INTRODUCTION

The “simple” job of the respiratory system, which is the delivery of oxygen to vasculature in the lungs and removal of carbon dioxide, is regulated by a complex system centered in the brain. The brain stem (medulla) generates signals transmitted to both the upper airway and main and accessory respiratory muscles to control the rate and pattern of breathing. Modification of the respiratory rate and pattern can be accomplished via afferent feedback from mechanoreceptors in the lung, airway, diaphragm, and chest wall, as well as chemoreceptors (monitoring pH and partial pressures of carbon dioxide [PCO₂] and oxygen [PO₂]) located centrally and peripherally. Additionally, the cortex and subcortex (supramedullary regions) can affect respiratory rate and pattern with volition, emotion, and onset of exercise.^1,2 In other words, respiration is the only vital function that has both an automatic (brain stem) and a voluntary (cortical) component.³

Because of the extensive network of input that can affect respiratory rate and pattern, patients with disease processes not directly affecting the upper and lower airways, pulmonary parenchyma, pulmonary circulation, pleural space, or chest wall may present with clinical signs of respiratory distress, dyspnea, or tachypnea. This becomes important to the veterinarian because patients with respiratory difficulty should be evaluated for both respiratory disease and nonrespiratory “look-alikes.” Specific nonrespiratory look-alikes include respiratory compensation for a metabolic acidosis, a decrease in oxygen content (e.g., anemia, dysfunctional hemoglobin), pain, anxiety, stress, drug-induced difficulties, hyperthermia, hypovolemia, abdominal enlargement, metabolic disease, and neurologic disease. A concise history from the owner, a thorough physical examination, and appropriate diagnostic techniques should all be used concurrently to differentiate respiratory system disease from these nonrespiratory look-alikes. Multiple concurrent disease processes are common.

pH and pCO₂ RECEPTOR ACTIVATION

The most common acid-base abnormality in small animals is metabolic acidosis.⁴ Metabolic acidosis is characterized by an increased hydrogen ion concentration, decreased pH, and decreased bicarbonate ion (HCO₃⁻) concentration (see Chapter 59, Acid-Base Disturbances).⁵ Metabolic acidoses most often result from a loss of bicarbonate-rich fluid from the body, increased hydrogen ion production, or decreased renal hydrogen ion excretion. In small animal medicine, the more common processes that cause metabolic acidoses are diabetic ketoacidosis, diarrhea-induced hyperchloremic acidosis, lactic acidosis, and uremic acidosis.⁵ The normal compensatory mechanism for metabolic acidosis is to expel additional carbon dioxide via hyperventilation, as evidenced by a decrease in the partial pressure of carbon dioxide in the peripheral arterial blood (PaCO₂). This compensatory mechanism is initiated as a result of the increased number of hydrogen ions stimulating peripheral and central chemoreceptors, which in turn increases alveolar ventilation (hyperventilation).⁵

Canine patients with metabolic acidosis disorders may demonstrate increased respiratory depth and rate reflecting an attempt to normalize systemic pH by blowing off carbon dioxide. The expected compensatory respiratory response is a decrement in PaCO₂ by 0.7 mm Hg per 1 mEq/L decrease in plasma bicarbonate concentration.⁵ Although data are limited, this respiratory compensation is less commonly observed in cats.⁶

Respiratory compensation may result in characteristic patterns such as Kussmaul respirations seen with diabetic ketoacidosis; this is clinically recognized as a deep, rhythmic breathing pattern.⁵ Although this may not be classically seen in veterinary medicine, compensatory hypocapnia should be differentiated from underlying lung disease in these patients.

pO₂ RECEPTOR ACTIVATION

Oxygen-sensing receptors located in the carotid and aortic bodies are stimulated to increase respiratory rate and depth when inadequate oxygen is delivered to their sites. Under normal circumstances, central respiratory drive is modified primarily by changes in arterial PCO₂, which leads to an increase in the hydrogen ion concentration. However, hypoxemia becomes the primary stimulation for ventilation when the partial pressure of oxygen in the peripheral arterial blood drops below 50 mm Hg (PaO₂ <50 mm Hg).⁷

Recall that the formula to determine arterial oxygen content (CaO₂) is:

Patients with anemia, hypovolemia, pericardial tamponade, or other types of blood flow obstruction (e.g., severe abdominal distention with gastric dilatation-volvulus) may appear tachypneic in an attempt to increase oxygen delivery. A decrease in oxygen delivery to chemoreceptors in the carotid and aortic bodies will stimulate an increase in respiratory rate and depth in order to deliver more oxygen to the alveoli for gas exchange. Clinically, this increase in respiratory rate and effort may result in a decrease in PaCO₂, even with coexisting pulmonary parenchymal disease, because carbon dioxide is 20 times more diffusible than oxygen, and is characterized by a steep dissociation curve.⁷ Anemia, whether from decreased production, blood loss, destruction, or sequestration, will significantly affect oxygen-carrying capacity and the delivery of oxygen to PO₂ chemoreceptors. In animals with acute blood loss, cardiac output is increased in an attempt to increase oxygen delivery by increasing heart rate and stroke volume; this is seen clinically as signs of hypovolemic shock. In chronically anemic patients, compensation occurs via increases in cardiac output or changes in the affinity of hemoglobin for oxygen.⁸

Patients with altered hemoglobin-oxygen binding, including methemoglobinemia (e.g., acetaminophen toxicity) or carboxyhemoglobinemia (e.g., carbon monoxide poisoning, smoke inhalation), will have a decreased SaO₂. It is important to recognize that pulse oximetry is inaccurate with dysfunctional hemoglobin.

Finally, patients with underlying heart disease may have an increased respiratory rate and altered respiratory pattern due to a decrease in cardiac output. Clinically this should be distinguished from primary respiratory disease (e.g., pleural effusion, pulmonary edema), which may also be present. In summary, patients with decreased oxygen delivery from either anemia or hypovolemia may have a component of tachypnea or dyspnea from carotid and aortic receptor stimulation or from simultaneous anatomic respiratory disease.