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Carbon Dioxide
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Carbon Dioxide

Carbon dioxide (CO2) is a colorless, odorless gas that is naturally present in the atmosphere. In the body, it is produced as a waste product of cellular metabolism and is transported in the blood to the lungs, where it is exhaled.

Carbon dioxide plays a crucial role in maintaining the body's acid-base balance. It helps regulate pH levels in the blood and body fluids, which is essential for normal cellular function. CO2 also plays a role in regulating blood flow and breathing rate.

Carbon dioxide (CO2) is a crucial biomarker that informs the status of various physiological processes within the human body. Understanding its definition, function, dietary sources, recommended intake, and interpretation of lab results can provide valuable insights into overall health and wellness.

Definition and Function

Definition: What is Carbon Dioxide?  [3., 9.] 

Carbon dioxide (CO2) is a colorless, odorless gas composed of one carbon atom bonded to two oxygen atoms. In human physiology, it is a byproduct of cellular metabolism and is primarily exhaled from the body.

In the human body, carbon dioxide (CO2) is produced during cellular metabolism and is transported in the bloodstream to the lungs for removal through exhalation. It plays vital roles in regulating blood pH, respiratory drive, and hemoglobin's oxygen-carrying capacity. 

Disruptions in CO2 levels can lead to physiological disturbances. 

CO2 is a byproduct of cellular respiration, where glucose and oxygen are converted into energy. 

The respiratory and circulatory systems work together to regulate CO2 levels, with gas exchange occurring in the lungs and tissues. 

CO2 also serves as a key regulator of blood pH, with excess CO2 being eliminated primarily through the lungs.

How is Carbon Dioxide Produced in the Body?  [3., 9.] 

Carbon dioxide (CO2) production in the body begins at the cellular level, primarily during the citric acid cycle, where energy from fats, sugars, and proteins is transformed into ATP, with CO2 as a byproduct. This CO2 diffuses from the cells into the bloodstream, where it is transported back to the lungs to be exhaled.

At the cellular level, CO2 is produced in the mitochondria and cytoplasm during the breakdown of glucose in the presence of oxygen, a process known as cellular respiration. The chemical equation for this process is:

C6H12O6 + 6O2 → 6CO2 + 6H2O + energy (ATP)

The CO2 produced during cellular respiration diffuses out of the cells and into the bloodstream, where it is carried in three main forms:

Dissolved CO2: About 10% of CO2 remains dissolved in the plasma or the blood's extracellular fluid matrix, maintaining a partial pressure of around 45 mmHg.

Bicarbonate (HCO3-): The majority of CO2 (about 70-80%) is transported as bicarbonate ions. CO2 combines with water in the presence of the enzyme carbonic anhydrase to form carbonic acid (H2CO3), which then dissociates into bicarbonate ions (HCO3-) and protons (H+). This reaction is reversible, allowing CO2 to be released in the lungs.

Carbaminohemoglobin: About 10-20% of CO2 binds to the amino terminus of hemoglobin and other proteins in the red blood cells to form carbaminohemoglobin. This binding is different from the site where oxygen binds to hemoglobin.

Carbon Dioxide Transport and Excretion 

CO2 transport is closely linked to oxygen delivery in the body through the Bohr and Haldane effects. The Bohr effect describes how an increase in CO2 and a decrease in pH in the blood lead to a reduced affinity of hemoglobin for oxygen, facilitating oxygen release in tissues. The Haldane effect explains how oxygenated blood has a reduced capacity to carry CO2, promoting CO2 release in the lungs.

In the lungs, CO2 is released from hemoglobin and converted back to its gaseous form to be exhaled. This process is facilitated by the reversal of the bicarbonate reaction in the red blood cells, driven by the enzyme carbonic anhydrase. The CO2 then diffuses out of the blood, through the capillary walls, and into the alveolar spaces, where it is expelled during exhalation.

CO2 also plays a crucial role in regulating blood pH. It is involved in buffering systems that maintain the acid-base balance in the body. Abnormalities in CO2 levels can lead to respiratory acidosis or alkalosis, conditions where the blood pH is imbalanced due to excess or insufficient CO2, respectively.

In summary, CO2 is produced as a byproduct of cellular respiration, transported in the blood in various forms, and ultimately expelled from the body through the lungs. It is also vital in regulating the pH of the blood, highlighting its importance in both respiratory and metabolic processes.

Effects of Diet on pH Balance and CO2 Levels [2.] 

Diet significantly influences human pH balance and carbon dioxide levels. The consumption of foods with a high acid load, such as meat, eggs, and cheese, can lead to low-grade metabolic acidosis (MA), which has various health implications. 

This condition can reduce bone mineral density, increase the risk of kidney stones, and exacerbate chronic kidney disease. It also contributes to hypercortisolism, which decreases insulin sensitivity and increases the risk of type 2 diabetes and nonalcoholic fatty liver disease. Additionally, high acid load diets can decrease muscle anabolism, increasing the risk of sarcopenia, particularly in the elderly.  [2.] 

Conversely, diets rich in fruits and vegetables, which have a negative potential renal acid load (PRAL), can help maintain a balanced pH level and reduce the risk of these health issues. 

Monitoring the acid-base balance through urinary pH measurement can be a useful non-invasive method to assess dietary acid load. 

Adjusting the diet to include more alkaline foods and reduce the intake of acidogenic foods can help maintain a healthy pH balance and reduce the risk of associated health complications.

Laboratory Assessment of Carbon Dioxide Levels

General Laboratory Testing Information and Sample Type

The laboratory assessment of CO2 levels in the body can be done through a Comprehensive Metabolic Panel (CMP) blood test, which measures the total amount of carbon dioxide in the blood, and through a urine pH test, which helps evaluate the body's acid-base balance and indirectly assess CO2 levels.

A CMP requires a blood sample, typically done via venipuncture.  Fasting is generally recommended prior to this test.  

A urine pH test is easily done as part of a standard urinalysis.  Fasting is not required, although the ordering healthcare provider may request specific procedures to obtain the sample: 

Proper hygiene preparation for a urinalysis test involves wiping the genital area clean with a provided antiseptic wipe before collecting the urine sample to minimize bacterial contamination.

It is also important to provide a clean-catch midstream urine sample to avoid contamination and ensure accurate results: a clean-catch midstream urine sample means that the person should begin urinating, pause to catch the urine in the collection container midstream, and then continue urinating to ensure the sample is free from contaminants.

6. Interpreting Test Results

Reference Range for Carbon Dioxide

It is important to consult with the laboratory company used to interpret carbon dioxide tests.  The reference range for carbon dioxide in a serum or plasma blood sample from one lab company is given as:  [1.] 

Adults: 20-29 mmol/L 

A urinalysis provides an indirect assessment of carbon dioxide levels by assessing pH or urine, which is related to the pH in the blood.  The urine pH reference range is given as:  [6.]

pH: 4.5-8

Clinical Significance of High Carbon Dioxide Levels  [10.]

Elevated CO2 levels in the blood is also known as hypercapnia.  

Hypercapnia is a condition where the partial pressure of carbon dioxide (PaCO2) in the blood rises above 45 mm Hg, leading to acid-base imbalance in the body. This can result from either an increase in CO2 production or a failure in the respiratory system to adequately eliminate CO2, often associated with hypoventilation.

Possible causes of hypercapnia include:

  • Increased metabolic production of CO2 (e.g., fever, thyrotoxicosis, sepsis, steroid use, overfeeding, metabolic acidosis, exercise)
  • Respiratory failure due to decreased respiratory drive, anatomical defects, neuromuscular issues, or increased dead space in the lungs
  • Inhalation of environmental air rich in CO2
  • Acute conditions like respiratory distress syndrome, asthma exacerbation, or COPD acute exacerbation
  • Chronic conditions like chronic obstructive pulmonary disease (COPD), obesity-hypoventilation syndrome, or central/obstructive sleep apnea
  • Neuromuscular disorders such as myasthenia gravis, poliomyelitis, or primary muscle disorders
  • Other factors like drug overdose, head or cervical cord injury, and pulmonary edema

Clinical Significance of Low Carbon Dioxide Levels  [11.] 

Hypocapnia, also known as hypocarbia, occurs when the levels of carbon dioxide (CO2) in the blood drop below the normal range of 35 mmHg, leading to respiratory alkalosis. 

This can result from either decreased CO2 production or increased CO2 loss, primarily through hyperventilation, and is regulated by the pulmonary and renal systems as well as the CO2/HCO3 pH buffering system.

Causes of hypocapnia include:

  • Central causes: head injury, stroke, hyperthyroidism, anxiety-hyperventilation, pain, fear, stress, drugs, medications such as salicylates, and various toxins.
  • Hypoxemic stimulation: hyperventilation in an attempt to correct hypoxia at the expense of CO2 loss.
  • Pulmonary causes: pulmonary embolisms, pneumothorax, pneumonia, and acute asthma or chronic obstructive pulmonary disease (COPD) exacerbations.
  • Iatrogenic causes: primarily due to hyperventilation in intubated patients on mechanical ventilation.

Biomarkers Related to Carbon Dioxide 

Bicarbonate (HCO3-): bicarbonate acts as a buffer, helping to maintain the pH balance by neutralizing excess acids in the blood.

Partial Pressure of Carbon Dioxide (PaCO2): PaCO2 indicates the amount of CO2 dissolved in the blood, with higher levels suggesting respiratory acidosis and lower levels indicating respiratory alkalosis.

pH: the pH level of blood indicates its acidity or alkalinity, with a normal range of 7.35-7.45; deviations from this range signal acidosis or alkalosis.

Anion Gap: the anion gap is the difference between the primary cations and anions in the blood, with an increased gap suggesting the presence of metabolic acidosis due to unmeasured anions.

Lactate: elevated lactate levels can indicate tissue hypoxia and lactic acidosis, a form of metabolic acidosis.

Total CO2 Content: total CO2 content, which includes bicarbonate, dissolved CO2, and carbonic acid, provides an indirect measure of the acid-base balance in the blood.

These biomarkers collectively provide a comprehensive assessment of the body's acid-base balance, helping to diagnose and monitor conditions that affect this balance.

Natural Ways to Optimize Carbon Dioxide Levels

A healthy lifestyle is the essential foundation to maintaining an optimal acid/base balance and therefore, optimal carbon dioxide levels.

Practice Controlled Breathing: techniques like slow, deep breathing or diaphragmatic breathing can help regulate respiration and maintain optimal CO2 levels.  This has been shown to upregulate protective genes that may benefit cognitive function.  [8.] 

Regular Exercise: engaging in regular physical activity improves respiratory function and enhances CO2 elimination through increased breathing efficiency.  [12.] 

Balanced Diet: a diet rich in fruits, vegetables, and whole grains supports overall metabolic health, which can help maintain proper CO2 levels.  [2.] 

Avoid Overbreathing: be mindful of not overbreathing or hyperventilating, especially during anxiety or stress, as this can lead to a rapid decrease in CO2 levels.  [4.] 

Quit Smoking: smoking can impair lung function and affect CO2 exchange; quitting smoking can help improve respiratory health and CO2 levels.  Smoking is known to alter many blood health parameters which also alter cellular metabolism, further affecting the acid/base balance in the body.  [7.]

Maintain a Healthy Weight: obesity can affect breathing patterns and lung function; maintaining a healthy weight can support optimal respiratory health and acid-base balance.  [5.] 

Stay in Well-Ventilated Areas: adequate ventilation is important to ensure a good supply of oxygen and proper elimination of CO2.

Incorporating these practices into your daily routine can help maintain healthy carbon dioxide levels in the blood and support overall respiratory health.

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What's 
Carbon Dioxide
?
Carbon Dioxide (CO2) is a natural waste product created by your body when it breaks down food to produce energy. This process, called metabolism, releases CO2 into your bloodstream, which you then breathe out. CO2 also plays a crucial role in keeping the right balance of acidity and alkalinity in your blood, making sure it's not too acidic or too basic. Additionally, CO2 helps deliver oxygen to your body's tissues. In short, CO2 is an essential part of your body's system for maintaining balance and ensuring your cells work correctly.
If Your Levels Are High
Elevated Carbon Dioxide levels might mean that your body isn't getting rid of this waste product as efficiently as it should. This could happen for various reasons, such as your lungs not working as well as they should, your body producing too much CO2, or an issue with how your body balances acids and bases. Some medications, like water pills (diuretics) or sleep aids (sedatives), could also play a role in raising CO2 levels. Possible underlying conditions that might contribute to this include lung problems like COPD, being overweight, and issues with your body's acid-base management. Keep in mind that these are just some potential causes, and there could be other factors at play.
Symptoms of High Levels
Symptoms of high levels of Carbon Dioxide may include shortness of breath, confusion, fatigue, headaches, and a flushed face.
If Your Levels are Low
If your carbon dioxide levels are lower than normal, it might mean that your body isn't making or holding onto enough CO2. This can happen if you're breathing too fast, which is sometimes caused by feeling anxious, stressed, or panicky. Low CO2 levels could also be a sign that your body isn't breaking down food properly to get energy, or it might be related to certain medications like diuretics. Additionally, long-term health issues like kidney disease could play a role, since your kidneys are important for keeping the right balance of CO2 in your body.
Symptoms of Low Levels
Symptoms of low levels of Carbon Dioxide might include shortness of breath, rapid heart rate, fatigue, confusion, and muscle twitching.

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See References

[1.] 001578: Carbon Dioxide, Total | Labcorp. www.labcorp.com. Accessed April 11, 2024. https://www.labcorp.com/tests/001578/carbon-dioxide-total

[2.] Dietary acid load: Mechanisms and evidence of its health repercussions. Nefrología (English Edition). 2019;39(4):343-354. doi:https://doi.org/10.1016/j.nefroe.2019.08.001 

[3.] Doyle J, Cooper JS. Physiology, Carbon Dioxide Transport. [Updated 2023 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532988/

[4.] Folgering H. The pathophysiology of hyperventilation syndrome. Monaldi Arch Chest Dis. 1999 Aug;54(4):365-72. PMID: 10546483. 

[5.] Lambert DC, Abramowitz MK. Obesity, Anion Accumulation, and Anion Gap Metabolic Acidosis: A Cohort Study. Kidney360. 2021 Sep 9;2(11):1706-1715. doi: 10.34067/KID.0003562021. PMID: 35372994; PMCID: PMC8785829.

[6.] Lerma E. Urinalysis: Reference Range, Interpretation, Collection and Panels. Medscape.com. Published July 3, 2019. https://emedicine.medscape.com/article/2074001-overview 

[7.] Malenica M, Prnjavorac B, Bego T, Dujic T, Semiz S, Skrbo S, Gusic A, Hadzic A, Causevic A. Effect of Cigarette Smoking on Haematological Parameters in Healthy Population. Med Arch. 2017 Apr;71(2):132-136. doi: 10.5455/medarh.2017.71.132-136. PMID: 28790546; PMCID: PMC5511531.

[8.] Moris JM, Cardona A, Hinckley B, Mendez A, Blades A, Paidisetty VK, Chang CJ, Curtis R, Allen K, Koh Y. A framework of transient hypercapnia to achieve an increased cerebral blood flow induced by nasal breathing during aerobic exercise. Cereb Circ Cogn Behav. 2023 Sep 13;5:100183. doi: 10.1016/j.cccb.2023.100183. PMID: 37745894; PMCID: PMC10514094. 

[9.] Patel S, Miao JH, Yetiskul E, et al. Physiology, Carbon Dioxide Retention. [Updated 2022 Dec 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482456/ 

[10.] Rawat D, Modi P, Sharma S. Hypercapnea. [Updated 2023 Jul 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK500012/ 

[11.] Sharma S, Hashmi MF. Hypocarbia. [Updated 2023 Feb 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493167/ 

[12.] Your lungs and exercise. Breathe (Sheff). 2016 Mar;12(1):97-100. doi: 10.1183/20734735.ELF121. PMID: 27066145; PMCID: PMC4818249.

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