The lung is, just like the intestines or the skin, an organ that has direct contact with the outside world. Its function is the basis of our existence: gas exchange via diffusion. In order to perform this enormous task each and every second of our life, it needs a transport system for waste gases and fresh air; a room in which the walls are thin enough for gas diffusion, and the transport services for gases in chemical bonds. Since histologists always take a very close look, you can read here how these tasks are carried out by these complex structures – breathtaking!
schematic picture of the lung pleura

Image:" The Lung Pleurea" by OpenStax College. License: (CC BY 3.0)

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General Principles of Airway Structures

Conducting passages of the human respiratory system

Image: “Conducting passages of the human respiratory system” by Lord Akryl. License: (Public Domain)

The airways are lined with a special kind of mucosa and are held open by reinforcements in their wall. The upper airways (nasal cavity and pharynx) are surrounded by bones; the wall of the lower airways contains a support frame made out of cartilage.

The mucosa (tunica mucosa) consists of the epithelial lamina, the lamina propria made out of connective tissue, and it holds the characteristic respiratory epithelium: ciliated pseudostratified columnar epithelium with goblet cells.

Location and Structure of Trachea and Main Bronchi

Below the glottis, the lower airways begin. The trachea is a long tube that runs from larynx to its bifurcation into the two main bronchi at the fourth/fifth thoracic vertebra. The right main bronchus (bronchus principalis dexter) supplies the right lung with its three lobes; the left main bronchus (bronchus principalis sinister) supplies the left lung with its two lobes. All in all, the bronchi bifurcate into smaller and smaller branches 23 times until reaching the alveoli.

The trachea is divided into a neck and a thoracic portion and is situated ventrally of the esophagus.

Main bronchi and trachea have a support frame consisting of 16-20 C- or hoof-shaped hyaline cartilage rings. Dorsally, these rings are open but the trachea is kept close by a connective tissue wall with embedded transversally running muscle fibers, called paries membranaceus. In longitudinal orientation, the cartilage rings are connected with each other by annular ligaments.

The whole support frame is referred to as the tunica fibro-musculo-cartilaginea.

Note: The structure of the trachea is relatively simple if one has understood the three-layered structure of the wall!

Microscopic Structure of the Trachea

Trachea Anatomy

Image: “Traecha” by BruceBlaus. License: (CC BY 3.0)

The wall of the trachea consists of three layers:

First layer of the trachea

Tunica mucosa: The inner layer of the mucosa carries respiratory epithelium (with the exception of the bifurcation: non-cornified squamous epithelium). In the lamina propria, there are sero-mucous glands (tracheal glands). The mucosa is rich in afferent nerve fibers (cough reflex).

Second layer of the trachea

Tunica fibro-musculo-cartilaginea: The most prominent structure in this layer is the hyaline cartilage ring, which has a strong perichondrium. The horizontally running tracheal muscle in the paries membranaceus closes the gap that the cartilage rings leave open dorsally. Contraction of the tracheal muscle results in a change in tracheal caliber due to the horizontal orientation of the muscle fibers.

The annular ligaments connect the cartilage rings with each other. In this layer, there also are a lot of elastic fibers in a longitudinal orientation. This makes the trachea and the main bronchi elastic tubes in the longitudinal dimension and capable of adapting to movement in the surroundings.

Third layer of the trachea

Tunica adventitia: This loose layer of connective tissue connects the trachea to its surrounding structures but also ensures movability of the trachea for the processes of swallowing and coughing.

Excursus: Tracheomalacia

An enlarged thyroid gland (struma) can obstruct the trachea. As a consequence, tracheomalacia can occur, which is characterized by softening of the cartilage rings and, hence, an enormous loss in stability.

Note: It is almost impossible to confuse the extrapulmonary airways (trachea and main bronchi) with other hollow organs in histological pictures if you remember its particular characteristics: macroscopy (cartilage rings), respiratory epithelium almost everywhere, and sero-mucous glands. This combination cannot be found in other hollow organs!
schematic picture of the lung pleura

Image:” The Lung Pleurea” by OpenStax College. License: (CC BY 3.0)

Preliminary Remark

The lung is located in the pleural cavity. The lobes of the lung are covered with the visceral pleura (pleura pulmonalis), which is in contact with the parietal pleura. Physiologically, adhesion between the two serous sheets is ensured by fluid in the pleural cavity. This thin layer of fluid keeps them together via capillary adhesion. This way, the surface of the lung can be moved against the thoracic walls, but cannot be separated from it. It has to follow all its movements.

Due to a lot of elastic fibers, the lung always tends to contract. The fibers are under constant tension and would reduce the lung to a fist-sized structure if the adhesion between lung surface and thoracic wall disappeared (pneumothorax; collapsing to the minimal volume).

Basically, the lung consists of the branches of the bronchial tree up to the air sacs (alveoli, end section of the bronchial tree) and the branches of the pulmonary arteries and veins. The latter are located intrapulmonarily (upper airways, trachea, and main bronchi are extrapulmonary).

The branching of the bronchi follows a dichotomous pattern, which means that two smaller branches arise from a larger one. From the trachea to the alveoli, the human lung is estimated to branch 21 to 23 times. Roughly 15 of these divisions form the air conducting part of the lung, the remaining ones include the respiratory bronchioles and the alveolar duct which is the gas exchanging part.

The main bronchi split into lobe bronchi (bronchi lobares; three on the right, two on the left) after they enter the lung and lie extrapulmonarily.

The lobe bronchi then split dichotomously inside the lung into segmental bronchi (bronchi segmentales). From this point on, the dichotomous splitting of the bronchi often occurs in an irregular manner: One branch gives rise to two unequal ones. The stronger one of these runs in the same direction as the large one did, while the other one makes a turn and can eventually run into the opposite direction with its following branches (hence, there are terminal branches and alveoli in central areas of the lung).

Segmental bronchi split into middle and small bronchi. The small bronchi become the terminal bronchioles and then the respiratory bronchioles. The last branchings form the alveolar duct and the alveoli.

Here is an overview of the branching of the bronchial tree:

  • Segmental bronchi
  • Bronchi
  • Bronchioles
  • Terminal bronchioles
  • Repiratory bronchioles
  • Alveolar duct and sacculus

Wall Structure of Intrapulmonary Airways

Bronchial anatomy detail of alveoli and lung circulation

Image: “Bronchial anatomy detail of alveoli and lung circulation” by Patrick J. Lynch. License: (CC BY 2.5)

Bronchi and segmental bronchi

The most important difference to the trachea is that in the intrapulmonary airways there are irregularly formed cartilage plates in the wall instead of hyaline cartilage rings. Also, there is no more paries membranaceus. Muscle cells are circularly arranged. The wall contains the following layers:

Tunica mucosa: The mucosa consists of respiratory epithelium and the lamina propria with embedded sero-mucous bronchial glands (glandulae bronchiales) and goblet cells. Elastic fibers, free cells of the immune system, and a continuous coat out of smooth muscles can be seen in the histological preparation.

Tunica musculo-fibro-cartilaginea: The support frame is formed by irregular hyaline cartilage plates, smooth muscles, and connective tissue. In the small bronchi, small elastic cartilage pieces can be found. The irregular cartilage pieces form the outer layer, the continuous circular muscle layer (tunica muscularis) is on the inside. Sero-mucous glands are situated between the cartilage pieces. They synthesize mucins for the epithelium covered mucous surface. Also, they secrete antibacterial substances, IgA, and protease inhibitors for the inactivation of tissue damaging proteases, which are liberated by immune cells.

Tunica adventitia: The loose peribronchial connective tissue forms a continuum, which accompanies the branches of the bronchial tree from the junction (hilum) to the bronchioles. This is where the private vessels of the bronchial tree, lymphatic vessels, and nerves run.


In contrast to the bronchi, the bronchioles mainly differ from the rest of the bronchial tree by not (!) having any cartilage pieces and glands.

Tunica mucosa: The mucosa has a ciliated single layer mostly cuboidal epithelium without goblet cells. A star-shaped lumen with a diameter of less than 1 mm is characteristic for the cross section of bronchioles.

Tunica adventitia: Via elastic fibers of the surrounding alveolar walls, the peribronchial connective tissue is indirectly connected with the lung surface and the interlobular and intersegmental connective tissue septa. Thus, a radial tension is exerted on the bronchioles, which keeps them open and prevents them from collapsing. This way, the lack of a support frame with cartilage can be compensated.

Terminal bronchioles

The final branching of the bronchioles represents the end of the conductive part of the airways. The epithelium contains non-ciliated secretory cells, the clara cells. They arch into the lumen like pistons. Apically, they contain secretory granules with proteins, which serve as a part of the natural immune response: the surfactant proteins SP-A and SP-D as well as clara cell protein CC 10 (clara cell 10 kDa protein).

These proteins decrease the anti microbial mechanism of tissue damaging inflammatory reactions. SP-A and SP-D also act as opsonins, which make phagocytosis of pathogens easier for immune cells. Clara cells are claimed to be the reserve for cell replacement in the distal airways.

Acini are all airways that arise from the terminal bronchioles.

Respiratory bronchioles

The gas exchanging part of the bronchial tree begins right here. The wall is fragmentary and contains embedded alveoli.

Alveolar ducts and sacculus

Alveolar ducts and sacculi are the vestibule of the alveoli. A ring of smooth muscles, collagenous, and elastic fibers reinforces the entrance to the alveoli.

The simple cuboid epithelium does not have kinocilia, clara cells can be found.

Note: In exams, especially the difference between bronchi and bronchioles in regard to their structure is a popular subject.

Gas Exchange in the Alveoli

Alveoli are polygonal spaces, which are filled with air. They are separated from each other by thin walls (interalveolar septa). The alveolar walls – the interalveolar septa – are structures in which gas exchange occurs via diffusion.

Collagen, fibrocytes, and elastic fibers, which are responsible for the lung’s retracting forces, form the connective tissue frame of the septa. In the septa, there are expanded capillary nets. The basal lamina of the capillary endothelium and the basal lamina of the alveolar epithelium cells are fused. Thus, both structures have a common basal lamina.

On both sides of the interalveolar septa, there is a thin epithelial cover of thin plate-like extensions of cytoplasm of the type I alveolar cells (pneumocytes), also referred to as covering cells. They have an extensive soma which covers the capillaries (blood air barrier) and lines the major part (95 %) of the alveoli.

In the niches between the flat type I cells – where they do not really interfere with gas exchange –, there are larger cuboid type II alveolar epithelial cells (pneumocytes). They contain a lot of organelles and lamellar corpuscles. They produce and secrete the surfactant. Type II cells are the replacement for type I cells.

All extensions of adjoining alveolar epithelial cells are connected with each other by tight junctions. Tight junctions are the most important barriers against intrusion of lymph out of the interstitium into the alveoli. The alveolar epithelium is not directly in contact with air, but it is covered with a liquid film. Its surface tension is decreased by the surfactant.

Structures of the Respiratory Zone

Image: “Structures of the Respiratory Zone” by philschatz. License: (CC BY 4.0)

Blood air barrier

In the area of the blood air barrier, there is close contact between alveoli and the capillaries.

Anatomically, it consists of a thin area of the following structures (from alveolus to capillary):

  • Surfactant film
  • Thin extension of type I alveolar epithelial cell
  • Fused basal membrane of capillary endothelium and alveolar epithelium
  • Endothelial cell (closed type)

In the human lung, the thickness of this tissue barrier amounts to only 0,6 micrometers and is thus very short for respiratory gas. The distance for diffusion between the air in the alveoli and erythrocyte is with 1,1 micrometers slightly longer since the fluid film on the alveolar epithelium and the blood plasma has to be passed beside the anatomic structures.

Excursus: Pulmonary Edema

Interstitial and alveolar pulmonary edema with small pleural effusions on both sides

Image: “Interstitial and alveolar pulmonary edema with small pleural effusions on both sides” by James Heilman. License: (CC BY-SA 3.0)

Commonly referred to as water in the lung, the pulmonary edema is an acute disease. Fluid accumulates in the connective tissue and the alveoli. A pressure rise in the capillaries can be caused by myocardial failure and, hence, backflow into the pulmonary circulation. The accumulation in the connective tissue (and thus in the blood air barrier) results in an impairment of diffusion and therefore gas exchange. Fluid transfers to the alveoli.

Surfactant – SURFace-ACTive-AgeNT

Without this substance, the surface tension at the water/air border would be so high that the alveoli would collapse in the course in expiration and would not inflate anymore (atelectasis = not inflated alveolus). A closer look at this substance is worthwhile:

The major part (90 %) of this anti-atelectasis factor consists of phospholipids (dipalmitoylphosphatidylcholine = lecithin) and 10 % are surfactant proteins. The phospholipids lower the surface tension of the fluid film on the alveolar surface. Surfactant is produced and secreted by type II pneumocytes and is stored in storing organelles (lamellar bodies).

Due to the amphiphilic character of the phospholipids, they spread as a monomolecular layer over the water/air border after exocytosis out of the type II cells. A great part of the surfactant is reused (recirculation: reuptake and renewed liberation out of type II cells), the rest is eliminated by alveolar macrophages.

Popular Exam Questions on the Airways

Solutions can be found below the references.

1. Organize the sero-mucous glands with respect to their location in the bronchial tree system.

  1. segmental bronchi
  2. terminal bronchioles
  3. trachea
  4. respiratory bronchioles
  5. main bronchi

2. Concerning the lung’s function, it is important that the lymph in the interstitium of the lung that originates from the blood capillaries cannot pass into the air space in the alveoli. Which structure forms this barrier?

  1. keratinized squamous epithelium
  2. atelectasis factor
  3. tight junctions between alveolar epithelial cells
  4. type II pneumocytes
  5. basal membrane

3. Component/s of the wall of respiratory bronchioles is/are:

  1. pseudostratified epithelium
  2. goblet cells
  3. elastic fibers
  4. cartilage
  5. bronchial glands

4. During a biopsy of a segmental bronchus, you find keratinized squamous epithelium. What do you conclude from this observation?

  1. Epithelial atrophy due to chemical noxae
  2. Inadequate blood supply
  3. Normal finding
  4. Metaplasia
  5. Hypotrophy

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