Guyton and Hall Physiology Chapter 24 - Circulatory Shock PDF

CHAPTER 24 UNIT IV Circulatory Shock and Its Treatment Circulatory shock means generalized inadequate blood This situatio...

CHAPTER 24 UNIT IV Circulatory Shock and Its Treatment Circulatory shock means generalized inadequate blood This situation can result from the following: (1) exces- flow through the body to the extent that the body tis- sive metabolic rate, so even a normal cardiac output is sues are damaged, especially because too little oxygen inadequate; or (2) abnormal tissue perfusion patterns, so and other nutrients are delivered to the tissue cells. Even most of the cardiac output is passing through blood vessels the cardiovascular system itself—the heart musculature, besides those that supply the local tissues with nutrition. walls of the blood vessels, vasomotor system, and other The specific causes of shock are discussed later in this circulatory parts—begins to deteriorate, so the shock, chapter. For the present, it is important to note that all of once begun, is prone to become progressively worse. them lead to inadequate delivery of nutrients to critical tissues and critical organs, as well as inadequate removal of cellular waste products from the tissues. PHYSIOLOGICAL CAUSES OF SHOCK CIRCULATORY SHOCK CAUSED BY WHAT HAPPENS TO THE ARTERIAL DECREASED CARDIAC OUTPUT PRESSURE IN CIRCULATORY SHOCK? Shock usually results from inadequate cardiac output. In the minds of many physicians, the arterial pressure Therefore, any condition that reduces the cardiac out- level is the principal measure of adequacy of circulatory put far below normal may lead to circulatory shock. Two function. However, the arterial pressure can often be seri- types of factors can severely reduce cardiac output: ously misleading. At times, a person may be in severe 1. Cardiac abnormalities that decrease the ability of shock and still have an almost normal arterial pressure the heart to pump blood. These abnormalities in- because of powerful nervous reflexes that keep the pres- clude in particular myocardial infarction but also sure from falling. At other times, the arterial pressure can toxic states of the heart, severe heart valve dys- fall to half of normal, but the person still has normal tissue function, heart arrhythmias, and other conditions. perfusion and is not in shock. The circulatory shock that results from diminished In most types of shock, especially shock caused by cardiac pumping ability is called cardiogenic shock. severe blood loss, the arterial blood pressure decreases This condition is discussed in Chapter 22, where it at the same time the cardiac output decreases, although is noted that as many as 70% of people who experi- usually not as much. ence cardiogenic shock do not survive. 2. Factors that decrease venous return also decrease TISSUE DETERIORATION IS THE END cardiac output because the heart cannot pump RESULT OF CIRCULATORY SHOCK blood that does not flow into it. The most com- mon cause of decreased venous return is dimin- Once circulatory shock reaches a critical state of severity, ished blood volume, but venous return can also be regardless of its initiating cause, the shock itself leads to reduced as a result of decreased vascular tone, espe- more shock. That is, the inadequate blood flow causes the cially of the venous blood reservoirs, or obstruction body tissues to begin deteriorating, including the heart to blood flow at some point in the circulation, espe- and circulatory system. This deterioration causes even cially in the venous return pathway to the heart. greater decreases in cardiac output, and a vicious cycle ensues, with progressively increasing circulatory shock, less adequate tissue perfusion, and more shock until death CIRCULATORY SHOCK WITHOUT occurs. It is with this late stage of circulatory shock that DIMINISHED CARDIAC OUTPUT we are especially concerned because appropriate physi- Occasionally, cardiac output is normal or even more than ological treatment can often reverse the rapid slide to normal, yet the person is in a state of circulatory shock. death. 293 UNIT IV The Circulation STAGES OF SHOCK fall to zero when about 40% to 45% of the total blood vol- ume has been removed. Because the characteristics of circulatory shock change with different degrees of severity, shock is often divided Sympathetic Reflex Compensations in Shock—Their into the following three major stages: Special Value to Maintain Arterial Pressure. The de- 1. A nonprogressive stage (sometimes called the com- crease in arterial pressure after hemorrhage, as well as de- pensated stage), in which the normal circulatory creases in pressures in the pulmonary arteries and veins compensatory mechanisms eventually cause full re- in the thorax, cause powerful sympathetic reflexes (initi- covery without help from outside therapy. ated mainly by the arterial baroreceptors and other vas- 2. A progressive stage, in which, without therapy, the cular stretch receptors, as explained in Chapter 18). These shock becomes steadily worse until death occurs. reflexes stimulate the sympathetic vasoconstrictor system 3. An irreversible stage, in which the shock has pro- in most tissues of the body, resulting in three important gressed to such an extent that all forms of known effects: therapy are inadequate to save the person’s life 1. The arterioles constrict in most parts of the system- even though, for the moment, the person is still ic circulation, thereby increasing the total periph- alive. eral resistance. We will now discuss the stages of circulatory shock 2. The veins and venous reservoirs constrict, thereby caused by decreased blood volume, which illustrate the helping maintain adequate venous return, despite basic principles. Then we will consider special character- diminished blood volume. istics of shock initiated by other causes. 3. Heart activity increases markedly, sometimes in- creasing the heart rate from the normal value of 72 beats/min to as high as 160 to 180 beats/min. SHOCK CAUSED BY HYPOVOLEMIA— In the absence of the sympathetic reflexes, only 15% to HEMORRHAGIC SHOCK 20% of the blood volume can be removed over a period Hypovolemia means diminished blood volume. Hemor- of 30 minutes before a person dies; in contrast, a per- rhage is the most common cause of hypovolemic shock. son can sustain a 30% to 40% loss of blood volume when Hemorrhage decreases the filling pressure of the circula- the reflexes are intact. Therefore, these reflexes extend tion and, as a consequence, decreases venous return. As the amount of blood loss that can occur without caus- a result, the cardiac output falls below normal, and shock ing death to about twice that which is possible in their may ensue. absence. Relationship of Bleeding Volume to Greater Effect of Sympathetic Nervous Reflexes in Cardiac Output and Arterial Pressure Maintaining Arterial Pressure Than in Maintaining Figure 24-1 shows the approximate effects on cardiac Cardiac Output. Referring again to Figure 24-1, note output and arterial pressure of removing blood from the that the arterial pressure is maintained at or near nor- circulatory system over a period of about 30 minutes. mal levels in the hemorrhaging person longer than is the About 10% of the total blood volume can be removed cardiac output. The reason for this difference is that the with almost no effect on arterial pressure or cardiac out- sympathetic reflexes are geared more for maintaining ar- put, but greater blood loss usually diminishes the cardiac terial pressure than for maintaining cardiac output. They output first and later the arterial pressure, both of which increase the arterial pressure mainly by increasing the to- tal peripheral resistance, which has no beneficial effect on cardiac output. However, the sympathetic constriction of the veins is important to keep venous return and cardiac 100 Arterial output from falling too much, in addition to their role in pressure maintaining arterial pressure. Cardiac output and arterial pressure (% of normal) Especially interesting is the second plateau occur- ring at about 50 mm Hg in the arterial pressure curve of 50 Cardiac Figure 24-1. This second plateau results from activation output of the central nervous system ischemic response, which causes extreme stimulation of the sympathetic nervous system when the brain begins to experience lack of oxy- 0 gen or excess buildup of carbon dioxide, as discussed in 0 10 20 30 40 50 Chapter 18. This effect of the central nervous system isch- % of total blood removed emic response can be called the “last-ditch stand” of the Figure 24-1 Effect of hemorrhage on cardiac output and arterial sympathetic reflexes in their attempt to keep the arterial pressure. pressure from falling too low. 294  Chapter 24 Circulatory Shock and Its Treatment Protection of Coronary and Cerebral Blood Flow by more shock, and the condition becomes a vicious cycle the Reflexes. A special value of the maintenance of nor- that eventually leads to deterioration of the circulation mal arterial pressure, even in the presence of decreas- and to death. ing cardiac output, is protection of blood flow through the coronary and cerebral circulations. The sympathetic Nonprogressive Shock—Compensated Shock UNIT IV stimulation does not cause significant constriction of the cerebral or cardiac vessels. In addition, in both vascular If shock is not severe enough to cause its own progres- beds, local blood flow autoregulation is excellent, which sion, the person eventually recovers. Therefore, shock of prevents moderate decreases in arterial pressure from sig- this lesser degree is called nonprogressive shock or com- nificantly decreasing their blood flows. Therefore, blood pensated shock, meaning that the sympathetic reflexes flow through the heart and brain is maintained essentially and other factors compensate enough to prevent further at normal levels as long as the mean arterial pressure does deterioration of the circulation. not fall below about 70 mm Hg, despite the fact that blood The factors that cause a person to recover from mod- flow in some other areas of the body might be decreased erate degrees of shock are the negative feedback control to as little as one-third to one-quarter normal by this time mechanisms of the circulation that attempt to return car- because of vasoconstriction. diac output and arterial pressure back to normal levels. They include the following: 1. Baroreceptor reflexes, which elicit powerful sympa- PROGRESSIVE AND NONPROGRESSIVE thetic stimulation of the circulation HEMORRHAGIC SHOCK 2. Central nervous system ischemic response, which Figure 24-2 shows an experiment that demonstrates elicits even more powerful sympathetic stimulation the effects of different degrees of sudden acute hem- throughout the body but is not activated significant- orrhage on the subsequent course of arterial pressure. ly until the arterial pressure falls below 50 mm Hg The animals in this experiment were anesthetized and 3. Reverse stress-relaxation of the circulatory system, bled rapidly until their arterial pressures fell to differ- which causes the blood vessels to contract around ent levels. The animals whose pressures fell immedi- the diminished blood volume so that the blood vol- ately to no lower than 45 mm Hg (groups I, II, and III) ume that is available more adequately fills the circu- all eventually recovered; the recovery occurred rapidly lation if the pressure fell only slightly (group I) but occurred 4. Increased secretion of renin by the kidneys and for- slowly if it fell almost to the 45-mm Hg level (group mation of angiotensin II, which constricts the pe- III). When the arterial pressure fell below 45 mm Hg ripheral arterioles and also causes decreased output (groups IV, V, and VI), all the animals died, although of water and salt by the kidneys, both of which help many of them hovered between life and death for hours prevent progression of shock before the circulatory system deteriorated to the stage 5. Increased secretion by the posterior pituitary gland of death. of vasopressin (antidiuretic hormone), which con- This experiment demonstrates that the circulatory sys- stricts the peripheral arterioles and veins and greatly tem can recover as long as the degree of hemorrhage is no increases water retention by the kidneys greater than a certain critical amount. Crossing this criti- 6. Increased secretion by the adrenal medullae of epi- cal threshold by even a few milliliters of blood loss makes nephrine and norepinephrine, which constricts the the eventual difference between life and death. Thus, peripheral arterioles and veins and increases the hemorrhage beyond a certain critical level causes shock heart rate to become progressive. That is, the shock itself causes still 7. Compensatory mechanisms that return the blood volume back toward normal, including absorp- tion of large quantities of fluid from the intesti- 100 I nal tract, absorption of fluid into the blood cap- (% of control value) 90 Arterial pressure II 80 III illaries from the interstitial spaces of the body, 70 IV 60 conservation of water and salt by the kidneys, 50 V and increased thirst and increased appetite for 40 30 salt, which make the person drink water and eat 20 VI 10 salty foods if they are able to do so 0 The sympathetic reflexes and increased secretion of 0 60 120 180 240 300 360 catecholamines by the adrenal medullae provide rapid Time (minutes) help toward bringing about recovery because they Figure 24-2 Time course of arterial pressure in dogs after different become maximally activated within 30 seconds to a few degrees of acute hemorrhage. Each curve represents average results from six dogs (curves I–VI). minutes after hemorrhage. 295 UNIT IV The Circulation Decreased cardiac output Decreased arterial pressure Decreased systemic blood flow Decreased cardiac nutrition Decreased nutrition of tissues Intravascular clotting Decreased nutrition of brain Decreased nutrition Tissue ischemia of vascular system Decreased vasomotor activity Increased Release of capillary toxins permeability Vascular dilation Decreased Venous pooling blood volume of blood Figure 24-3 Different types of positive feed- Cardiac depression Decreased venous return back that can lead to the progression of shock. The angiotensin and vasopressin mechanisms, as well 15 as the reverse stress-relaxation that causes contraction 0 time of the blood vessels and venous reservoirs, all require 10 Cardiac output (L/min) 2 hours to 60 minutes to respond completely, but they aid greatly 10 in increasing the arterial pressure or increasing the cir- 4 hours culatory filling pressure, thereby increasing the return of 41/2 hours blood to the heart. Finally, readjustment of blood volume by absorption 5 43/4 hours of fluid from the interstitial spaces and intestinal tract, as well as oral ingestion and absorption of additional quanti- 5 hours ties of water and salt, may require from 1 to 48 hours, but 0 recovery eventually takes place, provided the shock does −4 0 4 8 12 not become severe enough to enter the progressive stage. Right atrial pressure (mm Hg) Figure 24-4 Cardiac output curves of the heart at different times af- Progressive Shock—Caused by Vicious ter hemorrhagic shock begins. (These curves have been extrapolated Cycle of Cardiovascular Deterioration to the human heart from data obtained in dog experiments by Dr. Figure 24-3 shows some of the positive feedbacks that J.W. Crowell.) further depress cardiac output in shock, thus causing the shock to become progressive. Some of the more impor- animals, demonstrating progressive deterioration of the tant feedbacks are described in the following sections. heart at different times after the onset of shock. An anes- thetized animal was bled until the arterial pressure fell to Cardiac Depression. When the arterial pressure falls low 30 mm Hg, and the pressure was held at this level by fur- enough, coronary blood flow decreases below that required ther bleeding or retransfusion of blood, as required. Note for adequate nutrition of the myocardium, weakening the from the second curve in the figure that there was little heart muscle and decreasing the cardiac output more. deterioration of the heart during the first 2 hours, but by Thus, a positive feedback cycle has developed, whereby 4 hours, the heart had deteriorated about 40%. Then, rap- the shock becomes more and more severe. idly, during the last hour of the experiment (after 4 hours Figure 24-4 shows cardiac output curves extrapo- of low coronary blood pressure), the heart deteriorated lated to the human heart from studies in experimental completely. 296  Chapter 24 Circulatory Shock and Its Treatment Thus, one of the important features of progressive Release of Toxins by Ischemic Tissue. Shock has been shock, whether it is hemorrhagic in origin or has another suggested to cause tissues to release toxic substances, cause, is eventual progressive deterioration of the heart. In such as histamine, serotonin, and tissue enzymes, that the early stages of shock, this deterioration plays very little cause further deterioration of the circulatory system. Ex- role in the condition of the person, partly because deterio- perimental studies have proved the significance of at least UNIT IV ration of the heart is not severe during the first hour or so one toxin, endotoxin, in some types of shock. of shock, but mainly because the heart has reserve capa- bility that normally allows it to pump 300% to 400% more Cardiac Depression Caused by Endotoxin. Endotoxin blood than is required by the body for adequate tissue is released from the bodies of dead gram-negative bac- nutrition. In the latest stages of shock, however, deteriora- teria in the intestines. Diminished blood flow to the in- tion of the heart is probably the most important factor in testines often causes enhanced formation and absorption the final lethal progression of the shock. of this toxic substance. The circulating toxin then causes increased cellular metabolism, despite inadequate nutri- Vasomotor Failure. In the early stages of shock, vari- tion of the cells, which has a specific effect on the heart ous circulatory reflexes cause intense activity of the muscle, causing cardiac depression. Endotoxin can play a sympathetic nervous system. This activity helps delay major role in some types of shock, especially septic shock, depression of cardiac output and especially helps pre- discussed later in this chapter. vent decreased arterial pressure. However, there comes a point when diminished blood flow to the brain’s vaso- Generalized Cellular Deterioration. As shock becomes motor center depresses the center so much that it, too, severe, many signs of generalized cellular deterioration becomes progressively less active and, finally, totally inac- occur throughout the body. One organ especially affected tive. For example, during the first 4 to 8 minutes, complete is the liver, as illustrated in Figure 24-5. The liver is espe- circulatory arrest to the brain causes the most intense of cially affected mainly because of the lack of enough nutri- all sympathetic discharges, but by the end of 10 to 15 min- ents to support the normally high rate of metabolism in utes, the vasomotor center becomes so depressed that no liver cells, but also partly because of the exposure of the further evidence of sympathetic discharge can be dem- liver cells to any vascular toxin or other abnormal meta- onstrated. Fortunately, the vasomotor center usually does bolic factor occurring in shock. not fail in the early stages of shock if the arterial pressure Among the damaging cellular effects that are known to remains above 30 mm Hg. occur in most body tissues are the following: 1. Active transport of sodium and potassium through Blockage of Very Small Vessels by Sludged Blood. In the cell membrane is greatly diminished. As a re- time, blockage occurs in many of the very small blood sult, sodium and chloride accumulate in the cells, vessels in the circulatory system, and this blockage also and potassium is lost from the cells. In addition, the causes the shock to progress. The initiating cause of cells begin to swell. this blockage is sluggish blood flow in the microvessels. Because tissue metabolism continues despite the low flow, large amounts of acid, both carbonic acid and lac- tic acid, continue to empty into the local blood vessels and greatly increase the local acidity of the blood. This acidic effect, plus other deterioration products from the ischemic tissues, causes local blood agglutination, re- sulting in minute blood clots and leading to very small plugs in the small vessels. Even if the vessels do not be- come plugged, an increased tendency for the blood cells to stick to one another makes it more difficult for blood to flow through the microvasculature, giving rise to the term sludged blood. Increased Capillary Permeability. After many hours of capillary hypoxia and lack of other nutrients, the per- meability of the capillaries gradually increases, and large quantities of fluid begin to transude into the tissues. This phenomenon decreases the blood volume even more, with a resultant further decrease in cardiac output, mak- ing the shock still more severe. Capillary hypoxia does not cause increased capillary permeability until the late stages Figure 24-5 Necrosis of the central portion of a liver lobule during of prolonged shock. severe circulatory shock. (Courtesy Dr. J.W. Crowell.) 297 UNIT IV The Circulation 2. Mitochondrial activity in the liver cells, as well as Positive Feedback Deterioration of Tissues in Shock in many other tissues of the body, becomes severely and Vicious Cycle of Progressive Shock. All the fac- depressed. tors just discussed that can lead to further progression 3. Lysosomes in the cells in widespread tissue areas of shock are types of positive feedback—that is, each in- begin to break open, with intracellular release crease in the degree of shock causes a further increase in of hydrolases, which cause further intracellular the shock. However, positive feedback does not necessar- deterioration. ily lead to a vicious cycle. Development of a vicious cycle 4. Cellular metabolism of nutrients, such as glucose, depends on the intensity of the positive feedback. In mild eventually becomes greatly depressed in the last degrees of shock, the negative feedback mechanisms of stages of shock. The actions of some hormones are the circulation, including sympathetic reflexes, reverse depressed as well, including almost 100% depres- stress-relaxation mechanism of the blood reservoirs, and sion of the actions of insulin. absorption of fluid into the blood from the interstitial All these effects contribute to further deterioration of spaces, can easily overcome the positive feedback influ- many organs of the body, including especially the follow- ences and, therefore, cause recovery. In severe shock, ing: (1) the liver, with depression of its many metabolic however, the deteriorative feedback mechanisms become and detoxification functions; (2) the lungs, with eventual more and more powerful, leading to such rapid deteriora- development of pulmonary edema and poor ability to tion of the circulation that all the normal negative feed- oxygenate the blood; and (3) the heart, thereby further back systems of circulatory control acting together can- depressing its contractility. not return the cardiac output to normal. Considering once again the principles of positive feed- Patchy Areas of Tissue Necrosis Caused by Patchy back and vicious cycles discussed in Chapter 1, one can Blood Flows in Different Organs. Not all cells of the readily understand why there is a critical cardiac output body are equally damaged by shock because some tissues level above which a person in shock recovers and below have better blood supplies than others. For example, the which a person enters a vicious cycle of circulatory dete- cells adjacent to the arterial ends of capillaries receive bet- rioration that proceeds until death. ter nutrition than cells adjacent to the venous ends of the same capillaries. Therefore, more nutritive deficiency oc- IRREVERSIBLE SHOCK curs around the venous ends of capillaries than elsewhere. Figure 24-5 shows necrosis in the center of a liver lobule, After shock has progressed to a certain stage, transfusion the portion of the lobule that is the last to be exposed to or any other type of therapy becomes incapable of saving the blood as it passes through the liver sinusoids. the person’s life. The person is then said to be in the irre- Similar punctate lesions occur in heart muscle, versible stage of shock. Ironically, even in this irreversible although here a definite repetitive pattern, such as occurs stage, therapy can, on rare occasions, return the arterial in the liver, cannot be demonstrated. Nevertheless, the pressure and even the cardiac output to normal or near cardiac lesions play an important role in leading to the normal for short periods, but the circulatory system nev- final irreversible stage of shock. Deteriorative lesions also ertheless continues to deteriorate, and death ensues in occur in the kidneys, especially in the epithelium of the another few minutes to few hours. kidney tubules, leading to kidney failure and occasionally Figure 24-6 shows that transfusion during the irre- uremic death several days later. Deterioration of the lungs versible stage can sometimes cause cardiac output (as well also often leads to respiratory distress and death several as the arterial pressure) to return to nearly normal. How- days later, called the shock lung syndrome. ever, the cardiac output soon begins to fall again, and sub- sequent transfusions have less and less effect. By this time, Acidosis in Shock. Metabolic derangements that oc- multiple deteriorative changes have occurred in the heart cur in shocked tissue can lead to acidosis throughout the body. This results from poor delivery of oxygen to the tis- sues, which greatly diminishes oxidative metabolism of Hemorrhage the foodstuffs. When this occurs, the cells obtain most of 100 Cardiac output their energy by the anaerobic process of glycolysis, which (% of normal) 75 leads to excess lactic acid in the blood. In addition, poor Progressive stage blood flow through tissues prevents normal removal of 50 carbon dioxide. The carbon dioxide reacts locally in the Transfusion 25 cells with water to form high concentrations of intracel- Irreversible shock lular carbonic acid, which, in turn, reacts with various 0 tissue chemicals to form additional intracellular acidic 0 30 60 90 120 150 substances. Thus, another deteriorative effect of shock is Time (minutes) generalized and local tissue acidosis, leading to further Figure 24-6 Failure of transfusion to prevent death in irreversible progression of the shock. shock. 298  Chapter 24 Circulatory Shock and Its Treatment muscle cells that may not necessarily affect the heart’s by hemorrhage, except for one additional complicating immediate ability to pump blood but, over a long period, factor: the blood viscosity increases greatly as a result of depress heart pumping enough to cause death. Beyond increased red blood cell concentration in the remaining a certain point, so much tissue damage has occurred, so blood, and this increase in viscosity exacerbates the slug- many destructive enzymes have been released into the gishness of blood flow. UNIT IV body fluids, so much acidosis has developed, and so many Loss of fluid from all fluid compartments of the body other destructive factors are now in progress that even a is called dehydration; this condition can also reduce the normal cardiac output for a few minutes cannot reverse blood volume and cause hypovolemic shock similar to the continuing deterioration. Therefore, in severe shock, that resulting from hemorrhage. Some of the causes of a stage is eventually reached at which the person will die, this type of shock are the following: (1) excessive sweat- even though vigorous therapy might still return the car- ing; (2) fluid loss in severe diarrhea or vomiting; (3) excess diac output to normal for short periods. loss of fluid by the kidneys; (4) inadequate intake of fluid and electrolytes; or (5) destruction of the adrenal cortices, Depletion of Cellular High-Energy Phosphate with loss of aldosterone secretion and consequent failure Reserves in Irreversible Shock. The high-energy phos- of the kidneys to reabsorb sodium, chloride, and water, phate reserves in the tissues of the body, especially in the which occurs in the absence of the adrenocortical hor- liver and heart, are greatly diminished in severe shock. mone aldosterone. Essentially all the creatine phosphate has been degraded, and almost all the adenosine triphosphate has downgrad- HYPOVOLEMIC SHOCK CAUSED BY ed to adenosine diphosphate, adenosine monophosphate TRAUMA and, eventually, adenosine. Much of this adenosine then diffuses out of the cells into the circulating blood and is One of the most common causes of circulatory shock is converted into uric acid, a substance that cannot re-enter trauma to the body. Often, the shock results simply from the cells to reconstitute the adenosine phosphate system. hemorrhage caused by the trauma, but it can also occur New adenosine can be synthesized at a rate of only about even without hemorrhage because extensive contusion of 2% of the normal cellular amount an hour, meaning that the body can damage the capillaries sufficiently to allow once the high-energy phosphate stores of the cells are de- excessive loss of plasma into the tissues. This phenome- pleted, they are difficult to replenish. non results in greatly reduced plasma volume, with resul- Thus, one of the most devastating end results in shock, tant hypovolemic shock. and the one that is perhaps most significant for develop- Various attempts have been made to implicate toxic ment of the final state of irreversibility, is cellular deple- factors released by the traumatized tissues as one of the tion of these high-energy compounds. causes of shock after trauma. However, cross-transfusion experiments with normal animals have failed to show significant toxic elements. Traumatic shock, therefore, HYPOVOLEMIC SHOCK CAUSED BY seems to result mainly from hypovolemia, although PLASMA LOSS there might also be a moderate degree of concomitant Loss of plasma from the circulatory system, even without neurogenic shock caused by loss of vasomotor tone, as loss of red blood cells, can sometimes be severe enough discussed next. to reduce the total blood volume markedly, causing typi- cal hypovolemic shock similar in almost all details to that NEUROGENIC SHOCK—INCREASED caused by hemorrhage. Severe plasma loss occurs in the VASCULAR CAPACITY following conditions: 1. Intestinal obstruction may cause severely reduced Shock occasionally occurs without any loss of blood vol- plasma volume. Distention of the intestine in intes- ume. Instead, the vascular capacity increases so much tinal obstruction partly blocks venous blood flow in that even the normal amount of blood is incapable of fill- the intestinal walls, which increases intestinal capil- ing the circulatory system adequately. One of the major lary pressure, causing fluid to leak from the capil- causes of this condition is sudden loss of vasomotor tone laries into the intestinal walls and intestinal lumen. throughout the body, resulting especially in massive Because the lost fluid has high protein content, the dilation of the veins. The resulting condition is known as result is reduced total blood plasma protein, as well neurogenic shock. as reduced plasma volume. The role of vascular capacity in helping regulate circu- 2. Severe burns or other denuding conditions of the skin latory function was discussed in Chapter 15, where it was cause loss of plasma through the denuded skin ar- noted that an increase in vascular capacity or a decrease eas so that the plasma volume becomes markedly in blood volume reduces the mean systemic filling pres- reduced. sure, which reduces venous return to the heart. Dimin- The hypovolemic shock that results from plasma loss ished venous return caused by vascular dilation is called has almost the same characteristics as the shock caused venous pooling of blood. 299 UNIT IV The Circulation Causes of Neurogenic Shock. Some neurogenic factors Septic shock is extremely important to the clinician that can cause loss of vasomotor tone include the follow- because, other than cardiogenic shock, septic shock is ing: currently the most frequent cause of shock-related death 1. Deep general anesthesia often depresses the vaso- in the hospital. motor center enough to cause vasomotor paralysis, Some of the typical causes of septic shock include the with resulting neurogenic shock. following: 2. Spinal anesthesia, especially when this extends all 1. Peritonitis caused by spread of infection from the the way up the spinal cord, blocks the sympathetic uterus and fallopian tubes, sometimes resulting nervous outflow from the nervous system and can from an instrumental abortion performed under be a potent cause of neurogenic shock. unsterile conditions 3. Brain damage is often a cause of vasomotor paraly- 2. Peritonitis resulting from rupture of the gastroin- sis. Many patients who have had a brain concus- testinal system, sometimes caused by intestinal dis- sion or contusion of the basal regions of the brain ease or by wounds experience profound neurogenic shock. Also, even 3. Generalized bodily infection resulting from spread though brain ischemia for a few minutes almost al- of a skin infection such as streptococcal or staphy- ways causes extreme vasomotor stimulation and in- lococcal infection creased blood pressure, prolonged ischemia (lasting 4. Generalized gangrenous infection resulting spe- >5–10 minutes) can cause the opposite effect—total cifically from gas gangrene bacilli, spreading first inactivation of the vasomotor neurons in the brain through peripheral tissues and finally via the blood stem, with a consequent decrease in arterial pres- to the internal organs, especially the liver sure and development of severe neurogenic shock. 5. Infection spreading into the blood from the kidney or urinary tract, often caused by colon bacilli. ANAPHYLACTIC SHOCK AND Special Features of Septic Shock. Because of the mul- HISTAMINE SHOCK tiple types of septic shock, it is difficult to categorize this Anaphylaxis is an allergic condition in which cardiac out- condition. The following features are often observed: put and arterial pressure often decrease drastically. This 1. High fever condition is discussed in Chapter 35. It results primar- 2. Often marked vasodilation throughout the body, ily from an antigen-antibody reaction that rapidly occurs especially in the infected tissues after an antigen to which the person is sensitive enters 3. High cardiac output in perhaps half of patients, the circulation. One of the principal effects is to cause the caused by arteriolar dilation in the infected tissues basophils in the blood and mast cells in the pericapillary and by high metabolic rate and vasodilation else- tissues to release histamine or a histamine-like substance. where in the body, resulting from bacterial toxin The histamine causes the following: (1) an increase in stimulation of cellular metabolism and from a high vascular capacity because of venous dilation, thus caus- body temperature ing a marked decrease in venous return; (2) dilation of 4. Sludging of the blood, caused by red cell agglutina- the arterioles, resulting in greatly reduced arterial pres- tion in response to degenerating tissues sure; and (3) greatly increased capillary permeability, with 5. Development of micro–blood clots in widespread rapid loss of fluid and protein into the tissue spaces. The areas of the body, a condition called disseminated net effect is a great reduction in venous return and, some- intravascular coagulation; also, this causes the times, such serious shock that the person may die within blood clotting factors to be used up, so hemorrhag- minutes. ing occurs in many tissues, especially in the gut wall Intravenous injection of large amounts of histamine of the intestinal tract causes histamine shock, which has characteristics almost In early stages of septic shock, the patient usually does identical to those of anaphylactic shock. not have signs of circulatory collapse but only signs of the bacterial infection. As the infection becomes more severe, the circulatory system usually becomes involved SEPTIC SHOCK because of direct extension of the infection or secondarily Septic shock refers to a bacterial infection widely dissemi- as a result of toxins from the bacteria, with resultant loss nated to many areas of the body, with the infection being of plasma into the infected tissues through deteriorating carried through the blood from one tissue to another and blood capillary walls. There finally comes a point at which causing extensive damage. There are many varieties of sep- deterioration of the circulation becomes progressive in tic shock because of the many types of bacterial infections the same way that progression occurs in all other types that can cause it, and because infection in different parts of shock. The end stages of septic shock are not greatly of the body produces different effects. Most cases of sep- different from the end stages of hemorrhagic shock, even tic shock, however, are caused by Gram-positive bacteria, though the initiating factors are markedly different in the followed by endotoxin-producing Gram-negative bacteria. two conditions. 300  Chapter 24 Circulatory Shock and Its Treatment PHYSIOLOGY OF TREATMENT IN SHOCK drug takes the place of the diminished sympathetic actions and can often restore full circulatory function. REPLACEMENT THERAPY The second type of shock in which sympathomimetic Blood and Plasma Transfusion. If a person is in shock drugs are valuable is anaphylactic shock, in which excess caused by hemorrhage, the best possible therapy is usu- histamine plays a prominent role. The sympathomimetic UNIT IV ally transfusion of whole blood. If the shock is caused by drugs have a vasoconstrictor effect that opposes the vaso- plasma loss, the best therapy is administration of plasma. dilating effect of histamine. Therefore, epinephrine, nor- When dehydration is the cause, administration of an ap- epinephrine, or other sympathomimetic drugs are often propriate electrolyte solution can correct the shock. lifesaving. Whole blood is not always available, such as under Sympathomimetic drugs have not proved to be very battlefield conditions. Plasma can usually substitute ade- valuable in hemorrhagic shock. The reason is that in this quately for whole blood because it increases the blood type of shock, the sympathetic nervous system is almost volume and restores normal hemodynamics. Plasma can- always maximally activated by the circulatory reflexes; so not restore a normal hematocrit, but the body can usu- much norepinephrine and epinephrine are already cir- ally stand a decrease in hematocrit to about half of normal culating in the blood that sympathomimetic drugs have before serious consequences result if cardiac output is essentially no additional beneficial effect. adequate. Therefore, in emergency conditions, it is reason- able to use plasma in place of whole blood for treatment of hemorrhagic or most other types of hypovolemic shock. OTHER THERAPY Sometimes, plasma is unavailable. In these cases, Treatment by the Head-Down Position. When the various plasma substitutes have been developed that per- pressure falls too low in most types of shock, especially form almost exactly the same hemodynamic functions as in hemorrhagic and neurogenic shock, placing the patient plasma. One of these substitutes is dextran solution. with the head at least 12 inches lower than the feet helps in promoting venous return, thereby also increasing car- Dextran Solution as a Plasma Substitute. The principal diac output. This head-down position is the first essential requirement of a truly effective plasma substitute is that step in the treatment of many types of shock. it remain in the circulatory system—that is, it does not filter through the capillary pores into the tissue spaces. In Oxygen Therapy. Because a major deleterious effect of addition, the solution must be nontoxic and must contain most types of shock is too little delivery of oxygen to the appropriate electrolytes to prevent derangement of the tissues, giving the patient oxygen to breathe can be of ben- body’s extracellular fluid electrolytes on administration. efit in some cases. However, this intervention frequently To remain in the circulation, the plasma substitute must is far less beneficial than one might expect because the contain some substance that has a large enough molecu- problem in most types of shock is not inadequate oxygen- lar size to exert colloid osmotic pressure. One substance ation of the blood by the lungs but inadequate transport developed for this purpose is dextran, a large polysaccha- of the blood after it is oxygenated. ride polymer of glucose. Dextrans of appropriate molecular size do not pass through the capillary pores and, therefore, Treatment With Glucocorticoids. Glucocorticoids— can replace plasma proteins as colloid osmotic agents. adrenal cortex hormones that control glucose metabo- Few toxic reactions have been observed when using lism—are frequently given to patients in severe shock for purified dextran to provide colloid osmotic pressure; several reasons: (1) experiments have shown empirically therefore, solutions containing this substance have been that glucocorticoids frequently increase the strength of used as a substitute for plasma in fluid replacement the heart in the late stages of shock; (2) glucocorticoids therapy. stabilize lysosomes in tissue cells and thereby prevent the release of lysosomal enzymes into the cytoplasm of the cells, thus preventing deterioration from this source; and TREATMENT OF NEUROGENIC AND (3) glucocorticoids might aid in the metabolism of glucose ANAPHYLACTIC SHOCK WITH by the severely damaged cells. SYMPATHOMIMETIC DRUGS A sympathomimetic drug is a drug that mimics sympa- thetic stimulation. These drugs include norepinephrine, CIRCULATORY ARREST epinephrine, and a large number of long-acting drugs A condition closely allied to circulatory shock is circula- that have the same basic effects as epinephrine and tory arrest, in which all blood flow stops. This condition norepinephrine. can occur, for example, as a result of cardiac arrest or ven- In two types of shock, sympathomimetic drugs have tricular fibrillation. proven to be especially beneficial. The first of these is neu- Ventricular fibrillation can usually be stopped by rogenic shock, in which the sympathetic nervous system strong electroshock of the heart, the basic principles of is severely depressed. Administering a sympathomimetic which are described in Chapter 13. 301 UNIT IV The Circulation In the case of complete cardiac arrest, a normal cardiac Bibliography rhythm can sometimes be restored by immediately apply- Angus DC, van der Poll T: Severe sepsis and septic shock. 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