Introduction

By 2020, chronic obstructive pulmonary disease (COPD) is expected to be the third leading cause of death according to the epidemiological data.[1] Although the prognosis of these patients is improving with new treatment modalities,[2][3] the mortality in these patients is still high.

Tobacco smoking accounts for most cases of COPD in developed nations. The severity of the disease depends on the number of pack-years smoked and duration of smoking. This leads to progressive loss of lung function due to damage of air sacs.

However, in developing countries, environmental pollutants are the major cause of COPD. A significant population derives its domestic energy from biomass fuel.[4][5] This increases the burden of respiratory diseases globally. Dung cakes, residues from the agricultural crop, firewood are the commonly used biomass fuel. There are toxic fumes into the air in the form of particulate matter due to the burning of biomass fuel and consist of carbon monoxide, polyaromatic and polyorganic hydrocarbons, and formaldehyde.

Many COPD patients develop acute exacerbation and are admitted to intensive care units (ICU). Many factors affect the outcome, and one of the most important factors is the acid-base disorder occurring in COPD patients.

Function

Compensation by the body in COPD patients

Acute or Chronic Hypoxia in COPD Patients

Maintenance of ventilation-perfusion ratio by compensatory pulmonary vasoconstriction[6][7]: In COPD, the acute change that occurs immediately secondary to hypoxia is hypoxic pulmonary vasoconstriction. Alveolar dead space in COPD leads to inefficient gas exchange, which leads to a ventilation-perfusion mismatch. Therefore, the body tries to maintain the V/Q ratio by localized vasoconstriction in the affected lung areas that are not oxygenated well.

As COPD advances, these patients cannot maintain a normal respiratory exchange. COPD patients have a reduced ability to exhale the carbon dioxide adequately which leads to hypercapnia.[8][9] Chronic elevation of carbon dioxide over time leads to acid-base disorders and a shift of normal respiratory drive to hypoxic drive.

Hypercapnia and shift of normal respiratory drive to hypoxic drive to maintain respiratory hemostasis [10][11]: Carbon dioxide is the main stimulus for the respiratory drive in normal physiological states. An increase in carbon dioxide increases the hydrogen ions which lowers the pH. Chemoreceptors are more sensitive to alteration in acid-base balance. An increase in arterial carbon dioxide levels indirectly stimulates central chemoreceptors (medulla oblongata) and directly stimulates peripheral chemoreceptors (carotid bodies and aortic arch). Chemoreceptors are less responsive to oxygen levels. In COPD patients this effect is blunted as the chemoreceptors develop tolerance to chronically elevated arterial carbon dioxide level. This is when the normal respiratory drive shifts to hypoxic drive and the low oxygen level play a pivotal role in the stimulation of respiration through the chemoreceptors and maintain respiratory hemostasis. That is why the target pulse oximetry in these patients is 88% to 92%.

Renal compensation to maintain near-normal pH in COPD patients [12]: The lungs and the kidneys are the key organs responsible for keeping our body’s pH in balance. In COPD patients, kidneys compensate by retaining bicarbonate to neutralize pH.

Renal Compensation in COPD Patients to Maintain Acid-base Balance

The ph and the hydrogen ions concentration are determined by the ratio of bicarbonate/pCO2 and not by any single value. This can be explained by the Hasselbach equation.

• pH = 6.1 + log − HCO3/0.03pCO2

The metabolic disorders and respiratory disorders lead to alteration in bicarbonate and pCO2 respectively. The body tries to maintain and minimize changes in the pH by kicking in the compensatory mechanisms to keep the bicarbonate/pCO2 ratio constant. The compensation can be predicted to some extent and is based on primary metabolic or respiratory disorder.

In COPD patients, chronically elevated carbon dioxide shifts the normal acid-base balance toward acidic.[13] There is the retention of carbon dioxide which is hydrated to form carbonic acid. Carbonic acid is a weak and volatile acid that quickly dissociates to form hydrogen and bicarbonate ions. This results in respiratory acidosis. This primary event is characterized by increased pCO2 and a fall in pH on arterial blood gas analysis.

The response to acute and chronic respiratory acidosis is not to the same extent as both phases have a different compensatory mechanism. In acute hypercapnia, only 1 mEq of bicarbonate increases with every 10 mm Hg increase in pCO2. H+ ions buffering in the acute phase takes place by proteins (primarily hemoglobin) and other buffers (non-bicarbonate).

• H2CO3+ −Hb => HHb + −HCO3

The body has a mechanism to adapt to the adversities. The adjustment of the pH by the kidneys is much more effective in chronic respiratory acidosis, and it can be better tolerated as compared to the acute phase. In COPD patients with comorbidities, mixed acid-base disorders can be seen.[14]

In chronic respiratory acidosis in COPD patients, the body tries to compensate by retaining more bicarbonate to overcome acidosis. The renal compensation sets in and the kidneys adapt to excrete carbon dioxide in the form of carbonic acid and reabsorb more bicarbonate. It usually takes about 3 to 5 days for the maximum response. This helps in maintaining acid-base balance near normal and prevents the pH to become dangerously low.[15]

However, this effect is only at the blood level and not the brain. So, in long-term illness causing respiratory acidosis,[16] central nervous systems (CNS) symptoms such as headache, anxiety, sleep disturbance, and drowsiness can be seen.

Clinical Significance

COPD Patients with Renal Failure and COPD Exacerbation [17]

In these patients, the kidneys are unable to reabsorb bicarbonate to compensate for chronic respiratory acidosis. Over time, mixed respiratory and metabolic acidosis sets in causing dangerously low levels of pH. The mortality rate is much higher in these patients.

In addition, low pH can lead to deleterious effects on the heart. Low pH causes heart muscle and heart rhythm dysfunction which predisposes these patients to arrhythmias. In addition, it can also cause a drop in blood pressure.

Cautious use of Supplemental Oxygen to Prevent Hypercapnia [18]

If these patients are given supplemental oxygen that increases the saturation above 92%, it can lead to dangerously high levels of carbon dioxide that can lead to worsening respiratory acidosis. [19]

• The failure of the hypoxic drive
• Haldane effect: The increased partial pressure of oxygen in the blood displaces the carbon dioxide from hemoglobin and thereby increasing the CO2 level. [20]
• The increased partial pressure of oxygen reverses the hypoxic vasoconstriction at the pulmonary artery level which leads to the blood going to areas of lungs with no ventilation. Increasing dead space and thus increasing acidosis.
• The increased amount of oxygen displaces nitrogen, which leads to atelectasis.

Other Issues

Prognosis

Acidosis and comorbidities in COPD patients are poor prognostic indicators. At low pH, intubation and mortality rates are higher. Comorbidities, [21] especially renal failure in COPD, have a worse prognosis as the kidneys fail to compensate effectively resulting in severe acidosis in these patients and a lesser increase in bicarbonate level. [22]

Prevention of Hypercarbia Related Complications in COPD Patients

• Careful monitoring and proper management of COPD
• Smoking cessation
• Healthy lifestyle and regular exercise help prevent diseases that can worsen respiration

Enhancing Healthcare Team Outcomes

COPD is a complex disease and a cause of significant morbidity and mortality. It requires interprofessional care and the involvement of more than one subspecialties. This patient-centered approach involving a physician with a team of other health professionals, physiotherapists, respiratory therapists, dieticians, social workers, clinical psychologists, nurses, and support groups working together for the patient plays an important role in improving the quality of care in COPD patients. It not only decreases the hospital admission rates but also positively affect the disease outcome.

The family physician, based on the symptoms and smoking history, orders spirometry for determining the diagnosis and assessing the severity of the disease. The comorbidities and infections are a common cause of worsening COPD and COPD exacerbation. Therefore, the proper monitoring and management of COPD and the comorbidities are equally important in improving the survival of COPD patients. The patients with severe disease who experience exacerbations are managed in respiratory unit ICU. COPD exacerbation in patients with kidney disease needs to be treated in ICU where he/she can be taken care of by the different subspecialty physicians. On discharge, the collaboration between the hospital physicians and the family physician ensures the continuous care of the patient.

The complex management of COPD involves patient education, self-management, and pulmonary rehabilitation in addition to the above. Physicians and respiratory therapists assist with patient education, which primarily includes behavior/lifestyle modification, for example, smoking cessation, education about symptoms of COPD exacerbation, the importance of regular medications, and the proper use of prescribed medications. Self-management plan includes taking medications regularly, awareness of severe symptoms, and learning to live with their disease. Pulmonary rehabilitation is also an important intervention which not only improves dyspnea and exercises tolerance but also substantially reduces hospital admission rates. A physiotherapist can assist in pulmonary rehabilitation programs to help with exercise and overall conditioning. The nurse can assist with patient monitoring, education, and coordination of follow-up care. The pharmacist can help avoid drug-drug interactions and make recommendations in regards to appropriate therapy and dosing. Dieticians can assist patients who are overweight or underweight. Family physicians play an important role in discussing end-of-life and palliative care with the patients.

The communication between the team members taking care of the patient and regular assessment of the patient's condition helps maximize the respiratory potential of the patient and, hence cost-effectively decreases the disease burden.[23] [Level V]