I. STRUCTURE AND FUNCTION OF THE LUNG

The lung serves to bring air and blood into close proximity for gas exchange. It has a mechanical function, in that it acts as a bellows. Therefore, the tissue of the lung must be elastic. It is impossible to squeeze all of the air out of the lung; there is always a residual volume left. The lung must also be a water-tight structure; otherwise, pulmonary edema would result.

The structures of the lung, from largest to smallest, are: trachea, bronchi, terminal bronchioles, respiratory bronchioles, alveolar ducts, and alveolar sacs. The last three of these structures comprise the acinus; each acinus is supplied by a single terminal bronchiole. Three to five acini comprise a lobule, which is about an inch in diameter. The trachea, bronchi, and terminal bronchioles merely carry or conduct air to the other structures. The terminal bronchiole, which is about 1 mm in diameter, is the last structure to serve a purely conducting role. The respiratory bronchioles both conduct air and serve in respiration. The alveolar ducts and alveolar sacs are the respiratory zone -- their main function is gas exchange. The surface for gas exchange in the lung is bigger than a football field.

The right lung has three lobes (upper, middle, and lower). The left side has 2 lobes, an upper and a lower.

Like the skin and the GI tract, the lung is exposed to the environment. Unlike the first two, however, all of the structures below the larynx are kept sterile. Particles are caught in a raft of mucus, which is swept upward by beating cilia on the lung epithelial cells (akin to "body-surfing" in a mosh pit). This is called the mucociliary escalator. This process is impeded by smoking, alcohol, etc. At the alveolar level, large numbers of alveolar macrophages help maintain sterility by ingesting invaders. Gag and cough reflexes also help keep the lungs sterile, as do immune mechanisms (e.g., IgA).

The alveolus is a very delicate, fragile structure that is easily damaged. The alveolus does not contain ciliated cells. It is lined by Type I pneumocytes, which are thin, delicate, and flattened. It also contains Type II pneumocytes, which make surfactant, a substance that keeps the alveoli from collapsing.

Functions of the lung include:

1. Ventilation (V): refers to the bringing in and distribution of a volume of air. Ventilation requires the bellows-like action of the chest wall and diaphragm. Various diseases can cause localized narrowing of the airways, impairing the distribution of air.

Neuromuscular problems affecting the chest wall and/or diaphragm can also impair ventilation, as can stiff, rigid pleura.

2. Perfusion (Q): refers to circulation of blood in the lung. Blood and gas must be brought together in a matched fashion. A mismatch is referred to as a V-Q mismatch. Whether air and blood are reaching the same areas of the lung in a matched fashion can be determined by injecting a patient intravenously with a radioactive tracer and having him or her inhale another tracer. The distributions of the radioactive materials can then be imaged radiographically.

3. Diffusion: refers to the transfer or exchange of gas across the alveoli. The surface area of the lung is larger than a tennis court.

The lung has a limited repertoire of responses to injury, so many injurious agents may result in a similar clinical picture. Responses of the lung to diffuse injury include:

1. Bronchial responses:

• Spasm (as in asthma)
• Mucus production (seen in infection, asthma, smokers)
• Fibrosis (= scarring)
• Metaplasia or neoplasia

2. Parenchymal responses:

• Self-limited inflammation
• Sustained inflammation (leading to scarring or fibrosis)
• Capillary leak (e.g., adult respiratory distress syndrome) -- the alveoli are very fine and delicate; the capillaries within are very susceptible to injury.
• Emphysema
• Neoplasia

3. "Bystander" injury: The lung is injured by emboli or foreign materials carried in the blood (such as tumor cells or foreign material introduced by IV drug abuse). The lung is like a giant sieve positioned between the venous and arterial circulations and is therefore susceptible to "catching" these materials.

A "tennis racket" model can be used to demonstrate the pathological changes that the lung can undergo. The strings of the rackets represent the walls of the alveoli and the spaces between the strings represent the air spaces within the alveoli.

Normal lung:

Alveolar filling diseases:  Air spaces become filled with liquid or cells; seen in pneumonia or pulmonary edema.

Most pneumonias are bacterial. Although they are infectious conditions, they often are not contagious. That is because many of us harbor the bacteria that cause pneumonias; it is only when resistance is weakened that these organisms can flourish.

There are different ways to classify pneumonias. One way is anatomic. In lobar pneumonia, an entire lobe of the lung is filled with exudate. In bronchopneumonia, there is a patchy distribution of infection and inflammation.

1. Bronchopneumonia: is far more common than lobar pneumonia. Tends to affect both lungs (bilateral), tends to have a patchy distribution in the lung, and tends to affect the lower lobes. This type of pneumonia is very commonly acquired by hospitalized patients (a hospital-acquired infection is called a nosocomial infection) and is a frequent cause of death in people with chronic disease. Almost any organism can cause bronchopneumonia; Staphylococcus is an especially common cause. Strep and fungi can also be causes.

2. Lobar pneumonia: is characterized by a widespread, even distribution throughout one or more lobes of the lung. This pneumonia can be bilateral, but more usually affects only one lung. It is usually "community acquired" -- that is, acquired outside of the hospital. Pleuritis often accompanies lobar pneumonia. Only a few organisms can cause this pneumonia, including Streptococcus pneumoniae (which is the same as Pneumococcus and is the most common cause), Klebsiella (also called Friedlander's bacillus), and Legionella pneumophila. The latter organism causes Legionnaire's disease. This bacillus likes wet environments, and the disease may be spread by contaminated air conditioning, cooling towers, or plumbing fixtures. Infection with Klebsiella is often associated with alcoholism. Lobar pneumonia is usually fairly amenable to treatment.

If pneumonia is associated with pain, then there is most likely also infection of the pleural membranes covering the lung. The lung itself has no pain receptors.

Double pneumonia means two lobes are involved; "walking pneumonia" means the patient is well enough that he or she is not confined to bed.

In lobar and bronchopneumonia, the air spaces of the lung become filled with inflammatory exudate (remember the inflammation lecture??) This exudate contains fibrin, neutrophils, fluid, proteins, red blood cells, etc. The blood vessels in the interstitium may be dilated. The filling of airspaces during pneumonia is called consolidation (not condensation, as your text states).

In interstitial pneumonia, the air spaces are not filled. The walls of the alveoli become inflamed, but the inflammation does not spill out into the air spaces. That is because this is a milder infection, caused by viruses or mycoplasma (not to be confused with mycobacteria). One type of mycoplasma is called "PPLO". This type of pneumonia may also be referred to as primary atypical pneumonia. Also, infections with viruses call in lymphocytes, not neutrophils (remember the immunology lecture?). Interstitial pneumonia is usually community-acquired.

Viruses that can cause pneumonia include:

• Influenza (especially influenza A)
• Parainfluenza
• Respiratory syncytial virus
• Adenovirus
• Varicella (chickenpox)
• Herpesvirus hominis
• Cytomegalovirus
• Measles virus

Even though viral pneumonias tend to be mild, a problem is that they can set the stage for subsequent, more severe bacterial infections. However, some viral pneumonias can themselves be very severe, as in the influenza epidemic that occurred around the time of WWI.

Pneumonias can also be classified by their pathogenesis (i.e., how they arose). Some situations that predispose to pneumonia are:

• Partial obstruction, e.g., due to cancer or a congenital abnormality
• Aspiration of stomach contents: infective material, acids, and food may get into the lung. Can be very damaging.
• Embolic: a relatively uncommon cause
• Immunologic: due to complexes of antibodies and antigens

 

Complications of pneumonia can include:

1. Parenchymal

• Resolution of the infection may be delayed -- perhaps the causative organism is very virulent, or the patient is weak or immunosuppressed.
• Superinfection -- the original infecting organism is killed, but another (perhaps drug-resistant) agent grows in its place.
• Organization or carnification: the lung becomes solid, inelastic and meat-like due to scarring. Like cardiac muscle, lung tissue cannot regenerate.
• d) Necrosis (may lead to formation of an abscess)

2. Pleural

• Fibrinous pleuritis - known as pleurisy, associated with chest pain
• Sterile effusion
• Empyema: accumulation of pus in the pleural cavity. Often requires surgical drainage.

3. Bacteremic: infection can spread outside the lung, leading to endocarditis, meningitis, septic arthritis, etc.

A lung abscess can form if infected tissue becomes necrotic. The necrotic material is coughed up, leaving a hole behind. This abscess becomes filled with fluid, and, often, because this is the lung, air. A "fluid-air interface" (called a meniscus) may be seen on x-ray. Because the alveoli tear easily, the material in the abscess may spill out and be coughed up. Abscesses may form with pneumonias caused by virulent organisms (e.g., staph) or may result from aspiration of vomit. This may occur if someone who has recently eaten is anesthetized or as a result of seizures or being "falling-down drunk". Staph often causes multiple abscesses that are not putrid. Abscesses that form from aspiration of vomit are often caused by anaerobic organisms from the mouth and tend to be putrid and foul-smelling.

 

IV. Respiratory infections associated with HIV

Opportunistic respiratory infections seen in AIDS or otherwise immunosuppressed patients (e.g., organ transplant patients) include:

• Pneumocystis carinii (PCP): Formerly thought to be a parasite (protozoan), but now many consider it a fungus. Isolation of AIDS patients doesn't safeguard them from infection with this organism, since we all harbor it normally. However, it only flourishes in immunocompromised individuals. PCP pneumonia is the most common cause of death in AIDS patients.
• Cytomegalovirus (CMV) -- also present in healthy individuals. New infections can be of concern during pregnancy, since this virus can cross the placenta and involve the fetus.
• Mycobacterium avium intracellulare (MAI) -- not usually present in healthy people
• Mycobacterium tuberculosis -- not usually present.
• Various fungi
• Toxoplasma -- can involve lung, but is usually more of a problem in the brain. Also can affect fetus if a woman is infected for the first time while pregnant.

CF is a genetic disease in which abnormally thick and excessive mucus is formed in the lung. This mucus plugs up the bronchi and predisposes to infection (especially with Pseudomonas, which is very difficult to treat). A condition often associated with CF is bronchiectasis, where bronchi become dilated and have a "sac-like" quality. Bronchiectasis is a manifestation of severe and persistent lung infection. Researchers are exploring the feasibility of using gene therapy to treat CF. CF patients may eventually need a lung transplant. Many other organs may be involved, but it is usually the lung that is most severely affected.

Common and important theme: obstruction (in any organ) often leads to infection. In an older person who smokes, repeated infections of the lung may indicate a blockage due to cancer.

TB is becoming an increasing health problem as drug-resistant strains are appearing. A first infection with Mycobacterium tuberculosis is asymptomatic or "silent" in some 85 to 95% of people. The only change will be a positive PPD test. This infection is called primary tuberculosis. Active infection is usually confined to a small peripheral area of the lung. The bacilli usually become walled off and dormant. The localized, chronic inflammatory lesions of primary tuberculosis are called Ghon foci. The infection may spread to regional lymph nodes. The infected nodes and the Ghon foci together form what is called the Ghon complex. In 85 to 95% of patients, the infection will progress no further than this stage.

However, the bacteria may remain dormant for years or even decades. They can then become active again if the host is weakened (from surgery, old age, AIDS, cancer, etc.), leading to post-primary TB. This is not a reinfection, but rather an activation of what is already there. In post-primary TB, the infection tends to produce large cavities in the upper lobes of the lung bilaterally; it is thought that the organisms flourish there due to the relatively high oxygen content. It usually does not reactivate where the primary Ghon foci are; these tend to occur in the middle of the lung.

Sometimes in children or in immunocompromised individuals, the first infection with TB will become spread throughout the lung or even throughout the body via the blood. This form of the disease is called miliary TB because the infected tissue looks like millet seeds (the little whitish seeds in bird seed). Each little "seed" is a granuloma. Miliary TB can occur in organs other than the lung, and it can be almost silent with respect to symptoms, especially in the elderly.

The body responds to the TB bacillus by forming granulomas to wall off the infection (refer back to the inflammation lecture). These granulomas are localized areas of inflammation containing lymphocytes, macrophages, and giant cells, which are formed when macrophages fuse together. The infected tissue may become necrotic. The type of necrosis associated with TB is called caseous necrosis, because the tissue looks like cottage cheese (caseous means cheese-like).

In a tuberculin skin test, a small amount of purified protein derivative (PPD) from M. tuberculosis is injected beneath the skin. A delayed-type hypersensitivity reaction, marked by swelling and induration 48 hours later, indicates a positive result. Some important facts about this test include:

• A positive skin test means that you've been infected with Mycobacterium tuberculosis; it says nothing about the activity of the disease.
• The test is a test for hypersensitivity (refer back to the immunology lecture); it does not necessarily mean that one is immune to TB and won't get sick. A lot of the symptoms are due to the body's response to the organism, not to toxins produced by the TB bacillus.
• BCG (Bacillus of Calmette and Guerin) is a bacterium that resembles M. tuberculosis but does not cause disease. In many other countries, live BCG is used as a vaccine to provide some partial immunity to TB. However, it is not completely effective, and inoculation with BCG means you will now have a positive skin test, rendering the skin test useless as a screening tool. For those reasons, immunization with BCG is not performed in the US.
• Repeated skin testing does not eventually produce a positive response, since the test protein that is injected is not enough to elicit an immune response on its own (it's not large enough -- see immunology lecture). However, repeated testing could boost a weak positive response.
• A persistent positive response probably requires the continued presence of living bacilli.
• The induration (hardening) seen in a positive response is due to deposition of fibrin, not to formation of a granuloma.
• Answer to student question: about 5 to 10% of people who test positive will end up sick.

Some other TB-like diseases caused by fungi are histoplasmosis, which is especially prevalent in the Ohio Valley area, and Valley Fever, which is seen in the San Joaquin Valley in the southwestern US. Valley Fever is caused by a fungus called Coccidioides, which is soil-borne organism. Most people who become infected with Histoplasma do not get sick, but some otherwise healthy people do. Fungi such as Candida, Aspergillus, etc. can cause opportunistic infections in patients who are immunocompromised or have diabetes. Unlike TB, Coccidioides, and Histoplasma, these fungi do not cause formation of granulomas.

This is abbreviated COPD (or COLD). Patients with COPD have troubling moving air out; it is difficult for them to blow out a match, for example. Both chronic bronchitis and emphysema fall under this heading. Although these two diseases are different, elements of both may co-exist within the same patient. Usually, if they co-exist, it is the bronchitis that is more clinically significant. Chronic bronchitis is also far more common than emphysema. Asthma overlaps to some degree with chronic bronchitis, but it is a distinct entity. Chronic bronchitis can exist without being classified as COPD, which is marked by obstruction of airflow. However, more severe chronic bronchitis usually does involve airflow obstruction.

Chronic bronchitis is characterized by excessive, chronic mucus production and cough in the absence of infection, and it usually results from smoking. Although the "itis" in its name implies inflammation, it is the excessive mucus production that causes the problems. Bronchitis is potentially reversible up until the point where scarring of the lung begins to occur.

Like chronic bronchitis, emphysema results from smoking. In emphysema, the internal architecture of the lung is destroyed. There is a departitioning of the lung as the walls of the acini are ruptured and destroyed. This causes collapse of remaining acini and loss of elastic recoil (as Dr. Kane demonstrated vividly with his stick and rubber band model of the lung). The lung tends to remain expanded due to loss of elasticity, leading patients with emphysema to develop big, barrel chests. Since lung tissue cannot regenerate, emphysema causes irreversible damage. Loss of the alveolar septae not only leads to loss of elastic recoil, but also to loss of surface area for gas exchange. The tethers that hold airways open are also destroyed, so airways tend to collapse upon exhalation, resulting in airway obstruction. Superimposed chronic bronchitis can make the obstruction even worse.

Emphysema is thought to result from an imbalance between enzymes that degrade lung tissue (which come from inflammatory cells -- refer back to the inflammation lecture) and enzyme inhibitors. People with a genetic deficiency of a ₁-antitrypsin (which is just another name for the a ₁-proteinase inhibitor that I mentioned in the inflammation lecture) have insufficient inhibitor to counter the action of enzymes and so are at greatly increased risk for developing emphysema even at a young age and even if they don't smoke (this is a rare cause -- cigarette smoking is a much more usual cause.) Cigarette smoking is thought to increase levels of harmful enzymes and decrease the activity of enzyme inhibitors, thus leading to disease. Unlike bronchitis, emphysema is irreversible, since the destroyed lung tissue cannot regenerate. Attempts have been made to treat smokers with enzyme inhibitors, but immunologic reactions to the foreign proteins (since they are usually obtained from animals) are a problem.

Emphysema is usually worst in the upper lobes of the lungs. Emphysema confined to the center of lobules (centrilobular) is almost always associated with chronic bronchitis, which is usually the more severe problem clinically. Deficiency in a ₁-antitrypsin leads to a more generalized, diffuse, and severe form of emphysema.

People with COPD may be classified as "pink puffers" or "blue bloaters". Pink puffers characteristically suffer from emphysema. They overbreathe because they feel that they are not getting enough air and are often thin and wasted, since a lot of energy is expended trying to breathe. They are not cyanotic. Often, respiratory failure is the end-point for these patients; the damage is irreversible , and they cannot get better. Blue bloaters are cyanotic. They do not overbreathe -- for some reason, the normal central nervous system response that would speed up respiration to compensate for the cyanosis is blunted. They are bloated because they are edematous due to right heart failure (called cor pulmonale - right heart failure due to lung disease). Blue bloaters characteristically suffer from chronic bronchitis. In chronic bronchitis, the mucus secretion and inflammation are reversible, but irreversible scarring may also occur. Many patients with COPD have reversible components of chronic bronchitis and irreversible, emphysematous components.

Pink puffers often never leave the hospital -- once they get to the stage where they require hospitalization, little can be done for them (remember, emphysema is irreversible). Blue bloaters, on the other hand, may be constantly in and out of the hospital.

In emphysema, big air-filled spaces in the lung called bullae may develop. These can be removed to try to allow the rest of the lung to expand more fully, a procedure called lung reduction surgery.

Air-containing blisters called blebs may also develop on the pleural surface of the lung. These are not associated with emphysema. The typical patient with a bleb is a young, tall, muscular person in his (or her?) 20's who is undergoing physical exertion. These blebs can be treated surgically. The blebs are due to an inherent weakness in the lung and are not uncommon. They are usually not a serious problem. In some cases, they can lead to pneumothorax (collapse of the lung) when they rupture, allowing air into the pleural space.

Pulmonary edema (fluid in the airspaces) can result from heart disease or from toxins (noncardiogenic pulmonary edema).

 C. Asthma

Asthma is a very common and very complicated disease. It is a generally reversible obstruction of the lung marked by bronchospasm and increased secretions. It may be brought on by smoking, occupational exposure to certain chemicals, cold air, following exercise, or by certain drugs, including aspirin. A lot (maybe most) of asthma is due to allergic reactions. It can be exacerbated by infections or stress. Some people have sleep-associated asthma. Asthma is due to bronchi that are hyper-reactive to these various stimuli. Asthma patients tend to have hypertrophied muscle cells in the bronchial walls and too much mucus; often inflammation is also present. This scenario can predispose to infection. Edema may also be present. It is thought that asthma patients have defective neuroregulatory mechanisms for control of bronchial tone.

Restrictive disease is so named because it restricts the ability to take a deep breath, i.e., the lung is small, contracted and cannot expand properly. Therefore, air cannot get in. Causes include:

• Chest wall stiffness or immobility (e.g., muscle paralysis, deformities): the "bellows" function of the lung is not working.
• Pleural disease (fluid - called an effusion - or widespread fibrosis encases the lung like cement)
• Lung parenchymal disease (diffuse interstitial fibrosis or scarring; diffuse infiltration without scarring; edema)

Many types of injury can lead to diffuse interstitial fibrosis, including the disease sarcoid, mineral dusts (e.g., silica and asbestos), organic dusts (e.g., household dust, animal dander, fungi), therapeutic radiation, chemical fumes, certain drugs (e.g., chemotherapeutic agents), and collagen diseases such as lupus, scleroderma, and rheumatoid arthritis. It is often idiopathic. Other terms for diffuse interstitial fibrosis include idiopathic pulmonary fibrosis, usual interstitial pneumonia (UIP), fibrosing alveolitis, honeycomb lung (because of the appearance of the lung), and Hamman-Rich syndrome.

Sarcoid (or sarcoidosis) is a mysterious disease of unknown cause that affects blacks more than whites. It is quite common and can lead to diffuse scarring in some people. It can affect may organs, especially the lungs and hilar lymph nodes. Some have speculated that it may result from some type of infection.

In diffuse interstitial fibrosis, injury leads to alveolitis, which results in cellular and connective tissue alterations and, potentially, scarring. Normally, inflammation is self-limited and does not lead to scarring. However, in diffuse interstitial fibrosis, a vicious cycle is set up wherein inflammation is self-perpetuating -- inflammation leads to tissue damage leads to more inflammation, etc. Alveolitis is thus sustained and amplified. If you don't catch the problem early enough and remove the stimulus, the disease may become self-perpetuating, even when the stimulus is gone. This self-perpetuation distinguishes diffuse interstitial fibrosis from ARDS and BOOP, which are self-limited if the patient manages to survive.

Sometimes this alveolitis has an allergic component, as in farmer's lung, caused by a reaction to moldy hay, or pigeon fancier's disease, caused by a reaction to pigeon droppings and feathers. This is called extrinsic allergic alveolitis and is uncommon.

The lung has a limited repertoire of responses to acute injury. These include the following:

• Adult respiratory distress syndrome (ARDS) (also called diffuse alveolar damage): This is a very common response of the lung to all sorts of airborne and bloodborne injury, including burns, trauma, sepsis, administration of high levels of oxygen (for example, in patients being treated for respiratory failure), inhalation of toxins, etc. The capillaries become leaky, and the air spaces fill with exudate. The exudate and damaged cells may form a thick band called a hyaline membrane that lines the air spaces. It is potentially reversible, but it is a difficult disease to treat and has a high mortality. Patients are often put on ventilators, but the fact that oxygen itself can cause ARDS makes treatment tricky. Neonatal RDS (also called hyaline membrane disease) is a similar syndrome seen in premature newborns, particularly those delivered by C-section, who have lungs that are still immature. In this case, the capillary damage and leak result from lack of sufficient surfactant to keep the air spaces open.

• Bronchiolitis obliterans organizing pneumonia (BOOP): This is a relatively nonspecific term to describe a particular pattern of lung injury, often caused by drugs, infection, or immunological reactions. It is often a catch-all term for lung conditions that are not pneumonias. BOOP is marked by inflammation and obstruction of bronchi with pneumonia and fibrosis. The fibrosis (scarring) is reversible up to a point. Formation of fibrotic tissue can be suppressed with steroids.

Miscellaneous stuff on lung injury: Pneumoconiosis is chronic inflammation of the lung due to inhalation of dusts, such as silica, asbestos, and coal dust. Irritant gases, fumes, and smoke can lead to either ARDS and edema or chronic bronchitis depending on the level of exposure. The edema is noncardiogenic; it is due rather to leakage in damaged alveoli.

Systemic hypertension is often of unknown cause. In contrast, the cause of pulmonary hypertension is often apparent. Pulmonary hypertension may result from COPD or an embolus in a lung vessel. Pulmonary hypertension can lead to spasm and thickening of the pulmonary vessels, which can result in cor pulmonale.

Pulmonary emboli often arise from thrombi that form in the leg due to immobility (refer to the blood lecture -- flow is the best anticoagulant). The lung doesn't often become infarcted (that is, the lung tissue doesn't die) as a result of a large pulmonary embolus, because the lung has a dual blood supply (as does the liver). Both the pulmonary and bronchial arteries supply blood to the lung. Death from pulmonary embolus thus is a result of the actual vessel blockage, which prevents blood from becoming oxygenated. If a patient survives an embolus, he or she can be treated with anticoagulants to try to prevent a recurrence. A saddle embolus is one that sits astride the bifurcation of the pulmonary artery. It is one of the few natural conditions that can cause instant death. An embolus in a medium-sized vessel may lead to a local, wedge-shaped infarct. Blockage of small vessels does not usually result in an infarct, but may lead to pulmonary hypertension.

Pulmonary emboli are difficult to diagnose, because they are often asymptomatic. V-Q scans (see above) may reveal areas of blocked blood flow.

The lung and the kidney share certain antigens. As a result, immune damage to the lungs and the glomerulus of the kidney often go hand-in-hand. Also, both organs are "sieves" where immune complexes can deposit. One disease that can affect both organs is Wegener's granulomatosis (see also the cardiology lecture), which is often (not always) marked by anti-neutrophil cytoplasmic antibodies (ANCA). Another disease affecting both organs is Goodpasture's syndrome, which is caused by antibodies directed against the glomerular basement membrane. One may see pulmonary hemorrhage in these diseases.

Incidence of lung cancer in the US is decreasing in men but still increasing in women. Adenocarcinoma, followed by squamous cell carcinoma, is the most common type of lung cancer. Oat cell carcinoma (also called small cell carcinoma) is rarer but very aggressive and invariably fatal. Oat cell carcinoma is seldom treated surgically, because the tumor has almost always spread by the time it is discovered. Therefore, chemotherapy is the treatment of choice. A fourth type is called large cell carcinoma. Cancers often arise in the large bronchi. Pancoast tumors arise in the apex of the upper lobes and may lead to head, neck, and arm symptoms.

Lung cancers are notorious for producing paraneoplastic syndromes, such as clubbing of the fingers (which occurs for unknown reasons and may also be associated with other conditions), or various conditions that arise from abnormal production of hormones by the tumor cells (such as enlargement of the breasts in males). Increases may also been seen in ACTH (which leads to Cushing's syndrome), parathyroid hormone, ADH, etc. Oat cell carcinomas are especially notorious for producing hormones inappropriately.

The only benign tumor of note in the lung is the hamartoma, which is a cartilaginous tumor that looks like a kernel of popcorn on x-ray. Other malignant tumors include mesothelioma, which is strongly associated with exposure to asbestos and is a cancer of the pleura, and metastatic tumors, which often lodge in the lung. The vast majority of lung tumors are malignant, and the lung is a very common site of metastasis. Another lung tumor is a bronchial adenoma, which, despite its name, is malignant.

Lung cancer can lead to pneumonia -- a common theme in pathology is that obstruction predisposes to infection. Lung cancers may also lead to formation of cavities.

Fluid accumulating in the space between the lungs and the pleura is called a pleural effusion. It may be a transudate (protein-poor fluid) arising from decreased oncotic pressure (as in cirrhosis of the liver) or increased hydrostatic pressure in the blood (as in congestive heart failure or renal failure). A protein-rich exudate may form due to neoplasia or inflammatory conditions (TB, pneumonia, infarcts, rheumatoid arthritis, lupus).

A pneumothorax occurs when air enters the pleural cavity, often from a stab wound or other trauma or a ruptured bleb or bulla. This condition is not usually immediately life-threatening. In some instances, the chest may become pumped up with air if there is a flap-like opening that allows air into the pleural space but not out, a condition that usually results from trauma and is called a tension pneumothorax. The lung cannot be expanded, and the opposite lung may be compressed as well. This condition can be life-threatening. One may treat it by inserting a needle to let the air out.