Unit 1 Flashcards
Functions of CV system
o distributes dissolved gases & nutrients.
o removes metabolic waste
o contributes to systemic homeostasis by controlling temp, O2 supply, pH, ionic composition, nutrient supply
o quickly adapts to changes in conditions and metabolic demands
Systemic circulation is primarily arranged “in _______.”
parallel
Importance of systemic circulation being arranged in parallel:
o O2 blood visits only one organ system before returning to pulmonary circulation
o Changes in metabolic demand or blood flow in one organ do not significantly affect other organs
o Blood flow to different organs can be individually varied to match demand
Layers of the heart
o epicardium
o myocardium
o endocardium
epicardium
outer membrane = connective tissue & fat
myocardium
thick muscle layer of the heart
endocardium
inner membrane = endothelial cells, as in vessels
The pericardium encloses entire heart in a ___ ____ membranous sac that is/is not connected to walls of heart
fluid filled membranous sac
is NOT connected to the walls of the heart
The pericardium is:
flexible and compliant
OR
Stiff & non-compliant
Stiff & non-compliant, resists sudden distension of chambers.
Why is pericarditis problematic?
Pericarditis restricts the filling of the heart.
Two types of valves in the heart
atrioventricular (tricuspid and mitral) valves and
Semilunar (pulmonic and aortic) valves
What are valves made of?
o Valves = thin flaps (“cusps”) of fibrous tissue covered by endothelium.
o Mitral has two cusps (bicuspid), others have three
Sinoatrial (SA) node
o in wall of right atrium
o spontaneously depolarizes to initiate the heart beat
o intrinsic activity ~100 bpm
o highly regulated by autonomic nervous system and many humoral factors
Impulse spreads through atria via ___ _____
gap junctions
Atrioventricular (AV) node
between atria and ventricles, slows conduction to allow atrial contraction to precede ventricular contraction
His-Purkinje system
specialized cells that rapidly conduct depolarization to trigger coordinated ventricular contraction.
Most coronary blood flow occurs during _____.
Why?
diastole,
because of compression of microvasculature during systole.
The Right & left coronary arteries arise from where? The Major coronary arteries course along ______ surface of heart. Smaller branches enter _______
The root of the aorta
epicardial, myocardium
The left main coronary artery supplies:
The left atrium and left ventricle
The right coronary artery is located where? What does it supply?
- in groove between right atrium and right ventricle
* primary blood supply to right atrium and right ventricle, as well as posterior part of left ventricle
What do the coronary veins drain into?
drain into coronary sinus, which opens into right atrium near inferior vena cava
What does that aorta do to the pulsatile pressure?
dampens pulsatile pressure
Describe the walls of arteries
thick walled, resist expansion
Arterioles
- relatively thicker walls (more vascular smooth muscle)
- highly innervated by ANS nerves, circulating hormones, and local metabolites
- primary site of regulation of vascular resistance, via changes in diameter
What is the primary sire of regulation of vascular resistance via changes in diameter?
arterioles
Describe the walls of venules
thin walls relative to diameter compared to equivalent-sized arteries (but still some smooth muscle), not much elasticity
Arterial walls have 3 layers:
1) Tunica adventitia
2) Tunica media
3) tunica adventitia
Tunica adventitia
o outer layer
o mostly connective tissue = collagen and elastin
Tunica media
o middle layer
o mostly innervated vascular smooth muscle
o controls diameter of vessels, particularly resistance arteries
o not present in capillaries
Tunica intima
o inner layer of vessel lined with vascular endothelium:
o single continuous layer of endothelial cells
o very important in regulation of blood flow
o site of atherosclerotic plaque formation.
Microcirculation
o Defined as vasculature from the first-order arterioles to the venules
What regulates blood flow through the capillaries?
o Blood flow through capillary beds is determined by the pressure gradient , and is highly regulated via constriction/dilation of arterioles & precapillary sphincters
o precapillary sphincters = smooth muscle bands at junction of arteriole and capillaries
Structure of capillaries
o Capillaries do not have a smooth muscle layer, only endothelial cells surrounded by basement membrane
o Movement of substances between capillaries and tissue is driven by concentration and pressure gradients (more in hemodynamics lecture)
The difference between what drives blood flow through an organ?
arterial and venous pressure
the difference in pressure between the inside and outside of a vessel (across the wall) is called…
transmural pressure
Where is the pressure the highest?
aorta, elastic walls of the vessels dampen pulsatile pressure, but there is little resistance to flow, so there is not much of a drop in blood pressure through the arteries
Where does a big fall in pressure occurs (arterial side of things)
A big fall in pressure occur in the arterioles, aka the “resistance vessels
Describe the pressure in the capillaries and venous system
very low
Which has higher pressure, the systemic or pulmonary circulation?
systemic circulation»_space; pulmonary circulation
cardiac output from left and right sides of heart are ____, but ___ and ____ are different.
equal
resistance and pressure— much lower in pulmonary circulation
Total blood volume
5L
Which has a greater blood volume, arterial or venous system?
venous system, veins are known as “capacitance vessels”
Flow equation
Q = ΔP/R
Cardiac output equation
CO=(mean arterial pressure-venous pressure)/ Total peripheral resistance (TPR)
analogous relationships to Ohm’s law
where blood flow is like current, pressure is like voltage, and resistance is like… well, resistance.
What does flow REQUIRE?
flow requires a pressure difference
What must flow in equal?
Flow in MUST equal FLOW out
Assumptions of flow equation that are not really valid for cardiovascular system:
constant pressure, constant resistance, straight rigid tube. BUT, pressure and flow through the system as a whole can be approximated with the flow equation.
Poiseuille’s Equation
Flow=πr^4/8ηl
Most importantly, flow is dependent on the ____^4
radius of the vessel
The term πr^4/8ηl is also the inverse of what?
The term πr4/8ηl is also the inverse of resistance in the flow equation
In CV system, what is the major mechanism by which flow is controlled (vasoconstriction & vasodilation)?
vessel diameter is the major mechanism by which flow is controlled (vasoconstriction & vasodilation).
Poiseuille’s Law is only valid for
single vessels
Vessels in the systemic circulation are in (parallel/series)
parallel
Consequesnce of systemic circulation being in parallel
• Total resistance of a network of parallel vessels is lower than the resistance of single lowest resistance vessel in the system.
1/Rtotal= (1/R1) + (1/R2) + (1/R3)
• Changing the resistance of a single vessel in a parallel system has little effect on the total resistance of the system.
What vessels have (individually) the highest resistance? When considered in total, do they have high or low resistance?
capillaries are highest resistance of all vessels (smallest diameter), yet the total resistance of capillary beds is quite low and is independent of individual capillaries because there are many PARALLEL vessels.
Is the total resistance of a series of vessels is higher/lower than the resistance of any individual vessel?
Resistances in series are additive
Rtotal= R1 + R2 + R3
Blood flow through vessels in series is _____, but the pressure ______ through the series of vessels
constant
decreases
(e.g. pressure drops through the systemic circulation)
The flow equation assumes what kind of flow?
Flow equation assumes non-pulsatile laminar flow – so only approximate for CV system
In laminar flow, where is the velocity of blood the highest?
The velocity of the blood is fastest in the center, slower at the edge of the tube
factors that increase turbulent flow
large diameter, high velocity, low viscosity, abrupt changes in diameter, irregularities on tube walls.
Turbulent flow produces what kind of force? What are the effects of these forces?
shearing force – viscous drag of fluid flowing through tube, which exerts force on the walls. Shear forces can damage vascular endothelium, which promotes formation of thrombi and embolisms. Damage to the vascular endothelium is a first step in the development of atherosclerotic plaques.
Is arterial pressure constant in the aorta?
No. Heart pumps intermittently, creating pulsatile flow in the aorta — arterial pressure is not constant.
Systolic pressure=
= peak aortic (~arterial) pressure
Diastolic pressure=
=minimum aortic pressure
pulse pressure =
systolic – diastolic
Does the pulse vary in the capillaries?
in capillary beds, NO pulse variation, pressure (and thus flow) is continuous. Pulse pressure, mean pressure and velocity all decrease from aorta to capillaries.
Which requires more work, pulsatile or continuous pressure?
pulsatile flow requires more work – basically acceleration of mass vs. maintaining constant velocity (example: stop & go driving at rush hour uses more gas)
Mean arterial pressure (MAP). What does MAP depend on?
diastolic pressure + 1/3(systolic – diastolic)
o MAP depends on HR: approx correct for resting HR. At higher HRs, diastole is relatively shorter, so MAP approaches the average between systolic & diastolic pressures.
Is the mean arterial pressure the arithmetic average of systolic and diastolic pressures? Why
NO, because diastole is longer than systole (at resting heart rates)
Compliance equation
Compliance (C, in ml/mmHg) equals change in volume (ΔV, in ml) that results from a change in pressure (ΔP, in mmHg)
C=ΔV/ΔP
What is compliance?
Compliance represents the elastic properties of vessels (or chambers of the heart)-determined by relative proportion of elastin fibers versus smooth muscle and collagen in vessel walls.
Are arteries or veins more compliant?
Veins are more compliant than arteries – more ΔV per ΔP
Arteriosclerosis
loss of compliance from thickening and hardening of arteries. Some arteriosclerosis is normal with age
LAW OF LAPLACE
T=(ΔP*r) / μ T=tension or wall stress) ΔP is transmural pressure r is radius μ is wall thickness.
How is an aneurism explained by the law of LaPlace?
weakened vessel wall bulges outward, increasing the radius, increasing the tension that cells in the wall have to withstand to prevent the vessel from splitting open. Over time cells become weaker, allowing the wall to bulge more so that tension increases further, until the aneurysm ruptures.
Two types of cardiovascular transport
Bulk transport and transcapillary transport
Bulk transport
cargo from point A to point B in whole CV system. Can be applied also to consumption of a substance.
Transcapillary transport
movement of cargo between capillaries and tissue
Fick’s Principle
considers how much of a substance is used by a tissue. The amount used is equal to the amount that enters the tissue minus the amount that leaves, and the amount can be determined as the flow times the concentration
Xused=Q([x]i-[x]o)
Equation that applies Fick’s law to cardiac output based on myocardial O2 consumption
mVO2=CO([O2]a-[O2]v)
MVO2=myocardial O2 consumption
CO=cardiac output
[O2]a and [O2]v= arterial and venous oxygen concentrations
equation for CO using Fick’s law
CO=mVO2/([O2]a-[O2]v)
Fractional O2 Extraction (EO2)
EO2 is the amount of oxygen used by a tissue expressed as a fraction of the original (arterial) oxygen concentration.
EO2=([O2]a-[O2]v)/[O2]a
Two opposing forces determine solvent movement in transcapillary transport:
1) hydrostatic pressure, P
2) oncotic pressure, π
Hydrostatic pressure
fluid pressure as we have been considering so far – blood pressure in this case. Net hydrostatic pressure in a capillary bed is the difference between capillary pressure and interstitial pressure.
Hydrostatic pressure promotes FILTRATION (movement of fluid out of capillaries)
Oncotic Pressure, π
(colloid osmotic pressure)- osmotic force created by proteins in the blood and interstitial fluid.
Oncotic pressure of blood in capillaries (πc) is higher than oncotic pressure of interstitial fluid (πi)
Capillary oncotic pressure promotes REABSORPTION of fluid (movement of fluid into capillaries)
What are the major determinant of oncotic pressure?
α Globulin and albumin are major determinants of oncotic pressure.
Starling Equation for transcapillary transport (AKA Starling’s law of the capillary)
Flux=k[(Pc-Pi)-(πc-πi)]
Flux = net mvmt across capillary wall k = constant Pc = capillary hydrostatic pressure Pi = interstitial hydrostatic pressure πc = capillary oncotic pressure πi = interstitial oncotic pressure (Pc - Pi) = net hydrostatic pressure – tends to be outward (filtration) (πc – πi) = net oncotic pressure – tends to be inward (reabsorption)
Factors that increase blood pressure (hypertension) or reduce ______ pressure (liver disease) tend to promote _____. Excess filtration causes edema (swelling) in tissues.
oncotic
filtration
there is a tendency toward ______ on the arterial side and ______ on the venous side.
filtration
reabsorption
Net flux is regulated primarily by control of what?
capillary hydrostatic pressure (via vasoconstriction/vasodilation of arterioles).
How many heavy and light chains does cardiac myosin have?
Two heavy chains and 4 light chains.
What types of troponin are there in the heart?
TN-C, TN-I, TN-T
TN-C
Troponin C: Contains only one Ca2+- binding site
TN-I
Inhibitory troponin that contains a unique N-terminal extension of 32 amino acids which is highly regulated by phosphorylation (PKA sites)
TN-T
the part of the troponin complex that is bound to tropomyosin
What isoform of tropomyosin is found in the heart?
ONLY alpha troponin is found in the heart
Action potential depolarization opens what type of calcium channels leading to calcium influx?
L type calcium channels
Regulators of stroke volume
- preload
- afterload
- contractility
Does increasing preload increase or decrease the amount of tension developed?
Given the same stimulus, increasing the preload increases the amount of tension the muscle can develop
What mechanisms underly the length-tension relationship?
- extent of overlap
- Changes in Ca2+ sensitivity (amount of Ca2+ needed to genera tire a given force)
- Increases in Ca2+ release
Afterload
as the pressure that ventricle has to generate in order to eject blood out of the chamber.
Relationship between afterload and the velocity of shortening
the greater the afterload, the slower the velocity
Contractility
The force with which the heart contacts
What is the most important physiological regulator of contractility?
norepeinephrine (NE)
Substances that change the contractility are called:
ionotropes
Frank-Starling Law
AN INCREASE IN PRE-LOAD LEADS TO AN INCREASE IN STROKE VOLUME.
Technically, according the the Frank-Starling law, The stroke volume of the heart increases in response to an increase in the volume of blood filling the heart (the __________) when all other factors remain constant
end diastolic volume
Cardiac Output
volume of blood pumped per minute by left ventricle
Stroke volume
volume of blood pumped per beat.
CO=
arterial pressure/TPR
Two mechanisms for heart to control cardiac output
Heart rate and stroke volume (CO=HR x SV)
Which factor of CO is subject to more change?
HR can increase by a larger percentage than stroke volume can, so HR can produce larger changes in cardiac output
What factors determine the stroke volume?
Determined by the strength of contraction of the heart, venous return (“preload”), and vascular resistance (“after load”)
Strength of contraction of the heart is controlled via two mechanisms
- Length-dependent intrinsic mechanism = Frank-Starling Law
- Length-independent mechanism = Inotropy (or “contractility”)
Inotropy
contractility, or contraction of the myocardium
On average, CO must be equal to what value?
Cardiac output MUST equal venous return (on average). Venous return is the volume of blood flowing into right atrium per minute
Must the cardiac output be, on average, equal for the left and right sides of the heart?
yes. Having unequal cardiac output not he left or right side of the heart would result in edema
Isovolumetric contraction phase of the cardiac cycle
ventricle contracts, pressure increases. The initial increase in pressure immediately pushes the mitral valve closed because the ventricular pressure quickly exceeds that in the atrium, now relaxing. Aortic pressure is initially greater than the ventricular pressure, so aortic valve is closed during the initial stage of ventricular contraction. Thus, ventricular pressure increases dramatically because the ventricle is contracting but both valves are closed.
Ejection Phase of the cardiac cycle
As the ventricle continues to contract, the ventricular pressure exceeds that in the aorta, thus the aortic valve is pushed open and blood begins to flow. As the ventricle begins to relax, the ventricular pressure falls. Pressure decreases slowly at first, and ejection continues. When the ventricular pressure drops below the aortic pressure, the aortic valve closes.
Isovolumetric relaxation phase
The ventricle continues to relax with both valves closed, so the pressure falls rapidly.
As the ventricle continues to relax, the pressure eventually falls below that in the atrium, allowing the mitral valve to open and blood to flow into the ventricle, beginning a new cycle.
Pressure and volume changes in the left ventricle are bounded by two curves:
systolic pressure-volume relation and the end diastolic pressure-volume relation
End diastolic pressure-volume relationship (EDPVR)
Lower curve: plots left ventricular pressure as a function of LV volume.
P-V relationship during filling of heart BEFORE contraction. Determined by passive elastic properties of ventricle
The end-diastolic PVR represents the PRELOAD on the heart.
The end-diastolic PVR represents the ______ on the heart.
PRELOAD
Preload is strictly defined as…
ventricular wall tension at the end of diastole
Afterload is strictly defined as…
The load against which a muscle contracts, wall stress during contraction
For left ventricle, afterload ~ aortic pressure.
Systolic pressure-volume relationship (SPVR)
Upper curve, P - V relationship at peak of isometric contraction
• Max pressure that can be developed by the ventricle, depends on AFTERLOAD
• Steeper than EDPVR – pressure increases a lot even at low volume.
• Systolic PVR includes passive properties of the heart (ie, includes the diastolic pressure-volume relationship)
“Active tension”
difference in force between peak systolic pressure and end diastolic pressure curves, i.e., tension developed by the contraction itself, independent of the preload.
“STARLING CURVE” or “Ventricular function curve”
Plot of cardiac performance (such as active tension or CO or SV) as a function of preload (such as length or EDV)
Frank-Starling law of the heart is the mechanism by which the heart adapts to what?
INTRINSIC mechanism by which the heart adapts to changes in preload (in the normal physiological range)
Violation of Starling’s law corresponds to what?
Heart Failure
Three ways to state Starling’s Law:
a) Heart responds to an increase in EDV by increasing the force of contraction.
b) Healthy heart always functions on the ascending limb of the ventricular function curve
c) What goes in, must come out. Cardiac output MUST equal venous return and cardiac output from left and right ventricles MUST match (on average).
Molecular basis for Starling’s law (briefly)
a) Cardiac titin isoform is very stiff, resists stretch.
b) Ca2+ sensitivity of myofilaments increases as sarcomeres are stretched-same intracellular Ca2+ produces a greater force of contraction.
c) Closer lattice spacing – stretched sarcomeres have altered spacing between actin & myosin which results in more force generated per crossbridge.
Bainbridge reflex
o Stretch sinus node → increase in heart rate
o Another way in which increased venous return causes increased cardiac output
SV =
SV= EDV - ESV
Ejection Fraction (EF)=
EF = SV/EDV
= (EDV – ESV) / EDV
Stroke Work
energy per beat (in Joules), area INSIDE the PV loop diagram
o NOT the same for left & right sides of heart, since systemic circulation has higher pressure, left heart does more work
Factors that affect preload
o Blood volume (IV fluid, hemorrhage)
o filling pressure (venous blood pressure)
o filling time (reduced at high heart rates)
o resistance to filling (e.g., right atrial pressure, AV valve stenosis)
o resistance to emptying = afterload (e.g., hypertension, pulmonic or aortic stenosis; see below)
o reduced inotropy
Compliance is defined as ___/__; on PV plots, compliance is the reciprocal of the slope of the EDPVR.
ΔV/ΔP
EDPVR, Therefore the steeper the EDPVR = less compliant (stiffer).
Decreased compliance causes higher/lower EDV at any given pressure
lower
What effect does dilated cardiomyopathy have on ventricular compliance?
it can increase ventricular compliance
Holding afterload & inotropy constant, an increase in preload (increase EDV) causes:
The immediate effect is an increase in stroke volume via Starling’s law (i.e., the heart contracts with more force because sarcomere length is increased).
Factors that determine afterload
aortic pressure is the major determinant of afterload for the LV and pulmonary artery pressure is the main source of afterload for the RV. Also, Wall thickness and ventricular radius according to the Law of LaPlace, which shows that wall stress (T) increases as radius (r) increases and wall thickness (μ) decreases
If you hold preload & inotropy constant, and increase after load, what effect does this have on the next beat?
This causes a decrease in stroke volume on the next beat
- ventricle has to generate more pressure before the aortic valve opens, allowing less time for ejection
- From the force-velocity relationship, velocity is reduced when afterload is increased. Thus, in the relatively fixed time period of systole, the ventricle will develop less pressure, and the ejection velocity will be reduced. Overall, this means less blood is ejected (decreased SV).
Changes in _____ are particularly important in exercise — help to maintain high stroke volume even at high heart rate.
inotropy
(contractility) reflects the strength of contraction at any given preload and afterload
hold preload & afterload constant, increase isotropy, what is the result?
This results in a new Starling curve which corresponds to greater systolic pressure development any given volume. Increased inotropy is associated with increases in stroke volume and ejection fraction and a decrease in end systolic volume. These effects persist as long as the inotropy remains high (do not recover on next beat).
At what speed do pacemaker cells depolarize?
pacemaker cells slowly depolarize to threshold in the absence of extrinsic input
rhythmicity
The nature of pacemaker cells to will fire action potentials at a frequency of about 100/min
What types of nerves innervate the SA node?
The SA node is innervated by both sympathetic and parasympathetic axons
overdrive suppression
under normal circumstances AV node cells cells are driven by action potentials originating in the SA node; that is, an action potential will spread to them from the SA node before they reach threshold on their own, even though they have automaticity
Where is the AV node located?
on the right side of the inter-atrial septum near the opening of the coronary sinus.
Rank order the length of action potentials of skeletal muscle, myocardium, and SA/AV nodes
(slowest) SA/AV>Myocardium> Skeletal muscle (fastest)
Cardiac sodium channels (containing _____ as the principle subunit) are similar to sodium channels in neurons and skeletal muscle. How so?
NaV1.5
Depolarization causes them to activate rapidly and then inactivate.
Two overarching types of calcium channels:
High voltage activated (HVA) and low voltage activated (LVA)
What are the predominant calcium channels in ventricular and atrial myocardium and cells of the AV and SA node conductive pathways?
L-type calcium channels containing CaV1.2
L type calcium channels
channels that activate quickly in response to depolarization and subsequently inactivate in a manner dependent both on voltage (voltage-dependent inactivation, VDI) and cytoplasmic calcium (calcium dependent inactivation, CDI)
What type of drugs block L type calcium channels?
dihydropyridines, used as antihypertensive agents
T type calcium channels
LVA (low voltage activation) channels activated by weaker depolarizations that nose required for HVA channels. They are expressed in the SA node and the nervous system
IKr and IKs currents
“rapid” delayed rectifier (IKr)
and
“slow delayed rectifier” (IKs)
Both are time-dependent potassium currents
IK1 current
The “inward rectifier” channel: does not gate in the conventional sense- conductance = voltage dependent as a consequence of block by cytoplasmic constituents. Strong, “instantaneous” (< 1 ms) rectification- conduct inward K+ current at potentials below EK and only weakly pass outward K+ current at potentials slightly positive to EK.
IK1 channels are ideally suited for what?
ideally suited for holding cells near EK between action potentials without producing an outward current upon depolarization that would be energetically costly and make it more difficult to generate an action potential.
____is increased in response to ACh acting on muscarinic receptors- important for the parasympathetic nervous system to slow pacemaker activity
IKACh
If (or Ih)
(HCN tetramer) – “funny” current: turned off at depolarized potentials and turned on at hyper polarized potentials. Channel is permeable to both Na+ and K+. May play an important role in pacemaking by SA nodal cells.
The categorization of cardiac action potentials as fast or slow is based on:
whether the initial upstroke is rapid or slow.
______ have fast action potentials, while _____ have slow action potentials
Myocardial cells/cells of the rapid conduction pathways display fast action potentials.
The initial upstroke (phase 0) of a fast cardiac action potential is caused by what?
rapid depolarization caused by the entry of sodium ions (INa) through voltage-activated sodium channels
Phase 1 of the fast cardiac action potential
Following the rapid upstroke is a small, partial repolarization (phase 1), which is produced by a combination of inactivation of sodium current and activation of a transient potassium current IKto
Phase 2 of the fast cardiac action potential
prolonged plateau where voltage-activated, L-type calcium channels are open. The influx of Ca2+ is approx. balanced by an efflux of K+ ions (IKr and IKs) via delayed rectifier channels so that membrane potential remains at constant level (0 mV). The combination of inactivation of (ICa) and increasing activation of IKr and IKs causes termination of the plateau by a rapid repolarization (phase 3).
Phase 3 of the fast cardiac action potential
The combination of inactivation of (ICa) and increasing activation of IKr and IKs causes termination of the plateau by a rapid repolarization. IKr and IKs are de-activated, and inactivation of INa and ICa is removed
Phase 4 of the fast cardiac action potential
As a result of Ik channel de-activation, and removal of INa and ICa; the cell is held near EK (phase 4) by the inward rectifier (IK1).
absolute refractory period
a second action potential cannot be initiated until most of the inactivation of INa is removed
relative refractory period
the threshold for a second action potential remains elevated (relative refractory period) until after repolarization is complete (complete removal of inactivation of INa and deactivation of IKr and IKs has occurred
