Department of Physiology: CVS Physiology-Offline information

The Physics of Fluid Flow (see figure, figure)

Bernoulli's principle (A) and Poiseuille's law (B): In a tube or a blood vessel the total energy—the sum of the kinetic energy of flow and the Potential energy—is constant (Bernoulli's principle). According to the principle, the greater the velocity of flow in a vessel, the lower the lateral pressure distending its walls. When a vessel is narrowed, the velocity of flow in the narrowed portion increases and in the distending pressure decreases. Therefore, when a vessel is narrowed by a pathologic process such as an atherosclerotic plaque, the lateral pressure at the constriction is decreased and the narrowing tends to maintain itself. In addition, there is a linear drop in fluid pressure is according to Poiseuille's law, but the constriction produces an extra drop in pressure according to the Bernoulli Principle

Introduction to Blood Flow, Blood Pressure, and Resistance: Blood Flow: Is the volume of blood flowing through a vessel, an organ, or the entire circulation in a given period (ml/min). If we consider the entire vascular system, blood flow is equivalent to cardiac output (CO), and under resting conditions, it is relatively constant. At any given moment, however, blood flow through individual body organs may vary widely according to their immediate needs.

Blood pressure (BP), the force per unit area exerted on a vessel wall by the contained blood, is expressed in millimeters of mercury (mm Hg). For example, a blood pressure of 120 mm Hg is equal to the pressure exerted by a column of mercury 120 mm high. Unless stated otherwise, the term blood pressure means systemic arterial blood pressure in the largest arteries near the heart. The pressure gradient—the differences in blood pressure within the vascular system—provides the driving force that keeps blood moving, always from an area of higher pressure to an area of lower pressure, through the body.

Resistance is opposition to flow and is a measure of the amount of friction blood encounters as it passes through the vessels. Because most friction is encountered in the peripheral (systemic) circulation, well away from the heart, we generally use the term peripheral resistance. There are three important sources of resistance (figure): blood viscosity, vessel length, and vessel diameter.

Blood viscosity: The internal resistance to flow that exists in all fluids is viscosity and is related to the thickness or “stickiness” of a fluid. The greater the viscosity, the less easily molecules slide past one another and the more difficult it is to get and keep the fluid moving. Blood is much more viscous than water. Because it contains formed elements and plasma proteins, it flows more slowly under the same conditions. Blood viscosity is fairly constant, but conditions such as polycythemia (excessive numbers of red blood cells) can increase blood viscosity and, hence, resistance. On the other hand, if the red blood cell count is low, as in some anemias, blood is less viscous and peripheral resistance declines. Because blood is a viscous fluid, its movement through a vessel exerts a shear stress on the walls of the vessel. This is a force that wants to drag the inside surface (the endothelial cell layer) of the vessel along with the flow. The endothelial cells that line a vessel are able to sense (and possibly respond to) changes in the rate of blood flow through the vessel by detecting changes in the shear stress on them. Shear stress may also be an important factor in certain pathological situations. For example, atherosclerotic plaques tend to form preferentially near branches of large arteries where, for complex hemodynamic reasons beyond the scope of this text, high shear stresses exist.
Total Blood vessel length: The relationship between total blood vessel length and resistance is straightforward: the longer the vessel, the greater the resistance. For example, an infant’s blood vessels lengthen as he or she grows to adulthood, and so both peripheral resistance and blood pressure increase.
Blood vessel Diameter: Because blood viscosity and vessel length are normally unchanging, the influence of these factors can be considered constant in healthy people. However, blood vessel diameter changes frequently and significantly alters peripheral resistance. This is because the fluid close to the wall of a tube or channel is slowed by friction as it passes along the wall, whereas fluid in the center of the tube flows more freely and faster. You can verify this by watching the flow of water in a river. Water close to the bank hardly seems to move, while that in the middle of the river flows quite rapidly. In a tube of a given size, the relative speed and position of fluid in the different regions of the tube’s cross section remain constant, a phenomenon called laminar flow or streamlining (figure). The smaller the tube, the greater the friction, because relatively more of the fluid contacts the tube wall, where its movement is impeded.

The factors that determine the resistance are inter-related and were described by Poiseuille’s law in which the resistance is determined according to the following formula:
R = 8L η / π r⁴
R = Resistance, L = Length of tube, η = Viscosity of ﬂuid, r = Radius of tube.
Resistance varies inversely with the fourth power of the vessel radius (one-half the diameter). This means, for example, that if the radius of a vessel doubles, the resistance drops to one-sixteenth of its original value (r⁴ = 2 x 2 x 2 x 2 = 16 and R = 1/16). For this reason, the large arteries close to the heart, which do not change dramatically in diameter, contribute little to peripheral resistance. Instead, the small-diameter arterioles, which can enlarge or constrict in response to neural and chemical controls, are the major determinants of peripheral resistance. When blood encounters either an abrupt change in vessel diameter or rough or protruding areas of the tube wall (such as the fatty plaques of atherosclerosis), the smooth laminar blood flow is replaced by turbulent flow (figure), that is, irregular fluid motion where blood from the different laminae mixes. Turbulence dramatically increases resistance.

Relationship Between Flow, Pressure, and Resistance: Blood flow (F) is directly proportional to the difference in blood pressure (ΔP) between two points in the circulation, that is, the blood pressure, or hydrostatic pressure, gradient. Thus, when ΔP increases, blood flow speeds up, and when ΔP decreases, blood flow declines. Blood flow is inversely proportional to the peripheral resistance (R) in the systemic circulation; if R increases, blood flow decreases. We can express these relationships by the formula: F = ΔP / R. Of these two factors influencing blood flow, R is far more important than ΔP in influencing local blood flow because R can easily be changed by altering blood vessel diameter.

Active and reactive hypermemia (figure)

Blood ﬂow through individual blood vessels is determined by the vessel’s resistance to ﬂow (see figure)

Myocarditis is an inflammation of the myocardium that usually occurs as a complication of a viral infection, rheumatic fever, or exposure to radiation or certain chemicals or medications. Myocarditis often has no symptoms. However, if they do occur, they may include fever, fatigue, vague chest pain, irregular or rapid heartbeat, joint pain, and breathlessness. Myocarditis is usually mild and recovery occurs within two weeks. Severe cases can lead to cardiac failure and death. Treatment consists of avoiding vigorous exercise, a low-salt diet, electrocardiographic monitoring, and treatment of the cardiac failure.

Endocarditis refers to an inflammation of the endocardium and typically involves the heart valves. Most cases are caused by bacteria (bacterial endocarditis). Signs and symptoms of endocarditis include fever, heart murmur, irregular or rapid heartbeat, fatigue, loss of appetite, night sweats, and chills. Treatment is with intravenous antibiotics.

Valvular diseases: When heart valves operate normally, they open fully and close completely at the proper times. A narrowing of a heart valve opening that restricts blood flow is known as stenosis failure of a valve to close completely is termed insufficiency or incompetence. In mitral stenosis, scar formation or a congenital defect causes narrowing of the mitral valve. One cause of mitral insufficiency, in which there is backflow of blood from the left ventricle into the left atrium, is mitral valve prolapse (MVP). In MVP one or both cusps of the mitral valve protrude into the left atrium during ventricular contraction. Mitral valve prolapse is one of the most common valvular disorders, affecting as much as 30% of the population. It is more prevalent in women than in men, and does not always pose a serious threat. In aortic stenosis the aortic valve is narrowed, and in aortic insufficiency there is backflow of blood from the aorta into the left ventricle. Certain infectious diseases can damage or destroy the heart valves. One example is rheumatic fever, an acute systemic inflammatory disease that usually occurs after a streptococcal infection of the throat. The bacteria trigger an immune response in which antibodies produced to destroy the bacteria instead attack and inflame the connective tissues in joints, heart valves, and other organs. Even though rheumatic fever may weaken the entire heart wall, most often it damages the mitral and aortic valves.

Ischemic heart diseases: Partial obstruction of blood flow in the coronary arteries may cause myocardial ischemia, a condition of reduced blood flow to the myocardium. Usually, ischemia causes hypoxia (reduced oxygen supply), which may weaken cells without killing them. Angina pectoris, which literally means “strangled chest,” is a severe pain that usually accompanies myocardial ischemia. Typically, sufferers describe it as a tightness or squeezing sensation, as though the chest were in a vise. The pain associated with angina pectoris is often referred to the neck, chin, or down the left arm to the elbow. Silent myocardial ischemia, ischemic episodes without pain, is particularly dangerous because the person has no forewarning of an impending heart attack. A complete obstruction to blood flow in a coronary artery may result in a myocardial infarction (in-FARK-shun), or MI, commonly called a heart attack. Infarction means the death of an area of tissue because of interrupted blood supply. Because the heart tissue distal to the obstruction dies and is replaced by noncontractile scar tissue, the heart muscle loses some of its strength. Depending on the size and location of the infarcted (dead) area, an infarction may disrupt the conduction system of the heart and cause sudden death by triggering ventricular fibrillation. Treatment for a myocardial infarction may involve injection of a thrombolytic (clot-dissolving) agent such as streptokinase or t-PA, plus heparin (an anticoagulant), or performing coronary angioplasty or coronary artery bypass grafting. Fortunately, heart muscle can remain alive in a resting person if it receives as little as 10–15% of its normal blood supply. •

As noted earlier in the chapter, the heart of a heart attack survivor often has regions of infarcted (dead) cardiac muscle tissue that typically are replaced with noncontractile fibrous scar tissue over time. Our inability to repair damage from a heart attack has been attributed to a lack of stem cells in cardiac muscle and to the absence of mitosis in mature cardiac muscle fibers. A recent study of heart transplant recipients by American and Italian scientists, however, provides evidence for significant replacement of heart cells. The researchers studied men who had received a heart from a female, and then looked for the presence of a Y chromosome in heart cells. (All female cells except gametes have two X chromosomes and lack the Y chromosome.) Several years after the transplant surgery, between 7% and 16% of the heart cells in the transplanted tissue, including cardiac muscle fibers and endothelial cells in coronary arterioles and capillaries, had been replaced by the recipient’s own cells, as evidenced by the presence of a Y chromosome. The study also revealed cells with some of the characteristics of stem cells in both transplanted hearts and control hearts. Evidently, stem cells can migrate from the blood into the heart and differentiate into functional muscle and endothelial cells. The hope is that researchers can learn how to “turn on” such regeneration of heart cells to treat people with heart failure or cardiomyopathy (diseased heart).

SA abnormalities: If the SA node becomes damaged or diseased, the slower AV node can pick up the pacemaking task. Its rate of spontaneous depolarization is 40 to 60 times per minute. If the activity of both nodes is suppressed, the heartbeat may still be maintained by autorhythmic fibers in the ventricles—the AV bundle, a bundle branch, or Purkinje fibers. However, the pacing rate is so slow (20–35 beats per minute) that blood flow to the brain is inadequate. When this condition occurs, normal heart rhythm can be restored and maintained by surgically implanting an artificial pacemaker, a device that sends out small electrical currents to stimulate the heart to contract. A pacemaker consists of a battery and impulse generator and is usually implanted beneath the skin just inferior to the clavicle. The pacemaker is connected to one or two flexible leads (wires) that are threaded through the superior vena cava and then passed into the various chambers of the heart. Many of the newer pacemakers, referred to as activity-adjusted pacemakers, automatically speed up the heartbeat during exercise.

Heart sounds provide valuable information about the mechanical operation of the heart. A heart murmur is an abnormal sound consisting of a clicking, rushing, or gurgling noise that either is heard before, between, or after the normal heart sounds, or may mask the normal heart sounds. Heart murmurs in children are extremely common and usually do not represent a health condition. Murmurs are most frequently discovered in children between the ages of two and four. These types of heart murmurs are referred to as innocent or functional heart murmurs; they often subside or disappear with growth. Although some heart murmurs in adults are innocent, most often an adult murmur indicates a valve disorder. When a heart valve exhibits stenosis, the heart murmur is heard while the valve should be fully open but is not. For example, mitral stenosis produces a murmur during the relaxation period, between S2 and the next S1. An incompetent heart valve, by contrast, causes a murmur to appear when the valve should be fully closed but is not. So, a murmur due to mitral incompetence occurs during ventricular systole, between S1 and S2.

In congestive heart failure (CHF), there is a loss of pumping efficiency by the heart. Causes of CHF include coronary artery disease (see page 000), congenital defects, long-term high blood pressure (which increases the afterload), myocardial infarctions (regions of dead heart tissue due to a previous heart attack), and valve disorders. As the pump becomes less effective, more blood remains in the ventricles at the end of each cycle, and gradually the end-diastolic volume (preload) increases. Initially, increased preload may promote increased force of contraction (the Frank–Starling law of the heart), but as the preload increases further, the heart is overstretched and contracts less forcefully. The result is a potentially lethal positive feedback loop: Less-effective pumping leads to even lower pumping capability. Often, one side of the heart starts to fail before the other. If the left ventricle fails first, it can’t pump out all the blood it receives. As a result, blood backs up in the lungs and causes pulmonary edema, fluid accumulation in the lungs that can cause suffocation if left untreated. If the right ventricle fails first, blood backs up in the systemic veins and, over time, the kidneys cause an increase in blood volume. In this case, the resulting peripheral edema usually is most noticeable in the feet and ankles. •

Atrial fibrillation: The atria fail to contract when a person has atrial fibrillation, yet the amount of blood that fills the ventricles and that the ventricles eject is often sufficient to allow the person to live without obvious symptoms. However, the person may experience fatigue and difficulty exercising due to an inability to sufficiently increase the cardiac output. More seriously, thepooling of blood in the atria increases the chances of blood clot formation, causing a four- to fivefold increase in the risk
of stroke. This may be prevented with anticoagulants including aspirin, warfarin (which blocks the activation of vitamin K), and rivaroxaban (Xarelto), which inhibits factor
X activity in the clotting sequence .

Digitalis, or digoxin (Lanoxin), is a “cardiac glycoside” drug often used to treat people with congestive heart failure or atrialfibrillation. Digitalis inactivates the Na⁺/K⁺–ATPase pumps in the myocardial cell plasma membrane, interfering with their ability to pump Na⁺ out of the cell. This increases the activity of the Na⁺/Ca²⁺ exchange pumps in the plasma membrane, so that they pump more Na1 out of the cell and more Ca²⁺ into the cell. As the intracellular concentration of Ca²⁺ rises, so does the amount of Ca²⁺ stored in the sarcoplasmic reticulum. This increases the contractility (strength of contraction)
of the myocardium, which helps to treat congestive heart failure, and also slows the conduction of the impulses through the AV node, helping to treat atrial fibrillation.

Varicose veins are enlarged surface veins, generally in the lower limbs, which occur when venous congestion stretches the veins to the point that the venous valves no longer close effectively. Genetic susceptibility, occupations that require long periods of standing, obesity, age, and pregnancy (due to compression of abdominal veins by the fetus) are risk factors. Walking can reduce venous congestion, as can compression stockings and leg elevation; in bedridden patients, flexing and extending the ankle joints activates the soleus muscle pump to help move blood from the legs back to the heart. Surgical treatments of varicose veins include sclerotherapy (where chemicals are injected into the veins to scar them), laser therapy (using lasers to destroy the veins), ligation and stripping (tying off and removing the veins), and other techniques. Inadequate venous flow in a bedridden patient increases the risk of deep vein thrombosis, a dangerous condition that can lead to a venous thromboembolism (a traveling blood clot). Walking around as soon as possible after a surgery reduces the risk, as do the use of compression stockings and devices that compress the leg. Anticoagulant drugs or thrombolytic agents may sometimes be necessary to prevent or treat a thromboembolism so that it doesn’t result in a potentially fatal pulmonary embolism.

Circulatory shock: Is any condition in which blood volume is inadequate and cannot circulate normally, resulting in blood flow that cannot meet the needs of a tissue. Circulatory shock is of many types:

Hypovolemic shock results from a large-scale loss of blood, and may be characterized by an elevated heart rate and intense vasoconstriction.
Vascular shock is characterized by a normal blood volume, but extreme vasodilation, often related to a loss of vasomotor tone, resulting in poor circulation and a rapid drop in blood pressure. Vascular shock can be due to: anaphylactic shock, neurogenic shock, and septic shock. Transient vascular shock is due to prolonged exposure to heat, such as while sunbathing, resulting in vasodilation of cutaneous blood vessels.
Cardiogenic shock occurs when the heart is too inefficient to sustain normal blood flow, and is usually related to myocardial damage, such as repeated myocardial infarcts.

The body and cardiovascular responses to circulatory shock are summarized in the following figure.