3 CE Credits Shock Pathophysiology Elizabeth Thomovsky, DVM, MS, DACVECC Paula A. Johnson, DVM Purdue University Abstract: 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. hock is a condition that is commonly seen in practice but Anaerobic metabolism just as commonly is not completely understood. This review focuses on the body’s compensatory responses to shock and Production and release of lactate, cytokines, prostaglandins, nitric oxide, etc. S the clinical signs to help provide practitioners with a better under- standing of what shock is and how it can be categorized. Treatment is Increased capillary Decreased vasomotor tone discussed in the context ofThomovsky the pathophysiology E, et al. Shock pathophysiology but is .not Compend covered Contin Cellular swelling Thomovsky E, et al. Shock pathophysiology. Compend Contin permeability in depth. Educ Vet 2013;35(8)Educ Vet 2013;35(8). Definitions Interstitial edema The first difficulty comes in defining shock. At its most elemental, the definition can be stated as: Cellular dysfunction Circulatory collapse 1 oxygen delivery ≠ oxygen consumption (DO2 ≠ VO2). GI barrier breakdown + translocation of gut bacteria Glucose Glucose Consumptive coagulopathy Anaerobic AnaerobicMetabolism Metabolism. Pyruvate. Pyruvate Aerobic MetabolismAerobic Metabolism. cannot entercannot the TCA enter cycle the TCA and enterscycle and enters Pyruvate isPyruvate able to e isnter able to enter the Cori cyclethe Corito form cycle lactate. to form Lactate lactate. Lactate the TCA cyclethe TCA and iscycle and is can be usedcan by bethe used brain by and the heart brain in and heart in Death converted intoconverted large into large the short termthe shortfor energy term,forbut energy it is , but it is amounts ofamounts ATP. of ATP. overall an inefficientoverall an inefficientsource of source of 2 pyruvate2 pyruvate Figure 2. SequelaeFigure 2.of prolongedSequelae anaerobic of prolonged metabolism. anaerobic metabolism. cellular energycellular. energy. Oxygen Oxygen Oxygen Oxygen 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 TCA cycleTCA cycle Cori cycle Cori cycle tissues do not receive oxygen, normal cellular aerobic metabo- lism 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 dysfunc- tion and death. Additionally, sustained anaerobic metabolism results 2 lactate 2 lactate in the production of cytokines and substances such as lactate and 36 36 2 2 ATP ATP nitric oxide, which further complicate shock (FIGURE 2). ATP ATP 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 Figure 1. Aerobic versus anaerobic metabolism. TCA = tricarboxylic acid delivered throughout the body. In turn, cardiac output is defined Figure 1.FigureAerobic 1. versusAerobic anaerobic versus anaerobic metabolism. metabolism. TCA = tricarboxylic TCA = tricarboxylic acid. acid. Vetlearn.com | 2013 | Compendium: Continuing Education for Veterinarians™ E1 ©Copyright 2013 Vetstreet Inc. This document is for internal purposes only. Reprinting or posting on an external website without written permission from Vetlearn is a violation of copyright laws. Thomovsky E, et al. Shock pathophysiology. Compend Contin Educ Vet 2013;35(8). Shock Pathophysiology DO2 = CaO2 x CO It is less common that the body’s demand for oxygen is the driving force for the imbalance (i.e., that cardiac output is com- Preload Afterload pletely normal in a patient in shock). One example of this situation Contractility is overwhelming infection, in which the infection causes increased cellular metabolism (and therefore increased cellular oxygen CO = HR x SV 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 CaO2 = (SpO2 x 1.34 x [Hb]) + (0.003 x PaO2) A second example in which cardiac output can be normal in a Figure 3. The determinants of oxygen delivery in the body. CaO2 = arterial oxygen shock patient is when there is abnormal perfusion of tissues. content, = cardiac output, = oxygen delivery, = concentration of CO DO2 [Hb] When large numbers of cells are bypassed by oxygenated blood, an hemoglobin in the blood, HR = heart rate, PaO = partial pressure of oxygen in Figure 3. The determinants of oxygen delivery in the body. CaO2 = arterial oxygen content, CO =cardiac output, DO = oxygenimbalance delivery, [Hb] = in oxygen demand and delivery develops that can lead arterial blood, SV =stroke volume, SpO = % hemoglobin2 saturation with oxygen. 2 concentration of hemoglobin in the blood, HR = heart2 rate, PaO2 = partial pressure of oxygen in arterial blood, SV =stroke volume,to shock. SpO2 = %1,3–8 In cases of abnormal perfusion, the microcirculation hemoglobin saturation with oxygen. at the capillary and other small (≤100 µm) vessel level is typically as heart rate times stroke volume. Appreciating the interrelationship affected.2,4,7 The microcirculation responds in a variety of ways, between oxygen delivery and cardiac output is critical to under- culminating in increased permeability of the walls of the endo- standing the pathophysiology of shock and guiding treatment. thelium and regions of vasodilation and altered blood flow.4 This Table 1. Categories, Examples, Basic Definitions, and Pathophysiology of Shock Category of Shock Classic Example Basic Definition Pathophysiology/Events Leading to Shock Hypovolemic Decreased effective circulating blood Decreased effective circulating volume à decreased venous volume return à decreased stroke volume à decreased cardiac Absolute Absolute: bleeding output and blood delivery to tissues from wound (laceration) Relative Relative: bleeding into third space in body (hemoabdomen, fracture hematoma) Obstructive Gastric-dilatation Physical impediment to blood flow in Physical blockage to venous return/blood trapped distal to volvulus (dilated large vessels (predominantly veins) obstruction à decreased stroke volume à decreased stomach occludes cardiac output and blood delivery to tissues caudal vena cava) Cardiogenic Dilated cardiomyopathy Heart unable to pump blood (typically Decreased contractility à decreased cardiac output and caused by lack of contractility) blood delivery to tissues Distributive Sepsis (Gram-negative Multifactorial (one or more of the following): endotoxemia) 1. Vasodilation, especially peripheral Macrocirculatory vasodilation à blood trapped in periphery Anaphylaxis vessels (both microcirculation + à decreased venous return à decreased stroke volume à macrocirculation) decreased cardiac output and blood delivery to tissues Microcirculatory vasodilation à oxygen arrives at the tissues but is not delivered to the metabolizing cells due to vasodilation-driven shunting of blood away from the cells 2. Increased vessel permeability Increased vessel wall permeability à decreased effective (relative hypovolemia as fluid leaks circulating blood volumeà decreased venous return à out of vessels) decreased cardiac output and blood delivery to tissues 3. Decreased cardiac contractility due Decreased cardiac contractility à decreased cardiac output to effects of cytokine mediators and blood delivery to tissues (sepsis) or platelet activating factor (anaphylaxis) 4. Activation of the coagulation Multiple clot formation à small vessels occluded à system decreased venous return à decreased cardiac output and blood delivery to tissues Vetlearn.com | 2013 | Compendium: Continuing Education for Veterinarians™ E2 Thomovsky E, et al. Shock pathophysioloShock Pathophysiologygy. Compend Contin Educ Vet 2013;35(8). leads to less blood being delivered to other cells and local hypoxia of the by- Shock (decreased Decreased baroreceptor cardiac output) passed cells. Examples of such derange- activity (aortic and ments in microcirculation include the carotid bodies) systemic inflammatory response syn- 4 ↑[Na] (osmoreceptors); drome (SIRS) and reperfusion injury. Decreased decreased blood volume Additionally, in human medicine, use of Increased SNS baroreceptor (baroreceptors) tone activity (JG coronary artery bypass grafting can apparatus) physically re-route blood away from tis- Adrenal V1 receptors gland Release antidiuretic sues, causing those tissues to suffer from hormone/ vasopressin Epinephrine/ 4 Renin release (posterior pituitary) decreased oxygen delivery. norepinephrine (kidney) In an attempt to encompass and cate- release V2 receptors β1 receptors α receptors gorize the various types of shock, shock is bloodstream typically divided into categories that help Insert aquaporin channels collecting explain why oxygen delivery is not match- Increased heart Vaso- and veno- Angiotensinogen