Advanced Pathophysiology and Physiology: Module 3: Cardiovascular Physiology

11. Describe the anatomical pathways for action potential propagation through the heart including the SA node, atrium, AV node, ventricle, and Purkinje system

Pathway of heartbeat: (1) Begins in sinus atrial node (muscle connected to the atrial muscle. It acts as a pacemaker b/c the membrane likes sodium and the membrane potential -55 to 60 millivolts.) When the membrane potential reaches -40 millvolts, calcium channels open causing the action potential. After 100- 150 milliseconds, calcium channels close and the potassium channels open a bit more. Thus, returning the membrane potential to -55 millivolts. (2) The impulse than travels via the intermodal pathway to the A-V node. The cardiac impulses get delayed in the AV node and bundle, allowing the atria to contract, before the ventricles (3) This transmits the cardiac impulse throughout the atria.There are anterior and interior intermodal pathways. The anterior interior atrial band carries impulses to the left atrium. (4) Most of the delays in the A-V node. The delay in A- V mode is about 0.9 sec- 0.04 sec is in A- V bundle. The A-V bundle than takes impulse to the ventricles. There's normally a one way conduction though the bundles, the only conducting path between the atrial and ventricles is the A-V node, A-V bundle. (5) The AV Bundle impulse is divided into the left and right bundles branches. and action potential descend rapidly to the apex of each ventricle along the bundle branches. (6) The left and right bundles of Purkenje fibers take impulses to all different parts of the ventricles. Action potentials are carried by the purkinje fibers from the bundle branches to the ventricular walls. The rapid conduction from the atria ventricular wall to the ends of the purkinge fibers, allows the ventricular muscle cells to contract in unison, providing a strong contraction Fast conduction occurs because there's many gap junctions at the intercalated discs. Main arrival times SA node 0.00 sec A-V node 0.03 sec A-V bundle 0,12 sec Ventricular septum 0.16 sec. The entire impulse can take 0.22secs to reach the outermost areas of the ventricles. Videos: Action potentials originate in the sinal atrial node and travel across the wall of the atrium form the sinal atrial node to the sinal ventricular node. Action potentials pass slowly through the atrial ventricular node to give the atrium time to contract. They then pass rapidly along the atrial ventricular bundle which extends from the atrial ventricular node. Through the fibrous skeleton into the interventricular septum. The AV bundle divides into right and left bundle branches and action potential descend rapidly to the apex of each ventricle along the bundle branches. Action potentials are carried by the purkinje fibers from the bundle branches to the ventricular walls. The rapid conduction from the atria ventricular wall to the ends of the purkinge fibers, allows the ventricular muscle cells to contract in unison, providing a strong contraction.

Phase 2: Cardiac AP

Phase 2: Ca++ channels opens more. Although Na+ permeability has plummeted to its resting levels and repolarization has begun by this point, the calcium surge across the membrane prolongs depolarization potential briefly producing a plateau in the AP tracting. At the same time, K+ permeability decreases, which prolongs the plateau and prevents rapid repolarization. As long as Ca+ is entering the cells, the cells continue to contract. Plateau

Phase 3: Cardiac AP

Phase 3: K+ channels open more. During phase 3 (the "rapid repolarization" phase) of the action potential, the Ca2+ channels close, while the K+ channels remain open as more potassium leak channels open. This ensures a net outward positive current, corresponding to negative change in membrane potential, thus allowing more types of K+ channels to open. This net outward, positive current (equal to loss of positive charge from the cell) causes the cell to repolarize. The delayed rectifier K+ channels close when the membrane potential is restored to about -85 to -90 mV, while IK1 remains conducting throughout phase 4, which helps to set the resting membrane potential[21

Phase 4: Cardiac AP

Phase 4: Resting membrane potential. Phase 4 is the resting membrane potential, and describes the membrane potential when the cell is not being stimulated. The membrane is most permeable to K+(mainly due to leak channels) and relatively impermeable to other ions. The resting membrane potential is therefore dominated by the K+ equilibrium potential (-80mV) according to the K+ gradient across the cell membrane. However, phase 4 is also special and very important because all cardiac cells, which belong to the excitatory system have an unstable phase 4 - is the pacemaker potential. All can fire an electric impulse as the SAN does. Phase 4 is associated with heart diastole (relaxation) so is called diastolic depolarization.

10. Define and state the major factors affecting contractility of cardiac muscle.

Potassium= Excess potassium (hyperkalemia), decreases cardiac contractility, which could be caused by renal insufficiency or medications. The heart becomes dilated, flaccid and slows the heart rate. Elevation to 8-12mEq/L or 3x the normal value can cause death, due to arrhythmia. Clinically measures are taken to lower serum potassium levels. Calcium= When we consider the increase serum calcium strength and contractility. It makes sense that calcium would cause spastic contractions and low calcium would cause cardiac dilations. This is typically not a problem, but if it is it may be related to hyperparathyroidism. Book: Contractility (inotropism) is the intrinsic ability of myocardial cells to develop force at a given muscle cell length. Positive inotropic effects, increase in contractility. Negative inotropic effects, decrease in contractility.

Pulse Pressure

Pulse pressure is the difference between systolic pressure and diastolic pressure. If all other factors are equal, the magnitude of the pulse pressure reflects the volume of blood ejected from the left ventricle on a single beat, or the stroke volume. Costanzo, Linda S. (2013-05-27). Physiology, (Costanzo Physiology) (Kindle Locations 3934-3936). Elsevier Health Sciences. Kindle Edition.

Define Resistance

Resistance is the impatent to blood flow in a vessel. Blood flow to tissues is controlled in relation to tissue needs.

Autonomic Nerve Innervation with Conduction Velocity

Stimulation of the sympathetic nervous system produces an increase in conduction velocity through the AV node (positive dromotropic effect), which increases the rate at which action potentials are conducted from the atria to the ventricles. The mechanism of the sympathetic effect is increased ICa, which is responsible for the upstroke of the action potential in the AV node (as it is in the SA node). Stimulation of the parasympathetic nervous system produces a decrease in conduction velocity through the AV node (negative dromotropic effect), which decreases the rate at which action potentials are conducted from the atria to the ventricles. The mechanism of the parasympathetic effect is a combination of decreased ICa (decreased inward current) and increased IK-ACh (increased outward K+ current, which further reduces net inward current). conduction velocity through the AV node is slowed sufficiently (e.g., by increased parasympathetic activity or by damage to the AV node), some action potentials may not be conducted at all from the atria to the ventricles, producing heart block. The degree of heart block may vary.

7. Explain the function of the Valves.

The A-V valves (tricuspid and mitral) prevent backflow of blood from the ventricles to the atria during systole, and the semilunar valves (aortic and pulmonary artery valves) prevent backflow from the aorta and the pulmonary arteries in the ventricles during diastole. The valves open and close passively - d/t pressure gradients pushing them. The Aortic / Pulmonary Artery semilunar valves. (1) high pressure in the arteries at the end of systole cause the semilunar valvles to snap to a closed position.

Conduction Velocity route and reasoning for delays

The action potential originates in the SA node at what is called time zero. It then takes a total of 220 msec for the action potential to spread through the atria, AV node, and His-Purkinje system to the farthest points in the ventricles. Conduction through the AV node (called AV delay) requires almost one half of the total conduction time through the myocardium. The reason for the AV delay is that, of all the myocardial tissues, conduction velocity in the AV node is slowest (0.01 to 0.05 m/sec), making conduction time the longest,

(1) Explain the ionic basis of the cardiac action potential, including the ion channels and currents which underlie Phase 0, Phase 1, Phase 2, Phase 3 and Phase 4.

The cardiac syncytium is a network of cardiomyocytes connected to each other by intercalated discs that enable the rapid transmission of electrical impulses through the network, enabling the syncytium to act in a coordinated contraction of the myocardium. There is an atrial syncytium and a ventricular syncytium that are connected by cardiac connection fibres. Each syncytium function together as one, via gap junction with intercallated discs, are able to contract together. Intercallated discs with gap junctions, comprised of actin and myosin filaments, striated and filament lie parallel to each other. Intercalated discs- separate individual cells from each other the cells are fused together by permeable junctions called "gap junctions" allowing for rapid diffusion of ions. The plateau in AP of cardiac muscle, allows for the ventricular contraction to last 15x longer than skeletal muscle. *Note: In skeletal muscle AP caused by Na+ channels opening, In cardiac muscle you have Na+ channels and Na+ Ca+ channels (slower to open and remain open longer) = Na+ Ca+ - prolonged depolarization. *Ca not coming from SR - but outside. 2. After AP, K+ permeability decreases fivefold. = PLATEAU preventing return of voltage to its resting level. (-85 → +20)

9. Explain sympathetic and parasympathetic innervations and the ionic basis for alteration of pacemaker potential and heart rate. (Book Details)

The effects of the autonomic nervous system on heart rate are called chronotropic effects. ++ Positive chronotropic effects increases in the heart rate (stimulation of the sympathetic nervous system). Increasing the rate of depolarization and decreasing the threshold potential means that the SA node is depolarized to threshold potential more frequently and fires more action potentials per unit time (i.e increased heart rate) ++ Negative chronotropic effects decreases in heart rate (stimulation of the parasympathetic nervous system). The parasympathetic nervous system decreases heart rate through 3 effects on the SA node: (1) Slowing the rate of depolarization, (2) Hyperpolarizing the maximum diastolic potential so that more inward current is required to reach threshold potential, (3) Increasing the threshold potential. As a result, the SA node is depolarized to threshold less frequently and fires fewer action potentials per unit time (i.e decreased heart rate).

12. Describe the mechanisms by which cells in the SA node, the atria, AV node, Perkinje fibers and ventricular muscle cells generate electrical currents that can be detected at the skin surface as an ECG.

The hearts conduction system controls the generation and propagation of electrical signals. The sequence of events P-QRS-T, repeats with every heartbeat.ECG is not a tracking of a single actions potential, but an accumulation of the many action potentials that constitute the electrical activity of the heart. Propagation= continuation or movement or Action potentials, that cause the heart muscles to contract of for the heart to pump blood. This electrical activity can be measured by electrodes placed at different parts on the skin. From which a composite recording is produced in a form of a graph. This recording is known as an electrocardiogram (ECG/ EKG). What happens during a single beat of the heart and how they are depicted on an ECG.

Primary determining ion in RMP of cardiac cells

The resting membrane potential of cardiac cells is determined primarily by potassium ions (K+). The conductance to K+ at rest is high, and the resting membrane potential is close to the K+ equilibrium potential. Since the conductance to sodium (Na+) at rest is low, Na+ contributes little to the resting membrane potential. Costanzo, Linda S. (2013-05-27). Physiology, (Costanzo Physiology) (Kindle Locations 4039-4042). Elsevier Health Sciences. Kindle Edition.

Effects of Heart Rate AND Glycosides on Contractility

When the heart rate increases, contractility increases, when the heart rate decreases, contractility decreases. Effects of cardiac glycosides on contractility: Cardiac glycosides are a class of drugs that act as positive inotropic agents. Eg; Digoxin.

Frank Starling

When venous return of blood increases, the heart muscle stretches more, which makes it pump with a greater force of contraction. The Frank-Starling mechanism of the heart can be stated in another way: Within physiological limits, the heart pumps all the blood that comes to it without allowing excess accumulation of blood in the veins. Hall, John E. (2011-04-13). Pocket Companion to Guyton & Hall Textbook of Medical Physiology (Guyton Physiology) (Kindle Locations 1756-1758). Elsevier Health Sciences. Kindle Edition.

4. Explain the dual roles of the cardiac Ca channel

electrical and chemical **Read: Pages 140-141 of Costanzo relate to this and there is a more detailed explanation on pages 102-104 in Guyton and Hall. • During phase 2 of the cardiac action potential, the slow calcium channels open and cause plateau - "electrical" role. • At the same time, the in-flux of calcium from the extracellular fluid into the cytoplasm through the cardiac calcium channel promotes the release of the calcium that is stored within the sarcoplasmic reticulum into the cytoplasm. This process is called calcium-induced calcium release (CICR)- "chemical" role. Once the calcium is in the cytoplasm, it then binds to troponin C and allows the interaction between actin and myosin that leads to contraction of the myocyte. CICR occurs when the resulting Ca2+ influx activates ryanodine receptors on the SR membrane, which causes more Ca2+ to be released into the cytosol. In cardiac muscle, the result of CICR is observed as a spatio-temporally restricted Ca2+ spark. The result of CICR across the cell causes the significant increase in cytosolic Ca2+that is important in activating muscle contraction. The coordinated actions of these phosphorylated proteins then produce an increase in intracellular Ca2+ concentration. (1) There is phosphorylation of the sarcolemmal Ca2+ channels that carry inward Ca2+ current during the plateau of the action potential. As a result, there is increased inward Ca2+ current during the plateau and increased trigger Ca2+, which increases the amount of Ca2+ released from the sarcoplasmic reticulum. (2) There is phosphorylation of phospholamban, a protein that regulates Ca2+ ATPase in the sarcoplasmic reticulum. When phosphorylated, phospholamban stimulates the Ca2+ ATPase, resulting in greater uptake and storage of Ca2+ by the sarcoplasmic reticulum. Increased Ca2+ uptake by the sarcoplasmic reticulum has two effects: It causes faster relaxation (i.e., briefer contraction), and it increases the amount of stored Ca2+ for release on subsequent beats. Costanzo, Linda S. (2013-05-27). Physiology, (Costanzo Physiology) (Kindle Locations 4461-4470). Elsevier Health Sciences. Kindle Edition.

Electrocardiogram

• A P wave caused by the electrical potential generated from depolarization of the atria before their contraction. The P wave immediately precedes atrial contraction. • A QRS complex caused by the electrical potential generated from the ventricles before their contraction. The QRS complex immediately precedes ventricular contraction. • A T wave caused by the potential generated from repolarization of the ventricles. • The ventricles remain contracted until a few milliseconds after the end of the T repolarization wave. Hall, John E. (2011-04-13). Pocket Companion to Guyton & Hall Textbook of Medical Physiology (Guyton Physiology) (Kindle Locations 1919-1923). Elsevier Health Sciences. Kindle Edition.

Fun Facts

• The atria remain contracted until they are repolarized, but an atrial repolarization wave cannot be seen on the electrocardiogram because it is obscured by the QRS wave. • The P-Q or P-R interval on the electrocardiogram has a normal value of 0.16 second and is the duration of time between the first deflection of the P wave and the beginning of the QRS wave; this represents the time between the beginning of atrial contraction and the beginning of ventricular contraction. • The Q-T interval has a normal value of 0.35 second, which is the duration of time from the beginning of the Q wave to the end of the T wave. Hall, John E. (2011-04-13). Pocket Companion to Guyton & Hall Textbook of Medical Physiology (Guyton Physiology) (Kindle Locations 1932-1938). Elsevier Health Sciences. Kindle Edition.

Describe factors which influence conduction velocity in the heart. (Path ch.31) Costanza ch. 4

(1) Conduction velocity has the same meaning that in nerve and skeletal muscle fibers; the speed at which APs are propagated within the tissue (meters/ second). (2) Conduction velocity determines how long it takes the action potential to spread to various locations in the myocardium. As in nerve and skeletal muscle fibers, the physiologic basis for conduction of cardiac action potentials is the spread of local currents. In atrial, ventricular, and Purkinje fibers, this inward current of the upstroke is carried by Na+, and in the SA node, the inward current of the upstroke is carried by Ca2+. Conduction velocity depends on the size of the inward current during the upstroke of the AP. The larger the inward current, the more rapidly local currents will spread to adjacent sites and depolarize them to threshold. Conduction velocity also correlates with dV/dT, the rate of rise of the upstroke of the action potential, because dV/dT also correlates with the size of the inward curren. ** Conduction velocity does not depend on action potential duration, that action potential duration is simply the time it takes a given site to go from depolarization to complete repolarization (e.g., action potential duration in a ventricular cell is 250 msec). Action potential duration implies nothing about how long it takes for that action potential to spread to neighboring sites. Stimulation of the sympathetic nervous system produces an increase in conduction velocity through the AV node

Questions and Objectives for Exam Hall (2011): Chapters 9-11, 14 Costanzo (2013): Chapter 4

(1) Explain the ionic basis of the cardiac action potential, including the ion channels and currents which underlie Phase 0, Phase 1, Phase 2, Phase 3 and Phase 4. (2) Explain the significance of the refractory periods of the action potential. (3) Describe factors which influence conduction velocity in the heart. [Include the size of the inward current, impact of gap junctions and autonomic effects (sympathetic and parasympathetic stimulation)]. (4) Explain the dual roles of the cardiac Ca channel (5) Describe the sequence of depolarization in the normal heart. (6) Describe how contractility is assessed and define ejection fraction. (7) Explain the function of the Valves (8) Describe the Frank Starling Mechanism (9) Explain sympathetic and parasympathetic innervations and the ionic basis for alteration of pacemaker potential and heart rate. (10) Define and state the major factors affecting contractility of cardiac muscle. (11) Describe the anatomical pathways for action potential propagation through the heart including the SA node, atrium, AV node, ventricle, and Purkinje system (12) Describe the mechanisms by which cells in the SA node, the atria, AV node, Perkinje fibers and ventricular muscle cells generate electrical currents that can be detected at the skin surface as an ECG. (13) Describe basic principles of circulation, such as interrelationships of pressure, flow, and resistance (Ohm's law), Cardiac Output, Venous Return and their regulation

Driving Force for Blood Flow

* The pressure difference is the driving force for blood flow and the resistance is an impediment to flow.

Frank Starling Mechanism

-Within physiological limits the heart pumps all the blood that comes to it without excessive damming in the veins. - Extra stretch on cardiac myocytes makes actin and myosin filaments interdigitate to a more optimal degree for force generation (The more the heart is stretched during filling, the more strongly it will contract to pump the blood. This is why healthy hearts is able to pump at rest and oxygen demands are enough for exercise.) HF= decrease in stroke volume

13. Describe basic principles of circulation, such as interrelationships of pressure, flow, and resistance (Ohm's law), Cardiac Output, Venous Return and their regulation

13. Describe basic principles of circulation, such as interrelationships of pressure, flow, and resistance (Ohm's law), Cardiac Output, Venous Return and their regulation Blood pressure is the force exerted by the blood against any unit, area of vessel wall. Measured in mmHg. Pressure of 100mmHg, means that the force of the blood was sufficient to push a column of mercury 100mm high. Low pressures are sometimes reported in units/mm of water. 1mmHg= 13.6 mmHg of water. Resistance is the impatent to blood flow in a vessel. Blood flow to tissues is controlled in relation to tissue needs. Cardiac output is mainly controlled by local tissue flow. Arterial pressure is controlled independent if either local blood flow control or cardiac output control. Capillaries have the largest cross- sectional area of the circulation. Cross sectional area of capillaries is 10000 higher than that of the aorta. Capillaries= 2500cm. The majority of blood volume is in the veins. Total blood volume in humans us about 5L. Blood pressure profile in the circulatory system: Highest pressure are in aorta and large arteries. Blood pressure is lowest in the large veins in the vena cava Large pressure drop across the arterior- capillary junction. Characteristics of Blood Flow: Blood usually flows in streamlines with each layer of blood remaining the same distance from the wall, this type is called laminar flow. 'When the laminar flow occurs the velocity of blood in the center of the vessel is greater than that toward the outer edge creating a parabolic profile. Murmurs or bruits are imp in diagnosing vessel stenosis, vessel shunts and cardiac valvular lesions. Relationships b/w pressure, flow and resistance:- Q= P/R ( triangle p/r) Flow (Q) through a blood vessel is determined by: 1) the pressure difference ( triangle o or p1- p2) b/w the 2 ends of the vessel. P1= pressure at arteriol end and P2 pressure at venous end 2) Resistance (r) of the vessel (mmHg/ml/min) Flow= pressure difference/ resistance Book: Blood flow through a blood vessel or a series of blood vessels is determined by 2 factors: -Pressure difference b/w 2 ends of the vessel - Resistance of the vessel to blood flow. * The pressure difference is the driving force for blood flow and the resistance is an impediment to flow. * The relationship of flow, pressure and resistance is analogous to the relationship of current (I), voltage ( triangle V) and resistance (R) in electrical circuits, expressed by Ohm's law. The magnitude of blood flow (Q) is directly proportional to the size of the pressure difference (triangle P) or pressure gradient. The direction of blood flow is determined by the direction of the pressure gradient and always is from high to low pressure. Blood flow is inversly proportional to resistance (R). Increasing resistance, decrease flow, and decreasing resistance increases flow. The major mechanism for changing blood flow in the cardiovascular system is by changing the resistance of blood vessels, particularly the arterioles.

Affects of the ANS on contractility:

Affects of the ANS on contractility: Sympathetic nervous system, causes a positive inotropic effect. Increase peak tension, increased rate of tension development and faster rate of relaxation. Faster relaxation means that the contraction (twitch) is shorter allowing more time for refilling. Parasympathetic nervous system, causes a negative inotropic effect.

6. Describe how contractility is assessed

Assessment of contractility has been difficult, the rate of change of ventricular pressure, or dP/dt has been used as an index of contractility; especially the peak dP/dt. This index is affected by both preload and afterload; another index that is more reliable is (dP/dt)/P ejection fraction reflecting an increase in contractility and decreases in ejection fraction reflecting a decrease in contractility.

3. Describe factors which influence conduction velocity in the heart. (Path ch.31)

Automaticity, or the property of generating spontaneous depolarization to threshold, enables the SA and AV nodes to generate cardiac action potentials without any stimulus. Cells capable of spontaneous depolarization are called automatic cells. The automatic cells of the cardiac conduction system can stimulate the heart to beat even when the heart is removed from the body. Spontaneous depolarization is possible in automatic cells because the membrane potential does not "rest" during phase 4. Rhythmicity is the regular generation of an action potential by the heart's conduction system. The SA node sets the pace because normally it has the fastest rate of depolarization, which is why it is called the natural pacemaker of the heart. The SA node depolarizes spontaneously 60 to 100 times per minute. If the SA node is damaged, the AV node will become the heart's pacemaker at a rate of about 40 to 60 spontaneous depolarizations per minute. Although the heart's nodes and conduction system generate cardiac action potentials independently, the autonomic nervous system influences the rate of impulse generation (firing), depolarization, and repolarization of the myocardium and the strength of atrial and ventricular contraction; the rapid initiation of increased activity depends on the sympathetic and parasympathetic fibers of the autonomic nervous system.

9. Explain sympathetic and parasympathetic innervations and the ionic basis for alteration of pacemaker potential and heart rate.

Autonomic Effects on Heart= Parasympathetic and sympathetic innervation of the heart. Vagus nerves innervation of the heart are the parasympathetic piece. (1) Parasympathetic stimulation (rest and digest), decrease heart rate markedly and decrease cardiac contractility slightly. Parasympathetic Effects in heart rate: -Parasympathetic (vagal) nerves, which release acetylcholine at their ending innervate S-A node and A-V junctional fibers proximate to A-V node. -Causes hyperpolarization because of increased potassium permeability in response to acetylcholine. -This causes decreased transmission of impulses maybe temporarily stopping heart rate. -Ventricular escape occurs. (2) Sympathetic stimulation ( fight or flight): causes increase in heart rate, increase contractility with a heart rate of 180-200 beats/ min and cardiac output= 20L/min. Sympathetic Effects on the heart: -Releases norepinephrine at sympathetic ending which stimulates beta 1 adrenergic receptors which mediate the effects on the heart rate. -Causes increased sinal node discharge. -Increases rate of conduction of impulse -Increases force of contraction in atria and ventricles. Effects of sympathetic and parasympathetic stimulation on cardiac output: Changes in cardiac output relate to both changes in heart rate and changes in contractile strength of the heart. For each amount of stimulation, there's a leveling out of fact where the maximum stimulation of the heart, can't increase the amount of cardiac input, despite increase in right atrial pressure.

Describe basic principles of circulation, such as interrelationships of pressure

BP = CO X TPR BF = pressure difference/Resistance Pressure = Force ext

Describe basic principles of circulation, such as interrelationships of flow and resistance (Ohm's law)

Blood flow is inversly proportional to resistance (R). Increasing resistance, decrease flow, and decreasing resistance increases flow. The major mechanism for changing blood flow in the cardiovascular system is by changing the resistance of blood vessels, particularly the arterioles.

Define Blood Flow

Blood flow is the quantity of blood that passes a point in a circulation in a given time. Unit of blood flow is expressed as ml/min or L/min. Overall flow of circulation in an adult is 5L/min, which is the cardiac output (average). The magnitude of blood flow (Q) is directly proportional to the size of the pressure difference (triangle P) or pressure gradient. The direction of blood flow is determined by the direction of the pressure gradient and always is from high to low pressure. Q = (Triangle)P/ R 1. (Triangle) P = pressure difference between the two ends of the vessel 2. R = Resistance of the vessel

What determines Cardiac Output

Blood flow to tissues is controlled in relation to tissue needs. Because venous return is the sum of all local blood flows, anything that affects local blood flow also affects the venous return and cardiac output. The cardiac output curve is used to describe the ability of the heart to increase its output when right atrial pressure rises. Hall, John E. (2011-04-13). Pocket Companion to Guyton & Hall Textbook of Medical Physiology (Guyton Physiology) (Kindle Locations 3506-3507). Elsevier Health Sciences. Kindle Edition. For example, if the biceps muscle of the right arm is used repetitively to lift a weight, the metabolic rate of that muscle increases, causing local vasodilation. Blood flow to the biceps muscle thus increases, which in turn causes an increase in venous return and cardiac output. Remarkably, the increased cardiac output goes primarily to the area of increased metabolism, the biceps, because of its vasodilation. Hall, John E. (2011-04-13). Pocket Companion to Guyton & Hall Textbook of Medical Physiology (Guyton Physiology) (Kindle Locations 3450-3453). Elsevier Health Sciences. Kindle Edition.

Define Blood Pressure

Blood pressure is the force exerted by the blood against any unit, area of vessel wall. Measured in mmHg. Pressure of 100mmHg, means that the force of the blood was sufficient to push a column of mercury 100mm high. Low pressures are sometimes reported in units/mm of water. 1mmHg= 13.6 mmHg of water.

Laminar vs Turbulent Blood Flow

Blood usually flows in streamlines with each layer of blood remaining the same distance from the wall, this type of flow is called **LAMINAR FLOW** When laminar flow occurs, the velocity of blood in the center of the vessel is greater than that toward the outer edge. Causes of turbulant blood flow - High velocity, sharp turns, rough surfaces, rapid narrowing.

8. Describe the frank Starling Mechanism

Book: Frank Starling Mechanism states that the volume of blood ejected by the ventricle depends on the volume present in the ventricle at the end of diastole. The volume present at the end of diastole depends on the volume returned to the heart, or the venous return. Therefore, stroke volume and cardiac output correlate directly with end- diastolic volume, which correlates with venous return. The Frank Starling relationship governs normal ventricular function and ensures that the volume the heart ejects in systole equals the volume it receives in venous return. There is a relationship between stroke volume or cardiac output and ventricular end- diastolic volume. As venous return increases, end- diastolic volume increases, and because of the length tension relationship in the ventricles, stroke volume increases. In the physiologic range, the relationship b/w stroke volume and end- diastolic volume is nearly linear. Only when end- diastolic volume becomes high does the curve start to bend. At these high levels, the ventricle reaches a limit and is not able to "keep up" with venous return. Figure 4.22, pg 146 in Costanzo.

________ have the largest cross- sectional area of the circulation.

Capillaries, large pressure drop across arteriolar-capillary junction.

2. Explain the significance of the refractory periods of the action potential.

Cardiac muscle like all excitable tissue is refractory to restimulation during the action potential. Therefore, the refractory period of the heart is the interval of time where cardiac impulses cant re-excite an already excited area. There is also a relative refractory period during which the muscle is more difficult than normal to excite. Note that premature contractions do not cause wave summation, as occurs in skeletal muscle. The absolute refractory period: (the inexcitable period when Na+ channels are still open / closed / inactivated) lasts 250ms in cardiac muscle cells, nearly as long as the contraction. Contrast this to the 1-2ms refractory period of skeletal muscle and contractions last 20-100ms. The long cardiac refractory period normally prevents tetanic contractions, which would stop the hearts pumping action. From the beginning of phase 0 until part way through phase 3 when the membrane potential reaches -60mV, each cell is in an absolute refractory period, also known as the effective refractory period, during which it is impossible to evoke another action potential. This is immediately followed until the end of phase 3 by a relative (2) refractory period, during which a stronger-than-usual stimulus is required.[22][23] These two refractory periods are caused by changes in the state of sodium and potassium channel molecules. After rapid depolarization of the cell due to rapid influx of sodium ions the Vm (membrane potential) approaches 0mV and approaches sodium's equilibrium potential, which relinquishes sodium's electrochemical drive into the cell. Sodium channels than enter an "inactivated" state, due to closing of the sodium inactivation gate, in which they cannot be opened regardless of the strength of the excitatory stimulus—this gives rise to the absolute refractory period

Conducting cells: Most cells in heart are contractile cells

Conducting cells constitute the tissues of the SA node, the atrial internodal tracts, the AV node, the bundle of His, and the Purkinje system. Conducting cells are specialized muscle cells that do not contribute significantly to generation of force; instead, they function to rapidly spread action potentials over the entire myocardium. Another feature of the specialized conducting tissues is their capacity to generate action potentials spontaneously. Except for the SA node, however, this capacity normally is suppressed. Costanzo, Linda S. (2013-05-27). Physiology, (Costanzo Physiology) (Kindle Locations 4005-4009). Elsevier Health Sciences. Kindle Edition.

Mechanisms for changing contractility

Contractility correlates directly with the intracellular calcium concentration. So the larger the inward calcium current and the larger the intracellular stores, the greater the increase in intracellular calcium concentration and the greater the contractility.

Define contractility

Contractility, or inotropism, is the intrinsic ability of myocardial cells to develop force at a given muscle cell length. (1) Agents that produce an increase in contractility are said to have positive inotropic effects. Positive inotropic agents increase both the rate of tension development and the peak tension. *Contractility correlates directly with the intracellular Ca2+ concentration, which in turn depends on the amount of Ca2+ released from sarcoplasmic reticulum stores during excitation-contraction coupling. ** Excess potassium in extracellular fluid causes the heart to become more flaccid, and reduces the heart rate, thereby causing a large decrease in contractility.

5. Describe the sequence of depolarization in the normal heart.

Depolarization means the membrane potential has become less negative. Depolarization occurs when there is net movement of positive charge into the cell, which is called an inward current. During depolarization, the normal negative potential inside the fiber reverses and becomes slightly positive inside and negative outside. In the heart The P wave represents the wave of depolarization that spreads from the SA node throughout the atria, and is usually 0.08 to 0.1 seconds (80-100 ms) in duration. The brief isoelectric (zero voltage) period after the P wave represents the time in which the impulse is traveling within the AV node (where the conduction velocity is greatly retarded) and the bundle of His. The QRS complex consists of three waves: Q, R, and S. Collectively, these waves represent depolarization of the ventricles. Note that the total duration of the QRS complex is similar to that of the P wave. This fact may seem surprising because the ventricles are so much larger than the atria; however, the ventricles depolarize just as quickly as the atria because conduction velocity in the His-Purkinje system is much faster than in the atrial conducting system. SA → Bachman's Bundle → AV node → Bundle of HIS→ left and right bundle → Purkinje fibers.

Define Ejection Fraction.

Ejection Fraction: is the fraction of the end-diastolic volume ejected in each stroke volume, which is a measure of ventricular efficiency; Thus, Represents the percentage of the end-diastolic volume that is ejected with each beat. Normal EF is 65%-70%. EF is either measured directly or calculated (SV/EDV). EF declines as cardiac function deteriorates. When the EF falls to the 30% range, a patients exercise tolerance is severely limited because of the heart's inability to maintain an adequate CO. Costanzo, Linda S. (2013-05-27). Physiology, (Costanzo Physiology) (Kindle Locations 4445-4447). Elsevier Health Sciences. Kindle Edition.

Phase 0 of Cardiac AP

Fast Na+ channels open then slow Ca++ channels. Phase 0 is the rapid depolarization phase. Action potentials are unidirectional, all-or-none signals, because once they are initiated they only fire/move in one direction and happen fully at constant strength or not at all.[14][15]In heart pacemaker cells, phase 0 depends on the activation of L-type calcium channels instead of the fast Na+ current. The slope of phase 0 represents the maximum rate of potential change and is known as dV/dtmax. Its behavior is different in contractile and pacemaker heart cells. In heart muscle cells, this slope is directly proportional to the net ionic current.[16] This phase is due to the opening of the fast Na+ channels causing a rapid increase in the membrane conductance to Na+ (gNa)[nb 2] and thus a rapid influx of Na+ ions (INa) into the cell

Ohm's Law

If the arterial pressure is constant, this formula can be accurately used to predict changes in flow that are due to changes in total peripheral resistance. If we return to the example of an increase in the metabolic rate in a peripheral tissue, the increase in oxygen use that also occurs elicits local vasodilation and decreases total peripheral resistance, which causes an increase in oxygen delivery to local tissues, an increase in venous return, and an increase in cardiac output. Therefore a decrease in total peripheral resistance increases the cardiac output, and an increase in total peripheral resistance decreases it. Hall, John E. (2011-04-13). Pocket Companion to Guyton & Hall Textbook of Medical Physiology (Guyton Physiology) (Kindle Locations 3456-3465). Elsevier Health Sciences. Kindle Edition.

What happens during a single beat of the heart and how they are depicted on an ECG.

In a normal heart, each beat begins in the right atrium with an action potential signal from the SA node. The signal spread across nth atria, causing the muscle cells to depolarize and contract, inducing a phase known as atrial systole. On the ECG the atrial depolarization is represented by the P wave. The period of conduction that follows atrial systole, precedes contraction of the ventricles is depicted on ECG by QR segment. A flat ling following the P wave. When the signal leave the atria, it enters the ventricles by the A-V node. Located in the interatrial septum. It enters the bundle of His and spreads through the bundle branches and large diameter Purkinje fibers along the ventricles walls. As the signal spreads through the ventricles, a contractile fiber depolarize and contract very rapidly. Inducing ventricular systole. The ECG QRS complex represents this rapid ventricular depolarization. Atrial repolarization also occurs at this time. *Any atrial activity is hidden in the ECG by the QRS complex. Finally as the signal passes out the ventricles, the ventricular walls start to relax and recover. A state describe as ventricular diastole. The dome shape T wave on the ECG marks the ventricular repolarization.

Phase 1: Cardiac AP

K+ channels open Phase 1 of the myocyte action potential occurs with the inactivation of the fast Na+ channels. The transient net outward current causing the small downward deflection of the action potential is due to the movement of K+ and Cl- ions, carried by the Ito1 and Ito2 currents, respectively. Particularly the Ito1 contributes to the "notch" of some ventricular cardiomyocyte action potentials (image 1).

What is the ST segment, QT interval?

On the ECG the ST segment depicts the period when the ventricles repolarize. The QT interval represents the time it takes for both depolarization and repolarization of the ventricles to occur.