COPD is a group of lung disorders characterized by the obstruction of airflow in pulmonary airways. The most common cause of COPD is smoking. COPD is generally described as being predominantly caused by either emphysema pathophysiology (pink puffer) or chronic bronchitis pathophysiology (blue bloater). Many patients can have components of both. Note that we expect to see a decrease in the FEV1/ FVC ratio in patients with COPD.
The ventilation-perfusion (V/Q) ratio is the ratio between the amount of air getting to the alveoli (the alveolar ventilation, V, in ml/min) to the amount of blood being sent to the lungs (the cardiac output, Q, in ml/min). A liter of blood holds about 200 mL of oxygen and a liter of air holds about 200 mL of oxygen. This would suggest that if equal volumes of air and blood meet each other in the lungs then we would have a V/Q ratio of 1 for the optimal movement of oxygen to the blood. In reality, there is a greater movement of air in the upper portions of the lung relative to perfusion. This is because gravity pulls more blood towards the bottom of the lungs which creates a relatively greater perfusion in the bottom of the lung relative to the volume of air flow. As a result, a normal V/Q ratio is about 0.8.
COPD generally manifests with a low ventilation-perfusion ratio. However, in some instances emphysema can have a high V/Q ratio. Conditions like atelectasis, asthma, chronic bronchitis, hepatopulmonary syndrome, and conditions that cause pulmonary edema like pneumonia or left sided heart failure can create a V/Q mismatch characterized by a value less than 0.8. A low V/Q ratio is called a shunt. A shunt refers to blood that moves from the right to left side of the heart without getting adequately oxygenated and results in oxygen-poor blood being pumped throughout the body. There are other times besides a V/Q mismatch that we use the word “shunt.” A shunt may also refer to a patent foramen ovale, which is when a small opening that connects the atria of the heart that is usually sealed after birth remains open. It can also refer to a patent ductus arteriosus, which is an opening between the two major blood vessels that leave the heart that should close after birth. In both cases, oxygen-poor blood mixes with the blood being pumped into systemic circulation.
A high V/Q ratio is caused by increased dead space in the lungs. Respiratory dead space refers to air that enters the pulmonary system but does not participate in gas exchange. There are two categorizations of respiratory dead space:
- Anatomical dead space refers to air in the trachea, bronchi and bronchioles. The air in these regions is not in close enough proximity to an alveolus to actually participate in gas exchange.
- Alveolar dead space refers to alveoli that are ventilated but little gas exchange occurs. This can be due to damage or fluid retention in the respiratory membrane which decreases gas exchange because of a thickened membrane. It can also refer to a lack of blood flow through the pulmonary capillaries which would also decrease gas exchange due to decreased blood flow. Conditions that impair blood flow to a segment of the lungs include a pulmonary embolus, hypotension, or shock, all of which can cause a high V/Q ratio.
Emphysema (Pink Puffer)
Emphysema is a lung disease that manifests as an enlargement of air spaces and destruction of alveolar tissue. The tissue destruction results in the production of large air spaces next to the pleura on the surface of the lung known as blebs and large spaces within the lung parenchyma known as bullae. The two main causes of emphysema are smoking and inherited alpha-1-antitrypsin deficiency. Alpha-1-antitrypsin deficiency causes the signs and symptoms of emphysema at a young age (generally between the ages of 20 and 50). If a person with the deficiency smokes, then emphysema can be expected to occur much sooner. Air pollution and repeated respiratory tract infections can also contribute to emphysema.
Normally, alpha-1-antitrypsin is made in the liver and while traveling through the circulation of the lung it inhibits proteases that may cause excessive tissue destruction. Elastase is a protease that is particularly damaging to the lung if it is left unchecked because it digests the elastin in the alveoli and respiratory bronchiole walls. Proteases like elastase come from neutrophils, macrophages, and other inflammatory cells. Individuals who lack alpha-1-antitrypsin experience an excessive breakdown of elastin which presents with enlarged respiratory bronchioles and alveolar sacs that lack the ability to recoil (decreased elastance). This tissue damage causes the symptoms of emphysema which include dyspnea (difficult or labored breathing), shortness of breath, very reduced exercise capacity, reduced exhalation velocity and volume, and hyperinflation of the lungs.
Because elastase comes from inflammatory cells, anything that causes a chronic increase in lung inflammation can lead to more elastase that can potentiate emphysema development. Smoking appears to initiate inflammatory processes in the lungs which are followed by the influx of immune cells that can secrete elastase and other proteolytic enzymes. Alpha-1-antitrypsin would normally help protect the lung tissues during inflammation, but smoking inactivates alpha-1-antitrypsin by oxidizing essential amino acid components in the protein structure. This leads to a nearly 2000 fold decrease in alpha-1-antitrypsin activity so that it no longer effectively inhibits proteases like elastin.
There are two commonly recognized major forms of emphysema:
- Centriacinar or centrilobular emphysema is most commonly seen in smokers. Centriacinar emphysema involves the central portion of the respiratory lobule and is more often observed in the upper part of the lungs.
- Panacinar emphysema is most common in individuals with an alpha-1 antitrypsin deficiency. The panacinar version involves the peripheral portion of the respiratory lobule and is more often observed in the lower portion of the lungs.
Image by Becky T. BYU-Idaho F19
As a type of COPD you may think emphysema would cause a decreased V/Q ratio due to impaired ventilation. However, emphysema can present with a normal or even high V/Q ratio mismatch when the damaged lung parenchyma has reached a point that the alveoli clusters have merged and expanded. This causes the ventilatory volume to increase (higher V) while the capillary density remains about the same. This means there is more ventilation per perfusion and a higher V/Q ratio.
Patients with predominant emphysema have been nicknamed “pink puffers” because of their general ability to better ventilate or hyperventilate the lungs compared to those with bronchitis. However, without lung elastance it is much harder for them to exhale normally and requires contraction of accessory respiratory muscles (e.g. obliques and abdominals). The act of just breathing can take a lot of energy and these individuals tend to be thinner as a result. Also, collagen fibers within bronchiolar walls are also degraded, weakening respiratory passageways, and increasing the risk of collapse during expiration. If bronchioles collapse, this leads to air trapping which prevents ventilation of the lungs with oxygen-rich air. Individuals with emphysema will often purse their lips to create a back pressure that can help keep airways open (hence the term “puffer”). Prolonged expiration is always present for both pink puffers and blue bloaters, but can be more pronounced for pink puffers.
Image by Becky Torgerson BYU-I S18
Chronic Bronchitis (Blue Bloater)
Chronic bronchitis involves chronic infection and inflammation of the bronchioles within the lungs and is most commonly due to the effects of smoking. It is characteristic of increased mucus production, obstruction of small airways, and a chronic cough. The inflammation associated with chronic bronchitis results in hypertrophy and excess mucus production of the submucosal glands of the large respiratory airways (trachea and bronchi) as well as excess mucus production by goblet cells within the bronchiolar epithelium of the small airways. The toxins found in cigarette smoke also kill the ciliated cells that line the respiratory airways, thus preventing the removal of the increased mucus production. Without cilia, people with chronic bronchitis usually develop a productive cough, which is how they attempt to remove mucus from within the respiratory airways. The inflamed bronchioles also result in fibrosis of the bronchiolar walls which makes them more stiff and less compliant, thus compounding the diminished airway diameter due to increased mucus production. The excessive mucus retention in the airway also creates a more favorable environment for bacterial and viral infections, which occur more often in people with chronic bronchitis. Diagnosis is usually characterized by a chronic productive cough that has generally persisted for at least 3 consecutive months in the last 2 years.
COPD patients with primarily chronic bronchitis have been nicknamed “blue bloaters” due to the clinical manifestations of often being overweight and cyanotic as well as having a productive cough, respiratory infections, polycythemia, and cor pulmonale. There is generally a lower V/Q ratio for blue bloaters, which helps explain their hypoxemia and polycythemia. Note that chronic bronchitis patients can also experience air trapping, but this is compounded by excess mucus production.
Image by Austin Dean, BYU-I Spring 2016
Smoking cessation, an appropriate exercise regimen, and vaccination against influenza and pneumococcal infections all play an important role in the treatment of COPD. Beta-2 agonists, anticholinergics, and inhaled corticosteroids are also useful in the treatment of COPD because of their broncho-dilating effect. Oxygen therapy is prescribed for COPD patients when they become hypoxic and cyanotic. It is important not to administer the oxygen too fast to these patients because they have been getting used to an increased partial pressure of CO2 (PaCO2) for a long time. This often means that their O2 receptors have adapted to play a more dominant role in regulating ventilation than normal. Giving the patient too much O2 can decrease their ventilatory drive to breathe. This can cause a dangerous increase in PaCO2 levels which can cause acute respiratory acidosis.