Physiology, Alveolar Tension

Article Author:
Benjamin Seadler
Article Editor:
Sandeep Sharma
Updated:
9/20/2019 12:01:15 PM
PubMed Link:
Physiology, Alveolar Tension

Introduction

In the lungs, gas exchange from inspired air to the blood and vice versa occurs inside the alveoli. These microscopic structures are at the distal end of the bronchial airways. Alveoli expand during inhalation, taking in fresh oxygen, and shrink during exhalation, expelling carbon dioxide from the body.  A variety of factors, many of which are currently under research, determine the size and shape of individual alveoli.  Alveolar surface tension is one of the main components that determines whether alveoli will remain open and participate in gas exchange, or whether they will collapse.  This article will review the important elements of pulmonary anatomy, histology, and physiology which control alveolar tension.

Structure

The classical picture of the distal bronchus and its associated alveoli is that of a cluster of grapes, with each alveolus being a separate sphere from those around it.  More recent histologic research has revealed that the actual structure is much more complex. More recent literature describes the arrangement of alveoli like that of foam or froth.  Their shape is like polygons with flat sides, each alveolus sharing walls with its neighbor.  Numerous connections exist between individual alveoli, resulting in a complex system of airflow within the distal airways.[1]  The common "wall" between two neighboring alveoli is the inter-alveolar septum.  It consists of a single layer of epithelial cells inside the alveoli and a single layer of endothelial cells that make up the walls of pulmonary capillaries.  In between these layers is a variety of interstitial tissue which provides support and structure to the alveoli.[2]

Function

Alveoli are delicate structures, surrounded by walls that are at times only a few cells thick. The size of any alveolus at a specific point in time is determined by the balance between the forces that are attempting to collapse it with the forces that are trying to keep it inflated. Two of the main forces that work to collapse alveoli are the elastic properties of the lung itself and the surface tension of the water which partially occupies the inside of alveoli. These collapsing forces are crucial to exhale air after an inspiration but must be countered at end expiration to prevent the alveoli from collapsing completely.[1] One of the principal forces that prevent alveolar collapse is the extensive collagen extracellular matrix (ECM) running throughout the interalveolar septa, formed by fibroblasts in the interstitium. The ECM provides "radial traction": forces pulling in all directions away from the center of each alveolus, keeping it inflated. The other factor which prevents alveolar collapse is the presence of surfactant, produced by type II pneumocytes. Further explanation of the role of surfactant first relies on an understanding of the physical interactions of water molecules with one another.[2]

An individual water molecule composed of two hydrogen atoms and one oxygen atom is a polar structure. The electronegativity of oxygen creates a more negative charge in one side of the molecule, while the opposite side of the molecule has a more positive charge. When many water molecules are together, temporary bonds form between the negative regions on one molecule with the positive regions on its neighbor. These bonds create a force which pulls the water molecules closer and closer. This force is surface tension. When water is inside an alveolus, the surface tension on the exterior of the water collection pulls itself and the alveolus inwards. Without a mechanism to counter this collapsing force, the alveolus would collapse.[3] 

It was originally thought that the pressure needed to counter the collapsing force of surface tension was directly proportional to twice of surface tension and inversely proportional to the radius of alveoli = 2T/r. [1] This relationship is called Laplace's Law and this equation applies to spherical structures.  As mentioned previously, more recent research has discovered that alveoli are not isolated spheres with a single duct connected to them.  The alveoli have a shape that is polygonal with connections to multiple neighboring alveoli.  Given this structure, one cannot directly use Laplace's Law to calculate the collapsing force of the surface tension of water on an alveolus.  Nonetheless, the idea of pressure in a sphere being directly proportional to twice the surface tension and inversely proportional to the radius (P=2T/r) is an important one to contemplate.  As the radius of the sphere decreases, the pressure in the sphere increases as a result.   The increased pressure would cause air in the sphere to move proximally in the bronchial tree and for the sphere to collapse.  [1]

Humans, along with many other animals, possess a mechanism which serves to lower the surface tension of water within alveoli and the distal areas. Pulmonary surfactant is composed of approximately 90% lipids and 10% proteins. Type II pneumocytes secrete surfactant, and it gets metabolized by macrophages. The proteins found in surfactant play a diverse range of roles, many of which are the topic of research. They are involved in immunological defense against inhaled pathogens, mitigating interactions between other proteins and water, surfactant metabolism and homeostasis, among others.[3]  The lipids found in surfactant are mainly of phospholipid structure, a polar group on the "head" of the molecule with two nonpolar "tails" (see attached figure). As previously discussed, water is a polar molecule. Therefore, any substance which is also polar will mix easily among the molecules, so we call those substances hydrophilic. Non-polar molecules are hydrophobic. Looking at the structure of a phospholipid, it contains a hydrophilic head and two hydrophobic tails. A molecule possessing both hydrophilic and hydrophobic regions is termed amphipathic. When an amphipathic molecule mixes with water, the hydrophilic head forms temporary bonds with the charged regions of neighboring water molecules, as water would with itself. The hydrophobic tails do not form these bonds with water and therefore get pushed towards each other. The result is a sphere of surfactant molecules with their "head" regions on the outside of the sphere, facing water molecules, and the "tails" on the inside of the sphere facing each other. If one imagines a collection of water with thousands of these small surfactant "spheres" separating the neighboring water molecules it becomes easier to picture how exactly surfactant interrupts the temporary interactions of water molecules with each other, thereby lowering the surface tension. [2]

The most common of the phospholipids in surfactant is called dipalmitoylphosphatidylcholine (DPPC). While some additional lipids and proteins play a role in surface tension regulation, it is DPPC that is produced in the highest quantities by type II pneumocytes.[4]  Without its effects on the lungs, the collapsing forces on the alveoli and distal airways would overcome the forces attempting to keep them open, resulting in complete collapse and an inability to exchange gases in the lung. 

Pathophysiology

As discussed previously, surfactant is necessary to prevent the collapse of alveoli and distal airways.  Any process which interferes with the production, function, or metabolism of surfactant can have disastrous consequences on pulmonary function.  The disease first attributed to surfactant deficiency is neonatal respiratory distress syndrome, most commonly seen in premature neonates.  In these infants, the premature nature of their lungs (before 34 weeks of gestation) results in inadequate production of surfactant.  As such, their alveoli and distal airways cannot remain open, and they cannot effectively exchange oxygen for carbon dioxide.  For many years, the only hope at survival was to administer 100% oxygen and hope that the neonate's lungs would mature and produce surfactant before they died of hypoxemia or hypercapnia.[4] 

Other diseases that may be caused by or lead to abnormalities in surfactant production or function include adult respiratory distress syndrome (ARDS), alveolar proteinosis, obstructive lung diseases such as asthma and COPD, interstitial lung diseases including pulmonary fibrosis and hypersensitivity pneumonitis, infectious lung processes such as pneumonia, AIDS, and in patients who smoke.[3]

Clinical Significance

Thankfully for infants with respiratory distress syndrome, a treatment now exists to improve their pulmonary function until their lungs develop sufficiently to produce sufficient surfactant.  By administering exogenous surfactant into their lungs, the alveolar and distal airway collapse that lead to their respiratory distress is reversible. As mentioned previously, there are a wide variety of other pulmonary diseases that may cause or manifest with abnormalities in surfactant production, function, or metabolism.  Regrettably, at this time there is no routine use for exogenous surfactant in these diseases (besides neonatal respiratory distress syndrome) as it has not demonstrated clinical benefit in these patients.[4]



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References

[1] Prange HD, Laplace's law and the alveolus: a misconception of anatomy and a misapplication of physics. Advances in physiology education. 2003 Dec;     [PubMed PMID: 12594072]
[2] Knudsen L,Ochs M, The micromechanics of lung alveoli: structure and function of surfactant and tissue components. Histochemistry and cell biology. 2018 Dec;     [PubMed PMID: 30390118]
[3] Creuwels LA,van Golde LM,Haagsman HP, The pulmonary surfactant system: biochemical and clinical aspects. Lung. 1997;     [PubMed PMID: 8959671]
[4] Griese M, Pulmonary surfactant in health and human lung diseases: state of the art. The European respiratory journal. 1999 Jun;     [PubMed PMID: 10445627]