Obstructive lung diseases: Pathology review

While doing your rounds, you see two individuals. First is Elsa, a 66-year-old with a history of smoking 2 packs a day for the past 35 years. She came in with progressive shortness of breath and chronic, productive cough, which appeared two and a half years ago but recently got worse. On examination, she presents with pursed-lip breathing, barrel chest, and diminished breath sounds with wheezing. Spirometry was requested, and it showed signs of moderate respiratory obstruction, including an important reduction in forced expiratory volume in one second. The other individual is James, a 7-year-old with a history of wheezing and coughing episodes that began 2 years ago. The episodes used to be only during the winter, but in the past 6 months, they increased in frequency and severity. His father has a history of asthma, and the child himself has eczema. Physical examination and spirometry was normal.

Now, both seem to have some type of obstructive lung disease. But first a bit of physiology. The respiratory tree can be divided into the conducting zone, which consists of large airways like nose, pharynx, larynx, trachea, and bronchi; and the respiratory zone, consisting of respiratory bronchioles, alveolar ducts, and alveoli. Lining the lumen of the airways you’ve got the epithelium, mostly composed of one layer of ciliated pseudostratified columnar epithelial cells up until the beginning of terminal bronchioles, where it is replaced by cuboidal cells.

The ciliated pseudostratified columnar epithelial cells have hair-like projections called cilia. The cilia are responsible for eliminating larger particles like dust that reach the terminal bronchioles by moving them towards the pharynx, where they are coughed out. The epithelium also contains the goblet cell which makes the mucus within the airway. Going deeper past that layer you’ve got the basement membrane and loose connective tissue, called the lamina propria, which together with the epithelium makes up the mucosa. Beyond the mucosa, there is smooth muscle followed by more connective tissue, and together, these two layers make up the submucosa, which is where the bronchial mucinous glands that secrete the majority of the mucus into the lumen of the bronchi live. Finally, in the bronchi, but not the bronchioles, there is a layer of cartilage below the submucosa which stiffens the bronchus and helps to keep it open.

Ok, so obstructive lung diseases are a group of conditions, characterized by obstruction of airflow, which traps air inside the lungs. Now, because the airway is narrowed down or severely obstructed, exhaled air comes out more slowly than normal, and at the end of a full exhalation, an abnormally large amount of air still remain in the lungs. This an obstructive respiratory deficit, and it’s marked by several changes which can be seen on pulmonary function tests or PFTs, like spirometry and plethysmography. Spirometry is when you breathe into a tube attached to a machine called a spirometer, which measures the amount of air you breathe in and out, and how quick you do it. Plethysmography is when you are placed inside a sealed chamber and asked to breathe through a mouthpiece, which measures the pressure generated by your breathing to calculate the amount of air inside your lungs.

Ok, so in obstructive lung diseases, first, there’s an increase in residual volume or RV, which is the amount of air left in the lungs after exhaling as much as you can, and in functional residual capacity or FRC, which is the amount of air remaining in the lungs at the end of a normal exhalation. Second, there’s a small reduction in forced vital capacity or FVC, which measures the amount of air a person can breathe out forcefully after taking as deep a breath as possible, and a significant reduction in forced expiratory volume in one second or FEV1, which measures the total amount of air that can be forcibly exhaled in the first second of the FVC test. This is because these individuals have a narrow airway, which hinders how fast air can leave the lungs. Third, there’s a decrease in the ratio of FEV1 to FVC secondary to the disproportionate decrease in FVC and FEV1. The ratio measures the amount of air a person can forcefully exhale in one second relative to the total amount of air they can exhale. Ok, so this decrease in the ratio of FEV1 to FVC is considered the hallmark of obstructive lung disease and can also be used to figure out the severity of the obstruction.

Fourth, the total lung capacity is either normal or increased, unlike restrictive lung diseases, where it almost always is decreased. The reason why TLC may increase is that in some obstructive lung diseases, like emphysema, there’s air trapping and lungs hyperinflate. TLC is calculated by adding the volume of air left in the lungs after exhalation or the residual volume with the FVC.

Fifth, there might also be a V/Q mismatch, where the V stands for ventilation, which is the air you breathe in, and the Q stands for perfusion, which is blood flow. A V/Q mismatch happens because the blood flow is normal but the lungs don’t receive enough oxygen due to airway obstruction, and this is measured by a test called a pulmonary ventilation/perfusion scan. Over time, this can lead to hypoxemia, because there’s not enough oxygen in the blood.

In order to keep the V/Q ratio constant, as the ventilation decreases, the pulmonary vessels start to constrict in order to reduce perfusion to the areas that do not participate in gas exchange. This is called hypoxic vasoconstriction, and it leads to pulmonary hypertension. Over time, pulmonary hypertension puts a strain on the right heart, and can lead to right heart failure, or cor pulmonale; which manifests as jugular venous distention, peripheral edema, and hepatomegaly due to congestion.

Finally, it’s important to assess the gas exchange, which varies, depending on the particular disease. This is done by measuring the diffusing capacity of the lungs for carbon monoxide, also known as DLCO. This test involves asking the individual to inhale a small amount of carbon monoxide and seeing how well it diffuses.

Another high yield concept is how obstructive lung disease can change the flow-volume loop which is used to show airflow on the y axis as it relates to lung volume on the x axis. So imagine taking the deepest breath you can and then exhaling it out as forcefully as possible. The volume you’re gonna exhale is the forced vital capacity, and what will be left after maximal expiration will be the residual volume. And these two combined give us the total lung capacity. Now since in most cases of obstructive lung disease, the residual volume is increased while the total vital capacity is normal or increased, the loop will typically show a shift to the left.

Okay, now let’s look at each specific disease, starting with chronic obstructive pulmonary disease or COPD. The condition is characterized by obstruction of airflow due to either chronic bronchitis or emphysema. Sometimes patients can have one or the other; however, most patients have elements of both chronic bronchitis and emphysema at the same time. In addition, the triggers of the inflammation of the airway are often the same, and include environmental triggers, like inhalation of toxic substances such as tobacco smoke, or occupational pollutants like dust and silica.

Now, chronic bronchitis is an inflammation of the tracheobronchial tree that leads to increased mucus production. So what happens is that a trigger, usually smoking, irritates the mucosa of the airways, leading to hypertrophy and hyperplasia of mucinous glands in the main bronchi and goblet cells in the bronchioles. One test that’s used post-mortem is the Reid index, which measures the ratio of the thickness of the bronchial mucinous glands layer relative to the total thickness of the wall between the epithelium and the glands. Normally, the ratio should be less than 0.3, but for people with chronic bronchitis it can be over 0.4. Now hyperplasia and hypertrophy of the mucinous glands increases mucus production in both the main bronchi and the bronchioles, which causes airway obstruction.

Usually, signs and symptoms of chronic bronchitis include productive cough due to excess mucus secretion, and wheezing from the narrowing of the airways. Crackles or rales can be heard on auscultation of the lungs, which are caused by the popping open of small airways. There’s also hypoxemia and hypercapnia, both secondary to the mucus plugs blocking air exchange.

Additionally, the obstruction of the airflow can get so bad that deoxygenated blood from the right side of the heart reaches the left side without any participation in gas exchange in the pulmonary capillaries. This is called a shunt, and it’s the reason why some people develop cyanosis, which is a blue discoloration of the skin. So a high yield fact is that these individuals are sometimes referred to as “blue bloaters”. And finally, when there’s a mucus plug obstructing the airways, there’s a high risk for pneumonia behind the obstruction. Classic symptoms of pneumonia include high fever, chills, confusion or irritability, worsening dyspnea and changes in sputum color, thickness or amount.

The other COPD is emphysema, which is the permanent enlargement and loss of elasticity of the alveolar wall secondary to alveolar injury. This is caused by irritants like tobacco smoke that triggers inflammation in the alveoli. The way this happens is that neutrophils gather and release destructive proteases like elastase which breaks down the elastin in alveolar walls, making them weaker, so the alveoli collapse during exhalation. Alveoli also lose their ability to stretch and recoil so they can’t return to their normal shape. The result is alveoli trap a tiny bit of air distal to the point of collapse.

Now, alveoli are organized in clusters, called acini. And depending on which part of the acini are affected, we can have one of three types of emphysema. The most common one is centriacinar or centrilobular emphysema and it only damages the central or proximal alveoli of the acinus. This is the pattern seen with cigarette smoking and it typically affects the upper lobes of the lungs. There is also panacinar emphysema, where the entire acinus, usually in the lower lobes, is uniformly affected, and this is often associated with alpha-1 antitrypsin deficiency. Since the alveolar neutrophils are always releasing proteases to help clear the debris, the body protects itself by releasing alpha-1 antitrypsin, which is a protease inhibitor that prevents excessive collateral damage. Now, those with alpha-1 antitrypsin deficiency have no way to stop the proteases, so they end up with damaged air sacs earlier in life, especially if they smoke, since it will attract more neutrophils to the area.

And finally we have paraseptal emphysema, in which the distal alveoli of the acinus are most affected, and this type typically affects the lung tissue on the periphery of the lobules, near the interlobular septa that separate each lobule.

When it comes to signs and symptoms, people with emphysema typically experience shortness of breath. To counteract this, patients might exhale slowly through pursed lips, which increases the pressure inside the alveoli to prevent them from collapsing. A high yield term to describe these individuals is “pink puffers” since in the earlier stages of the disease, the alveoli are still able to participate in gas exchange, and they don’t look cyanotic. Additionally, due to the air-trapping and hyperinflation of the lungs can also cause individuals to develop a barrel-shaped chest. Over time, though, as more and more alveoli are damaged, emphysema can lead to hypoxemia.

Now, COPD diagnosis is based on history, clinical findings, and a series of tests. To start with, pulmonary function tests can help detect any changes in lung volumes associated with obstructive lung disease. Next, if COPD seems likely, an inhaled bronchodilator, like albuterol is given to the person, and pulmonary function tests are measured again to see if the obstruction is reversible. Reversibility is defined as more than 12% increase in FEV1 after administering the bronchodilator. Ok so note that unlike asthma, COPD is an irreversible disease so giving a bronchodilator should not change the values too much. This means that if the FEV1 doesn’t increase by more than 12% after the bronchodilator, then COPD is the likely diagnosis. Next, it’s important to find out if the individual has predominantly chronic bronchitis, emphysema or both.