Introduction

Respiration is the process by which the respiratory substrate is broken down to release energy. The 2 main operating factors of cell respiration are aerobic and anaerobic respiration, where aerobic respiration requires the presence of oxygen and anaerobic respiration does not. The most common respiratory substrate is glucose, which has a 6-carbon compound. The substrate is metabolized through glycolysis, the TCA cycle, the electron transport chain, and oxidative phosphorylation. Cells can produce and store ATP through these cycles, and carbon dioxide is produced as a by-product. It is important to understand the carbon dioxide levels produced from different substrates because toxic levels can destroy the body. Healthcare professionals can recommend that a patient alter his or her diet, particularly for those with pulmonary and liver conditions, to increase the release of CO₂ and avoid respiratory fatigue and utilize it as a prognostic factor, respectively.[1] The respiratory quotient, or the respiratory ratio (RQ), is the volume of carbon dioxide released over the volume of oxygen absorbed during respiration. It is a dimensionless number used in calculating the basal metabolic rate when estimated from carbon dioxide production to oxygen absorption. Oxygen uptake is a form of indirect calorimetry and is measured by a respirometer directly at the tissue or mouth.

Respiratory Ratio

RQ = Vol CO₂ released/Vol O₂ absorbed

It is calculated for a particular substrate ie, carbohydrates, organic acid, fat, and protein. Carbohydrates are oxidized through aerobic respiration, producing an equal ratio of CO₂ release and oxygen consumption. Subsequently, the RQ for fat, protein, and anaerobe is 0.7, 0.8, and 0, respectively. If a mixture of the substrates is consumed, then the RQ ratio collectively is 0.8.[2]

Function

When inspired oxygen is collected in the alveolar sac, perfusion occurs through the alveoli's capillary network. This perfused oxygen is transported by the red blood cell to the surrounding tissues. As blood travels through the capillary bed, oxygen is released from the RBC to the respective tissue site. Concurrently, the tissue releases CO₂ through metabolic processes into the red blood cells, delivering it to the lungs.

Normal Respiration

• Vol CO₂ = 200 mL/min and Vol O₂ = 250 mL/min, resulting in 0.8 respiratory ratio

In the presence of macronutrients, oxygen is required to break down carbohydrates, fat, and protein. Carbohydrates (C₆H₁₂O₆ + 6O₂) have a 6-carbon chain and metabolize via glycolysis to form 2 pyruvate substrates, releasing CO₂ as a by-product when converting to acetyl CoA. CO2 is a by-product in the Krebs cycle when 2-carbon acetyl CoA reacts with 4-carbon citrate, producing 3 CO2 in each metabolizing cascade. Suppose the starting molecule is a fatty acid containing 12, 18, 20, or 22 carbon molecules. In that case, it goes through the process of beta-oxidation to form acetyl Co-A, which does not generate carbon dioxide. Therefore, less CO2 is generated for every oxygen consumed when using fat over carbohydrates as fuel.

Related Testing

Indirect Calorimetry

To validate RQ, it is important to calculate heat production by first measuring pulmonary gas exchange, known as indirect calorimetry. The method for measuring inspired oxygen and expired carbon dioxide is to calculate the resting energy expenditure (REE) and respiratory quotient (RQ). REE allows nutritionists to understand how much they need to feed their patients.

Respiratory Quotient and Respiratory Exchange Ratio[3]

Respiratory Exchange Ratio (RER) directly measures Vol CO₂ released/Vol O₂ absorbed at the mouth and does not require invasive procedures. On the other hand, the respiratory quotient measures directly at the tissue, requiring an arterial and venous catheter while monitoring blood pressure for optimal results.

Carbohydrates are oxidized through aerobic respiration using RER, resulting in an equal ratio of CO₂ release and oxygen consumption; this implies that 100% of carbohydrates are consumed to produce ATP.

• C₆H₁₂O₂ + 6 O₂  -> 6CO₂ + 6 H₂O + Energy
•  RQ= 6 CO₂ /6 O₂ = 1.0

When fat is oxidized and measured using RER, the outcome is reduced CO₂ production for every oxygen molecule consumed.

• C₁₆H₃₂O₂ + 23 O₂ -> 16CO₂ + 16 H₂O + Energy
• RQ= 16 CO₂ / 23 O₂ = 0.7

When protein is the respiratory substrate, it reduces CO₂ production for every oxygen molecule consumed.[4]

• C₇₂H₁₁₂N₁₈O₂₂ + 77 O₂ -> 63O₂ + 38 H₂O + Energy
• RQ= 63 CO₂ / 77 O₂= 0.9

Clinical Significance

Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a pulmonary disease that causes chronic obstruction of airflow. Chronic inflammation of the bronchioles, along with mucous production, causes them to become deformed and narrow, limiting the airflow as a person exhales. Because the patient cannot fully exhale, carbon dioxide remains in the alveoli due to the loss of elasticity of the sac. The patients suffer from shortness of breath, productive cough, respiratory acidosis, and complicated pneumonia. In 1992, a study showed that carbohydrate-rich food increases the production of CO₂, leading to an increase in respiratory rate and eventually respiratory failure. On the contrary, fat-rich meals decrease the production of CO₂, leading to reduced alveolar ventilation and minor improvement in respiration in patients who initially have an RQ ratio greater than 0.75.[5] 

Non-Insulin Dependent Weight Gain

The respiratory quotient can be used to predict weight gain in non-insulin-dependent diabetic patients. Normally, a diabetic patient has insulin-resistant receptors, which results in hyperglycemia. This prevents metabolization from occurring via glycolysis, therefore increasing lipolysis. As mentioned, an increase in lipolysis reduces the production of CO₂. A study done in 1998 demonstrated an inverse correlation between RQ ratio and serum glucose levels in non-insulin-dependent diabetes mellitus treated with oral hypoglycemic agents or insulin. Patients on the oral hypoglycemic agents with a higher BMI verified that their RQ ratio was much higher than those of average BMI. After following them for a year, a weight gain of 3 kg was noticed in 50% of the patients, and an increase in the RQ ratio. This study concluded that the RQ ratio is a valid predictor for weight gain in diabetics treated with oral agents.[6]

Nutrition Guide for Sick Patients

The indirect calorimetry and respiratory energy expenditure aids in calculating the ideal kcal patients need to consume per day, especially when unable to estimate caloric requirements, inadequate clinical response to a predicted equation, or clinical signs of over and under-feeding. Patients who are morbidly obese or suffering from sepsis have an alteration in their VCO₂ release and VO₂ consumption. For this reason, a daily RQ and indirect calorimetry are essential to optimize their diet and reduce hospital stays.[7][8]

• REE = (kcal/d)= (VO₂ x 3.94) + (VCO₂ x 1.11) x 1440