Continuing Education Activity

According to epidemiological data, chronic obstructive pulmonary disease (COPD) is expected to be the third leading cause of death. Although the prognosis of affected patients is improving with new treatment modalities, the mortality in these patients is still high. Tobacco smoking accounts for most cases of COPD in developed nations. However, in developing countries, environmental pollutants are the major cause of COPD. Nearly 90% of COPD-related mortality among individuals younger than 70 years of age occurs in low- and middle-income countries. This activity reviews the causes of COPD, the options for evaluation, treatment, and prevention, and discusses the role of the interprofessional team in managing and educating patients with COPD.

Objectives:

• Explain the association between tobacco use and chronic obstructive pulmonary disease.
• Describe the association between environmental pollution and chronic obstructive pulmonary disease.
• Summarize how acid-base disorders influence chronic obstructive pulmonary disease.
• Review the compensatory mechanisms that can occur in chronic obstructive pulmonary disease.

Introduction

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

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 the duration of smoking, leading to progressive lung function loss due to alveolar damage. However, in developing countries, environmental pollutants are the major cause of COPD. Nearly 90% of COPD-related mortality among individuals younger than 70 years of age occurs in low- and middle-income countries (LMIC).[4] This increased mortality in LMIC is due to the use of biomass fuel to generate energy modes.[5][6] Specifically, residues from the agricultural crop and firewood are the commonly used biomass fuel. Due to the burning of biomass fuel, there are toxic fumes in the air in the form of particulate matter consisting of carbon monoxide, polyaromatic and poly-organic 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 in COPD patients. The function and clinical significance of COPD are discussed in this review article. The natural history, diagnosis, prognosis, and treatment of COPD are discussed in another article. 

Function

Compensation by the Body in Patients with COPD

Acute or Chronic Hypoxia in COPD Patients

Maintenance of ventilation-perfusion ratio by compensatory pulmonary vasoconstriction: 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 and 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.[7][8]

As COPD advances, these patients cannot maintain a normal respiratory exchange. COPD patients have a reduced ability to exhale carbon dioxide adequately, which leads to hypercapnia.[9][10] Over time, chronic elevation of carbon dioxide 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: Carbon dioxide is the main stimulus for the respiratory drive in normal physiological states. 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 levels. 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 maintaining respiratory hemostasis. That is why the target pulse oximetry in these patients is 88% to 92%.[11][12]

Renal compensation to maintain near-normal pH in COPD patients: The lungs and the kidneys are the key organs responsible for keeping the body’s pH in balance. In COPD patients, kidneys compensate by retaining bicarbonate to neutralize pH.[13]

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, and the Hasselbach equation can explain this.

• 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 activating the compensatory mechanisms to keep the bicarbonate/pCO2 ratio constant. The compensation can be predicted to some extent based on primary metabolic or respiratory disorders.

In COPD patients, chronically elevated carbon dioxide shifts the normal acid-base balance toward acidic.[14] 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 resulting 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 different compensatory mechanisms. In acute hypercapnia, only 1 mEq of bicarbonate increases with every 10 mm Hg increase in pCO2. H+ ions buffering in the acute phase occurs via proteins (primarily hemoglobin) and other buffers (non-bicarbonate).

• H2CO3+ −Hb => HHb + −HCO3

The body has a mechanism to adapt to adversities. Adjusting the pH by the kidneys is much more effective in chronic respiratory acidosis and can be better tolerated than in the acute phase. In COPD patients with comorbidities, mixed acid-base disorders can be seen.[15]

The body tries to compensate for chronic respiratory acidosis in COPD patients 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 maintain acid-base balance near normal and prevents the pH from becoming dangerously low.[16]

However, this effect is only at the blood level, not the brain. So, in long-term illness causing respiratory acidosis, central nervous systems (CNS) symptoms such as headache, anxiety, sleep disturbance, and drowsiness can be seen.[17]

Clinical Significance

COPD Patients with Renal Failure and Acute COPD Exacerbation 

The kidneys cannot reabsorb bicarbonate in these patients to compensate for chronic respiratory acidosis. Over time, mixed respiratory and metabolic acidosis sets in, causing dangerously low pH levels. The mortality rate is much higher in these patients.

In addition, low pH can lead to harmful 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. However, acute Hypercapnia per se due to acute COPD exacerbation does not predict increased mortality. In contrast, chronic Hypercapnia has been shown to lead to a decreased five-year survival.[18]

Cautious use of Supplemental Oxygen to Prevent Hypercapnia 

There is emerging evidence to support conservative administration of O2 (to achieve O2 saturation between 88-94%), particularly in patients hospitalized for COPD exacerbation.[19][20]

In patients with COPD, oxygen treatment can lead to an acute increase in CO2, but the effect of O2 on the hypoxic ventilatory drive is relatively small.[21] The rise in CO2 is mainly due to VQ mismatch leading to increased dead space.[22] The Haldane effect also contributes to the rise of CO2 but to a lesser degree.

Other Issues

Prognosis

Acidosis and comorbidities in COPD patients are poor prognostic indicators. At low pH, intubation and mortality rates are higher. Comorbidities, 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.[23][24]

Prevention of Hypercarbia-Related Complications in COPD Patients

• Careful monitoring and proper management of COPD
• Smoking cessation
• A 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 subspecialty to create a healthcare team. 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 a vital role in improving the quality of care in COPD patients. It not only decreases the hospital admission rates but also positively affects the disease outcome.

Based on the symptoms and smoking history, the family physician orders spirometry to determine the diagnosis and assess the disease's severity. The comorbidities and infections are common causes of worsening COPD and COPD exacerbation. Therefore, properly monitoring and managing COPD and its comorbidities are equally crucial in improving the survival of COPD patients. The patients with severe diseases who experience exacerbations are managed in the respiratory unit ICU. COPD exacerbation in patients with kidney disease needs to be treated in the ICU, where they can be taken care of by the different subspecialty physicians. On discharge, the collaboration between the hospital and the family physician ensures the continuous maintenance 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 the disease.

Pulmonary rehabilitation is also necessary to improve dyspnea and exercise tolerance and substantially reduce 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 follow-up care coordination. The pharmacist can help avoid drug-drug interactions and make recommendations regarding 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 interprofessional team members caring for the patient, accurate documentation of the patient's status, and regular assessment of the patient's condition helps maximize the respiratory potential of the patient and, hence cost-effectively decreases the disease burden.[25]