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systems test 2
written exam
246
Physiology
Professional
02/25/2008

Additional Physiology Flashcards

 


 

Cards

Term
Which organs are directly involved in the exchange between the blood compartment and the outside environment?
Definition

lungs

gi tract

kidneys

skin 

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
axial streaming
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
vessel radius
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
right
Term
Which ventricle can produce higher pressures?
Definition
left
Term
How long does each cardiac cycle take?
Definition
0.8 seconds
Term
What is systole?
Definition
contraction/ejection segment
Term
What is diastole?
Definition
filling period segment
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
both valves are closed
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
atria depolarization
Term
What does the a wave indicate?
Definition
atrial contraction
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
slow action potential
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
ventricular arrhythmias
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
no deflection
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
no deflection
Term
What causes the P wave?
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
What causes the T wave?
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
What is the ST segment?
Definition
the interval when the ventricles are depolarized
Term
What is the QT interval?
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
central venous pressure
Term
What are the major determinants of central venous pressure?
Definition
venous tone, blood volume, body position
Term
What directly determines stroke volume?
Definition
preload
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
inverse
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
5-6 L/min
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
20 mL/100 mL
Term
At rest, how much oxygen do tissues extract?
Definition
5 mL /100 mL
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
heart rate
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
preload
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
stroke volume
Term
What is the formula for ejection fraction?
Definition
SV/LVEDV x 100%
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
diffusion limited
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
PGI2, NO, CD39
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
endothelin, PGI2, NO
Term
What factors produced by the endothelium modulate fibrinolysis?
Definition
t-PA, u-PA, PAI
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
megakaryocytes
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
ADP, TxA2, thrombin
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
thrombin
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
COX-2 inhibitors
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 

Term
What does GPVI signaling result in?
Definition
the release of intracellular calcium and the activation of protein kinase C
Term
What results from the release of calcium and the activation of protein kinase C?
Definition
production of thromboxane A2 and the release of ADP from platelet dense granules
Term
How does aspirin work?
Definition
inhibits COX 1 and thus suppresses thromboxane A2 production
Term
How is thromboxane A2 synthesized by activation of phospholipase A2?
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
Term
What does the binding of thromboxane A2, ADP and thrombin to a G protein coupled receptor trigger?
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
Term
What does thrombin mediated activation of PAR1 and PAR4 enable the platelet to do?
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 

Term
What effect does ADP have on clot formation?
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
Term
What does Plavix do?
Definition
targets P2Y12, reduces the incidence of acute MI, stroke, and vascular death in high risk patients
Term
Which drugs are integrin alpha IIb beta 3 blockers?
Definition
ReoPro, integrilin, tirofiban
Term
What is phosphatidylserine required for?
Definition
factors VIIIa and IXa to form functional intrinsic Xase, the final cleavage event in the formation of a functional prothrombinase
Term
What are the three steps in the extrinsic pathway of thrombin generation?
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) 

Term
What 4 things does thrombin do?
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) 

Term
How is a prothrombin time performed and what does it measure?
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

 

 

Term
What defects occur in the most common hemophilias?
Definition
defects in FIXa or FVIIIa. these factors from the Xase, a reinforcing clotting pathway
Term
Deficiencies in which factors cause bleeding?
Definition

VII

X

prothrombin (II)

fibrinogen

V

VIII (hemophilia A)

IX (hemophilia B)

XI 

Term

How does the aPTT test work?

What factor is it independent of?

Which factors is it dependent on? 

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 

Term

Which factors are dependent on vitamin K?

 

Which domain do these have in common?

 

What does this domain do? 

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 

Term
What does warfarin (coumadin) do?
Definition
inhibits the modification of the Gla domain into a stretch of gamma carboxyglutamate residues
Term
What is TFPI (tissue factor protease inhibitor)?
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
Term
What does anti-thrombin III do?
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
Term
What does heparin do?
Definition
it enhances the binding of antithrombin II to thrombin about 10000-fold, thus it is an anticoagulant
Term

What does fibrinolysis do?

 

What initiates it? 

Definition

degrades fibrin clots after the injury has been repaired

 

tissue plasminogen activator (tPA) 

Term
What does tPA do?
Definition
binds to fibrin, which induces a conformational change that allows it to cleave plaminogen to generate plasmin
Term
What does plasmin do?
Definition
cleaves fibrin into small soluble peptides known as fibrin degradation products
Term
What does PAI-1 (plasminogen activator inhibitor) do?
Definition
binds tPA, forming n inactive enzyme-inhibitor complex
Term
What does alpha 2-anti plasmin do?
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
Term
What is TAFI (thrombin activated fibrinolysis inhibitor)?
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
Term
During which phase does the majority of the coronary blood flow occur?
Definition
diastole
Term
What is the most importatnt determinant of myocardial blood flow?
Definition
oxygen demand of the heart
Term
How are metabolic need and blood flow connected in the heart?
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
Term
What is myocardial stunning?
Definition
the temporary decrease in ventricular function in the absence of permanent damage following a period of ischemia
Term
What is myocardial hibernation?
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
Term
What are treatments for myocardial hibernation?
Definition
coronary angioplasty or bypass surgery to restore blood flow and function to the affected tissue
Term
What is the benefit of nitrate based vasodilators? Under what conditions is it beneficial?
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 

Term
Which gets more flow, subendocardial tissue or subepicardial tissue?
Definition
subendocardial
Term
Which is more work: pressure work or volume work?
Definition
pressure work
Term
What can the vascular endothelium release to modulate the activity of vasoconstrictors or vasodilators?
Definition
EDRF (NO) and PGI2 (vasodilators) or endothelin (vasoconstrictors)
Term
Which substances does the vascular endothelium release to preserve a non-thrombogenic surface?
Definition
PGI2 (can disaggregate platelets) and 13-HODE and NO (repel blood cells from the endothelium)
Term
What does tissue plasminogen activator do?
Definition
used clincally to open thrombosed coronary arteries to eliminate thrombosis, produced by the vascular endothelium
Term
How does endothelium-derived relaxing factor cause smooth muscle relaxation?
Definition
activates soluble guanylyl cyclase in the smooth muscle cells, giving rise to cGMP which has a role in relaxation
Term
How is EDRF (NO) synthesized in endothelial cells?
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
Term
What are the characteristic post-translational modifications of eNOS and where is it targeted to?
Definition

myristoylated at Gly-2 and palmitoylated on Cys-15 and 26

 

plasmalemmal caveolae 

Term
What are caveolae?
Definition
specialized domains of the plasma membrane that may serve to sequester signaling proteins
Term
What happens when eNOS is bound to caveolin?
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)
Term
What are five biological effects of NO?
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 

Term
What are teh main three consequences of endothelial dysfunction?
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) 

Term
Why is there a reduced response to endothelium-dependent vasodilators after myocardial ischemia?
Definition
reduced NO production by the coronary arteries in response to increased superoxide radical formation
Term
How does hypercholesterolemia result in endothelial dysfunction?
Definition
loss of EDRF/NO
Term
How does NO retard aterogenesis?
Definition
attenuates LDL-oxidation and inhibits the expression of cell adhesion molecules
Term
How does NO loss seen in diabetes mellitus aggrevate its effects?
Definition
associated with accelerated ateroscelosis and several microvascular complications such as nephropathy, retinopathy, neuropathy
Term
What happens to skin blood flow with continued exposure to cold?
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
Term
What is the response of skin circulation to heat?
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.
Term
What is the vasodilator produced as a result of stimulation of sympathetic cholinergic fibers innervating the sweat glands?
Definition
bradykinin
Term
What is reactive hyperemia?
Definition
a period of increased blood flow following a period of interrupted flow
Term
What causes the low blood flow to skeletal muscle at rest?
Definition
tonic sympathetic vasoconstrictor activity acting to maintain the arterial blood pressure
Term
What signals that muscle blood flow should be increased?
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
Term
Where is the thermolytic center and what does it respond to?
Definition
anterior region of the hypothalamus, responds to a heat load, activation elicits heat dissipating effector mechanisms
Term
Where is the thermogenic center and what does it respond to?
Definition
posterior region of the hypothalamus, activation elicits heat conservation effector mechanisms
Term
What is nonshivering thermogenesis, what signals it, what protein is formed, and what does it do?
Definition

an autonomic response that causes lipolysis and an uncoupling of oxidative phosphorylation

 

epinephrine and TSH

 

thermogenin

 

disturbs the normal H+ gradient 

Term
What does the sensitivity of baroreceptors depend on?
Definition
pulse pressure
Term
Stretch in the atria induces release of which hormones?
Definition
ADH and ANP (atrial natriuretic peptide) both of which increase urine output
Term
What is the mechanism of BP rise due to epinephrine administration?
Definition

1 direct myocardial stimulation that increases the strength of ventricular contraction

2 an increased heart rate

3 vasoconstriction 

Term
What is the effect of intravenous infusion of isoproterenol?
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
Term
What is the effect of an intravenous infusion of norepinephrine?
Definition

systolic, diastolic and pulse pressures increase

cardiac output unchanged or decreased

total peripheral resistance raised

compensatory vagal reflex-increases stroke volume

Term
What do ACE inhibitors do?
Definition
increase the levels of kinins in tissues and plasma
Term
What causes hypovolemic shock?
Definition
hemorrhage, dehydration, burns. result in a fall in blood volume which then causes a fall in blood pressure
Term
What is septic shock?
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
Term
What is cardiogenic shock?
Definition
impairment of cardiac function results in a fall in cardiac output which causes the fall in blood pressure
Term
What is anaphylactic shock?
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
Term
What is neurogenic shock?
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
Term
What hormone is essential for a full restoration of plasma volume after hemorrhage?
Definition
cortisol
Term
What does the release of endogenous opiods by the CNS after prolonged hypotension cause?
Definition
mediation of the compensatory autonomic adaptations to blood loss
Term
What opiod antagonist improves cv function and survival in various forms of shock?
Definition
naloxone
Term
What happens if the reticuloendothelial system becomes depressed?
Definition
aggrevates hemodynamic changes caused by blood loss due to an increase in the level of endotoxins
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