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schematic picture of the lung pleura

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


Introduction

The airway facilitates mechanical respiration, and is divided into:

  • a conducting system
  • an interchange system

Mechanical respiration occurs via various steps:

  1. Inhalation of air
  2. Warming, cleaning, and moistening of air in the larger airways
  3. In the lungs, oxygen is obtained from the air and delivered to the blood while CO2 is removed from the peripheral blood circulation into the lungs.

The air is then exhaled after gaseous exchange.

Airway Structure: General Principles

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 by a special 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 of special cartilage.

The mucosa (tunica mucosa) consists of the epithelial lamina, the lamina propria consisting of connective tissue. It contains the characteristic respiratory epithelium, which is a ciliated pseudostratified columnar epithelium with goblet cells.

Location and Structure of Trachea and Main Bronchi

The lower airways start below the glottis. The trachea is a long tube that runs from the larynx, and bifurcates 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. Overall, the bronchi divide into nearly 23  smaller branches before they reach the alveoli.

The trachea is divided into neck and thoracic portions, and is located ventral to the esophagus.

The main bronchi and trachea are supported by a frame of 16–20 C- or hoof-shaped hyaline cartilage rings. These rings are open dorsally but the trachea is closed by a connective tissue wall containing transverse muscle fibers known as paries membranaceus. The cartilage rings are connected to each other longitudinally by annular ligaments.

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

Note: The tracheal structure is relatively easy to understand based on the three-layered structure of the wall!

Microscopic Structure of the Trachea

Trachea Anatomy

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

The wall of the trachea consists of three layers:

1. Tunica mucosa: Tunica mucosa is the inner layer of the mucosa consisting of respiratory epithelium, except for the bifurcated non-cornified squamous epithelium. The lamina propria contains sero-mucous glands (tracheal glands). The mucosa is rich in afferent nerve fibers (cough reflex).

2. Tunica fibro-musculo-cartilaginea: The most prominent structure in tunica fibro-musculo-cartilaginea is the hyaline cartilage ring, which contains a strong perichondrium. The horizontal tracheal muscle in the paries membranaceus closes the dorsal gap due to the cartilage rings. Contraction of the tracheal muscle alters the tracheal caliber due to the horizontal orientation of the muscle fibers.

The annular ligaments connect the cartilage rings with each other. This layer contains multiple elastic fibers oriented longitudinally, which facilitates the adaptation of trachea and the main bronchial elastic tubes arranged longitudinally to the surrounding movements.

3. Tunica adventitia: The tunica adventitia is a loose layer of connective tissue, which not only connects the trachea with its surrounding structures but also ensures tracheal flexibility during  swallowing or coughing.

Excursus: Tracheomalacia

An enlarged thyroid gland (struma) obstructs the trachea, resulting in tracheomalacia, which is characterized by softening of the cartilage rings and loss of stability. The anteroposterior diameter of the trachea is lost. It is characterized by tracheal collapse during times of increased airflow causing cough, crying or feeding difficulty.

Note: It is almost impossible to confuse the extrapulmonary airways (trachea and main bronchi) with other hollow organs histologically as long as you remember its key features: macroscopic cartilaginous rings, abundant respiratory epithelium, and sero-mucous glands. This combination cannot be found in any other hollow organ!
schematic picture of the lung pleura

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

The lung is located in the pleural cavity. The lobes of the lung are covered by the visceral pleura (pleura pulmonalis), which is in contact with the parietal pleura. Physiologically, adhesion between the two serous sheets is ensured by the pleural fluid. The thin layer of fluid ensures the  capillary adhesion between the sheets. Thus, the lung surface can be moved against the thoracic walls, but cannot be separated from it during its movements.

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

Basically, the lung consists of branches of the bronchial tree until the air sacs (alveoli; the end of the bronchial tree) and the branches of pulmonary arteries and veins. The latter are intrapulmonary, whereas the upper airways, the trachea, and the main bronchi are extrapulmonary in location.

The bronchi are dichotomous, which means that the two smaller branches arise from a larger one. The human lung branches an estimated 21 to 23 times from the trachea to the alveoli. Nearly 15 such branches form the conducting airway in the lung, while the remainder including the respiratory bronchioles and the alveolar duct are involved in gas exchange.

The main bronchi split into lobe bronchi (bronchi lobares; three on the right, two on the left) after they enter the lungs, and are extrapulmonary.

The lobe bronchi then split dichotomously inside the lung into segmental bronchi (bronchi segmentales). The dichotomous splitting of the bronchi continues, often irregularly as a single branch divides into two unequal ones. The stronger branch runs in the same direction as the large one, while the remaining one turns and eventually runs in the opposite direction. Hence, the central areas of the lung carry terminal branches and alveoli.

Segmental bronchi split into middle and small bronchi. The small bronchi become terminal bronchioles and then respiratory bronchioles, and terminate in the alveolar duct and the alveoli.

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

  • Segmental bronchi
  • Bronchi
  • Bronchioles
  • Terminal bronchioles
  • Respiratory 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 bronchi are distinguished from the trachea by irregular cartilage plates instead of hyaline cartilage rings in the walls of intrapulmonary airways. Further, the paries membranaceus no longer exists. Muscle cells are arranged circularly. The wall contains the following layers:

Tunica mucosa: The tunica 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 of smooth muscles are found in the histological preparation.

Tunica musculo-fibro-cartilaginea: The supporting framework is composed of irregular hyaline cartilage plates, smooth muscles, and connective tissue. Small fragments of elastic cartilage are found in the small bronchi, and form the outer layer. The continuous circular muscle layer (tunica muscularis) is located on the inside. Sero-mucous glands located between the cartilages synthesize mucins for the mucous-covered epithelial 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, supplied by the nerves and lymphatic vessels of the bronchial tree.

Bronchioles

In contrast to the bronchi, the bronchioles mainly differ from the rest of the bronchial tree by the absence of cartilage and glands.

Tunica mucosa: The mucosa comprises a single layer of mostly ciliated cuboidal epithelium without goblet cells. Each of the bronchioles encloses a star-shaped lumen with a diameter of less than 1 mm.

Tunica adventitia: The peribronchial connective tissue is indirectly connected to the lung surface via elastic fibers of the surrounding alveolar walls, the interlobular and intersegmental connective tissue septa. The radial tension exerted on the bronchioles keeps them open and prevents their collapse, thereby compensating for the lack of a cartilage framework.

Terminal bronchioles

The final branching of the bronchioles represents the end of the conductive airway. The epithelium comprises non-ciliated secretory cells, the Clara cells. They arch into the lumen-like pistons. Apically, they contain secretory granules comprising the surfactant proteins SP-A and SP-D as well as the Clara cell protein CC 10 (Clara cell 10 kDa protein), which contribute partly to the natural immune response.

These proteins decrease the antimicrobial mechanism of tissue-damaging inflammatory reactions. SP-A and SP-D also act as opsonins, which facilitate phagocytosis of pathogens by immune cells. Clara cells serve as the reserve for cell replacement in the distal airways.

Acini are airways that originate from the terminal bronchioles.

Respiratory bronchioles

Respiratory bronchioloes are the smallest bronchioles (<0.5 mm in diameter) that connect the terminal bronchioles to the alveolar ducts. The gas exchange in the bronchial tree is initiated in the respiratory bronchioles. The wall is fragmentary and contains embedded alveoli.

Alveolar ducts and sacculus

Alveolar ducts and sacculi represent the vestibules of the alveoli. A ring of smooth muscles, collagenous, and elastic fibers reinforce the entrance to the alveoli.

The simple cuboid epithelium contains mostly club cells or Clara cells, and not kinocilia.

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 (or the interalveolar septa) are structures in which gas exchange occurs via diffusion.

Collagen, fibrocytes, and elastic fibers, which generate the forces of retraction in the lung, form the connective tissue frame of the septa. Expanded capillary nets occur within the septa. The basal lamina of the capillary endothelium is fused with the basal lamina of the alveolar epithelium. Thus, both structures carry a common basal lamina.

The interalveolar septa is covered bilaterally by a thin epithelial layer of plate-like cytoplasmic extensions of type I alveolar cells (pneumocytes), also referred to as covering cells. They contain an extensive soma, which covers the capillaries (blood-air barrier) and lines the major portion (95%) of the alveoli.

The space between the flat type I cells, which is not involved in gas exchange, is filled with larger cuboid type II alveolar epithelial cells (pneumocytes). They contain a several organelles and lamellar corpuscles, which produce and secrete the surfactant. Type II cells replace 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 lymphatic drainage from the interstitium into the alveoli. The alveolar epithelium is not directly in contact with air but is covered by 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

The blood-air barrier provides a close contact between alveoli and capillaries, and is thus also known as the alveolar-capillary barrier or membrane. Since the gaseous exchange occurs here, the barrier is essential to prevent the formation of gas bubbles within the blood vessels.

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

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

In the human lung, the thickness of this tissue barrier is only 0.6 μm and thus facilitates respiratory gas exchange. The diffusion between the air in the alveoli and erythrocytes occurs at about 1.1 μm, which allows the passage of fluid film through the alveolar epithelium and the blood plasma in addition to other 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, pulmonary edema is an acute disease. Fluid accumulates in the connective tissue and the alveoli making it difficult to breathe. A pressure build-up in the capillaries may be caused by myocardial failure and leads to backup of blood in the pulmonary circulation. The accumulation in the connective tissue (and thus in the blood-air barrier) impairs diffusion, and therefore, hinders gaseous exchange. Fluids are transferred to the alveoli. Non-cardiogenic causes of pulmonary edema include severe pneumonia and other respiratory tract diseases.

Sudden/acute pulmonary edema is an emergency that presents with dyspnea, a feeling of suffocation or drowning, wheezing or gasping for breath, anxiety, chest pain, and palpitations.

Prompt treatment using diuretics and addressing the underlying ailments such as cardiac failure or severe infection can resolve pulmonary edema.

Surfactant – SURFace-ACTive-AgeNT

Without surfactants, the enormous surface tension at the water/air interface leads to irreversible collapse of alveoli during exhalation (atelectasis = not inflated alveolus).

The major component (90%) of the anti-atelectasis factor consists of phospholipids (dipalmitoylphosphatidylcholine = lecithin) and the remainder (10%) is composed of 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  organelles  known as lamellar bodies.

Due to the amphiphilic properties (hydrophilic and hydrophobic) of phospholipids, they spread as a monomolecular layer over the water/air interface following exocytosis of the type II cells. A majority of the surfactant is recirculated via reuptake and release from type II cells, and the remainder is eliminated by alveolar macrophages.

Review Questions

Solutions can be found below the references.

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

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

2. To ensure pulmonary function, the lymph in the pulmonary interstitium originating in the blood capillaries is not diffused across the barrier separating the air space from the alveoli. What is the nature of this barrier?

  1. Keratinized squamous epithelium
  2. Atelectasis factor
  3. Tight junctions between alveolar epithelial cells
  4. Type II pneumocytes
  5. Basal membrane

3. The 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. The presence of keratinized squamous epithelium in a biopsy of segmental bronchus suggests:

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