Shock's two faces quiz

Shock's two faces: hypoxemic shock and oxygen carrying capacity

By Kenichiro Yagi, BS, RVT, VTS (ECC, SAIM)

“Please name the types of shock.” When asked this, many will often think of hypovolemic, cardiogenic, distributive, and obstructive shock. Hypovolemic shock involves impaired blood flow to tissues, or perfusion, due to loss in intravascular blood volume often seen in conditions involving fluid loss or reduced intake. Cardiogenic shock occurs when cardiac disease prevents the heart from creating adequate forward flow. Distributive shock results when a significant loss of vascular tone and vasodilation causes a relative hypovolemia. Obstruction of major vessels and blood flow leads to obstructive shock. Shock has two faces, and the four types mentioned represent shock resulting from circulatory failure leading to loss of perfusion. What about the other face? Before we discuss further, let’s first define shock.


Shock is defined as a state of inadequate cellular energy production. ATP is considered the “currency of cellular energy”, providing energy for cellular processes required to maintain life. ATP is involved in cellular signaling, DNA and RNA synthesis, muscle contraction, cytoskeletal maintenance, active transporting, and many other cellular functions. A finite amount of ATP is available within a body, and constant recycling is required to keep up with energy demands. In the presence of oxygen, 38 ATP molecules are generated from metabolism of a single glucose molecule undergoing oxidative phosphorylation in the mitochondria. In contrast, a single glucose molecule yields two ATP molecules through anaerobic metabolism. The presence of oxygen is imperative in efficient energy generation. Hemodynamic compromise impairs oxygen delivery (DO2) through the blood. 

The other face consists of metabolic and hypoxemic shock, different from the previously mentioned types of shock as both can occur without hemodynamic compromise. Metabolic shock occurs when the substrate for energy production is lacking (hypoglycemia), or mitochondrial function is impaired (cyanide toxicity). Hypoxemic shock occurs when there is not enough oxygen contained in the circulating blood volume (arterial oxygen content, CaO2) to meet metabolic demands. Given that respiratory function is normal, CaO2 is largely dependent on the level of hemoglobin (Hgb) molecules present (98% in a healthy patient), with some oxygen carried in a dissolved gas form (2%). Each red blood cell (RBC) contains approximately 280 million hemoglobin molecules, each able to carry four oxygen molecules. The circulating RBC mass represents one’s oxygen carrying capacity.


Anemia is most accurately described as a deficiency in the blood’s oxygen carrying capacity due to a reduction in the circulating red cell mass. Measurement of total red cell mass requires specialized testing and is difficult to accomplish in clinical practice. Measurement of PCV, HCT, Hgb, and RBC count are more common methods in the assessment of erythrocyte content of blood. Thus, anemia is commonly defined as a reduction in these values, and occurs when the rate of red blood cell loss or destruction exceeds the rate of production. These values represent a concentration of RBCs, and its correlation to RBC mass is variable due to the effect of changes in intravascular volume. Anemia is considered clinical when DO2 is unable to meet oxygen consumption (VO2) leading to tissue hypoxia, increasing serum lactate level, and decreasing blood pH. Patients will show compensatory signs such as tachycardia, tachypnea, and increased respiratory effort to attempt for better DO2 through improvement in cardiac output and blood oxygenation. In a gradual and chronic anemia, these compensatory mechanisms as well as physiologic and behavioural changes help maintain cardiac output and reduce oxygen consumption, allowing adequate compensation until very significant depletion of oxygen carrying capacity occurs. In acute anemia, these compensatory mechanisms do not improve oxygen delivery significantly or quickly enough. Regardless of the chronicity of the anemia, inability to compensate leads to further signs of weakness, collapse, and eventually impaired level of consciousness and death.  

Anemia can result from RBC loss, RBC destruction, or reduced RBC production. Blood can be lost through internal or external hemorrhaging. Trauma, surgical accidents, and ruptured neoplasms can cause physical damage to vessels resulting in acute or gradual hemorrhaging. Coagulation factor deficiencies, thrombocytopenia, and thrombocytopathia or hyperfibrinolysis, a state of accelerated clot removal, may render a patient unable to prevent bleeding. Parasitism can lead to external hemorrhage (fleas, ticks, lice) or internal hemorrhage (ancylostoma, uncinaria). Gastrointestinal ulcers and hemorrhagic gastroenteritis are GI-specific sources of hemorrhage.

Hemolysis can be intravascular (destruction of RBC within the blood stream) or extravascular (phagocytosis by macrophages in the spleen, liver, bone marrow, and lymph nodes). Intravascular hemolysis will result in the presence of free hemoglobin in the plasma, leading to hemoglobinemia and hemoglobinuria. Exposure to toxins that cause Heinz body formation (onion, garlic, propylene glycol, acetaminophen, vitamin K1, K3, benzocaine, copper, naphthalene, skunk musk, zinc) will stimulate removal of RBCs by the phagocytic system or cause direct lysis. Cats are more prone to Heinz body formation, but are also more forgiving towards red cells containing Heinz bodies, allowing for a longer survival time. Because of this, feline RBCs may show Heinz bodies without anemia. Hemolysis may occur with severe hypophosphatemia (<0.5mmol/L), immune-mediated hemolysis, and significantly altered blood rheology.

A reduction in RBC production can occur due to reduced levels of erythropoietin (EPO), a hormone produced by the renal interstitial fibroblasts stimulating erythropoiesis, typically occurring in kidney disease. A reduction of EPO receptors and iron exporting is seen in chronic inflammatory diseases reducing RBC production. Bone marrow dysfunction due to bacterial/viral infections, irradiation, toxicities, and marrow displacing tumours will lead to a loss of erythropoietic stem cells. Deficiency of nutrients important in Hgb or RBC production (folic acid, vitamin B12, cobalt) due to lack of intake, inhibition of metabolism, or genetic defects will lead to a reduction in production, or production of defective RBCs.
Patients with chronic kidney disease often become anemic through multiple mechanisms. EPO production by the kidneys is diminished. Other factors include uremic toxins leading to a lowered red cell half-life, hemorrhagic loss due to GI ulcers, increased bleeding tendencies due to platelet dysfunction, and inhibition of iron store release. Suppression of erythropoiesis by the parathyroid, and reduced nutrient intake, may also contribute.
Formation of dysfunctional hemoglobin species will impair Hgb function as oxygen carriers, compromising oxygen carrying capacity. Methemoglobinemia occurs when the animal is exposed to high levels of oxidative compounds (acetaminophen, phenazopyridine, skunk musk, vitamin K3, benzocaine) or genetic defects in the reducing enzyme, Cb5R. Significant methemoglobinemia manifests in chocolate-brown coloured blood. Treatment lies in eliminating the oxidative factor through diuresis and administration of medication enhancing elimination. Smoke inhalation, exposure to car exhaust, heating systems, and gasoline-powered generators, can lead to carbon monoxide toxicity, forming carboxyhemoglobin. Carboxyhemoglobin has a 50% reduction in oxygen carrying capacity, with significant amounts leading to cherry red coloured mucous membranes. Treatment is administered via oxygen therapy for competitive displacement of carbon monoxide. Ingestion of sulfur-containing chemicals can lead to sulfhemoglobinemia giving blood a green colour. This is rare, but previously reported.


Regardless of the cause of decreased hemoglobin levels or modification of hemoglobin, the primary treatment is to address the underlying cause. In the meantime, the patient may reach a point where oxygen delivery is not sufficient due to inadequate arterial oxygen content. A red cell transfusion or administration of hemoglobin-based oxygen carrier solution will help supplement the oxygen carrying capacity as the underlying cause is addressed. Because both of these options are not without risk, the need for oxygen carrying capacity supplementation should be carefully considered. Technicians with thorough knowledge of physiology, clinical signs, and treatment of hypoxemic shock will have the best chance of influencing a positive patient outcome.

This article is based on Mr. Yagi’s presentation at the International Veterinary Emergency and Critical Care Society Symposium in San Diego, CA.CVT