PULMONARY

HISTOLOGY

Divisions of the Respiratory System

• The conducting portion, which consists of the nasal cavities,

nasopharynx, larynx, trachea, bronchi, bronchioles, and terminal

bronchioles

• The respiratory portion, where the system's main function of gas

exchange occurs, consisting of respiratory bronchioles, alveolar

ducts, and alveoli

• Most of the nasal cavities and the respiratory system's conducting

portion is lined with mucosa having ciliated pseudostratified columnar

epithelium commonly known as respiratory epithelium

Respiratory Epithelium

• Respiratory epithelium is the classic example of pseudostratified ciliated columnar epithelium.

• Usually rests on a very thick basement membrane (BM) and has several cell types, some columnar, some basal, and all contacting the basement membrane.

• Ciliated columnar cells are most abundant, with hundreds of long robust cilia on each of their bulging apical ends that provide a lush cover of cilia on the luminal surface.

• Most of the small rounded cells at the basement membrane are stem cells and their differentiating progeny, which together make up about 30% of the epithelium.

• Mucus-secreting goblet cells (G) and intraepithelial lymphocytes and dendritic cells are also present in respiratory epithelium.

• The lamina propria is well-vascularized

The olfactory mucosa is a pseudostratified epithelium, containing basal stem cells

and columnar support cells in addition to the bipolar olfactory neurons. The

dendrites of these neurons are at the luminal ends and have cilia specialized with

many membrane receptors for odor molecules.

Mucus

Cilia

Supporting Cells

Olfactory Neurons

Basal Cells

Lamina Propria

3 Cells of Olfactory Epithelium

• Olfactory neurons are bipolar neurons present throughout this epithelium. Their nuclei form an irregular row near the middle of this thick epithelium. The apical (luminal) pole of each olfactory cell is its dendrite end and has a knoblike swelling with about a dozen basal bodies. The axons leave the epithelium and unite in the lamina propria as very small nerves that then pass to the brain through foramina in the cribriform plate of the ethmoid bone.

• Supporting cells are columnar, with broad, cylindrical apexes containing the nuclei and narrower bases. On their free surface are microvilli submerged in a fluid layer. Well-developed junctionalcomplexes bind the supporting cells to the olfactory cells.

• Basal cells are small, spherical or cone-shaped cells near the basal lamina. These are the stem cells for the other two types, replacing the olfactory neurons every 2 to 3 months and support cells less frequently.

The lamina propria of the olfactory

epithelium possesses large serous

glands, the olfactory glands (of Bowman),

which produce a constant flow of fluid

surrounding the olfactory cilia and

facilitating the access of new odoriferous

substances.

Larynx

Larynx

• Below the epiglottis and laryngeal vestibule, the mucosa projects into

the lumen bilaterally with two pairs of folds separated by a narrow

space.

• The upper immovable vestibular folds are partly covered with typical

pseudostratified respiratory epithelium overlying numerous

seromucous glands and occasional lymphoid nodules.

• The lower vocal folds have features important for phonation or sound

production:

• Stratified squamous epithelium protects the mucosa from abrasion and desiccation

from rapid air movement.

• A dense regular bundle of elastic connective tissue, the vocal ligament, supports the

free edge of each vocal fold.

• Deep to the mucosa of each vocal fold are large bundles of striated fibers that

comprise the vocalis muscle.

The state of contraction of the vocalis

muscle and other muscles of the larynx

regulates the width of space between the

vocal folds and thus sound production

Trachea

Trachea

• The trachea is lined with typical respiratory mucosa in which the

lamina propria contains numerous seromucous glands producing

watery mucus.

• A series with about a dozen C-shaped rings of hyaline cartilage in the

submucosa reinforces the wall and keeps the tracheal lumen open.

• The open ends are bridged by a bundle of smooth muscle called the

trachealis muscle and a sheet of fibroelastic tissue attached to the

perichondrium.

• The entire organ is surrounded by adventitia.

Trachealis Muscle

• The trachealis muscle relaxes during swallowing to facilitate the

passage of food.

• The muscle strongly contracts in the cough reflex to narrow the

tracheal lumen and provide for increased velocity of the expelled air

and better loosening of material in the air passage.

Bronchi

Intrapulmonary Bronchi

• The mucosa of the larger bronchi is structurally similar to the tracheal

mucosa except for the organization of cartilage and smooth muscle.

• In the extrapulmonary (primary) bronchi most cartilage rings

completely encircle the lumen, but as the bronchial diameter

decreases, cartilage rings are gradually replaced with isolated plates

of hyaline cartilage.

• Small mucous and serous glands are abundant, with ducts opening

into the bronchial lumen.

• The lamina propria also contains crisscrossing bundles of spirally

arranged smooth muscle and elastic fibers which become more

prominent in the smaller bronchial branches.

Bronchial Wall

Bronchioles

Bronchioles

• Bronchioles are typically designated as the intralobular airways with

diameters of 1 mm or less, formed after about the 10th generation of

branching

• They lack both mucosal glands and cartilage

• The epithelium decreases in height and complexity to become ciliated

simple columnar or simple cuboidal epithelium

• The ciliated epithelial lining of bronchioles begins the mucociliary

apparatus or escalator, important in clearing debris and mucus by

moving it upward along the bronchial tree and trachea.

Clara Cells

Clara Cells

• Most numerous in the cuboidal epithelium of terminal bronchioles are

Clara cells, or exocrine bronchiolar cells, which have nonciliated,

dome-shaped apical ends with secretory granules.

• Functions

• Secretion of surfactant lipoproteins and mucins on the epithelial surface

• Detoxification of inhaled xenobiotic compounds by enzymes of the SER

• Secretion of antimicrobial peptides and cytokines for local immune defense

• In a stem cell subpopulation, injury-induced mitosis for replacement of the

other bronchiolar cell types.

Respiratory Bronchioles

• Each terminal bronchiole subdivides into two or more respiratory bronchioles that include saclike alveoli and represent the first-part respiratory region of this organ system.

• The respiratory bronchiolar mucosa is structurally identical to that of the terminal bronchioles, except for a few openings to the alveoli where gas exchange occurs.

• The mucosa lining consists of Clara cells and ciliated cuboidal cells, with simple squamous cells at the alveolar openings and extending into the alveolus.

• Proceeding distally along the respiratory bronchioles, alveoli are more numerous and closer together.

• Smooth muscle and elastic connective tissue make up the lamina propria.

Bernoulli’s Principle

• Bernoulli’s Principle

• As air moves faster, the pressure decreases

• As air moves slower, pressure increases

• Since the total cross sectional area of the respiratory tract actually

increases due to branching in parallel bronchioles, the air velocity is

slower within each bronchiole

• Low speed of air less need for reinforcement less cartilage

• The higher pressure prevents collapse of airways, whereas in areas

like the trachea, high speeds=low pressure and cartilage is needed

for reinforcement.

Alveoli

Alveoli

• Distal ends of respiratory bronchioles branch into tubes called alveolar ducts that are completely lined by the openings of alveoli. Both the alveolar ducts and the alveoli themselves are lined with extremely attenuated squamous cells.

• Each alveolus resembles a small rounded pouch open on one side to an alveolar duct or alveolar sac.

• Between neighboring alveoli lie thin interalveolar septa consisting of scattered fibroblasts and sparse extracellular matrix (ECM), notably elastic and reticular fibers, of connective tissue.

• The arrangement of elastic fibers enables alveoli to expand with inspiration and contract passively with expiration; reticular fibers prevent both collapse and excessive distention of alveoli.

• The interalveolar septa are vascularized with the richest capillary networks in the body

Blood Air Barrier

• Air in the alveoli is separated from capillary blood by three

components referred to collectively as the respiratory

membrane or blood-air barrier.

• Two to three highly attenuated, thin cells lining the alveolus

• Type I and II Pneumocytes

• The fused basal laminae of alveoli and capillary

• The thin endothelial cells of the capillary.

Type I Alveolar Cells

• Type I alveolar cells are attenuated cells that line alveolar surfaces.

• Maintain the alveolar side of the blood-air barrier and cover about

95% of the alveolar surface.

• These cells are so thin that the TEM was needed to prove that all

alveoli have an epithelial lining

• Organelles are grouped around the nucleus, reducing the thickness of

the cytoplasm at the blood-air barrier to as little as 25 nm.

• In addition to desmosomes, all type I epithelial cells have occluding

junctions that prevent the leakage of tissue fluid into the alveolar air

space

Type II

Type II Alveolar Cells

• Cuboidal cells that bulge into the air space (2-5%) of alveolar surface

• Type II cells divide to replace their own population after injury and to provide progenitor cells for the type I cell population.

• Nuclei are rounded and cytoplasm is typically lightly stained with many vesicles.

• Many vesicles of type II alveolar cells are lamellar bodies, which contain various lipids, phospholipids, and proteins that are continuously synthesized and released at the apical cell surface• Acts as pulmonary surfactant.

• The surfactant film lowers surface tension at the air-epithelium interface, which helps prevent alveolar collapse at exhalation and allows alveoli to be inflated with less inspiratory force, easing the work of breathing.

Alveolar Macrophages

• Alveolar macrophages, also called dust cells, are found in alveoli and

in the interalveolar septum

• Active macrophages in alveoli can often be distinguished from type II

pneumocytes because they are slightly darker due to their content of

dust and carbon from air and complexed iron (hemosiderin) from

erythrocytes

Vascular Networks

• 1) Pulmonary circulation, carrying O2-depleted blood

• 2) Bronchial circulation, carrying systemic, nutrient-rich blood.

• The pulmonary arteries and veins are relatively thin-walled as a result of the low pressures (25 mm Hg systolic, 5 mm Hg diastolic) within the pulmonary circuit. Within the lung, the pulmonary artery branches and accompanies the bronchial tree with its branches sharing the adventitia of the bronchi and bronchioles.

• Thinner walls, much lower ratio of wall diameter to lumen diameter, much lower pressure and lower resistance than systemic arteries.

• At the level of the alveolar duct, the branches of this artery form the dense capillary networks in the interalveolar septa that contact the alveoli.

Overview

Mucociliary Clearance and CF

• Cilia of the respiratory epithelium move the mucus blanket towards

the pharynx where it is swallowed or expectorated.

• Goblet cells secrete the blanket of mucus that moistens and collects

particles from the air coming in through the nasal cavity .

• In CF, blockage of the chlorine channels prevents secretion of water

and mucous becomes thick and sticky interfering with ciliary motility.

Asthma

• Asthma is a common condition produced by chronic inflammation

within the bronchial tree of the lungs. The disorder is characterized by

sudden constrictions of the smooth muscle in bronchioles called

bronchospasms, or bronchial spasms. The resulting difficulty in

breathing can be very mild to severe.

• Epinephrine and other sympathomimetic drugs relax the muscle and

increase the bronchiole diameter by stimulating the sympathetic

nervous system, and they are administered during asthma attacks.

• When the thickness of the bronchial walls is compared with that of the

bronchiolar walls, the bronchiolar muscle layer is seen to be

proportionately greater.

Alpha 1 Anti-trypsin and Emphysema

• Elastic fiber damage and loss is the basis of emphysema

• Chronic respiratory exposure to tobacco smoke inhibits alpha1-

antitrypsin, an inhibitor of elastase enzymes (secreted by alveolar

macrophages and neutrophils) that attack elastic tissue

• Emphysema primarily affects respiratory bronchioles and alveoli,

which become expanded and unable to expel air efficiently during

exhalation

Infant Respiratory Distress Syndrome

• Infant respiratory distress syndrome, the leading cause of death in

premature babies, is due to incomplete differentiation of type II

alveolar cells and a resulting deficit of surfactant and difficulty in

expanding the alveoli in breathing.

• Treatment involves insertion of an endotracheal tube to provide both

continuous positive airway pressure (CPAP) and exogenous

surfactant, either synthesized chemically or purified from lungs of

cattle.

• STEROIDS WORK TOO…