Symposium on Shock
The Unified Concept of Shock A. Wendell Nelson, D.V.M., Ph.D.*
SHOCK: A diseased state characterized by capillary perfusion insufficient to maintain normal cell function. Shock is a specific circulatory-metabolic disease which may be initiated by any of several alterations in homeostasis. Abnormal perfusion of the microcirculation and subsequent cellular metabolic derangements are common to all types of shock whether hypovolemic, cardiogenic, or vasogenic in origin.
BASIC CAUSES OF SHOCK There are three basic causes of shock-hypovolemia, myocardial insufficiency, and vasodilation. Clinical disease that results in a shock state may involve one, two, or three of these basic causes.
Hypovolemic Hypovolemic shock is brought about by any situation which decreases the circulating blood volume to a point which causes a reduction in venous return and cardiac output. Hypovolemia is commonly thought of as a loss of circulating blood from the body. Other causes of hypovolemia are loss of protein and fluids resulting from extensive burns, gastrointestinal fluid losses from vomiting, diarrhea, and generalized peritonitis, and blunt trauma to soft tissue resulting in edema and hemorrhage. Later stages of hypovolemic shock may be complicated by septic disease and myocardial depression.
Cardiogenic Cardiogenic shock is failure of the heart to pump adequately the blood presented to it, thus causing a decrease in cardiac output. Car*-\ssociate Professor of Clinical Sciences. Surgical Laboratory. College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado l"eterinary Clinics of North America- Vol. 6, No.2, May 1976
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diogenic shock in man develops after severe myocardial infarction, a disease entity rarely encountered in animals. The veterinary clinician is seldom faced with pure cardiogenic shock except in cases of acute decompensation of animals with chronic heart failure. However, myocardial insufficiency may complicate the later stages of shock created by other lesions (i.e., hypovolemia, vasodilation). Myocardial insufficiency and failure can be brought about by increased cardiac rate during periods of hypotension. The elevated heart rate shortens the length of diastolic time and the lowered diastolic pressure constitutes a lowered driving force for coronary perfusion. This combination causes a severe decrease in myocardial perfusion resulting in decrease in contractility of the myocardium. In contrast to hypovolemic and vasogenic shock, there can be a rise in central venous pressure because the heart is not able to pump the blood returning to it. When cardiac failure is part of a terminal shock condition related to hypovolemia or vasodilation, the central venous pressure may be normal or low. Vasogenic
Uncomplicated vasogenic shock is uncommon in domestic animals. This condition is caused by acute vasodilation mediated through the autonomic nervous system as a result of extreme psychologic stimuli or pain or through the release of local agents (i.e., histamine, bradykinin). The venous system contains approximately 60 per cent of the circulating blood volume and is normally under a mild degree of constriction due to sympathetic stimuli. In addition the vessels supplying the splanchnic organs and skeletal musculature are under similar tone during digestive and physical rest respectively. Partial or complete release of the vascular system from sympathetic control will result in a rapid decrease in venous return. In animals vasogenic shock is frequently related to the terminal phases of septic or hypovolemic shock. Failure of sympathetic nervous system, circulating catecholamine perpetuation of peripheral vasoconstriction, and increased levels of vasodilating agents (histamine, serotonin, polypeptides) collaborate to produce this terminal phase. BASIC SHOCK CYCLE The specific details on each clinical shock syndrome will be covered in subsequent sections. Each inciting cause of shock results in the common signs of decreased venous return and cardiac output. The entire shock cycle evolves from this point and is self-perpetuating unless specific therapy is initiated. Once the decrease in cardiac output has caused a reduced capillary circulation, the shock cycle has been initiated. The rate of progression of the system into the shock state will depend on the severity of the initiating lesion.
THE UNIFIED CONCEPT OF SHOCK
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The early response to a decrease in cardiac output is a lowering of arterial blood pressure. This is sensed by the arterial and venous baroreceptors, and afferent nerves from these locations pass to the vasomotor centers of the brain stem. These centers stimulate the sympathetic nervous system, which results in an elevated heart rate, increased force of contraction of the heart, and peripheral vasoconstriction. In addition, the pituitary gland is stimulated to release antidiuretic hormone causing increased water resorption by the renal tubules. This augments plasma volume. The intensity of sympathetic activity and catecholamine (epinephrine and norepinephrine) release will depend on the responsiveness of the arterial blood pressure to this activity. The inability of vasoconstriction to return blood pressure to normal results in sustained vasoconstriction of the entire vascular system with the exception of the vessels supplying the brain and heart. In acute hypovolemia, maximal endogenously stimulated vasoconstriction is reached when the systolic aortic blood pressure is less than 40 mmHg (in the dog). At this point the diastolic pressure is less than 30 mmHg and the system will not constrict further with adrenergic agents, although increases in heart rate can occur. Sustained constriction of precapillary arterioles and precapillary sphincters and venules causes decreased capillary perfusion and tissue ischemia. Tissue ischemia leads to cell hypoxia and a decrease in aerobic metabolism. The reduction in aerobic metabolism results from lack of adequate oxygen to bind hydrogen ions. The accumulation of H + inhibits the hydrogen ion transfer through the cytochrome system. This reaction slows the activity of the citric acid cycle and glucose metabolism is terminated at pyruvic acid with lactic acid formation. Blocking of glucose metabolism at pyruvic acid results in a 94 per cent loss in energy production per mole of glucose metabolized. Thus, the net effect is a decrease in available energy for cell function and an accumulation of an ionized organic acid (lactic acid). Additional intracellular acidosis is produced by the accumulation of organic acids from partial metabolism of fats and amino acids. The acid radicals escape to the extracellular fluid and result in acidemia. The developing acidemia stimulates the sympathetic cenler as well as the respiratory center which results in an elevated heart rate and respiratory rate. These feedback mechanisms are aimed at increasing cardiac output, oxygen availability to the pulmonary blood, and blood flow to the tissues. The decrease in energy (ATP) production brought about by the hypoxic state of the tissues decreases the ability of the tissue to maintain its normal function (i.e., secretion, contraction). This interferes with the selective permeability of the cell membranes leading to the absorption of water into the cell and alteration of the intracellular electrolytes. Similar changes affect the cell organelles, particularly the
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limiting membrane of lysosomes which can break down, liberating the contained hydrolytic enzymes resulting in tissue autolysis. The inability to rephosphorylate ADP to ATP causes the ADP to be degraded to AMP and adenosine to release the energy-containing phosphate bonds. Adenosine is then degraded to hypoxanthine which is able to get out of the cell where it is degraded. The loss of hypoxanthine from the cell removes the basic building block for ATP and thus limits the ability of the cell to regain ATP production with the onset of increased tissue perfusion. The metabolic lesions produced by the loss of cell energy results in cell death. When this process gains significant proportions, the patient enters an irreversible state and death ensues regardless of the treatment received.
BASIS OF PHYSICAL SIGNS OF SHOCK The vasoconstriction initiated by a decrease in blood pressure results in a decreased blood flow in the skin which allows the temperature of the skin to decrease. Simultaneously sweat gland stimulation (parasympathetic) results in moisture accumulation on the skin surface. Severe blood flow reduction in the splanchnic vasculature leads to gastrointestinal hypermobility followed by stasis and mucosal necrosis. The hypermobility may result in multiple defecation and blood-tinged feces. The ensuing stasis and mucosal necrosis lead to bacterial proliferation and absorption of viable bacteria, bacterial toxins and metabolites, enzymes, and so forth, from the intestinal lumen. Depressed urine output may be caused from low (60 mmHg) arterial blood pressure, tubular necrosis, and injury resulting from tissue breakdown products ("crush syndrome"). These will cause elevated plasma levels of urea, ammonia, creatinine, and potassium. Elevated respiratory rate is a compensatory mechanism to alleviate the developing metabolic acidemia and results in low (
The Unified Concept of Shock A. Wendell Nelson, D.V.M., Ph.D.*
SHOCK: A diseased state characterized by capillary perfusion insufficient to maintain normal cell function. Shock is a specific circulatory-metabolic disease which may be initiated by any of several alterations in homeostasis. Abnormal perfusion of the microcirculation and subsequent cellular metabolic derangements are common to all types of shock whether hypovolemic, cardiogenic, or vasogenic in origin.
BASIC CAUSES OF SHOCK There are three basic causes of shock-hypovolemia, myocardial insufficiency, and vasodilation. Clinical disease that results in a shock state may involve one, two, or three of these basic causes.
Hypovolemic Hypovolemic shock is brought about by any situation which decreases the circulating blood volume to a point which causes a reduction in venous return and cardiac output. Hypovolemia is commonly thought of as a loss of circulating blood from the body. Other causes of hypovolemia are loss of protein and fluids resulting from extensive burns, gastrointestinal fluid losses from vomiting, diarrhea, and generalized peritonitis, and blunt trauma to soft tissue resulting in edema and hemorrhage. Later stages of hypovolemic shock may be complicated by septic disease and myocardial depression.
Cardiogenic Cardiogenic shock is failure of the heart to pump adequately the blood presented to it, thus causing a decrease in cardiac output. Car*-\ssociate Professor of Clinical Sciences. Surgical Laboratory. College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado l"eterinary Clinics of North America- Vol. 6, No.2, May 1976
173
174
A.
WENDELL NELSON
diogenic shock in man develops after severe myocardial infarction, a disease entity rarely encountered in animals. The veterinary clinician is seldom faced with pure cardiogenic shock except in cases of acute decompensation of animals with chronic heart failure. However, myocardial insufficiency may complicate the later stages of shock created by other lesions (i.e., hypovolemia, vasodilation). Myocardial insufficiency and failure can be brought about by increased cardiac rate during periods of hypotension. The elevated heart rate shortens the length of diastolic time and the lowered diastolic pressure constitutes a lowered driving force for coronary perfusion. This combination causes a severe decrease in myocardial perfusion resulting in decrease in contractility of the myocardium. In contrast to hypovolemic and vasogenic shock, there can be a rise in central venous pressure because the heart is not able to pump the blood returning to it. When cardiac failure is part of a terminal shock condition related to hypovolemia or vasodilation, the central venous pressure may be normal or low. Vasogenic
Uncomplicated vasogenic shock is uncommon in domestic animals. This condition is caused by acute vasodilation mediated through the autonomic nervous system as a result of extreme psychologic stimuli or pain or through the release of local agents (i.e., histamine, bradykinin). The venous system contains approximately 60 per cent of the circulating blood volume and is normally under a mild degree of constriction due to sympathetic stimuli. In addition the vessels supplying the splanchnic organs and skeletal musculature are under similar tone during digestive and physical rest respectively. Partial or complete release of the vascular system from sympathetic control will result in a rapid decrease in venous return. In animals vasogenic shock is frequently related to the terminal phases of septic or hypovolemic shock. Failure of sympathetic nervous system, circulating catecholamine perpetuation of peripheral vasoconstriction, and increased levels of vasodilating agents (histamine, serotonin, polypeptides) collaborate to produce this terminal phase. BASIC SHOCK CYCLE The specific details on each clinical shock syndrome will be covered in subsequent sections. Each inciting cause of shock results in the common signs of decreased venous return and cardiac output. The entire shock cycle evolves from this point and is self-perpetuating unless specific therapy is initiated. Once the decrease in cardiac output has caused a reduced capillary circulation, the shock cycle has been initiated. The rate of progression of the system into the shock state will depend on the severity of the initiating lesion.
THE UNIFIED CONCEPT OF SHOCK
175
The early response to a decrease in cardiac output is a lowering of arterial blood pressure. This is sensed by the arterial and venous baroreceptors, and afferent nerves from these locations pass to the vasomotor centers of the brain stem. These centers stimulate the sympathetic nervous system, which results in an elevated heart rate, increased force of contraction of the heart, and peripheral vasoconstriction. In addition, the pituitary gland is stimulated to release antidiuretic hormone causing increased water resorption by the renal tubules. This augments plasma volume. The intensity of sympathetic activity and catecholamine (epinephrine and norepinephrine) release will depend on the responsiveness of the arterial blood pressure to this activity. The inability of vasoconstriction to return blood pressure to normal results in sustained vasoconstriction of the entire vascular system with the exception of the vessels supplying the brain and heart. In acute hypovolemia, maximal endogenously stimulated vasoconstriction is reached when the systolic aortic blood pressure is less than 40 mmHg (in the dog). At this point the diastolic pressure is less than 30 mmHg and the system will not constrict further with adrenergic agents, although increases in heart rate can occur. Sustained constriction of precapillary arterioles and precapillary sphincters and venules causes decreased capillary perfusion and tissue ischemia. Tissue ischemia leads to cell hypoxia and a decrease in aerobic metabolism. The reduction in aerobic metabolism results from lack of adequate oxygen to bind hydrogen ions. The accumulation of H + inhibits the hydrogen ion transfer through the cytochrome system. This reaction slows the activity of the citric acid cycle and glucose metabolism is terminated at pyruvic acid with lactic acid formation. Blocking of glucose metabolism at pyruvic acid results in a 94 per cent loss in energy production per mole of glucose metabolized. Thus, the net effect is a decrease in available energy for cell function and an accumulation of an ionized organic acid (lactic acid). Additional intracellular acidosis is produced by the accumulation of organic acids from partial metabolism of fats and amino acids. The acid radicals escape to the extracellular fluid and result in acidemia. The developing acidemia stimulates the sympathetic cenler as well as the respiratory center which results in an elevated heart rate and respiratory rate. These feedback mechanisms are aimed at increasing cardiac output, oxygen availability to the pulmonary blood, and blood flow to the tissues. The decrease in energy (ATP) production brought about by the hypoxic state of the tissues decreases the ability of the tissue to maintain its normal function (i.e., secretion, contraction). This interferes with the selective permeability of the cell membranes leading to the absorption of water into the cell and alteration of the intracellular electrolytes. Similar changes affect the cell organelles, particularly the
176
A.
WENDELL NELSON
limiting membrane of lysosomes which can break down, liberating the contained hydrolytic enzymes resulting in tissue autolysis. The inability to rephosphorylate ADP to ATP causes the ADP to be degraded to AMP and adenosine to release the energy-containing phosphate bonds. Adenosine is then degraded to hypoxanthine which is able to get out of the cell where it is degraded. The loss of hypoxanthine from the cell removes the basic building block for ATP and thus limits the ability of the cell to regain ATP production with the onset of increased tissue perfusion. The metabolic lesions produced by the loss of cell energy results in cell death. When this process gains significant proportions, the patient enters an irreversible state and death ensues regardless of the treatment received.
BASIS OF PHYSICAL SIGNS OF SHOCK The vasoconstriction initiated by a decrease in blood pressure results in a decreased blood flow in the skin which allows the temperature of the skin to decrease. Simultaneously sweat gland stimulation (parasympathetic) results in moisture accumulation on the skin surface. Severe blood flow reduction in the splanchnic vasculature leads to gastrointestinal hypermobility followed by stasis and mucosal necrosis. The hypermobility may result in multiple defecation and blood-tinged feces. The ensuing stasis and mucosal necrosis lead to bacterial proliferation and absorption of viable bacteria, bacterial toxins and metabolites, enzymes, and so forth, from the intestinal lumen. Depressed urine output may be caused from low (60 mmHg) arterial blood pressure, tubular necrosis, and injury resulting from tissue breakdown products ("crush syndrome"). These will cause elevated plasma levels of urea, ammonia, creatinine, and potassium. Elevated respiratory rate is a compensatory mechanism to alleviate the developing metabolic acidemia and results in low (
