Lung histology

Hey everyone! This is Nicole from Kenhub, and welcome to our tutorial on the histology of the lung. In this tutorial, we’re going to be talking about the histology of the lower respiratory tract starting with some basic concepts so you’ll be able to make connections between the gross anatomy and the microscopic structures we’ll be discussing later. After that, we’ll start travelling down the lower respiratory tract and we’ll be discussing the histology of bronchi and how it differs from that of bronchioli.

We’ll then talk about the terminal bronchiolus, the respiratory bronchioles, and the histology of the alveoli. And then we’ll make some remarks on the distinct features and the cytology of the alveoli. With regards to clinical notes, we’ll talk about a common disease of the lower respiratory tract known as asthma, and finally, we’ll summarize the key points of this lecture. So, let’s start with the basics.

In this tutorial, we’ll be looking at a histological slide of the apex of the lung which is the top of the lung and is the region that we’re currently highlighting in green. And now we’re going to switch to the histological slide. We chose to show this slide first because we can use it to identify several distinguishing features of lung histology which will tell us that we’re looking at respiratory tissue.

So, let’s begin by talking about the appearance of this slide, and the first thing that tells you that this is lung tissue is that it looks like an expanded net of tissue over empty space. So we know that the lung fills with air and expands, and in this slide, you can see how the expansion is preserved during the preparation of histology slides – and we can see it here as an empty space, circumscribed only by thin walls forming incomplete circles around the air. These thin walls are the walls of the alveoli but don’t worry we’ll explore these structures in much more detail a little bit later in the tutorial.

So what we just saw comes in a bit of contrast to what we’re currently looking at. And this is a histological section of a fetal lung, specifically, a lung at sixteen weeks of gestation, which will put it in the pseudo-glandular phase of development. The entire air-conducting bronchial tree up to the terminal bronchioli are set down in this phase but contrary to their respiratory structures we’ll see in the following slides of the tutorial, this slide features a condensed structure which can be said to resemble other tubuloacinous glands. But let’s take a bit of a closer look at the section of the pulmonary apex.

The next elements which may catch your attention are large, hollowed out circular spaces and circular spaces filled with blood cells. So, the first group of structures that we’re looking at are collectively known as bronchi, and you may notice that some are larger than others and that as they get smaller, they’re epithelial lining tends to create folds.

The second group of structures contains the branches of the pulmonary arteries and veins, and these are the blood vessels. You can see that these vary in size. They contain no folds but can usually be discriminated from other structures due to the presence of blood cells inside of them.

Finally, there’s another element you should be able to recognize when looking at a lung slide, and this is the visceral pleural membrane, and we’re going to be switching to another image just to understand this membrane a little bit better.

So in this image, we can see that we’ve highlighted the visceral pleura, and this is the portion of the pleura covering the lungs. The visceral pleura consists of mesothelial cells, elastic tissue, and a sparse fibrocollagenous substrate mainly around the blood vessels and lymph vessels. Its role is to minimize friction between the lung and the chest wall which is also lined by another pleural membrane, the parietal pleura.

So before we proceed to discussing the different parts and the features of the bronchial tree, it’s of course best if we familiarize ourselves with the pulmonary vasculature.

So the structure that we’ve currently highlighted is the pulmonary artery, and as you can see, we highlighted the lumen with a bluish-purple color just to indicate that the pulmonary arterial vessels carry deoxygenated blood to the lungs for reoxygenation. And we can tell that this is an artery by the fact that it has relatively thick walls surrounding it, almost half the size of its lumen, and much thicker than the vessel’s endothelium. And this thickness is mostly due to the muscularis or medial layer of the vessel and, despite the fact that the pulmonary circulation handles much lower pressures than the systemic circulation, the pulmonary artery still has to deal with higher pressures than the pulmonary veins, so thus the thicker wall. And that’s probably a good time to remind you that pulmonary arteries carry deoxygenated blood from the right ventricle of the heart to the alveoli.

We’re now looking at the pulmonary veins. And if we look at the endothelium and the wall thickness again, we’ll notice that the wall is not as dense as that of the previous slide. Pulmonary veins may have thinner walls than the pulmonary arterial branches, and they also tend to be more isolated away whereas arteries tend to travel alongside bronchi. It would be difficult to compare veins to arteries in this image but we can underline the fact that veins are more isolated by not finding any bronchial structure near the highlighted vessel.

In this image, we’ve highlighted a large bronchus and we can identify bronchi by their hollow lumen, their epithelial lining, and the presence of cartilage on their walls. Let’s firstly look at the lumen of the bronchus. So when we’re looking at the cross-section of a bronchus, what we’ll see is a lumen in the shape of a circle or an ovoid. And the presence of equally spaced mucosal folds makes the lumen appear like a flower with its petals extending outward and you can see that in our image.

So if we imagine bronchi as elongated tubes, we can also imagine a central line parallel to all the walls of the tube and this is what we would consider the axis of the bronchus. And if we cut a section perpendicular to that axis, we can see the bronchial walls forming a circle around its central axis just as so it happens in the case of our image. And if we happen to look at a longitudinal section parallel to the axis of the bronchus, we may see it having a more elongated shape. And since the section would be parallel to the mucosal folds, it would not look like a flower but it would look more like the smaller bronchiole structures that we see in the surrounding area.

The next structure we’ll be discussing is the mucosa which is the innermost layer of the bronchial wall. So the mucosa lines the airway and presents a pseudostratified columnar ciliated epithelial layer as well as mucus-secreting goblet cells. The role of the mucosa is to produce mucus which lubricates the lumen of the airway and also captures inhaled exogenous air contaminants. The cilia in the epithelium then help to move the mucus against the flow of air and gravity to the mouth helping clear the airway of any contaminants.

The submucosa is located under the epithelium. It contains smooth muscle fibers, fibroblasts, and seromucous glands which secrete their products to the lumen of the bronchus. These elements are seen between discontinuous plates of hyaline cartilage like the one seen in the image. And right now the area highlighted consists mostly of fibroblasts which we can identify by their spindle-shaped nuclei.

So a distinguishing feature of bronchi is the presence of hyaline cartilage. We can see hyaline cartilage highlighted in green in our image, and this cartilage consists of chondrocytes scattered inside of matrix of type II collagen of their own creation. And it provides structural support to the bronchus and helps it maintain its shape during respiration.

Finally, you may have noticed a blood vessel near the bronchus that we were looking at and by the looks of it, it has a muscular layer and is circular in shape so this is an artery. It’s not uncommon to find arteries adjacent to bronchi. After all, the pulmonary vasculature closely follows the bronchial tree but what we’re highlighting in this slide is the artery’s tunica externa which is also known as tunica adventitia. Note that this tunica is not only covering the artery but extends beyond the artery to attach to the adjacent bronchus. And this is a common feature of the bronchial tree, the tunica externa is the outermost layer of blood vessel and its role is to anchor the blood vessel to adjacent structures.

Let’s move a little bit further down our bronchial tree. And as we do that, we can see the bronchi gradually reducing in diameter until they become bronchioli. And notice that despite being smaller, the bronchiolus we see in our image is still accompanied by a blood vessel. So we’re currently looking at the lumen of a bronchiolus, and if we look at the adjacent epithelial layer, we will notice pseudostratified columnar epithelium. Let’s now have a look at the structures surrounding the bronchiolus.

And in this image, we have highlighted the circular layer of smooth muscle which controls the shape and elasticity of the bronchiolus. And this is where we should point out that contrary to bronchi, bronchioli due to their smaller size do not need cartilage for support so their smooth muscle layer is actually pretty adequate to keep them from ballooning during inspiration and from flattening out during expiration. And another important thing to note is that bronchioli also lack submucosal glands.

Alright, as you can see, we’re starting to get a much clearer picture of alveoli so we must be looking at a higher magnification, and we can also assume that we’re near the end of the bronchial tree.

So in this image, you can see a terminal bronchiole highlighted as a whole. So, here we are, looking again at a terminal bronchiole highlighted in green, and in this illustration we can see its relationship to adjacent structures such as the respiratory bronchioles and the bronchioli. And do note that we can only see arterioles and venules here, and this mostly due to vessels thinning as they approach the end of the bronchial tree. But also due to the fact that the walls of the bronchial tree are simply getting thinner, so the blood can be oxygenated by inspired air.

Another thing you might notice about this image is that it primarily features the terminal bronchiole but it can be certainly be used to further examine bronchial anatomy and in this image, we can see the transition of bronchi to bronchioli to the terminal bronchioli. Alright, and in this image, we’re currently highlighting the lumen of the terminal bronchiole and you may see that some of the cells that are present in this lumen but this is actually an artifact of the histological preparation.

Alright, let’s have a look at the epithelium of this structure. And if we look closely at the epithelial layer, it consists of ciliated cuboidal cells and this is because terminal bronchioli have a simple layer of ciliated cuboidal cells. In addition to their simple ciliated cuboidal epithelium, the epithelium of the terminal bronchiolus also contains a specific type of cell known as club cells which are, interesting fact, originally known as Clara cells.

Club cells contain many mitochondria and abundant endoplasmic reticulum as well as large secretory vesicles; however, they do not secrete mucus. Their function is yet to be determined, although they are speculated either to contribute to the defense of the bronchiole against inspired contaminants or to be stem cells and to help regenerate the bronchiolar epithelial lining.

Finally, the terminal bronchiole is surrounded by a thin layer of smooth muscle, and you can see the smooth muscle cells with their spindle-shaped nuclei. And as you can see, this muscle is spirally arranged around the bronchiole and helps maintain the lumen open during respiration.

Alright, we’re still moving down our bronchial tree and as we keep moving, we can see that the terminal bronchioles are gradually becoming what are called respiratory bronchioles. So if you look near the highlighted area, you should notice arteries and arterioles suspended by their respiratory bronchioles by its adventitia. It’s quite difficult for respiratory bronchioles to be accompanied by an artery and pathologists can also use the features of the mucosa to identify respiratory bronchioles but this is a little bit less typical as the mucosa is sometimes damaged during the fixation or the sectioning process.

But, regardless, the mucosa of the respiratory bronchioles is similar to that of terminal bronchioles. So we’re talking about simple ciliated cuboidal epithelium with club cells, and what differs from the histology of terminal bronchioles is that the continuity of the walls of respiratory bronchioles is interrupted by alveoli as you can see here. And also that in such locations, the epithelium is replaced by squamous epithelium similar to that present in alveoli. And in this image, you can see how the epithelium thins out as we approach the alveoli.

Gas exchange takes place wherever there’s such epithelium as long as there is a convenient amount of oxygen and blood supply to that region, and at this point, we should also note that each respiratory bronchiole and the alveoli derived from it organize a functional unit for gas exchange which is known as the acinus.

And moving further distally from the respiratory bronchiole, we can see the alveolar duct. The walls of the alveolar duct are interrupted by alveoli. You can also notice an obvious bulging into the lumen of the duct and this is a typical characteristic of the alveolar duct. These knobs consist of smooth muscle and alveolar ducts branch off into two or more alveolar sacs.

Alright, again, we have highlighted its lumen with a green highlight. Alveolar sacs are clusters of independent alveoli located at the terminal part of the airway and are lined by type I alveolar epithelial cells.

So now we’re reaching the alveoli, and alveoli are the terminal part of the airway, and this is where most of the gas exchange takes place. So, as you can see, alveoli have very thin walls consisting only of a single layer of epithelial cells and in the following, we will go into further detail on the cell types found in alveoli and some distinguishing features of the alveolar wall.

So, if we take a closer look at the walls of the alveoli, we can see that some cells are thin and flattened out while others are a little bit more bulgy. The thin ones are pneumocytes type I or type I alveolar cells and the larger ones are called pneumocytes type II or type II alveolar cells. And let’s now talk about each of these.

So, type I pneumocytes are the thin cells of the walls of alveoli we previously discussed and their main function is to maintain the air-blood barrier and to allow for gas exchange. And their thin shape enables gas to easily diffuse to underlying blood vessels but also in addition to their structural support and diffusion properties, these cells also help synthesize the basal lamina of the alveolus.

So this cell we’ve now highlighted is known as a type II pneumocyte or alveolar cell and they contribute to gas exchange indirectly by secreting surfactant which is a complex of lipids and protein that helps reduce surface tension in alveoli and keeps them from collapsing. I want to talk a little bit about some structures called alveolar macrophages, and these are immune cells responsible for the defense and protection of the alveoli from foreign contaminants and microbes.

Alright, let’s leave the cytology of the alveoli behind us now and have a look at the alveolar septa.

So these septa separate adjacent alveoli and as you can see, their thickness is not uniform and this is because the septa may consist of different types of pneumocytes which is we saw before differ in thickness. Alright now, the alveoli are the site where gas exchange occurs. This gas exchange occurs when oxygen travels from the alveolar lumen to the pulmonary capillaries and the highlighted area in our image shows just that – a pulmonary capillary. So you can tell it is a blood vessel and not an alveolar septum because if you’d look at it closely, you’ll be able to see a couple of non-nucleated cells and these are red blood cells. In this image, we can see another perspective of pulmonary capillaries, and as you can see, the pulmonary capillary surrounds the alveolus like a plexus.

Alright, thanks for sticking with me throughout this tutorial. We’re almost done. I just want to take you through some clinical notes. And as we mentioned in the top of the tutorial, we were going to talk about a very common disease associated with the lungs, and that is asthma.

So, asthma is a disease characterized by hyperresponsiveness of the airways to exogenous stimuli. So what does that mean?

So, when we say hyperresponsiveness, we specifically mean the following. So, number one, the airways become inflamed and histologically, we would see that inflammation has an increase in the neutrophils, T-cells and eosinophils; and number two, the airways would become obstructed by mucus, which means that the mucous glands would hypersecrete mucus; number three would be airway edema, due to the bronchial microvasculature dilating and histologically, you can imagine this as the airway wall swelling due to an increase in interstitial fluid; and number four would be prolonged constriction of smooth muscle known as bronchospasm and triggered by the release of mediators from mast cells and basophils.

So this would mean that the walls themselves would contract.

So, we’re currently looking at the bronchiolus, however, in asthma, as you may already have noticed is a disease that is relevant throughout the bronchial tree and, of course, therefore it means it can affect any level of the parts of the lungs that we’ve seen today.

Asthma can be due to many causes; however, it’s usually caused by an inhaled allergen which the patient has already encountered in the past.

So let’s talk a little bit about pathophysiology. In the case of asthma, the allergen enters the airways and crosses the bronchial epithelium. It then interacts with receptors on the surface of mast cells which normally responds to the endogenous immunoglobulin E – and these are known as IgE receptors – and when these receptors are activated, they induce de-granulation which is a process which leads the mast cells to release the content of their granules. The mediators that are released are responsible for the pathological response we talked about earlier.

And that’s all we have to say about asthma.

Now that we finished that, let’s briefly sum up what we talked about today. Thanks for sticking with me so far.

So let’s go back to our image of the histology slide which shows a piece of lung along with the airways and the blood vessels. And today, we talked about how to identify lung tissue by recognizing the alveoli as an expanded tissue net over the slide and we contrasted this appearance to the appearance of fetal lungs which have not yet expanded. We also learned to tell arteries from veins apart and the one thing I do hope you remember from this tutorial is that arteries have thicker walls than veins do.

We started exploring the bronchial tree. So, within the bronchial tree, we started with the bronchi which we saw to be supported by strong cartilaginous walls which were lined by pseudostratified ciliated columnar epithelium and they were also accompanied by great vessels. Then we moved down the bronchial tree and we saw the diameter of the airway decreasing. The bronchi becoming bronchioli and cartilaginous walls giving way to smooth muscle support. The epithelium then progressed from pseudostratified to simple and from columnar to cuboidal as we moved further down the bronchial tree. And when we reached the terminal bronchiole, we could no longer see big blood vessels associated with the airway and we started identifying distinct cytological features like the club cells.

Eventually, we reached the respiratory bronchiole which doesn’t have a continuous wall like most proximal parts of the airway but it has a wall which also hosts alveoli. Then we discussed the acinus, which is a respiratory unit of the respiratory bronchiole and all the alveoli branching off that single bronchiole.

Leaving the bronchial tree behind us, we focused on the alveoli and we presented their cytology, their thinner type I pneumocytes and the fatter type II pneumocytes as well as the macrophages that can be found patrolling the alveolus. Then we finally closed this section by discussing other features of the alveoli such as the alveolar septa. And finally, we presented the clinical entity of asthma being a disease of the bronchial tree characterized by hyperresponsiveness of the airway.

Alright, thanks for sticking with me throughout this tutorial. Best of luck studying, and see you next time!