Lung

• 1. Introduction

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  The lungs of an adult human together weigh roughly 1.3 kilograms, yet inside that modest mass hide approximately 2,400 kilometers of airways. That branching tangle ends in 300 to 500 million microscopic alveoli, each one a tiny pocket where oxygen crosses into the blood. The membrane doing that work is barely half a micrometer to two micrometers thick. It separates the air you breathe from the bloodstream by a film thinner than almost anything else in the body.

  These are the primary organs of the respiratory system, found in many animals including humans. Their job sounds simple. They pull oxygen from the atmosphere into the bloodstream, and they push carbon dioxide back out, a swap called gas exchange. But the organ that performs it is far stranger than its job description suggests.

  How does an outpouching of the early digestive tube become this vast surface? Why does the right lung carry three lobes while the left makes do with two? What happens in the first ten seconds of a newborn's life, when a fluid-filled organ takes its first breath of air? And why do creatures as different as birds, crocodiles, spiders, and lungfish all need versions of the same idea? The answers run from a fetus floating in the amniotic sac to a snail breathing through a hole called a pneumostome.

• 2. An Asymmetric Pair

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  The left lung carries an indentation called the cardiac notch, a notch cut into its border to make room for the heart that shares its space. This asymmetry runs through the whole organ. The right lung is bigger and heavier than the left, and the right has three lobes while the left has only two. Where the right lung gets a middle lobe, the left lung offers a homologous feature instead, a projection of the upper lobe called the lingula, a name that means "little tongue."

  Both lungs are conical, with a narrow rounded apex at the top and a broad concave base resting on the convex surface of the diaphragm. The apex reaches up into the root of the neck, climbing just above the level of the sternal end of the first rib. Each lung stretches from near the backbone to the front of the chest, and downward from the lower trachea to the diaphragm.

  The medial surfaces, facing the center of the chest, are pressed and grooved by their neighbors. On the right lung sit grooves for the azygos vein, the superior vena cava, the brachiocephalic artery, the oesophagus, and the inferior vena cava. The left lung carries a curved groove for the aortic arch above its hilum, with the descending aorta grooved below it. At the hilum of each lung, the blood vessels and airways pass in to form the root of the lung, alongside bronchopulmonary lymph nodes.

  Each lung sits inside a pleural sac made of two pleurae. The outer parietal pleura lines the inner wall of the rib cage, while the inner visceral pleura clings directly to the lung surface. Between them is the pleural cavity, a potential space holding a thin layer of lubricating pleural fluid that lets the walls slide over each other as you breathe, without much friction. That same visceral pleura folds inward as fissures, dividing each lung into its lobes.

• 3. The Branching Tree

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  The trachea splits at a ridge called the carina into a right and left primary bronchus. From there the airways divide and divide again, into secondary or lobar bronchi feeding each lobe, then tertiary or segmental bronchi feeding the bronchopulmonary segments. Each segment has its own bronchus and its own arterial supply, which makes it a discrete unit. A surgeon can remove one segment without seriously harming the tissue around it.

  The bronchi in the conducting zone are reinforced with hyaline cartilage that holds the airways open. As the tubes narrow into bronchioles, the cartilage disappears and smooth muscle takes over, which is why the cartilage-free terminal bronchioles are also called membranous bronchioles. This conducting zone does more than carry air. It warms incoming air to 37 degrees Celsius, humidifies it, and cleans it, trapping particles in mucus that the cilia sweep upward in a process called mucociliary clearance.

  The respiratory zone begins where terminal bronchioles branch into respiratory bronchioles. This is the start of the acinus, a terminal respiratory unit that includes the respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli, measuring up to 10 millimeters across. A secondary pulmonary lobule, the smallest part of the lung visible without aid, is likely made of between 30 and 50 primary lobules.

  The alveoli themselves are lined by two cell types. Type I cells are flat and squamous, providing 95 percent of the surface area with walls thin enough for easy gas exchange, yet they cannot divide. Type II cells cluster in the corners, secrete lung surfactant, and can divide and differentiate into type I cells to replace them. Watching over both is the alveolar macrophage, which clears away debris including stray red blood cells forced out of vessels. Connecting neighboring alveoli are tiny passages in their walls called the pores of Kohn.

• 4. Two Bloodstreams

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  The lungs receive deoxygenated blood from the heart and hand it back oxygenated, the loop known as the pulmonary circulation. But that is only half their plumbing. A separate bronchial circulation delivers oxygenated blood to the airways themselves, carried by usually three bronchial arteries leaving the aorta, two to the left lung and one to the right, branching alongside the bronchi.

  The blood volume held in the lungs averages about 450 millilitres, roughly 9 percent of the entire circulatory system's blood. That figure is not fixed. It can swing from one-half to twice the normal volume. In the event of blood loss through hemorrhage, blood stored in the lungs can partly compensate by shifting automatically into the systemic circulation.

  Nerves of the autonomic nervous system steer the airways. Parasympathetic input arrives by the vagus nerve, and when acetylcholine stimulates it, the smooth muscle of the bronchi constricts and glands secrete more. A sympathetic tone runs the other way, with norepinephrine acting on beta 2 adrenoceptors to cause bronchodilation. The act of breathing itself starts in the respiratory center of the brainstem, sending signals along the phrenic nerve from the cervical plexus down to the diaphragm.

• 5. From Foregut To First Breath

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  During the fourth week of embryogenesis, a lung bud appears below the foregut, the same tube that forms the upper digestive system. The respiratory tract grows by branching morphogenesis, the repeated splitting of each branch tip, governed largely by four genes: the signalling protein sonic hedgehog, the fibroblast growth factors FGF10 and FGFR2b, and bone morphogenetic protein BMP4. FGF10 plays the most prominent role, while sonic hedgehog inhibits it.

  At the end of the fourth week the lung bud divides into right and left primary bronchial buds. In the fifth week the right branches into three secondary buds and the left into two, which is why the lobes number three on the right and two on the left. From week 16 to week 26 the bronchi enlarge and the tissue grows richly vascularised. From the 26th week until birth, the blood-air barrier itself is established, as type I cells for gas exchange and type II cells for surfactant appear. Around the seventh month, the primitive alveoli emerge, marking the point where a premature baby could survive.

  While this happens the fetus floats in the fluid-filled amniotic sac, so the lungs do not breathe. Blood is diverted away from them through the ductus arteriosus. At birth the lungs are still filled with fetal lung fluid and are not inflated. The newborn's central nervous system reacts to the sudden change in temperature and environment, triggering the first breath within about ten seconds of delivery. The fluid is quickly absorbed or exhaled, the diversionary duct closes, and the lungs begin to respire on their own.

  The lungs arrive far from finished. At birth only around one sixth of the adult lung's alveoli are present, and their alveolar septa carry a double capillary network rather than the single network of the mature lung. The alveoli keep forming into early adulthood. Vitamin A turns out to be crucial here, since deficiency reduces the formation of the alveolar walls and alters the respiratory epithelium, predisposing the lung to disease.

• 6. More Than Breathing

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  Surfactant proteins SFTPA1, SFTPB, and SFTPC rank among the most distinctly lung-specific proteins the body makes, expressed in type II pneumocytes. Of roughly 20,000 protein-coding genes expressed in human cells, almost 75 percent show up in the normal lung, yet fewer than 20 are highly lung-specific. Among the standouts are the dynein DNAH5 in ciliated cells and the secreted SCGB1A1 protein in the mucus-making goblet cells.

  The lungs help regulate blood pressure as part of the renin-angiotensin system. The inner lining of their blood vessels secretes angiotensin-converting enzyme, ACE, which converts angiotensin I into angiotensin II. By expelling carbon dioxide, the lungs also help manage the blood's acid-base balance.

  Several blood-borne substances are excreted through the lungs, including certain prostaglandins, leukotrienes, serotonin, and bradykinin. The lungs filter small blood clots out of the veins before they can reach the arteries and cause strokes. They provide the air and airflow behind speech, along with sighs and gasps. Research even suggests the lungs play a role in producing blood platelets.

  Defence is built into the tissue itself. The respiratory mucosa secretes immunoglobulin A against infection, while goblet cells release mucus carrying antimicrobial compounds such as defensins, antiproteases, and antioxidants. Larger particles never get far. They deposit in the mouth and oropharynx, or are caught in nasal hair, leaving the deep airways protected by the steady upward beat of the cilia.

• 7. When The Tissue Fails

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  Smoking sits behind much of what goes wrong in the lung. With persistent stress from smoking, the airway basal cells become disarranged and lose the regenerative ability they need to repair the epithelial barrier. These disorganised basal cells drive the major airway changes characteristic of COPD, and under continued stress they can undergo malignant transformation. The breakdown of alveolar tissue from tobacco smoking leads to emphysema, which can grow severe enough to become COPD.

  Elastase, an enzyme that breaks down the elastin in the lung's connective tissue, can also cause emphysema. It is normally held in check by the acute-phase protein alpha-1 antitrypsin, so a deficiency in that protein lets emphysema develop. Obstructive lung diseases, which include asthma, bronchiectasis, and COPD, all share airway obstruction that limits how much air reaches the alveoli, and they are diagnosed with pulmonary function tests such as spirometry.

  Restrictive lung diseases work differently, restricting the amount of lung tissue taking part in respiration. Pulmonary fibrosis replaces working tissue with fibrous connective tissue, sometimes from occupational exposures such as coalworker's pneumoconiosis. Infections bring their own dangers, from tuberculosis as a major cause of bacterial pneumonia to an Aspergillus fumigatus infection that can form an aspergilloma in the lung. In the United States certain species of rat can transmit a hantavirus that causes untreatable hantavirus pulmonary syndrome.

  Pressure problems threaten the organ from outside. A pneumothorax, a collapsed lung, is an abnormal collection of air in the pleural space that uncouples the lung from the chest wall. Scuba divers ascending while holding their breath with fully inflated lungs can burst alveoli and leak high-pressure air into that space. Lung cancer, meanwhile, comes in two main primary types, small-cell and non-small-cell carcinomas, with smoking the major risk factor, and screening now recommended in the United States for high-risk populations.

• 8. Breathing Without Bellows

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  The lungs of birds are relatively small and fixed in size, yet they connect to eight or nine air sacs reaching through much of the body and into spaces within the bones. Air travels continuously from the rear air sacs, through the lungs, to the front sacs before being exhaled, which earns them the name "circulatory lungs" rather than the "bellows-type lungs" of most other animals. Inside run millions of tiny parallel passages called parabronchi, lined with small atria where gas exchange happens by diffusion in a cross-current process.

  Reptiles take a different path. Most have a single bronchus running down the center of each lung, with branches reaching pockets that are larger and fewer than mammalian alveoli, giving a sponge-like texture. Snakes and limbless lizards usually keep only the right lung, while amphisbaenians reverse the arrangement with a major left lung. Crocodilians use a hepatic piston method, pulling the liver back with a muscle anchored to the pubic bone called the diaphragmaticus to create negative pressure, while turtles, unable to move their ribs, push air with their forelimbs and pectoral girdle.

  Amphibians keep things simple, with balloon-like lungs where gas exchange is limited to the outer surface. They force air in by buccal pumping, lowering the floor of the mouth to fill it, then pressing the throat to drive air down. Because they can also breathe across their skin, all known lungless tetrapods are amphibians, including most salamander species and the caecilian Atretochoana eiselti, all of them small and thread-like to maximise skin surface.

  Lungs even appear in three groups of fish: the coelacanths, the bichirs, and the lungfish. The coelacanth carries a nonfunctional, unpaired vestigial lung wrapped in a fatty organ. Far from the vertebrates, some arachnids breathe through book lungs, the coconut crab uses branchiostegal lungs to survive on land, and land snails breathe through a pneumostome opening into the mantle cavity. The thread tying all of it together reaches back to simple sacs, outpocketings of the oesophagus that let early bony fish gulp air in oxygen-poor water, making the lungs of vertebrates homologous to the gas bladders of fish.