CASE 51 A 62-year-old man undergoes surgery to correct a herniated disc in his spine. The patient is thought to have an uncomplicated surgery until he complains of extreme abdominal distention and pain about 1 hour after surgery. He is noted to be hypotensive and tachycardic. On examination, his abdomen is distended and tense, with severe rebound pain indicating peritoneal irritation. He is taken back immediately to the operating room, where they find a large amount of blood in his abdomen (2 L) and a small puncture site in the descending aorta with active bleeding. A graft is placed in the aorta to stop the bleeding and repair the injury site. The patient is transfused with blood intraoperatively and is taken to the intensive care unit in critical condition. What would be the response of the sympathetic system to this patient s decrease in arterial pressure? What would be the response of the renin-angiotensin-aldosterone system to the decreased arterial pressure? How would antidiuretic hormone (ADH) play a role in this situation?
410 CASE FILES: PHYSIOLOGY ANSWERS TO CASE 51: HEMORRHAGIC SHOCK Summary: A 62-year-old man presents for back surgery, which is complicated by injury to the aorta with resultant hemorrhagic shock. Response of sympathetic system: Increased heart rate and contractility, and increased total peripheral resistance. Response of the renin-angiotensin-aldosterone system: Increased angiotensin II causes further vasoconstriction, and aldosterone increases sodium-chloride reabsorption in the kidney to increase blood volume. Response of ADH: Causes vasoconstriction and increases water reabsorption in the kidney. CLINICAL CORRELATION Circulatory shock can have many different etiologies, including hemorrhage, sepsis, and neurogenic causes. The physiologic response is essentially the same for all the etiologies. All the processes include hypotension, which triggers stimulation of the sympathetic system, increases renin production leading to aldosterone production, and increases ADH secretion. If the circulatory volume is not replaced quickly, the resulting peripheral vasoconstriction, so as to maintain blood supply to the heart, lung, and brain, will result in ischemia to other end organs, such as the kidney and liver. Monitoring urine output is a good way to assess intravascular volume. If the patient is making adequate urine, the kidneys are being perfused and the intravascular volume is probably adequate. After replacement of fluids and/or blood, the underlying cause needs to be addressed and treated. APPROACH TO PHYSIOLOGIC ADAPTATION TO HEMORRHAGE Objectives 1. Know the causes of circulatory shock. 2. Understand the body s response to shock (shunt to brain, heart, and lungs). 3. Know the role of blood pressure as an indicator of shock state. 4. Describe the treatment of circulatory shock. Definitions Circulatory shock: A condition in which cardiac output is compromised and no longer meets the metabolic demands of the tissues, leading to damage to the peripheral circulation. Heart failure: A condition in which the ability of the heart to pump blood through the circulation is compromised; the heart tissue has been damaged.
CLINICAL CASES 411 DISCUSSION Regulation of the cardiovascular system and blood flow to the tissues constitute a complex process involving the function of both the heart and the systemic circulation. Circulatory shock is a condition that can be characterized as peripheral circulatory failure in which there is inadequate perfusion of the peripheral tissues. The peripheral circulation no longer meets the metabolic demands of the tissues. This differs from heart failure, in which the ability of the heart to pump blood is compromised; this, of course, can lead to circulatory shock. The causes of circulatory shock are varied. Several conditions can lead to circulatory shock, as outlined below: 1. Inadequate circulatory volume. The reduced blood volume leads to a reduction in cardiac output as a result of inadequate venous pressure (reduced ventricular filling pressure). This typically occurs with hemorrhage, sepsis, or conditions of hypovolemia. 2. Impaired ability of the heart to pump blood to the circulation. In these conditions, the heart tissue is compromised so that it cannot pump adequate blood to the circulation even if the venous pressure is normal or elevated. This is, of course, observed in heart failure (reduced contractility). 3. A compromise in the autonomic system that controls the vasculature. Loss of autonomic control leads to reduced vascular tone, causing venous pooling and arteriolar dilation that ultimately result in a reduction in venous and arterial pressure. This can be caused by lesions of the central nervous system. Conditions leading to shock are normally progressive. A loss of blood volume, by hemorrhage, for example, will lead to sequential decreases in circulating blood volume, venous return, ventricular filling, stroke volume, cardiac output, and in turn mean arterial pressure. If blood loss is greater than 30 percent, or so, or if mean arterial pressure falls much below 70 mm Hg, as may occur in heart failure, progression into circulatory shock can occur if the problem leading to these conditions is not corrected rapidly. During the initial hypotensive states, a number of cardiovascular reflexes are activated in an attempt to compensate for a fall in mean arterial pressure. The reduced blood volume and the fall in mean arterial pressure are sensed by low-pressure receptors (volume receptors in the atria, pulmonary veins) and high-pressure baroreceptors (carotid, aortic, and afferent arteriole baroreceptors), respectively; both types of receptors sense the pressure/volume changes and induce an increase in sympathetic nervous activity. This leads to an increase in heart rate, cardiac contractility, and venoconstriction that will serve to elevate mean arterial pressure. Interestingly, this response also leads to selective arteriolar constriction of the extremities, including the skin, skeletal muscle, kidney, and gastrointestinal tract, thereby shunting
412 CASE FILES: PHYSIOLOGY blood away from those tissues. Although local autoregulatory mechanism may respond to this constriction by inducing a subsequent easing of this constriction, partially returning blood flow toward normal, sympathetic-induced vasoconstriction will prevail in severe cases of hypotension. However, the vasculature serving the brain and heart and to some extent the lungs is not markedly vasoconstricted, and normal autoregulation of blood flow prevails so that blood flow to these tissues is not compromised to the same degree. Hence, the system tries to maintain adequate blood flow to these two vital organs at the expense of other tissues and organs. Further, other systems come into play in an attempt to restore blood volume and mean arterial pressure. The low blood pressure and the increased sympathetic activity induce the release of renin from the afferent arteriole of the kidney, activating the reninangiotensin-aldosterone system and leading to aldosterone-induced reabsorption of Na + and Cl - from the cortical collecting duct of the kidney, along with water retention. The hypotension also leads to secretion of ADH from the posterior pituitary, leading to enhanced water reabsorption along the entire length of the cortical and medullary collecting ducts of the kidney in an attempt to return extracellular volume toward normal. Other secondary compensatory processes are also active (see the references at the end of this case). If the compensatory systems noted above do not restore mean arterial pressure adequately, the circulatory system will continue to deteriorate with a further fall in blood pressure in which perfusion of peripheral tissues may be compromised irreversibly, a condition referred to as irreversible shock. In these conditions, the fall in arterial pressure will not reverse even if blood volume is restored to normal levels. The reasons underlying irreversible shock are many. Ischemic tissues release metabolites and other vasodilator molecules that counteract the vasoconstrictor stimuli. Desensitization of the vascular adrenoceptors or depletion of neurotransmitters may contribute to the loss of vasoconstrictor ability. Compromised perfusion of heart tissue can lead to necrosis of heart muscle, and release of cardiotoxic molecules from various organs can lead to reduced contractility. Various other factors may contribute to the decline in the cardiovascular system (see the references at the end of this case). The end result is that the cardiovascular system becomes so compromised that the system will not recover, even with intervention, and the patient eventually will die. Although the fall in blood pressure would appear to be the defining factor leading to shock, it is really a fall in cardiac output that is most critical. During the progression of shock, mean arterial pressure is observed to fall. The body has numerous processes in place to attempt to correct for alterations in low blood pressure, such as baroreceptors, the renin-angiotensin-aldosterone system, and ADH, as outlined above, and so a sudden drop in blood pressure will be defended against. Even so, cardiac output may be reduced so that the underlying problem can be masked partially. Other signs of reduced cardiac output should be apparent, however, such as low urine output caused by reduced blood flow to the kidney, elevated ADH levels, and pale and cold skin resulting from increased sympathetic activity.
CLINICAL CASES 413 The treatment of circulatory shock includes only a limited number of options. The primary defect is low cardiac output that arises from a reduced venous pressure or ventricular filling pressure. This has been treated most successfully by expansion of the blood volume or resuscitation. Three categories of volume expanders traditionally have been employed: (1) whole blood, (2) cell-free fluids with colloids (added plasma for oncotic balance), and (3) colloid-free metabolic fluids. Good results typically have been observed with the colloid-free fluids, such as lactated Ringer solution, although plasma or whole blood can be more effective in less severe cases. As circulatory shock continues, the capillaries become highly permeable, allowing leakage of macromolecules such as plasma proteins. Normally, the permeability to macromolecules is low so that plasma proteins represent a major osmotic solute (osmotic pressure) in the capillary, and this is critical to osmotic reabsorption of fluid that filtered out of the capillaries. With a highly leaky state of the capillaries during shock, the plasma proteins are so permeable across the capillary wall that they do not provide a significant osmotic force. This leads to movement of fluid into the interstitial space, causing pooling or edema. Hence, although plasma or whole blood generally is most effective, along with volume expanders in the more severe cases, the colloid-free fluids, such as lactated Ringer solution, tend to be just as effective if not more so. Of course, only erythrocytes can provide oxygen-carrying capacity through hemoglobin. Regardless of the volume expander employed, treatment with any volume expander will lead to considerable peripheral edema. However, the benefits of an increased cardiac output far outweigh the problems associated with peripheral edema. COMPREHENSION QUESTIONS [51.1] An individual comes to the emergency room complaining of weakness, dizziness, and fatigue. She states that she has had diarrhea for several days. Examination reveals a low blood pressure and tachycardia consistent with low cardiac output. Plasma bicarbonate is low, and other plasma electrolytes are unremarkable. Urine volume was minimal. The patient most likely has which of the following? A. Congestive heart failure B. Edema C. Excessive fluid loss in the stool D. Internal hemorrhage E. Renal failure
414 CASE FILES: PHYSIOLOGY [51.2] An individual was in a car accident and is brought to the emergency room in an unconscious state. Examination shows a very low blood pressure (80/40 mm Hg), tachycardia, a very weak thready pulse, a distended abdomen, and clammy skin. Laboratory values indicate a very low hematocrit (18%) and hypoalbuminemia. He is diagnosed as having internal hemorrhage leading to severe hypovolemia and circulatory shock. To avoid having the patient go into irreversible shock, the emergency room doctor immediately should initiate which of the following treatments? A. Administration of colloid-free volume expanders (eg, normal saline or lactated Ringer solution) B. Administration of epinephrine to induce vasoconstriction C. Administration of oxygen to improve blood oxygenation D. Initiation of a platelet transfusion [51.3] A 35-year-old man had a tractor accident and lost approximately 1500 ml of blood. His initial blood pressure is 90/60 mm Hg, and the heart rate is 120 beats per minute. On resuscitation with intravenous lactated Ringer solution, his blood pressure increases to 110/70 mm Hg. Two hours later, he is noted to have significant peripheral edema of the hands and feet. Which of the following is the best explanation for the edema? A. Capillary leakage B. High-output congestive heart failure C. Infiltration of the intravenous line through the vein D. Low oncotic pressure Answers [51.1] C. Diarrhea over several days can lead to dehydration from loss of fluid in the stool. In severe cases, the individual can become volumedepleted to the point of circulatory collapse. The reduced blood volume and the fall in mean arterial pressure will be sensed by both low-pressure receptors (volume receptors in the atria, pulmonary veins) and high-pressure baroreceptors (carotid, aortic, and afferent arteriole baroreceptors), inducing increased sympathetic nervous activity. This leads to an increase in heart rate, cardiac contractility, and venoconstriction that will serve to elevate mean arterial pressure. In addition, the increase in sympathetic nervous activity stimulates the release of renin from the afferent arteriole, activating the renin-angiotensin-aldosterone system and leading to aldosterone-induced reabsorption of Na + and Cl from the cortical collecting duct; this also stimulates secretion of ADH from the posterior pituitary, leading to enhanced water reabsorption along the entire length of the cortical and medullary collecting ducts of the kidney. All responses to the hypovolemia represent an attempt to return extracellular volume toward normal. To correct the problem fully, the cause of the diarrhea must be addressed.
CLINICAL CASES 415 [51.2] A. The best immediate therapy for a person in hemorrhagic shock is usually isotonic crystalloid colloid-free solution such as normal saline, until red blood cells are available. These agents are usually stocked immediately in the emergency center, whereas blood products require the blood bank to ensure matching blood type. The infusion will increase vascular volume and restore hemodynamics to near normal. Crystalloid such as normal saline cannot restore the hematocrit, but a patient normally can withstand a decrease in hematocrit of up to 20% or so without serious consequences. The use of vasoconstrictors and oxygen can be helpful, but again, if the volume depletion is severe, replacement of fluids will be essential to avoid having the patient go into irreversible shock. [51.3] A. Diffuse capillary leakage is the primary reason for the peripheral edema that occurs regardless of which resuscitation fluid is used. PHYSIOLOGY PEARLS Circulatory shock can arise from many causes, such as heart failure, hemorrhage, sepsis, hypovolemia, and lesions of the central nervous system. The primary defect in circulatory shock is inadequate cardiac output, not just a fall in mean arterial pressure. The body aggressively defends against a reduction in mean arterial pressure by activating multiple processes, including baroreceptor reflexes and the sympathetic nervous system, carotid bodies, the renin-angiotensin-aldosterone system, and ADH release. Blood volume expanders can be used to treat circulatory shock, but only if the patient has not reached the irreversible phase of shock. REFERENCES Boulpaep EL. Integrated control of the cardiovascular system. In: Boron WF, Boulpaep EL, eds. Medical Physiology: A Cellular and Molecular Approach. New York: Saunders; 2003:Chap 24. Downey JM. Heart failure and circulatory shock. In: Johnson LR, ed. Essential Medical Physiology. 3rd ed. San Diego, CA: Elsevier Academic Press; 2003:Chap 64.
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