Histology of the Respiratory System Department of histology, cytology and embryology KhNMU

The respiratory system includes the lungs , system of passages (airways) and structures of ventilating mechanism, that link the site of gas exchange with the external environment. It is customary to divide the respiratory system into 3 principle regions: a conducting portion, consisting of the nasal cavity, nasopharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles. a respiratory portion, consisting of respiratory bronchioles, alveolar ducts, atria, alveolar sacs and alveoli. ventilating mechanism , which creates pressure differences that move air. It includes the diaphragm, rib cage, intercostal muscles, abdominal muscles and elastic connective tissue in the lungs.

Development of the Respiratory System Developmental Stages (Human) 1.Embryonic phase (3-7 weeks) Initial budding and branching of the lung buds from the primitive foregut. Ends with the development of the presumptive broncho-pulmonary segements. Presumptive - 1 : based on probability or presumption 2 : being an embryonic precursor with the potential for forming a particular structure or tissue in the normal course of development

2.Pseudoglandular phase (7-16) weeks Further branching of the duct system (up to 21 further orders) generates the presumptive conducting portion of the respiratory system up to the level of the terminal bronchioles. They are embedded within a rapidly proliferating mesenchyme. The structure has a glandular appearance.

3. Canalicular phase (16-24) weeks The onset of this phase is marked by extensive angiogenisis within the mesenchyme that surrounds a dense capillary network. The diameter of the airways increases with a consequent decrease in epithelial thickness to a more cuboidal structure. The terminal bronchioles branch to form several orders of respiratory bronchioles. The developing respiratory tree, giving rise to chondrocytes, fibroblasts and myoblasts.

4.Terminal sac phase (24-36) weeks Branching and growth of the terminal sacs or primitive alveolar ducts. Functional type I & type-II pneumonocytes differentiate via several intermediate stages from pluripotent epithelial cells in the prospective alveoli. These cells then flatten, increasing the epithelial surface area by dilation of the saccules, giving rise to immature alveoli. Maturation of the alveoli continues by further enlargement of the terminal sacs, deposition of elastin foci and development of vascularised septae around these foci.

5.Alveolar phase (36 weeks - term/adult) Maturation of the lung indicated by the appearance of fully mature alveoli begins at 36 weeks, though new alveoli will continue to form for approximately three years. A decrease in the relative proportion of parenchyma to total lung volume still contributes significantly to growth for 1 to 2 years after birth, thereafter all components grow proportionately until adulthood.

There are changes in the epithelial lining of the respiratory tree as one proceeds from the nasal cavity to the alveoli of the lungs: Pseudostratified Columnar Ciliated=> Simple Columnar =>Simple Cuboidal => Simple Squamous Epithelium.

Conducting Portion System of ducts Nose Nasopharynx Larynx Trachea Conducts air to all parts of the lungs Nose Nasopharynx Larynx Trachea Bronchi Bronchioles Preterminal bronchioles Terminal bronchioles Conditioning of the air Warming, moistening and removal of particulate materials

Trachea 20 C-shaped cartilaginous rings Paries membranaceus Connective tissue that fills gap between the two posterior ends Neighbouring rings Connected by regular dense connective tissue Continuous with perichondrium of cartilaginous rings

Trachea 1. Mucosa Pseudostratified columnar epithelium with cilia and goblet cells 2.Lamina propria,Elastic & Collagen fibers 3.Submucosa Mixed glands and lymph follicles 4. Fibrocartilagenous Layer Hyaline Cartilage & SMC 5.Adventitial layer

Low Magnification of a Cross Section Through the Trachea 1. Lumen 2. Pseudostratified ciliated columnar epithelium 3. Submucosa 4. Hyalin cartilage 5. Perichondrium 6. Adventitia 7. Mixed glands 8. Secretory duct

Epithelium of the Trachea Lumen 2. Cilia 3. Columnar epithelial cells 4. Basal membrane 5. Lamina propria 6. Basal cell layer 7. Goblet cell

Respiratory epithelial cell types 1.Ciliated columnar cells 2.Mucous goblet cells 3.Brush cells 4.Basal cells 5.Small granule cells

Bronchi Extrapulmonary bronchi Two primary bronchi Histologically similar to the trachea Intrapulmonary bronchi Secondary bronchi (Lobar) - 5 Bronchopulmonary segmental bronchi –Tertiary (Lobular)- 20

Intrapulmonary Bronchi Mucosa Pseudostratified columnar containing cilia and goblet cells Lamina propria - elastica changes into longitudinally arranged elastic fibers Smooth muscle Between mucosa and cartilage Mixed glands - between muscle layer and cartilagous plates Cartilage Irregular shaped cartilaginous plates

Three-dimensional Representation of an Intrapulmonary Bronchus Bronchi Three-dimensional Representation of an Intrapulmonary Bronchus cartilage plate lamina propria pseudostratified columnar epithelium with cilia and goblet cells smooth muscle

Bronchioles Branches of bronchi Penetrate lung lobule at its apex Preterminal bronchiole inside the lobule Preterminal bronchiole Branches into terminal bronchioles Branch further

Bronchioles Mucosa Epithelium in the larger bronchioles Simple columnar epithelium with cilia Tall, non-ciliated secretory cells – cells of Clara In smaller bronchioles Tall cuboidal epithelium Goblet cells have disapeared higher up in the bronchioles Lamina propria Thin elastic layer

Bronchioles Muscle layer Connective tissue Same as that of the bronchi Connective tissue Attaches bronchioles to surrounding tissue No glands or cartilage are present

Terminal bronchioles – end point of Conducting portion Respiratory bronchioles – beginning of Respiratory Portion

Respiratory Portion Consists of smaller ducts and sacs Respiration takes place Respiratory bronchioles Alveolar ducts Alveolar sacs Alveoli

Respiratory Bronchioles Schematic of the Respiratory Portion of a Lung Lobule Respiratory bronchioles Branch from terminal bronchioles Alveoli Thin bulging sacs in walls Gas exchange takes place Smooth muscle respiratory bronchiole alveolar ducts alveoli interalveolar septum sacculus alveolaris

High Magnification of the Lung Demonstrating a Respiratory Bronchiole High cuboidal epithelium 2. Alveolus 3. Interalveolar septum 4. Lumen

Alveolar Ducts, Alveolar Sacs and Alveoli Long passages into which respiratory bronchioles open Alveolar ducts open directly into small spaces Alveoli Interalveolar septa Separate neighboring alveoli Alveolar sacs Air spaces surrounded by clusters of alveoli Elastic and reticular fibers Arranged around the capillaries

1. Alveolar sacs 2. Alveoli 3. Interalveolar septa

Blood – Air Barrier Separation Between Air and Bloodstream Cytoplasm of epithelium lining the alveoli Basal lamina of the epithelium Basal lamina of the capillary endothelium Cytoplasm of capillary endothelium

Alveolar epithelium – Pneumocytes Simple squamous alveolar epithelial cells – Type 1 cells -Thin cytoplasm Large Secretory cells – Type 2 (secretory cells) - Secrete surfactant & Decrease surface tension Alveolar macrophages - Type 3 (dust cells)

Pulmonary surfactant is a surface-active lipoprotein complex (phospholipoprotein) formed by type II alveolar cells. It is 2-layer molecular film on the alveolar surface. The proteins and lipids that comprise the surfactant have both a hydrophilic region and a hydrophobic region. The main lipid component of surfactant, (DPPC)- dipalmitoylphosphatidylcholine.

Functions of surfactant 1. Decrease surface tension 2 . Functions of surfactant 1.Decrease surface tension 2.To increase pulmonary compliance 3.To prevent atelectasis (collapse of the lung) at the end of expiration. 4.To facilitate recruitment of collapsed airways.

Pulmonary Surfactant

Pores and Lambert-sinuses Alveolar pores Direct contact between 2 alveoli Infections can spread from one lobe to another via this route Lambert sinuses Short cannel Connects terminal bronchioles with alveoli

Acinus is a Structural and Functional Unit of the Lung

Terminal Part of the Lungs