книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

Blood Vessels and Blood Flow

In the systemic circulation, blood is ejected from the left ventricle to the aorta and returns to the right atrium via the venae cavae (!A). As a result, the mean blood pressure (!p. 206) drops from around 100 mmHg in the aorta to 2–4 mmHg in the venae cavae (!A2), resulting in a pressure difference ( P) of about 97 mmHg (pulmonary circulation; !p. 122).

where Q is the blood flow (L · min– 1) and R is the flow resistance (mmHg · min · L–1). Equation 8.1 can be used to calculate blood flow in a given organ (R = organ resistance) as well as. in the entire cardiovascular system, where Q is the cardiac output (CO; !p. 186) and R is the total peripheral flow resistance (TPR). The TPR at rest is about 18 mmHg · min · L–1.

The aorta and greater arteries distribute the blood to the periphery. In doing so, they act as a hydraulic filter because (due to their high compliance, V/ Ptm) they convert the intermittent flow generated by the heart to a nearly steady flow through the capillaries. The high systolic pressures generated during the ejection phase cause the walls of these blood vessels to stretch, and part of the ejected blood is “stored” in the dilated lumen (windkessel). Elastic recoil of the vessel walls after aortic valve closure maintains blood flow during diastole. Arterial vessel compliance decreases

Flow velocity (V) and flow rate (Q) of the

blood. Assuming an aortic cross-sectional area

(CSA) of 5.3 cm2 and a total CSA of 20 cm2 of all

.

downstream arteries (!A5), the mean V

(during systole and diastole) at rest can be calculated from a resting CO of 5.6 L/min: It equals 18 cm/s in the aorta and 5 cm/s in the arteries (!A3). As the aorta receives blood only during the ejection phase. (!p..90), the maximum resting values for V and Q in the

the flow resistance (R) in a tube of known length (l) is dependent on the viscosity (η) of the fluid in the tube (!p. 92) and the fourth

power of the inner radius of the tube (r4). Decreasing the radius by only about 16% will therefore suffice to double the resistance.

The lesser arteries and arterioles account for nearly 50% of the TPR (resistance vessels; !A1 and p. 187 A) since their small radii have a much stronger effect on total TPR (R !1/r4) than their large total CSA (R !r2). Thus, the blood pressure in these vessels drops significantly. Any change in the radius of the small arteries or arterioles therefore has a radical effect on the TPR (!p. 212ff.). Their width and that of the precapillary sphincter determines the amount of blood distributed to the capillary beds (exchange area).

Although the capillaries have even smaller radii (and thus much higher individual resistances than the arterioles), their total contribution to the TPR is only about 27% because their total CSA is so large (!A1 and p. 187 A). The exchange of fluid and solutes takes place across the walls of capillaries and postcapillary venules. Both vessel types are particularly. suitable for the task because (a) their V is very small (0.02–0.1 cm/s; !A3) (due to the large total CSA), (b) their total surface area is very large (approx. 1000 m2), (3) and their walls can be very thin as their inner radius (4.5 µm) is extremely small (Laplace’s law, see below).

Transmural pressure Ptm [N/m2], that is, the pressure difference across the wall of a hollow organ (= internal pressure minus external pressure), causes the wall to stretch. Its materials must therefore be able to withstand this stretch. The resulting tangential mural tension T [N/m] is a function of the inner radius r [m] of the organ. According to Laplace’s law for cylindrical (or spherical) hollow bodies,

Ptm ! T/r (or Ptm ! 2 T/r, resp.) [8.3a/b]

Here, T is the total mural tension, regardless how thick the wall is. A thick wall can naturally withstand a given Ptm more easily than a thin one. In order to determine the tension exerted per unit CSA of the wall (i.e., the stress requirements of the wall material in N/m2), the thickness of the wall (w) must be considered. Equation 8.3 a/b is therefore transformed to

Ptm ! T ! w/r (or Ptm ! 2 T ! w/r, resp.) [8.4a/b]

The blood collects in the veins, which can accommodate large volumes of fluid (!A6). These capacitance vessels serve as a blood reservoir (!p. 186).

Cardiac Cycle

The resting heart rate is 60–80 beats per minute. A cardiac cycle (!A) therefore takes roughly 1 s. It can be divided into four distinct phases: (I) contraction phase and (II) ejection phase, both occurring in systole; (III) relaxation phase and filling phase (IV), both occurring in diastole. At the end of phase IV, the atria contract (phase IVc). Electrical excitation of the atria and ventricles precedes their contraction.

The cardiac valves determine the direction of blood flow within the heart, e.g., from the atria to the ventricles (phase IV) or from the ventricles to the aorta or pulmonary artery (phase II). All cardiac valves are closed during phases I and III (!A, top). Opening and closing of the valves is controlled by the pressures exerted on the two sides of the valves.

Cardiac cycle. Near the end of ventricular diastole, the sinoatrial (SA) node emits an electrical impulse, marking to the beginning of the

(!A4) and is followed by ventricular excitation

(QRS complex of the ECG). The ventricular pressure then starts to rise ( !A2, blue line) until it exceeds the atrial pressure, causing the atrioventricular valves (mitral and tricuspid valves) to close. This marks the end of diastole. The mean end-diastolic volume (EDV) in the ventricle is now about 120 mL (!A4) or, more precisely, 70 mL/m2 body surface area.

The isovolumetric contraction phase now begins (phase I, ca. 50 ms). With all valves are closed, the ventricles now contract, producing the first heart sound (!A6), and the ventricular pressure increases rapidly. The slope of this ascending pressure curve indicates the maximum rate of pressure developed (maximum dP/dt). The semilunar valves (aortic and pulmonary valves) now open because the pressure in the left ventricle (!A2, blue line) exceeds that in the aorta (black broken curve) at about 80 mmHg, and the pressure in the right ventricle exceeds that in the pulmonary artery at about 10 mmHg.

The ejection phase (now begins phase II; ca. 210 ms at rest). During this period, the pressure in the left ventricle and aorta reaches a maximum of ca. 120 mmHg (systolic pressure). In the early phase of ejection (IIa or rapid ejec-

tion phase), a large portion of the stroke volume (SV) is rapidly expelled (!A4) and the blood flow rate reaches a maximum (!A5). Myocardial excitation subsequently decreases (T wave of the ECG, !A1) and ventricular pressure decreases (the remaining SV fraction is slowly ejected, phase IIb) until it falls below that of the aorta or pulmonary artery, respectively. This leads to closing of the semilunar valves, producing the second heart sound (!A6). The mean SV at rest is about 80 mL or, more precisely, 47 mL/m2 body surface area. The corresponding mean ejection fraction (SV/ EDV) at rest is about 0.67. The end-systolic volume (ESV) remaining in the ventricles at this point is about 40 mL (!A4).

The first phase of ventricular diastole or isovolumetric relaxation now begins (phase III; ca. 60 ms). The atria have meanwhile refilled, mainly due to the suction effect created by the lowering of the valve plane during ejection. As a result, the central venous pressure (CVP) decreases (!A3, falls from c to x). The ventricular pressure now drops rapidly, causing the atrioventricular valves to open again when it falls short of atrial pressure.

The filling phase now begins (phase IV; ca. 500 ms at rest). The blood passes rapidly from the atria into the ventricles, resulting in a drop in CVP (!A3, point y). Since the ventricles are 80% full by the first quarter of diastole, this is referred to as rapid ventricular filling (phase IVa; !A4). Ventricular filling slows down

(phase IVb), and the atrial systole (phase IVc) and the awave of CVP follows (!A2,3). At a normal heart rate, the atrial contraction contributes about 15% to ventricular filling. When the heart rate increases, the duration of the cardiac cycle decreases mainly at the expense of diastole, and the contribution of atrial contraction to ventricular filling increases.

The heart beats produce a pulse wave (pressure wave) that travels through the arteries at a specific pulse wave velocity (PWV): the PWV of the aorta is 3–5 m/s, and that of the radial artery is 5–12 m/s. PWV is. much higher than the blood flow velocity (V), which peaks at 1 m/s in the aorta and increases proportionally to (a) decreases in the compliance of aortic and arterial walls and (b) increases in blood pressure.

Isovolumetric contraction

Atrial systole

Aortic pressure

Left ventricular pressure

Left atrial pressure

Central venous pressure (CVP)

Left ventricular volume

Flow rate

in aortic root

Heart sounds

Duration

mmHg 2

!

an AP. The slope of their APs therefore rises more sharply than that of a pacemaker potential (!A). A resting potential prevails between APs, i.e. spontaneous depolarization normally does not occur in the working myocardium. The long-lasting myocardial AP has a characteristic plateau (!p. 59 A). Thus, the firststimulated parts of the myocardium are still in a refractory state when the AP reaches the laststimulated parts of the myocardium. This prevents the cyclic re-entry of APs in the myocardium. This holds true, regardless of whether the heart rate is very fast or very slow since the duration of an AP varies according to heart rate (!B2).

Role of Ca2+. The incoming AP opens voltagegated Ca2+ channels (associated with dihydropyridine receptors) on the sarcolemma of myocardial cells, starting an influx of Ca2+ from the ECF (!p. 63/B3). This produces a local increase in cytosolic Ca2+ (Ca2+ “spark”) which, in turn, triggers the opening of ligand-gated, ry- anodine-sensitive Ca2+ channels in the sarcoplasmic reticulum (Ca2+ store). The influx of Ca2+ into the cytosol results in electromechanical coupling (!p. 62) and myocardial contraction. The cytosolic Ca2+ is also determined by active transport of Ca2+ ions back (a) into the Ca2+ stores via a Ca2+-ATPase, called SERCA, which is stimulated by phospholamban, and

(b) to the ECF. This is achieved with the aid of a

Ca2+-ATPase and a 3Na+/Ca2+ exchange carrier that is driven by the electrochemical Na+ gradient established by Na+-K+-ATPase.

Although the heart beats autonomously, efferent cardiac nerves are mainly responsible for modulating heart action according to changing needs. The autonomic nervous system

(and epinephrine in plasma) can alter the following aspects of heart action: (a) rate of impulse generation by the pacemaker and, thus, the heart rate (chronotropism); (b) velocity of impulse conduction, especially in the AV node (dromotropism); and (c) contractility of the heart, i.e., the force of cardiac muscle contraction at a given initial fiber length (inotropism).

These changes in heart action are induced by acetylcholine (ACh; !p. 82) released by parasympathetic fibers of the vagus nerve (binds with M2 cholinoceptors on pacemaker cells), by norepinephrine (NE) released by sympathetic nerve fibers, and by plasma epi-

nephrine (E). NE and E bind with !1-adreno- ceptors (!p. 84ff.). The firing frequency of the SA node is increased by NE and E (positive chronotropism) and decreased by ACh (negative chronotropism) because these substances alter the slopes of the PP and the MDP in the SA cells (!B3a and c). Under the influence of ACh, the slope of the PP becomes flatter and the MDP becomes more negative gK rises. In versely, slope and amplitude of PP rises under the influence of E or sympathetic stimuli (higher If ) due to a rise in cation (Na+) conductance and, under certain conditions, a decrease in the gK. Only NE and E have chronotropic effects in the lesser components of the impulse conduction system. This is decisive when the AV node or tertiary pacemakers take over.

ACh (left branch of vagus nerve) decreases the velocity of impulse conduction in the AV node, whereas NE and E increase it due to their negative and positive dromotropic effects, respectively. This is mainly achieved through changes in the amplitude and slope of the up-

stroke of the AP (!B3c and B4), gK and gCa.

In positive inotropism, NE and E have a direct effect on the working myocardium. The resulting increase in contractility is based on an increased influx of Ca2+ ions from the ECF triggered by !1-adrenoceptors, resulting in an increased cytosolic Ca2+. This Ca2+ influx can be inhibited by administering Ca2+ channel blockers (Ca2+ antagonists). Other factors that increase cardiac contractility are an increase in AP duration, resulting in a longer duration of Ca2+ influx, and inhibition of Na+-K+-ATPase

(e.g., by the cardiac glycosides digitalis and strophanthin). The consequences are: flatter Na+ gradient across the cell membrane ! decreased driving force for 3 Na+/Ca2+ exchange carriers ! decreased Ca2+ efflux ! increased cytosolic Ca2+ conc.

When the heart rate is low, Ca2+ influx over time is also low (fewer APs per unit time), allowing plenty of time for the efflux of Ca2+ between APs. The mean cytosolic Ca2+ conc. is therefore reduced and contractility is low. Only by this indirect mechanism are parasympathetic neurons able to elicit a negative inotropic effect (frequency inotropism). NE and E can exert their positive inotropic effects either indirectly by increasing the high heart or directly via !1-adrenoceptors of the working