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LLU: Medicine: Anatomy: Histology Mentor: Respiratory

Histology Mentor

RESPIRATORY SYSTEM

 

I. HISTOLOGICAL FEATURES

A. Conducting passages or airways

1. Functions associated with that of conducting gases to and from the lungs.

a. "Air conditioning" - filter, add moisture, warm the air, trap and destroy hostile organisms.

b. Olfaction - special mucosa in roof of nasal cavity

c. Phonation - larynx

2. Histology

a. Ala of nose

1. External surface - thin skin with especially large sebaceous glands, small hair follicles

2. Internal surface - sweat glands, small sebaceous glands and large hair follicles (vibrissae help to filter large particles from inspired air). Epithelium - first part keratinized, but becomes non-keratinized near the respiratory epithelium

3. Support - skeletal muscle on outer surface of hyaline cartilage

b. Olfactory mucosa

1. Lamina propria - many small serous (Bowman's) glands and bundles of unmyelinated olfactory nerves that pass through the cribriform plate of the ethmoid bone to end in the olfactory bulb.

2. Epithelium - 4 cell types

a. basal cells - nuclei near basal lamina are capable of proliferating and replacing the other cells in the epithelium even the nerve cells.

b. olfactory cells - bipolar neurons: central processes form unmyelinated olfactory nerves; peripheral process extends to surface of epithelium where it is expanded to form the olfactory vesicle (not bulb) which bears very long non-motile cilia. These are the receptors. The small, dark, round olfactory cell nuclei are in the middle of the epithelium.

c. sustentacular cells - columnar, most superficial nuclei. These are attached to the olfactory cells at their apex by junctional complexes and granules in their apex indicate a secretory function.

d. brush cells with large, blunt microvilli. May be sensory, since fibers of the trigeminal nerve end in relation to these

c. Nasal passage - warms, humidifies and filters the air

1. Lamina propria - This is a very vascular connective tissue with large, thin-walled veins near the surface that can become engorged (swell bodies) to restrict air flow. Small mixed serous glands are present as is an abundance of diffuse lymphoid tissue with occasional nodules.

2. Respiratory epithelium lines the nasal passage and the respiratory tract. It has a prominent basement membrane that is easily seen with the light microscope because it includes a very thick reticular lamina. It is classified as pseudostratified columnar epithelium with goblet cells and contains several cell types. Chronic exposure to irritants can cause this epithelium to undergo metaplasia altering its cellular composition or even becoming stratified squamous. In its early stages this is reversible.

a. Ciliated cells with microvilli between cilia, function to move mucus towards oropharynx.

b. Brush cells - non-ciliated cells with short, blunt microvilli, associated with nerve endings and may be sensory.

c. Goblet cells secret mucus.

d. Small basally placed granule cells are part of the diffuse neuroendocrine system (DNES). Hormones secreted include serotonin, dopamine, somatostatin and calcitonin.

e. Basal cells that replicate to replenish the epithelium.

d. Soft palate and uvula

1. Oral surface - stratified squamous non-keratinized; mucous glands in submucosa surrounded by fat

2. Skeletal muscle support

3. Pharyngeal surface - pseudostratified ciliated columnar (cilia beat toward oral pharynx) and often, due to metaplasia, stratified columnar to squamous epithelium. Small mixed glands in lamina propria and diffuse lymphoid cells are more numerous than in oral mucosa. No true submucosa.

e. Epiglottis

1. Elastic cartilage support

2. Epithelium - stratified squamous non-keratinized on the lingual side, becoming thinner on the side facing the glottis.

3. Mixed glands present in the deep part of the lamina propria, that is also rich in elastic fibers.

f. Larynx (Drawing of section in frontal plane)

1. Lining epithelium

2. Exocrine glands (not present in true vocal fold)

3. False vocal fold

4. True vocal fold

5. Vocalis muscle (skeletal)

6. Hyaline cartilage(thyroid cartilage)

7. Fibrous connective tissue

1. Gross appearance - vocal folds - false vocal fold (ventricular fold) is superior to, and true vocal fold is inferior to, the ventricle.

2. Epithelium varies from place to place. Also from time to time, chronic irritation can cause pseudostratified columnar epithelium to undergo metaplasia to stratified columnar or even stratified squamous.

3. Vocal cord - elastic c.t. with some collagen covered by stratified squamous non-keratinized epithelium - no glands in the region of the vocal fold.

4. False vocal fold contains mixed glands.

5. Intrinsic muscle (vocalis, etc.) Is skeletal and deep to the vocal cord (elastic ligament).

6. Support provided by hyaline cartilage (thyroid, cricoid, lower part of arytenoids) and elastic cartilage (upper arytenoids, corniculate, and cuneiform).

g. Trachea and primary bronchi

1. Hyaline cartilage

2. Pseudostratified ciliated columnar epithelium

3. Smooth muscle (trachealis)

4. Mixed gland

5. Adventitia

1. Support - "C" shaped hyaline cartilage rings open dorsally with trachealis muscle (smooth) extending between tips of the cartilage.

2. Epithelium - respiratory pseudostratified ciliated with goblet cells with a prominent basement membrane.

3. Lamina propria - the inner portion is rich in longitudinally oriented bundles of elastic fibers, especially next to an outer layer of loose connective tissue that contains fat and mixed glands. Posteriorly the glands penetrate the trachealis muscle. The glands of the trachea are stimulated to secrete by parasympathetic nerves. Many plasma cells are associated with these glands.

h. Secondary bronchi - these have what is called by radiologists a centimeter branching pattern.

1. Support - irregular hyaline cartilage plates become progressively smaller and disappear when bronchi are about 1 mm in diameter.

2. Mucosa similar to trachea, except smooth muscle is arranged in the lamina propria in a spiral pattern and increases relatively as bronchi get smaller. Epithelium becomes progressively thinner to become low columnar with cilia; glands become progressively fewer, disappearing when cartilage plates disappear.

B. Terminal branches and lung lobules.

1. Terminal branches of respiratory tree. These have the millimeter branching pattern.

a. Bronchioles and terminal bronchioles are not supported by cartilage but depend on the elasticity of the lung to remain open. They are surrounded by a spiral of smooth muscle. Goblet cells disappear before the terminal bronchiole is reached. At that point, the epithelium is simple columnar (or cuboidal) with cilia. Non-ciliated cells are also found here and are known as Clara cells. They are important because of their high capacity to metabolize drugs and their contribution to the surface active agents of the lung. Richly innervated neuroepithelial bodies are special aggregates of neuroendocrine cells belonging to the diffuse neuroendocrine system.

b. Respiratory bronchioles - studded by alveoli; simple cuboidal epithelium; cilia are found in some parts of the respiratory bronchioles.

c. Alveolar duct - surrounded by and terminates in alveoli and alveolar sacs. Smooth muscle and elastic fibers surround openings into these spaces.

d. Alveolar sacs - surrounded by alveoli

2. Alveolus - the ultimate respiratory tissue

a. Cells

1. Principal lining cell - simple squamous or Type I pneumocyte - also called low alveolar cell.

2. Great alveolar cell - granular pneumocyte or Type II pneumocyte - source of surfactant (a complex mixture of lipids especially dipalmitoyl phosphatidylcholine, carbohydrates, and protein) contains dense lamellated bodies derived from lysosomes.

3. Alveolar macrophages - (dust cells) enter the alveolar spaces from the capillaries in the alveolar septa and sweep the surface of the respiratory epithelium. These can replicate in the lung, but are also replenished by cells from the bone marrow. Removed by degeneration, returning to lymph or via ciliary movement to the pharynx. In pneumonia alveoli become filled with neutrophils.

b. Interalveolar septum

1. Stroma and capillaries - Capillaries are continuous with occluding junctions. Due to margination the concentration of leukocytes in the capillaries is enriched relative to that found in peripheral blood. PMN 104 fold, lymphocytes 47 fold, monocytes 86 fold. Cell Tiss Res. 271:469-476, 1993


2. Lining cells - Type I and Type II alveolar cells (pneumocytes) have intricate occluding junctions.

3. Contractile interstitial cells

4. Alveolar pores of Kohn - function is not clear, but could provide alternative routes of ventilation.

3. Primary and secondary lung lobules

a. Primary - formed by 1 terminal bronchiole and its branches. It is also called an acinus.

b. Secondary - composed of a bronchiole and terminal bronchioles arising from it and thus it includes many primary lobules. It is best defined by the interlobular septum which contains the veins draining the lobule. This septum is incomplete in the adult.

4. Blood vessels and pleura

a. Pulmonary arteries - follow bronchial tree to alveolar ducts where continuous capillaries form the network in the walls of alveoli. Supernumerary arteries that follow the veins, provide a collateral blood supply.

b. Pulmonary veins - begin in the c.t. septa around secondary lobules and follow the septa to join the pulmonary arteries around bronchioles at the apex of the secondary lobule.

c. Bronchial arteries and veins (near the hilus) supply airways. The larger airways have a fenestrated capillary bed.

5. Lymphatic drainage - follows both bronchial tree and the pulmonary veins in the septa at the periphery of lobules. Macrophages containing pigment (carbon) may be found in lymph tissue along airways.

C. Development

1. Organogenesis - endoderm from laryngotracheal groove forms epithelium of conducting airways and alveoli.

2. Fetus 4 months - distinctively gland-like; airways look like ducts and cuboidal epithelium of alveoli like acini.

3. New born - expansion of alveoli occurs during first day or so of life.

4. Growth - by retrograde alveolization of bronchioles.

II. FUNCTIONAL CONSIDERATIONS

A. Air flow and cross-sectional area of airways. The smallest cross-sectional area of the airways is at the larynx and the 8th generation of the airways. From the 8th generation onward, with each bifurcation of the bronchi and bronchioles, the total cross-sectional area increases exponentially. This means that the maximum rate of flow in the terminal bronchioles is extremely small. In fact, essentially no convection of gases occurs in the alveoli as a result of respiratory movements. Therefore, gas exchange in the alveoli depends largely on diffusion. On the other hand, the presence of alveolar pores and the possibility of differential constriction of bronchioles may make serial ventilation possible.

B. Alveolar gas exchange - In the most attenuated regions of the alveoli to reach the erythrocyte plasma membrane oxygen must pass through

1. a layer of surfactant rich in a variety agents especially dipalmitoyl phosphatidylcholine
2. plasma membranes and cytoplasm of pneumocyte type I cells.
3. fused basement membrane derived from both pneumocytes and endothelial cells
4. endothelial cell plasma membranes and cytoplasm. Erythrocytes are in close contact with the endothelial cells.

C. Stroma and Respiratory movements - elastic fibers in the alveolar walls and surrounding the airways form a network of fibers that stretches from the visceral pleura to the airways. These are kept stretched by the negative pressure in the space between the visceral and parietal pleura. When air is allowed to enter that space the lung collapses and becomes nonfunctional. When the elastic fibers degenerate, as in emphysema, a positive pressure must be exerted to push the air out of the lung and this causes the bronchioles to collapse making it more difficult to get the air out.

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