11 Respiratory system

The exchange of gases, such as carbon dioxide and oxygen, between the air and blood takes place in the lungs. In the alveoli, balloon-like structures in the lungs, gases diffuse between the inside and outside of the body by the process of simple diffusion, based on concentration gradient. A system of air passages brings the air to the respiratory membrane in the alveoli. Air enters the body through the nostrils, passes through the nasal cavity, flows through the pharynx and larynx to the trachea. The trachea branches into right and left bronchi that, in turn, branch into several divisions of smaller bronchi that continue to get smaller and smaller in size. Finally, bronchi become bronchioles which, after a few divisions, start out-pocketing as alveoli.

In addition to providing the way for gases, the air passages help to warm, moisturize , and clean the air before it touches the delicate surfaces of the alveoli. Part of the nasal cavity is involved in smell-sensing and is covered by specialized olfactory epithelium. 

Gross anatomy of the respiratory system

The respiratory system can be divided into the conducting portion and the respiratory portion.

 

Figure 1: Major organs of the respiratory system

The conducting portion delivers air to the lungs. It extends from the nasal cavity to the terminal bronchioles in the lungs and includes:

  • Pharynx
  • Laynx
  • Trachea
  • Several levels of bronchi – main, lobar, segmental, etc.
  • Several levels of bronchioles
  • terminal bronchioles – the last level of bronchioles that do not allow the exchange of gases

The respiratory portion of the respiratory system is where gas exchange takes place. This portion involves alveoli and the smallest bronchioles. The respiratory portion includes:

  • respiratory bronchioles that are the continuation of terminal bronchioles
  • alveolar ducts
  • alveoli

Respiratory epithelium

All parts of the respiratory system, except for the nasal vestibule, are covered by the specialized respiratory epithelium.

Most of the conducting portion of the respiratory tract is covered by pseudostratified ciliated columnar epithelium. The ciliated epithelium is a part of the filtration mechanism for air before it gets to the deepest portions of the lungs.

 

The respiratory epithelium is primarily composed of ciliated columnar epithelial cells and interspersed with a number of goblet cells (Figure 2). Goblet cells are columnar epithelial cells (not ciliated) that produce and secrete mucus that is used to trap dust and pollen particles. The cilia of regular epithelial cells beat in a constant sweeping motion, propelling the mucus and debris upwards toward the throat or the nasal cavity.

Figure 2: Goblet cells in the lining of the bronchus.

Under the microscope, the pseudostratified epithelium looks like uneven rows of elongated nuclei. The apical side of these cells is covered by cilia, the membrane extensions that resemble tiny hairs. Goblet cells that lack cilia are interspersed in varying numbers between the regular ciliated epithelial cells. In H/E staining, goblet cells are characterized by lighter colored cytoplasm filled with poorly stained, basophilic (pink) mucus.

The respiratory epithelium changes as it descends down the respiratory tract.

In the nasal vestibule, close to the nostrils, the epithelium starts as stratified sqamous epithelium that is an extension of the epidermis of the skin. In the nasal cavity, it quickly changes into the pseudostratified ciliated columnar epithelium, the major covering epithelium in the conducting portion of the respiratory system. Pseudostratified cilliated epithelium also covers the internal surfaces of the paranasal sinuses.

Figure 3: Pseudostratified ciliated columnar epithelium of the trachea

Pseudostratified ciliated columnar epithelium continues throughout the pharynx, larynx, trachea, all bronchi, and larger bronchioles. In bronchioles, the epithelium changes to simple columnar epithelium and then simple cuboidal epithelium.

In respiratory bronchioles, the epithelium flattens to become simple squamous epithelium that also makes up the walls of the alveoli. Simple squamous epithelial cells in the alveoli are a part of the respiratory membrane, and are the thinnest cells in the body. The alveolar epithelial cells are also called pneumocytes type I, in contrast to pneumocytes type II, other alveolar cells that produce and secrete surfactant.

Regional characteristics of the respiratory system

Nasal cavity and olfactory epithelium

The nose is the major entrance to the respiratory passages. During breathing, air enters and exits through the nose into the frontal part of the nasal cavity called the nasal vestibule. The nasal vestibule is lined by keratinized, stratified squamous epithelium containing nasal hairs that prevent the entry of big particles of dirt or insects into the nasal cavity. This epithelium transitions into pseudostratified ciliated columnar epithelium with mucus producing goblet cells that lines the remaining structures in the nasal cavity, and the internal surfaces of the paranasal sinuses.

The nose is also the location of the sense of smell (a.k.a. olfaction.) A special olfactory epithelium is located on the surface of the superior nasal concha, the upper bony shelf in the nasal cavity. Olfactory epithelium is specialized for the reception of smell, and different from the rest of the respiratory epithelium nearby.  It  is tall, pseudostratified columnar epithelium without goblet cells.

There are three types of cells within the olfactory epithelium:

  • olfactory receptor cells
  • sustentacular cells
  • basal cells.

Olfactory epithelial cells are modified neurons interspersed within the olfactory epithelium. The cell bodies of these olfactory neurons reside within the epithelium and have cilia that project onto the surface. These cilia are not visible in light microscope. The axons of these neurons extend to the olfactory bulb located within the cranial cavity.

 

Figure 4: Olfactory epithelium

Sustentacular cells are similar to respiratory epithelium. These cells provide structural and metabolic support to the epithelium.

Basal cells are cuboidal epithelial cells that reside deep within epithelium and are the stem cells that play a role in the regeneration of the nasal epithelium.

Larynx

The larynx, commonly known as the voice box, is a cartilaginous structure that connects the pharynx to the trachea. The larynx is made of nine cartilages. The three large cartilages provide structure to the larynx:

  • the thyroid cartilage
  • the cricoid cartilage
  • the epiglottis

The three smaller, paired cartilages (for a total of six) that are involved in the creation of sound by regulating the position and tension of the vocal cords are:

  • the arytenoid cartilages
  • corniculate cartilages
  • uneiform cartilages

The larynx is covered in pseudostratified ciliated columnar epithelium with mucus-producing goblet cells.

The epiglottis is a large, flat flap cartilage that controls entry to the trachea. During breathing, the epiglottis is in an upright position and keeps the entry to the trachea open. During swallowing, the epiglottis covers the entry to the trachea, redirecting food to the esophagus.

Figure 5: Section through the epiglottis.
Figure 6: Elastic cartilage of the epiglottis at higher magnification.

The thyroid, cricoid, and arytenoid cartilages are made of hyaline cartilage. The epiglottis, corniculate, and cuneiform are elastic cartilages.

Trachea and bronchi

The trachea (windpipe) starts at the larynx and ends at the division into two main bronchi, right and left. C-shaped, half rings of hyaline cartilage stacked up on one another form the front of the trachea; while in the back, muscle and elastic connective tissue connect the ends of the rings to form a stiff but elastic tube. The rings of cartilage provide structural support and prevent the trachea from collapsing.

Figure 7: Cross-section through the trachea. Partially visible esophagus is in the back of the trachea. On the sides are partially visible lobes of thyroid gland.

The inside of the trachea is lined with pseudostratified ciliated columnar epithelium, which is continuous with the larynx. This epithelial layer has mucus producing goblet cells that are only visible at high magnification. Underneath the epithelium is the lamina propria that contains submucosal glands that also produce mucus. The next layer is the hyaline cartilage, followed by the smooth muscle layer.

Figure 8: The section through the trachea. 1. Respiratory epithelium 2. Lamina propria with a small number of glands 3. Hyaline cartilage 4. Smooth muscle

The trachea divides into the left and right main bronchi. As the bronchi extend deeper into the lungs, they continue to split into secondary and tertiary bronchi that are smaller in diameter. The collective term used for these multiple-branched bronchi is the bronchial tree.

The main function of the bronchi is to provide a passageway for air to move into and out of the lungs. The repiratory epithelium and mucus that line the multiple levels of the bronchial tree trap debris and pathogens.

Bronchi are histologically similar to the trachea. They are lined with pseudostratified ciliated columnar epithelium interspersed with goblet cells. The cartilage is no longer circular but divided into several plates that surround the lumen of the bronchus. The lamina propria of bronchi contains much more numerous submucosal glands.

Figure 9: Bronchus at low magnification. Notice several plates of cartilage encircling the bronchus.
Figure 10: Section through the main bronchus at high magnification.

Bronchioles

Eventually, bronchi transform into even smaller bronchioles. The walls of bronchioles are composed only of epithelium and smooth muscle. Bronchioles do not have cartilage or submucosal glands, which, along with their smaller size, distinguish them from bronchi. Larger bronchioles are lined by ciliated or non-ciliated simple columnar epithelium that transitions to cuboidal epithelium in the smaller bronchioles. Terminal bronchioles are the end of the conducting zone.

Alveoli

Alveoli (singular: alveolus) are the site of gas exchange in the lungs. Alveoli form by the out-pocketing of the respiratory bronchioles and alveolar ducts. All alveoli that derive from the single alveoli duct are connected together and form a lobule.

Alveoli are thin-walled, sac-like structures made from a single layer of flattened simple squamous epithelial cells also known as type I pneumocytes. Type I pneumocytes are the thinnest cells in the body, which facilitates gas exchange across their surface. Each avleolus is wrapped up in capillaries that pick up or give away the gas they bring to the lungs. Therefore, in the wall of the alveolus, there are two cells that directly touch, a pneumocyte type I and endothelial cells of the capillary. This provides the shortest possible distance for gas diffusion. We call these places of direct contact the respiratory membrane.

In addition to the type I pneumocytes, alveoli also contain type II pneumocytes, cuboidal epithelial cells frequently residing in the corners of alveolar spaces. Type II pneumocytes are responsible for the production and secretion of surfactant. Surfactant is a fluid composed of phospholipids and proteins that coats the surface of alveolar spaces to reduce surface tension, allowing for alveoli to expand and remain open. In addition, type II pneumocytes play a crucial role in tissue repair in the lungs. Following damage to type I pneumocytes, type II pneumocytes divide and differentiate into type I pneumocytes, thereby restoring alveolar structure.

Finally, alveolar spaces contain a resident population of alveolar macrophages that are often mistaken for type II pneumocytes. These macrophages phagocytize debris within alveoli, which can include surfactant, edema fluid, red blood cells, and pathogens (e.g. bacteria.)

Figure 11: Lung tissue. Alveoli and alveolar ducts.
Figure 12: Alveolar cells

Regional characteristics of the respiratory system are summarized in the table below.

Region

Histological characteristics

Nasal Cavity

Stratified squamous epithelium in the front of the nasal cavity
Pseudostratified ciliated columnar epithelium with goblet cells in the back of the nasal cavity
Olfactory epithelium at the roof of the nasal cavity  over the superior nasal concha

Larynx

Pseudostratified ciliated columnar epithelium
Elastic cartilage in the epiglottis, hyaline cartilage in thyroid and cricoid cartilages
Some taste buds on the epiglottis

Trachea

Pseudostratified ciliated epithelium with goblet cells
Rings of hyaline cartilage
Glands under epithelium in the lamina propria
Smooth muscle

Bronchi

Pseudostratified ciliated columnar epithelium with goblet cells
Plates of hyaline cartilage
Smooth muscle
Glands may be present in lamina propria

Large bronchioles

Pseudostratified ciliated columnar epithelium with goblet cells
Smooth muscle

Smaller bronchioles

Simple columnar or cuboidal epithelium
Smooth muscle

Alveoli

Squamous epithelium (type I pneumocytes)
Surfactant cells (type II pneumocytes)
Macrophages

 

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Histology Copyright © by Malgosia Wilk-Blaszczak. All Rights Reserved.

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