Cardiovascular Flashcards
Mention the layers of the heart from inner to outer layer
Endocardium
Myocardium
Visceral layer of serous pericardium
Pericardial cavity
Parietal layer of serous pericardium
Fibrous pericardium
Endocardium
1) Endothelium -> simple squamous epithelial tissue with areolar connective tissue
2) Functions
o Prevents blood in heart from clotting -> releases PGI2 and NO which inhibits platelet activation and aggregation.
o Act as a barrier between blood and tissue.
o Makes tight junctions which controls movement between cells.
o Continues as endothelium in blood vessels
o Lines the outer layer of the valves in the heart
Myocardium
1) Cardiac muscle tissues:
a. Contractile Cardiac Muscle
b. Non-Contractile Cardiac Muscle
o SA node -> nodal, auto-rhythmic cells, that can generate AP and set sinus rhythm
o AV node
o Bundle of His
o Bundle branches (right and left)
o Purkinje fibers
2) Functions:
a. Non-Contractile cardiac muscle -> generates and conducts action potentials.
b. Contractile cardiac muscle -> contracts as a unit to pump blood through and out of the heart.
Visceral layer of serous pericardium
o Also called epicardium
o Mesothelium: simple squamous with loose areolar connective tissue
o Secretes pericardial serous fluid into the cavity to lubricate tissue layers.
Pericardial cavity
o Contains serous fluid - usually has no blood under normal physiologic conditions.
o Prevents friction from two serous layers rubbing against each other.
Parietal layer of the serous pericardium
o Continuous with the epicardium
o Mesothelium: simple squamous + loose areolar connective tissue
o Secretes pericardial serous fluid into the cavity to lubricate tissue layers.
Fibrous pericardium
Tissue -> dense fibrous irregular connective tissue
Function:
o Anchors heart to surrounding structures
o Prevents heart from overfilling with blood because it’s not a distensible or “stretchy” tissue
o Protects the heart because it is a tough tissue
From where does the RA receives blood?
Received deoxygenated blood from three vessels:
o Cranial Vena Cava -> brings blood from structures above the diaphragm (head and neck and forelimbs)
o Caudal Vena Cava -> brings blood from structures below the diaphragm (abdomen, liver, hindlimb)
o Coronary Sinus -> brings blood from coronary circulation
From where does the LA receives blood?
Receives oxygenated blood from 4 pulmonary veins
o Two left pulmonary veins from the left lung
o Two right pulmonary veins from the right lung
Auricles
1) Left Auricle or left atrial appendage -> increases space and volume of right atrium. Thrombi very commonly forms here in heart disease (especially cats)
2) Right auricle or right atrial appendage -> increases space and volume of right atrium. Thrombi formation happens but not as common.
Heart valves / chordae tendineae / papillary muscle structure
1) Valve structure -> they are four annulus rings of fibrous tissue, and leaflets tissue hang from these annulus rings.
2) Chordae tendineae
o Anchors the leaflets to papillary muscles
o Collagen cords of connective tissue
o Attached to the cusps of the valves
o Keeps valve tight to prevent them from ballooning back into the atrium and causing blood backflow
3) Papillary muscles
o Projections of the myocardium
o Anchors the chordae tendineae
o If ischemic, muscles weaken -> unable to contract -> valve flaps loosen -> valve regurgitation
Atrioventricular valves
Between atria and ventricles -> prevents backflow of blood from ventricles into atria.
1) Tricuspid Valve -> between RA and RV. Contains three leaflets
2) Bicuspid or Mitral Valve -> between LA and LV. Contains two leaflets
Semilunar valves
o Have three crescent shaped cusps
o Between ventricles and pulmonary trunk and aorta
o Pulmonary trunk splits into the left and right pulmonary arteries
o Aorta -> Ascending aorta -> aortic arch -> descending aorta
1) Pulmonary Semilunar valve -> between RV and Pulmonary trunk
2) Aortic Semilunar Valve -> between LV and Ascending Aorta.
o Two coronary arteries arise from the aorta just beyond the semilunar valves;
o During diastole, the increased aortic pressure above the valve’s forces blood into the coronary arteries and thence into the musculature of the heart.
T/F The atrial and ventricular types of muscle contract in much the same way as skeletal muscle, except that the duration of contraction is much longer
TRUE
4 pacemakers in the heart?
SA node
AV node
Bundle of His
Purkinje fibers
The body decides who is the pacemaker is whoever is faster:
The SA node is normally 70-80 bpm
AV node 40-60bpm
Bundle of His about 40bpm
Purkinje fibers 15bpm
Therefore normally, the SA node is the one who dictates the HR and purkinje fibers is as a last resource in case the other pacemakers do not work.
What is the purpose of the gap junctions within the intercalated discs?
o Cardiac muscle is striated, similar to skeletal muscle but with some differences
o Cardiac muscle is a syncytium -> the muscle fibers are separated by intercalated discs (cell membranes that separate individual cardiac muscle cells)
o At each intercalated disc, the cell membrane fuse with one another to form permeable “communicating” junctions called “gap junctions”
o Gap junctions allow rapid diffusion of ions -> action potential travels rapidly.
How many syncytium is the heart composed off?
Two: atrial (walls of the 2 atria) and ventricular (walls of the 2 ventricles) syncytium.
T/F - The action potential recorded in a ventricular muscle fiber averages about 105mV, which means that the intracellular potential rises from a very negative value, about −85mV, between beats to a slightly positive value, about +20mV during each beat
TRUE
For how long the membrane rests depolarized?
0.1-0.2sec or 100-200milisec
That creates a plateau, typical of ventricular muscle cell action potential
What are the consequences of the plateau in ventricular action potentials?
Causes ventricular contraction to last as much as 15 times more compared to skeletal muscle
What are the major differences between cardiac and skeletal muscle that account for the differences in action potential?
o Action potential of skeletal muscle is caused almost entirely by the sudden opening of fast Na channels. They are called fast because they remain open for only a few thousands of a second and then they close.
o In cardiac muscle, the action potential is due to the opening of TWO type of channels:
* Same fast Na channels as in skeletal muscle
* L-type Ca channels (also called calcium-Na channels)
o The L-type Ca channels differs from the fast sodium channels in that they are slower to open (that is why there is a brief depolarization when K starts going out as Ca channels are slow to open) and, even more important, remain open for several tenths of a second.
o During this time, a large quantity of both calcium and sodium ions flows through these channels to the interior of the cardiac muscle fiber, and this activity maintains a prolonged period of depolarization, causing the plateau in the action potential
o The second major difference -> immediately after the onset of the action potential, the permeability of the cardiac muscle membrane for potassium ions decreases about fivefold, an effect that does not occur in skeletal muscle.
o The decreased potassium permeability greatly decreases the outflux of positively charged potassium ions during the action potential plateau and thereby prevents early return of the action potential voltage to its resting level - again, helps maintain the plateau phase.
What happens when the L-type Ca channels close?
o They close at the end of 0.2 to 0.3 second
o The influx of calcium and sodium ions ceases -> the membrane permeability for potassium ions also increases rapidly.
o This rapid loss of potassium from the fiber immediately returns the membrane potential to its resting level, thus ending the action potential.
Summary of phases of ventricular action potential
o Phase 0 (depolarization), fast sodium channels open. When the cardiac cell is stimulated and depolarizes, the membrane potential becomes more positive. Voltage-gated Na channels (fast Na channels) open and permit Na to rapidly flow into the cell and depolarize it. The membrane potential reaches about +20 millivolts before the Na channels close.
o Phase 1 (initial repolarization), fast Na channels close. The Na channels close, the cell begins to repolarize, and K ions leave the cell through open K channels.
o Phase 2 (plateau), Ca channels open and fast K channels close. A brief initial repolarization occurs and the action potential then plateaus as a result of increased Ca permeability and decreased K permeability. The voltage-gated Ca channels open slowly during phases 1 and 0, and Ca enters the cell. Potassium channels then close, and the combination of decreased K efflux and increased Ca influx causes the action potential to plateau.
o Phase 3 (rapid repolarization), Ca channels close and slow K channels open. The closure of Ca channels and increased K permeability, permitting K to rapidly exit the cell, ends the plateau and returns the cell membrane potential to its resting level.
o Phase 4 (resting membrane potential) averages about −90 millivolts.
What does it means “excitation-contraction coupling”?
o Refers to the mechanism by which the action potential causes the myofibrils of muscle to contract.
What is the sarcolemma
True cell membrane surrounding each muscle fiber
Each muscle fiber contains hundreds to thousands of muscle myofibrils
What is the sarcoplasm
The spaces between the myofibrils are filled with intracellular fluid called sarcoplasm
It contains larges amounts of K, Mg and Ph and a lot of mitochondria that supply with energy for the contraction.
Differences between cardiac / skeletal “excitation-contraction coupling”
o Same as for skeletal muscle, when an action potential reaches the cardiac muscle membrane, it spreads to the interior of the cardiac muscle fiber along the membranes of the transverse (T) tubules.
o The T tubule action potentials in turn act on the membranes of the longitudinal sarcoplasmic tubules to cause release of calcium ions into the muscle sarcoplasm from the sarcoplasmic reticulum.
o The calcium will promote sliding of the actin and myosin filaments along one another, which produces the muscle contraction.
o In the cardiac muscle, addition to the calcium ions that are released into the sarcoplasm from the cisternae of the sarcoplasmic reticulum, calcium ions also diffuse into the sarcoplasm from the T tubules themselves at the time of the action potential, which opens voltage-dependent calcium channels in the membrane of the T tubule.
o Ca entering the cell then activates Ca release channels (ryanodine receptor channels), in the sarcoplasmic reticulum membrane, triggering the release of Ca into the sarcoplasm. Calcium ions in the sarcoplasm then interact with troponin to initiate cross-bridge formation and contraction.
o Without the calcium from the T tubules, the strength of cardiac muscle contraction would be reduced considerably because the sarcoplasmic reticulum of cardiac muscle is less well developed than that of skeletal muscle and does not store enough calcium to provide full contraction.
When Ca2+ enters the cardiac muscle cell, what is the name of the receptors they activate to produce more release of Ca2+ from the sarcoplasmic reticulum?
Ryanodine receptor channel
Once relaxation occurs, how does Ca2+ gets out of the cell? How is the electrical gradient maintained?
Via the NCX anti porter (3Na in, 2Ca out)
Via the Na/K ATPase
T/F - The strength of skeletal muscle contraction is hardly affected by moderate changes in extracellular fluid Ca2+ concentration because skeletal muscle contraction is caused almost entirely by Ca2+ released from the sarcoplasmic reticulum inside the skeletal muscle fiber.
TRUE
How much is the delay in conduction to pass the impulse from the atrium to the ventricles?
0.1 sec
This delay is important to allow the atria contract ahead of the ventricles, therefore pumping blood into them.
What is the cardiac cycle?
Events that occur from the beginning of one heartbeat to the beginning of the next one.
T/F - Increasing HR decreases the duration of the cardiac cycle
TRUE
Which phase of the cardiac cycle is greatly reduced when HR increases? Why is that important?
o The duration of the action potential and the systole decreases, but not by as great a percentage as does the diastole.
o Because the heart beating at a very fast rate does not remain relaxed long enough to allow complete filling of the cardiac chambers before the next contraction.
How much % of blood flows into the ventricles before the atria contract?
80%
How much % of blood the contraction of the atria adds to the ventricular filling?
20%
T/F - The atria function as primer pumps that increase the ventricular pumping effectiveness as much as 20 percent. However, the heart can continue to operate under most conditions even without this extra 20 percent.
TRUE - when the atria fail to function, the difference is unlikely to be noticed unless a person exercises.
What is the “a wave”
Is caused by atrial contraction. The right atrial pressure increases 4 to 6 mm Hg during atrial contraction, and the left atrial pressure increases about 7 to 8 mm Hg.
What is the “c wave”
Occurs when the ventricles begin to contract; it is caused partly by slight back flow of blood into the atria at the onset of ventricular contraction but mainly by bulging of the A-V valves backward toward the atria because of increasing pressure in the ventricles.
What is the “v wave”
Occurs toward the end of ventricular contraction; it results from slow flow of blood into the atria from the veins while the A-V valves are closed during ven- tricular contraction. Then, when ventricular contraction is over, the A-V valves open, allowing this stored atrial blood to flow rapidly into the ventricles and causing the v wave to disappear.
What is the rapid filling of the ventricles?
As soon as systole is over and the ventricular pressures fall to their low diastolic values, the moderately increased pressures that have developed in the atria during ventricular systole immediately push the A-V valves open and allow blood to flow rapidly into the ventricles.
How long does it last the rapid filling?
1/3 of the diastole
Isovolumetric contraction
o Immediately after ventricular contraction begins, the ventricular pressure rises abruptly causing the A-V valves to close.
o Then an additional 0.02 to 0.03 second is required for the ventricle to build up sufficient pressure to push the aortic and pulmonary valves open against the pressures in the aorta and pulmonary artery.
o Therefore, during this period, contraction is occurring in the ventricles, but no emptying occurs. Cardiac muscle tension is increasing but little or no shortening of the muscle fibers is occurring.
Ejection period
When the LV pressure rises slightly above 80 mm Hg (and the RV pressure rises slightly above 8 mm Hg), the ventricular pressures push the semilunar valves open. Immediately, blood begins to pour out of the ventricles.
How much is the % of blood from the end of diastole that is ejected during systole?
60%
Difference between rapid and slow ejection?
o 70% of the blood ejected by the ventricles flows out during the first third of the ejection period -> rapid ejection period.
o Remaining 30% empties during the next 2/3 of systole -> slow ejection period.
Isovolumetric relaxation
o At the end of systole, ventricular relaxation begins suddenly, allowing both the right and left intraventricular pressures to decrease rapidly.
o The elevated pressures in the distended large arteries that have just been filled with blood from the contracted ventricles immediately push blood back toward the ventricles, which snaps the aortic and pulmonary valves closed.
o For another 0.03 to 0.06 second, the ventricular muscle continues to relax, even though the ventricular volume does not change as the AV valves are still closed -> period of isovolumic or isometric relaxation.
o During this period, the intraventricular pressures rapidly decrease back to their low diastolic levels. Then the A-V valves open to begin a new cycle of ventricular pumping.
End-diastolic volume
o During diastole, normal filling of the ventricles increases the volume of each ventricle to about 110 to 120mL.
o This volume is called the end- diastolic volume.
Stroke volume
o As the ventricles empty during systole, the volume decreases about 70mL, which is called the stroke volume output.
End systolic volume
o The remaining volume in each ventricle after systole, about 40 to 50mL
Ejection fraction
The fraction of the end-diastolic volume that is ejected — usually equal to about 0.6 (or 60 percent).
T/F - When the heart contracts strongly, the end-systolic volume may decrease to as little as 10 to 20mL
TRUE
T/F - When large amounts of blood flow into the ventricles during diastole, the ventricular end-diastolic volumes can become as great as 150 to 180mL in the healthy heart.
TRUE
T/F - Both increasing the end-diastolic volume and decreasing the end-systolic volume, the stroke volume output can be increased to more than double that which is normal.
TRUE
T/F - The heart valves open actively when blood flow is needed
FALSE - They close and open passively. They close when a backward pressure gradient pushes blood backward, and they open when a forward pressure gradient forces blood in the forward direction.
T/F - The A-V valves require almost no backflow to cause closure, whereas the much heavier semilunar valves require rather rapid backflow for a few milliseconds.
TRUE
T/F - The papillary muscles relax when the ventricles contract
FALSE - They contract when the ventricular walls contract.
T/F - The papillary muscles help close the valves
FALSE - they pull the valves inward toward the ventricles to prevent their bulging too far backward toward the atria during ventricular contraction.
Differences of semilunar valves and AV valves
o High pressures in the arteries at the end of systole cause the semilunar valves to snap closed, in contrast to the much softer closure of the A-V valves.
o Because of smaller openings, the velocity of blood ejection through the aortic and pulmonary valves is far greater than that through the much larger A-V valves.
o Because of the rapid closure and rapid ejection, the edges of the aortic and pulmonary valves are subjected to much greater mechanical abrasion than are the A-V valves.
o The A-V valves are supported by the chordae tendineae, which is not true for the semilunar valves.
T/F - The entry of blood into the arteries during left ventricular systole causes the walls of these arteries to stretch and the pressure to increase to about 120 mm Hg.
TRUE
What is the incisura
o An incisura occurs in the aortic pressure curve when the aortic valve closes.
o This is caused by a short period of backward flow of blood immediately before closure of the valve, followed by sudden cessation of the back flow.
Diastolic aortic pressure
Around 80mmHg
First heart sound
Close of AV valves
Second heart sound
Close of semilunar valves
Above which left ventricular volume the diastolic pressure starts increasing rapidly?
150mL
Partly because of fibrous tissue in the heart that will stretch no more and partly because the pericardium that surrounds the heart becomes filled nearly to its limit.
At what volume the left ventricle has his maximal systolic pressure?
150-170mL
o As the volume increases further, the systolic pressure actually decreases, because at these great volumes, the actin and myosin filaments of the cardiac muscle fibers are pulled apart far enough that the strength of each cardiac fiber contraction decreases.
LV volume / intraventricular pressure graph - draw and explain
Maximum systolic pressure for left ventricle
250-300mmHg
Maximum systolic pressure for right ventricle
60-80mmHg
Draw and explain the volume-pressure diagram
Cardiac preload
Usually considered to be the end-diastolic pressure when the ventricle has become filled.
Cardiac afterload
o The pressure in the aorta leading from the ventricle.
o Sometimes the afterload is loosely considered to be the resistance in the circulation rather than the pressure.
Why is the rate of oxygen consumption by the heart an excellent measure of the chemical energy liberated while the heart performs its work?
Because approximately 70 to 90 percent of this energy is normally derived from oxidative metabolism of fatty acids, with about 10 to 30 percent coming from other nutrients, especially lactate and glucose.
Which mechanism are used to control how much volume of blood to pump?
1) Intrinsic cardiac regulation of pumping in response to changes in volume of blood flowing into the heart - Frank Starling mechanism and increased stretch of RA.
2) Control of HR and contractility by the ANS
Venous return
Amount of blood that flows into the heart from the veins
T/F Each peripheral tissue of the body controls its own local blood flow, and all the local tissue flows combine and return by way of the veins to the right atrium.
TRUE
How is it called the heart’s intrinsic ability to adapt to increasing volumes of inflowing blood?
Frank-Starling mechanism of the heart.
What does the Frank-Starling mechanism means
That the greater the heart muscle is stretched during filling, the greater is the force of contraction and the greater the quantity of blood pumped into the aorta.
Explain the Frank-Starling mechanism and the RA stretch.
o When an extra amount of blood flows into the ventricles, the cardiac muscle is stretched to a greater length.
o This stretching in turn causes the muscle to contract with increased force because the actin and myosin filaments are brought to a more nearly optimal degree of overlap for force generation.
o Therefore, the ventricle, because of its increased pumping, automatically pumps the extra blood into the arteries.
o This ability of stretched muscle, up to an optimal length, to contract with increased work output is characteristic of all striated muscle, not only the cardiac muscle.
o Stretch of the right atrial wall directly increases the heart rate by 10 to 20 percent, which also helps increase the CO, although its contribution is much less than that of the Frank-Starling mechanism.
Right and left ventricular volume output curves - draw and explain
Describe the control of the heart by the sympathetic system
o The pumping effectiveness of the heart also is controlled by the sympathetic and parasympathetic (vagus) nerves.
o Sympathetic nerves -> can increase the heart rate from the normal rate of 70bpm up to 180 to 200 and, rarely, 250bpm.
o Sympathetic stimulation increases the force of heart contraction to as much as double the normal rate -> increases the volume of blood pumped and increases the ejection pressure.
o Sympathetic stimulation often can increase the maximum cardiac output as much as twofold to threefold, in addition to the increased output caused by the Frank-Starling mechanism.
o Inhibition of the sympathetic nerves to the heart can decrease cardiac pumping to a moderate extent. Under normal conditions, the sympathetic nerve fibers to the heart discharge continuously at a slow rate that maintains pumping at about 30 percent above that with no sympathetic stimulation.
o When the activity of the sympathetic nervous system is depressed below normal, both the heart rate and strength of ventricular muscle contraction decrease, decreasing the level of cardiac pumping as much as 30 percent below normal
Describe the control of the heart by the parasympathetic system
o Strong stimulation of the parasympathetic nerve fibers in the vagus nerves to the heart can stop the heartbeat for a few seconds, but then the heart usually “escapes” and beats at a rate of 20 to 40 beats/min as long as the parasympathetic stimulation continues.
o In addition, strong vagal stimulation can decrease the strength of heart muscle contraction by 20 to 30 percent.
o The vagal fibers are distributed mainly to the atria and not much to the ventricles, where the power contraction of the heart occurs -> the effect of vagal stimulation is mainly to decrease the heart rate rather than to decrease the strength of contractility.
o However, the great decrease in heart rate combined with a slight decrease in contractility can decrease ventricular pumping 50% or more.
Effect of sympathetic and parasympathetics stimulation on the cardiac function curve - draw and explain
o The ventricular function curves here represent the function of the entire heart rather than of a single ventricle.
o It shows the relation between right atrial pressure at the input of the right heart and cardiac output from the left ventricle into the aorta.
o At any given right atrial pressure, the cardiac output increases during increased sympathetic stimulation and decreases during increased parasympathetic stimulation.
Effects of excess K in the extracellular fluid on the heart
o Heart becomes dilated and flaccid and slows heart rate down.
o Large quantities of potassium can block conduction of the cardiac impulse from the atria to the ventricles through the A-V bundle.
o Elevation of K to only 8 to 12 mEq/L can cause severe weakness of the heart, abnormal rhythm, and death.
o High extracellular fluid potassium concentration partially depolarizes the cell membrane, causing the membrane potential to be less negative.
o As the membrane potential decreases, the intensity of the action potential also decreases, which makes contraction of the heart progressively weaker.
Effects of excess Ca in the extracellular fluid on the heart
o Excess calcium ions cause effects almost exactly opposite to those of potassium ions, causing the heart to move toward spastic contraction.
o This effect is caused by a direct effect of calcium ions to initiate the cardiac contractile process.
o Deficiency of calcium ions causes cardiac weakness, similar to the effect of high potassium.
o Calcium ion levels in the blood normally are regulated within a very narrow range.
Effect of temperature on heart function
o Increased body temperature (like fever,) greatly increases the heart rate, sometimes to double the normal rate.
o Decreased temperature greatly decreases heart rate, which may fall to as low as a few beats per minute when a person is near death from hypothermia in the body temperature range of 60° to 70°F.
o These effects presumably result from the fact that heat increases the permeability of the cardiac muscle membrane to ions that control heart rate, resulting in acceleration of the self-excitation process.
o Contractile strength of the heart often is enhanced temporarily by a moderate increase in temperature, such as that which occurs during body exercise, but prolonged elevation of temperature exhausts the metabolic systems of the heart and eventually causes weakness.
o Optimal function of the heart depends greatly on proper control of body temperature.
Sinus node
o Small, flattened, ellipsoid strip of specialized cardiac muscle localized on the right atrium.
o The fibers of this node have almost no contractile muscle filaments
o The sinus nodal fibers connect directly with the atrial muscle fibers so that any action potential that begins in the sinus node spreads immediately into the atrial muscle wall.
What is the automaticity of the heart?
o Some cardiac fibers have the capability of self-excitation -> can cause automatic rhythmical discharge and contraction.
o This capability is especially true of the fibers of the heart’s specialized conducting system, including the fibers of the sinus node.
o The sinus node ordinarily controls the rate of beat of the entire heart.
Resting membrane potential of sinus nodal fiber and ventricular fibers
o Sinus nodal fiber between discharges has a negativity of about −55 to −60mV
o Ventricular fibers at −85 to −90mV
o The reason is that the cell membranes of the sinus fibers are naturally leaky to Na and Ca (leak IN), and positive charges of the entering Na and Ca neutralize some of the intracellular negativity.
Differences between ventricular and SA action potentials
o At -55mV (SA node), fast Na channels are probably inactivated -> any time the membrane potential remains less negative than about −55 millivolts for more than a few milliseconds, the inactivation gates on the inside of the cell membrane close the fast Na channels and remain so.
o Only the slow Ca channels can open and cause the action potential.
o As a result, the atrial nodal action potential is slower to develop than the action potential of the ventricular muscle.
o After the action potential does occur, return of the potential to its negative state occurs slowly as well, rather than the abrupt return that occurs for the ventricular fiber.
Explain how the nodal fibers are self-excitable
o Because of the high Na concentration in the extracellular fluid outside the nodal fiber, as well as a moderate number of already open sodium channels, positive sodium ions from outside the fibers normally tend to leak to the inside.
o Therefore, between heartbeats, influx of positively charged sodium ions causes a slow rise in the resting membrane potential in the positive direction.
o The resting potential gradually rises and becomes less negative between each two heartbeats.
o When the potential reaches a threshold voltage of about −40mV, the L-type calcium channels become activated, thus causing the action potential.
o Therefore, the inherent leakiness of the sinus nodal fibers to sodium and calcium ions causes their self-excitation.
How are those fibers not depolarized constantly if they have Na and Ca leaky channels?
o Two events occur to prevent such a constant state of depolarization.
1) The L-type Ca channels close within about 100 to 150msec after opening.
2) At about the same time, greatly increased numbers of potassium channels open.
o Both of these effects reduce the intracellular potential back to its negative resting level and therefore terminate the action potential.
Hyperpolarization of SA node fibers
o The potassium channels remain open for another few tenths of a second, temporarily continuing movement of positive charges out of the cell.
o That results in excess negativity inside the fiber -> hyperpolarization.
o The hyperpolarization state is what carries the resting membrane potential down to about −55 to −60mV at the termination of the action potential.
Vasomotor tone effectors
Overview of cardiovascular neurohormonal control
Vasomotor center - medulla oblongata I
Baroreceptors
T/F - When there is hypertension, the nucleus tracts solitarius will stimulate the SNS and inhibit the PNS
FALSE - it will inhibit the SNS causing vasodilation and stimulate the PNS causing bradycardia
T/F During hypotensive states, the NTS it is unable to inhibit the SNS therefore there is vasoconstriction and unable to stimulate PNS therefore tachycardia is seen
TRUE
Autonomic nervous system general organization
ANS and cardiac myocytes
ANS and blood vessels - I
ANS and vasculature - II
o The endothelium communicates with the vascular smooth muscle.
Parasympathetic NS receptors
Heart muscarinic receptors
Main function of muscarinic 2 receptors
Inhibition
o Stimulation of M2 receptors leads to inability of the Gs protein to stimulate adenylate cyclase to produce cAMP
T/F - Ach binding to M2 vascular receptors will increase NO, producing vasodilation.
TRUE
Primary effect on VENOUS vascular tone, does not regulate arterial BP.
T/F - NE is a catecholamine derived from the amino acid tyrosine
TRUE
T/F - NE is synthesized within the nerve axon and stored within vesicles
TRUE
What is the rate limiting step in the production of NE?
The conversion of tyrosine to DOPA via the enzyme tyrosine hydroxylase
NE from never terminals vs NE from adrenal glands
Where can adrenergic receptors be located?
o Presynaptic - like the alpha2 that modulate the release of NE
o Postsynaptic - on effector organs
Postsynaptic adrenergic receptors
o Junctional - immediately associated with a sympathetic nerve (nerve -> tissue)
o Non-junctional - not directly associated with a nerve - mainly affected by circulating E/NE
T/F - Adrenergic receptor - 2 identical receptors can have entirely different effects depending on what tissue they are located on, even if G protein is the same
TRUE
Effects of different pressors
Norepinephrine and alpha receptors
Alpha 1 and alpha 2 adrenoreceptors
Presynaptic alpha 2 receptors
T/F - Postsynaptic alpha 1 receptors are inhibited by phenoxybenzamine and prazosin
TRUE
T/F - Presynaptic alpha 2 receptors are ________ (stimulated/inhibited) by dexmedetomidine and _______ (stimulated/inhibited) by yohimbine / antisedan
Stimulated
Inhibited
Non-alpha adrenergic receptors coupled to a Gq protein
B adrenoreceptors
B adrenoreceptors location
B1 and Gs protein
Other stimulants of cAMP in the heart
Other stimulants of cAMP
Why glucagon can be used in B blocker overdose?
Because all B receptors will be blocked, and glucagon can have the same effects -> increase cAMP -> increase HR and contractility, independent of the B receptors
T/F - B receptors in heart and in smooth muscle both use Gs protein but have opposite effects B1 and B2 -> B1 in heart will cause contraction, B2 in vascular smooth muscle, vasodilation
TRUE
Vascular smooth muscle B-adrenoreceptors
Adrenergic receptor comparison
Vasculature G protein pathways and drugs
What do kinase enzymes do?
Add a phosphorus - phosphorylates
What do phosphates enzymes do?
Remove phosphate group from its substrate - dephosphorylation -> opposite of kinases. Usually inactivates.
Clinically relevant 2nd messengers
GCRP subfamilies
GCRP - cyclase
GPCR - Phosphodiesterases
GPCS - kinases
T/F - cAMP is important in the heart because it will not only activate pkA and release intracellular calcium, but it will also act on the L-tye voltage calcium channels allowing more Ca to come in
TRUE
Gi pathway
Gq pathway
Cardiac G protein 2nd messengers
How does myocyte B1 stimulation and increased cAMP will increase HR?
o It will increase the rate of depolarization increasing the If (funny current)
o Opening of L-type voltage gated Ca channels - lower threshold potential
How does acetylcholine, Gi and decreased cAMP causes decrease in HR?
o Decreases in If (funny current) -> decreased rate of depolarization
o Inhibition of L-type voltage gated Ca channels -> increases threshold
o Activation of GIRKach (K channels) -> membrane hyperpolarization
Effects of ANS on AV node action potential
T/F - Gq can contribute to myocardial hyperthrophy
TRUE
T/F - Vascular tone -> we will have vasoconstriction any time the Gq protein is stimulated
TRUE
E/NE -> alpha 1 receptors
Vasopressin -> V1 receptors
Ach -> M3 -> if it binds M2 on the endothelial effects -> release of NO, vasodilation
AgII -> AT1
ET1 (endothelin 1) -> ETA
T/F - Vascular tone - with Gs protein we will have vasodilation
TRUE
Vasculature smooth muscle contraction and relaxation -> actions of pkA
Via myosin light chain kinase, MLCK (phosphorylation of myosin -> vasocontration) and myosin phosphatase, MMP (dephosphorylation of myosin -> vasodilation).
T/F - Smooth muscle contraction is myosin regulated
TRUE
Once myosin is phosphorylated it allows a good positioning of acting and myosin.
T/F - Cardiac muscle is actin regulated
TRUE
Change in conformation in the troponin complex and contraction can occur
TN-C -> calcium binding site -> regulates contraction
TN-I -> inhibits active site on actin
TN-T -> tropomyosin binding protein
G protein mediated smooth muscle contraction
G protein mediated smooth muscle relaxation
Phosphodiesterases overview
Phosphodiesterase inhibitors
Methylated xantines
o Non-selective PDEI
o- Chocolate components (theobromine), theophylline - spread effects throughout the body - increased cAMP generalized - increased HR and BP
Pimobendan effects
o Calcium sensitizer -> troponin regulatory complex does a better job binding Ca -> increase contractility w/o increasing intracellular calcium.
o Vascular smooth muscle vasodilator -> via PDEI3, increased cAMP
NO overview
Types of NO
NO mediated vasodilation - I
NO mediated vasodilation II
sGC - soluble guanyl cyclase
NO in disease states
Types of muscle fibers
o Thick filament regulated - myosin
o Thin filament regulated - troponin complex on actin
Name of the pump that puts Ca back in the sarcoplasmic reticulum so muscles can relax
SERCA2
Inhibited by phospholamban -> more Ca in cytosol
If phospholamban is inactivated -> more Ca pumped in the SR -> B adrenergic stimulation is one of the ways with increased relaxation
Because in the next cycle there will be more Ca in the SR, more Ca will be released -> increase force of contraction
This is how there is both increased lusitropy and inotropy
Pumps involved in cardiac cycle
What is Bachmann’s bundle
o A branch of the internodal tract
o From the right atrium directed towards the left atrium
Distribution of blood flow in different parts of the circulatory system
Basic principles of circulatory function
o Blood flow to most tissues is controlled according to the tissue need. When a particular tissue demands increased flow -> the microvessels of each tissue continuously monitor tissue needs, and in turn act directly on the local blood vessels, dilating or constricting them, to control local blood flow.
o Cardiac output is the sum of all local tissue flows
o Arterial pressure regulation is generally independent of either local blood flow control or cardiac output control.
Blood flow through a vessel is determined by?
o Pressure difference of the blood between the 2 ends of the vessel (pressure gradient)
o Vascular resistance - as a result of the friction between the flowing blood and the intravascular endothelium
o Can be calculated using Ohm’s law:
F = P1-P2 / R
Be also familiar with
o R = P1-P2 / F
o P1-P2 = F x R
What is laminar flow and its consequences
o When blood flows at a steady rate through a long, smooth blood vessel, it flows in streamlines, with each layer of blood remaining the same distance from the vessel wall.
o When laminar flow occurs, the velocity of flow in the center of the vessel is far greater than that toward the outer edges.
o The fluid in the middle of the vessel can move rapidly because many layers of slipping molecules exist between the middle of the vessel and the vessel wall; thus, each layer toward the center flows progressively more rapidly than the outer layers.
When does turbulent flow develops
o When the rate of blood flow becomes too great, when it passes by an obstruction in a vessel, when it makes a sharp turn, or when it passes over a rough surface.
o The blood flows crosswise in the vessel and along the vessel, usually forming whorls in the blood, called eddy currents.
o The blood flows with much greater resistance -> eddies add tremendously to the overall friction of flow in the vessel.
What does the Reynold’s number tell us
o The measure of the tendency for turbulence to occur
o Proportional to velocity of blood flow (v, in cm/sec), diameter (d, in cm) of blood vessel and density of blood
o Inversely proportional to viscosity of blood (in poise).
o If it is > 2000 -> turbulence will happen in a straight, smooth vessel
o Normally between 200-400 -> turbulent flow will occur at some branches but die pretty quick.
Conversion mmHg to cmH2O
1mmHg = 1.36cm H2O
Conductance of a vessel?
Inverse of resistance
C = 1/R
Poiseuille’s law
o F is the rate of blood flow.
o ΔP is the pressure difference between the ends of the vessel.
o r is the radius of the vessel.
o l is length of the vessel.
o η is viscosity of the blood.
o The rate of blood flow is directly proportional to the fourth power of the radius of the vessel.
Factors that will affect blood viscosity, therefore blood flow?
Hematocrit and plasma proteins
What is blood flow autoregulation?
The ability of each tissue to adjust its vascular resistance and to maintain normal blood flow during changes in arterial pressure between approximately 70 and 175 mmHg
T/F - The veins are much more distensible than the arteries.
TRUE - the veins, on average are about eight times more distensible than the arteries.
Vascular compliance
o The total quantity of blood that can be stored in a given portion of the circulation for each mm Hg pressure rise
o Vascular compliance = increase in V / increase in P
Main factors affecting pulse pressure?
o Stroke volume
o Compliance of the arterial tree
Pulse pressure = stroke volume / arterial compliance
Abnormal pressure pulse contours - draw and explain
Why is no incisura in the aortic pulse contour with aortic regurgitation?
Because there is no aortic valve to close
T/F Pressure pulses are damped in the smaller arteries, arterioles and capillaries
TRUE
o The cause of this damping is for 2 reasons:
1) Resistance to blood movement in the vessels. the greater the resistance, the more difficult the flow.
2) Compliance of the vessels -> the more compliant a vessel, the greater the quantity of blood required at the pulse wave front to cause an increase in pressure.
o The degree of damping is almost directly proportional to the product of resistance times compliance.
What are the Korotkoff sounds?
o Caused mainly by blood jetting through the partly occluded vessel (when measuring a BP) and by vibrations of the vessel wall.
o The jet causes turbulence in the vessel beyond the cuff, and this turbulence sets up the vibrations heard through the stethoscope.
T/F - MAP - it is not equal to the average of systolic and diastolic pressure because at normal heart rates, a greater fraction of the cardiac cycle is spent in diastole than is systole
TRUE
What is the central venous pressure?
Pressure in the RA
What determines movement through the capillary membrane?
Starling forces:
Capillary and interstitial hydrostatic pressure
Capillary and interstitial oncotic presure
What is vasomotion?
o Intermittent contraction of the metarterioles and precapillary sphincters
o Blood usually does not flow continuously through the capillaries. Instead, it flows intermittently, turning on and off every few seconds or minutes due to vasomotion
How is vasomotion regulated?
o The most important factor affecting the degree of opening and closing of the metarterioles and precapillary sphincters is the concentration of oxygen in the tissues.
o When the rate of oxygen usage by the tissue is great so that tissue oxygen concentration decreases below normal, the intermittent periods of capillary blood flow occur more often, and the duration of each period of flow lasts longer.
T/F - The capillaries in various tissues have extreme differences in their permeabilities.
TRUE - for example, the membranes of the liver capillary sinusoids are so permeable that even plasma proteins pass through these walls, almost as easily as water and other substances.
What are the factors that short term, regulate or affect the autoregulation of local tissue blood flow?
o Oxygen -> reduced O2 availability causes vasodilation
o Autoregulation of blood flow:
* Metabolic theory -> if BP increases -> too much flow -> too much nutrients -> washes out vasodilatory substances -> vasoconstriction
* Myogenic mechanism -> present in other organs too -> high BP -> stretch of blood vessels -> vasoconstriction
o Endothelial-derived substances (relaxing or constricting factors):
* NO -> released from healthy endothelial cells in response to different stimuli
* Endothelin -> released from damaged endothelium and causes vasoconstriction.
What are the factors that long term, regulate or affect the autoregulation of local tissue blood flow?
o Changes in tissue vascularity - creating new vessels as a result of a chronic increased demand of blood flow.
o Development of collateral circulation - when a blood vessel gets blocked
o Vascular remodeling in response to chronic changes in BP / blood flow
Humoral control of circulation
Vasoconstrictor agents:
E/NE
AgII
Vasopressin
Vasodilatory agents:
Bradykinin
Histamine
Define bradyarrhythmia
Bradycardia associated with clinical sings (dog <60bpm, cats <100bpm)
DDX for bradyarrhythmias
Alterations in autonomic tone
Electrolyte imbalances
Drug exposure
Trauma
Hypoxia
Inflammation / infiltration of myocardium
Degenerative disease of the conduction system
T/F Sinus bradycardia is normally secondary to systemic disease
TRUE
What is a wandering pacemaker?
Changes in p wave amplitude in relation to the respiratory cycle and it is normally when vagotonia is the cause of bradycardia
Sick sinus syndrome
o Disease of the conduction system
o Periods of normal SR or sinus bradycardia
o Periods of long sinus arrest that can last up to 10-12 seconds because junctional and ventricular pacemakers fail to initiate escape beats.
o Variant - bradycardia tachycardia syndrome -> periods of paroxysmal tachycardia followed by a temporal failure of the sinus rhythm to resume when tachycardia ends.
* It is due to an exaggerated normal physiologic response of the sinus node to the effect of the tachyarrhythmia - called overdrive suppression
o Old mini Schnauzers and Terrier breeds commonly affected by SSS
1st degree AV block
o Prolonged PR interval
o AV node fibrosis, increased vagal tone, drugs that delay AV conduction (digoxin, Ca channel blockers, B blockers)
2nd degree AV block
o When some p not followed by QRS
o High grade -> when more atrial impulses fail to be conducted than are conducted.
o Mobitz type I - progressive PR interval ending by a blocked P wave (Wenckebach’s phenomenon) - usually bening and does not require treatment
o Mobitz type II - unexpected blocked p waves. PR before and after are normal. More likely to worsen and result in clinical signs.
How can we differentiate between Mobitz I and II?
Atropine - 0.04mg/Kg IV or glycopyrrolate 0.01mg/kg IV
Mobitz I will improve.
Mobitz II unchanged or worsens.
3rd degree AV block
o Absence of conducted p waves to ventricles.
o Electrical ventricular activation depends on scape beats
o Ventricular rate normally 20-60bpm in dogs and 60-120bpm in cats.
o Myocardial fibrosis, inflammation or infiltration, potentially drug toxicity (Ca2+ channel blockers)
o In cats often associated with structural heart disease.
Atrial standstill
o Lack of visible atrial activity on EKG
o Temporary or persistent - persistent is rare.
o Persistent - English Springer Spaniels, predisposed to developing AV block. Young dogs. genetic etiology. Long term prognosis guarded.
o Hyperkalemia most common cause
* First change is narrowing and taller T wave
* Decrease HR with reduced p amplitude and WRS widening
* Undetectable p waves
AV blocks medical treatment
o Parasympathicolytic meds (atropine / glycopyrrolate)
o Dopamine / dobutamine - increased HR and systolic function. Indicated in B blocker overdose
o Isoproterenol (pure B agonist) - improves conduction in AV node. Given as CRI.
o Terbutaline / aminophylline - mild chronotropic effects, can temporarily increase HR in dogs with SSS.
Pacemaker therapy
o Transcuteanous pacing -> in emergency situations, painful, only under general anesthesia.
o Temporary transvenous pacing -> lead in R side of heart connected to a generator external to the patient. Can be done under sedation.
* Can be used as stabilization until permanent pacemaker improving patient stability.
* Can be used to support patients with transient bradycardia (diltiazem toxicity)
Definition of tachyarrhythmias
o Rapid cardiac rhythm that originate t¡in the atria or AV junction (about bundle of His)
o Or, it involves the atria or AV junction as critical component of a tachyarrhythmia circuit
o Classified into atrial tachyarrhythmias or AV node dependent tachyarrhythmias - helps guide therapy.
How can we differentiate DCM from tachycardia-induced cardiomyopathy?
We cannot. Once treatment is started, tachycardia-induced cardiomyopathy can be partially or completely reversed.
T/F - A narrow QRS complex will almost always be an SVT
TRUE
T/F - It is very challenging to differentiate a ventricular arrhythmia from a SVT with BBB
TRUE
How can we try to differentiate ventricular arrhythmia from SVT +/- BBB
o Identification of p waves -> if there are p waves related to QRS, indicative of SVT with aberration.
o QRS fusion completes -> hallmark of ventricular tachyarrhythmia
o If tachycardia terminates with vagal maneuvers -> supraventricular in origin. If not, it can be both.
o If tachycardia ends with administration of lidocaine -> most likely ventricular in origin.
What is an irregularly irregular SVT with no organized atrial activity seen?
Afib
Steps to differentiate atrial vs AV node regular SVT
o If an SVT continues despite AV block - atrial in origin
o If a VPC terminates the SVT - more likely that is AV node dependent
o if vagal maneuver terminates the SVT - more likely AV node.
How can we do a vagal maneuver in a small animal
o Carotid sinus massage
o Sustained, gentle compression applied for 5-10 seconds over the carotid sinus -> immediately caudal to the dorsal aspect of the larynx.
Which cardiac drugs can we use that will act on the SA node?
B-blockers
Ca channel blockers
Digitalis
Class III (amiodarone, stall)
Which cardiac drugs can we use that will act on the AV node?
Main ones:
B blockers
Ca channel blockers
Digitalis glycosides
Others that can be used:
Class IC
Class III
Adenosine
Which cardiac drugs can we use that will act on the atrial myocardium?
Class IA
Class IC
Class III
Which cardiac drugs can we use that will act on accessory pathways?
Class IA
Class IC
Class III
Comparing diltiazem, esmolol and adenosine slowing down the AV node conduction, which one is more effective?
Diltiazem - slowed AV node conduction while maintaining good hemodynamic parameters.
Esmolol - caused severe drop in LV contractility
Adenosine at 2mg/kg was ineffective.
Explain the terms
Inotropy
Chronotropy
Dromotropy
Lusitropy
Inotropy - contractility
Chronotropy - rate
Dromotropy - conduction
Lusitropy - relaxation
Consequences of Ca2+ channel blockers
Hypotension
Negative chronotropy
Negative dromotropy
Negative isotropy
Impared insulin release
Effects on peripheral vasculature, cardiac muscle and pancreatic B cells -> can lead to hemodynamic collapse with high doses.
Effects of antiarrhythmics on ventricular action potential curves
Summary of sites of action of antiarrhythmics
3 mechanisms of ventricular tachycardia
Starling forces equation
Revised Starling principle equation
o Now instead of oncotic pressure of interstitial space, we replace if for oncotic pressure of subglycocalyx space, that is much lower.
o Subglycocalyx is almost protein free, oncotic pressure much lower compared to interstitium.
o The membrane osmotic reflection coefficient now it has to be that of the glycocalyx rather than the endothelium.
Difference between Starling and the new revised Starling principle in terms of fluid movement
o Interstitial oncotic pressure replaced for subglycocalyx oncotic pressure
o Instead of having filtration at the pre-capillary arterioles and absorption at the post-capillary venules, we have NO absorption at the post-capillary venules, just les filtration
Effect of Starling forces and revised version on fluid flux (graphs)
% of CO that goes to different organs
Describe abnormalities of myocyte calcium ion cycling in patients with heart failure
Draw the Frank Starling relashipnship of CO and preload curve and show how it is shifted during increased adrenergic drive in health (ex. Exercise), and during low-output heart failure. How diuretics, positive inotropes and vasodilators affect the curve?
o Arterial vasodilators (amlodipine or hydralazine) -> shift the curve upward in a manner similar to a positive inotrope.
o Venous vasodilators (nitrates) -> reduce preload through an increase the capacitance of the venous system and shift the curve leftward, similar to diuretics.
o Mixed vasodilators (ACE inhibitors) result in a combination of both upward and leftward adjustment”
Define/explain how SAM occurs in cats with HCM
Abnormal drag forces are responsible for systolic movement of the MV leaflets toward the septum that results in dynamic—as opposed to fixed—left ventricular outflow tract obstruction and, usually, concurrent mitral valve regurgitation
What is cardiorenal syndrome?
Risk of Cardiorenal syndrome based on fluid status
Why is it important to monitor CO?
Indicator dilution method
o Clinical gold standard.
o CO = vol indicator (temp patient - temp indicator) / f time
Swan Ganz
o From Ra -> RV -> PA
o Measures temperature changes - we inject a big bolus of 0.9%NaCl
o There is a thermometer at the tip of the catheter that will measure temperature drops.
o Temperature in graph is negative cause it is less than initial temperature
o Curve will tell us CO
Swan Ganz - graph, which one has lower or higher CO?
Swan Ganz catheter parts
PAP diagram
Swan Ganz information
Comparison of direct Fick method vs thermodilution 1 - theoretical bases and equipment
Comparison of direct Fick method vs thermodilution 2 - advantages and limitations
LiDCO
o Lithium dilution cardiac output is a minimally invasive indicator dilution technique for the measurement of cardiac output.
o Any arterial line works, does not need to be the femoral (like with PiCCO)
o Lithium injected via central line. From an artery, sample is collected and machine detects amount of lithium.
o Limitations: bleeding out (operator, depending on how much sampling, blood loss over time), indicator stable over time (will not leave the body easy over time), clots, cytokines inflammation.
CO status
o Saline velocity dilution method (aka ultrasound velocity dilution method)
o Ultrasound dilution method. Injects saline in the system and causes hemodilution. The viscosity of the blood changes for that period of time. That is the indicator, the viscosity change, not the saline itself.
o In this case arterial catheter is connected to a central line, there is no blood loss like in LiDCO methods.
o Less invasive than PAC, blood returned to the patient, no indicator accumulation.
o Reasonable bias and limits of agreement.
o Limitations - placement of arterial line. Patient should be sedated. Not bad for small patients.
Pulse contour method
o Arterial line -> arterial pulse wave. The stronger the heart pumps, the stronger the arteries pump.
o Had good correlation in humans the AUC from the arterial line. For every AUC it gives you a SV.
o It correlates well in stable patients where CO is constant, when it changes there is not good correlation
Fick principle
Fick method equations
Fick principle w/CO2 (NICO)
Fick (NICO) equation
Capnography
