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Compendium August 2013 (Vol 35, No 8)

Shock Pathophysiology

by Elizabeth Thomovsky, DVM, MS, DACVECC, Paula A. Johnson, DVM


    Shock, defined as the state where oxygen delivery to tissues is inadequate for the demand, is a common condition in veterinary patients and has a high mortality rate if left untreated. The key to a successful outcome for any patient in shock involves having a clear understanding of the pathophysiology and compensatory mechanisms associated with shock. This understanding allows more efficient identification of patients in shock based on clinical signs and timely initiation of appropriate therapies based on the type and stage of shock identified.

    Shock is a condition that is commonly seen in practice but just as commonly is not completely understood. This review focuses on the body’s compensatory responses to shock and the clinical signs to help provide practitioners with a better understanding of what shock is and how it can be categorized. Treatment is discussed in the context of the pathophysiology but is not covered in depth.


    The first difficulty comes in defining shock. At its most elemental, the definition can be stated as:

    oxygen delivery ≠ oxygen consumption (DO2 ≠ VO2).1

    Most cases of shock are the result of decreased delivery of blood to tissues. When blood is not delivered to tissues, oxygen is not delivered. Oxygen is critical for normal cellular function; when the tissues do not receive oxygen, normal cellular aerobic metabolism ceases and anaerobic metabolism ensues. As a result, cells are unable to produce adequate amounts of ATP (FIGURE 1) to sustain normal metabolic function, ultimately leading to cellular dysfunction and death. Additionally, sustained anaerobic metabolism results in the production of cytokines and substances such as lactate and nitric oxide, which further complicate shock (FIGURE 2).

    Multiple factors determine oxygen delivery to cells (FIGURE 3); however, the simplest way to envision oxygen delivery is to consider the body’s cardiac output as being roughly equivalent to the blood delivered throughout the body. In turn, cardiac output is defined as heart rate times stroke volume. Appreciating the interrelationship between oxygen delivery and cardiac output is critical to understanding the pathophysiology of shock and guiding treatment.

    It is less common that the body’s demand for oxygen is the driving force for the imbalance (i.e., that cardiac output is completely normal in a patient in shock). One example of this situation is overwhelming infection, in which the infection causes increased cellular metabolism (and therefore increased cellular oxygen demand). Increases in cellular metabolism alone can cause a state of shock before or in addition to the development of decreased cardiac output secondary to the infection.1,2

    A second example in which cardiac output can be normal in a shock patient is when there is abnormal perfusion of tissues. When large numbers of cells are bypassed by oxygenated blood, an imbalance in oxygen demand and delivery develops that can lead to shock.1,3–8 In cases of abnormal perfusion, the microcirculation at the capillary and other small (≤100 µm) vessel level is typically affected.2,4,7 The microcirculation responds in a variety of ways, culminating in increased permeability of the walls of the endothelium and regions of vasodilation and altered blood flow.4 This leads to less blood being delivered to other cells and local hypoxia of the bypassed cells. Examples of such derangements in microcirculation include the systemic inflammatory response syndrome (SIRS) and reperfusion injury.4 Additionally, in human medicine, use of coronary artery bypass grafting can physically re-route blood away from tissues, causing those tissues to suffer from decreased oxygen delivery.4

    In an attempt to encompass and categorize the various types of shock, shock is typically divided into categories that help explain why oxygen delivery is not matching oxygen demand. However, it is important to remember that clinical cases of shock usually do not fall neatly into one category and often straddle several categories. The four categories described in this article are listed in TABLE 1, along with an explanation of why each category meets the basic definition of shock.

    Compensation for Shock

    Regardless of the cause, when tissues are not properly supplied with oxygen, the body attempts to remedy the situation by initiating a series of neural and hormonally mediated compensatory mechanisms. The end goal of these mechanisms is to increase cardiac output and blood vessel tone in an attempt to better supply the cells with oxygen. These compensatory mechanisms can be grouped into three separate categories: (1) effects exerted within minutes (acute), (2) effects exerted in 10 minutes to 1 hour (moderate), (3) and effects exerted within 1 to 48 hours (chronic).1 In general, the body responds by increasing heart rate, increasing peripheral vascular tone, and attempting to increase stroke volume, all in an effort to improve cardiac output and keep perfusion to tissues intact. Stroke volume is improved by increasing the amount of blood returned to the heart (e.g., venous return). One way to increase venous return is to shunt blood from small (less important), peripheral vessels to the heart to supply the myocardium, lungs, and brain. The kidneys provide a second way to improve venous return by retaining fluid to bolster the total blood volume. FIGURE 4 summarizes these various compensatory mechanisms; the following text discusses the compensation in more detail.

    Acute Compensatory Mechanisms


    Acute compensatory effects are limited to those affecting heart rate and redistributing peripheral blood back to the heart. They are mediated by the sympathetic nervous system (SNS) and catecholamine release and take effect within 30 seconds to a few minutes.1 As cardiac output decreases, impulse generation by the baroreceptors at the carotid sinus and aortic arch in the heart decreases. Under normal conditions, baroreceptor impulses work to inhibit the vasoconstrictor center of the medulla and increase stimulation of the vagal center in the brain, leading to vasodilation. When the baroreceptor impulses are decreased, the vasomotor center in the brain operates unchecked and SNS signals from the brain increase. These increased SNS signals cause release of norepinephrine from the adrenal gland and the nerve endings themselves. Norepinephrine binds to α-adrenergic receptors on blood vessels to cause vasoconstriction and binds to β1-adrenergic receptors in the myocardium to cause an increase in heart rate and contractility1,2 (FIGURE 4).

    A second important stimulus of catecholamine secretion is hypoxemia.2 This can be true hypoxemia, represented by a global decrease in arterial oxygen content, or relative hypoxemia, caused by microcirculatory derangements that shunt blood away from tissues. Chemoreceptors that sense the oxygen content of the blood are located in the carotid artery and aorta. Those in the carotid artery sense decreased oxygen delivery to the brain and, therefore, stimulate the vasomotor center to increase SNS stimulation regardless of peripheral blood pressures.2 In the aorta, decreases in peripheral blood pressure are signaled by decreased baroreceptor stimulation and chemoreceptors are activated as a result of decreased oxygen delivery.2 Both baroreceptor and chemoreceptor signals lead to increased SNS signals from the vasomotor center in the brain.


    Cortisol is also rapidly mobilized in the acute stages of shock (within minutes).1 Cortisol is released from the adrenal gland in response to corticotropin-releasing hormone (CRH) from the hypothalamus and also by stimulation via adrenocorticotropic hormone.7 Stimuli such as pain and mental or physical stress can lead to increases in CRH production. These stimuli are generated in or transmitted through the brain to the hypothalamus. Cortisol has many effects, and it is not completely understood which effect is the most important in shock; however, stimulation of glycogenolysis and mobilization of fat and protein stores for gluconeogenesis are often considered the most important.1 Release of glucose into the bloodstream provides a readily accessible energy source. We believe that the most important effects of this glucose surge are to supply endothelial cells in the blood vessels with energy to continue contraction, feed the myocardial cells to continue contraction, and allow brain cells to function in the short term.

    Transcapillary Shifts

    A final mechanism that aids in the acute improvement in blood volume is transcapillary shifting of fluid from the interstitium to the vasculature. This happens at the capillary level, primarily in cases of hypovolemic shock11 (FIGURE 5). When the pressure within the capillaries drops secondary to hypovolemia and vasoconstrictive shunting of blood, Starling’s forces dictate that fluid will move from an area of higher pressure (the interstitium) into an area of lower pressure (the vessel). Fluid continues to move until the dilution of proteins in the blood vessels (decreasing oncotic pressure in the blood vessel) is balanced with the concentration of proteins in the interstitium (increasing oncotic pressure). Additionally, as fluid moves out of the interstitium into the vascular space, fluid volume and, therefore, pressure decrease in the interstitium (decreasing hydrostatic pressure).

    An additional step during transcapillary fluid shifting involves movement of proteins into the blood from storage sites in the mesentery and liver.11 These proteins increase oncotic pressure in the blood vessels to continue to help draw fluid from the interstitium into blood vessels and maintain the extra fluid within the blood vessels.11          

    Moderate Compensatory Mechanisms

    The next level of compensation starts within about 10 minutes to 1 hour after the body enters the shock state.

    Angiotensin II

    Baroreceptors in the juxtaglomerular apparatus near the renal glomerulus sense decreased blood flow from decreased cardiac output. This decreases impulse generation in the baroreceptors, which in turn leads to renin secretion. Renin causes conversion of angiotensinogen to angiotensin I in the bloodstream. Angiotensin I is converted to angiotensin II in the lungs under the influence of angiotensin-converting enzyme. Angiotensin II binds to angiotensin receptors on the blood vessels and causes vasoconstriction. The vasoconstriction not only improves blood vessel tone to maintain perfusion to the tissues but also, more importantly, forces blood from less important peripheral tissues (including the splanchnic circulation) to the brain and heart to improve venous return and cardiac output.2 Angiotensin II also retains water and sodium in the kidneys to help maintain blood volume through renal artery vasoconstriction, which reduces filtration of blood through direct effects on the tubules that are not completely elucidated.1      


    Vasopressin is released from the posterior pituitary gland in response to increased osmolarity (i.e., less water and more sodium in the blood that passes by the osmoreceptors in the hypothalamus) or decreased effective circulating blood volume as sensed by the baroreceptors and stretch receptors (in the right and left atria). The atrial stretch receptors are active when there is a large volume in the atria and work to inhibit vasopressin secretion; when the atria are less full, more vasopressin is released because of lack of inhibition. Even small alterations—a 1% change in osmolarity or a 10% decrease in blood volume—lead to release of vasopressin.7 Other stimuli, including nausea and hypoxia, also develop in patients with shock and cause further release of vasopressin.7 Vasopressin binds to V1 receptors on the arterioles, causing vasoconstriction. As with angiotensin or norepinephrine, this improves vascular tone in an effort to maintain delivery of blood to tissues. Additionally, it increases return of blood from the peripheral tissues to the heart so that venous return and cardiac output are maintained.

    Chronic Compensatory Mechanisms

    If the patient survives the shock situation, the final stages of compensation involve replacing the blood volume in the body. This takes place from 1 to 48 hours after insult.


    At the same time that angiotensin II is exerting its effects on blood vessels and the kidney, it is also stimulating the adrenal glands to secrete aldosterone from the adrenal gland cortex.1 Aldosterone increases sodium reabsorption in the distal convoluted tubule of the kidney. Water follows the sodium and is reabsorbed into the blood vessels, increasing blood volume. Whenever blood volume is increased, there is improved venous return (and therefore cardiac output).

    Antidiuretic Hormone

    Vasopressin has another effect in the body as antidiuretic hormone (ADH). Vasopressin and ADH are the same hormone; the two names reflect the two divergent effects in the body. When produced, ADH binds to V2 receptors in the collecting ducts of the kidney.1 This induces insertion of aquaporin channels into the collecting ducts to allow reabsorption of water from the ducts. ADH also stimulates thirst to increase the amount of water in the body and thereby improve blood volume and venous return.

    Clinical Signs Associated With Shock

    Building on the basic physiology of the shock response allows better understanding of the clinical signs associated with an animal presenting in shock. Patients go through three stages of shock: compensatory, acute decompensatory, and late decompensatory. Other terms for these stages are compensatory reversible shock, uncompensated reversible shock, and uncompensated irreversible shock.3 In the compensated stage, by virtue of the various physiologic mechanisms discussed above, the patient is able to maintain oxygen delivery to the tissues to preserve normal cellular metabolism. In the acute stage of decompensation, the demand for oxygen is greater than the delivery despite the action of the physiologic mechanisms; therefore, the cells are forced to switch to anaerobic metabolism, which yields less energy. In the later stages of decompensation, inappropriate oxygen delivery continues and the cellular demand for oxygen is not met, causing further anaerobic metabolism and less available ATP to the cells.

    In veterinary medicine, determination of the patient’s stage of shock is based largely on the physical examination findings for that patient. See TABLE 2 for a summary of the physical examination findings found at each stage of shock and TABLE 3 for the reasons each finding exists at that stage.

    The physical examination finding that has the most variability in cases of shock is the mucous membrane color. Based purely on the physiologic responses to which a patient is exposed during compensated shock, the expected mucous membrane color is pale because of vasoconstrictive shunting of blood away from the mucous membranes. However, in some cases, the mucous membranes can appear hyperemic.9,10 Hyperemic mucous membranes may be seen in diseases in which vasodilation overwhelms the vasoconstriction expected in compensated shock. Notable examples are septic shock and SIRS, in which vasodilatory mediators such as nitric oxide and cytokines that directly dilate the blood vessels are produced, leading to vasodilation.9,10 Later, in decompensatory shock, the pallor seen in SIRS and sepsis patients is caused by a lack of blood delivery to the mucous membranes, not vasoconstrictive mechanisms.

    Cats may not display the classic sign of tachycardia seen in dogs. While there is no clear reason for this species difference, cats in shock that tend to display bradycardia (heart rate <140 bpm) or relative bradycardia (heart rate <160 bpm) are often septic or have SIRS.9,10


    In veterinary medicine, treatment for shock should be aimed at addressing the basic pathophysiologic mechanisms. Gauging a response to treatment for patients in shock is based on normalizing vital parameters and, often, peripheral blood pressure. There are very limited options available to clinicians to treat cases of shock (FIGURE 6).

    Hypovolemic shock is primarily treated by large-volume fluid resuscitation. Crystalloid fluid doses for patients in shock are 90 mL/kg/h in dogs and 60 mL/kg/h in cats. It is recommended to give one-quarter to one-third of the calculated fluid dose to the animal in a bolus as quickly as possible and then reassess the patient’s vital parameters. The fluid bolus can be repeated as many times as necessary until the parameters have normalized or the hourly amount has been met. Further or additional steps might include administration of boluses of colloids (typically 5 to 10 mL/kg repeated until the patient is stabilized or to a maximum dose of 20 mL/kg for colloids such as hetastarch).

    Obstructive shock is treated with fluids administered at shock doses in a vascular location where the fluids will return to the heart and not be trapped distal to the obstruction. For example, a patient with gastric dilatation-volvulus (GDV) should receive fluid in the cephalic veins, not the lateral saphenous veins. When applicable, the clinician should also attempt to relieve the obstruction (e.g., surgery to relieve GDV).

    Cardiogenic shock does not involve decreased blood volume and instead is a failure of the heart to effectively pump blood to tissues. It is treated with positive inotropes (e.g., dobutamine) without fluid therapy. In some cases, drugs that cause vasodilation and reduce afterload, such as nitroprusside, are also used to improve cardiac output. It is important to limit or forgo fluid therapy in patients with cardiogenic shock because the heart may already be fluid overloaded by shunting of blood to the heart caused by vasoconstriction during compensation.

    Distributive shock is the most difficult form of shock to treat because it involves derangement of the microvasculature as well as the macrovasculature. These patients are treated with shock doses of fluids to improve hypovolemia resulting from increases in vascular permeability and maldistribution of fluids into the dilated vessels. Patients also require treatment with drugs to promote vasoconstriction, such as vasopressin, dopamine, epinephrine, or norepinephrine and, in some cases, positive inotropes to improve myocardial depression (dobutamine). Finally, the underlying cause of the distributive shock must be addressed. Diseases leading to distributive shock may not only cause hypercoagulability (which can obstruct blood vessels) and release cytokines that cause depression of the myocardium but also, if untreated, prevent resolution of the patient’s condition. Also complicating the situation is the fact that improving macrovascular parameters such as heart rate or peripheral blood pressure does not necessarily mean that microcirculation (capillary perfusion) has been restored.4,8 However, at this time, clinicians do not have a clinically dependable bedside diagnostic test or tool that allows assessment of the microcirculatory response to resuscitation.

    In any treatment situation, continuous reassessment of the patient’s vital parameters and status to determine whether resuscitation efforts have been successful is most important. If the patient does not seem to be improving as hoped, continue to administer treatment as suggested by the patient’s condition, but reassess the patient with a complete physical examination to look for indications of occult hemorrhage (e.g., into a body cavity or a fracture hematoma) that would lead to ongoing signs of hypovolemic shock. It is important to document that a refractory patient is not suffering from hypoglycemia caused by depleted liver stores occurring after exuberant cortisol release. Finally, especially in trauma patients, if the patient does not improve with resuscitation, imaging of body cavities is indicated to look further for blood loss or other abnormalities, such as pneumothorax, that might decrease venous return to the heart and further the shock condition.

    Shock is a complex interaction between the inciting event and the body’s compensatory mechanisms. In understanding basic pathophysiology, clinicians should be able to better recognize patients in shock and to logically determine the best steps for resuscitation of these patients.

    Downloadable PDF

    1. Hall JE. Circulatory shock. In: Guyton and Hall Textbook of Medical Physiology. 12th edi. Philadelphia, PA: Saunders Elsevier; 2011:273-282.

    2. Bonanno FG. Physiopathology of shock. J Emerg Trauma Shock 2011;4(2):222-232.

    3. Brown SGA. The pathophysiology of shock in anaphylaxis. Immunol Allergy Clin North Am 2007;27:165-175.

    4. Elbers PWG, Ince C. Bench-to-bedside review: mechanisms of critical illness—classifying microcirculatory flow abnormalities in distributive shock. Crit Care 2006;10:221.

    5. Ben-Shoshan M, Clarke AE. Anaphylaxis: past, present and future. Allergy 2010;66:1-14.

    6. Moranville MP, Mieure KD, Santayana EM. Evaluation and management of shock states: hypovolemic, distributive and cardiogenic shock. J Pharm Pract 2011;24(1):44-60.

    7. Woolf PD. Endocrinology of shock. Ann Emerg Med 1986;15:1401-1405.

    8. Szopinski J, Kusza I, Semionow M. Microcirculatory responses to hypovolemic shock. J Trauma 2011;71(6):1779-1787.

    9. Boag AK, Hughes D. Assessment and treatment of perfusion abnormalities in the emergency patient. Vet Clin North Am Small Animal Pract 2005;35(2):319-342.

    10. deLaForcade AM, Silverstein DC. Shock. In: Silverstein DC, Hopper K, eds. Small Animal Critical Care Medicine. St. Louis, MO: Saunders Elsevier; 2009:41-45.

    11. Boulpaep EL. Integrated control of the cardiovascular system. In: Boron WF, Boulpaep EL, eds. Medical Physiology: a Cellular and Molecular Approach. Philadelphia, PA: Elsevier Saunders; 2003:574-590.

    References »

    NEXT: Canine Struvite Urolithiasis (August 2013)


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