My love affair with the pleural space

The pleural space is one of the most slippery mysteries of the body. It is formed by two opposing serous membranes with a small amount of fluid in between holding the surfaces together. It is a “space” that is not really there; a sort of double negative existential wonder whose meaning seems perpetually out of reach. To deepen the mystery, when the pleural space is removed, the lungs function perfectly well. Clearly, however, the pleura and space between serve some purpose. A space that isn’t there and doesn’t have to be there; you can see why it’s so easy to love.

All animals with lungs, save one, have pleura. Swathes of articles have been written about the pleura and careers made and ruined on the back of this non‐existent space.

In this article, I share the wonders of the pleura, including interesting pieces of anatomy and physiology and some great stories from nature and history to help you to love this space that really isn’t there.

Embryology and anatomy

The pleural cavity is created between the 4–7 weeks of embryologic development and is lined by the splanchnopleure and somatopleure.1 These embryonic components of visceral and parietal pleurae develop different anatomic characteristics. Both pleurae have two layers: a superficial mesothelial cell layer facing the pleural space and an underlying connective tissue layer. A primitive body cavity with stretchable mesothelial cells endows the subsequently developed lungs with a great deal of flexibility to expand and even hyperexpand in some situations.

The pleura folds back onto itself at the hilum to form a two‐layered membrane structure: the parietal and visceral pleurae.2 The right and left pleural sacs are separate, touching each other anteriorly, opposite the second and third pieces of the sternum.3 This information could save your life if stuck in the American wilderness, so read on.

The parietal pleura lines the inner surface of the rib cage, the diaphragm inferiorly (although not completely to the lateral edge, leaving a space), and medially over the mediastinum. It derives its blood supply from the intercostal arteries, with venous drainage into the systemic circulation and, at the periphery of the rib cage and lateral hemidiaphragm, is innervated by branches of the intercostal nerves.2,3 Trauma or inflammation in these regions results in pain localised in the cutaneous distribution of those nerves.4 The central diaphragm is innervated by the phrenic nerve which explains why pain can be referred to the shoulder or neck. The irregular distribution of pleural pain has long been recognised by physicians, with Laennec (physician, flute maker, and inventor of the stethoscope) noting this.5 Pleural pain may also be referred to the abdomen by a mechanism that is not clear. Lower lobe pneumonia in children can present this way, as can pulmonary embolus.4

The visceral pleura lines the lung and is reflected on itself in the fissures. It derives its blood supply from the bronchial arteries and venous drainage through the pulmonary veins. It has no nerve supply.2,3

Between the parietal and visceral layers of the pleura is a potential space, sometimes grandiosely called the pleural cavity. It contains a small amount of fluid — a few millilitres in a normal human. Surface tension of the fluid draws the pleura together, obliterating the space.3

An anatomical curiosity that I have always enjoyed and turns out to be a good thing for respiratory physicians to know about is the Sibson fascia. At the apex of the lung, the parietal pleura merges with the Sibson fascia that “caps” the lung.2 Occasionally, a patient presents with their lung apex appearing on inspiration above and behind the clavicle. This is caused by a weakness in the fascia that allows the lung to expand superiorly, the pleura stretching with the lung. This is usually an innocuous phenomenon, making for a good party trick and alarming to worried aunts.

Physiology

Some of the functions of the pleura are known, but a unifying theory that brings the physiology together is lacking. Pleural fluid is thought to lubricate the lungs facilitating smooth movement across each other as the lung inflates and deflates. The capillary action of the fluid maintains the contact between the pleural surfaces when the recoil pressure (outwards) of the chest wall and the elastic forces of the lung (inwards) are balanced at functional residual capacity.6,7 The surface tension is disrupted in the presence of air in the pleural space (ie, pneumothorax), allowing the lung to collapse inwards.7,8 The relative forces exerted by the chest wall and elastic lung recoil and lymphatic drainage pressure contribute to the negative pleural pressure. There are competing theories for the pleural space pressure gradient, the pleural pressure being more negative at the apex and less negative at the base. The standard explanation is that the weight of the lungs (plus blood) and mediastinal contents are greater at the bases, the other that capillary forces are maximal at the apex, where the pleural fluid film is thinnest.8

Let’s consider pleural fluid homeostasis, knowledge of which helps understand various diseases of the pleural space. In a healthy adult, about 0.26 mL of fluid/kg body weight is contained within each pleural cavity.9 This fluid is produced predominantly on the parietal surface with transcellular and paracellular mechanisms contributing to a mostly protein‐free filtrate. The fluid balance is dependent on the balance of hydrostatic and oncotic pressure differences between the systemic and venous circulations and the pleural space. Absorption occurs predominantly through the mesothelial lining of the visceral pleura and into the pulmonary lymphatics, which is why conditions such as lymphangitis carcinomatosa cause pleural effusions.10 Remarkably, the flow rate of these vessels can increase by a factor of about 20 in response to increases in pleural liquid formation. Respiratory movements enhance removal of the pleural fluid by the lymphatics.11

Another model of pleural space function is one of “capillarity”, which suggests the lungs are floating in the pleural fluid. This assumes buoyancy pressures are important to consider in the complex physiology of the pleural space. This is explained by Archimedes’ hydrostatic paradox and suggests that a very large body (the lungs) can float in a minimal body of water (the pleural fluid).8,12 Eureka!

The other physiological consideration for lovers of the pleura is its mysterious role in respiratory mechanics. There is not a clearly defined role for the pleura.13 Not even the doyen of pulmonary physiology, Professor John West, knows.14 The lack of certainty is fortunate, in my mind, as it leaves lots of room for speculation and belief systems, crushing the usual rigour of science. The pleura may aid lung inflation by assisting the mechanical coupling between the lung and the chest wall, the slightly negative pleural pressure at functional residual capacity preventing atelectasis by maintaining positive transpulmonary pressure. Traditional teaching is that the actions of the diaphragm and chest wall expanding with inspiration increase the negative pleural pressure, drawing air into the lungs.14 Expiration is facilitated in the reverse, with passive chest wall and lung recoil creating a positive pleural pressure, driving air from the lungs. Cute, except that there is no space in which to create a negative pressure and when the pleural space is definitively closed after pleurodesis, respiration keeps on going. However, it is a scientific enough sounding narrative to sell to medical students for whom physiology is rapidly becoming an abstraction when compared with the grander questions, such as does the patient know they are breathing? Another theory is that the pleura serves as an elastic serous membrane to allow changes in lung shape with respiration.15

You can choose the physiology that suits you best and enjoy it!

Dysfunction

Many things can happen to the pleura. It can be breached from outside (parietal pleura) or inside (visceral pleura), allowing equalisation of air pressure with the atmosphere, causing a pneumothorax. The pneumothorax can be spontaneous or acquired. It can be small, medium or large, but no one can agree on how to measure this.16

The pleura can fill with fluid, transudative and exudative, and the difference has sunk many a student in their quest for examination glory. The pleural space can be as capricious as medical examiners and just as inconsistent. Far be it for me to torment more readers with the differences between a transudate and exudate.13 Just be aware that sometimes the fluid is chyle and in a case in which I was involved, coloured chyle —matching the colour of the liquid ingested — was noted draining into the intercostal catheter shortly after the ingestion.17,18

The pleural space can fill with air, pus, blood or chyle or a mixture of these, it doesn’t discriminate. When overfull, it squashes the pliant lungs beneath, making it hard to breathe. We don’t notice when it’s there or not there but notice when it’s full. To respiratory physicians, the lungs are our hero, Batman if you like; the pleural space is the Riddler.

Lessons from nature

Unlike most mammals, including humans, the buffalo and American bison have a single pleural space.19 The American First Nations people took advantage of this, bringing down the large animal by breaching the pleural space with a spear or arrow, creating a pneumothorax that collapsed both lungs. I first learned about this when a patient after a double lung transplant had a surveillance lung biopsy from one side and presented soon after with bilateral pneumothoraces and had bilateral drains inserted! I didn’t appreciate that the clam shell chest access for double lung transplant created a single (“buffalo”) pleural space and the patient only needed one drain. I am not the only one to have missed this point.20

Bizarre (perhaps) is the realisation that elephants don’t have a pleural space at all.21 The gap between the parietal and visceral pleura is filled with loose connective tissue. This is thought to be an evolutionary adaption to the problem of “snorkelling” in water. The weight of the water displaced by the elephant creates a large transthoracic pressure (about 150 mmHg), which would either rupture the small parietal pleural capillaries or create a large transudative pleural effusion.22,23 I will complete the story by commenting that this physiological explanation of elephant pleura is the basis of a hypothesis that the elephant evolved as an aquatic animal.23 That and the fact it has internal gonads with no gubernaculum.

Surgery across the pleural space

Intrathoracic surgery posed a great problem for surgeons long after the introduction of anaesthesia (c.1840s). Physicians had known for centuries that opening the thorax would create a pneumothorax with deflation of the ipsilateral lung.24 Doing this deliberately was unsafe and rarely attempted. The basic physiology of a negative pleural pressure was recognised, but dealing with this to enable surgery was not possible at the turn of the 20th century. German‐born Ferdinand Sauerbruch (1875–1951) solved the problem, initially, by operating on anaesthetised dogs whose bodies were in a large glass container but their heads outside, sealed with a rubber collar, and with portholes for surgical access, likewise sealed by rubber cuffs. A small pump kept the pressure in the glass container below atmospheric pressure, and he observed that the lung did not collapse.25 After operating on 80 dogs and rabbits, he created a negative pressure operating theatre for people, with the patient’s head outside, attended by the anaesthetist, and with the rest of the patient and the surgeons inside. This allowed the lung to remain inflated when the chest was open.26 In those days, spontaneous ventilation was necessary for anaesthesia. The surgical staff in the negative pressure theatre were unaffected because they could develop a more negative pleural pressure than the ambient negative pressure of the operating room (around –10 mmH₂O). This revolutionary idea allowed Sauerbruch to operate safely on patients with heart and lung problems for the first time.25 It was not long after his revolutionary idea that intubation and positive pressure ventilation during anaesthesia were developed and his negative pressure operating theatre rapidly became obsolete. Now the lungs remain inflated during thoracic surgery, as positive airway pressure obviates the need to breathe by creating a negative pleural pressure.

Famous pneumothoraces

Alexander the Great (356–323 BCE) always led his troops from the front. In the battle against the Mallians (now in Pakistan) in 326 BCE, Alexander ascended the wall of the fortified acropolis and jumped down among the enemy. He was severely wounded, an arrow piercing the left side of his thorax and passing into the lung. Air and blood breathed out of the wound. He quickly fainted, suggesting a tension pneumothorax. He was carried from the battlefield on his shield, but importantly, the arrow was not removed. It seems likely that Alexander (if he regained consciousness) and his soldiers had sufficient battlefield experience to know that the arrow should be left in place until it could be surgically removed. Once Alexander regained consciousness, he ordered the shaft of the arrow broken off and his bodyguard Perdiccas to use his own sword to enlarge the wound and gently remove the arrowhead.27 This resulted in further haemorrhage and Alexander fainted again. After that, it is not clear what interventions were instituted, but it is unlikely chest drainage was available. Alexander’s soldiers thought he had died, which is likely to have been a common result of such an injury. However, Alexander was a healthy young man and recovered fully, but his soldiers took some convincing, initially suspecting the news of his survival was wartime propaganda! Given his subsequent active lifestyle, it is likely that Alexander’s lung reinflated.

Famous empyema thoracis

Hippocrates described various techniques for diagnosing thoracic empyema including palpation, auscultation (listening for succussion noises), and lateral positioning (the infected side is heavy causing pressure when positioned “up”). He recommended various medicinal and physical cures, the last being surgical drainage, including a hollow tin tube for lavage once the pus was thin.28

King George V (of the United Kingdom) had pneumonia complicated by empyema in 1928.29 For the first time, x‐ray was performed outside of a hospital (an x‐ray machine was loaded onto a truck and brought to Buckingham Palace). The x‐ray confirmed the presence of right lower lobe pneumonia. This was in the pre‐antibiotic era and so the natural history of the infection had to play out, at least to a certain point. With the King being close to death from sepsis, the royal surgeon, Lord Dawson, established the presence of an empyema by aspirating 80 mL of pus with a needle and syringe. The King was transferred to a private hospital where the surgical team performed a thoracotomy, removing a rib to allow a sufficiently large drain to be placed, as was the standard surgical approach of the day. King George’s recovery was slow, with pus draining from his wound for 6 months and a second procedure required. At one point, rumours circulated that Ferdinand Sauerbruch was to be sent for to fix the King’s chest. I suspect British pride, and the events of 1914–1918, precluded this from happening, but it makes for a good story.

Thoracic empyema claimed the life of a number of the greats of medicine. The famous French surgeon Guillaume Dupuytren (of Dupuytren’s contracture fame) wrote about his experience of empyema and the poor results of drainage (often using a heated trocar thrust between the ribs). Dying from an empyema, he famously said: “I would rather die at the hands of God than at the hands of man under operation”.30 The great doyen of American and British medicine at the turn of the past century, Sir William Osler (1849–1919), bled to death following surgical intervention for a loculated empyema.31

Conclusion

The march of science has proceeded at double time but still left some mysteries behind. Thank heavens. It would be a pity to know everything, leaving nothing to speculate on or wonder at. Thank you pleura, both parietal and visceral and the bit in between.