa and IXa to form functional intrinsic Xase, the final cleavage event in the formation of a functional prothrombinase |
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Term
| What are the three steps in the extrinsic pathway of thrombin generation? |
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Definition
1 expose tissue factor, binds VII, claves to VIIa 2 VIIa cleaves X to Xa, IX to IXa 3 Xa claves II (prothrombin) to IIa (thrombin) |
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Term
| What 4 things does thrombin do? |
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Definition
1 cleaves fibrinogen 2 activates platelets 3 stimulates the expressuion of tissue factor 4 cleaves V to Va (part of the prothrombinase complex) and converts VIII to VIIIa (forms part of the Xase) |
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Term
| How is a prothrombin time performed and what does it measure? |
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Definition
blood collected in citrate to chelate free Ca++, plasma collected by centrifugation, Ca++ added along with a source of tissue factor, time to clot is measured |
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Term
| What defects occur in the most common hemophilias? |
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Definition
| defects in FIXa or FVIIIa. these factors from the Xase, a reinforcing clotting pathway |
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Term
| Deficiencies in which factors cause bleeding? |
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Definition
VII X prothrombin (II) fibrinogen V VIII (hemophilia A) IX (hemophilia B) XI |
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Term
How does the aPTT test work? What factor is it independent of? Which factors is it dependent on? |
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Definition
citrated plasma is collected and exposed to Ca++, phopholipids, and a negatively charged surface and clotting time is measured FVII FXII, HK, PK, FXI, FIX, FVIII, FV, FX, prothrombin and fibrinogen |
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Term
Which factors are dependent on vitamin K? Which domain do these have in common? What does this domain do? |
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Definition
II, VII, IX, X Gla domain: a region that is transcribed as a stretch of glutamates but is post-translationally modified to form a stretch of gamma-carboxyglutamate residues in a K dependent reaction promotes binding of Ca++ and binding of tghese factors to platelet membranes, vastly enhancing their activity |
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Term
| What does warfarin (coumadin) do? |
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Definition
| inhibits the modification of the Gla domain into a stretch of gamma carboxyglutamate residues |
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Term
| What is TFPI (tissue factor protease inhibitor)? |
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Definition
| binds and inhibits FXa and VII a, this inhibition is one reason why the pathway is a clinically important contributor to the total of amount of thrombin formed |
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Term
| What does anti-thrombin III do? |
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Definition
| contains an arginine that makes it look like a stubstrate to thrombin, however it lacks additional structures requried for the cleavage to be completed, thus it is a suicide substrate |
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Term
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Definition
| it enhances the binding of antithrombin II to thrombin about 10000-fold, thus it is an anticoagulant |
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Term
What does fibrinolysis do? What initiates it? |
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Definition
degrades fibrin clots after the injury has been repaired tissue plasminogen activator (tPA) |
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Term
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Definition
| binds to fibrin, which induces a conformational change that allows it to cleave plaminogen to generate plasmin |
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Term
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Definition
| cleaves fibrin into small soluble peptides known as fibrin degradation products |
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Term
| What does PAI-1 (plasminogen activator inhibitor) do? |
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Definition
| binds tPA, forming n inactive enzyme-inhibitor complex |
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Term
| What does alpha 2-anti plasmin do? |
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Definition
| binds and inhibits plasmin, prevents excessive plasmin formation in the general circulation (plamin bound to fibrin protected from inactivation), but allows it in the controlled environment of the clot |
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Term
| What is TAFI (thrombin activated fibrinolysis inhibitor)? |
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Definition
| a protein cleaved and activated by thrombin, cleaves a specific site on fibrin where plasminogen would bind, thus it inhibits formation of plasmin from plasminogen |
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Term
| During which phase does the majority of the coronary blood flow occur? |
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Definition
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Term
| What is the most importatnt determinant of myocardial blood flow? |
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Definition
| oxygen demand of the heart |
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Term
| How are metabolic need and blood flow connected in the heart? |
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Definition
| with increased metabolism and dephosphorylation of ATP and ADP, 5'neucleotidase converts AMP to adenosine. adenosine is a potent coronary vasodilator, in response flow is increased |
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Term
| What is myocardial stunning? |
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Definition
| the temporary decrease in ventricular function in the absence of permanent damage following a period of ischemia |
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Term
| What is myocardial hibernation? |
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Definition
| if there is sufficient flow to the ventricle to prevent permanent damage but insufficient flow for contraction of the affected portion of the ventricle |
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Term
| What are treatments for myocardial hibernation? |
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Definition
| coronary angioplasty or bypass surgery to restore blood flow and function to the affected tissue |
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Term
| What is the benefit of nitrate based vasodilators? Under what conditions is it beneficial? |
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Definition
a decrease in preload and afterload upon the left ventricle resulting in a decrease in the metabolic demand of the heart when the decrease in the metabolic demand of the heart is greater than any decrease in blood flow caused by the reduction in aortic pressure following administration of the vasodilating agent |
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Term
| Which gets more flow, subendocardial tissue or subepicardial tissue? |
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Definition
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Term
| Which is more work: pressure work or volume work? |
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Definition
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Term
| What can the vascular endothelium release to modulate the activity of vasoconstrictors or vasodilators? |
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Definition
| EDRF (NO) and PGI2 (vasodilators) or endothelin (vasoconstrictors) |
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Term
| Which substances does the vascular endothelium release to preserve a non-thrombogenic surface? |
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Definition
| PGI2 (can disaggregate platelets) and 13-HODE and NO (repel blood cells from the endothelium) |
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Term
| What does tissue plasminogen activator do? |
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Definition
| used clincally to open thrombosed coronary arteries to eliminate thrombosis, produced by the vascular endothelium |
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Term
| How does endothelium-derived relaxing factor cause smooth muscle relaxation? |
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Definition
| activates soluble guanylyl cyclase in the smooth muscle cells, giving rise to cGMP which has a role in relaxation |
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Term
| How is EDRF (NO) synthesized in endothelial cells? |
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Definition
| product of the action of a calcium/calmodulin dependent oxygenase, nictric oxide synthase, which oxidezes a guanidinium nitrogen of L-arginine to yield NO and citrulline |
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Term
| What are the characteristic post-translational modifications of eNOS and where is it targeted to? |
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Definition
myristoylated at Gly-2 and palmitoylated on Cys-15 and 26 plasmalemmal caveolae |
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Term
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Definition
| specialized domains of the plasma membrane that may serve to sequester signaling proteins |
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Term
| What happens when eNOS is bound to caveolin? |
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Definition
| it is inactive because caveolin directly froms an inhibitory complex with eNOS and abrogates the activation of eNOS by calmodulin (calmodulin/Ca activates the enzyme and increases production of NO) |
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Term
| What are five biological effects of NO? |
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Definition
inhibits platelet aggregation prevents WBC from adhering to the endothelium prevents superoxide radical induced damage of the cell membrane inhibits smooth muscle proliferation stimulates endothelial cell regeneration |
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Term
| What are teh main three consequences of endothelial dysfunction? |
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Definition
1 loss of vasodilator activity 2 activation of inflammatory signals (recruitment of leukocytes which release free radicals) 3 increased pro-thrombogenic activity (increase adhesion of platelets) |
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Term
| Why is there a reduced response to endothelium-dependent vasodilators after myocardial ischemia? |
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Definition
| reduced NO production by the coronary arteries in response to increased superoxide radical formation |
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Term
| How does hypercholesterolemia result in endothelial dysfunction? |
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Definition
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Term
| How does NO retard aterogenesis? |
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Definition
| attenuates LDL-oxidation and inhibits the expression of cell adhesion molecules |
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Term
| How does NO loss seen in diabetes mellitus aggrevate its effects? |
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Definition
| associated with accelerated ateroscelosis and several microvascular complications such as nephropathy, retinopathy, neuropathy |
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Term
| What happens to skin blood flow with continued exposure to cold? |
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Definition
| at first blood flow is decreased, but then over time begins to increase (cold vasodilation); a local reflex initiated in pain fibers acts to inhibit the sympatheitc outflow to arterioles and the AV anastomoses; results in alternating periods of vasoconstriction and vasodilation |
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Term
| What is the response of skin circulation to heat? |
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Definition
| sympathetic vasoconstriction is inhibited, the arterioles, AV anastomose, and veins dilate. blood flow to the skin increases and heat is transferred from the core to the surface to be lost to the environment. |
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Term
| What is the vasodilator produced as a result of stimulation of sympathetic cholinergic fibers innervating the sweat glands? |
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Definition
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Term
| What is reactive hyperemia? |
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Definition
| a period of increased blood flow following a period of interrupted flow |
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Term
| What causes the low blood flow to skeletal muscle at rest? |
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Definition
| tonic sympathetic vasoconstrictor activity acting to maintain the arterial blood pressure |
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Term
| What signals that muscle blood flow should be increased? |
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Definition
| increased pressure (due to increased peripheral resistance with increased vasoconstriction) is sensed by the baroreceptors of the carotid and sympathetic outflow to the blood vessels is inhibited and muscle blood flow is greatly increased |
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Term
| Where is the thermolytic center and what does it respond to? |
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Definition
| anterior region of the hypothalamus, responds to a heat load, activation elicits heat dissipating effector mechanisms |
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Term
| Where is the thermogenic center and what does it respond to? |
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Definition
| posterior region of the hypothalamus, activation elicits heat conservation effector mechanisms |
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Term
| What is nonshivering thermogenesis, what signals it, what protein is formed, and what does it do? |
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Definition
an autonomic response that causes lipolysis and an uncoupling of oxidative phosphorylation epinephrine and TSH thermogenin disturbs the normal H+ gradient |
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Term
| What does the sensitivity of baroreceptors depend on? |
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Definition
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Term
| Stretch in the atria induces release of which hormones? |
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Definition
| ADH and ANP (atrial natriuretic peptide) both of which increase urine output |
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Term
| What is the mechanism of BP rise due to epinephrine administration? |
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Definition
1 direct myocardial stimulation that increases the strength of ventricular contraction 2 an increased heart rate 3 vasoconstriction |
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Term
| What is the effect of intravenous infusion of isoproterenol? |
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Definition
| lowers peripheral vasular resistance primarily in skeletal muscle but also in renal and mesenteric vascular beds. diastolic pressure falls, systolic same or rise, cardiac output increased |
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Term
| What is the effect of an intravenous infusion of norepinephrine? |
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Definition
systolic, diastolic and pulse pressures increase cardiac output unchanged or decreased total peripheral resistance raised compensatory vagal reflex-increases stroke volume |
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Term
| What do ACE inhibitors do? |
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Definition
| increase the levels of kinins in tissues and plasma |
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Term
| What causes hypovolemic shock? |
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Definition
| hemorrhage, dehydration, burns. result in a fall in blood volume which then causes a fall in blood pressure |
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Term
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Definition
| caused by bacterial infections, release of cv toxins, release of vasodilator mediators. sustained vasodilation causes a dramatic decrease in total peripheral resistance which in turn causes a fall in blood pressure |
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Term
| What is cardiogenic shock? |
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Definition
| impairment of cardiac function results in a fall in cardiac output which causes the fall in blood pressure |
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Term
| What is anaphylactic shock? |
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Definition
| intense allergic reaction which tiggers immune response and release of vasodilators. sustained vasodilation cuases a dramatic decrease in total peripheral resistance which then cuases a fall in bp |
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Term
| What is neurogenic shock? |
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Definition
| loss of vasomotor tone throughout the body. leads to massive dilation of arterioles and veins and also dramatic decreases in heart rate and myocardial contractility, the total cv system becoems depressed |
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Term
| What hormone is essential for a full restoration of plasma volume after hemorrhage? |
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Definition
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Term
| What does the release of endogenous opiods by the CNS after prolonged hypotension cause? |
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Definition
| mediation of the compensatory autonomic adaptations to blood loss |
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Term
| What opiod antagonist improves cv function and survival in various forms of shock? |
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Definition
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Term
| What happens if the reticuloendothelial system becomes depressed? |
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Definition
| aggrevates hemodynamic changes caused by blood loss due to an increase in the level of endotoxins |
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