Cardiac Physiology
if you decrease the diameter of a tube by 50%, you increase the resistance by _________
16 fold
what is the normal range for CI?
2.5-4 L/min/m^2
what is the normal range for SI?
40-60 mL/beat/m^2
what is the normal EF?
60-80%
what is the normal SV range in a 70 kg male?
60-90 mL
what part of heart has the fastest conduction velocity? slowest?
A-V node 0.01 - 0.05 m/sec (slowest) Atria 0.5 - 1.0 m/sec His Purkinje 2.0 - 4.0 m/sec (quickest)
at rest, what part of the autonomic system controls the heart ?
At rest, the heart is under parasympathetic control.
blood flow in the cardiovascular system is changed largely d/t alterations in __________________
Blood flow in the CV system is changed largely due to alterations in resistance of blood vessels. change in pressure also changes flow
calculate CO
CO = SV x HR
How do you calculate CI?
CO/BSA
2. Discuss the steps in excitation-contraction coupling related to cardiac muscle.
Ca++ Influx - during action potential plateau ICa-L Ca++ Efflux Na+- Ca++ Exchange (fueled by Na+-K+ pump) Sarcolemma Ca++ pump (ATPase) Ca++ Storage and Release SR AP spreads along the surface membrane and to t-tubules at the z-line Ca++ entry is ICa-L (the Ca++ current) CICR Ca++ entry acts as a trigger for the release of Ca++ from the SR The amount of Ca++ released from SR is graded and depends on The amount of Ca++ stored in the SR How much of a Ca++ trigger Intracellular Ca++ increases The amount of force created is related to [Ca++] Ca++ binds to troponin-C Complex causes Tn-I to move out of the way on the thin filament Actin and myosin cross-bridges form, cycle and generate force Relaxation is a function of [Ca++] returning to its resting level. Troponin C - Ca++ complex comes apart - no force generated Cardiomyocytes are capable of coordinated contraction, controlled through the gap junctions of intercalated discs. The gap junctions spread action potentials to support the synchronized contraction of the myocardium. In cardiac, skeletal, and some smooth muscle tissue, contraction occurs through a phenomenon known as excitation contraction coupling (ECC). ECC describes the process of converting an electrical stimulus from the neurons into a mechanical response that facilitates muscle movement. Action potentials are the electrical stimulus that elicits the mechanical response in ECC. In cardiac muscle, ECC is dependent on a phenomenon called calcium-induced calcium release (CICR), which involves the influx of calcium ions into the cell, triggering further release of ions into the cytoplasm. The mechanism for CIRC is receptors within the cardiomyocyte that bind to calcium ions when calcium ion channels open during depolarization, releasing more calcium ions into the cell. Similarly to skeletal muscle, the influx of sodium ions causes an initial depolarization; however, in cardiac muscle, the influx of calcium ions sustains the depolarization so that it lasts longer. CICR creates a "plateau phase" in which the cell's charge stays slightly positive (depolarized) briefly before it becomes more negative as it repolarizes due to potassium ion influx. Skeletal muscle, by contrast, repolarizes immediately. Pathway of Cardiac Muscle Contraction The actual mechanical contraction response in cardiac muscle occurs via the sliding filament model of contraction. In the sliding filament model, myosin filaments slide along actin filaments to shorten or lengthen the muscle fiber for contraction and relaxation. The pathway of contraction can be described in five steps: An action potential, induced by the pacemaker cells in the sinoatrial (SA) and atrioventricular (AV) nodes, is conducted to contractile cardiomyocytes through gap junctions. As the action potential travels between sarcomeres, it activates the calcium channels in the T-tubules, resulting in an influx of calcium ions into the cardiomyocyte. Calcium in the cytoplasm then binds to cardiac troponin-C, which moves the troponin complex away from the actin binding site. This removal of the troponin complex frees the actin to be bound by myosin and initiates contraction. The myosin head binds to ATP and pulls the actin filaments toward the center of the sarcomere, contracting the muscle. Intracellular calcium is then removed by the sarcoplasmic reticulum, dropping intracellular calcium concentration, returning the troponin complex to its inhibiting position on the active site of actin, and effectively ending contraction as the actin filaments return to their initial position, relaxing the muscle.
chronotropy
HR
How does Ca++ affect contractility?
Increases, more force Increases troponin C CA complexes to increase contractility from more cross bridge formation
what parts of the heart does the SNS innervate? what does it cause?
Innervates atria, ventricle, and conducting system (SA, AV nodes) NE acts on beta 1 receptors to increase contractility, HR, conduction velocity
how does the body produce a postive chronotropic effect in the heart?
NE released via SNS NE acts on B1 receptors in the SA node activation of the receptor increases I-f conductance increased I-f conductance = increased rate of phase 4 depolarization = SA node depolarized to threshold more frequently SA node fires more action potentials per unit time
what area of the heart has the longest AP? fastest?
PKJ are the longest AVN=SAN for shortest AP PKJ>vent>atria>AVN=SAN SAN: 150 msec atrium 150-200 msec ventricle : 200 msec
how does BP vary throughout the CV system? why is this important?
Pressure drives flow Blood flow requires a driving force aorta = 100 mmhg arteries = 100 arterioles = 50 capillaries = 20 veins = 10
relaxation of cardiac muscle - how is intracellular calcium handled
Relaxation is a function of [Ca++] returning to its resting level. Troponin C - Ca++ complex comes apart - no force generated Sarcolemmic processes Ca++ current: Ca++ mainly enters the cell during each AP as ICa-L. Na+- Ca++ Exchange: cell must get rid of Ca++ that it gains during the AP to keep a steady state. The Na+- Ca++ exchanger uses energy in the Na+ gradient to get rid of Ca++ during diastole (3Na+ for each Ca++). Sarcolemmic Ca++ pump: a Ca++-ATPase located in the sarcolemma acts as a pump to remove Ca++ from the cell (requires ATP). Other organelles SR Ca++-ATPase pump on the SR membrane sequesters Ca++ Ca++ is also released from the SR Increasing cytoplasmic Ca++ increases the amount of Ca++ stored in the SR and decreasing cytoplasmic Ca++ decreases the amount stored. Mitochondria Can accumulate Ca++. It is slow and requires very high cytoplasmic Ca++ levels. Not important physiologically
what is Reynolds number? what is the equation?
Reynolds number predicts whether blood flow will be laminar or turbulent it is unitless Re = (density x velocity x diameter)/viscosity
8. List the cells in the heart that can serve as pacemakers.
SA, AV, PKJ
9. Understand the normal flow of electricity in the heart.
SA, AV, bundle of his, bundle branches, purkinje fibers
what variables determine CO?
SV and HR
calculate stroke index
SV/BSA
calculate EF
SV/EDV EDV-ESV/EDV
what affects the viscosity of blood? how does viscosity affect flow?
Temperature: incr T = decr η Hematocrit: incr Hct = incr η Shear rate (γ): incr γ = decr η flow is inversely related to velocity
how do you calculate velocity?
V= Q/A V=Q/πr^2
from where does the SNS fibers arise to innervate the heart?
arise from the cervical and thoracic spinal cord to the superior cervical, stellate and thoracic ganglia from the ganglia are the superior cardiac nerve, middle cardiac nerve, inferior cardiac nerve
what are the properties of arteries?
arteries carry blood to the tissues. they have low volume and are under high pressure. arteries are thick walled and elastic
what type of blood vessel has the greatest resistance? why?
arterioles Flow = (Pressure difference) / resistance* In other words, there will be flow in the vessel as long as there is a pressure difference between the two ends, but it'll be offset by resistance. The higher the resistance, the slower the flow. Pressure difference = Flow x resistance So, if you keep flow constant, the pressure difference INCREASES when there is resistance.
what are the properties of arterioles?
arterioles are smooth muscle that are always contracted they are innervated by alpha 1 receptors to cause vasoconstriciton they are innervated by beta 2 receptors to cause relaxation (esp skeletal muscle) the arterioles have the highest resistance to blood flow high volume the arterioles are the gate keepers - they control blood flow to organs
what is happening during the p wave on the EKG
atrial systole
how is blood flow related to pressure and resistance? what is this equation called?
blood flow is determined by the pressure change between the entrance and the exit of a vessel, as well as the vessels resistance Q = ΔP / R Ohms law
describe turbulent flow
blood moves chaotically and in many directions more energy is required to move blood through murmurs can be heard when flow is turbulent
what two factors affect mean systemic pressure
blood volume and distribution
1. Compare and contrast cardiac muscle tissue and skeletal muscle tissue.
both appear striated cardiac muscle have one or 2 nuclei, whereas skeletal muscle has many cardiac muscle cells have the ability to contract via their own intrinsic rhythm (automaticity), skeletal muscle must be excited by a motor nerve cardiac cells are attached via intercalated discs gap junctions are in cardiac cells to allow contraction as a single unit, skeletal muscle undergoes recruitment Cardiac muscle Has its own excitability ( SA node , AV node , Bundle of His Skeletal Muscle Excited by motor nerve Cardiac Action potential transmits to the contractile muscle via gap junction Skeletal Acetylcholine binds to muscle membrane and produce an action potential Cardiac Action potential prorogate along T tubules Skeletal Action potential prorogate along T tubules Cardiac AP activates dihydropyridine receptors on T tubules and cause an influx of extracellular Ca+2 into the muscle cell Skeletal AP stimulate dihydropyridine receptors on T tubules and does not cause an influx of extracellular Ca+2 into the muscle cell cardiac Increase intracellular Ca+2 ions activate rynodine receptors and release Ca+2 ions from sarcoplasmic reticulam. Skeletal Activated dihyrdopyrine receptors mechanically stimulate rynodine receptors and release Ca+2 ions from sarcoplasmic reticulam. cardaic Ca+2 binds to troponin C and initiate muscle contraction skeletal Ca+2 binds to troponin C and initiate muscle contraction Each cardiac muscle cell has a single (sometimes two) centrally located nucleus. Like skeletal muscle, cardiac muscle cells are striated (horizontal lines on image on next slide) due to a similar arrangement of contractile proteins. Unique to the cardiac muscle are a branching morphology and the presence of intercalated discs found between muscle fibers. The intercalated discs stain darkly and are oriented at right angles to the muscle fibers. They are often seen as zigzagging bands cutting across the muscle fibers. Gap junctions at intercalated discs help spread the AP They have low resistance In the intercellular spaces, there is supporting tissue with an extensive network of capillaries. ensures adequate delivery of oxygen and nutrients to meet the high metabolic demands of cardiac cells. Mechanism for cardiac muscle contraction similar to that in skeletal muscle Cardiac action potential duration is longer Sarcomere Thin filaments Actin, troponin, tropomyosin Thick filaments Myosin z-line to z-line Where thick and thin filaments overlap = A band Thin filament which shortens during muscle contraction = I band Fewer myofibrils (bundles of sarcomeres) Force per cross sectional area is less Cardiac SR has smaller volume than skeletal SR Cardiac muscle has more mitochondria which make up 25-30% of cell volume t-tubules At each z-line in ventricle and wider than those in skm Fewer in number and narrower in atria (than ventricle) None in Purkinje fibers Macroscopically, cardiac fibers are interwoven where skeletal fibers run in parallel Cardiac cells form overlapping helically arranged sheets
how can pulse pressure be used as an indicator for sv?
by rearranging the compliance equation, we can solve for (stroke) volume compliance = V/P C = ΔV / ΔP V= C x ΔP SV = pulse pressure x compliance
what are the properties of capillaries?
capillaries lie within the tissues. they are a single layer of epithelium. exchange of materials occur in the capillaries - very thin membrane the capillaries have the largest cross sectional area - this is important when considering velocity (slower velocity for nutrient exchange d/t large cross sectional area)
dromotropy
conduction velocity the speed at which the AP excitation moves down the cell
10. Define conduction velocity and how it varies in different parts of the myocardium.
conduction velocity is the speed at which an AP propagates through a region of cardiac tissue AV = slowest (0.01-0.05 m/sec) atria - 0.5-1 m/sec PKJ = quickest 2-4 m/sec
inotropy
contractility
what marks the beginning and end of diastole?
diastole begins when the AV closes and ends when the MV closes
what happens to the total resistance when more vessels are added?
even less total resistance
what are the principles and concepts that describe blood flow wihtin the CV system?
flow, resistance, pressure, capacitance (compliance)
where does isovolumetric relaxation occur on the LV pressure volume loop?
from closure of the AV to opening of the MV
where does isovolumetric contraction occur on the LV pressure volume loop?
from the closure of the MV to the opening of the AV
from where do the PNS fibers arise
from the dorsal motor nucleus of the vagus nerve in the medulla the nucleus ambiguus
what happens at the end of the t wave on the EKG?
here, the MV opens and rapid ventricular filling occurs S3 is heard in very compliant athletes or volume overload reduced ventricular filling follows
what happens to reynolds number in the case of anemia?
in anemia, there is less hct, so viscosity is decreased according to Nr, decreased velocity causes increased turbulence
what does increasing afterload do to the end systolic volume and SV?
increasing afterload increases ESV and decreases SV
what does increasing contractility do to ESV and SV
increasing contractility decreases ESV and increases SV
what does increasing preload do the the EDV? SV?
increasing preload increases both EDV and SV
what parts of the heart does the PNS innervate? what actions does it elicit?
innervates the SA, AV nodes, and the atria only minimal contribution to the ventricle ACh stimulates M2 receptors to slow HR, decrease contractility, decrease conduction velocity
what happens to mean systemic pressure when TPR increases/decreases?
it is not affected venous return and CO decrease when TPR is increased and vice versa RAP not affected
what is the mean systemic pressure
it is the pressure that would be measured throughout the CV system if the heart was stopped the mean systemic pressure is the pressure at which there is no venous return
How does a reduction in the duration of the action potential affect contraction?
less force of contraction d/t less calcium from shorter AP Decreased trigger for CICR
what is happening during the R wave in the QRS
mitral valve closes = S1 ventricular contraction begins aortic valve is not open yet isovolumentric contraction
what happens to distribution of blood when venous compliance decreases?
more volume is moved to the stressed arteries -> increased BV and BP mean systemic pressure increases
describe laminar flow
parabolic flow (U shaped) with the fastest flow velocity towards the center, and the highest degree of shear closest to the vessel wall center has less shear and higher flow
what factors determine conduction velocity
rate of depolarization cell properties diameter of muscle fiber
lusitropy
relaxation
what happens if blood volume increases and the unstressed (veins) are full to capacity?
stressed volume (vol in the arteries) will increase, as well as MAP mean systemic pressure increases
what marks the beginning and end of systole?
systole begins when the MV closes and ends when the AV closes
how does the body produce a negative chronotropic effect in the heart?
the PNS releases ACh, which activates M2 receptors activation of M2 receptors decrease I-f conductance = decreased rate of phase 4 depolarization activation of M2 receptor also increases outward K current = hyperpolarization of the cell = further away from theshold = harder for AP to fire SA node fires less AP per unit time the PNS has no effect on the His PKJ
how does the body produce a negative inotropic effect in the heart?
the PNS releases ACh, which acts on the muscarinic receptors (mostly in atrial mucsle) once activated, calcium conductance during plateau of AP is decreased and outward k is increased (this shortens the duration of the AP and decreases I-Ca) together, there is a decreased amoutn of calcium entering teh atrial cells, decreased trigger, and decreased amount released from the SR
how does the body produce a negative dromotropic effect in the heart?
the PNS releases Ach which acts on the M2 receptors. when acticated, this causes a decrease in the calcium conductance, which is responsible for upstroke decrease calcium conductance decreases dV/dT outward k current is increased the rate at which the atria conduct their AP to the ventricle is decreased and the AP is prolonged AV delay is increased - the AV node conducts less atrial beats
how does the body produce a postive dromotropic effect in the heart?
the SNS releases NE which acts on B1 receptors on the AV node activation causes increased conductance of calcium (which is responsible for upstroke) increased Ca conductance in the AV node causes an increase in the rate of rise of upstroke (dV/dT). this increases the rate at which atria conduct their AP to the ventricle and allows for a more rapid recovery period AV delay is decreased and AV node conducts more atrial beats
how does the body produce a postive inotropic effect in the heart?
the SNS releases NE which acts on beta 1 receptors (ventricles>atria) this increases calcium conductance during the plateau of the AP increased calcium conduction = increased peak tension = increased rate of tension development (dT/dt) beta 1 receptor activation also induces phosphorylation of phospholamban, which controls the Ca ATPase in the SR -> more calcium in stored in the SR and faster relaxation occurs finally, beta 1 receptor activation also decreases teh affinity of TnC for calcium, causing faster relaxation
how is compliance affected in the aging artery? how does this affect pressure and volume?
the aging artery has less compliance. this means that for a given pressure, their arteries will have less volume
where is cross sectional area the smallest in the CV system?
the aorta
what is happening during the NEAR end of the t wave on the ECG?
the aortic valve closes = S2 ventricular relaxation begins the mitral valve is not yet open isovolumetric relaxation
what is happening during the J point on the ECG?
the aortic valve opens at the J point at this time, rapid ejection of blood from the ventricles occurs
5. Identify how varying factors change the cardiac function curve.
the cardiac function curve can be influenced by contractility and afterload (TPR) an increase in contractility or decrease in afterload will cause an upward shift of the curve - decreases RAP and increases CO a decrease in contractility or increase in afterload will cause a downward shift of the curve - increases RAP and decreases CO
4. Understand the relationship described in the cardiac function curve.
the cardiac function curve describes the relationship between blood flow into the heart versus blood flow out of the heart as RAP increases, CO increases (until a point)
what is the magnitude of ion current in the AP based on?
the conductance of the membrane for that particular ion the driving force (determined by the difference of the RMP and the nernest potential for that ion)
what is the law of laplace?
the law of laplace relates tension and pressure of a sphere since tension controls sarcomere length, they are are related to pressure, radius, and wall thickness via law of laplace pressure = (2xwall thickness x tension)/ radius
why do we care where the vascular and cardiac function curves intersect?
the point at where the two curves intersect is the pressure at which they are in equilibrium if the curves intersect at 2 mmHg, then when RAP = 2 mmHg blood going in = blood going out
define blood flow velocity
the rate of movement of blood per time unit cm/sec
what creates resistance to blood flow?
the size of the vessel - diameter and length (smaller and longer create resistance) the viscosity of blood the arrangement of blood vessels - serial versus parallel (parallel = less resistance)
what is conduction velocity
the speed at which an action potential propagates through a region of cardiac tissue
what happens to the total resistance of vessels in parallel if one of the individual resistances increased?
the total resistance would increase but would still be less than the individual resistances
7. Understand how varying factors change the vascular function curve.
the vascular function curve can be affected by blood volume and TPR when blood volume decreases, RAP and venous return decrease when blood volume increases, RAP and venous return increase increased TPR will cause decreased venous return decreased TPR will cause increased venous return
6. Identify the relationship described in the vascular function curve.
the vascular function curve shows the relationship between RAP and venous return - as RAP increases, venous return decreases
how does the compliance differ between arteries and veins? what does this mean for volume and pressure?
the veins have higher compliance, so at a given pressure, the veins will have more volume than the artery
what is the purpose of blood vessels?
to serve as a conduit to and from tissues to regulate blood flow to organs (the arterioles vasoconstriction/relax prn)
what happens to total resistance when vessels are in parallel?
total resistance is less
what are properties of veins?
veins carry blood from the tissues, back to the heart they have high volume and low pressure unstressed able to constrict (venoconstriction) consist of endothelium, smooth msucle, and CT less elastic than arteries able to hold a lot of blood - high capactiance under sympathetic control
what happens to velocity as cross sectional area increases?
velocity decreases
what happens to velocity as flow increases?
velocity increases
how do you calculate compliance? (capacitance)
volume/pressure the volume of blood a vessel can hold at a given pressure
12. Describe the differences in the action potential between atria, ventricle and SA node.
• Action potential in atrium - Has a stable resting potential (-90mv) • Approaches the K+ equilibrium potential • Action potential duration is ~150-200 msec - Rapid Upstroke • Due to inward Na+ current (INa) - Exhibits Phases 0 - 4 • The ionic basis for the action potential in the ventricles, atria, and Purkinje system is relatively the same. • Action potential in ventricle - Has a stable resting potential (-90mv) • Approaches the K+ equilibrium potential • Action potential duration of ~250 msec - Rapid Upstroke • Due to inward Na+ current (INa) - Exhibits Phases 0 - 4 • Action potential in SA Node - Has an unstable resting potential • Action potential duration of ~150 msec • Phase 4 spontaneous depolarization - Creates automaticity - Rapid upstroke • INa does not cause Phase 0 - here, it's ICa - Exhibits Phases 0, 3, and 4
11. Describe the phases of the action potential.
• Phase 0 - Upstroke (depolarization) - Makes the membrane potential LESS NEGATIVE • Phase 1 - Initial repolarization • Phase 2 - Plateau - In and out currents are EQUAL, hence the straight line (Plateau) • Phase 3 - Repolarization - Makes the membrane potential MORE NEGATIVE • Phase 4 - Electrical diastole (resting potential)