1. General Remarks:

     In this chapter, we will consider the physiological principles which are involved in some disorders of the heart and circulation. No attempt will be made to cover all the diseases of the circulatory system; a few will be chosen, because they illustrate normal and abnormal physiology particularly well. The conditions we will deal with are high blood pressure, hemorrhage and shock, arteriosclerosis and coronary thrombosis, and chronic congestive heart failure.

2. High Blood Pressure:

     High blood pressure is a very common disease. Since the blood pressure of a group of normal persons varies just as do their height, it is difficult to say just what the criterion for the diagnosis of high blood pressure should be. Most physicians would consider a blood pressure higher than 140 / 90 to be suspiciously high, but this may be a normal figure for some people (See also the Table in Chapter 11). The decision whether an individual blood pressure is abnormally high is best left to a physician.

     High blood pressure is a serious disease. Persons with high blood pressure are more likely than others to have hardening of the arteries (See Part 4). This in turn may lead to obstruction in the arteries supplying the brain, the heart itself, or the kidneys. In the first case, a "stroke" may result; in the second a "heart attack"; in the third, the kidney may gradually be destroyed over a period of years, and death may occur from kidney failure.

     There are a few cases of high blood pressure in which the cause is known. For example, abnormal growth of a part of the adrenal gland may lead to the formation of excessive amounts of adrenaline and nor-adrenaline. High blood pressure results from the presence of these in the blood. The abnormal growth is called a pheochromocytoma.

     Another kind of high blood pressure in which the cause seems to be known is observed when the aorta is severely narrowed in the chest. Delivery of adequate amounts of blood to the lower parts of the body through the narrowed aorta is difficult. Other arterial channels develop and the blood pressure becomes high. This is called coarctation of the aorta.

     The great majority of cases of high blood pressure have no known cause. These are called essential hypertension. "Essential" in the name means simply that the cause is unknown.

     Despite the fact that the cause is often unknown, physiological principles can aid us considerably in understanding the disease and even in developing treatments for it.

     For example, we know that essential hypertension is a disease in which the arterial pressure is elevated. The cardiac output is usually only slightly elevated. From this we can deduce that the peripheral resistance is high.

     Measurements of pressures in various parts of the circulation have shown that the greatest pressure drop in the circulation (that is to say the greatest part of the peripheral resistance) is in the arterioles. If the peripheral resistance is elevated, we must suspect that there is arteriolar vaso-constriction.

     It is also known from observations on hypertensive people that the distribution of the cardiac output is basically normal (except for reduced blood flow to the kidneys). Therefore, we must seek the cause of hypertension in some factor or factors that bring about arteriolar vasoconstriction in all areas of the body. On the other hand, if a drug or circumstance could be found which would bring about vasoconstriction in all areas of the body it might be useful in the treatment of hypertension.

     It has sometimes been argued that this is a dangerous thing to do, and that if the blood pressure is high, it must serve a useful purpose by being high. There is no evidence that this is the case, and there is ample evidence that there are no adverse consequences to be feared when the blood pressure of a person with high blood pressure is lowered.

     Several substances have been suspected as the cause of the generalized vasoconstriction. Of these, most suspicion was, for a time, placed on renin, a substance which can be found in the normal kidney.

     It was believed that renin, normally locked in the kidney, was somehow released into the blood stream where acting on a blood protein, it caused the formation of an active vasoconstrictor substance, angiotensin. In support of this idea was the fact that the effects of renin on the circulation are almost identical with the findings in high blood pressure. Furthermore, renin is released from the kidney in circumstances similar to those which can bring about high blood pressure in experimental animals and men. Against the idea is the fact that renin is very rarely found in the blood of men with essential hypertension; and even in experimental animals, renin is not usually found after high blood pressure has developed and stabilized. The most serious objection to the idea that renin is the cause of high blood pressure is the fact that removal of one or both kidneys, which removes the source of renin, does not lower the blood pressure of hypertensive animals, and may raise the blood pressure of the normal animal.

     Much interest has centered around the possibility that salt (sodium chloride) is responsible for hypertension. People and animals on high salt intake develop hypertension; low salt diets are often successful in lowering the blood pressure of hypertensive persons. One of the best drugs used today in treating high blood pressure aids the elimination of salt from the body. How salt exerts its effects on blood pressure is not yet clear.

     Another idea concerning the cause of high blood pressure has to do with the aortic arch and carotic sinus reflexes. It will be recalled that these operate in such a manner that when the blood pressure falls vasoconstriction occurs; when the blood pressure rises, there is vasodilation. These reflexes therefore stabilize the blood pressure in the normal range, just as the thermostat of a house with both heating and air conditioning serves to keep the temperature in the normal range.

     In a house equipped with a thermostat, abnormally high temperatures will result if the temperature sensing elements become insensitive to high temperatures. In the same way, if the pressure sensing elements of the barostatic reflexes become insensitive to high pressure, an abnormally high blood pressure would be expected to result.

     There is strong evidence that this is so in both animal and human hypertension. The barostatic sensing elements behave as if the blood pressure were low when it is normal and normal when it is high.

     This has opened a new approach to the treatment of high blood pressure. The barostatic nerves in the neck are simply stimulated electrically at a rate which corresponds to the blood pressure as it actually is rather than as it is erroneously reported by the sensing elements. Some very remarkable cases where high blood pressure has been lowered in man after all other means had failed have been reported.

     At the present time, the most practical means for the treatment of high blood pressure is the restriction of dietary salt and the administration of drugs to cause salt losses by the kidney. In addition, drugs acting to interfere with the normal mechanism of adrenaline and nor-adrenaline release have proved very valuable. Some of the drugs act on centers in the brain; others act at the autonomic ganglia; and still others act at the sympathetic nerve endings. Which treatment, if any is best for an individual case, cannot always be predicted in advance. A long period of trial and constant careful watching of the patient by a physician is sometimes necessary before the best choice of drugs can be made.

3. Hemorrhage and Shock:

     In both hemorrhage and shock there is a reduction in the circulating blood volume. In hemorrhage the blood loss is usually from a large vessel and occurs quite suddenly. In shock, the blood volume declines progressively, but the lost volume is not lost through large vessels and may not even disappear from the body, although it leaves the circulation.

     The adjustments of the circulation which occur after a single large loss of blood are, in order:

(1) Constriction of Arterioles: this increases the peripheral resistance and side in the restoration of blood pressure. It is brought about through a combination of factors. The barostatic reflexes are activated, the adrenal medulla releases adrenaline and nor-adrenaline, and the kidneys release renin.

(2) Constriction of Veins: The same mechanisms which are involved in the arteriolar constriction operate to produce constriction of the veins. This constriction propels blood toward the heart and increases the cardiac output toward the normal level.

(3) Replacement of Volume: as the arterioles constrict the pressure in the capillaries falls; when the hydrostatic pressure falls below the osmotic pressure due to the proteins, fluid which was outside the capillaries is, so to speak, drawn into them. This fluid contains water and the same dissolved materials as are normally present in the plasma, but no proteins. Thus, it can be used as a partial replacement of the lost volume, but it does not contain either the proteins or the red blood cells which have been lost.

(4) Replacement of Proteins: The liver is probably the source of plasma proteins. It is not known what the stimulus is which makes the liver increase its production of proteins to make up the loss.

(5) Replacement of the Red Blood Cells: red cells are produced primarily in bone marrow. The probable stimulus for their production is a reduction in the oxygen level in the whole body. When red blood cells are lost, the oxygen level in bone marrow is probably lowered; this may be one of many stimuli which act to cause increased red cell formation in the marrow.

     The above describes what happens after a single, uncomplicated loss of blood. Usually, if the blood loss is not immediately fatal, the restoration of the normal situation, which begins in a few seconds with arteriolar constriction, is complete in a few weeks, when the lost red cells are completely replaced.

     Uncomplicated hemorrhages, however, are quite rare. Usually there is tissue injury at the same time, or the fluid loss may continue over a long time period. The combination of tissue injury and fluid loss leads to a condition called surgical or traumatic shock. This is best defined as a progressive failure of the circulation in which the blood volume does not fill the blood vessels tightly. Clearly, this can result from loss of blood volume or from increase in the capacity of the vascular system, or both.

     Although there has been and continues to be very active research on shock, its exact cause is by no means certain. In fact, it is not at all certain that all forms of shock are the same. For example, shock may be produced by the injection of a material from certain bacteria called "endotoxin" or it may be produced by the slow intravenous infusion of adrenaline. Both have the same consequence- -progressive failure of the circulation--but they may evolve in quite different ways. Again, the type of circulatory collapse seen after a large bone, such as the thigh bone, is broken would seem to have a different course from the others.

     Recognizing that shock may come about in a variety of ways, it is still possible to make some generalizations about the condition:

1. The condition is brought about by a harmful change. This is called the insult. It may be the administration of endotoxins, the crushing of a limb, the fracture of a bone, too much handling of the internal organs at surgery, or an extensive burn of the skin.

2. The usual response to the insult is a rise in blood pressure or no change. The cardiac output, however, begins to fall. Despite the fall in cardiac output, the blood pressure remains normal. The same mechanisms operate to maintain this normality as operate after hemorrhage. This is spoken of as the phase of compensation.

3. The cardiac output continues to fall. The compensatory mechanisms become unable to maintain the arterial blood pressure; there is a progressive fall of blood pressure. This is called the phase of decompensation.

4. When the arterial blood pressure falls below a certain level and stays there for some time certain organs are not well enough supplied with blood to remain alive. These organs, notably the heart and the brain, die bit by bit. The treatment of shock at this point is hopeless, for the dead tissues cannot recover. This phase of shock is called the phase of irreversibility.

     Before irreversibility, shock can be managed and irreversibility averted by administering whole blood, plasma, or even salt solution. During decompensation, nor-adrenaline may be used to help in maintaining blood pressure. In animal experiments, nothing has been found useful in the treatment of irreversible shock; there is, however, no sure method of recognizing irreversible shock beside the fact that it cannot be treated successfully. For this reason, it would not be advisable to continue treatment of a patient in shock as long as life continued.

     The ability to maintain life in patients in whom a vital organs such as the brain may be partially dead has raised some unanswered questions in medical ethics. These have been debated recently in the popular press, but no satisfactory solution has appeared.

     Another treatment which has been proposed is the use of large doses of antibiotics which act to kill the intestinal organisms which may produce endotoxins. Some remarkably good results have been obtained by the use of this type of treatment in some forms of shock; in other forms of shock antibiotic treatment has been less successful.

4. Arteriosclerosis and Coronary Thrombosis:

     Arteriosclerosis means hardening of the arteries. The form of arteriosclerosis most likely to produce important disease is atherosclerosis. This is a condition in which there is deposition of a mushy substance (probably cholesterol) just outside the innermost layer of the arteries.

     These deposits occur in a patchy way. Some vessels may be heavily involved; others may not be affected at all. Often the existence of the arterial disease is first shown as a disease of the organ supplied by the artery. If, for example, there is atherosclerosis in an artery supplying a part of the brain, there may be no symptoms at all until the brain tissue supplied by that artery dies suddenly because of shortage of blood. One form of this is a "stroke".

     This can also happen in the arteries supplying the heart muscle (coronary arteries). There may be considerable coronary atherosclerosis without any heart symptoms until the affected artery or one of its branches suddenly plugs up. When this occurs, the area of the heart muscle supplied by the blood vessel dies; its death is usually associated with a crushing chest pain and with electrocardiographic abnormalities. This is the condition usually referred to as a "heart attack". The plugging of the vessel which leads to the heart attack is called a coronary thrombosis and the death of heart muscle tissue which follows the plugging is called myocardial infarction.

     The cause of atherosclerosis is not known at the present time. This disease has been difficult to study because it does not occur spontaneously with any frequency in any animal besides man (baboons show it rarely). It can be produced in rabbits, monkeys, and dogs by feeding a diet which is extremely high in cholesterol; but the cholesterol levels required to produce the disease in laboratory animals are so much greater than what could conceivably be taken in any human diet as to put the significance of dietary cholesterol in the causation of the disease into question.

     In the absence of real data, speculation abounds. It has been suggested that high fat diets cause the disease; it has also been suggested that diets high in "saturated" are at fault while "polyunsaturated fats" tend to prevent the disease. The evidence, though suggestive is not compelling.

     It does, however, seem to be true that atherosclerosis is more common among overweight than underweight persons, that it tends to occur in diabetics, and that there is more of it in persons who smoke than in those who do not.

     To illustrate the complexity of the problem of the cause of atherosclerosis, take the last statement that atherosclerosis is more common in smokers than in non-smokers. This might mean that smoking contributed to the formation of atherosclerosis; or it might mean that atherosclerosis affects only some personality types, and these are the personality types who also tend to take up smoking.

     Even after the formation of an atheroma in an artery has begun, the area supplied by that artery is usually unaffected. One of four things, however, may now happen:

1. The atheroma may enlarge so greatly that the flow of blood through the artery is restricted or even blocked entirely.

2. The atheroma may act as a place at which little blood elost may form. These may occur slightly or in "showers."

3. The atheroma may expand enough to break the lining of the vessel. This may lead to clotting. Another possibility is that blood may enter the atheromatous area, expanding the atheroma and blocking off the vessel.

4. The fourth possibility is probably much more common than has ever been realized--the atheroma may simply disappear and the vessel return to its normal condition.

     If any of the first three events occurs, and if the organ supplied by the artery is a vital one, the consequences may be disastrous. If, for example, the arteries of the brain are affected, strokes may develop, as noted in Chapter 5. Besides major strokes such as those which produce paralysis on one side of the body there may be transient ischemic attacks in which the function of the brain is temporarily disorganized. These may lead to temporary dizziness, confusion, loss of vocabulary, emotional disturbances, etc. It is one of the utmost importance to recognize these "transient ischemic attacks," for they are quite often the warning that a stroke will occur. Unfortunately, most patients (and many doctors) do not take them as seriously as they should, particularly since they pass off. Surgical techniques have developed to a point where atheromatous sections of artery can be replaced. The results of such treatment have been very good; early recognition is, therefore, vital.

     When the artery affected by atheromatous disease is the coronary artery, the disturbed function is, of course, that of the heart muscle. Sometimes (but not always) the first indication of coronary arterial disease is chest pain on exertion (angina pectoris). Most often, there are no warning signs at all. A normally functioning heart in which an atheroma has progressed to the point of coronary occlusion may respond in one of three ways:

1. The occlusion may result in infarction of so much muscle mass that the heart cannot keep up with the requirements of the circulation. It fails within a few beats.

2.The occlusion may be smaller, but the muscle supplied can no longer maintain its normal electrical state--the outside of the cell is usually positive, the inside negative. After myocardial infarction, both outside and inside become neutral. The healthy neighboring heart muscle is therefore charged with respect to the infarcted area. This sets up currents which are quite abnormal and are followed by abnormal uncoordinated contractions (ventricular fibrillation). In a sense, the heart has electrocuted itself.

3. The infarcted area may die, but it may not be followed by abnormal contractions. There are changes which can be seen in the electrocardiogram; eventually the infarcted area is replaced by scar tissue and the heart becomes normal except in so far as part of its muscle is lost. In such a person (one who has recovered from a heart attack) the heart may function quite normally at rest or during mild to moderate exercise. It may not be able to keep up with demands of the circulation during severe exercise.

     It should however always be remembered that a person who has had a heart attack probably has atheromatous disease of his coronary arteries. It is therefore more probable that a person who has had a heart attack will have a new one than will a person who has never had a heart attack. Some doctors like to use preventive treatment in patients; the use of drugs which delay clotting is one type of treatment which has been widely recommended. The obvious difficulty with this type of treatment is that the person so treated may lose blood excessively, even fatally, after minor injuries.

5. Chronic Congestive Heart Failure:

     This is a condition in which one side of the heart or the other (or both) is unable to deliver enough power to maintain the circulation during activity. Obviously, there are degrees of this disease. In some cases, all activities except the most extreme ones are possible; in other cases moderate activity becomes impossible; in still others, the heart cannot keep up with anything more than the minimum level of activity. For example, the exertion of dressing may present more of a circulatory load than the heart can handle.

     The symptoms tend to be in the lungs, when the left side of the heart is failing, or in the systemic circulation when the right side is involved.

     It will be convenient for this discussion to define a term often used loosely, the cardiac reserve. We will use it here as the difference between the power requirement made by the circulation on the heart and the ability of the heart in that person to deliver power. For example, if the left heart in certain circumstances is required to deliver power at the rate of 2 watts and can actually deliver 6 watts, the reserve is 4 watts. Evidently, if the circulatory demand increased to 6 watts, there would be no reserve; if it increased to 7 watts, the heart would fail.

     In normal people, the left heart is required to develop about 1 watt of power in resting circumstances and can develop 5 watts in the best circumstances. Thus, there is a 4 watt reserve in the left heart. The right heart is usually required to develop 1/4 watt at rest; this can go up to 2 watts; the reserve of the right heart is therefore, 1 3/4 watts.

     The relationship between resting work, best work (ability), and reserve is shown in Figure 257. In part (a) of this Figure the "ability" is shown to be equal to the sum of "resting requirement" and "reserve." In part (b) the resting requirement is increased. The reserve decreases by "encroachment from below.

     In part (c) the circulatory requirement is normal, but the heart muscle is damaged. The reserve is now decreased by "encroachment from above." In part (d) a damaged heart muscle is being asked to do more than normal work at rest. The reserve is encroached upon from both above and below.

     Using the concept of "cardiac reserve" we can define heart failure a little better. Any heart can fail, even a normal one; the degree to which physical activity is limited by the heart is a function of the cardiac reserve.

     Thus a person with 3 watts of cardiac reserve in his left heart might not be quite able to do physical exercise as a normal person, but only rarely would he be exerting himself so much as to be in heart failure. He might, for example, find himself less able to climb stairs than a normal person.

     A person with one watt of cardiac reserve (whether the encroachment was from above or below, or both) would find himself unable to perform easy tasks. Walking would be difficult; stair climbing would be impossible.

     A person with 0.5 watts of cardiac reserve might not have cardiac problems while lying still in bed. If, however, he fell asleep and had an exciting dream, which elevated his blood pressure and increased his cardiac output, he might go immediately into heart failure.

a. Causes of Chronic Congestive Heart Failure:

     In general, heart failure results more often from damage to the heart muscle (encroachment from above) than from increased resting load (encroachment from below). However, by some mechanism which is not clearly understood, encroachment from below may lead to encroachment from above. For example, arterial hypertension, which raises the work of the heart also decreases its ability to perform maximally. (This is apart from the "heart attacks" which may occur in persons with high blood pressure.) In aortic insufficiency, the original encroachment is from below, since the ventricle must eject at each beat an extra volume equal to the volume that leaked into it past the faulty valves during diastole. In time, however, the ventricular muscle is damaged and the encroachment is both from above and below.

     Right- and Left-Sided Heart Failure: When the reserve of either side of the heart is small, the ventricle in question will frequently have to make use of the Starling mechanism (by which the heart, as it fails, gains power). The affected side of the heart will be dilated, its diastolic pressures will be high; and the veins that empty into that side will not empty as freely as normally. The stretched veins may commute the increased pressure back to the capillaries; and the disturbed relationship between hydrostatic and colloid osmotic pressures here may lead to edema.

     When the right side of the heart is the one primarily affected, the veins which are distended are those which drain the body. The capillaries in which pressure relationships are disturbed are those of the body. The edema is an edema of the whole body, though it is usually noticed first in the feet and ankles. A patient with right sided heart failure may have swollen and obvious neck veins and a doughy appearance to the skin due to the excess fluid.

     The picture is very different in left sided heart failure. The individuals affected are in more trouble than those with pure right sided heart failure since impaired respiration can damage the heart further. In many cases, however, the failure of the left heart leaves so much extra pressure in the pulmonary circuit that the right heart also fails. This is actually advantageous, for the failing right heart does not supply the blood which would overload the failing left heart, so a pulmonary edema, which threatens life, is replaced by a systemic edema, which does not.

b. Treatment of Heart Failure:

     Emergency treatment of patients with left heart failure is usually designed to decrease the work of the left heart and improve its performance. The work may be decreased by a number of simple maneuvers--one is bleeding, which keeps blood away from the chest and lowers blood pressure--that reduce the work of the heart. Sometimes, the application of tourniquets at a pressure which prevents venous return from the arms and legs is life-saving. The improvement of heart performance is usually brought about by digitalis or digitalis-like drugs.

     Right-sided heart failure does not usually represent as serious an emergency as left-sided failure. The treatment is basically aimed at diminishing the volume of the edema fluid. This is primarily a solution of sodium chloride in water. By eliminating salt from the diet and increasing the ability of the kidney to eliminate salt, the amount of fluid available to form edema is reduced. This will be considered in more detail in Chapter 23.

Continue to Chapter 17.