Chronic Obstructive Pulmonary Disease (COPD), Compensatory

Measure
Parul Pahal; Sandeep Sharma1.

1
 Baptist Regional Medical Center

Last Update: September 7, 2018.

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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.
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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],
[6]: 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 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 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. Increase in carbon dioxide increases the hydrogen ions which lowers the
pH. Chemoreceptors are more sensitive to alteration in acid-base balance. Increase in arterial
carbon dioxide levels indirectly stimulates central chemoreceptors (medulla oblongata) and
directly stimulate peripheral chemoreceptors (carotid bodies and aortic arch). Chemoreceptors
are less responsive to oxygen level. 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 the
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 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 retention of carbon dioxide which is hydrated to form carbonic acid.
Carbonic acid is a weak and volatile acid which quickly dissociates to form hydrogen and
bicarbonate ions. This results in respiratory acidosis. This primary event is characterized by
increased pCO2  and 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 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 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 system (CNS) symptoms such as headache, anxiety,
sleep disturbance, and drowsiness can be seen.
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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 the 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.
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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.
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