Cardiovascular physiology Flashcards
The time it takes a randomly jumping particle to move a distance x in one specific direction increases with the square of distance. While diffusion across a short distance, such as the neuromuscular gap ( 0,1 micrometer) takes only 5 millionths of a second, diffusion across the heart wall (approximately 1 cm) is hopelessly slo, taking over…?
half a day.
Fig 1,2 is an ex of this slow transport. It shows the heart of a patient who suffered a coronary thrombosis (obstruction of the blood supply to the heart wall). The pale area in the wall is muscle which has died from lack of oxygen even though the adjacent cavity (the left ventricle) was fully of richly oxygenated blood. The patient died simply because a distance of a few millimeters reduced diffusion transport to an inadequate rate.
Table 1.1: time taker for a glucose molecule to diffuse a specified distance in one direction
Table 1.1: time taker for a glucose molecule to diffuse a specified distance in one direction
Clearly, for distance greater than approximately 0.1 mm a faser transport system is needed, ant this is provided by the cardiovascular system. Fig 1.3
Clearly, for distance greater than approximately 0.1 mm a faser transport system is needed, ant this is provided by the cardiovascular system. Fig 1.3
The cardiovascular system still relies of diffusion for the uptake of molecules at points of close proximity to the environment (e.g. oxygen uptake into lung capillaries), but it then transports them rapidly over large distances by sweeping them along in a stream of pumped fluid. This form of transport is called …………?
This form of transport is called bulk flow or convective transport.
Convective transport required an energy input and this is provided by the heart.
Convective transport required an energy input and this is provided by the heart.
In man convection takes only …..to carry oxgen over a meter or more from the lungs to the smallest blood vessels of the limbs (capillaries).
30 s
Over the final 10-20 microns separating the capillary from the cells, diffusion is again the main transport process.
First and foremost function of the cardiovascular system?
Convection of oxygen, glucose, amino acids, fatty acids, vitamins, drugs and water to the tissues and the rapid washout of metabolic waste products like carbon dioxide, urea, and creatinine. The cardiovascular system is also part of a control system in that it distributes hormones to the tissue and even secretes some hormones itself. (e.g. atrial natriuretic peptide).
In addiiton, the circulation plays a vital role in temperature regulation, for it regulates the delivery of heat from the core of the body to the skin, and a vital role in reproduction.
Circulation to individual organs are mostly in …………. (e.g cerebral and coronary circulations) but a few are in ………. (liver, renal tubules)
Circulation to individual organs are mostly in parallel (e.g cerebral and coronary circulations) but a few are in series (liver, renal tubules)
Fig 1.4: General arrangement of the circulation showing right and left sides of the heart in series.
Fig 1.4: Note that the bronchial venous blood drains anomolously into the …………. atrium
Note that the bronchial venous blood drains anomolously into the left rather than right atrium
Pulmonary circulation: Venous blood enters the right atrium from the 2 major veins; the ………..and ………..vena cavae, then flows through a valve into the right ventricle.
Venous blood enters the right atrium from the 2 major veins; the superior and inferior vena cavae, then flows through a valve into the right ventricle.
Ventricular systole forces part of the blood out through the pulmonary artery and into the lungs at a low pressure. Gases exchange by diffusion in the lung air sacs (alveoli) raising the blood oxygen content from approximately …….. ml/l (venous blood) to ………. ml/l. The oxygenated blood returns through the …………… to the left atrium and left ventricle.
Ventricular systole forces part of the blood out through the pulmonary artery and into the lungs at a low pressure. Gases exchange by diffusion in the lung air sacs (alveoli) raising the blood oxygen content from approximately 150 ml/l (venous blood) to 195 ml/l. The oxygenated blood returns through the pulmonary veins to the left atrium and left ventricle.
The LV contracts virtually simultaneously with the right and ejects the same volume of blood but at a much……………… The blood flows through the aorta and the branching arterial system into fine thin-walled tubes called capillaries
The LV contracts virtually simultaneously with the right and ejects the same volume of blood but at a much higher pressure. The blood flows through the aorta and the branching arterial system into fine thin-walled tubes called capillaries.
Capillaries: Here the ultimate function of the cardiovascular system is fulfilled as dissolved gases and nutrients diffuse between the ……………. and the ……………. The circulation of the blood is completed by the venous system which conducts blood back to the venue cavae.
Here the ultimate function of the cardiovascular system is fulfilled as dissolved gases and nutrients diffuse between the capillary blood and the tissue cells. The circulation of the blood is completed by the venous system which conducts blood back to the venue cavae.
Cardiac output is?
The volume of blood ejected by one ventricle during 1 minute.
The cardiac output depends on?
Both volume ejected per contraction (stroke volume) and the number of contractions per minute (heart rate).
In a resting 70 kg adult the stroke volume is………. ml, and the HR is ca 65-75 beats/min; so the resting cardiac output is approximately ……… per min or roughly ….. per min.
In a resting 70 kg adult the stroke volume is 70-80 ml, and the HR is ca 65-75 beats/min; so the resting cardiac output is approximately 75 ml x 70 per min or roughly 51 per min.
The cardiac output is not fixed, however, and adapts rapidly to chaining internal or external circumstances occurs. In severe exercises for example, when oxygen demand can increase tenfold, the heart responds with a fourfold increase in output, or even more in athletes. These changes imply that special control systems must exist for regulating the heart beat, and these controls (chapters 3 and 6)
The cardiac output is not fixed, however, and adapts rapidly to chaining internal or external circumstances occurs. In severe exercises for example, when oxygen demand can increase tenfold, the heart responds with a fourfold increase in output, or even more in athletes. These changes imply that special control systems must exist for regulating the heart beat, and these controls (chapters 3 and 6)
Distribution of cardiac output: The output of the RV passes to the lungs alone. What about the output from the LV?
The output of the LV is in general distribute to the peripheral tissues in proportion to their metabolic rate; resting skeletal muscle for ex accounts for around 20% of the cardiac output. Fig 1.5.
The output of the LV is in general distribute to the peripheral tissues in proportion to their metabolic rate; resting skeletal muscle for ex accounts for around 20% of the cardiac output. Fig 1.5.
This egalitarian principle is overridden, however, where the particular function of an organ requires a higher blood flow: the kidneys consume only …. % of the body’s oxygen yet receive …..% of the cardiac output since this is necessary for their excretory function.
This egalitarian principle is overridden, however, where the particular function of an organ requires a higher blood flow: the kidneys consume only 6% of the body’s oxygen yet receive 20% of the cardiac output since this is necessary for their excretory function.
As a result, some other tissues are relatively ill-supplied and, rather surprisingly, cardiac muscle is one of them. Consequently, it is compelled to extract an unusually ugh proportion of the oxygen content of the blood, namely 65-75%.
The distribution of te CO is not fixed, however, it is actively adjusted to meet varying conditions.
A good ex of this is provided by heavy exercise; where the proportion of the cardiac output going to the skeletal muscle increases to ….. % or more, owing to ………….
A good ex of this is provided by heavy exercise; where the proportion of the cardiac output going to the skeletal muscle increases to 80% or more, owing to widening of the vessels supplying blood to the muscle (vasodilation)
The main factor driving blood along the blood vessels after it has left the heart?
The gradient of pressure along the vessel.
Ventricular ejection raises aortic blood pressure to approximately ………. mmHg above atmospheric pressure while the pressure in the great veins is close to …………., and the pressure difference drives blood from artery to vein.
Ventricular ejection raises aortic blood pressure to approximately 120 mmHg above atmospheric pressure while the pressure in the great veins is close to atmospheric pressure, and the pressure difference drives blood from artery to vein.
Arterial pressure is pulsatile, however, not steady, because the heart ejects blood intermittently; between successive ejection phases the systemic arterial pressure decays from 120 mmHg to approximately 80 mmHg, while pulmonary pressure decays from 25 mmHg to 10 mmHg.
The conventional way of writing this is 120/80 mmHg and 25/10 mmHg.
Arterial pressure is pulsatile, however, not steady, because the heart ejects blood intermittently; between successive ejection phases the systemic arterial pressure decays from 120 mmHg to approximately 80 mmHg, while pulmonary pressure decays from 25 mmHg to 10 mmHg.
Fig 1.6
The conventional way of writing this is 120/80 mmHg and 25/10 mmHg.
The conventional units are mmHg above atmospheric pressure. Why?
Because human blood pressure is measured clinically with a mercury column taking atmospheric pressure as the reference of zero level.
(See Appendic “pressure”)
Fig 1.6: The profile of blood pressure and velocity in the systemic circulation of a resting man. The abscissa represents distance along the vessels. Velocity at any level is the ………… divided by the total……………. of the vascular bed at that point.
Velocity at any level is the cardiac output divided by the total cross-sectional area of the vascular bed at that point.
Simple “law of flow”:
The relation between a pulsatile flow and pulsatile pressure is quite complex, but is is useful at this stage to consider a simpler situation; such as water flowing along a rigid tube under a steady pressure gradient. Under these conditions: flow (Q (med dot över Q)) is directly proportional to the pressure difference between the ….. (P1) and …..(P2) of the tube.
Under these conditions: flow (Q) is directly proportional to the pressure difference between the inlet (P1) and outlet (P2) of the tube.
Q = P1-P2
By inserting a proporitonality factor (K) into the expression we can change it into an equation describing flow
Q = K (P1-P2)
Where K is called the hydraulic conductance of the tube. Conductance is the reciprocal of resistance (R) , so we can also write:
Q = (P1-P2)/R
(Q med dot över)
This expression is a form of Darcy’s law of flow and is analogous to Ohm’s lax for an electrical current. (I = delta V/R)
(se 1.4 s 16)
It states that flow is proportional to driving pressure (P1-P2) and is inversely proportional to they hydraulic resistance.
Flow is often represent by Q with a dot above (the Q) because ….?
Flow is often represent by Q because Q stands for quantity of fluid and the dot denotes rate of passage, this being Newton’s original calculus notation.
It should be noted that flow is by definition a rate (the passage of a volume or mass per unit time) and the common expression “rate of flow” is really rather muddling and best avoided.
It should be noted that flow is by definition a rate (the passage of a volume or mass per unit time) and the common expression “rate of flow” is really rather muddling and best avoided.
The total resistance of the systemic circulation in man is around ………. mmHg per ml/min, while that of the pulmonary circulation is only ……. mmHg per ml/min, and the latter low value explains why a very low pressure suffices to drive the cardiac output through the lungs.
The total resistance of the systemic circulation in man is around 0.02 mmHg per ml/min, while that of the pulmonary circulation is only 0.003 mmHg per ml/min, and the latter low value explains why a very low pressure suffices to drive the cardiac output through the lungs.
The law of flow helps us to understand how the blood flow to an organ is regulated. Equation 1.3 shows that there are essentially only 2 ways of altering flow. Which ones?
Either the driving pressure must be changed or else the vascular resistance.
In normal subjects blood pressure is in fact kept roughly constant, and it is changes in vascular resistance that regulate local blood flow.
In normal subjects blood pressure is in fact kept roughly constant, and it is changes in vascular resistance that regulate local blood flow. EX: Salivation.
During salivation, for ex, blood flow to the salivary glands can increase 10 times due to a fall in vascular resistance to 1/10 its former value, while the driving pressure (arterial pressure) does not increase at all. Changes in vascular resistance are brought about by contraction or relaxation of the vessels, so we should next consider their structure.
The aorta and pulmonary artery divide into smaller arteries, which branch progressively to form narrow high resistance vessel called arterioles. Fig 1.8.
Arterioles branch into innumerable capillaries, which ten converge to form venues and veins. The characteristic dimensions of these various vessels are set out in Table 1.2
The aorta and pulmonary artery divide into smaller arteries, which branch progressively to form narrow high resistance vessel called arterioles. Fig 1.8.
Arterioles branch into innumerable capillaries, which ten converge to form venues and veins. The characteristic dimensions of these various vessels are set out in Table 1.2
(human vessels)
Structure of the blood vessel wall:
With the exception of the capillaries, all blood vessels have the same basic three-layered plan consisting of a …………(innermost layer), ………….(middle layer) and ………….. (outer layer)
Structure of the blood vessel wall:
With the exception of the capillaries, all blood vessels have the same basic three-layered plan consisting of a tunica intima (innermost layer), tunica media (middle layer) and tunica adventitia (outer layer)
Fig 1.7
The tunica intima (inner layer) consists of flat ……….. resting on a thin layer of ………. tissue.
Flat endothelial cells resting on a thin layer of connective tissue.
The endothelial layer is the main barrier to plasma proteins and also secretes many vasoactive product, but it is mechanically weak.
The tunica media (middle layer) supplies mechanical strength and contractile power. It consists of …………… cells arranged circularly and embedded in a matrix of ………… and ……..fibers.
It consists of spindle-shaped smooth muscle cells arranged circularly and embedded in a matrix of elastin and collagen fibers.
Internal and external ………… (sheets) mark the boundaries of the media.
Internal and external elastic laminae (sheets) mark the boundaries of the media.
The tunica adventitia (outer layer) is a ……….. tissue sheath with no distinct outer border which holds the vessel loosely in place.
The tunica adventitia (outer layer) is a connective tissue sheath with no distinct outer border which holds the vessel loosely in place.
The tunica adventitia of the larger arteries contains small ………….. and in the largest arteries they penetrate into the outer 2/3 of the media too. Their task is to nourish the thick media of large vessels.
The tunica adventitia of the larger arteries contains small blood vessels, the vasa vasorum (literally “vessels of vessels”), and in the largest arteries they penetrate into the outer 2/3 of the media too. Their task is to nourish the thick media of large vessels.
Functional classification:
The circulation is constructed on the sond economical principle that each vessel must fulfill at least one other function in addition to the conduction of blood. The structure of the vessel is specially adapted to this function and the following functional categories are recognized:
Elastic arteries Muscular arteries Resistance vessels Exchange vessels The arteriovenous anastomosis Capacitance vessels
Elastic arteris: (diameter 1-2 cm in man). The ………….., have very distensible walls because their tunica media is particularly rich in …………….., a protein which is six times more extensible than rubber.(see Table 1.3). This enables the major arteries to expand and receive the stroke volume during ventricular ejection and to recoil during diastole, thereby converting the intermittent ejection of blood by the heart into a continuous flow through the more distal vessels. Another protein, ………., forms a meshwork of strong fibrils in the media. ……… is 100 times stiffer than …………. and its role seems to be to prevent overdistension.
Elastic arteris: (diameter 1-2 cm in man). The pulmonary artery, aorta, and major branches, like the iliac arteries, have very distensible walls because their tunica media is particularly rich in elastin, a protein which is six times more extensible than rubber.(see Table 1.3). This enables the major arteries to expand and receive the stroke volume during ventricular ejection and to recoil during diastole, thereby converting the intermittent ejection of blood by the heart into a continuous flow through the more distal vessels. Another protein, collagen, forms a meshwork of strong fibrils in the media. Collagen is 100 times stiffer than elastin and its role seems to be to prevent overdistension.
Muscular arteries:
Diameter 0.1-1 cm in man. In medium to small arteries like the …………………… arteris, the tunica media is thicker relative to the …………. diameter, and it contains more ………………. See fig. 1.8. Tabl 1.3.
Diameter 0.1-1 cm in man. In medium to small arteries like the popliteal, radial, cerebral and coronary arteris, the tunica media is thicker relative to the lumen diameter, and it contains more smooth muscle. See fig. 1.8. Tabl 1.3.
Muscular arteries: The muscular arteries act as low-resistance conduits, and their thick walls help prevent collapse at sharp bends like the knee joint. They have a rich autonomic nerve supply, and can contract but they are not in general important in the regulation of blood flow because ……………
The muscular arteries act as low-resistance conduits, and their thick walls help prevent collapse at sharp bends like the knee joint.
They have a rich autonomic nerve supply, and can contract but they are not in general important in the regulation of blood flow because their resistance is low.
Patients bleeding due to acute trauma: Profound contraction of the media prevent patients to bleed to death. Contraction of muscular arteries can also occur physiologically in cerebral arteries, and the limbs of diving animals.
Resistance vessels:
The arterioles have the thickest wall of all vessels relative to their lumen, the ratio of wall thickness to lumen diameter being approximately ……….
The arterioles have the thickest wall of all vessels relative to their lumen, the ratio of wall thickness to lumen diameter being approximately 1.0. Fig 1.8.
Resistance vessels:
The muscular walls of the larger arterioles are richly innervated by vasoconstrictor nerve fibres but the terminal arterioles or met arterioles (diameter 10-40 um) are poorly innervated and possess only …….ayers of smooth muscle cells.
The muscular walls of the larger arterioles are richly innervated by vasoconstrictor nerve fibres but the terminal arterioles or met arterioles (diameter 10-40 um) are poorly innervated and possess only 1-3 layers of smooth muscle cells.
Resistance vessels:
Because of their ………. and ………….. (Table 1.2) the arterioles form the chief resistance to blood flow in the systemic circulation.
Because of their narrow lumen and limited numbers (Table 1.2) the arterioles form the chief resistance to blood flow in the systemic circulation: The press profile in Fig 1.6 confirms this since the pressure drop across the systemic arterioles is much bigger than across any other class of vessel.
Resistance vessels: Because arterioles dominate the resistance to flow through an organ they are able to control the local blood flow and their major role is to match local blood flow to local need.
When they dilate (vasodilation) the resistance to flow ……… and blood flow i………, while vasoconstriction has the reverse effect. Arterioles may thus be regarded as the taps of the circulation, turning local blood flow up or down under the guidance of neural and chemical signals.
When they dilate (vasodilation) the resistance to flow falls and blood flow increases, while vasoconstriction has the reverse effect. Arterioles may thus be regarded as the taps of the circulation, turning local blood flow up or down under the guidance of neural and chemical signals.
Resistance vessels:
The terminal arteriole has one further role; by contracting hard it can prevent blood from flowing through the group of capillaries which arise from it, and can thus regulate the number of functioning capillaries in the tissue. (This job used to be attributed to pre capillary sphincters but it now seems that discrete sphincters only occur in a few tissues, such as the ………..
The terminal arteriole has one further role; by contracting hard it can prevent blood from flowing through the group of capillaries which arise from it, and can thus regulate the number of functioning capillaries in the tissue. (This job used to be attributed to pre capillary sphincters but it now seems that discrete sphincters only occur in a few tissues, such as the mesentery.
Exchange vessels:
The capillaries are tiny (diameter 4-7 um) and short (250-750 um) and they are so numerous that most cells are no further than 10-20 um from the nearest capillary. The capillary wall is reduced to a single layer of ………… cells, and the thinness of this layer, approximately ……..um, facilitates the rapid passage of metabolites between blood and tissue.
The capillaries are tiny (diameter 4-7 um) and short (250-750 um) and they are so numerous that most cells are no further than 10-20 um from the nearest capillary. The capillary wall is reduced to a single layer of endothelial cells, and the thinness of this layer, approximately 0.5 um, facilitates the rapid passage of metabolites between blood and tissue.
Exchange vessels:
The capillary wall is reduced to a single layer of endothelial cells, and the thinness of this layer, approximately 0.5 um, facilitates the rapid passage of metabolites between blood and tissue.
Some exchange also takes place further downstream across slightly larger vessels called post capillary or pericytic venues (diameter 15-50 um), which are microscopic venues lacking the complete smooth muscle coat of larger venues. Some gas exchange also occurs across the walls of small …………. before blood even reaches capillaries, so the functional category of “exchange vessel” actually embraces both sides of the true capillary network
Some exchange also takes place further downstream across slightly larger vessels called post capillary or pericytic venues (diameter 15-50 um), which are microscopic venues lacking the complete smooth muscle coat of larger venues. Some gas exchange also occurs across the walls of small arterioles before blood even reaches capillaries, so the functional category of “exchange vessel” actually embraces both sides of the true capillary network
Exchange vessels:
Although capillaries are extremely narrow, the capillary bed as a whole offers only a moderate resistance to flow. This is partly because of a special kind of ………..(chapter 7) and partly because the total cross-sectional area of the capillary bed is ………
Although capillaries are extremely narrow, the capillary bed as a whole offers only a moderate resistance to flow. This is partly because of a special kind of flow (chapter 7) and partly because the total cross-sectional area of the capillary bed is very large (Fig 1.6, Table 1.2).
Exchange vessels:
The large cross-sectional area of the capillary bed has the added advantage of slowing the velocity of the blood down to ……….. mm/s, rather as a river slows down when its channel broadens. This slowing allows the red cell a period of ……… s in the capillary, time enough for it to unload its oxygen and take up carbon dioxide.
The large cross-sectional area of the capillary bed has the added advantage of slowing the velocity of the blood down to 0.5-1 mm/s, rather as a river slows down when its channel broadens. This slowing allows the red cell a period of 1-2 s in the capillary, time enough for it to unload its oxygen and take up carbon dioxide.
The arteriovenous anastomosis:
In a few tissues, notably the …..and ………………, there are shunt vessels (diameter 20-135 um) which pass directly from arterioles to venues and bypass the capillary bed. Their thick muscular walls are innervated by sympathetic nerves
The arteriovenous anastomosis:
In a few tissues, notably the skin and nasal mucosa, there are shunt vessels (diameter 20-135 um) which pass directly from arterioles to venues and bypass the capillary bed. Their thick muscular walls are innervated by sympathetic nerves and in human skin they help in temperature regulation.
(chapter 12)
Capacitane vessles:
Venules (diameter 50-200 um) and veins differ principally in size and number rather than wall structure. They have thin walls which are easily ………. or ……….., and as a result their blood content can vary enormously.
Venules (diameter 50-200 um) and veins differ principally in size and number rather than wall structure. They have thin walls which are easily distended or collapsed, and as a result their blood content can vary enormously.
Capacitane vessles:
The wall of venues comprises an ……………………
The wall of venues comprises an intima, a thin media composed of collagen and smooth muscle, and an adventitia.
Capacitane vessles:
In limb veins the intima possesses pairs of semilunar valves that prevent any back flow of venous blood; but the ………………. lack functional valves.
In limb veins the intima possesses pairs of semilunar valves that prevent any back flow of venous blood; but the large central veins and veins of the head and neck lack functional valves.
Capacitane vessles: Venules and small veins are ……. ……… than arterioles and arteries. (Table 1.2) so they offer a low resistance to flow and a pressure difference of just ………-…… mmHg suffices to derive the cardiac output from venule to vena cava.
Venules and small veins are more numerous than arterioles and arteries. (Table 1.2) so they offer a low resistance to flow and a pressure difference of just 10-15 mmHg suffices to derive the cardiac output from venule to vena cava.
Capacitane vessles:
The main function of the venous system, besides returning blood to the heart, is to act as a…….
The main function of the venous system, besides returning blood to the heart, is to act as a variable reservoir of blood holding about 2/3 of the circulating blood volume—their capacitance function Much of this capacity is located in the numerous venues and small veins of diameter 20 um to 4 mm.
Capacitane vessles:
Moreover, many veins are innervated by ………………, so their volume can be actively controlled; at times of physiological stress they constrict and displace blood into the heart and arterial system.
Moreover, many veins are innervated by vasoconstrictor nerve fibers, so their volume can be actively controlled; at times of physiological stress they constrict and displace blood into the heart and arterial system.
Plumbing of the vascular circuits:
The systemic circulation is made up of numerous specialized circuits supplying the brain, kidneys, gut, etc. Usually the blood supply to an organ arises directly from the aorta so that each organ is supplied at full pressure, without any interference by other organs. (see Fig 1.4) This form of plumbing is called ……………….
The systemic circulation is made up of numerous specialized circuits supplying the brain, kidneys, gut, etc. Usually the blood supply to an organ arises directly from the aorta so that each organ is supplied at full pressure, without any interference by other organs. (see Fig 1.4) This form of plumbing is called “in parallel”.
A few organs are connected “in series” with another organ —that is to say they obtain their blood “second-hand” from the venous outflow of another organ, an arrangement called a ………system.
A few organs are connected “in series” with another organ —that is to say they obtain their blood “second-hand” from the venous outflow of another organ, an arrangement called a portal system.
The biggest portal system is that supplying the ……, which receives approximately ……..% of its blood from the intestine and spleen via the ……vein. F
The biggest portal system is that supplying the liver, which receives approximately 72% of its blood from the intestine and spleen via the portal vein.
Fig 1.4.
(The portal vein enters the liver at the “porta hepatic” or gateway of the liver; and this is how the term “portal system” arose)
The liver also receives a direct arterial supply via the ……………., so its circuitry is partly in …… and partly in ……….. Portal systems have the advantage of transporting a valuable commodity directly from one site to another (e.g. product of digestion from the intestine to the liver) without any dilution of the material in the general circulation.
The liver also receives a direct arterial supply via the hepatic artery, so its circuitry is partly in series and partly in parallel. Portal systems have the advantage of transporting a valuable commodity directly from one site to another (e.g. product of digestion from the intestine to the liver) without any dilution of the material in the general circulation.
Portal systems also exist in the kidney where effluent blood from the ………… supplies the ………….., and in the brain where a portal system carries hormones from the …………. to the …………………
Portal systems also exist in the kidney where effluent blood from the glomerulus supplies the tubules, and in the brain where a portal system carries hormones from the hypothalamus to the anterior pituitary gland.
A portal system has one serious weakness, however; the down/stream tissue receives partially …………. blood under a …………… pressure head, and as a result the downstream tissue is very vulnerable to damage during episodes of …………… (low arterial pressure). Renal tubular damage in particular is a not uncommon complication of severe ………….
A portal system has one serious weakness, however; the down/stream tissue receives partially deoxygenated blood under a reduced pressure head, and as a result the downstream tissue is very vulnerable to damage during episodes of hypotension (low arterial pressure). Renal tubular damage in particular is a not uncommon complication of severe hypotension.
Central control of the cardiovascular system:
The behavior of the heart and blood vessels has to be regulated in order to deal with varying environmental and internal stresses. This involves ……… and ………….., which are coordinated by the ……. and higher regions of the …….
The behavior of the heart and blood vessels has to be regulated in order to deal with varying environmental and internal stresses. This involves nervous and neuroendocrine reflexes, which are coordinated by the brainstem and higher regions of the brain.
Central control of the cardiovascular system:
One of the most important cardiovascular reflexes, the arterial …………….., safeguards blood flow to the brain by maintaining arterial blood pressure.
The arterial baroreceptor reflex
Central control of the cardiovascular system:
…………. in the walls of major arteries sense changes in blood pressure, and reflexly alter the activity of ………….. nerves controlling the heart and blood vessels. This produces changes in ………., peripheral ………. and venous ……….., and these responses help to restore arterial blood pressure to normal.
Baroreceptors in the walls of major arteries sense changes in blood pressure, and reflexly alter the activity of autonomic nerves controlling the heart and blood vessels. This produces changes in cardiac output, peripheral resistance and venous capacitance, and these responses help to restore arterial blood pressure to normal.
Cardiac cycle:
The mature heart is built upon a collagenous skeleton in the shape of a fibrotendinous ring (the …………….), which is located at the arterioventricular junction.
The mature heart is built upon a collagenous skeleton in the shape of a fibrotendinous ring (the annulus fibrosus), which is located at the arterioventricular junction.
The atria and ventricles contract in sequence, resulting in a cycle of pressure and volume changes, and a thorough knowledge of the cycle is needed for the diagnosis of valvular defects.
The atria and ventricles contract in sequence, resulting in a cycle of pressure and volume changes, and a thorough knowledge of the cycle is needed for the diagnosis of valvular defects.
The volume of blood in a ventricle at the end of the filling phase is called the end-diastolic volume and is typically around 120 ml in an adult human. With the closure of the aortic and pulmonary valves, each ventricle once again becomes a ………………….
The volume of blood in a ventricle at the end of the filling phase is called the end-diastolic volume and is typically around 120 ml in an adult human. With the closure of the aortic and pulmonary valves, each ventricle once again becomes a closed chamber.
The mature heart is built upon a collagenous skeleton in the shape of a fibrotendinous ring (the annulus fibrosus), which is located at the arterioventricular junction.
The muscular atria and ventricles are attached to either side of this ring, and the ring is perforated by 4 ………….; each containing a …….
The muscular atria and ventricles are attached to either side of this ring, and the ring is perforated by 4 apertures; each containing a valve.
As well as functioning as the mechanical base of the heart, the fibroendinous ring insulates the ventricles electronically from the atria.
As well as functioning as the mechanical base of the heart, the fibroendinous ring insulates the ventricles electronically from the atria.
Humans: The apex of the heart is formed by the LV and there anterior surface is formed by the RV and RA. The inferior surface of the heart and the pericardium rest on the central tendon of the diaphragm.
The apex of the heart is formed by the LV and there anterior surface is formed by the RV and RA. The inferior surface of the heart and the pericardium rest on the central tendon of the diaphragm.
RA and tricuspid valve:
The RA is a thin-walled muscular chamber which receives the venous return from the ………… and the ……………… (the main vein draining ……………..)
The RA is a thin-walled muscular chamber which receives the venous return from the vena cavae and the coronary sinus (the main vein draining heart muscle)
Fig 2.2a
The wall near the entrance of the superior vena cava also contains the ………………..
The wall near the entrance of the superior vena cava also contains the cardiac pacemaker, the “sparking plug” that initiates each heart beat.
The right atrium communicates with the right ventricle through the tricuspid valve which as it name implies has three cusps, although it is sometimes difficult to distinguish all three.
The right atrium communicates with the right ventricle through the tricuspid valve which as it name implies has three cusps, although it is sometimes difficult to distinguish all three.
OBS: speciesskillnad
Tricuspid valve: It is the large …………. cusp which is mainly responsible for valve closure.
It is the large anterior cusp which is mainly responsible for valve closure.
Each cups is a flexible flap of connective tissue, roughly 0.1 mm thick, covered by endothelium. The free margin of the cusp is tethered by tendinous strings, called ……………….., to an inward projection of the ventricle wall, the papillary muscle. The papillary muscle contracts and tenses the chordae tendinea during systole and this helps prevent the valve from inverting into the atrium during systole.
Each cups is a flexible flap of connective tissue, roughly 0.1 mm thick, covered by endothelium. The free margin of the cusp is tethered by tendinous strings, called chordae tendinea, to an inward projection of the ventricle wall, the papillary muscle. The papillary muscle contracts and tenses the chordae tendinea during systole and this helps prevent the valve from inverting into the atrium during systole.
Right ventricle and pulmonary valve:
The anterior wall of the right ventricle is about 0.5 cm thick in man, and resembles a pocket tacked around the septum. Fig 2.2b
Expulsion of blood is produced chiefly by the free anterior wall approaching the septum, rather like an old-fashioned bellows.
The anterior wall of the right ventricle is about 0.5 cm thick in man, and resembles a pocket tacked around the septum. Fig 2.2b
Expulsion of blood is produced chiefly by the free anterior wall approaching the septum, rather like an old-fashioned bellows.
The outlet from the ventricle into the pulmonary artery is guarded by the pulmonary valve, which, like the aortic valve, consists of ….equal sized, baggy cusps.
The outlet from the ventricle into the pulmonary artery is guarded by the pulmonary valve, which, like the aortic valve, consists of 3 equal sized, baggy cusps.
Left atrium and mitral valve:
The left atrium receives blood from the pulmonary veins and transmits it into the left ventricle through a bicuspid valve. The large anterior and small posterior cusps are thought to look like a bishop’s mitre, hence the name “mitral valve”. The cusp margins are attached by chordae tendinae to 2 papillary muscles in the left ventricle.
The left atrium receives blood from the pulmonary veins and transmits it into the left ventricle through a bicuspid valve. The large anterior and small posterior cusps are thought to look like a bishop’s mitre, hence the name “mitral valve”. The cusp margins are attached by chordae tendinae to 2 papillary muscles in the left ventricle.
left ventricle and aortic valve: The chamber of the left ventricle is conical and ejection of blood is produced by a reduction in both ……….. and …………..
The chamber of the left ventricle is conical and ejection of blood is produced by a reduction in both diameter and length.
LV: The wall is around ……… times thicker than that of the right ventricle because it has to …………….
The wall is around three times thicker than that of the right ventricle because it has to generate higher pressures.
LV: The muslce orientation changes progressively across the wall: the innermost (endocarp-dial) muscle fibres are oriented …………, running from the base of the heart (the fibrotendinous ring) to the apex (tip of the left ventricle); the central fibres run …………; the outermost or epicardial fibre again run ……………..; and intermediate fibres run …………… Fig 2.2c
the innermost (endocarp-dial) muscle fibres are oriented longitudinally, running from the base of the heart (the fibrotendinous ring) to the apex (tip of the left ventricle); the central fibres run circumferentially; the outermost or epicardial fibre again run longitudinally; and intermediate fibres run obliquely. Fig 2.2c
LV: The muslce orientation changes progressively across the wall.
When the chamber contracts, it twists forwards and the apex taps agains the chest wall, producing the apex beat.
The muslce orientation changes progressively across the wall.
When the chamber contracts, it twists forwards and the apex taps agains the chest wall, producing the apex beat. (This can be felt in the fifth, left intercostal space, about 10 cm from the midline)
The root of the aorta contains a …………….-cusp valve similar to the pulmonary valve.
The root of the aorta contains a three-cusp valve similar to the pulmonary valve.
The heart is enclosed in a fibrous sac or pericardium, which is lined by a layer of ………….. and is lubricated by pericardial fluid.
The heart is enclosed in a fibrous sac or pericardium, which is lined by a layer of mesothelium and is lubricated by pericardial fluid.
The lower surface of the pericardium is fused to the diaphragm, and as the diaphragm descends during inspiration, it pulls the heart into a more vertical orientation.
The lower surface of the pericardium is fused to the diaphragm, and as the diaphragm descends during inspiration, it pulls the heart into a more vertical orientation.
Mechanical events of the cardiac cycle:
The cardiac cycle has 4 phases, and we will begin, arbitrarily, at a moment when both the atria and ventricles are in diastole (relaxed). The timings below refer to a human cycle of …… s duration (67 beats/min), and the data have been acquired by a combination of echocardiography, cardiac categorization, electrocardiogrpahy, and cardiometry.
The cardiac cycle has 4 phases, and we will begin, arbitrarily, at a moment when both the atria and ventricles are in diastole (relaxed). The timings below refer to a human cycle of 0.9 s duration (67 beats/min), and the data have been acquired by a combination of echocardiography, cardiac categorization, electrocardiogrpahy, and cardiometry.
Ventricular filling duration: …..s
Inlet valves (tricuspid and mitral): open Outlet valves (pulmonary and aortic: closed
0.5 s
Ventricular diastole lasts for nearly ……. of the cycle at rest, providing ample time for refilling the chamber.
Ventricular diastole lasts for nearly 2/3 of the cycle at rest, providing ample time for refilling the chamber.
Initially the atria too are in diastole and blood flows passively from the great veins through the open atrioventricular valves into the ventricles.
Initially the atria too are in diastole and blood flows passively from the great veins through the open atrioventricular valves into the ventricles.
There is an initial phase of rapid filling, lasting about 0,15 s (Fig 2,3), which has a curious feature; even though ventricular volume is …………, ventricular pressure is …………
There is an initial phase of rapid filling, lasting about 0,15 s (Fig 2,3), which has a curious feature; even though ventricular volume is increasing, ventricular pressure is falling. Fig 2.4, also Fig 6.10
Diastole: There is an initial phase of rapid filling, lasting about 0,15 s (Fig 2,3), which has a curious feature; even though ventricular volume is increasing, ventricular pressure is falling. Reason?
The ventricular wall is recoiling elastically from the deformation of systole, and is in effect sucking blood into the chamber. As the ventricle reaches its natural volume, filling slows down, and further filling required distension of the ventricle by the pressure of the venous blood; ventricular pressure now begins to rise.
Diastole: In the final third of the filling phase, the atria contract and force some additional blood into the ventricle.
In the final third of the filling phase, the atria contract and force some additional blood into the ventricle.
Diastole: In the final third of the filling phase, the atria contract and force some additional blood into the ventricle.
In the resting subjects, this atrial boost is quite small and enhances ventricular filling by only 15-20%: indeed, the absence of an atrial boost in patients suffering from atrial fibrillation (ineffective atrail contractions, makes little difference to resting cardiac output. During exercise, however, when heart rate is high the time available for passive ventricular filling is curtailed, and the atrial boost becomes important.
In the final third of the filling phase, the atria contract and force some additional blood into the ventricle.
In the resting subjects, this atrial boost is quite small and enhances ventricular filling by only 15-20%: indeed, the absence of an atrial boost in patients suffering from atrial fibrillation (ineffective atrail contractions, makes little difference to resting cardiac output. During exercise, however, when heart rate is high the time available for passive ventricular filling is curtailed, and the atrial boost becomes important.
The volume of blood in a ventricle at the end of the filling phase is called the?
End-diastolic volume, EDV (typically around 120 ml in an adult human)
The corresponding end-diastolic pressure (EDP) is a few mmHg.
Table: 2.1: The EDP is a little higher in the left ventricle than in the right: Why?
The reason being that the left ventricle is thicker and therefore less easily distended.
Isovolumetric contraction:
As atrial systole begins to wane, ventricular systole commences. It last 0.35 s and is divided into a brief isovolumetric phase and a longer ………… phase.
As atrial systole begins to wane, ventricular systole commences. It last 0.35 s and is divided into a brief isovolumetric phase and a longer ejection phase.
Isovolumetric contraction:
As soon as ventricular pressure rises fractionally above atrial pressure, the …………. are forced …………..by the reversed pressure gradient.
As soon as ventricular pressure rises fractionally above atrial pressure, the atrioventricular valves are forced shut by the reversed pressure gradient.
Isovolumetric contraction:
Backflow during closure is minimal. Why?
because the cusps are already approximated by vortices behind them in the late filling phase
As soon as ventricular pressure rises fractionally above atrial pressure, the atrioventricular valves are forced shut by the reversed pressure gradient.
The ventricle is now a closed chamber, and the growing wall tension causes a steep rise in the pressure of the trapped blood: indeed the maximum rate of rise of pressure (…………) max, is frequently used as an index of cardiac ………………….
The ventricle is now a closed chamber, and the growing wall tension causes a steep rise in the pressure of the trapped blood: indeed the maximum rate of rise of pressure (dP/dt) max, is frequently used as an index of cardiac contractility.
Ejection: Duration 0.3 s
Inlet valves: closed
Outlet valves: open
Ejection: Duration 0.3 s
Inlet valves: closed
Outlet valves: open
Ejection:
When ventricular pressure exceeds arterial pressure, the outflow valves are forced open and ejection begins.
When ventricular pressure exceeds arterial pressure, the outflow valves are forced open and ejection begins.
Ejection:
…………..of the stroke volume are ejected in the first half of the ejection phase (phase of rapid ejection, approximately 0.15 s), and at first blood is ejected faster than it can escape out of the arterial tree.
As a result, much of it has to be accommodated by ………….. of the large elastic arteries, and this drives arterial pressure up to its maximum or ………….level.
3/4 of the stroke volume are ejected in the first half of the ejection phase (phase of rapid ejection, approximately 0.15 s), and at first blood is ejected faster than it can escape out of the arterial tree.
As a result, much of it has to be accommodated by distension of the large elastic arteries, and this drives arterial pressure up to its maximum or systolic level.
Ejection: Vortices behind the cusps of the open aortic valve prevent the cusps from blocking the adjacent opening of the coronary arteries.
Vortices behind the cusps of the open aortic valve prevent the cusps from blocking the adjacent opening of the coronary arteries.
As systole weakens and the rate of ejection slow down, the rate at which blood flows away through the arterial system begins to ……. the ejection rate and pressure begins to fall.
Active ventricular contraction actually ceases about ….. of the way through the ejection phase, but a slow outflow continues for a while owing to the momentum of the blood.
As systole weakens and the rate of ejection slow down, the rate at which blood flows away through the arterial system begins to exceed the ejection rate and pressure begins to fall.
Active ventricular contraction actually ceases about 2/3 of the way through the ejection phase, but a slow outflow continues for a while owing to the momentum of the blood.
As the ventricle begins to relax, ventricular pressure falls below arterial pressure by 2 to 3 mmHg, but the ………… of the blood prevents immediate valve closure. The reversed pressure gradient, however, progressively decelerates the outflow, as shown in the lower trace of Fig 2.4, until finally a brief back flow (comprising less than 5 % of stroke volume) closes the outflow valve
As the ventricle begins to relax, ventricular pressure falls below arterial pressure by 2 to 3 mmHg, but the outward momentum of the blood prevents immediate valve closure. The reversed pressure gradient, however, progressively decelerates the outflow, as shown in the lower trace of Fig 2.4, until finally a brief back flow (comprising less than 5 % of stroke volume) closes the outflow valve
(see fig 2.4)
Valve closure creates a brief pressure rise in the arterial pressure trace called the ………….
For the rest of the cycle, arterial pressure gradually ………. as blood runs to the periphery.
Valve closure creates a brief pressure rise in the arterial pressure trace called the dicrotic wave.
For the rest of the cycle, arterial pressure gradually decline as blood runs to the periphery.
It must be emphasized that the ventricle does not empty completely; the average ejection fraction in man is 0.67, corresponding to a stroke volume of 70-80 ml in adults. The residual end-systolic volume of about 50 ml acts as a …… which can be utilized to increase stroke volume in ………..
It must be emphasized that the ventricle does not empty completely; the average ejection fraction in man is 0.67, corresponding to a stroke volume of 70-80 ml in adults. The residual end-systolic volume of about 50 ml acts as a reserve which can be utilized to increase stroke volume in exercise.
Isovolumetric relaxation:
Duration 0.08 s
Inlet valves: closed
Outlet valves: closed:
Isovolumetric relaxation:
Duration 0.08 s
Inlet valves: closed
Outlet valves: closed:
With closure of the aortic and pulmonary valves, each ventricle once again becomes a closed chamber. Ventricular pressure falls very rapidly owing to ……………..
With closure of the aortic and pulmonary valves, each ventricle once again becomes a closed chamber. Ventricular pressure falls very rapidly owing to the mechanical recoil of collagen fibres within the myocardium, which were tensed and deformed by the contracting myocytes.
When ventricular pressure has fallen just below atrial pressure, the ………………. open and blood floods in from the atria.
The atria have been refilling during ventricular systole, and this leads us to consider next the atrial cycle.
When ventricular pressure has fallen just below atrial pressure, the atrioventricular valves open and blood floods in from the atria.
The atria have been refilling during ventricular systole, and this leads us to consider next the atrial cycle.
Atrial cycle and central venous pressure cycle:
The cycle of events in the atria produces a cycle of …………… in the veins of the thorax and neck (jugular veins) because the veins are in open communication with the atria.
The cycle of events in the atria produces a cycle of pressure changes in the veins of the thorax and neck (jugular veins) because the veins are in open communication with the atria.
Atrial cycle and central venous pressure cycle:
A direct record of pressure in an atrium or jugular vein reveals that there are 2 main pressure waves per cycle, called the …. and …. waves, and a third smaller wave, the ….wave. (see dashed line in Figure 2.4)
A direct record of pressure in an atrium or jugular vein reveals that there are 2 main pressure waves per cycle, called the A and V waves, and a third smaller wave, the C wave. (see dashed line in Figure 2.4)
Atrial cycle and central venous pressure cycle:
The A wave is an increase in pressure caused by ………, and the A stand for …………
The A wave is an increase in pressure caused by atrial systole, and the A stand for atrial.
Atrial cycle and central venous pressure cycle:
Atrial systole produces a slight ………… of blood through the valveless venous entrances; this briefly reverses the flow in the venue cavae and raises central venous press to ……………
Atrial systole produces a slight reflux of blood through the valveless venous entrances; this briefly reverses the flow in the venue cavae and raises central venous press to its maximum point (3-5 mmHg).
Atrial cycle and central venous pressure cycle:
The next event, the C wave, occurs earlier in the RA than in the neck. In the atrium, it is caused by the …………… bulging back into the atrium as it closes.
In there internal jugular vein, the C wave is caused partly by expansion of the ………… artery, which lies alongside the vein and presses on it during systole: C stands for ………..
The next event, the C wave, occurs earlier in the RA than in the neck. In the atrium, it is caused by the tricuspid valve bulging back into the atrium as it closes.
In there internal jugular vein, the C wave is caused partly by expansion of the carotid artery, which lies alongside the vein and presses on it during systole: C stands for carotid.
Atrial cycle and central venous pressure cycle:
After the C wave, there comes a sharp fall in pressure; called the ………., which is caused by atrial relaxation, and venous inflow reaches its peak velocity during this phase.
After the C wave, there comes a sharp fall in pressure; called the X descent, which is caused by atrial relaxation, and venous inflow reaches its peak velocity during this phase.
See fig 7.20, chapter 7
Atrial cycle and central venous pressure cycle:
As the atria fill, atrial pressure begins to rise again, producing the …. wave, the …. refers to the simultaneously occurring …………….
As the atria fill, atrial pressure begins to rise again, producing the V wave, the V refers to the simultaneously occurring ventricular systole.
Atrial cycle and central venous pressure cycle:
Finally, the atrioventricular valves open and the atria empty passively into the ventricles, producing the sharp …………
Finally, the atrioventricular valves open and the atria empty passively into the ventricles, producing the sharp Y descent.
The cycle of atrial pressure is mirrored in the internal and external jugular veins of the neck, because the latter are in open communication with ………………..
The cycle of atrial pressure is mirrored in the internal and external jugular veins of the neck, because the latter are in open communication with the superior vena cava.
The pulsating jugular veins are readily visible in a recumbent lean subject and this enables the physician to assess the central venous pressure cycle by simple inspection.
Atrial cycle and central venous pressure cycle:
The pulsating jugular veins are readily visible in a recumbent lean subject and this enables the physician to assess the central venous pressure cycle by simple inspection.
What the eye particularly notices in the ned are 2 sudden collapses of the vein, corresponding to the … and …. descents. Examination of the jugular pulse is a regular clinical procedure because certain diseases produce characteristic abnormalities in the pulse. Tricuspid incompetence, for example, can produce exaggerated ….. waves, because blood leaks back through the incompetent valve during ventricular systole.
What the eye particularly notices in the ned are 2 sudden collapses of the vein, corresponding to the X and Y descents. Examination of the jugular pulse is a regular clinical procedure because certain diseases produce characteristic abnormalities in the pulse. Tricuspid incompetence, for example, can produce exaggerated V waves, because blood leaks back through the incompetent valve during ventricular systole.
Effect of heart rate on phase duration:
The timings given earlier for the cardiac cycle refers to a resting subject, but when the heart is beating 180 times per min (close to the normal maximum in people), the duration of the entire cycle is only …….. s, and all phases of the cycle have to be shortened.
0.33 s
The various phases do not, however, all shorten to an equal degree (see Fig 2.5).
Effect of heart rate on phase duration:
The various phases do not all shorten to an equal degree during exercise/stress:
Ventricular systole does shorten, but only to about 0.2 s, and this leaves a mere 0.13 s for refilling during diastole. Passive filling remains important, but ………………. contributes relatively more than at rest.
Ventricular systole does shorten, but only to about 0.2 s, and this leaves a mere 0.13 s for refilling during diastole. Passive filling remains important, but atrial systole contributes relatively more than at rest.
Even with the help of atrial systole, 0.12 s is about the minimum interval that allows an adequate refilling of the human ventricle.
Effect of heart rate on phase duration:
Further increase in heart rate (above normal tachycardia), such as the pathological tachycardia which occurs in the Wolf-Parkinson —-White syndrome (> 250 beats/min), actually causes cardiac output to decline rather than increase, because ………….?
Further increase in heart rate, such as the pathological tachycardia which occurs in the Wolf-Parkinson —-White syndrome (> 250 beats/min), actually causes cardiac output to decline rather than increase, because refilling during diastole becomes inadequate. Diastolic interval is thus the chief factor limiting the maximum useful heart rate.
Clinical aspects of the human cardiac cycle:
The cardiac cycle is assessed in routine clinical practice by examining various physical signs, such as the …………..
The cardiac cycle is assessed in routine clinical practice by examining various physical signs, such as the arterial pulse, the jugular venous pulse, the apex beat, and the heart sounds.
The heart sounds:
When a heart valve closes, the cusps balloon back as they suddenly check the momentum of refluxing blood. The sudden ……… in the cusps sets up a brief vibration, rather as a sail …………. when suddenly filled by a gust of wind. The vibration is transmitted through the walls of the heart and arteries to the chest wall, where it can be heard through a stethoscope. Provided that the valve is normal, it is only …….. that is audible; as with a well-oiled door, opening is ………..
When a heart valve closes, the cusps balloon back as they suddenly check the momentum of refluxing blood. The sudden tension in the cusps sets up a brief vibration, rather as a sail slaps audibly when suddenly filled by a gust of wind. The vibration is transmitted through the walls of the heart and arteries to the chest wall, where it can be heard through a stethoscope. Provided that the valve is normal, it is only closure that is audible; as with a well-oiled door, opening is silent.
2 heart sounds are normally clearly audible per beat, the first and second heart sounds. They are usual represented as lubb-dubb followed by a pause, roughly in waltz time; the first heart sound (lubb) is the one immediately after the pause.
Lubb-dubb should not be taken too seriously, for it appears that only English-speaking hearts go lubb-dubb, while German ones of doop-teup and Turkish ones rrupp-ta.
Phonocardiogram; microphone placed on the ……..
Precordium
Fig 2.3
The first heart sound, a vibration of roughly ….. cycles/s (…… Hertz), is caused by closure of the …………….. valves, which close virtually simultaneously.
The first heart sound, a vibration of roughly 100 cycles/s (100 Hertz), is caused by closure of the tricuspid and mitral valves, which close virtually simultaneously.
The second sound is of similar frequency (100 Hz) and is caused by closure of the aortic and pulmonary valves. The second sound is sometimes audibly “split”, with an initial …. component and a fractionally delayed …….. component; the sounds might then be represented as lubb-terrupp.
The second sound is sometimes audibly “split”, with an initial aortic component and a fractionally delayed pulmonary component; the sounds might then be represented as lubb-terrupp.
Splitting of the second sound is common in healthy young people during inspiration, because …………… increases the filling of the right ventricle; this raises its …………………, which in turn prolongs the right ventricular …………. time and slightly delays …………………………
Splitting of the second sound is common in healthy young people during inspiration, because inspiration increases the filling of the right ventricle; this raises its stroke volume, which in turn prolongs the right ventricular ejection time and slightly delays pulmonary valve closure.
2 additional sounds besides the first and second sounds can be detected by phonocardiography, but they are of low frequency and difficult for untrained ears to detect.
2 additional sounds besides the first and second sounds can be detected by phonocardiography, but they are of low frequency and difficult for untrained ears to detect.
The third heart sound is common in young people and is caused by the …………. of blood into the relaxing ventricles during ……………
The third heart sound is common in young people and is caused by the rush of blood into the relaxing ventricles during early diastole.
The fourth sound occurs just before the first sound, and is caused by ………………….
The fourth sound occurs just before the first sound, and is caused by atrial systole.
Anatomically, the 4 heart valves lie very close together under the sternum (humans), but fortunately each valve is best heard over a distinct auscultation area, some distance away, because the vibration from each valve propagates through the chamber fed by the valve.
Anatomically, the 4 heart valves lie very close together under the sternum (humans), but fortunately each valve is best heard over a distinct auscultation area, some distance away, because the vibration from each valve propagates through the chamber fed by the valve.
There are 2 fundamental classes of valvular abnormality,………… and ………..
There are 2 fundamental classes of valvular abnormality, stenosis, and incompetence.
There are 2 fundamental classes of valvular abnormality, stenosis, and incompetence: In either case blood passes through the valve in a turbulent jet, setting up a high-frequency vibration which is heard as a murmur.
There are 2 fundamental classes of valvular abnormality, stenosis, and incompetence: In either case blood passes through the valve in a turbulent jet, setting up a high-frequency vibration which is heard as a murmur.
Benign murmurs in the young: Caused by turbulence in the ventricular outflow tract. This “benign” systolic murmur is caused by turbulence in the ventricular outflow tract. This benign systolic murmur is especially marked during pregnancy, strenuous exercise and anemia.
Benign murmurs in the young: Caused by turbulence in the ventricular outflow tract. This “benign” systolic murmur is caused by turbulence in the ventricular outflow tract. This benign systolic murmur is especially marked during pregnancy, strenuous exercise and anemia.
Electrocardiography:
P wave peak coincide with the onset of?
atrial contraction
QRS complex is followed almost immediately by?
The onset of ventricular contraction and the first heart sound.
The T wave is produced by electrical recharging of the ventricles, and since this marks the onset of ……… it is closely followed by the second heart sound.
diastole
Echo: A beam of ultrasound is directed across the heart from a precordial ultrasonic emitter ( a piezoelectrical crystal), and reflections of the sound from the walls and valves are collected and used to built up a linear record of their motion.
A beam of ultrasound is directed across the heart from a precordial ultrasonic emitter ( a piezoelectrical crystal), and reflections of the sound from the walls and valves are collected and used to built up a linear record of their motion.
Cardiac catheterization:
A catheter is treaded through the antecubital vein and advanced under X-ray guidance through the right atrium into the RV, or even into the pulmonary artery.
A catheter is treaded through the antecubital vein and advanced under X-ray guidance through the right atrium into the RV, or even into the pulmonary artery.
The aorta and LV can be reached by a catheter introduced through the …….artery
Femoral artery
The intracardiac catheter can be put to one of the following uses:
Cine-angiography
Radionuclide angiography
Intracardiac pressure measurement
Intracardiac pacing
Cine-angiography:
A radio-opaque contrast medium is injected through the catheter and the progress of the medium through the cardiac chambers is followed by X-ray cinematography (cardiac angiography). This displays the movement of the heart wall and reveals any valvular regurgitation.
A radio-opaque contrast medium is injected through the catheter and the progress of the medium through the cardiac chambers is followed by X-ray cinematography (cardiac angiography). This displays the movement of the heart wall and reveals any valvular regurgitation.
Radionuclide angiography:
A recent extention of the angiographic method is to inject a gamma-ray emitting isotope into a central vein and record the gamma emission with a scintillation camera placed over the precordium. Not only can images of the heart in diastole and systole be computed but also, from the fall in counts produced by each ejection, the ventricular ejection fraction can be measured.
A recent extention of the angiographic method is to inject a gamma-ray emitting isotope into a central vein and record the gamma emission with a scintillation camera placed over the precordium. Not only can images of the heart in diastole and systole be computed but also, from the fall in counts produced by each ejection, the ventricular ejection fraction can be measured.
Intracardiac pressure measurement:
Chamber pressures can be recorded by connecting the catheter to an external pressure transducer, or by mounting a miniature transducer in the tip of the catheter. The pressure drop across a closed valve serves as an excellent test of its ……………
. A pulmonary artery catheter can also be wedged in the pulmonary arterioles, and the recorded “wedge pressure” is often used as an estimate of …………………..
Chamber pressures can be recorded by connecting the catheter to an external pressure transducer, or by mounting a miniature transducer in the tip of the catheter. The pressure drop across a closed valve serves as an excellent test of its competence. A pulmonary artery catheter can also be wedged in the pulmonary arterioles, and the recorded “wedge pressure” is often used as an estimate of pulmonary capillary pressure.
Intracardiac pacing:
This is a therapeutic application of the cardiac catheter, in which a wire catheter is wedged in the ventricle and used to simulate each heart beat from an external electrical device, thereby replacing the heart’s own pacemaker.
This is a therapeutic application of the cardiac catheter, in which a wire catheter is wedged in the ventricle and used to simulate each heart beat from an external electrical device, thereby replacing the heart’s own pacemaker.
Cardiac excitation and contraction:
The human work cell is typically 10-20 um in diameter and 50-100 um long with a single central nucleus. The contraction of the myocyte is caused by the shortening of its ……………..
The contraction of the myocyte is caused by the shortening of its sarcomeres.
Cardiac muscle is almost incapable of ……………. phosphorylation, unlike skeletal muscle.
Cardiac muscle is almost incapable of anaerobic phosphorylation, unlike skeletal muscle.
The potential difference between the interior and exterior of a myocyte can be measured by driving a fine ……….. into the cell.
The potential difference between the interior and exterior of a myocyte can be measured by driving a fine microelectrode into the cell.
The resting membrane potential approximates to …+ equilibrium potential, modified by a slight inward background current of …+
The resting membrane potential approximates to K+ equilibrium potential, modified by a slight inward background current of Na+
Autonomic nerves adjust heart rate by altering the rate of rise of the pacemaker potential and, in the case of parasympathetic fibers, by increasing the resting membrane potential.
Autonomic nerves adjust heart rate by altering the rate of rise of the pacemaker potential and, in the case of parasympathetic fibers, by increasing the resting membrane potential.
Overview:
An isolated heart taken from a cold-blooded animal will continue to beat for a long period if placed in a beaker containing an appropriate solution. This simple experiment proves that cardiac contraction is initiated within the heart itself, unlike skeletal muscle, external nerves are not essential. The heart beat is in fact initiated by?
By a special electrical system in the walls of the heart, and this system is constructed of modified muscle cells.
Cardiac muscle cells, or “myocytes” falls into 2 broad classes: which ones?
The majority of work cells whose task is contraction, while a minority are specialized cells making up an electrical system whose task is to excite the work cells.
The electrical system consists of
1) a group of cells forming the sino-atrial node or “pacemaker” which discharges spontaneously at regular intervals.
2) Elongated cells called conduction fibres that transmit the resulting electrical impulse quickly to the ventricular work cells.
1) a group of cells forming the sino-atrial node or “pacemaker” which discharges spontaneously at regular intervals.
2) Elongated cells called conduction fibres that transmit the resulting electrical impulse quickly to the ventricular work cells.
When the electrical stimulus reaches the ordinary work cell, the latter is excited and fires off an action potential. This leads to a rise in calcium ion concentration within the cell, which in turn activated the contractile proteins of the cell.
When the electrical stimulus reaches the ordinary work cell, the latter is excited and fires off an action potential. This leads to a rise in calcium ion concentration within the cell, which in turn activated the contractile proteins of the cell.
Ultrastructure of the work cell:
Branching cells and their junctions.
The human work cell is typically 10-20 um in diameter and 50-100 um long, with a single central nucleus. The cell is branched and is attached to adjacent cells in an end-to-end fashion.
The human work cell is typically 10-20 um in diameter and 50-100 um long, with a single central nucleus. The cell is branched and is attached to adjacent cells in an end-to-end fashion.
Fig 3.1
The end-to-end junction, or intercalated disc, has a characteristic stepped profile in cross-section, and it contains 2 kinds of smaller specialized junctions; namely ……….. and …………
The end-to-end junction, or intercalated disc, has a characteristic stepped profile in cross-section, and it contains 2 kinds of smaller specialized junctions; namely desmosomes and gap junctions.
As a result of these electrical connections the myocardium acts as an electrically continuous sheet and this enables excitation to reach every cell.
Function of desmosomes?
Hold the adjacent cells together, probably by means of a proteoglycan glue located in the 25 nm-wide gap between the cell membranes.
Function of the gap junction or nexus?
Is a region of very close apposition of the adjacent cell membranes and is thought to be the electrically conductive region through which ionic currents flow from cell to cell.
The myofibril and the sarcomere:
The work cell is packed with long branching contractile bundles whose diameter is around 1 um. They are called myofibril-like units: why?
Because of their resemblance to the myofibrils of skeletal muscle, or myofibrils for brevity.
Each myofibril is composed of smaller units called ………….; which are joined end to end; they are also aligned across the cell, giving the myocyte its characteristic striated appearance under the microscope.
Each myofibril is composed of smaller units called sarcomeres; which are joined end to end; they are also aligned across the cell, giving the myocyte its characteristic striated appearance under the microscope.
The sarcomere is the basic contractile unit and is defined as the material between two Z lines: a Z line is a ………… composed of a protein, a…………
The sarcomere is the basic contractile unit and is defined as the material between two Z lines: a Z line is a thin dark-staining partition composed of a protein, alpha-actinin.
The saromere is 2.0-2.2 um long in resting myocytes and contains 2 kinds of interdigitating filament: a thick filament made of the protein myosin, and a thin filament composed chiefly of actin, another protein.
The saromere is 2.0-2.2 um long in resting myocytes and contains 2 kinds of interdigitating filament: a thick filament made of the protein myosin, and a thin filament composed chiefly of actin, another protein.
The thick filaments, of diameter 11 nm and length 1.6 um, lie in …… in a …….. region of the sarcomere called the …. band.
The thick filaments, of diameter 11 nm and length 1.6 um, lie in parallel in a central region of the sarcomere called the A band. (the A stands for anisotropic, a reference to its appearance through a polarizing microscope).
The thin filaments, of diameter 6 nm and length 1.05 um, are rooted in the ….. line and form the pale….. band (isotropic band); the latter is only approximately 0.25 um wide because most of the length of the thin filament protrudes into the A band in between the myosin rods.
As well as actin, the thin filaments contain the proteins …… and ………
The thin filaments, of diameter 6 nm and length 1.05 um, are rooted in the Z line and form the pale I band (isotropic band); the latter is only approximately 0.25 um wide because most of the length of the thin filament protrudes into the A band in between the myosin rods.
As well as actin, the thin filaments contain the proteins troponin and tropomyosin.
Tubular systems: The surface membrane, or ……………., is invaginated opposite the Z line into a series of fine transverse tubules (……. tubules), which run into the interior of the cell and thus help to ……….. the numerous myofibrils almost simultaneously.
The surface membrane, or sarcolemma, is invaginated opposite the Z line into a series of fine transverse tubules (T tubules), which run into the interior of the cell and thus help to activate the numerous myofibrils almost simultaneously.
The T tubular system is well developed in………… myocytes but is scanty in ……….. cells.
The T tubular system is well developed in ventricular myocytes but is scanty in atrial cells.
The internal ends of the T-tubules are c ………. , so the ………….. fluid is never in direct contact with intracellular fluid.
The internal ends of the T-tubules are closed, so the extracellular fluid is never in direct contact with intracellular fluid.
Within the cell there is a second, separate system of tubules called the ……………, with few if any surface connections:
Sarcoplasmic reticulum
The sarcoplasmic reticulum is developed from ……….. and it consists of a closed set of anastomosing …………… coursing over the myofibrils. The sarcoplasmic tubules expand into flattened sacs called subcarcolemmal cistern near the T-tubules, and in section a T-tubule and adjacent cisterns are often seen as a pair, ord “diad”. The cistern contain a store of …………. that can be released to activate the contractile machinery.
The sarcoplasmic reticulum is developed from endoplasmic reticulum and it consists of a closed set of anastomosing tubules coursing over the myofibrils. The sarcoplasmic tubules expand into flattened sacs called subcarcolemmal cistern near the T-tubules, and in section a T-tubule and adjacent cisterns are often seen as a pair, ord “diad”. The cistern contain a store of calcium ions that can be released to activate the contractile machinery.
Contraction of the myocte is caused by shortening of its …………..
Contraction of the myocte is caused by shortening of its sarcomeres
Contraction of the myocte is caused by shortening of its sarcomeres. Direct inspection shows that the …. bands shorten, but the ….. band does not. This is one of the key observations indicating that contraction is caused by the ……. filaments of the ….. band sliding into the spaces between the thick filaments of the …..band —the sliding filament mechanism.
Contraction of the myocte is caused by shortening of its sarcomeres. Direct inspection shows that the I bands shorten, but the A band does not. This is one of the key observations indicating that contraction is caused by the thin filaments of the I band sliding into the spaces between the thick filaments of the A band —the sliding filament mechanism.
Contraction of the myocte is caused by shortening of its sarcomeres.
The filaments are propelled past each other by the repeated making and breaking of cross bridges between the……………….. These cross bridges are actually the heads of ………… molecules, which protrude from the side of the ……… filament as illustrated in Fig 3.3
The filaments are propelled past each other by the repeated making and breaking of cross bridges between the thin and thick filaments. These cross bridges are actually the heads of myosin molecules, which protrude from the side of the thick filament as illustrated in Fig 3.3
Mechanism of contraction: At rest, the actin sites, with which the myosin heads would react, are blocked by …………. Contraction is initiated by a sudden rise in the concentration of free intracellular calcium ions, which bind to …………., a component of the troponin complex. This alters the position of the adjacent chain, allowing the ………… head to bind to the ………..
Force and movement is produced by a subsequent change in the angle of this cross bridge (i.e the attached myosin head), after which the head disengages and the process repeats itself at a new ….. site. This process occurs at numerous similar sites along the filament, and in this way the ….. filament “rows” itself into the space between the thin filaments.
The most important point about the whole process from the physiological point of view is that the number of cross bridges formed, and therefore the force of the contraction, depends directly on the concentration of ……….. within the myocyte.
At rest, the actin sites, with which the myosin heads would react, are blocked by tropomyosin. Contraction is initiated by a sudden rise in the concentration of free intracellular calcium ions, which bind to troponin C, a component of the troponin complex. This alters the position of the adjacent chain, allowing the myosin head to bind to the actin.
Force and movement is produced by a subsequent change in the angle of this cross bridge (i.e the attached myosin head), after which the head disengages and the process repeats itself at a new actin site. This process occurs at numerous similar sites along the filament, and in this way the thick filament “rows” itself into the space between the thin filaments.
The most important point about the whole process from the physiological point of view is that the number of cross bridges formed, and therefore the force of the contraction, depends directly on the concentration of free calcium ions within the myocyte.
Fig 3.3
Mechanism of contraction:
The energy for cross bridge cycling is provided by …………… , which is broken down during the process into inorganic ………. by an …………. site on the …….. head.
The energy for cross bridge cycling is provided by adenosine triphosphate (ATP) , which is broken down during the process into inorganic phosphate and adenosine disphosphate (ADP) by an ATPase site on the myosin head.
Mechanism of contraction:
In order to maintain an adequate supply of ATP, the myocyte processes an exceptionally high density of …………….., which lie in row between the myofibrils and form 30-35% of the cell volume.
In order to maintain an adequate supply of ATP, the myocyte processes an exceptionally high density of mitochondria, which lie in row between the myofibrils and form 30-35% of the cell volume.
Mechanism of contraction: ATP is manufactured in mitochondria by ……………………, for which oxygen is obligatory, and this is why cardiac performance is directly dependent on ………….. blood flow.
Cardiac muscle is almost incapable of ……….phosphorylation, unlike skeletal muscle.
Mechanism of contraction: ATP is manufactured in mitochondria by oxidative phosphorylation, for which oxygen is obligatory, and this is why cardiac performance is directly dependent on coronary blood flow.
Cardiac muscle is almost incapable of anaerobic phosphorylation, unlike skeletal muscle.
Mechanism of contraction:
The release of calcium from the cisternal store, which activated the contractile machinery, is itself triggered by a change in the ……………….. the cell membrane.
The release of calcium from the cisternal store, which activated the contractile machinery, is itself triggered by a change in the electrical potential across the cell membrane.
Resting membrane potential of a work cell:
The potential difference between the interior and exterior of a myocyte can be measured by driving a fine ………… into the cell (a ……………. is simply a piece of glass tubing which has been heated, drawn out and filled with a conducting solution).
The potential difference between the interior and exterior of a myocyte can be measured by driving a fine microelectrode into the cell (a microelectrode is simply a piece of glass tubing which has been heated, drawn out and filled with a conducting solution).
The intracellular electrode is connected to an amplifier and a voltmeter, and the other lead of the voltmeter is connected to an electrode outside the cells.
Resting membrane potential of a work cell: The intracellular potential of the resting myocyte is found to be …..to ……….. mV (i.e. …………. lower than the ………….. potential). In work cels this resting membrane potential is stable until external excitation is applied, but in sino-atrial (SA) node cells and many conduction fibres it is unstable, drifting towards ……. with time.
Resting membrane potential of a work cell: The intracellular potential of the resting myocyte is found to be -60 mV to -90 mV (i.e. 60-90 mV lower than the extracellular potential). In work cels this resting membrane potential is stable until external excitation is applied (see Fig 3.4a), but in sino-atrial (SA) node cells and many conduction fibres it is unstable, drifting towards zero with time.
(this more complex situation is considered in section 3.7)
Fig 3.4:
Different shapes of action potential at different sites. Note the unstable resting potential in the ……………… Some …………… also have unstable resting potentials.
Note the unstable resting potential in the pacemaker cell (SA node). Some purkinje fibres also have unstable resting potentials.
The resting potential is due primarily to two factors: which ones?
- The high concentration of potassium ions in the intracellular fluid and
- the high permeability of the cell membrane to potassium ions compared with other ions.
The intracellular K+ concentration is about ……. times higher than the extracellular K+ concentration, so there is a continuous tendency for K+ to diffuse ……….. the cell down its concentration gradient.
The intracellular K+ concentration is about 35 times higher than the extracellular K+ concentration, so there is a continuous tendency for K+ to diffuse out of the cell down its concentration gradient.
Table 3.1
There is a continuous tendency for K+ to diffuse out of the cell down its concentration gradient.
However, the negative intracellular ions, mainly organic phosphates and charged proteins, cannot accompany the K+ ions. Why?
Because the cell membrane is impermeable to them.
Fig 3.5
The outward diffusion of a small number of potassium ions therefore creates a very slight separation of charge, and leaves the cell interior negative with respect to the exterior.
There is a continuous tendency for K+ to diffuse out of the cell down its concentration gradient.
However, the negative intracellular ions, mainly organic phosphates and charged proteins, cannot accompany the K+ ions.
The outward diffusion of a small number of potassium ions therefore creates a very slight …………….., and leaves the cell interior …………… with respect to the exterior.
The outward diffusion of a small number of potassium ions therefore creates a very slight separation of charge, and leaves the cell interior negative with respect to the exterior.
Because the electrical charge on a single ion is very large indeed, just ……….. excess negative ion per (10 upphöjt i 15) ion pairs is sufficient to produce the resting potential.
A numerical imbalance of this size is of course far too tiny to be detected by chemical methods.
Because the electrical charge on a single ion is very large indeed, just one excess negative ion per (10 upphöjt i 15) ion pairs is sufficient to produce the resting potential.
A numerical imbalance of this size is of course far too tiny to be detected by chemical methods.
If the negative intracellular potential were big enough, the electrical attraction of the cell interior for the positive potassium ions could fully offset the outward diffusion tendency of the ions, creating a dynamic ………….. in which there was no further net movement of K+ out of the cell. The electrical potential at which this would happen is called the …………………
If the negative intracellular potential were big enough, the electrical attraction of the cell interior for the positive potassium ions could fully offset the outward diffusion tendency of the ions, creating a dynamic equilibrium in which there was no further net movement of K+ out of the cell. The electrical potential at which this would happen is called the potassium equilibrium potential.
The equilibrium potential is, by definition, equal in magnitude to the outward-driving effect of the concentration gradient, or chemical potential as it is called; and the latter depends on the ion concentration outside the cell (Co) relative to that inside (Ci).
The equilibrium potential is, by definition, equal in magnitude to the outward-driving effect of the concentration gradient, or chemical potential as it is called; and the latter depends on the ion concentration outside the cell (Co) relative to that inside (Ci).
The exact relation between equilibrium potential of ionic species X (Ex) and the ionic concentration ratio is given by the Nernst equation 3.1 s 40.
The exact relation between equilibrium potential of ionic species X (Ex) and the ionic concentration ratio is given by the Nernst equation 3.1 s 40.
Experimentally, it has been found that when the extracellular potassium concentration is increased, as can happen in certain medical conditions, the myocyte resting potential ……….. in proportion to the logarithm of the extracellular potassium concentration, as predict by the Nernst equation.
Experimentally, it has been found that when the extracellular potassium concentration is increased, as can happen in certain medical conditions, the myocyte resting potential declines (grows less negative) in proportion to the logarithm of the extracellular potassium concentration, as predict by the Nernst equation.
In hypokalemia, the devaiton increases because potassium conductance declines.
see Fig 3.6
Non-equilibrium due to background currents.
Fig 3.6 shows that the resting membrane potential always …….. …… of the potassium equilibrium potential. This is due to a small inward current of positively charged ions, mainly ………….ions, which is known as the “inward” background current (i b).
shows that the resting membrane potential always falls a little short of the potassium equilibrium potential. This is due to a small inward current of positively charged ions, mainly sodium ions, which is known as the “inward” background current (i b).
Non-equilibrium due to background currents.
Although the permeability of the resting membrane to sodium is only 1/10th to 1/100th of its permeability to potassium, both the electrical gradient and the chemical gradient for Na+ are directed into the cell, and their sum, the electrochemical gradient drives a small inward current of ……+ into the cell.
Although the permeability of the resting membrane to sodium is only 1/10th to 1/100th of its permeability to potassium, both the electrical gradient and the chemical gradient for Na+ are directed into the cell, and their sum, the electrochemical gradient drives a small inward current of Na+ into the cell.
Tab 3.1
Fig 3.5
Non-equilibrium due to background currents.
The chemical gradient for Na+ are directed …… the cell, and their sum, the electrochemical gradient drives a small inward current of Na+ ….. the cell. As a result, the resting membrane potential is 10-20 mV more ……. than the potassium equilibrium potential. Moreover, because the resting potential is not quite negative enough to fully counteract the outward diffusion of K+ ions, there is a continuous trickle of K+ …… of the cell, producing an …… background current (ik).
The chemical gradient for Na+ are directed into the cell, and their sum, the electrochemical gradient drives a small inward current of Na+ into the cell. As a result, the resting membrane potential is 10-20 mV more positive than the potassium equilibrium potential. Moreover, because the resting potential is not quite negative enough to fully counteract the outward diffusion of K+ ions, there is a continuous trickle of K+ out of the cell, producing an outward background current (ik).
Non-equilibrium due to background currents.
In work cells, the outward current Ik is ………….. to the inward current Ib, so the resting membrane potential is ……… despite the continuous slow exchange of potassium for sodium.
In work cells, the outward current Ik is equal to the inward current Ib, so the resting membrane potential is stable despite the continuous slow exchange of potassium for sodium.
Ohm’s law and the importance or relative ionic permeabilities:
The size of the ……………… is given by Ohms’ law, which state that current (i) is proportional to the potential difference (delta x V) and to the electrical conductance (g-the reciprocal of resistance): i = g.delta V
The size of the background currents is given by Ohms’ law, which state that current (i) is proportional to the potential difference (delta x V) and to the electrical conductance (g-the reciprocal of resistance): i = g.delta V
In the case of a cell membrane, the conductance is proportional to its ionic permeability. For potassium ions the potential difference driving the current is the difference between the ………… Em and the ……………. Ek, so the background potassium current ik is, by Ohm’s law: se 3.2. s 40.
In the case of a cell membrane, the conductance is proportional to its ionic permeability. For potassium ions the potential difference driving the current is the difference between the resting membrane potential Em and the potassium equilibrium potential Ek, so the background potassium current ik is, by Ohm’s law: se 3.2. s 40.
Similarly, the inward background current of sodium ions, ib, is by Ohm’s law: se 3.3 s 40
The importance of the ratio of sodium permeability to potassium permeability in setting the membrane potential:
The expression tells us: The resting potential is a potassium equilibrium potential (-94 mV) modified by a fraction of the sodium equilibrium potential (+ 41 mV). The fraction in question is 1/10 if te ratio of gNa to gK is 1:10. This simplified constant field equation therefore predicts that the resting potential should be …….
(-94 + 4.1)/1.1
or -82 mV
And this is reasonably close to the potential in many work cells.
Function of sarcolemmal ion pumps:
The cell is in effect a chemical battery, and the chemical which powers the battery,……is slowly but continuously leaking out of the cell.
potassium
Unchecked, the concentrations of both potassium and sodium would eventually equilibrate across the cell membrane, leaving the battery flat. This is prevented, however, by active pumps in the sarcolemmal membrane, whose function is to preserve the chemical composition of the interior.
The cell is in effect a chemical battery, and the chemical which powers the battery, potassium, is slowly but continuously leaking out of the cell.
Unchecked, the concentrations of both potassium and sodium would eventually equilibrate across the cell membrane, leaving the battery flat. This is prevented, however, by …?
This is prevented, however, by active pumps in the sarcolemmal membrane, whose function is to preserve the chemical composition of the interior.
A sodium-potassium exchange pump simultaneously transport sodium ions ….. of the cell and potassium ions ….. the cell, and the pump rate is enhanced by a rise in …………. Na+ or ……………K+ koncentration.
A sodium-potassium exchange pump simultaneously transport sodium ions out of the cell and potassium ions into the cell, and the pump rate is enhanced by a rise in intracellular Na+ or extracellular K+ koncentration.
Fig 3.5
The exchange of Na+ for K+ is not quite 1 for 1; slightly more …… are pumped out than …… in, and the pump is therefore electrogenic.
The exchange of Na+ for K+ is not quite 1 for 1; slightly more Na+ are pumped out than K+ in, and the pump is therefore electrogenic.
The exchange of Na+ for K+ is not quite 1 for 1; slightly more Na+ are pumped out than K+ in, and the pump is therefore electrogenic.
It must be stressed however, that this effect makes only a minor contribution to the membrane potential; blocking the Na+-K+ pump by ouabain causes only small immediate decrease in membrane potential, because the chief factor generating the resting potential is the…………………
Pumping is an active process and consumes metabolic energy in the form of ……….
It must be stressed however, that this effect makes only a minor contribution to the membrane potential; blocking the Na+-K+ pump by ouabain causes only small immediate decrease in membrane potential, because the chief factor generating the resting potential is the potassium concentration gradient.
Pumping is an active process and consumes metabolic energy in the form of ATP.
The sarcolemmal membrane also possesses calcium pumps which expel intracellular calcium ions that have entered the cell during the action potential. The predominant pump is a ……….in which the passage of 3 extracellular sodium ions across the membrane causes the expulsion of 1 intracellular Ca2+ ion.
calcium-sodium exchange pump
The predominant pump is a calcium-sodium exchange pump in which the passage of 3 extracellular sodium ions across the membrane causes the expulsion of 1 intracellular Ca2+ ion.
The entry of the excess Na+ ion contributes to the inward background current. The Na+-Ca2+ exchange is not powered directly by ATP but is driven by the ……………, rather as a water-wheel is turned by a water gradient. It therefore depends indirectly on the Na+-K+ pump, since it is the Na+-K+ pump that set s up the ……………..
This point is important for understanding the effects of digoxin.
The entry of the excess Na+ ion contributes to the inward background current. The Na+-Ca2+ exchange is not powered directly by ATP but is driven by the downhill sodium concentration gradient, rather as a water-wheel is turned by a water gradient. It therefore depends indirectly on the Na+-K+ pump, since it is the Na+-K+ pump that set s up the sodium gradient. This point is important for understanding the effects of digoxin.
In addition to the sodium-driven calcium pump, the membrane may also possess a few calcium pumps powered directly by ………. Together the calcium pumps maintain the intracellular Ca2+ at an extremely low concentration in resting monocytes, namely 10 -7 M
In addition to the sodium-driven calcium pump, the membrane may also possess a few calcium pumps powered directly by ATP.. Together the calcium pumps maintain the intracellular Ca2+ at an extremely low concentration in resting monocytes, namely 10 -7 M
Action potential of a work cell:
The action potential, which triggers contraction, is an abrupt reversal of the membrane potential to a …………. value. (see Fig 3.4).
The action potential, which triggers contraction, is an abrupt reversal of the membrane potential to a positive value. (see Fig 3.4).
Action potential of a work cell:
In a work cell it is normally initiated by the action potential of an adjacent cell, which draws charge passively from the resting membrane (Fig 3.15) and thereby ………….. its potential.
In a work cell it is normally initiated by the action potential of an adjacent cell, which draws charge passively from the resting membrane (Fig 3.15) and thereby reduced its potential.
Action potential of a work cell:
When the potential reaches a threshold value between -…. mV and -….. mV, the membrane’s ionic permeability suddenly changes; the cell very rapidly ……….. (loses its negative charge) and overshoots to a ………. potential of …… mV to ….. mV. The membrane then immediately begins to depolarize, but when it reaches…………. mV it becomes relatively stable for a long period (200-400 ms). This stage is called the “plateau”, and it causes the cardiac action potential to last far longer than a nerve or skeletal muscle action potential (1-4 ms). Finally the membrane depolarizes, though only 1/1000th of the rate of depolarization, to regain its resting potential.
When the potential reaches a threshold value between -70 mV and -60 mV, the membrane’s ionic permeability suddenly changes; the cell very rapidly depolarizes (loses its negative charge) and overshoots to a positive potential of +20 mV to +30 mV. The membrane then immediately begins to depolarize, but when it reaches zero to -20 mV it becomes relatively stable for a long period (200-400 ms). This stage is called the “plateau”, and it causes the cardiac action potential to last far longer than a nerve or skeletal muscle action potential (1-4 ms). Finally the membrane depolarizes, though only 1/1000th of the rate of depolarization, to regain its resting potential.
Action potentials differ somewhat in form between the various cardiac cells. Atrial potentials last …….. ms and are triangular in most species; ventricular potentials are longer (…………. ms) and more rectangular owing to a more distinct plateau at approximately 0 mV; and Purkinje cells have the ……… potentials, up to ……. ms, with a distinct initial spike followed by a long plateau at approximately -20 mV.
Action potentials differ somewhat in form between the various cardiac cells. Atrial potentials last 150 ms and are triangular in most species; ventricular potentials are longer (400 ms) and more rectangular owing to a more distinct plateau at approximately 0 mV; and Purkinje cells have the longest potentials, up to 450 ms, with a distinct initial spike followed by a long plateau at approximately -20 mV.
The action potential is generated by a sequence of changes in sarcolemmal permeability to ………………, which allows ionic currents to flow passively down their electrochemical gradients. The depolarization spike is caused by an extremely rapid increase in permeability to …………… ions; at the threshold potential, voltage-sensitive ………… channels (fast channels), open very quickly and increase the sodium conductance of the sarcolemma around 100 times.
This allows a rapid flux of sodium ions into the cell (the first inward current, i Na) and drives the potential towards the sodium equilibrium potential.
The action potential is generated by a sequence of changes in sarcolemmal permeability to Na+, Ca2+, and K+, which allows ionic currents to flow passively down their electrochemical gradients. The depolarization spike is caused by an extremely rapid increase in permeability to sodium ions; at the threshold potential, voltage-sensitive sodium channels (fast channels), open very quickly and increase the sodium conductance of the sarcolemma around 100 times (see Fig 3.7 and 3.8)
This allows a rapid flux of sodium ions into the cell (the first inward current, i Na) and drives the potential towards the sodium equilibrium potential. Table 3.1
The membrane potential does not quite reach E Na because an outward potassium current is still flowing. The situation at the overshoot is in effect a mirror image of the resting situation, and for sodium:potassium conductance ratio of 10:1. Equation 3.2 predicts an overshoot potential of + 29 mV. The overshoot is brief because the fast channels are self-inactivating.
Their patency is controlled by 2 different “gates”, which are probably charged intramembranous particles. The “m” or activating gate opens quickly at threshold potential, producing the sudden rise in sodium permeability. The “h” or inactivation gate begins to close at the same time as the m gate opens, but it moves less quickly; it inactivates the channel automatically after a few milliseconds. The membrane potential then begins to fall again, owing to an outward current of K+
The membrane potential does not quite reach E Na because an outward potassium current is still flowing. The situation at the overshoot is in effect a mirror image of the resting situation, and for sodium:potassium conductance ratio of 10:1. Equation 3.2 predicts an overshoot potential of + 29 mV. The overshoot is brief because the fast channels are self-inactivating.
Their patency is controlled by 2 different “gates”, which are probably charged intramembranous particles.
The “m” or activating gate opens quickly at threshold potential, producing the sudden rise in sodium permeability. The “h” or inactivation gate begins to close at the same time as the m gate opens, but it moves less quickly; it inactivates the channel automatically after a few milliseconds. The membrane potential then begins to fall again, owing to an outward current of K+
Action potential: Plateau and calcium ions:
Events up to this point have been similar to those in a nerve. Next, however, the myocyte displays its unique feature; the plaeau. This is produced by a small but sustained ………… current of …………… ions, the second inward current (iSI), which prevent the myocyte from depolarizing rapidly like a nerve. The current consists mainly of ……… ions flowing into the cell down their electrochemical gradient, plus a small contribution from …….. ions.
This is produced by a small but sustained inward current of positive ions, the second inward current (iSI), which prevent the myocyte from depolarizing rapidly like a nerve.
The current consists mainly of calcium ions flowing into the cell down their electrochemical gradient, plus a small contribution from sodium ions.
Action potential: Plateau and calcium ions:
The calcium current is caused by a rise in ……….. permeability to calcium (see Fig 3.8), which is due to the opening of “……. channels” selectively permeable to calcium ions.
The calcium current is caused by a rise in sarcolemmal permeability to calcium (see Fig 3.8), which is due to the opening of “slow channels” selectively permeable to calcium ions.
Action potential: Plateau and calcium ions:
The slow Ca-channles are voltage-contolled channels which begin to activate slowly when the cell depolarizes beyond -……. mV (i.e during rapid depolarization) and they stay open for 200-400 ms. The total conductance of the slow channels is much less than that of the fast sodium channels, and the inward Ca2+ current is quite small, but it is sufficient, almost, to counterbalance the ever-present outward …..+ current. In this way it almost stabilizes the potential at 0 mV to -20 mV.
The slow Ca-channles are voltage-contolled channels which begin to activate slowly when the cell depolarizes beyond -35 mV (i.e during rapid depolarization) and they stay open for 200-400 ms. The total conductance of the slow channels is much less than that of the fast sodium channels, and the inward Ca2+ current is quite small, but it is sufficient, almost, to counterbalance the ever-present outward K+ current. In this way it almost stabilizes the potential at 0 mV to -20 mV.
Action potential: Plateau and calcium ions:
The outward K+ current is itself reduced during the plateau owing to a …………….. (Fig 3.8). This can be viewed as an economy measure, minimizing the number of potassium and calcium ions exchanged during the long plateau and so reducing the eventual energy cost of the action potential.
The outward K+ current is itself reduced during the plateau owing to a fall in the membrane permeability to potassium. (Fig 3.8). This can be viewed as an economy measure, minimizing the number of potassium and calcium ions exchanged during the long plateau and so reducing the eventual energy cost of the action potential.
The existence of the two distinct inward currents, i Na and I SI, has been proved by the use of tetrotoxin, which blocks only the fast, sodium channels (see Fig 3.9).
The existence of the two distinct inward currents, i Na and I SI, has been proved by the use of tetrotoxin, which blocks only the fast, sodium channels (see Fig 3.9).
Action potential: Plateau and calcium ions:
Fig 3.9 also illustrates an important action of adrenaline, namely, it increases the ………………… current. This contributes to the increase in ………….. force produced by adrenaline-
Fig 3.9 also illustrates an important action of adrenaline, namely, it increases the size of the calcium current. This contributes to the increase in contractile force produced by adrenaline-
Action potential: Plateau and calcium ions:
The inward current during the late part of the part of the plateau may be due partly to ………. ions passing in through the ……..-calcium exchange pump (see earlier). One observation favoring this view is that removal of …………….. from the extracellular fluid ……………. the plateau phase.
The inward current during the late part of the part of the plateau may be due partly to sodium ions passing in through the sodium-calcium exchange pump (see earlier). One observation favoring this view is that removal of sodium from the extracellular fluid shortens the plateau phase.
The long plate is important for 2 reasons. Which ones?
- The cell is electrically unexcitable, or refractory during the long period of depolarization (200-400 ms), and since active contraction is weakening by the time the cell becomes depolarized and re-excitable.
Consequently, the mechanical response of the myocardium is normally confined to a single twitch: a fused series of twitches, such as produce a sustained contraction in skeletal muscle, is not possible in myocardium. A sustained myocardial contraction would of course be fatal. - The cardiac action potential does more than just initiate contraction: the plateau phase also directly influences the strength of contraction, because the influx of calcium ions influences the intracellular concentration of calcium. Large plateau currents, such as those stimulated by adrenaline and noradrenaline, are associated with more forceful contractions.
Repolarization and potassium ions:
The potassium conductance gradually increases towards the end of the plateau phase (see Fig 3.8) and, as the slow channels inactivate, the ………. ……. current begins to dominate, producing depolarization to resting potential.
The potassium conductance gradually increases towards the end of the plateau phase (see Fig 3.8) and, as the slow channels inactivate, the outward K+ current begins to dominate, producing depolarization to resting potential.
Se table 3.2: Ionic currents in a myocardial work cell
Ionic currents in a myocardial work cell
Inward means from the extracellular to the intracellular compartment.
Quantity of ions exchange per action potential.
It must be stressed that all the ionic currents are small and the change in intracellular ion concentration resulting from an action potential is tiny. Students often assume that the rush of sodium into the cell must raise intracellular Na+ very substantially. Correct?
No; this is to mistake speed for quantity. In reality only about 40 million sodium ions enter a single myocyte during depolarization, and as the cell contains around 200000 million sodium ions, the intracellular concentration increase by only 0.02%. For intracellular potassium, the change is only 0.001% ( see Appendix Ion exchange).
The Na+-K+- and Na+-Ca2+ pumps are therefore able to restore the chemical composition of the sarcoplasm for only a modest expenditure of metabolic energy.
Excitation-contraction coupling and the calcium cycle:
The link between electrical excitation and muscle contraction is provided by calcium ions. The arrival of an action potential causes the sarcoplasmic concentration of calcium ions to rise sharply; from 0.1 uM to around 5 uM, and some of the calcium binds to …………….. to activate the contractile proteins.
The link between electrical excitation and muscle contraction is provided by calcium ions. The arrival of an action potential causes the sarcoplasmic concentration of calcium ions to rise sharply; from 0.1 uM to around 5 uM, and some of the calcium binds to troponin C to activate the contractile proteins.
Fig 3.3
Excitation-contraction coupling and the calcium cycle:
The correlation between free intracellular calcium ions and contraction has been elegantly demonstrated by the use of aequorin, a protein extracted from luminescent jelly-fish. Aequorin emits a blue light in the presence of … …….. , and she aequorin is microinjected into myocytes, a faint blue flash is emitted immediately before each contraction. See fig 3.10 and 3.12.
The correlation between free intracellular calcium ions and contraction has been elegantly demonstrated by the use of aequorin, a protein extracted from luminescent jelly-fish. Aequorin emits a blue light in the presence of free calcium ions, and she aequorin is microinjected into myocytes, a faint blue flash is emitted immediately before each contraction.
If the free cytosolic calcium ion concentration is increased (e.g. by …………..), more cross bridges are activated and contractile forces increases.
If the free cytosolic calcium ion concentration is increased (e.g. by adrenaline), more cross bridges are activated and contractile forces increases.
How does the action potential produce a 50-fold rise in sarcoplasmic free Ca2+ concentration? The calcium ions arrive from at least 2 sources……
- The store of bound calcium in the sarcoplasmic cistern and
- The second inward current of the plateau.
Right side of Figure 3.11
Se fig 3.11
3.11
- Sarcoplasmic cisternae: an internal source of calcium:
The cistern of the sarcoplasmic reticulum contain a store of calcium ions linked to special quick-release sites. As the spike of depolarization travels into the cell along the ……….., it causes the cistern to release calcium ions from the quick-release sites. Some additional Ca2+ may also be released from sites on the ………. of the sarcolemma. The ions diffuse the micrometer or so into the sarcomere very rapidly, and the cell begins to develop …………. within a few milliseconds. Fig 3.10
The cistern of the sarcoplasmic reticulum contain a store of calcium ions linked to special quick-release sites. As the spike of depolarization travels into the cell along the T-tubule, it causes the cistern to release calcium ions from the quick-release sites. Some additional Ca2+ may also be released from sites on the inner surface of the sarcolemma. The ions diffuse the micrometer or so into the sarcomere very rapidly, and the cell begins to develop tension within a few milliseconds. Fig 3.10
- Sarcoplasmic cisternae: an internal source of calcium:
Stimulated by the raised sarcoplasmic calcium level, the sarcoplasmic reticulum then …………… calcium back into its interiors (see Fig 3.11 left side). In combination with the sarcolemmal …………pumps, this reduces the calcium concentration in the sarcoplasm and terminates the contraction.
Stimulated by the raised sarcoplasmic calcium level, the sarcoplasmic reticulum then actively pumps calcium back into its interiors (see Fig 3.11 left side). In combination with the sarcolemmal Na+-Ca2+ pumps, this reduces the calcium concentration in the sarcoplasm and terminates the contraction.
- Sarcoplasmic cisternae: an internal source of calcium.
Autoradiographic studies indicate that the sarcoplasmic reticulum are some ……… from the release sites, so stored calcium has then to be transported back to the release sites near the ….. lines. This is a relatively slow process taking 200 ms or more during diastole.
Autoradiographic studies indicate that the sarcoplasmic reticulum are some distance from the release sites, so stored calcium has then to be transported back to the release sites near the Z lines. This is a relatively slow process taking 200 ms or more during diastole.
Because the restocking process i slow, the quantity of calcium available at the release sites (and therefore the force of contraction) is influenced by the interval between beats, as described in section 6.8: The Bowditch effect.
Second inward current: an external source of calcium:
During the plateau, an influx of external calcium ions boosts the intracellular calcium content. Thus, extracellular calcium enhances the contractile force of the heart. This is evidently due to its influx during the second inward current, since the force of myocardial contraction correlated with the size of the current; and if the calcium current is increased by ……….., contractile force increases too.
During the plateau, an influx of external calcium ions boosts the intracellular calcium content. Thus, extracellular calcium enhances the contractile force of the heart. This is evidently due to its influx during the second inward current, since the force of myocardial contraction correlated with the size of the current; and if the calcium current is increased by adrenaline, contractile force increases too.
The way that the calcium current influences contraction is, however, less direct than might be first supposed, for the number of calcium ions entering the myocyte during a single action potential is actually too small to have much direct effect on intracellular calcium concentration. Rather, the effect of the calcium current on contraction arises in 2 indirect ways.
First, the arrival of the extracellular ions in the sarcoplasm helps to stimulate the release of calcium from the internal store, a phenomenon called “…………………..”. Second, the influx of ………….. calcium ions increases the amount of …………… calcium available for re-uptake into the store, which becomes available in subsequent beats.
First, the arrival of the extracellular ions in the sarcoplasm helps to stimulate the release of calcium from the internal store, a phenomenon called “calcium-induced calcium release”. Second, the influx of extracellular calcium ions increases the amount of intracellular calcium available for re-uptake into the store, which becomes available in subsequent beats.
Size of the internal calcium store:
The size of the intracellular store of calcium depends on the balance between the ……….. of extracellular calcium ions during the ………… and their expulsion by the ……………… during ……………….
The size of the intracellular store of calcium depends on the balance between the influx of extracellular calcium ions during the plateau and their expulsion by the sarcolemmal pumps during diastole.
The size of the intracellular store of calcium depends on the balance between the influx of extracellular calcium ions during the plateau and their expulsion by the sarcolemmal pumps during diastole.
The size of the intracellular store, and with it the contractile force, depends therefore on
1) the ………….Ca2+ concentration and
2) the relative duration of systole (the calcium ………..) and diastole (the calcium …………..)
1) the extracellular Ca2+ concentration and
2) the relative duration of systole (the calcium influx phase) and diastole (the calcium efflux phase)
This point is considered further in section 6.8 (The Bowditch effect)
Action of digoxin:
Digoxin is a cardiac glycoside produced by foxgloves, and it has been used for over two centuries to treat heart failure because it enhances myocardial power. It achieves this by ……
By increasing the level of intracellular calcium, as illustrated in Fig 3.12. Its immediately pharmacological action, however, is to slow down the sarcolemmal Na+-K+ exchange pump, by inhibiting the membrane ATPase that powers it. This produces a rise in intracellular sodium concentration and a fall in the sodium gradient across the cell membrane. Since the Ca2+-Na+ exchange pump is itself driven by the sodium gradient (Fig 3.5) calcium expulsion is slowed and calcium accumulate in the cell.
Pacemaker and conduction system:The sino-atrial node or pacemaker:
The mammalian heart beat is initiated by the sino-atrial (SA) node, a strip of modified muscle roughly 20 mm long x 4 mm wide in man, located on the ………..wall of the RA close to the ………….
The mammalian heart beat is initiated by the sino-atrial (SA) node, a strip of modified muscle roughly 20 mm long x 4 mm wide in man, located on the posterior wall of the RA close to the super vena cava.
Fig 3.13
The sino-atrial node is so called because?
Because it evolved from the sinus venous, an antechamber to the right atrium in lower vertebrates.
The sinus node is composed of small …….. with only scanty ……… and an electrically unstable cell membrane (see later).
The sinus node is composed of small myocytes with only scanty myofibrils and an electrically unstable cell membrane (see later).
As a result of their unstable resting membrane potential, the nodal cells generate an action potential roughly once every …….. This excites the adjacent atrial work cells and a wave of depolarization then spreads across the two atria, passing from cell at a rate of approximately… m/s and initiating atrial systole.
As a result of their unstable resting membrane potential, the nodal cells generate an action potential roughly once every second. This excites the adjacent atrial work cells and a wave of depolarization then spreads across the two atria, passing from cell at a rate of approximately 1 m/s and initiating atrial systole.
Atrioventricular node:
After passing down the atrial septum the electrical impulses reaches the atrioventricular node (AV node), which is a small mass of …….and………… situation in the lower, posterior region of the atrial septum.
After passing down the atrial septum the electrical impulses reaches the atrioventricular node (AV node), which is a small mass of cells and connective tissue situation in the lower, posterior region of the atrial septum.
The AV node marks the start of the only electrical connection across the ………………., which otherwise completely insulates the atria from the ventricles.
The AV node marks the start of the only electrical connection across the annulus fibrosis, which otherwise completely insulates the atria from the ventricles.
The AV node marks the start of the only electrical connection across the annulus fibrosis, which otherwise completely insulates the atria from the ventricles.
The impulse is delayed in the node for approximately …… s (at resting heart rates), owing to the complex circuitry of the cells and their small diameter (2-3 um), which reduces the conduction velocity to only …… m/s. The resulting delay is functionally very important because it allows the atria sufficient time to contract before the ventricles are activated.
The impulse is delayed in the node for approximately 0.1 s (at resting heart rates), owing to the complex circuitry of the cells and their small diameter (2-3 um), which reduces the conduction velocity to only 0.05 m/s. The resulting delay is functionally very important because it allows the atria sufficient time to contract before the ventricles are activated.
The main bundle (bundle of His) and its branches:
A bundle of fast-conducting muscle fibers, called the bundle of His, next conveys the electrical impulse from the AV node across the …………….. into the fibrous upper part of the interventricular septum.
Here the bundle turn ……………and runs along the crest of the muscular septum (see fig 3.13) , giving off the so-called “left bundle branch” which really comprises 2 sets of fibres, one ………. and one ……….. These course down the left side of the septum to supply the left ventricle. The remaining bundle, the right bundle branch, runs down the right side of the septum and supplies the right ventricle.
A bundle of fast-conducting muscle fibers, called the bundle of His, next conveys the electrical impulse from the AV node across the annulus fibrosis into the fibrous upper part of the interventricular septum.
Here the bundle turn forwards and runs along the crest of the muscular septum (see fig 3.13) , giving off the so-called “left bundle branch” which really comprises 2 sets of fibres, one anterior and one posterior. These course down the left side of the septum to supply the left ventricle. The remaining bundle, the right bundle branch, runs down the right side of the septum and supplies the right ventricle.
The bundle fibres are wide, fast-conducting myocytes arranged in a regular end-to-end fashion. They terminate in an extensive network of large fibres in the subendocardium which were described by the Hungarian histologist Purkinje.
The bundle fibres are wide, fast-conducting myocytes arranged in a regular end-to-end fashion. They terminate in an extensive network of large fibres in the subendocardium which were described by the Hungarian histologist Purkinje.
The Purkinje fibres are the …… cells in the heart and their large diameter (40-80 um) endows them with a high conduction velocity (3-5 m/s); their role is to distribute the electrical impulse rapidly to the ………… work cells. From the ………… the impulse spreads from work cell to work cell as approximately 0.5-1 m/s, and excite the whole ventricular mass as near simultaneously as possible.
The Purkinje fibres are the widest cells in the heart and their large diameter (40-80 um) endows them with a high conduction velocity (3-5 m/s); their role is to distribute the electrical impulse rapidly to the endocardial work cells. From the endocardium the impulse spreads from work cell to work cell as approximately 0.5-1 m/s, and excite the whole ventricular mass as near simultaneously as possible.
Dominance:
There are other potential pacemaker sites in the heart, besides the SA node: The SA node normally sets the heart rate simply because its cells have the fastest intrinsic rate of firing and thus “get there first”. The cells of the bundle of His are also capable of spontaneous firing, albeit at the slower rate of 40 per min and some Purkinje cells can generate their own rhythm too, though even more slowly (approximately 15 per min). There is thus a gradient of intrinsic firing rates along the electrical system. The lower cells are normally excited from the SA node, however, before they have time to fire spontaneously, and this is called “dominance” by the SA node.
The SA node normally sets the heart rate simply because its cells have the fastest intrinsic rate of firing and thus “get there first”. The cells of the bundle of His are also capable of spontaneous firing, albeit at the slower rate of 40 per min and some Purkinje cells can generate their own rhythm too, though even more slowly (approximately 15 per min). There is thus a gradient of intrinsic firing rates along the electrical system. The lower cells are normally excited from the SA node, however, before they have time to fire spontaneously, and this is called “dominance” by the SA node.
The existence of an alternative, albeit slower pacemaker is revealed in a pathological condition called “heart block”, in which there is a blockage of the normal electrical connection across the annulus fibrosis. This prevents the SA node from dominating the bundle of His, and cells in the bundle then take over the pacemaker role, driving the ventricles at their own intrinsic rate of about 40 beats/min.
The existence of an alternative, albeit slower pacemaker is revealed in a pathological condition called “heart block”, in which there is a blockage of the normal electrical connection across the annulus fibrosis. This prevents the SA node from dominating the bundle of His, and cells in the bundle then take over the pacemaker role, driving the ventricles at their own intrinsic rate of about 40 beats/min.
Nodal electricity:
The pacemaker potential:
Myocytes can be divided into ……….with stable resting membrane potentials and ………… with unstable membrane potentials.
Myocytes can be divided into work cells with stable resting membrane potentials and pacemaker cells with unstable membrane potentials.
The resting membrane potential of a SA node cell is only about ……mV, and it decays …………. as illustrated in Fig 3.4 and 3.14
The resting membrane potential of a SA node cell is only about -60 mV, and it decays spontaneously as illustrated in Fig 3.4 and 3.14
The resting membrane potential of a SA node cell is only about -60 mV, and it decays spontaneously. This slowly declining potential is called the ……….. (pr pre-potential) and when it reaches threshold (approximately -…. mV in nodal cells) it triggers an action potential, which sparks off the next heart beat.
This slowly declining potential is called the pacemaker potential (pr pre-potential) and when it reaches threshold (approximately -40 mV in nodal cells) it triggers an action potential, which sparks off the next heart beat.
The slope of the pacemaker potential determines the time taken to reach the threshold value, so the slope governs heart rate; the steeper the slope the sooner threshold is reached and the shorter the time between beats.
The slope of the pacemaker potential determines the time taken to reach the threshold value, so the slope governs heart rate; the steeper the slope the sooner threshold is reached and the shorter the time between beats.
Since the pacemaker slope is steeper in SA node cells than elsewhere in the electrical system, the SA node has the highest ……………….. and initiates each heart beat.
Since the pacemaker slope is steeper in SA node cells than elsewhere in the electrical system, the SA node has the highest intrinsic firing rate and initiates each heart beat.
The SA node has the highest intrinsic firing rate and initiates each heart beat.
The decay of the pacemaker potential is caused by a gradual ……… in membrane permeability to ……………… ions, which is reflected in a fall in total membrane conductance (see Fig 3.7).
The decay of the pacemaker potential is caused by a gradual fall in membrane permeability to potassium ions, which is reflected in a fall in total membrane conductance (see Fig 3.7).
The decay of the pacemaker potential is caused by a gradual fall in membrane permeability to potassium ions, which is reflected in a fall in total membrane conductance.
As a result, the ………. background current iK falls progressively, allowing the …………… background current (termed if in nodal cells) to depolarize the cell slowly (see Fig 3.14).
As a result, the outward background current iK falls progressively, allowing the inward background current (termed if in nodal cells) to depolarize the cell slowly (see Fig 3.14).
The decay of the pacemaker potential is caused by a gradual fall in membrane permeability to potassium ions, which is reflected in a fall in total membrane conductance. As a result, the outward background current iK falls progressively, allowing the inward background current (termed if in nodal cells) to depolarize the cell slowly (see Fig 3.14).
As the potential approaches -……mV, some low-threshold voltage-gated channels permeable to …….. ions begin to open, so a small inward current of C……. ions contributes to the final third of the pacemaker potential
As the potential approaches -40 mV, some low-threshold voltage-gated channels permeable to calcium ions begin to open, so a small inward current of Ca2+ ions contributes to the final third of the pacemaker potential
Nodal action potentials:
The nodal potential is slow-rising and small in amplitude, somewhat like the potential of a tetrodotoxin-blocked work cell (compare Fig 3.4 and 3.9). This is because the nodal cell lacks functional fast …….. channels, its action potential is generated solely by isI, the slow inward current of predominantly ………..ions. See table 3.3.
This is because the nodal cell lacks functional fast sodium channels, its action potential is generated solely by isI, the slow inward current of predominantly calcium ions. See table 3.3.
The transmission of excitation:
The spread of excitation from the SA node into the atria, conduction system and ventricles is mediated by local electrical currents acting ahead of the action potential.
In the active depolarized region, the exterior of the cell membrane is ……….. charged with respect to the interior, while in the resting zone ahead it is …………..charged (see Fig 3.15).
The spread of excitation from the SA node into the atria, conduction system and ventricles is mediated by local electrical currents acting ahead of the action potential.
In the active depolarized region, the exterior of the cell membrane is negatively charged with respect to the interior, while in the resting zone ahead it is positively charged (see Fig 3.15).
In the active depolarized region, the exterior of the cell membrane is negatively charged with respect to the interior, while in the resting zone ahead it is positively charged (see Fig 3.15).
The 2 regions are connected by a conducting medium; the …………., so positive charge flows in the opposite direction along the cell axis via the gap junctions of the ………………..discs and depolarizes the inside of the membrane.
The process is in fact the discharging of a capacitor, the ……
When the resting membrane has been depolarized to threshold it generates an action potential and the entire process moves on: and since the membrane to the rear is refractory, the excitation progresses u…………..
The 2 regions are connected by a conducting medium; the extracellular fluid, so positive charge flows in the opposite direction along the cell axis via the gap junctions of the intercalated discs and depolarizes the inside of the membrane.
The process is in fact the discharging of a capacitor, the lipid cell membrane.
When the resting membrane has been depolarized to threshold it generates an action potential and the entire process moves on: and since the membrane to the rear is refractory, the excitation progresses unidirectionally.
The rate of conduction is greater in …….. cells, because they have a lower axial ……….. It is also great in cells with large, rapid rising action potentials, because these create bigger propagating ………..
The rate of conduction is greater in wider cells, because they have a lower axial resistance. It is also great in cells with large, rapid rising action potentials, because these create bigger propagating currents.
Nervous control of heart rate:
The pacemaker is innervated by autonomic nerves and its intrinsic rate is continuously modified by activity in these nerved.
Nervous control of heart rate:
The pacemaker is innervated by autonomic nerves and its intrinsic rate is continuously modified by activity in these nerved.
Increased activity in the sympathetic nerves innervating the SA node speeds up the heart rate (tachycardia), while increased activity of the parasympathetic nerves slows it down (bradycardia).
Increased activity in the sympathetic nerves innervating the SA node speeds up the heart rate (tachycardia), while increased activity of the parasympathetic nerves slows it down (bradycardia).
Sympathetic and parasympathetic fibers also innervate the AV node, shortening or lengthening the transmission delay respectively.
Sympathetic and parasympathetic fibers also innervate the AV node, shortening or lengthening the transmission delay respectively.
Both sets of autonomic nerve are continuously active at rest but vagal inhibition predominated: if both systems are blocked the ……………..heart rate turns out to be around 105 beats/min in a young adult (human).
Both sets of autonomic nerve are continuously active at rest but vagal inhibition predominated: if both systems are blocked the intrinsic heart rate turns out to be around 105 beats/min in a young adult.
Physiological alterations of heart rate are usually due to reciprocal changes in —————; for example; the tachycardia of exercise is induced by both an increase in ………….. activity and a simultaneous decrease in ………………activity.
Physiological alterations of heart rate are usually due to reciprocal changes in autonomic nerve activity; for example; the tachycardia of exercise is induced by both an increase in sympathetic activity and a simultaneous decrease in vagal activity.
Pacemaker rate is also sensitive to temperature, and during a fever the heart rate increases by approximately …. beats/min per celsius.
Pacemaker rate is also sensitive to temperature, and during a fever the heart rate increases by approximately 10 beats/min per celsius.
The temperature effect is put to practical use during open heart surgery, where cooling is used to slow the heart.
Mechansim of action of parasympathetic fibres:
The parasympathetic nerve terminals act by releasing a neurotransmitter substance called ……………., which bind to receptor molecules in the cell membrane, the …………..receptors.
The parasympathetic nerve terminals act by releasing a neurotransmitter substance called acethylcholine, which bind to receptor molecules in the cell membrane, the muscarinic receptors.
The parasympathetic nerve terminals act by releasing a neurotransmitter substance called acethylcholine, which bind to receptor molecules in the cell membrane, the muscarinic receptors. Receptor activation produces a virtually immediate bradycardia due to 2 effects: Which ones?
1) The pacemaker potential becomes more negative (hyper polarization) and 2) The rate of upward drift of the pacemaker potential is reduced. See Fig 3.16.
As a result of these 2 changes, the potential takes longer to reach threshold and the internal between beats increases.
Mechansim of action of parasympathetic fibres:
The hyperpolarization is induces by a rise in membrane permeability to potassium due to the opening of additional K+ channels; this increased the outward background current and shift the membrane potential closer towards the potassium equilibrium potential.
The opening of the additional K+ channels is mediated by an intramembrane protein called a ……………….., which may directly link the muscarinic receptor to the K+ channels.
The hyperpolarization is induces by a rise in membrane permeability to potassium due to the opening of additional K+ channels; this increased the outward background current and shift the membrane potential closer towards the potassium equilibrium potential.
The opening of the additional K+ channels is mediated by an intramembrane protein called a G-protein, which may directly link the muscarinic receptor to the K+ channels.
Mechansim of action of parasympathetic fibres:
The reduced slope of the pacemaker potential is due to a reduction in the depolarizing …….. current i nersänkt f; the effect on slope lasts longer than the hyperpolarization, and this is not yet fully understood.
The reduced slope of the pacemaker potential is due to a reduction in the depolarizing inward current i nersänkt f; the effect on slope lasts longer than the hyper polarization, and this is not yet fully understood.
Examples of vagal bradycardia in man include:
Sinus arrhythmia; slowing of the heart during each expiration.
Slowing of the heart at the onset of fainting and during diving.
An extreme example of vagal bradycardia has been given rise to an everyday expression; playing possum; to fool its attachers the opossum feint death by collapsing with a profound bradycardia.
Mechanism of action of sympathetic fibres:
The sympathetic nerve terminals act by releasing the neurotransmitter…………. (………….. in the American literature).
The sympathetic nerve terminals act by releasing the neurotransmitter noradrenaline (norepinephrine in the American literature).
Noradrenaline binds to cell membrane receptors called……………, and over the course of several beats this leads to an increase in firing rate. See Fig 3.17
Beta 1 adrenoreceptors
The hormone adrenaline (epinephrine) acts similarly. Adrenaline and noradrenaline, known collectively as the …………….., not only increase the HR (their ……….. action) but also increase the force of myocardial contraction (…………. action).
The hormone adrenaline (epinephrine) acts similarly. Adrenaline and noradrenaline, known collectively as the catecholamines, not only increase the HR (their chronotropic action) but also increase the force of myocardial contraction (inotropic action).
The chronotropic effect of the catecholamines is mediated by an increase in the rate of rise of the pacemaker potential, which takes less time to reach threshold. The steeper rise is due to?
Due to an increase in the inward background current i f (nersänkt f), which is carried by Na+ and Ca2+ ions.
See fig 3.17
The chronotropic effect of the catecholamines is mediated by an increase in the rate of rise of the pacemaker potential, which takes less time to reach threshold.
If the heart is to function effectively at the higher rate, however, all the phases of the cardiac cycle must be shortened.and catecholamines have 3 additional chronotropic effects which help achieve this. Which ones?
1: They shorten all the conduction delay in the AV node
2: They shorten the plateau of the work cell action potential by increasing the outward potassium current; this shortens systole
3: They increase the rate of relaxation of myocytes by stimulating the cisternal pumps to take up free cytosolic Ca2+ more rapidly.
These additional effects help to preserve the diastolic period available for refilling.
The inotropic (stengthening) effect of the catecholamines is mediated by an increase in the inward ………. during the plateau This enhances the intracellular …………….. over the course of several beats.
The inotropic (stengthening) effect of the catecholamines is mediated by an increase in the inward calcium current during the plateau. This enhances the intracellular calcium store over the course of several beats. (see Fig 3.9 and 3.17).
Mechanism of action of sympathetic fibres: The biochemical events that link receptor activation to changes in ionic channels are an area of very active current research. (see appendix second messengers).
The effects of beta-adrenoreceptor activation seem to be mediated by an intramembrane protein, the …………., which activates a membrane-bound enzyme, …………… The latter catalyses the formation of an intracellular “second messenger”, ……………, which activated protein kinase.
The effects of beta-adrenoreceptor activation seem to be mediated by an intramembrane protein, the Gs-protein, which activates a membrane-bound enzyme, adenylate cyclase. The latter catalyses the formation of an intracellular “second messenger”, cyclic adenosine monophosphate (cAMP), which activated protein kinase.
Mechanism of action of sympathetic fibres:
The effects of beta-adrenoreceptor activation seem to be mediated by an intramembrane protein, the Gs-protein, which activates a membrane-bound enzyme, adenylate cyclase. The latter catalyses the formation of an intracellular “second messenger”, cyclic adenosine monophosphate (cAMP), which activated protein kinase
Protein kinase is an intracellular enzyme which, via ………….., influences the number of functional ……………. channels in the sarcolemma, and the activity of the cisternal calcium pumps.
Protein kinase is an intracellular enzyme which, via phosphorylation, influences the number of functional calcium channels in the sarcolemma, and the activity of the cisternal calcium pumps.
Effect of selected extracellular factors:
Severe extracellular electrolyte disturbances will in general be “A bad thing” for cardiac function.
Hypocalcemia reduced …………., while extreme hypercalcemia arrest the heart in …….. But it is probably hyperkalemia (a raised concentration of extracellular potassium ions) that is most often a problem in clinical practice.
Severe extracellular electrolyte disturbances will in general be “A bad thing” for cardiac function.
Hypocalcemia reduced myocardial contractility, while extreme hypercalcemia arrest the heart in systole. But it is probably hyperkalemia (a raised concentration of extracellular potassium ions) that is most often a problem in clinical practice.
Hyperkalemia:
The normal potassium concentration in extracellular fluid is ………. mV, and a level of only ……. mM K+ can arrest the heart in diastole.
The normal potassium concentration in extracellular fluid is 3.5-5.5 mV, and a level of only 7.5 mM K+ can arrest the heart in diastole.
Hyperkalemia:
Chronic hyperkalemia can arise gradually during renal failure, acidosis or potassium overloading and its direct effect is to …………….. the resting membrane potential by ………… the potassium equilibrium potential.
The action potential is altered too, because the gradual …………. in resting potential allows ……………….
Chronic hyperkalemia can arise gradually during renal failure, acidosis or potassium overloading and its direct effect is to reduce the resting membrane potential by lowering the potassium equilibrium potential. See Fig 3.6
The action potential is altered too, because the gradual redcution in resting potential allows plenty of time for the inactivation gates (h gates) of the fast Na+ channels to close.
Hyperkalemia:
The action potential is altered too, because the gradual redcution in resting potential allows plenty of time for the inactivation gates (h gates) of the fast Na+ channels to close.
At a resting potential of -70 mV, about half of the h gates are closed, while at -50 mV they are all closed. As a result the action potential has a ……………………
At a resting potential of -70 mV, about half of the h gates are closed, while at -50 mV they are all closed. As a result the action potential has a sluggish rise and a small amplitude (see Fig 3.18)
Hyperkalemia:
At a resting potential of -70 mV, about half of the h gates are closed, while at -50 mV they are all closed. As a result the action potential has a sluggish rise and a small amplitude (see Fig 3.18)
Small action potentials produce only small propagating currents, so the conduction of a small action potential is easily ………., leading to………… Moreover, the action potential becomes ……….., which reduced the total influx of …………. and leads to a weakening of the heart beat.
Small action potentials produce only small propagating currents, so the conduction of a small action potential is easily blocked, leading to arrhythmias and heart block. Moreover, the action potential becomes shorter, which reduced the total influx of Ca+ ions and leads to a weakening of the heart beat.
Some drugs affecting cardiac electricity:
The actions of many anti-arrhythmic drugs (e.g. quinidine, procainamide, lignocaine) are still ill-understood, but two classes of drug, beta-adrenoreceptor blockers and calcium-channel blockers, are better understood.
Some drugs affecting cardiac electricity:
The actions of many anti-arrhythmic drugs (e.g. quinidine, procainamide, lignocaine) are still ill-understood, but two classes of drug, beta-adrenoreceptor blockers and calcium-channel blockers, are better understood.
General beta-antagonists like propranolol and oxprenolol, and selective beta1-antagonists like atenolol and metoprolol, block the beta1-adrenoreceptors on nodal and work cells. This interrupt the tonic sympathetic drive to the heart, reducing ………….and…………… Since this also reduced cardiac output and work, beta blockers are often used in the treatment of hypertension (any angina)
General beta-antagonists like propranolol and oxprenolol, and selective beta1-antagonists like atenolol and metoprolol, block the beta1-adrenoreceptors on nodal and work cells. This interrupt the tonic sympathetic drive to the heart, reducing heart rate and contractile force. Since this also reduced cardiac output and work, beta blockers are often used in the treatment of hypertension (any angina)
Verapamil and nifedipine (the dihydropyridines) are a relatively new class of drug which act chiefly on high-threshold voltage-gated …………. channels involved in the plateau phase (……-type channels). These channels are partially blocked, impairing the slow inward current of ………….. ions. This ………………the duration of the action potential and produces a negative inotropic (weakening) effect. These …………….-channel blockers are used to treat certain arrhythmias.
Verapamil and nifedipine (the dihydropyridines) are a relatively new class of drug which act chiefly on high-threshold voltage-gated calcium channels involved in the plateau phase (L-type channels). These channels are partially blocked, impairing the slow inward current of Ca2+ ions. This reduced the duration of the action potential and produces a negative inotropic (weakening) effect. These calcium-channel blockers are used to treat certain arrhythmias.
Summary: The resting membrane potential approximates to a ……….+ equilibrium potential, modified by a slight inward background current of …….+. Ionic pumps maintain the intracellular composition but do not directly generate the membrane potential.
The resting membrane potential approximates to a K+ equilibrium potential, modified by a slight inward background current of Na+. Ionic pumps maintain the intracellular composition but do not directly generate the membrane potential.
Summary: The action potential of work cells arises from a rapid inward current of ………+, followed by a slow inward current of (chiefly) ……….. ions which gives rise to a prolonged plateau. The potential do not only excites contraction but also influences contractile force, by affecting the intracellular …………..+ level.
The action potential of work cells arises from a rapid inward current of Na+, followed by a slow inward current of (chiefly) calcium ions which gives rise to a prolonged plateau. The potential do not only excites contraction but also influences contractile force, by affecting the intracellular Ca2+ level.
Summary: In nodal cells, a decaying pacemaker potential is generated by a decaying ………….. conductance. This triggers a sluggish action potential which is generated solely by the slow inward current.
In nodal cells, a decaying pacemaker potential is generated by a decaying potassium conductance. This triggers a sluggish action potential which is generated solely by the slow inward current.
Autonomic nerves adjust heart rate by altering the rate of rise of the pacemaker potential and, in the case of parasympathetic fibres, by increasing …………………..
Autonomic nerves adjust heart rate by altering the rate of rise of the pacemaker potential and, in the case of parasympathetic fibres, by increasing the resting membrane potential.
What is electrocardiography?
The process of recording the potential changes at the skin surface resulting from the depolarization and depolarization of heart muscle.
The spread of excitation through the myocardium involves small currents flowing through the extracellular fluid. See fig 3.15
These extracellular currents create slight potential differences at the body surface because the extracellular fluid is a continuous conducting medium between the heart and skin.
The size of the potential differences at the surface depends on the……………………..which in turn depends on the …………………. being activated.
The size of the potential differences at the surface depends on the size of the cardiac extracelllular current, which in turn depends on the mass of myocardium being activated.
The minute differences in skin potential (approximately 1 mV) are picked up by metal contact
contact electrodes, measured by a millivoltmeter and recorded on a moving paper strip to produce the ECG.
There are 3 main deflections per cardiac cycle; the p-wave, corresponding to atrial depolarization, the QRS complex, corresponding to ventricular depolarization, and the T wave; corresponding to ventricular depolarization.
There are 3 main deflections per cardiac cycle; the p-wave, corresponding to atrial depolarization, the QRS complex, corresponding to ventricular depolarization, and the T wave; corresponding to ventricular depolarization.
During ventricular excitation, a large mass of muscle is activated almost synchronously, and this produces a large deflection in the ECG: The QRS complex.
During ventricular excitation, a large mass of muscle is activated almost synchronously, and this produces a large deflection in the ECG: The QRS complex.
Myocardial ischemia affects not only the ST segment, but also the T wave, causing it to invert.
Myocardial ischemia affects not only the ST segment, but also the T wave, causing it to invert.
The size and orientation of the cardiac dipole in the frontal plane change continuously as excitation spreads through the ventricle.
The size and orientation of the cardiac dipole in the frontal plane change continuously as excitation spreads through the ventricle.
The ECG is an invaluable aid to the diagnosis of many cardiac disorders, such as?
- Myocardial ischema
- Ventricular hypertrophy
- Irregular rhythms (arrhythmias).
Principle of electrocardiography:
The size of the potential differences at the surface depends on the size of the cardiac extracellular current, which in turn depends on the mass of myocardium being activated. Since the mass of the conduction system is tiny, its depolarization does not register on a surface ECG, though nodal and bundle activity can be recorded from an intracardiac electrode introduced by cardiac catheterization. With the usual surface ECG, however, only the activity of atrial and ventricular working muscle is detected.
The size of the potential differences at the surface depends on the size of the cardiac extracellular current, which in turn depends on the mass of myocardium being activated. Since the mass of the conduction system is tiny, its depolarization does not register on a surface ECG, though nodal and bundle activity can be recorded from an intracardiac electrode introduced by cardiac catheterization. With the usual surface ECG, however, only the activity of atrial and ventricular working muscle is detected.
Relation of ECG waves to cardiac action potentials:
The 2 regions where the trace returns to baseline (the isoelectric state) are called the ……. interval and …….. segment.
The 2 regions where the trace returns to baseline (the isoelectric state) are called the PR interval and ST segment.
These ECG features are compared with the underlying cardiac action potentials in Fig 4.3 and with the mechanical events of the cycle in Fig 2.3
Fig 4.3
Note that the ECG voltage scale is much smaller than that for the ………….. potentials. Note also that the …….. (dashed line) depolarizes before the ……..which is why the T wave is upright.
Fig 4.3
Note that the ECG voltage scale is much smaller than that for the membrane potentials. Note also that the base (dashed line) depolarizes before the apex, which is why the T wave is upright.
The first event of the cardiac cycle, the SA node depolarization, does not register on the ECG because………………….
The first event of the cardiac cycle, the SA node depolarization, does not register on the ECG because nodal mass is too tiny.
The P wave coincides with the ……………, not with …………..
The P wave coincides with the upstrokes of the atrial action potentials, not with contraction, contraction follows during the PR interval.
PR interval: The interval between the beginning of the P wave and the beginning of the QRS complex is always called the PR interval even when it is, strictly-speaking, a P-Q interval. It represents …….
The time taken for excitation to spread over the atria and through the conduction system to reach the ventricular septum
Much of the PR interval is produced by the ………………. through the atrioventricular node, which allows time for atrial systole to develop.
Much of the PR interval is produced by the delay in conduction through the atrioventricular node, which allows time for atrial systole to develop.
The ECG is isoelectric during the PR interval despite the existence of a potential difference between atria (depolarized) and ventricles (polarized) because ……………………..breaks the electrical circuit and no current flows.
The ECG is isoelectric during the PR interval despite the existence of a potential difference between atria (depolarized) and ventricles (polarized) because the insulating annulus fibrosus breaks the electrical circuit and no current flows.
Respir sinus arrhythmia: Decreased hear rate during expiration due to increased ……. discharge. The change is partly a reflex from ………….. receptors, but it persists in anesthetized animals even when ventilation is paralyzed, so the vagal periodicity also arises centrally. Chapter 13
Decreased hear rate during expiration due to increased vagal discharge. The change is partly a reflex from pulmonary stretch receptors, but it persists in anesthetized animals even when ventilation is paralyzed, so the vagal periodicity also arises centrally. Chapter 13
Note that the size of the R wave is reduced during inspiration. Why?
Because the descending diaphragm pulls the heart into a more vertical orientation
Premature beat: As the ventricle is then refractory; the next impulse from the SA node fails to excite the ventricle and there is a ………….., which the patient may notice.
Premature beat: As the ventricle is then refractory; the next impulse from the SA node fails to excite the ventricle and there is a compensatory pause (CP), which the patient may notice.
“My heart keeps missing a beat doctor”
Stokes-Adams attacks: What is this?
The patient may experience sudden faints, such as due to third degree AV block.
Atrial fibrillation: Irregular oscillations (f) replace the normal P waves, and the atrial undergo a continuous uncoordinated rippling motion, probably due to a ………………mechanism. Excitation is transmitted irregularly to the ventricles producing a highly characteristic radial pulse (upper trace) which i s irregularly irregular in timing, and in amplitude (due to ………….)
Irregular oscillations (f) replace the normal P waves, and the atrial undergo a continuous uncoordinated rippling motion, probably due to a circus mechanism. Excitation is transmitted irregularly to the ventricles producing a highly characteristic radial pulse (upper trace) which i s irregularly irregular in timing, and in amplitude (due to variation in passive filling time.
Ventricular fibrillation: se fig 4.9: An ectopic beat occurs during the vulnerable period (latter half of the T wave): The ventricle is vulnerable at this moment because some fibres have repolarized while others are still refractory, so circus pathways can be triggered. This initiates a series of rapid uncoordinated excitations, producing ineffective writhing movements = ventricular fibrillation. Causes include?
Ischaemia, anaesthetic overdosage, and electrocution. There is no cardiac output or peripheral pulse, and death follows within minutes.
Since ventricular depolarization coincides with depolarization of atrial cells (see fig 4.3), the latter is masked by the QRS complex.
Since ventricular depolarization coincides with depolarization of atrial cells (see fig 4.3), the latter is masked by the QRS complex.
ST segment: This coincides with the plateau of the ……………… and rapid ejection occurs during this period.
ST segment: This coincides with the plateau of the ventricular action potential, and rapid ejection occurs during this period.
The first heart sound follows just after the ….wave, and the second sound a little after the …. wave.
The first heart sound follows just after the S wave, and the second sound a little after the T wave. Fig 2.3
Since the ventricle is uniformly depolarized, the ST segment is normally isoelectric. If, however, part of the myocardium is damaged by ischemia (a poor blood supply), there is an apparent depression of the ST segment, a useful clinical sign in people.
Since the ventricle is uniformly depolarized, the ST segment is normally isoelectric. If, however, part of the myocardium is damaged by ischemia (a poor blood supply), there is an apparent depression of the ST segment, a useful clinical sign in people.
Fig 4.9g
The electrical effect of ischemia is to ………… the …………… l of the hypoxic myocytes, and since ventricular polarization is then non-uniform, a current, called the resting injury current, flows between the healthy myocytes and ischemic cells. This shifts the baseline of the ECG (i.e the T-P and P-R regions) and leave the ST segment apparently depressed relative to the new baseline.
The electrical effect of ischemia is to reduce the resting potential of the hypoxic myocytes, and since ventricular polarization is then non-uniform, a current, called the resting injury current, flows between the healthy myocytes and ischemic cells. This shifts the baseline of the ECG (i.e the T-P and P-R regions) and leave the ST segment apparently depressed relative to the new baseline.
T wave, and why it is normally upright (people):
Ventricular repolarization produces a broad asymmetrical upright wave, the T wave. At first acquaintance it may seem odd that the T wave is upright when depolarization is a process of opposite sign to depolarization. The reason is?
The myocytes of the base and epicardium have briefer action potential than the myocytes of the apex and endocardium. See fig 4.3. Repolarization therefore begins in the base and epicardium, followed by the apex and endocardium. Depolarization on the other hand spreads from apex and endocardium to base and epicardium. See Fig 4.4.
Thus depolarization occurs in reverse sequence to depolarization, producing the upright T wave.
People: Myocardial ischemia affects not only the ST segment but also the ………., causing it to invert.
People: Myocardial ischemia affects not only the ST segment but also the T wave, causing it to invert. See Fig 4.9g
Standard limb leads: To understand the shape of the QRS complex we must consider:
1) The position of the recording electrodes relative to the heart.
2) The concept of the heart as an electrical ……..
3) The changes in ……… orientation during excitation.
1) The position of the recording electrodes relative to the heart.
2) The concept of the heart as an electrical dipole
3) The changes in dipole orientation during excitation.
Standard limb leads: Taking the electrode positions first, the ECG is routinely recorded via three electrodes, one on each arm and one on the left leg. In addition, recordings are commonly made from electrodes on the chest wall (the six unipolar precordial leads) but these will not be described here, since our primary concern is with general principles rather than detailed clinical practice.
Taking the electrode positions first, the ECG is routinely recorded via three electrodes, one on each arm and one on the left leg. In addition, recordings are commonly made from electrodes on the chest wall (the six unipolar precordial leads) but these will not be described here, since our primary concern is with general principles rather than detailed clinical practice.
The three limb electrodes can be connected across a voltmeter in three different combinations, called the bipolar limb leads. See Fig 4.5. They are:
........................= lead I ..................... = lead II ................. = lead III
Right arm-Left arm= lead I
Right arm-Left leg = lead II
Left arm-Left leg = lead III
Since the limbs act as volume conductors to the trunk, the electrodes form a triangle around the heart, called ………….?
Einthoven’s triangle
The three leads in effect view the heart from three different angles in the ………..plane
Frontal plane
Lead I forms the top of the triangle, oriented horizontally across the chest, and this angle is taken as ……………
Lead 1 forms the top of the triangle, oriented horizontally across the chest, and this angle is taken as zero
Lead II is oriented more vertically, at roughly …… grader to lead I, and lead III at roughly ……….grader.
Lead II is oriented more vertically, at roughly 60 grader to lead I, and lead III at roughly 120 grader.
The electronics are arranged so that an upward deflection occurs when the positive pole of a potential difference is directed ……………. the ………. (lead I) or ………….. (leads II and III).
The electronics are arranged so that an upward deflection occurs when the positive pole of a potential difference is directed towards the left arm (lead I) or left leg (leads II and III).
We must therefore consider the overall polarity of the heart during excitation.
Cardiac dipole:
At any one instant during the spread of excitation through the ventricle, there exists a resting zone with a diffuse cloud of positive extracellular charges (see Fig 4.6a). Just as a diffuse mass can be represented by a centre of gravity, so a diffuse charge can be represented as a singel charge at its electrical centre or pole.
During the spread of excitation, the heart has 2 such poles, one ………… and one ………..; it is an electrical …………..
At any one instant during the spread of excitation through the ventricle, there exists a resting zone with a diffuse cloud of positive extracellular charges (see Fig 4.6a). Just as a diffuse mass can be represented by a centre of gravity, so a diffuse charge can be represented as a singel charge at its electrical centre or pole.
During the spread of excitation, the heart has 2 such poles, one negative and one positive; it is an electrical dipole.
A dipole is surrounded by positive and negative potential fields,which grow weaker with increasing distance. The potential differences can be measured by a voltmeter aligned across the two poles. If the voltmeter is placed exactly at right angles to the dipole; what happens?
It will register no difference in potential.
See Fig 4.6b
This extreme case highlights a crucial point; The potential difference actually recorded depends on the orientation of the recording electrodes relative to the dipole. This is because a dipole is a vector quantity having direction as well as magnitude.
The symbol for a vector is?
An arrow whose length represents vector size and whose direction represents the vector’s angle.
Like a force vector, the cardiac vector can be resolved into 2 components at right angles and it is the magnitude of the component directed at the recording lead which is actually registered. See fig 4.6c.
Like a force vector, the cardiac vector can be resolved into 2 components at right angles and it is the magnitude of the component directed at the recording lead which is actually registered. See fig 4.6c.
Vector sequence:
The size and orientation of the cardiac dipole in the frontal plane changes ………….. as excitation spreads through the ventricles. (For simplicity, only orientations in the frontal plane are described her, but as the ventricles are 3-dimensional bodies lying in an oblique, rotated position, the dipole rawly lies purely in the frontal plane).
he size and orientation of the cardiac dipole in the frontal plane changes continuously as excitation spreads through the ventricles. (For simplicity, only orientations in the frontal plane are described her, but as the ventricles are 3-dimensional bodies lying in an oblique, rotated position, the dipole rawly lies purely in the frontal plane).
Vector sequence:
The first region to depolarize is the…
And next?
And lastly?
- The left side of the inter ventricular septum, activated by the left bundle branch. See fig 4.7
This creates a small dipole directed to the right, about 120 grader to the horizontal. - Next, the remaining septum and most of the endocardium depolarize. The epicardium is still polarized and the bulky left ventricle predominates, creating a large dipole directed to the left, about 60 grader to the horizontal.
The last region to be excited is the base of the ventricles close to the annulus fibosus, so the final dipole is small and directed upwards.
As Fig 4.7 shows, this sequence of ventricular activation causes the cardiac vector to swing round in an anti-clockwise direction, and to wax and wane in size over approximately 90 ms.
Why the QRS complex is complex:
From the lead positions and vector sequence it is possible to understand why the QRS wave contains negative waves and why the QRS complex differs from lead to lead.
As a simple example; consider the ventricular dipole at three instants; the beginning, middle and end of excitation, as seen be leads I and III. In the particular case illustrated in Fig 4.8, the small initial dipole at approximately 120 grader is directed obliquely away from lead I. Resolving the vector, we find a small component directed at 180 grader, which isin the opposite direction to lead I (0 grader), so lead I records a small negative deflection or Q wave. At the same instant lead III (120 grader) records a positive deflection —the beginning of an R wave, with no preaching Q wave. After 50 ms, the dipole has a large component directed at lead I, which records a large upward deflection, the R wave. Lead III is a t right angles to the dipole at this instant, and so records zero potential difference. By 90 ms the dipole has swung round to -100 grader, in the case illustrated, amusing small negative deflection in both leads I and III, i.e. S wave.
Thus, the same event produced a QRS complex in lead I, but an RS complex in lead III.
It must be emphasized that there are many variations from the pattern illustrated owing to variations in cardiac orientation
Why the QRS complex is complex:
From the lead positions and vector sequence it is possible to understand why the QRS wave contains negative waves and why the QRS complex differs from lead to lead.
As a simple example; consider the ventricular dipole at three instants; the beginning, middle and end of excitation, as seen be leads I and III. In the particular case illustrated in Fig 4.8, the small initial dipole at approximately 120 grader is directed obliquely away from lead I. Resolving the vector, we find a small component directed at 180 grader, which isin the opposite direction to lead I (0 grader), so lead I records a small negative deflection or Q wave. At the same instant lead III (120 grader) records a positive deflection —the beginning of an R wave, with no preaching Q wave. After 50 ms, the dipole has a large component directed at lead I, which records a large upward deflection, the R wave. Lead III is a t right angles to the dipole at this instant, and so records zero potential difference. By 90 ms the dipole has swung round to -100 grader, in the case illustrated, amusing small negative deflection in both leads I and III, i.e. S wave.
Thus, the same event produced a QRS complex in lead I, but an RS complex in lead III.
It must be emphasized that there are many variations from the pattern illustrated owing to variations in cardiac orientation.
See Fig 4.8
Electrical axis of the heart.
The direction of the largest dipole is called the electrical axis of the heart, and in Fig 4.7 this is about 60 grader below the horizontal.
The electrical axis can be estimated roughly by comparing the size of the R wave in leads I, II, and III. If for example the largest R wave is in Lead II, the electrical axis is closer to 60 grader than to 0 grader or 120 grader. Conversely, the lead with the smallest QRS complex and R and S waves of nearly equal height lies roughly at ………………. to the electrical axis.
n of the largest dipole is called the electrical axis of the heart, and in Fig 4.7 this is about 60 grader below the horizontal.
The electrical axis can be estimated roughly by comparing the size of the R wave in leads I, II, and III. If for example the largest R wave is in Lead II, the electrical axis is closer to 60 grader than to 0 grader or 120 grader. Conversely, the lead with the smallest QRS complex and R and S waves of nearly equal height lies roughly at right angles to the electrical axis.
The normal range for the electrical axis is very wide; from -30 to + 110 grader. It depends partly on the …………………. It also becomes more vertical during each ……………… as the pericardium is pulled down by the descending diaphragm. See Fig 4.9a. The axis depends too on the ………….. of the wall of the right and left ventricles.
The normal range for the electrical axis is very wide; from -30 to + 110 grader. It depends partly on the anatomical orientation of the heart in the chest, being more vertical in a tall person with a narrow thorax. It also becomes more vertical during each inspiration as the pericardium is pulled down by the descending diaphragm. See Fig 4.9a. The axis depends too on the relative thickness of the wall of the right and left ventricles.
The axis depends too on the relative thickness of the wall of the right and left ventricles. Hypertrophy of the left ventricle shift the electrical axis to the ………..(…….. deviation), while hypertrophy of the right ventricle produces ……….. axis deviation.
The axis depends too on the relative thickness of the wall of the right and left ventricles. Hypertrophy of the left ventricle shift the electrical axis to the left (left axis deviation), while hypertrophy of the right ventricle produces right axis deviation.
Palpitations: benign or bad?
Sinus arrhythmia: A physiological slowing of the sino-atrial discharge rate during each expiration. Sinus arrhythmia is caused by?
A phasic rise in vagal activity during expiration, and it is especially marked in children an young adults.
Other arrhythmias are pathological (inte alla väl?) and may arise from some of the following mechanisms:
-Ectopic beats.
-Heart block (main bunds or a bundle branch may fail to conduct normally)
Complete heart block kan cause a sudden collapse, called a Stokes-Adam attack.
-An abnormal conduction pathway may allow the wave of excitation to travel in a circle (circus): the circle causes a recurring re-entry of excitation just after myoctytes emerge from their refractory period; so the process becomes self-perpetuating. The circus mechanism may underlie the relatively harmless condition of atrial fibrillation. See Fig 4.9f and the rapidly fatal condition of ventricular fibrillation. A classic example of the circus process is provided by the Wolff-Parkonson-White syndrome
Fig 4.9
A classic example of the circus process is provided by the Wolff-Parkonson-White syndrome, which is characterized by episodes of paroxysmal tachycardia or “palpitations” where the ventricles beat at over 200 per min.
The syndrome is caused by an anomalous electrical connection across the annulus fibrosus called the ………………, which allows the ventricular excitation wave to re-enter the atrial and re-excite the ……….. prematurely.
A classic example of the circus process is provided by the Wolff-Parkonson-White syndrome, which is characterized by episodes of paroxysmal tachycardia or “palpitations” where the ventricles beat at over 200 per min.
The syndrome is caused by an anomalous electrical connection across the annulus fibrosus called the bundle of Kent, which allows the ventricular excitation wave to re-enter the atrial and re-excite the AV node prematurely.
Drugs like …………..and…………… prolong the ………………….. period, which renders re-entry more difficult and terminates some circus arrhythmias. The calcium blocker verapamil shortens the action potential and upsets the timing of ………………, so it too can terminate a circus movement.
Drugs like quinidine and procainamide prolong the refractory period, which renders re-entry more difficult and terminates some circus arrhythmias. The calcium blocker verapamil shortens the action potential and upsets the timing of re-entry, so it too can terminate a circus movement.
Assessment of cardiac output:
Cardiac output is defined as?
The volume of blood ejected by one ventricle in one minute: it equals the stroke volume multiplied by heart rate.
In human subjects the output can be measured by a variety of methods, which either measure the cardiac output ……………(The Fick principle and the dilution methods) or measure stroke volume and heart rate ………….. (Doppler and radionuclide methods). The output can also be assessed indirectly by echo and by examining a subject’s peripheral pulse.
In human subjects the output can be measured by a variety of methods, which either measure the cardiac output as a whole (The Fick principle and the dilution methods) or measure stroke volume and heart rate separately (Doppler and radionuclide methods). The output can also be assessed indirectly by echo and by examining a subject’s peripheral pulse.
Ina anesthetized animals, direct methods requiring surgery can also be employed, such as the placing of an electromagnetic flow meter around the aorta.
This chapter concentrate on the methods which are currently most important in medicine: beginning with the gold standard method based on Fick’s principle.
Fick’s principle and the measurement of cardiac output:
The rate at which the circulation takes up oxygen from the lungs kust equal the change in oxygen concentration in the pulmonary blood multiplied by the pulmonary blood flow. Since the pulmonary blood flow is of course the output of the right ventricle, this offers a way of determining the cardiac output.
The rate at which the circulation takes up oxygen from the lungs kust equal the change in oxygen concentration in the pulmonary blood multiplied by the pulmonary blood flow. Since the pulmonary blood flow is of course the output of the right ventricle, this offers a way of determining the cardiac output.
The amount of oxygen carried into the lungs in venous blood per minute is the ……………. times venous ……………..concentration
The amount of oxygen carried into the lungs in venous blood per minute is the blood flow times venous oxygen concentration
O2 in venous blood entering the lungs per minute: se formel s 70
O2 in venous blood entering the lungs per minute: se formel s 70
The amount of oxygen carried into the lungs in venous blood per minute is the blood flow times venous oxygen concentration
Similarly: the amount of oxygen carried out of the lungs per minute in the blood equals ……….. times arterial ………….concentration.
Similarly: the amount of oxygen carried out of the lungs per minute in the blood equals blood flow times arterial oxygen concentration.
O2 in arterial blood leaving the lungs per minute: se formel s 70
O2 in arterial blood leaving the lungs per minute: se formel s 70
The amount of oxygen taken up by the blood during its passage through the lungs therefore equals …..over one minute.
se formel s 70
In a steady state, this oxygen uptake must equal the loss of oxygen from the alveolar gas in the lungs over one minute (V O2)
Oxygen consumption by the alveolar cells can be neglected.
Oxygen consumption by the alveolar cells can be neglected.
We can therefore write:
Alveolar oxygen removed per min = blood oxygen ………….. per min .
Alveolar oxygen removed per min = blood oxygen gained per min .
Or in terms of the arteriovenous concentration difference:
Ca-Cv
V o2 = Q x (Ca-Cv).
This is Fick’s expression, and it tells us that the rate of oxygen …………. from alveolar gas (ml/min) equals pulmonary …………. (litres/min) times the ……………………. in oxygen concentration (ml/litre)
V o2 = Q x (Ca-Cv).
This is Fick’s expression, and it tells us that the rate of oxygen uptake from alveolar gas (ml/min) equals pulmonary blood flow (litres/min) times the arteriovenous difference in oxygen concentration (ml/litre)
Since pulmonary blood flow is actually the output of the right ventricle, we can rearrange the Fick expression to give the cardiac output.
V o2 = Q x (Ca-Cv). This is Fick's expression, and it tells us that the rate of oxygen uptake from alveolar gas (ml/min) equals pulmonary blood flow (litres/min) times the arteriovenous difference in oxygen concentration (ml/litre) Since pulmonary blood flow is actually the output of the right ventricle, we can rearrange the Fick expression to give the cardiac output. Cardaic output (1/min) =
Oxygen uptake rate (ml/min)/
ArterialO2 conc-VenousO2 conc
(ml/l)
Se s 70
se ex s 70 hur det här kan räknas ut/användas.
Practical aspects of Fick’s theoretical method:
Only became practical in man in the 1940s when progress in cardiac cauterization allowed mixed venous blood to be sampled from the right ventricle.
Samples from peripheral veins are unsuitable for this purpose. Why?
Because their oxygen concentration varies: It is 170 ml per litre in renal venous blood, but only 70 ml per litre in coronary venous blood. Venous blood only becomes fully mixed and uniform in the right ventricle outflow tract and pulmonary artery. The problem of obtaining a sample of fully mixed venous blood was finally solved in 1929, when a german physician passes a ureteric catheter through his own arm vein and into the right heart; watching its progress on an x-ray screen.
The Fick method is now as follows: Describe how?
The subject’s resting oxygen consumption is measured over 5 to 10 min by spirometry, or by collection of expired air in a Douglas bag. During this period, an arterial blood sample is taken from the brachial radial or femoral artery, and a mixed venous sample is taken from the pulmonary artery or right ventricle outflow tract by a cardiac catheter, introduce through the antecubital vein. The oxygen content of each blood sample is measured and the cardiac output calculated as above.
Fick’s method is the yardstick by which new methods are usually judged but it has certain limitations: Limitation of the Fick’s method?
It is slow, and beat-by-beat changes in stroke volume cannot be followed. The method is only valid in the steady state, so the transient early response to exercise cannot be measured. The method is invasive, and cannot be used during severe exercise because the cardiac catheter may provoke arrhythmias in a violently beating heart. An indirect version, in which catheterization is avoided and Cv estimated by analysis of rebreathed gas, is less accurate and rarely used today.
The Fick principle generalized:
The principle is quite genial, and applies to any perfused organ in which material or heat is exchanges at a steady rate.
In general terms the flux J of material or heat between the fluid and the perfused organ equals the fluid flow (Q) multiplied by the concentration change between the inlet (C in) and outlet (C out)
J = Q (C out-C in)
Se s 71. Q med prick över.
In physiology, Fick’s principle is widely used to work out the rate at which an organ consumes nutrients like glucose or fatty acids, from measurements of blood flow and the arteriovenous concentration difference for the nutrient.
Indicator dilution and thermal dilution methods:
Indicator dilution method:
In Hamilton’s indicator dilution method, a known mass of a foreign substance (the indicator) is injected rapidly into a …………. or into ……………….. The indicator must be one that is confined to the bloodstream and easy to assay; for example the dye indocyanine green, or albumin labelled with radio iodine. Describe how this work:
In Hamilton’s indicator dilution method, a known mass of a foreign substance (the indicator) is injected rapidly into a central vein or into the right heart. The indicator must be one that is confined to the bloodstream and easy to assay; for example the dye indocyanine green, or albumin labelled with radio iodine.
The bolus of indicator becomes diluted in the returning venous blood, passes through the heart and lungs, and is ejected into the systemic arteries (see Fig 5.2 a). Samples of arterial blood are taken at frequent intervals from the radial or femoral artery, and the concentration of the indicator in the arterial plasma is plotted against time.
Indicator dilution method:
For simplicity, let us at first suppose that the concentration of indicator in the ejected bolus is uniform, as in Fig 5.2b.
The concentration against time plot tells us:
1) The time t needed for the bolus to pass a given point.
2) The average concentration of indicator in the bolus over that period.
Concentration C, is by definition the injected mass, m, divided by the volume of plasma, V, in which the indicator became distributed:
C= m/V.
Concentration C, is by definition the injected mass, m, divided by the volume of plasma, V, in which the indicator became distributed:
C= m/V.
For example, if 2 mg of indicator produces a mean plasma conc of 1 mg/l, the volume of distribution must be…?
2 litres.
For example, if 2 mg of indicator produces a mean plasma conc of 1 mg/l, the volume of distribution must be 2 litres. If this volume takes t seconds to pass a fixed point, the left ventricle evidently pumps plasma along at rate V/t (2 litres in 20 s in Fig 5.2b, or 6 litres/min.
If this volume takes t seconds to pass a fixed point, the left ventricle evidently pumps plasma along at rate V/t (2 litres in 20 s in Fig 5.2b, or 6 litres/min.
For example, if 2 mg of indicator produces a mean plasma conc of 1 mg/l, the volume of distribution must be 2 litres. If this volume takes t seconds to pass a fixed point, the left ventricle evidently pumps plasma along at rate V/t (2 litres in 20 s in Fig 5.2b, or 6 litres/min. In other words, the cardiac output of plasma can be calculated as:
Cardiac output of plasma=
V/t =
mass of indicator m/mean concentration C x time t
Se se 72
The output of blood is then easily calculated, being the output of plasma divided by l-haemotocrit (haemotocrit is the fraction of blood consisting of cells).
V/t =
mass of indicator m/mean concentration C x time t
Se se 72
The output of blood is then easily calculated, being the output of ………………divided by 1-…………………….
The output of blood is then easily calculated, being the output of plasma divided by 1-haemotocrit
(haemotocrit is the fraction of blood consisting of cells).
Cardiac output of plasma =
mass of indicator/Area under C-t curve.
In reality the C-t plot is not of course a square wave, it is a curve which rises to a peak and decays exponentially. See Fig 5.2c, but the above expression still applies.
The exponential decay is caused by the ventricle ejecting only a fraction of its content with each systole, leaving some indicators behind. Indicator-free venous blood returning to the hart during each diastole dilutes the residual indicator, and this in turn is only partially ejected in the next systole, and so on.
After about 15 s, however, the decay curve is disrupted by a “recirculation hump”. This is caused by blood of high indicator concentration returning to the heart after completing one transit of the myocardial circulation (the shortest route back). To apply the above dilution equation, we must find the area under a C-t curve uncomplicated by recirculation, and this is done by extrapolating the early part of the decay curve, before the recirculation hump.
A semi-logarithmic plot facilitates the extrapolation, because it converts the the exponential decay into a straight line; the latter is then extrapolated to a negligible concentration (conventionally 1% of the peak value) as in Figure 5.2c. The area under the corrected C-t curve is computed and used to calculate cardiac output.
Pros and cons: the results agree with Fick’s direct method to +/- 5%. The dilution method has an improved time resolution (30 s, cf.> 5 min for Fick’s method) and can be used in exercise, since ventricular catheterization is not required.
The error involved in extrapolating the decay curve may be short and distort, this can be a serious limitation.
Thermal dilution method:
This variant of the dilution method is widely used in cardiac departments. Instead of a foreign chemical, temperature is used as the indicator. A known volume of cold saline is injected quickly into the ……………… and the dilution of the cold saline by warm blood is recorded by a thermistor-tipped catheter (Swan-ganz catheter) in the more distal ………..Cardiac output can then be calculated from the area under the temperature-time plot from and the amount of heat (i.e. cold) injected.
This variant of the dilution method is widely used in cardiac departments. Instead of a foreign chemical, temperature is used as the indicator. A known volume of cold saline is injected quickly into the right atrium, right ventricle or pulmonary artery, and the dilution of the cold saline by warm blood is recorded by a thermistor-tipped catheter (Swan-ganz catheter) in the more distal pulmonary artery. Cardiac output can then be calculated from the area under the temperature-time plot from and the amount of heat (i.e. cold) injected.
The major advantage of the thermal dilution method:
The recirculation problem is circumvented because the saline warms up to body temperature long before it returns to the right side. Another advantage is that the ejection fraction can be calculated from the step rise in temperature that follows each refilling of the heart by warm blood.
One problem with the thermal dilution method?
Heat transfer across the walls of the right ventricle and pulmonary artery, which can cause over-estimation of the distribution volume and therefore cardiac output; a computed correction is usually made for this.
Pulsed Doppler method:
This is an increasingly popular method in which a pulse of ultrasound is directed down the ascending aorta from a transmitter crystal at the suprasternal notch. Some of the ultrasound is reflected back by the red cells, and this is collected and analysed. Since the cells have a high velocity, the frequency of the returning sound waves is different from that of the transmitted signal; this is the Doppler effect, analogue to the change in pitch of a car siren as it speeds past.
This is an increasingly popular method in which a pulse of ultrasound is directed down the ascending aorta from a transmitter crystal at the suprasternal notch. Some of the ultrasound is reflected back by the red cells, and this is collected and analysed. Since the cells have a high velocity, the frequency of the returning sound waves is different from that of the transmitted signal; this is the Doppler effect, analogue to the change in pitch of a car siren as it speeds past.
Pulsed Doppler method:
The average blood velocity across the aorta at each instant is computed from the spectrum of frequencies in the returning signal, and the velocity is plotted against time as in Figure 5.3. To convert the time-averaged ……….. (cm/s) to ……… (cm3/s) the diameter of the aorta must be measured by echo (see section 2.5) and the ………….. area (pi x r upphöjd i 2) then multiplied by mean ………………..
The result, aortic flow, represents ……… minus …………. blood flow.
Although the Doppler method has calibration and “noise” problems, it has the enormous advantages of non-invasiveness and speed, and can record each individual ejection.
Pulsed Doppler method:
The average blood velocity across the aorta at each instant is computed from the spectrum of frequencies in the returning signal, and the velocity is plotted against time as in Figure 5.3. To convert the time-averaged velocity (cm/s) to flow (cm3/s) the diameter of the aorta must be measured by echo (see section 2.5) and the cross-sectional area (pi x r upphöjd i 2) then multiplied by mean velocity.
The result, aortic flow, represents cardiac output minus coronary blood flow.
Although the Doppler method has calibration and “noise” problems, it has the enormous advantages of non-invasiveness and speed, and can record each individual ejection.
See Fig 5.3 s 75
See Fig 5.3 s 75
What is the oldest, fastest, cheapest and easiest method of assessing cardiac output, albeit subjectively?
It is to lay a finger on the radial pulse.
HR can be measured, and the finger also senses whether the pulse is sting or weak, a strong pulse being associated with a large stroke volume (e.g.exercise) and a weak pulse associated with a low stroke volume (e.g hemorrhage).
Peripheral pulse examination: What the finger actually detects is the …………….. of the artery as pressure rises during systole. The rise in pressure, or “pulse pressure” equals ……………….., and this is easily measure with a sphygmomanometer.
What the finger actually detects is the expansion of the artery as pressure rises during systole. The rise in pressure, or “pulse pressure” equals systolic pressure minus diastolic pressure, and this is easily measure with a sphygmomanometer.
The relation between pulse pressure and stroke volume is illustrated in Fig 5.4.
Most of the stroke volume (…..-……%) is temporarily accommodated in the elastic arteries, owing to the resistance of the arteriolar system to runoff. The dissension of the elastic arteries …………… the blood pressure, and the amount by which pressure …………. depends partly on the stroke volume and partly on the distensibility in the arterial system.
Most of the stroke volume (70-80%) is temporarily accommodated in the elastic arteries, owing to the resistance of the arteriolar system to runoff. The dissension of the elastic arteries raises the blood pressure, and the amount by which pressure rises depends partly on the stroke volume and partly on the distensibility in the arterial system.
Distensibility or “compliance” is defined as
As change in volume per unit change in pressure
See Fig 5.4 s 76
See Fig 5.4 s 76
Compliance = increase in ………./ increase in ………………..
Compliance = increase in volume/ increase in pressure
Rearranging this, we can see how pulse-pressure related to stroke volume
Compliance = increase in volume/ increase in pressure
Rearranging this, we can see how pulse pressure related to stroke volume.
Pulse pressure =
Pulse pressure =
Stroke volume (minus initial runoff)/compliance
In a young adult, arterial compliance is around 2 ml per mmHg at normal pressures. Unfortunately, however, the compliance is not a constant, and is affected by 3 factors: which ones?
1) High arterial pressures and volumes reduce arterial compliance; this is evident from the curvature of the arterial pressure-volume relation in Fig 5.4.
2) High ejection velocities reduce compliance because the artery wall is a viscoelastic material (see Appendix) and needs time to expand. During exercise the pulse pressure increases proportionately more than stroke volume because there is less time available for viscous relaxation in the wall.
3) Advancing age is associated with arteriosclerosis, a hardening of the artery walls, which reduces compliance and leads to large pulse pressures in the elderly
Because arterial compliance is so variable, and also because the percentage runoff during early systole with peripheral resistance, the pulse pressure offers only an indirect assessment of ………………
Nevertheless, within its limitations the peripheral pulse provides an exceedingly convenient indication of changes in cardiac output in an individual patient from day to day.
Because arterial compliance is so variable, and also because the percentage runoff during early systole with peripheral resistance, the pulse pressure offers only an indirect assessment of stroke volume.
Nevertheless, within its limitations the peripheral pulse provides an exceedingly convenient indication of changes in cardiac output in an individual patient from day to day.
Radionuclide angiography and other methods:
An iv injection of radionuclide is given and the number of counts emanating from the ………. is monitored by a precordial gamma camera.
An iv injection of radionuclide is given and the number of counts emanating from the ventricles is monitored by a precordial gamma camera.
Radionuclide angiography:
The radionuclide is commonly a compound of technetium that binds to red cells. The ……… and …………….. can be calculated from the difference between the radioactive content of the ventricles in diastole and in systole.
The ejection fraction and stroke volume can be calculated from the difference between the radioactive content of the ventricles in diastole and in systole.
Echocardiography:
See section 2.5 and Fig 6.20.
The end-diastolic and end-systolic diameters of the ventricle can be estimated using echo: These measurements can be converted into …………. if some assumptions are made about chamber …………
These measurements can be converted into stroke volume if some assumptions are made about chamber shape.
Electromagnetic flowpower:
This technique is used only in animal experiments, because it is necessary to place a curved magnet with its poles directly on either side of the aorta or pulmonary artery. Since blood is an electrical conductor, the flowing blood induces an electrical potential as it cuts the magnetic field: the measured potential is proportional to blood velocity (cm/s).
The internal diameter of the vessel must be known to convert mean velocity to flow. Being small, this device can be left inside a conscious animal, transmitting a signal by telemetry (radio waves), and in this way much has been learned about the regulation of stroke volume of unfettered exercising animals.
Electromagnetic flowpower:
This technique is used only in animal experiments, because it is necessary to place a curved magnet with its poles directly on either side of the aorta or pulmonary artery. Since blood is an electrical conductor, the flowing blood induces an electrical potential as it cuts the magnetic field: the measured potential is proportional to blood velocity (cm/s).
The internal diameter of the vessel must be known to convert mean velocity to flow. Being small, this device can be left inside a conscious animal, transmitting a signal by telemetry (radio waves), and in this way much has been learned about the regulation of stroke volume of unfettered exercising animals.
Control of stroke volume and cardiac output:
CO ranges from 4-7 l/min in a human adult at rest. CI is the product of ?
HR and stroke volume, and is usually altered by changes in both factors.
Control of stroke volume:
The cardiac output correlates with the body surface area, which is about 1.8 m2 in a 70 kg adult, and the cardiac output per unit surface area (the cardiac index) averages 3 litres/min per m2. In everyday life, however, the output is continually changing in response to circumstances.
The cardiac output correlates with the body surface area, which is about 1.8 m2 in a 70 kg adult, and the cardiac output per unit surface area (the cardiac index) averages 3 litres/min per m2. In everyday life, however, the output is continually changing in response to circumstances.
Moving from the lying position to standing r………….. CO by approximately 20%, while sleep ……………. it by approximately 10%.
A heavy protein meal or excitement and fear can ……………. the output by 20-30%. Pregnancy gradually ………….. the output by 40%.
Moving from the lying position to standing reduces CO by approximately 20%, while sleep reduces it by approximately 10%.
A heavy protein meal or excitement and fear can increase the output by 20-30%. Pregnancy gradually raises the output by 40%.
Heavy exercise causes the greatest increase, by as much as ….. times in untrained students and …… times in Olympic athletes.
Diseased heart, on the other hand have a much more ………… of outputs.
Heavy exercise causes the greatest increase, by as much as 4 times in untrained students and 6 times in Olympic athletes.
Diseased heart, on the other hand have a much more restricted range of outputs.
Table 6.1
CO is the product of HR and stroke volume, and is usually altered by changes in both factors. In exercise, the rate and stroke volume both increase but in other circumstances they can change in opposite directions. Give ex of such circumstances:
After a hemorrhage, for example, HR increases while stroke volume decreases.
The autonomic nerves controlling HR are described in chapter 5, chapter 6 concentrates on the control of stroke volume and its coordination with HR and vascular factors to determine the CO.
The autonomic nerves controlling HR are described in chapter 5, chapter 6 concentrates on the control of stroke volume and its coordination with HR and vascular factors to determine the CO.
Stroke volume is regulated primarily by 2 opposing factors: which ones?
The energy with which the myocytes contract and the arterial pressure against which they have to expel the blood. (see Fig 6.1)
A highly energetic contraction produces a ………… stroke volume, other being equal, while a high arterial pressure ………… ejection and ……………. the stroke volume, other things again being equal.
A highly energetic contraction produces a large stroke volume, other being equal, while a high arterial pressure opposes ejection and reduces the stroke volume, other things again being equal.
Fig 6.1
The energy of contraction of the myocyte is a variable, regulated quantity, and be increases by 2 processes:
1) Stretching the cells during diastole enhances their subsequent contractile energy, and since the stretch of the relaxed ventricle depends on the pressure distending it, contractile energy is regulated indirectly by the ventricular end-diastolic pressure = Starling’s law of the heart.
2) The innate strength with which a myocyte contracts from a given initial stretch, or “contractile” as it is called, can be increased by nervous, hormonal and chemical influences, for example, by noradrenaline or extracellular calcium ions.
The arterial pressure opposing ejection has a negative effect on stroke volume. This is because..?
Because the immediate effect of active tension is not to produce ejection but to raise intraventricular pressure during the isovolumetric phase of the cardiac cycle. (See section 2.2)
Ejection cannot begin until ventricular pressure exceeds arterial pressure, and this consumes a substantial part of the energy available per contraction.
If arterial pressure is raised, more of the contractile energy is consumed in raising the pressure in the isovolumetric phase and less remains for ejection.
Arterial pressure depends partly on total peripheral resistance (TPR), so any rise in TPR tends to diminish the …………
Arterial pressure depends partly on total peripheral resistance (TPR), so any rise in TPR tends to diminish the stroke volume.
Stroke volume is thus governed by three factors. Which ones?
1) stretch during diastole, which depends on ventricular end-diastolic pressure
2) contractility, which is modulated by sympathetic nerve activity and other chemical influences
3) arterial pressure, which opposes ejection and is influenced by TPR. See Fig 6.1
To study the effect of stretch a relaxed muscle is stretched to a known length by means of a small weight or preload, and is then stimulated electrically (see Fig 6.2). If the muscle is anchored between 2 rigid points, excitation cannot cause shortening; it produces tension (force) alone which can be measured by a force transducer. Contraction at constant length is called?
An isometric contraction, and is very analogous to isovolumetric contraction in vivo.
The active tension generated during an isometric contraction is found to increase steeply with initial length, as shown by the length-tension relations in Figures 6.2 and 6.3. This demonstrates that stretching the relaxed myocardium……………………contractile energy.
The active tension generated during an isometric contraction is found to increase steeply with initial length, as shown by the length-tension relations in Figures 6.2 and 6.3. This demonstrates that stretching the relaxed myocardium enhances its subsequent contractile energy.
To study the ability of muscle tho shorten, one end of the muscle is left free to move but is compelled to lift a weight (which is called….?), so that it shortens under a constant tension. This is called an………contraction.
Isotonic contraction
and the weight is called the afterload?
In intact ventricle, the afterload is related to …………. pressure and ventricular ………..
In intact ventricle, the afterload is related to arterial pressure and ventricular radius.
If the afterload is increased both the velocity of ………….. and the amount of ……………. are reduced. See Fig 6.2.
If the afterload is increased both the velocity of contraction and the amount of shortening are reduced. See Fig 6.2.
If the resting papillary muscle is stretched by raising the preload, and the isotonic contraction repeated, the muscle now contracts with …………. velocity and achieves a …………… shortening.
If the resting papillary muscle is stretched by raising the preload, and the isotonic contraction repeated, the muscle now contracts with a greater velocity and achieves a greater shortening.
These mentioned observations reinforce the conclusion that the energy of contraction of isolated myocardium is a function of the resting fibre length
The sarcomere length-tension relation:
The process of stretching a relaxed muscle affects the length of the basic contractile unit, the ……………, and this affects its contractile energy.
The sarcomere length-tension relation: The process of stretching a relaxed muscle affects the length of the basic contractile unit, the sarcomere, and this affects its contractile energy.
Studies of sarcomere length by laser diffraction show that maximum contractile energy develops at sarcomere length of 2.2-2.3 um. The sarcomere length in intact hearts at normal end-diastolic pressures (0-9 mmHg) is below this optimal value, so the intact ventricle normally operates on the ascending limb of the length-tension curve.
Studies of sarcomere length by laser diffraction show that maximum contractile energy develops at sarcomere length of 2.2-2.3 um. The sarcomere length in intact hearts at normal end-diastolic pressures (0-9 mmHg) is below this optimal value, so the intact ventricle normally operates on the ascending limb of the length-tension curve.
Beyond 2.2-2.3 um, contractile force decays, but it is very difficult to stretch sarcomeres beyond this point, even in vitro, because they become very stiff; it is therefore most unlikely that sarcomere lengths above 2.3 um are ever produced in intact hearts during life.
Mechanisms underlying the length-tension relation:
How does an increase in sarcomere length enhance the active tension?
Part of the explanation is that at sarcomere lengths below 2.0 um, the opposing actin filaments overlap each other, and this interferes with the formation of actin-myosin cross bridges, and hence with force generation. See Fig 6.3 top.
When this interference is reduced by stretching the sarcomere to 2.0 um, contractile force increases
Exactly the same actin-actin overlap mechanism operates in skeletal muscle, yet the length-tension curve of cardiac muscle is much …….. than that of skeletal muscle.
Exactly the same actin-actin overlap mechanism operates in skeletal muscle, yet the length-tension curve of cardiac muscle is much steeper than that of skeletal muscle, indicating that some additional factor is at work in the myocardium.
Fig 6.3
The upper curve of Fig 6.3 shows the length-tension relation for skinned fibres when all the potential cross bridges at each sarcomere length are activated by a high Ca2+ bath.
A physiological concentration of calcium activates only a fraction of the cross bridges, so tension is reduced (lower curve), and this curve closely resembles that for intact, unskinned fibres.
The curve for partially activated fibres is much steeper than that for fully activated fibres and gradually approaches the latter curve as sarcomere length is increased. This indicates that the fraction of potential cross bridges activated by physiological concentrations of Ca 2+ increases the stretch (length-dependent activation)
Fig 6.3
The upper curve of Fig 6.3 shows the length-tension relation for skinned fibres when all the potential cross bridges at each sarcomere length are activated by a high Ca2+ bath.
A physiological concentration of calcium activates only a fraction of the cross bridges, so tension is reduced (lower curve), and this curve closely resembles that for intact, unskinned fibres.
The curve for partially activated fibres is much steeper than that for fully activated fibres and gradually approaches the latter curve as sarcomere length is increased. This indicates that the fraction of potential cross bridges activated by physiological concentrations of Ca 2+ increases the stretch (length-dependent activation)
Length-dependent activation appears to be due to an increase in the sensitivity of the contractile proteins to ………. with stretch, as shown in Figure 6.4
Length-dependent activation appears to be due to an increase in the sensitivity of the contractile proteins to calcium with stretch, as shown in Figure 6.4
The curve relating active tension to Ca2+ conc in skinned myocytes is shifted to the left when sarcomere length is increased, and there is a substantial reduction in the calcium conc needed to produce 50% of maximal tension. This phenomenon is known as the ………………….
The curve relating active tension to Ca2+ conc in skinned myocytes is shifted to the left when sarcomere length is increased, and there is a substantial reduction in the calcium conc needed to produce 50% of maximal tension. This phenomenon is known as the length-dependence of calcium sensitivity.
See Fig 6.4
Length-dependence of calcium sensitivity: How the sensitivity to Ca2+ is increased is still under investigation, but there is growing evidence that troponin ……. may be the length sensor.
How the sensitivity to Ca2+ is increased is still under investigation, but there is growing evidence that troponin C may be the length sensor.
Starling’s law of the heart:
The effect of diastolic stretch on the contraction: See fig 6.5:
Distension during diastole caused the development of a greater pressure during systole, indicating that the energy of contraction depended on …………
The effect of diastolic stretch on the contraction: See fig 6.5:
Distension during diastole caused the development of a greater pressure during systole, indicating that the energy of contraction depended on diastolic distension.
Starling showed that diastolic stretch influences stroke volume.
Starling showed that diastolic stretch influences stroke volume.
The central venous pressure (CVP) is the pressure in the great veins at their point of entry into the…………..
right atrium.
The pressure distending the right ventricle, the right ventricular end-diastolic pressure (RVEDP) is almost equal to the ………………
The pressure distending the right ventricle, the right ventricular end-diastolic pressure (RVEDP) is almost equal to the CVP. Similarly, pulmonary vein pressure governs left ventricle end-diastolic pressure, LVEDP. A general term for all these pressures is “filling pressure”.
In Starling’s classic experiments (see fig 6.6), the isolated heart and lungs of a dog were perfused with wam oxygenated blood from a venous reservois, the height of which above the heart controlled CVP. The aortic pressure opposing outflow from the left ventricle was held constant by a variable resistance called a Starling resistor, and the combine stroke volumes of the two ventricle were recorded by a bell cardiometer. Being isolated and denervated, the heart-lung preparation was free of nervous or hormonal influences.
In Starling’s classic experiments (see fig 6.6), the isolated heart and lungs of a dog were perfused with wam oxygenated blood from a venous reservois, the height of which above the heart controlled CVP. The aortic pressure opposing outflow from the left ventricle was held constant by a variable resistance called a Starling resistor, and the combine stroke volumes of the two ventricle were recorded by a bell cardiometer. Being isolated and denervated, the heart-lung preparation was free of nervous or hormonal influences. Fig 6.6
The major findings with the heart-lung preparation by Starlings group were:
1) Active response to central venous pressure: When CVP is increased, ventricular end-diastolic pressure ……….., and this increases the ……………. (see Fig 6.7a).
- Active response to central venous pressure: When CVP is increased, ventricular end-diastolic pressure rises, and this increases the end-diastolic volume. (see Fig 6.7a).
It should be noted that this effect is non-linear and tails off at high end-diastolic pressures. Fig 6.5b
The stretched ventricle develops a greater contractile energy, which results in the ejection of a greater stroke volume, provided mean arterial pressure is fixed.
Although a rise in CVP initially increase the filling pressure only on the right side of the heart, the LV ………….increases too within a few beasts because the increased RV output raises the pressure in the pulmonary vessels, which in turn raises the filling pressure for the LV.
Although a rise in CVP initially increase the filling pressure only on the right side of the heart, the LV stroke volume increases too within a few beasts because the increased RV output raises the pressure in the pulmonary vessels, which in turn raises the filling pressure for the LV.
The major findings with the heart-lung preparation by Starlings group were:
2) Active response to arterial pressure. The direct effect of arterial pressure is to oppose ejection. See Section 6.7, but when arterial pressure is raised in a heart-lung preparation, stroke volume declines only transiently and is restored within a few beats (ssee Fig 6.7b). The reason is?
The reason is that, since output is transiently reduced by the pressure load while input continues unchanged, the ventricle distends, this increases its contractile energy and restores stroke volume.
The major findings with the heart-lung preparation by Starlings group were:
3) The ventricular function curve/Starling curve, which is?
A graph whose ordinate is stroke volume or any other measure of contractile energy and whose abscissa is filling pressure or any other index of resting fibre length is called a ventricular function curve, or Starling curve. See Fig 6.8.
For the abscissa, CVP is often chosen because human CVP is easily measured by cathetization and is an important regulator of average fibre length. However, its relation to fibre length is indirect and non-linear. Other indices of stretch include RVEDP, LVEDP, ventricular end-diastolic volume measured by echo; all are indirect indices of resting fibre length.
For the ordinate, stroke volume can serve as an index of contractile energy if mean arterial pressure is held constant, as in the heart-lung preparation. However, it obviously takes more energy to eject blood at a high pressure than at a low pressure, and the product of stroke volume and ……………………….. (the stroke work) is a better energy index.
For the ordinate, stroke volume can serve as an index of contractile energy if mean arterial pressure is held constant, as in the heart-lung preparation. However, it obviously takes more energy to eject blood at a high pressure than at a low pressure, and the product of stroke volume and mean arterial pressure (the stroke work) is a better energy index.
See Section 6.4.
Stroke volume and stroke work increase as a ……………….function of CVP between zero and 10 mmHg, forming the ascending limb of the Starling curve. In the human LV in situ, the curve almost reaches a plateau above 10 mmHg LVEDP (see Fig 6.8b). During standing and sitting, human LVEDP is 4-5 mmHg, and the heart is on the ascending limb f the curve, while in a supine subject /LVEDP 8-9 mmHg) the heart operates close to the plateau.
Stroke volume and stroke work increase as a curvilinear function of CVP between zero and 10 mmHg, forming the ascending limb of the Starling curve. In the human LV in situ, the curve almost reaches a plateau above 10 mmHg LVEDP (see Fig 6.8b). During standing and sitting, human LVEDP is 4-5 mmHg, and the heart is on the ascending limb f the curve, while in a supine subject /LVEDP 8-9 mmHg) the heart operates close to the plateau.
In isolated dog hearts, the curve peaks at about 20 mmHg and then falls off (See Fig 6.8a), but such preparations are probably never completely normal and it si doubted whether human hearts ever reach this descending limb.
In isolated dog hearts, the curve peaks at about 20 mmHg and then falls off (See Fig 6.8a), but such preparations are probably never completely normal and it si doubted whether human hearts ever reach this descending limb.
Stroke voluem declines in the over-distended preparation partly because the distended atrioventricular valves begin to leak and partly because the reduced curvature of the cardiac wall impairs the conversions of active tension into pressure. (Laplace’s law)
Is the shape of the Starling curve similar for the right and left ventricle?
Yes, except that the LV has slightly higher filling pressures. See Fig 6.8 and Table 2.1
This is because the LV has thicker, less distensible walls, and LVEDP has to be 4-5 mmHg higher than RVEDP to produce an equivalent stretch and output.
The results shown in Fig 6.8 establish that the greater the stretch of the ventricle in diastole, the greater the …….. …………. achieved in systole.
The results shown in Fig 6.8 establish that the greater the stretch of the ventricle in diastole, the greater the stroke work achieved in systole.
“The energy of contraction of a cardiac muscle fibre, like that of a skeletal muscle fibre, is proportional to the ……………….at rest” This deduction now honoured as Starling’s law of the heart, has been amply confirmed by the direct studies illustrated in Fig 6.2 and 6.3
“The energy of contraction of a cardiac muscle fibre, like that of a skeletal muscle fibre, is proportional to the initial fibre length at rest” This deduction now honoured as Starling’s law of the heart, has been amply confirmed by the direct studies illustrated in Fig 6.2 and 6.3
Laplace’s law and wall tension:
When one attempts to relate the pumping behavior of the intact ventricle to the contractile properties of isolated muscle, the ……….. of the cavity is important as all as ………. and …………… In any hollow chamber it is the ………….. that relates wall tension to internal pressure, as pointed out in 1806 by Laplace (a french mathematician).
When one attempts to relate the pumping behavior of the intact ventricle to the contractile properties of isolated muscle, the radius of the cavity is important as all as CVP and arterial pressure. In any hollow chamber it is the radius that relates wall tension to internal pressure, as pointed out in 1806 by Laplace (a french mathematician).
Laplace’s law states that the pressure P within a sphere is proportional to the ……………(which equals stress, S, times wall thickness, w), and is inversely proportional to the …………
Laplace’s law states that the pressure P within a sphere is proportional to the wall tension (which equals stress, S, times wall thickness, w), and is inversely proportional to the radius, r.
Laplace’s law: The involvement of radius is readily understood by considering the wall’s curvature (See Fig 6.9); as radius increases, curvature is ………. so a smaller component of the wall tension is angled towards the cavity, generating ……… pressure.
(See Fig 6.9); as radius increases, curvature is reduced, so a smaller component of the wall tension is angled towards the cavity, generating less pressure.
Thus, the curvature of the ventricle wall determines how effectively the active wall tension is converted into intraventricular pressure.
Since the Frank- Starling mechanism requires some increase in chamber size, it also involves a …………. in mechanical efficiency, and this becomes a dominating effect in grossly dilated, failing hearts. (See Chapter 15)
Since the Frank- Starling mechanism requires some increase in chamber size, it also involves a small fall in mechanical efficiency, and this becomes a dominating effect in grossly dilated, failing hearts. (See Chapter 15)
See Fig 6.9
See Fig 6.9
Laplace’s law can be re-arranged to give S = ……….., and this form helps us to understand what governs the afterload on myoctyres in an intact heart. T
Laplace’s law can be re-arranged to give S = Pr/2W, and this form helps us to understand what governs the afterload on myoctyres in an intact heart.
The afterload is the stress, S, during systole, and from the statement S= Pr/2W, we can see that it depends not only on ………….. pressure but also on chamber ,,,,,,,,, and …………….
The afterload is the stress, S, during systole, and from the statement S= Pr/2W, we can see that it depends not only on arterial pressure but also on chamber radius and wall thickness.
Since both pressure and radius decline in the later stages of ejection, there is a gradual reduction in afterload, which facilitates ………….. Any contraction in which afterload changes is not a truly isotonic one, and is called ……………..
Since both pressure and radius decline in the later stages of ejection, there is a gradual reduction in afterload, which facilitates late ejection. Any contraction in which afterload changes is not a truly isotonic one, and is called auxotonic.
Stroke work and the pressure-volume loop:
The energy expanded in systole results partly in ……. formation and partly in external mechanical work in the form of an …………………………. in the arterial system.
The energy expanded in systole results partly in heat formation and partly in external mechanical work in the form of an increase in the pressure and volume of blood in the arterial system.
Mechanical work is, by definition, the applied ……. (F) times the …….. it moves (L);
1 …………… of work equals 1 …….. force displaced over 1 metro.
Mechanical work is, by definition, the applied force (F) times the distance it moves (L);
1 joule of work equals 1 newton force displaced over 1 metro.
1 joule of work equals 1 newton force displaced over 1 metro.
This definition has to be adapted for a fluid, where force is applied not by a point but by a surface such as the ventricle wall.
The active force exerted on the blood by the ventricle in systole equals the rise in ……….. (delta P times the …………… A, since pressure is force per unit area).
If the wall moves an average distance L, a volume (delta x V) equal to L X A is displaced into the aorta. Fig 6.10.
Thus, the work performed per beat, or stroke work (W) is equal to the formel s 87.
In other word, stroke work equals the rise in ……………… x ……………..
The active force exerted on the blood by the ventricle in systole equals the rise in pressure (delta P times the wall area A, since pressure is force per unit area).
If the wall moves an average distance L, a volume (delta x V) equal to L X A is displaced into the aorta. Fig 6.10.
Thus, the work performed per beat, or stroke work (W) is (se formel s 87).
In other word, stroke work equals the rise in ventricular blood pressure x volume ejected (stroke volume).
In other word, stroke work equals the rise in ventricular blood pressure x volume ejected (stroke volume).
Ventricular blood pressure varies throughout the ejection phase, so to evaluate stroke work properly it is necessary to construct a graph of ventricular pressure against volume as in Figure 6.10
Ventricular blood pressure varies throughout the ejection phase, so to evaluate stroke work properly it is necessary to construct a graph of ventricular pressure against volume as in Figure 6.10
Fig 6.10: Line A-B in a) shows ventricular filling. In the initial rapid-filling phase pressure is falling because elastic recoil of the relaxing ventricle exerts a suction effect. In the later slow-filling phase, a rise in pressure drives the increase in volume, so the line coincides with the passive pressure-volume curve of the relaxed ventricle (see Fig 6.10b).
Line A-B in a) shows ventricular filling. In the initial rapid-filling phase pressure is falling because elastic recoil of the relaxing ventricle exerts a suction effect. In the later slow-filling phase, a rise in pressure drives the increase in volume, so the line coincides with the passive pressure-volume curve of the relaxed ventricle (see Fig 6.10b).
Fig 6.10: During isovolumetric contraction (line B-C) the heart is “working” very hard in thevery-day sense of the word (consuming metabolic energy and oxygen to generate force), but since no blood in transported out of the system, the ventricle accomplishes no external work.
During isovolumetric contraction (line B-C) the heart is “working” very hard in thevery-day sense of the word (consuming metabolic energy and oxygen to generate force), but since no blood in transported out of the system, the ventricle accomplishes no external work.
This phase can be linked to a man trying to push over a house; he accomplishes no external work but consumes a lot of oxygen in the process.
Figure 6.10: At point C the aortic valve opens; the height of line BC is set by the ………………….. In the ejection phase (C-D) external work is accomplished.
At point C the aortic valve opens; the height of line BC is set by the diastolic arterial pressure. In the ejection phase (C-D) external work is accomplished.
Figure 6.10: At point D (end systolic pressure) the aortic valve closes, and line D-A represents isovolumetric relaxation. Since the total stroke work is the sum of the ………. x displaced ……….. at each instant, it equals the total ………….. within the pressure-volume loop.
At point D (end systolic pressure) the aortic valve closes, and line D-A represents isovolumetric relaxation. Since the total stroke work is the sum of the pressure gain x displaced volume at each instant, it equals the total area within the pressure-volume loop.
Fig 6.10b shows how the Frank-Starling mechanism affects the pressure-volume loop. The loop is confined within the 2 lines. The lower confine is the ……………….. curve as explained above; each contraction begins from this line. The upper confine is the curve relating systolic pressure to end-diastoic volume in a purely ……………. (see Fig 6.5b).
shows how the Frank-Starling mechanism affects the pressure-volume loop. The loop is confined within the 2 lines. The lower confine is the end-diastlic pressure-volume curve as explained above; each contraction begins from this line. The upper confine is the curve relating systolic pressure to end-diastoic volume in a purely isovolumetric contraction (see Fig 6.5b). This line depicts the contractile energy available due to the Frank-Starling mechanism. If ejection were prevented, ventricular pressure would just reach this upper confine.
Fig 6.10b shows how the Frank-Starling mechanism affects the pressure-volume loop.
Loop 1 represents a normal cycle, in which ejection occurs. The ………….. valve closes when the end-systolic pressure and volume reach the upper confining line.
Loop 1 represents a normal cycle, in which ejection occurs. The aortic valve closes when the end-systolic pressure and volume reach the upper confining line.
Fig 6.10b shows how the Frank-Starling mechanism affects the pressure-volume loop.
In loop 2, the end-diastolic volume has been raised, …………….. the contractile energy by the Frank-Starling mechanism.
Stroke volume increases, providing that the …………….. opposing ejection is prevented from rising.
In loop 2, the end-diastolic volume has been raised, increasing the contractile energy by the Frank-Starling mechanism.
Stroke volume increases, providing that the arterial pressure opposing ejection is prevented from rising.
In loop 2, the end-diastolic volume has been raised, increasing the contractile energy by the Frank-Starling mechanism.
Stroke volume increases, providing that the arterial pressure opposing ejection is prevented from rising.
If, however, the arterial pressure is raised, as in loop 3, more of the available energy goes into raising ……………… pressure and stroke volume ………….., though the stroke work (loop area) is unchanged.
If, however, the arterial pressure is raised, as in loop 3, more of the available energy goes into raising ventricular pressure and stroke volume decreases, though the stroke work (loop area) is unchanged.
Fig 6.10b shows how the Frank-Starling mechanism affects the pressure-volume loop.
If ejection is prevented totally, as in line 4, stroke volume and stroke work are ………….., but maximum systolic pressure is generated.
If ejection is prevented totally, as in line 4, stroke volume and stroke work are zero, but maximum systolic pressure is generated.
Control of ventricular filling and central venous pressure:
Because of the Frank-Starling mechanism, ………………… has an important effect on stroke work, and the factors that regulate end-diastolic volume are therefore very important physiologically.
Because of the Frank-Starling mechanism, ventricular end-diastolic volume has an important effect on stroke work, and the factors that regulate end-diastolic volume are therefore very important physiologically.
End-diastolic volume (EDV) depends primarily on the distensibility of the ventricle and on the transmural pressure distending the relaxed chamber: Transmural pressure is the ……….pressure minus the …………. pressure (intrathoracic pressure). As noted earlier, ventricular distensibility ……….. with stretch (rather like the distensibility of a bicycle tyre), so EDV becomes less and less sensitive to diastolic pressure above …….mmHg. See Fig 6.10b.
Transmural pressure is the internal pressure minus the external pressure (intrathoracic pressure). As noted earlier, ventricular distensibility decreases with stretch (rather like the distensibility of a bicycle tyre), so EDV becomes less and less sensitive to diastolic pressure above 10 mmHg. See Fig 6.10b.
Pressure outside the heart:
Intrathoracic pressure falls from about -5 cmH2O at the end of expiration to -10 cmH2O at the end of inspiration. Inspiration thus produces a ………. effect around the heart and central veins, ……………. right ventricular filling.
Inspiration thus produces a suction effect around the heart and central veins, enhancing right ventricular filling.
Inspiration thus produces a suction effect around the heart and central veins, enhancing right ventricular filling.
Conversely, when intrathoracic pressure becomes ……….., as for example during a forced expiration (Valsalva manoeuvre) ventricular filling is ……… Pressure outside the ventricle also becomes …………… in patients with constrictive …………. and pericardial …………. impairing filling and output.
Conversely, when intrathoracic pressure becomes positive, as for example during a forced expiration (Valsalva manoeuvre) ventricular filling is reduced. Pressure outside the ventricle also becomes positive in patients with constrictive pericarditis and pericardial effusion, impairing filling and output.
Pressure inside the heart: control of ventral venous pressure (CVP):
End-diastolic pressure in the right ventricle is nearly equal to ……………….; so the latter plays a key role in regulating ……..volume.
End-diastolic pressure in the right ventricle is nearly equal to central venous pressure; so the latter plays a key role in regulating stroke volume.
CVP is set by the following factors:
1) Blood volume: About ……. of the entire blood volume is located in the venous system, so the greater the blood volume, the greater the average venous pressure. Conversely, hemorrhage or dehydration reduces the blood volume and lowers CVP; unless compensated for by …………….
1) Blood volume: About 2/3 of the entire blood volume is located in the venous system, so the greater the blood volume, the greater the average venous pressure. Conversely, hemorrhage or dehydration reduces the blood volume and lowers CVP; unless compensated for by venoconstriction.
CVP is set by the following factors:
2)gravity: Gravity, ……… the and the …………… together govern the distribution of venous blood between peripheral veins and thoracic veins.
Gravity, venous tone the and the muscle pump together govern the distribution of venous blood between peripheral veins and thoracic veins.
In a standing man, gravity redistributes around 500 ml of blood from the intrathoracic vessels into the veins of the lower limbs (venous pooling). This ………. the CVP and stroke volume …………….
In a standing man, gravity redistributes around 500 ml of blood from the intrathoracic vessels into the veins of the lower limbs (venous pooling). This reduces the CVP and stroke volume declines.
Conversely, lying down redistributes venous blood from the lower limbs into the thoracic vessels, and stroke volume increases.
CVP is set by the following factors:
3) Peripheral venous tone: The veins of the skin, kidneys and splanchnic system are innervated by ……………….capable of exciting venoconstriction. The nervous systems can thus except some control over the proportion of blood in the peripheral veins and thereby influence CVP.
Peripheral venous tone: The veins of the skin, kidneys and splanchnic system are innervated by sympathetic nerves capable of exciting venoconstriction. The nervous systems can thus except some control over the proportion of blood in the peripheral veins and thereby influence CVP.
