RESPIRATORY SYSTEM

RESPIRATORY SYSTEM. URINARY SYSTEM.

 

Respiration is a term used to describe two different but interrelated processes: cellular respiration and mechanical respiration. Cellular respiration is the process in which cell derive energy by degradation of organic molecules. Mechanical respiration is the process by which oxygen required for cellular respiration is absorbed from the atmosphere into the blood vascular system and the process by which carbon dioxide is excreted into the atmosphere. Mechanical respiration occurs within the respiratory system.

The respiratory system consists basically of the lungs and airways (i.e., pharynx, larynx, trachea, bronchi). Specialized for gaseous exchange between blood and air, including the uptake of oxygen and release of carbon dioxide, it is functionally divisible into 2 major parts: the conducting and respiratory portions.

The respiratory system is divided anatomically into two pails, the upper and lower respiratory tracts, which are separated by the pharynx. The pharynx is the best considered functionally and histologically as part of the gastrointestinal tract despite its important role as an airway.

Ventilating mechanism This mechanism, which creates pressure differences that move air into (inspiration) and out of (expiration) the lungs, includes the diaphragm, rib cage, intercostal muscles, abdominal muscles, and the elastic connective tissue in the lungs. Inspiration (inhalation) is active, involving muscle contraction To inhale, the intercostal muscles lift the ribs while the diaphragm and abdominal muscles lower the floor of the thoracic cavity. This enlarges the cavity, creating a vacuum that draws air through the airways. The incoming air expands the airways, inflates the lungs, and stretches the elastic connective tissue. Expiration (exhalation) is more passive: Relaxing the muscles allows the elastic fibers to retract, contracting the lungs and forcing air out.

Conducting portion The walls of this system of tubes are specialized to carry air to and from the site of gas exchange without collapsing under the pressures created by the ventilating mechanism. This portion also conditions the air, warming, moistening, and cleaning it to enhance gas exchange. It includes the nasal cavity, nasopharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles.

Respiratory portion This portion is distinguished by alveoli, small, saccular structures whose thin walls enable the gas exchange between air and blood. Alveoli occur in clusters at the end of the bronchial tree. These clusters extend (like rooms from a hallway) from the walls of respiratory bronchioles, alveolar ducts, and atria and alveolar sacs.

Wall Structure: Like the digestive tract, the tubelike respiratory tract has layered walls whose lining epithelium derives from endoderm. The wall layers include an epithelium, a lamina propria that contains mucous glands as well as cartilages that prevent the tract from collapsing under pressure, smooth muscle that regulates the luminal diameter, and an adventitia that contains collagen and elastic fibers. Each of these layers undergoes gradual changes as the wall’s overall thickness decreases from nasal cavity to alveoli.

Respiratory epithelium. The epithelium lining most of the tract is ciliated pseudostratified columnar with goblet cells; it is generally referred to as respiratory epithelium. As the respiratory tract undergoes successive branching and its lummal diameter decreases, the epithelium gradually drops in height, and loses first goblet cells and then cilia as it approaches the alveoli.

Epithelial cell types

Ciliated columnar cells are predominate in the tract, has about 300 motile cilia on its apical surface; there are associated basal bodies in the apical cytoplasm. Their main function is protection.

Mucous goblet cells are the second most numerous type. They secrete the mucus that covers the epithelium and traps and removes bacteria and other particles from inspired air. Cilia projecting from columnar cells sweep the contaminated mucus toward the mouth for disposal.

Endocrine cells produce hormones, which have influence on conducting portion, they regulate muscle contraction.

Basal cells – small round cells lie on the basal lamina but do not reach the lumen. They appear to be stem cells that can replace the other cell types.

Small granule cells resemble basal cells, but they contain many small cytoplasmic granules and exhibit DNES activity (Clara cells). Their main function is to destroy surfactant.

Brush cells also columnar, these cells lack cilia; they often have abundant apical microvilli. Two types are present: One resembles an immature cell and apparently serves to replace dead ciliated or goblet cells. The other has nerve endings on its basal surface and appears to be a sensory receptor.

Small granule cells and brush cells appear only in lower pans of conducting portion and in bronchioles.

Lamina propria consists of loose connective tissue and contains mucous glands in the upper tract (from the nasal cavity to the bronchi). Its elastic fiber content increases toward the alveoli. Skeletal connective tissue support begins as cartilage and bone in the nasal cavity and becomes cartilage only in the larynx. It gradually decreases, disappearing at the level of the bronchioles.

Smooth muscle begins in the trachea, where it joins the open ends of the C-shaped tracheal cartilages. In the bronchi, many layers of smooth muscle cells encircle the walls in a spiral. From this point, the thickness of the muscle layer gradually decreases until it disappears at the level of the alveolar ducts.

 

NASAL CAVITY

 

NASAL CAVITY is divided by the nasal septum into 2 bilaterally symmetric cavities that open to the exterior through the nares (nostrils). Each cavity consists of 2 chambers-a vestibules and a nasal fosses—which differ in position, size, and wall structure.

Vestibule: The smaller, wider, anterior chamber of each side, it lies just behind the nares. The medial septum and lateral walls are supported by cartilage, and the epithelial lining is a continuation of the epidermis that covers the nose. Just inside, the epithelium is keratinized, containing many sebaceous and sweat glands as well as thick short hairs called vibrissae, which filter large particles from inspired air. Deeper in the vestibule, the epithelium changes from keratinized to nonkeratniized stratified squamous and then to respiratory epithelium just before entering the nasal fossa.

Nasal Fossa: This is the larger, narrower, and more posterior chamber on each side. Here the septum and lateral walls are lined by respiratory epithelium. They are supported by the bone of the skull and contain mucous glands and venous sinuses in the lamina propria.

Three curved bony shelves, termed conches, or turbinate bones, project into each fossa from its lateral wall. These help warm and moisten the air by increasing the mucosal surface area and forming a system of baffles that cause turbulence and slow the airflow through the cavity. Alternating from side to side every 20-30 minutes, venous plexuses (swell bodies) in the conchal mucosa engorge with blood, causing it to swell. This action restricts airflow, directing it through the other side of the nose, and thus helps prevent overdrying of the mucosal surface. Arterial vessels in the fossa walls create a countercur- rent system that warms air by directing blood flow from posterior to anterior (opposite to the flow of inspired air) in a series of small arches. Specialized olfactory epithelium is present in the roof of each fossa.

PARANASAL SINUSES. These are dilated cavities in the frontal, maxillary, ethmoidal, and sphenoidal bones around the nose and eyes. Their thin respiratory epithelial lining has few goblet cells and is bound tightly to the periosteum of the surrounding bones by a lamina propria that contains a few small mucous glands. Mucus produced here drains into the nasal fossa through small openings that are protected by the conches.

NASOPHARYNX. The upper part of the pharynx, the nasopharynx is a broad single cavity overlying the soft palate. It is continuous anteriorly with the nasal fosses and inferior!)’ with the oral part of the pharynx (oropharynx). The walls, lined by respiratory epithelium, are supported by bone and skeletal muscle.

LARYNX. A bilaterally symmetric tube, the larynx iies in the neck between the base of the oropharynx and the trachea. During swallowing, its opening is protected by the epiglottis. Its walls, supported by several laryngeal cartilages in the lamina propria, contain skeletal muscle and house the vocal apparatus.

Epiglottis: This flap of tissue extends toward the oropharynx from the anterior border of the larynx. It is covered on its superior surface by nonkeratinized stratified squamous epithelium and on its inferior surface by respiratory epithelium. The lamina propria contains a few mucous glands and a small plate of elastic cartilage. During swallowing, the backward motion of the tongue forces the epiglottis over the laryngeal opening, directing food away from the airway and into the esophagus. After swallowing, the elastic cartilage helps to reopen and maintain the airway.

Laryngeal Cartilages: Several cartilages frame the laryngeal lumen and serve as attachments for the skeletal muscles that control the vocal apparatus. The larger thyroid, cricoid, and most of the paired arytenoid cartilages are hyaline, while the smaller ones—the paired cuneiform and corniculate, the epiglottis, and the tips of the arytenoids—are elastic.

Vocal Apparatus: The broad part of the larynx, below the epiglottis and surrounded by the thyroid cartilage, contains 2 bilaterally symmetric pairs of mucosal folds.

False vocal cords (vestibular folds) These are the upper pair of folds in the larynx. They are covered by respiratory epithelium and contain serous glands whose ducts open mainly into the cleft that separates them from the lower pair of folds.

True vocal cords This lower pair of folds is covered by stratified squamous epithelium; each contains 2 major structures: a large bundle of elastic fibers that run front to back, called the vocal ligament; and a bundle of skeletal muscle that runs parallel to the ligament, called the vocal muscle. Air forced through the larynx by the ventilating mechanism causes the true cords to vibrate. The vocal muscle regulates the tension of the cords, while other muscles control the shape and position of the laryngeal lumen. In this way, the laryngeal muscles control the pitch (frequency) and other aspects of the sounds produced by the vibrating cords. The cords also assist the epiglottis in preventing foreign objects from reaching the lungs; they close to build up pressure what coughing is required to dislodge materials blocking the airway.

 

TRACHEA

 

This 10-cm tube extends from the larynx to the primary bronchi. It is lined by respiratory epithelium, and its lamina propria contains mixed seromucous glands that open onto its lumen. Its most characteristic feature is the presence of 16-20 C-shaped hyaline cartilage rings whose open ends are directed posteriorly. The opening is bridged by a fibroelastic ligament that prevents overdistention as well as by smooth muscle bundles (tracheal muscle) that constrict the lumen and increase the force of airflow during coughing and forced expiration.

 

 

Trachea, identified by the presence of hyaline cartilage in its wall. To the left of the cartilage is the mucosa, including epithelium and its underlying connective tissue. The cartilage ring is immediately covered, on both surfaces, with bright pink perichondrium.

 

The wall of trachea consists of 4 tunics: mucosa, submucosa, fibro-cartilages and adventitia. Mucosa has 3 layers – ciliated epithelium, lamina propria and poorly defined muscularis mucosa. Submucosa contains mucous glands. Hyaline cartilage in the trachea is C-shaped. Outermost tunic – adventitia consists of loose connective tissue with numerous blood vessels and nerves.

 

 

Detail of pseudostratified ciliated columnar epithelium lining the trachea. Note the presence of pale goblet cells. Foreign particles are trapped in mucus secreted by goblet cells and then moved up (and out of) the respiratory tract by the beating cilia. A pale and quite thick basement membrane underlies this epithelium.

 

 

Posterior wall of the trachea with smooth muscle (pink strand near epithelium) replacing cartilage in the wall. The cartilage is basophilic in color. Structurally, it is a C-shaped ring, incomplete posteriorly, but with the trachealis muscle spanning the gap between the ends of the “C”.

 

 

The trachealis muscle (smooth muscle) is the bright pink band in the middle of the field. Notice how cellular the c.t. under the epithelial layer is. Wandering blood cells, especially lymphocytes and eosinophils, are usually found here.

 

Longitudinal, parasagittal section of trachea showing a series of darkly stained cartilage rings cut across. The rings are thicker anteriorly (at the right) than they are posteriorly (at the left). If this were a true mid-sagittal section, the cuts at the left would be of trachealis muscle instead of cartilage, so this section is clearly off-cen ter. The lining of the wide open lumen would be typical, pseudostratified “respiratory” epithelium. NOTE: Primary bronchi are essentially like the trachea in structure (but with continuous ring of cartilage). Lower portions of the respiratory tract appear in sections of lung and they show progressive loss of the various components characteristic of the trachea; that is, less and less cartilage, progressively lower epithelium, gradual loss of gob let cells, and finally loss of cilia and smooth muscle.

 

LUNGS

 

LUNGS. Their structure is similar to exocrine gland: they contain secretory portion and ducts. Secretory portion are alveoli with air and ducts are bronchial tree (system of branching bronchi).

BRONCHIAL TREE. This begins where the trachea branches to form 2 primary bronchi, one of which penetrates the hilum of each lung. The hilum is also the site at which arteries and nerves enter and veins and lymphatic vessels exit the organ. These structures, together with the dense connective tissue that binds them, form the pulmonary root. The bronchial tree undergoes extensive branching within the lungs. The changes in wall structure that accompany the progress of the bronchial tree toward the alveoli occur gradually and not at sharp boundaries.

 

An intrapulmonary bronchus with several separate pieces of hyaline cartilage in its wall. A thin layer of bright pink smooth muscle lies between the cartilage and the mucosa. (The mucosa, as always, consists of epithelium and underlying connective tissue.) In the upper left quadrant of the field is a large branch of the pulmonary artery, with it s bright pink tunica media (smooth muscle coat). Arterial branches accompany the branching respiratory tree all along the way.

 

An intrapulmonary bronchus with a patch of cartilage along its lower edge. Notice the field of alveoli and small branching terminals all around, typical of lung.

 

All bronchi have similar structure: mucous, submucous, cartilages and adventitia. Mucous is covered by respiratory epithelium, under which is lining lamina propria and in bronchi appear smooth muscles. Respiratory epithelium undergoes progressive transition from a tall, pseudostratified columnar, ciliated form in primary bronchi to a simple, cuboidal, non-ciliated form in the smallest airways.

Goblet cells are numerous in primary bronchi, but decrease in number and are absent in the terminal bronchioles. Lamina propria has a similar structure as in the upper part of conducting portion. A layer of smooth muscles lies deep in mucosa and becomes increasingly prominent as the airway diameter decreases. It reaches its greatest prominence in the terminal bronchioles. Smooth muscle tone controls the diameter of the conducting passages and thus controls resistance to airflow within the respiratory tree. The autonomic nervous system, adrenal medullary hormones and local factors modulate smooth muscle tone.

Submucosal connective tissue contains serous and mucous glands which becomes progressively less numerous in the narrowed airways and are not present beyond the tertiary bronchi. Cartilages provide a supporting skeleton for the bronchi and prevent the collapse of these airways during respiration. The cartilage framework in primary bronchi is arranged into flattened, interconnected plates of hyaline cartilage. The cartilage framework in secondary bronchi is reduced to a few irregular plates of hyaline cartilage. Tertiary bronchi have some elastic islands. In terminal bronchioles and bronchioles cartilages are absences.

 

 

Detail of previous wall, showing the large chondrocytes of the cartilage. The epithelium lining the lumen looks pseudostratified still. A layer of pink smooth muscle lies between it and the cartilage. Considerable elastic tissue lies in the respiratory wall as well, but is not distinguishable in H&E stain.

 

Primary (Principal) Bronchi: There are 2 primary bronchi, one entering each lung. Their histologic appearance is quite similar to that of the trachea, but their cartilage rings and spiral bands of smooth muscle completely encircle their respective lumens. The path of the right primary bronchus is more vertical than that of the left. As a result, foreign objects that reach the bronchi are more likely to lodge in the right side of the bronchial tree.

Secondary Bronchi: These lobar bronchi are branches that arise directly from the rjrimarv bronchi; each supplies one pulmonary lobe Since trie right lung has 3 lobes and the left only 2, the right primary bronchus gives rise to 3 secondary bronchi and the left primary bronchus gives rise to 2. Their histologic structure is similar to that of the primary bronchi except that their supporting cartilages (and those of the smaller bronchi) are arranged as irregular plates, of cartilage, rather than as rings.

Tertiary Bronchi: Arising directly from the secondary bronchi, which they resemble histologically, each of these segmental bronchi supplies one bronchopulmonary segment (pulmonary lobule). Although each lung has 10 such segments, the different number of secondary bronchi causes the tertiary branching pattern to differ between the right and left lungs. Except for a decrease in overall diameter, the histologic appearance of tertiary bronchi is identical to that of secondary bronchi. Tertiary bronchi may branch several times to form successively sraaller branches that are considered bronchi as long as their walls contain cartilage and glands.

Bronchioles: These are branches of the smallest bronchi. The largest bronchioles differ from the smallest bronchi only by the absence of cartilage and glands in their walls. Large bronchioles are lined by typical respiratory epithelium; as they branch further, the epithelial height and complexity decrease to simple ciliated columnar or cuboidal. Each bronchiole gives rise to 5-7 terminal bronchioles.

Terminal Bronchioles: The smallest components of the conducting portion of the respiratory system, these are lined by ciliated cuboidal or columnar epithelium and have no goblet cells. (The elimination of goblet ceils before the cilia in the lower

reaches of the bronchial tree is important in preventing individuals from drowning in their own mucus.) The lining here also includes dome-shaped cilia-free Clara cells, whose cytoplasm contains glycogen granules, lateral and apical Golgi complexes, elongated mitochondria, and a few secretory granules. Although the function of these cells is unclear, they may be serous secretory cells substituting for mucous goblet cells at this level. Each terminal bronchiole branches to form 2 or more respiratory bronchioles, which form a respiratory portion. Morpho-functional unit of respiratory portion is acinus, which consists of respiratory bronchioles, alveolar duets and alveolar sacs.

 

 

A branching portion of the respiratory tree. No cartilage is visible here, so we’ll say it’s a bronchiole. Note a lymphatic nodule in the fork of the tree; such nodules may be found randomly along the respiratory tree. Note also the cross-cuts of pulmonary artery branches accompanying the tree. Cuts of alveoli of the lung fill the surrounding field.

 

Respiratory Bronchioles: These are the first part of the respiratory portion, with a cuboidal epithelial without cilia, lining that resembles that of the terminal bronchioles but which is interrupted by thin-walled saccular evaginations called alveoli. The number of alveoli increases as the respiratory bronchioles proceed distally. As the alveoli increase iumber, the cilia decrease until they disappear. Lamina propria and smooth muscles are bad developed.

Alveolar Ducts: These are simply the distal extensions of the respiratory bronchioles where the alveoli are so dense that the wall consists almost entirely of these sacs, and the lining has been reduced to small knobs of smooth muscle covered by cilia-free simple cuboidal cells. The knobs appear to project inio the elongated lumen of the duct, each resting atop a thin septum that separates adjacent alveoli. The alveolar clue: can thus be likened to a long hallway with so many doorways leading to small rooms (alveoli), that the hallway (the alveolar duct) appears almost to lack walls.

 

Lung:

·                    a = alveoli, with thin interalveolar septa between them

·                    b = smooth muscle in its wall

·                    c = blood vessel, filled with r.b.c.’s

·                    d = bronchiole (again, no cartilage in its wall)

 

Atria and Alveolar Sacs: Atria are the distal terminations of alveolar ducts. The arrangement is comparable to a long hallway (alveolar duct) leading to a rounded foyer (atrium). The foyer has small doorways leading to some small rooms (alveoli), but also has 2 or more larger doorways leading into short, dead-end hallways (alveolar sacs). The short hallways are also lined by small rooms (alveoli). The difference between atria and alveolar sacs is that the atria open into alveolar ducts, alveoli, and alveolar sacs, while the alveolar sacs open only into alveoli and atria. Although these distinctions can be made fairly easily in sections cut longitudinally through the entire system of passageways beginning with the alveolar duct, such perfect cuts are relatively rare in standard slides of lung tissue. More often, the various components are cut in oblique or cross section, and only the openings to the alveoli are seen, making it hard to distinguish between the sacs and the atria. In such cases, the only useful clue is the size of the knobs that project into the passageways. Those projecting into alveolar sacs lack smooth muscle and are thus smaller than those projecting into either the atria or the alveolar ducts.

 

 

Lung:

·                    b = respiratory bronchiole with alveolus (a) in its wall. Most of the wall of the bronchiole has a definite line of dark along it, signifying a cuboidal or columnar epithelium (simple, rather than pseudostratified by now).

·                    d & c = alveolar duct. Its wall consists almost entirely of alveoli, which have only a simple squamous lining, too flat to be visible here.

·                    e = alveoli (the smallest respiratory units)

·                    f = blood vessel (branch of pulmonary artery still)

 

Another view of terminal branches of respiratory tree in the lung. In the middle of the field is a small terminal bronchiole branching off into three or four alveolar ducts to the right. The bronchiole has a definite, pink epithelial lining, while the walls of the alveolar ducts consist mainly of alveoli. The bronchiole is called terminal simply because it’s the last generation of bronchiole before alveoli start to appear in the wall. Just before the alveolar ducts branch off, you can see a couple of small alveolar outpocketings in the bronchiole wall, thus making this short segment a respiratory bronchiole.

 

(Note: along the top of this field is a wall of a bronchus, with two very small, basophilic patches of cartilage just under the pink layer of smooth muscle.)

 

Lung

·                    a = inflated alveolar ducts

·                    c & d = blood vessels filled with r.b.c.’s

·                    e = bronchiole. Note pink simple columnar epithelium and absence of cartilage. Blue = connective tissue.

 

 

The outer reaches of two lung lobules, with a connective tissue septum running vertically between them. The lower edge of the tissue here is the visceral pleura. Lymphatic vessels (a) and veins (b) run in the septa at the periphery of each lobule. Arteries, as we’ve noted previously, typically follow the branchings of the respiratory tree itself f. At (c) there is a bronchiole. The mucosa lining its lumen is typically thrown into folds or scallops because of contraction of smooth muscle and elastic fibers in the wall.

Detail of inter-alveolar septa which form the shared walls of alveoli. The large spaces here are alveoli, filled with air. In the septa, orange is the red blood cells and brown is the nuclei of the capillary endothelium and alveolar cells. Every surface facing the alveolar air spaces is lined by simple squamous epithelium of the alveolar walls.

ALVEOLI. Occurring only in the respiratory portion (which their presence distinguishes from the conducting portion), these small sacs open into a respiratory bronchiole, an alveolar duct, an atrium, or an alveolar sac. They are separated from one another by thin walls termed interalveolar (or alveola;-) septa. Alveoli wall is covered by simple squamous epithelium, which contains three cell types.

 

 

Detail of the septa between alveolar spaces. The small spaces within the septa are empty capillary lumens. Nuclei belong mainly to endothelial cells and alveolar epithelium; it would take EM to identify which is which with certainty. A few might also be fibroblasts or wandering c.t. cells. Very fine collagenous and elastic fibers also accompany the capillaries. As you can see, especially in the capillaries in the center and in the upper left of the field, the combined thickness of capillary endothelium plus simple squamous alveolar epithelium separating blood from air, is extremely thin.

 

Type I cells also called type I alveolar cells, type 1 pneumocytes, and squamous alveolar cells, these are squamous epithelial cells that make up 97% of the alveolar surfaces. They are specialized to serve as very thin (often only 25 nra in width) gas-permeable components of the blood-air barrier. Their organelles (eg, Golgi complex, endoplasmic reticulum, mitochondria) cluster around the nucleus. Much of the cytoplasm is thus unobstructed by organelles, except for the abundant small pinocytotic vesicles that are involved in the turnover of pulmonary surfactant and the removal of small particles from the alveolar surfaces. They attach to neighboring epithelial cells by desmosomes and occluding junctions. “The latter reduce pleural effusion—leakage of tissue fluid into the alveolar lumen. Type 1 cells can be distinguished from the nearby capillary endothelial cells by their position bordering the alveolar lumen and by their slightly more rounded nuclei. Main function is gas exchange.

Type II cells are also called type II alveolar cells, type II pneumocytes, great alveolar cells cells, cover the remaining 3% of the alveolar surface. They are interspersed among the type I cells, to which they attach by desmosomes and occluding junctions. Type II cells are roughly cuboidal with round nuclei; they occur most often in small groups at the angles where alveolar septal walls converge. At the electron microscope level, they contain many mitochondria and a well-developed Golgi complex., but they are mainly characterized by the presence of large, membrane-limited lamellar (multilamellar) bodies. These structures, which exhibit many closely apposed concentric or parallel membranes (lamellae), contain phospho­lipids, glycosaminoglycans, and proteins. Type II cells are secretory cells. Their secretory product, pulmonary surfactant, is assembled and stored in the lamellar bodies, which also carry it to the apical cytoplasm. There, the bodies fuse with the apical plasma membrane and release surfactant onto the alveolar surface.

EM of alveolar wall with a Type II cell (or granular pneumocyte). It is a rounded or cuboidal cell, in contrast to the very flat Type I alveolar lining cell. To compare the differences in cell thickness, look in the lower part of the micrograph where you see capillary endothelium (1), basal lamina (2), and alveolar Type I epithelium (3) making up the very thin blood-air interface. The large, vacuolated, rather ragged looking vesicles in the cytoplasm of the Type II cell are lamellar bodies containing the precursor of alveolar surfactant.

Alveolar macrophages Known also as dust cells, these large monocyte-derived representatives of the mononuclear phagocyte system are found both on the surface of alveolar septa and in the interstitium. Macrophages are important in removing any debris that escapes the mucus and cilia in the conducting portion of the system. They also phagocytose blood cells that enter the alveoli as a result of heart failure. These alveolar macrophages, which stain positively for iron pigment (hemosiderin), are thus designated heart failure cells. They came from the blood and phagocyse toxins and nicotine.

 

 

EM showing basal lamina (1) between squamous alveolar epithelium (2 = Type I cell) and capillary endothelium (3). The nucleus at upper right belongs to the endothelial cell lining the capillary. The dark structure is a red blood cell. The capillary plus the alveolar linings on both sides constitute the interalveolar septum that lies between two alveolar spaces.

 

Pulmonary Surfactant: Continuously synthesized and secreted by type II alveolar cells onto the alveolar surfaces, pulmonary surfactant is removed from these surfaces by alveolar macrophages and by type I and II alveolar cells Its composition and continuous turnover allow it to serve 2 major functions. Not only does it reduce surface tension in the alveoli, it is also thought to have some bactericidal effects, cleaning the alveolar surface and preventing bacterial invasion of the many capillaries in the septa. The surfactant forms a thin 2-layer film over the entire alveolar surface. The film consists of an aqueous basal layer (hypophase) composed mainly of protein, which is covered by a monomolecular film of phospholipid (mainly dipalmitoyl lecithin) whose fatty acid tails extend into the lumen. By reducing surface tension, the surfactant helps prevent collapse of the alveoli curing expiration. It thus eases breathing by decreasing the force required to reopen the alveoli during the next inspiration. Because surfactant secretion begins in the last weeks of fetal development, premature infants often suffer a condition called hyaline membrane disease, evidenced by respiratory distress (labored breathing) caused by the lack of surfactant. Luckily, surfactant secretion can be induced by administering glucocorticoids, significantly improving the infant’s condition and chances for survival.

Alveolar Lining Regeneration: Daily turnover of about 1% of the type II cells, whose mitotic progeny form both type I and type II cells, allows for normal alveolar lining renewal. When these lining cells are destroyed by inhaling toxic gases, replacements for both types of cells are similarly derived from the surviving type II cells.

 

Interalveolar Septa

 

The structural features of these septa, which are specialized for gas exchange, are critically important to respiratory function. The septa consist of 2 simple squamous epithelial layers with the interstitium sandwiched between them. The interstitium consists of continuous (nonfenestrated) capillaries embedded in an elastic connective tissue that includes elastic and collagen fibers, ground substance, fibroblasts, mast cells, macrophages, leukocytes, and contractile interstitial cells that contract in response to epinephrine and histamine. This elastic tissue is an important component of the ventilating mechanism. Gas exchange occurs between the air in the alveolar lumen and the blood in the interstitial capillaries.

 

Alveolar pores

 

One or more pores may interrupt each septum. These connect adjacent alveoli and may help to equalize pressure and allow collateral air circulation thus maximizing the use of available alveoli when some small airways are blocked.

 

Blood-air barrier. This term refers to the structures that oxygen and carbon dioxide must cross to be exchanged. It includes the following layers: a. The layer of pulmonary surfactant on the alveolar surface: b The cytoplasm of the squamous epithelial (type I alveolar) cells; c. The fused basal lamina sandwiched between the type 1 alveolar and capillary endothelial ceils; and d The cytoplasm of the squamous endothelial cells lining the interstitial capillaries.

 

 

PULMONARY CIRCULATION

Blood Supply: The lungs have a dual blood supply: the functional (pulmonary) circulation and the systemic (nutrient) circulation. The 2 systems communicate with one another through extensive anastomoses near the capillary beds.

1. Functional circulation is provided by the pulmonary arteries and veins, Pulmonary arteries arising from the heart’s right ventricle as large-diameter elastic arteries, the pulmonary arteries branch and enter the lung at the pulmonary root. They follow the branching pattern of the bronchial tree to carry oxygen-poor blood to the lungs’ capillary beds for oxygenation. Smaller branches (less than 1 mm in diameter) are of the muscular type, with a definitive internal elastic lamina. Pulmonary arteries have a thin intima and thinner media than do other arteries of equal size.

Pulmonary veins collect oxygenated blood from the capillaries of the lungs and return it to the left atrium of the heart for distribution through the aorta and its branches. The larger branches of these veins accompany the bronchi, but the smaller branches travel unaccompanied in the connective tissue septa that separate the broncho-pulmonary segments. The thin intima of these vessels differs from other veins in that it lacks valves and contains a rich elastic fiber network in its subendothelial layer. While the media is absent in vessels smaller than 100 nm, in larger vessels it contains both smooth muscle and elastic fibers. The adventitia is thicker than that of pulmonary arteries. 2. Systemic circulation is provided by the bronchial arteries and veins.

2. Bronchial arteries. Typical muscular arteries arising from the aorta or from intercostal arteries, these are always smaller than the accompanying branches of the pulmonary arteries. The bronchial arteries enter at the pulmonary root and follow the branching pattern of the bronchial tree to the level of the respiratory bronchioles. Here they anastomoze with branches of the pulmonary artery. Branches of the bronchial arteries carry oxygen-rich blood to capillaries in the bronchi, bronchioles, interstitium, and pleura. The blood collects in submucosal venous plexuses in various parts of the bronchial tree before entering the bronchial veins.

Bronchial veins are typical small veins that carry blood from the submucosal bronchial venous plexuses and always accompany the bronchial tree Bronchial veins following the larger bronchi, empty into the azygous, hemiazygous, or posterior intercostal veins. Those associated with the smaller portions of the bronchial tree empty directly into branches of the pulmonary veins.

RESPIRATORY SYSTEM IS INNERVATED by autonomic nerve system. Parasympathetic motor fibers (branches of the vagus nerve) stimulate bronchial constriction, whiie sympathetic fibers cause bronchial dilation. Sympathomimetic drags such as isoproterenol are used to stimulate bronchodilation during asthma attacks.

 

THE PLEURA

 

This serous membrane has 2 layers, one covering die lungs (visceral pleura) and the other covering the internal wall of the thoracic cavity (parietal pleura). Like the peritoneum and the pericardium, the pleura consists of a thin squamous mesothelium attached to the organ or wall by a thin layer of connective tissue that contains collagen and elastic fibers. Bordered by the mesothelial cells, the narrow pleural cavity lies between the parietal and visceral pleurae. The cavity normally contains only a thin film of lubricating fluid that (together with the smooth mesothelial surfaces) reduces the friction between the lung surfaces and thoracic walls that would otherwise accompany the respiratory movements. Certain diseases and wounds allow excess air or fluid to enter the pleural cavity, increasing its size and restricting respiratory movement. White small amounts с fair and fluids can be absorbed, larger amounts may precipitate lung collapse and require medical intervention.

 

Disorders of the lungs

 

Metaplasia. This refers to the change in tissue organization or type undergone by epithelia in response to changes in the physical or chemical environment. For example, a smoker’s respiratory epithelium typically develops more goblet cells in response to high pollutant levels and fewer ciliated cells in response to carbon monoxide. These changes, which are reversible, frequently cause congestion of the smaller airways.

Pulmonary emphysema is a serious lung disorder, characterized by the obstruction of bronchioles, the trapping of air in passages, and a loss of pulmonary elasticity. Since expiratioormally results from elastic recoiling of the lungs, emphysema is a state of chronic hyperinflation, as the victim is unable to empty his lungs on forced expiration. In severe cases the chest is enlarged in all dimensions (barrel chest). Pulmonary emphysema is frequently associated with

chronic bronchitis, asthma, and other conditions that may cause inflammatory damage to the bronchioles; it is a chronic, slowly progressive disease, causing irreversible structural damage to the lung.

The rapidly rising incidence of emphysema is related first to the fact that people are living longer and this is degenerative disease. Second, the most common cause is related to heavy cigarette smoking. There is no cure for emphysema and supportive procedures only can be used.

Pneumonia is the condition in which there is inflammation of lung, tissue or of walls of the bronchi. The former is called lobar pneumonia and the latter bronchopneumonia. Pneumonia may be caused by bacteria or by viruses. When fluid collects in the alveoli, causing the lung to become solid and firm, the condition is called consolidation.

Tuberculosis is an inflammation of the lungs caused by Mycobacterium tuberculosis. In response to the bacteria, which destroy parts of the lung tissue, the body synthesizes fibrous connective tissue around the infection sites in an attempt to isolate them. Because the tubercles are inelastic, they interfere with the full recoling of the lung during expiration. In addition, the thick fibrous tissue increases the difficult)’ of alveolar gas diffusion.

The incident of lung cancer is increasing; it is not a simple matter of better detection techniques. Some cases of lung cancer are due to metastases, or the transfer of abnormal cells from one organ (the primary site) to another not directly connected with it. For example, cancerous cells from a kidney tumor may break free and carried to the lungs by way of the blood or the lymphatic system; this is called metastatic cancer of the lung. However, primary pulmonary cancer, which begins in the lungs, is the most common form of cancer in males today, and it is becoming increasingly common in female. This great increase in lung cancer incidence appears to have a direct relationship to heavy cigarette smoking over long periods of time. Many heavy smokers have in their lung tissue what appear to be precancerous ceils long before cancerous cells can be detected. These precancerous cells will gradually disappear if an individual abstains from smoking, and the odds of getting lung cancer will gradually go down to almost normal, but this reversal will take years.

Urinary system

 

The constancy of many materials in the extracellular fluid is determined by the activity of the kidneys. Since the normal function of all body cells is determine4d by this constancy, it is easy to understand the importance of normal renal function. Not only do all living cells constantly take materials from the blood during metabolic activity but they also release many metabolic waste products into the blood as they perform their vital functions as growth, repair and maintenance. The lungs remove carbon dioxide as a volatile gas, and some other metabolic wastes are removed by the large intestine. It remains for the kidneys to remove a wide range of water-soluble products, particularly those referred to as nitrogenous wastes. Water is eliminated from the body by several routes such as the skin, lungs and large intestine, but most of it is released as urine resulting from kidney function.

The kidney are the last of our boundary organs to be considered and, like a skin, lungs, and intestine, their activity is determined by the fact that the primary functional tissue found here is epithelial. We should then expect to find the basic activities of absorption, secretion, and protection as we found in the other boundary organs. Except for the initial formation of the glomerular filtrate by blood pressure through a selective membrane and special properties determined by anatomical arrangements of the functional units called the nephrons, the basic activities of the kidneys are essentially no different from those: of the other boundary organs.

The kidneys also regulate the fluid and electrolyte balance of the body and are the site of production of the hormones renin and erythropoietin. Renin participates in the regulation of blood pressure, and erythropoietin is a growth factor that stimulates the production of erythrocytes.

The urinary system consists of the paired kidneys and ureters and the unpaired bladder and urethra.

 

 

Anatomy of kidney. In the lower picture, notice positions of cortex, medullary pyramids, calyces, pelvis, blood vessels. Beginning with the minor calyces, and continuing on through the ureter, the lining is transitional epithelium.

 

STRUCTURE OF THE KIDNEYS

 

The kidneys are located in the posterior part of the abdominal cavity, one or either side of the vertebral column, behind the peritoneum. They rest on the psoas

major and the quadratus lumborum muscles and on part of diaphragm. The kidneys are not fixed in a rigid position against the abdominal wall, since they move with the diaphragm during inspiration. However, they are embedded in a mass of adipose tissue around which is found a supporting layer of fibrous tissue called the renal fascia.

Each kidney has a concave medial border, the hilum—where nerves enter, blood and lymph vessels enter and exit, and the ureter exits—and a convex lateral surface. The renal pelvis, the expanded upper end of the ureter, is divided into two or three major calyces. Several small branches, the minor calyces, arise from each major calyx.

 

 

Vascular arrangement. Follow renal artery to interlobar arteries to arcuate arteries to interlobular arteries. A kidney lobule lies between two interlobular arteries.

The kidney can be divided into an outer cortex and an inner medulla. The renal cortex is granular and reddish brown in appearance. It arches over the pyramids of the medulla and deeps between adjacent pyramids. These inward extensions of cortical substance are called the renal columns of Bertini.

 

 

Cortex of kidney – alternating straight rays and convoluted portions (with glomeruli). One longitudinally cut interlobular artery (pale pink contents) can be seeear the extreme left border of the picture, running up the middle of a convoluted portion, among glomeruli.

 

 

Medullary region. There are some longitudinal cuts of pale collecting tubules (at left center) and several blood vessels filled with pale pink fluid (to the right). Epithelium of collecting tubules is regular, block-like, simple cuboidal, with unusually clear cell walls. Other tubules in the field are thick and thin limbs of loops of Henle.

In humans, the renal medulla is darker in colour and consists of 10-18 conical or pyramidal structures, the medullary pyramids. From the base of each medullary pyramid, parallel arrays of tubules, the medullary rays, penetrate the cortex. Each medullary ray consists of one or more collecting tubules together with the straight portions of several nephrons. The mass of cortical tissue surrounding each medullary pyramid is a renal lobe, and each medullary ray forms the center of a conical renal lobule.

Nephron – is microscopic unit of structure and function. Each kidney is composed of 1 millioephrons. Each nephron consists of a dilated portion, the renal corpuscle; the proximal convoluted tubule; the thin and thick limbs of Henle’s loop; and the distal convoluted tubule. The collecting tubules and ducts, whose embryologic origin differs from that of the nephron, collect the urine produced by nephrons and conduct it to the renal pelvis. The renal pelvis is a funnel-shaped sac that forms the upper expended end of the ureter.

 

 

Nephrons emptying into a collecting tubule. Notice that the closer to the medulla a glomerulus lies, the longer the loop of Henle is. Also notice that the inner zone of the medulla (lowest section of the picture) contains only thin limbs of the loop of Henle, plus collecting ducts. This is the area where the counter-current mechanism for urine concentration (carried out between the tubules and the surrounding peritubular capillaries) is most active. To make his drawing clear, the artist has made one accommodation that is not quite accurate histologically; namely, within the cortex, the straight positions of the nephrons (that is, the thick and thin portions of the loops of Henle) shoul d lie immediately next to the collecting duct, thus making up the medullary ray. The glomeruli and convoluted portions of the nephrons would then lie on either side of the ray. The ray is the central axis of a lobule.

 

Each renal corpuscle consists of a tuff of capillaries, the glomerulus, surrounded by a double-walled epithelial capsule called Bowman’s capsule.

 

 

Renal corpuscle with connection to proximal tubule at lower border. This, then, would be a cut through the urinary pole of the corpuscle.

 

 

Detail of wall of renal corpuscle. The space is the lumen of Bowman’s capsule that receives glomerular filtrate from the capillary loops. Left wall is simple squamous parietal lining. The visceral lining of podocytes on the right wall of the space is too irregular to be seen clearly in light microscopy because it is following the curves of the individual capillaries.

The internal layer (the visceral layer) of the capsule envelops the capillaries of the glomerulus. The external layer forms the outer limit of the renal corpuscle and is called the parietal layer of Bowman’s capsule. Between the two layers of Bowman’s capsule is the urinary space, which receives the fluid filtered through the capillary wall and the visceral layer. Each renal corpuscle has a vascular pole, where the afferent arteriole enters and the efferent arteriole leases, and a urinary pole, where the proximal convoluted tubule begins. After entering the renal corpuscle, the afferent arteriole usually divides into two to five primary branches, each subdividing into capillaries and forming the renal glomerulus.

The parietal layer of Bowman’s capsule consists of a simple squamous epithelium supported by a basal lamina. At the urinary pole, the epithelium changes to the simple columnar epithelium characteristic of the proximal tubule.

During embryonic development, the epithelium of the parietal layer remains relatively unchanged, whereas the internal, or visceral, layer is greatly modified. The cells of this internal layer, the podocytes, have a cell body from which arise several primary processes. Each primary process gives rise to numerous sec­ondary processes, called pedicels, that embrace the capillaries of the glomerulus. At a periodic distance of 25 nm, the secondary processes are in direct contact with the basal lamina. However, the cell bodies of podocytes and many primary processes do not touch the basal lamina. The pedicels from one podocyte embrace more than one capillary; on a single capillary, the pedicels of two podocytes alter­nate in positioext to the basal lamina. Although pedicels contain few or no organelles, microfilaments and microtubules are numerous.

The secondary processes of podocytes interdigitate, defining elongated spaces about 25 nm wide— the filtration slits. Spanning adjacent processes (and thus bridging the filtration slits) is a diaphragm about 6 nm thick that is comparable to the diaphragm encountered in fenestrated endothelial cells. The cytoplasm of podocytes contains numerous free ribosomes, a few cisternae of rough endoplasmic reticulum, infrequent mitochondria, and a prominent Golgi complex. Podocytes have bundles of actin microfilaments in their cytoplasm that give them a contractile capacity.

 

EM of triangular shaped podocyte with its many terminal end feet (foot processes) touching the basement membrane (dark) which is shared on its other surface by endothelium of a capillary.

 

 

Detail of end feet of podocyte on the basement membrane. The basement membrane (basal lamina) is continuous, but the fenestrated capillary endothelium has pores. Glomerular filtrate passes from the capillary lumen, through the layers seen here, into the lumen of Bowman’s capsule (where the foot processes are lying). Between the foot processes a re thin slit membranes.

Between the fenestrated endothelial cells of the glomerular capillaries and the podocytes that cover their external surfaces is a thick basement membrane. This membrane is believed to be the filtration barrier that separates the urinary space and the blood in the capillaries. The basement membrane is derived from the fusion of capillary and podocyte-produced basal laminae. With the aid of the electron microscope, one can distinguish a central electron-dense layer lamina densa; on each side, a more electron-lucent layer (lamina rara). The two electron-lucent laminae rarae contain fibronectin, which may serve to bind them to the cells. The lamina densa is a meshwork of type IV collagen and laminin in a matrix containing the negatively charged proteoglycan heparan sulfate. Thus, the glomerular basal lamina is a selective macromolecular filter in which the lamina densa acts as a physical filter, whereas the anionic sites in the laminae rarae act as a charge barrier. Particles greater than 10 nm in diameter do not readily cross the basal lamina, and negatively charged proteins with a molecular mass greater than that of albumin pass across only sparingly.

In diseases such as diabetes mellitus and glomerulonephritis, the glomerular filter is altered and becomes much more permeable to proteins, with the subsequent release of protein into the urine (proteinuria).

The endothelial cells of glomerular capillaries have a thin cytoplasm that is thicker around the nucleus, where most of the organelles are clustered. The fenestrae of these cells are larger (70 – 90 nm in diameter) and more numerous than those in the capillaries of other organs, and they lack the thin diaphragm commonly observed spanning the openings of other fenestrated capillaries. These cells may act as macrophages to clean the basal lamina of particu-1 ate material that accumulates during the filtration process.

Besides endothelial cells and podocytes, the glomerular capillaries have mesangial cells adhering to their walls in places where the basal lamina forms a sheath that is shared by two or more capillaries. The cytoplasmic extensions of mesangial cells penetrate between endothelial cells to reach the capillary lumen. The cells synthesize the extracellular matrix that surrounds them and contribute to the support of the capillary walls.

 

Proximal Convoluted Tubule

 

At the urinary pole of the renal corpuscle, the squamous epithelium of the parietal layer of Bowman’s capsule is continuous with the columnar epithelium of the proximal convoluted tubule. This tubule is longer than the distal convoluted tubule and is therefore more frequently seeear renal corpuscles in the cortical labyrinth.

The proximal convoluted tubule is lined with simple cuboidal epithelium. The cells of this epithelium: 1. have an acidophilic cytoplasm that results from the 2. presence of numerous elongated mitochondria. 3. The ceil apex has abundant microvilli, which form a brush border. Because the cells are large, each transverse section of a proximal tubule contains only three to five spherical nuclei, usually located in the center of the cell, the space of this tubule is smaller as compare to distal one. In the living animal, proximal convoluted tubules 5. have a wide lumen and are surrounded by peritubular capillaries. In routine histologic preparations, the brush border is usually disorganized and the peritubular capillary lumens are greatly reduced in size or collapsed.

The apical cytoplasm of these cells has numerous canaliculi between the bases of the microvilli; these canaliculi affect the capacity of the proximal tubule cells to absorb macromolecules. Pinocytotic vesicles are formed by e\ aginations of the apical membranes and contain macromolecules (mainly proteins with a molecular mass less than 70 kDd) that have passed across the glomerular filter. The pinocytolic vesicles fuse with lysosomes where macromolecules are degraded, and monomers are returned to the circulation.

6. The basal portions of these cells have abundant membrane invaginations and lateral interdigitations with neighboring cells. The Na7K. -AT’Pase (sodium pump) responsible for actively transporting sodium ions out of the cells is localized in these basolateral membranes. 7. Mitochondria are concentrated at the base of the cell and arranged parallel to the long axis of the cell and perpendicular to the

basement membrane. This mitochondrial location and the increase in die area of the cell membrane at the base of the cell are characteristic of cells engaged in active ion transport. Because of the extensive interdigitation of the lateral membranes, no discrete cell margins can be observed (in the light microscope) between cells of the proximal tubule.

 

 

Dark pink = proximal tubule. Lighter, low cuboidal epithelium (as at top left) = distal tubule.

 

 

Higher EM of proximal tubule with its brush border (arrow), which indicates absorption by the cell.

 

 

EM of base of epithelium of proximal convoluted tubule. Note basement (basal) lamina and the great infolding of the cell membrane. These folds, plus the many mitochondria lying in them, tend to give the cytoplasm a striated look in light microscopy. The many folds also provide increased cell surface for passage of absorbed fluid and ions into t he peritubular capillary below.

 

Henle’s Loop

 

Henle’s loop is a U-shaped structure consisting of a thick descending limb, which is very similar in structure to the proximal convoluted tubule; a thin descending limb; a thin ascending limb; and a thick ascending limb, which is very similar in structure to the distal convoluted tubule. In the outer medulla, the thick descending limb, with an outer diameter of about 60 μm} narrows to about 12 μm and continues as the thin descending limb. The lumen of this segment of the nephron is wide because the wall consists of squamous epithelial cells whose nuclei protrude only slightly into the lumen. Well prominent meshwork of secondary capillaries surrounds the tubules of loop of Henle. In routine histologic preparations this compound of nephron could be recognized by thin wall, which is made up of flattened cells.

 

 

Thin segment of Loop of Henle (in the middle), with a simple squamous lining.

Distal Convoluted Tubule

 

When the thick ascending limb of Henle’s loop penetrates the cortex, it preserves its histologic structure but becomes tortuous and is called the distal convoluted tubule, the last segment of the nephron. This tubule is lined with simple cuboidal epithelium.

 

 

Large pale tubules are collecting tubules, with clear epithelial cell boundaries. Brighter pink tubules are thick portions of loops of Henle; these are basically like distal convoluted tubules in their histology, so would be ascending limbs.

 

 

Proximal and distal convoluted tubules (EM). Distal has no brush border. Peritubular capillaries lie in the connective issue between tubules.

 

In histologic sections, the distinction between the proximal and distal convoluted tubules, which are both found in the cortex, is based on certain charac­teristics. Cells of proximal tubules are larger than cells of distal tubules; they have brush borders, which distal tubule cells lack; and they are more acidophilic. The lumens of the distal tubules are larger, and because distal tubule cells are flatter and smaller than those of the proximal tubule, more cells and more nuclei are seen in the distal tubule than in the proximal tubule in the same histologic section. The apical canaliculi and vesicles that characterize the proximal tubule are absent in the distal tubule. Cells of the distal convoluted tubule have elaborate basal membrane invaginations and associated mitochondria indicative of their ion-trans porting function.

Collecting Tubules & Ducts

 

Urine passes from the distal convoluted tubules to collecting tubules that join each other to form larger, straight collecting ducts, the papillary ducts of Bellini, which widen gradually as they approach the tips of the medullary pyramids.

The smaller collecting tubules are lined with cuboidal epithelium and have a diameter of approximately 40 μm. As they penetrate deeper into the medulla, their cells increase in height until they become columnar. The diameter of the collecting duct reaches 200 μm near the tips of the medullary pyramids.

Collecting tubules are composed of two types of cells: dark and light. Along their entire extent, collecting tubules and ducts are composed of ceils that stain weakly with the usual stains. They have an electron-lucent cytoplasm with few organelles and almost no invaginations of the basal cell membrane.

In collecting tubules and cortical collecting ducts, a dark-staining intercalated cell is also seen; its significance is not understood. The intercellular limits of the collecting tubule and duct cells are clearly visible in the light microscope, because there are no interdigitations between the lateral margins of adjacent cells. Cortical collecting ducts are joined at right angles by several generations of smaller col­lecting tubules that drain each medullary ray. In the medulla, collecting ducts are a major component of the urine-concentrating mechanism (dark-staining cells produce IT ions).

 

types of nephrons

 

The renal corpuscles of the nephrons lie in the cortex. The extent of the loop of Henle development depends on the position of the renal corpuscles. Those nephrons with the renal corpuscles in the outer two-thirds of the cortex are called cortical nephrons; the glomeruli are usually smaller. Due to the size of loops of Henle, they are subdividing into two groops: with short and long loop. All nephrons participate in the processes of filtration, absorption, and secretion.

Approximately one seventh of all nephrons are located near the corticomedullary junction and are therefore called juxtamedullary nephrons. Juxtamedullary nephrons, however, are of prime importance in establishing the gradient of hypertonicity in the medullary interstitium—the basis of the kidneys ability to produce hypertonic urine. Juxtamedullary nephrons have very long Henle’s loops, extending deep into the medulla. These loops consist of a short thick descending limb, long thin descending and ascending limbs, and a thick ascending limb.

 

Blood Circulation

 

Each kidney receives blood from its renal artery, which usually divides into two branches before entering the organ. One branch goes to the anterior part of the kidney, the other to the posterior part. While still in the hilum, these branches give rise to arteries that branch again to form the interlobar arteries located between the renal pyramids. At the level of the corticomedullary junction, the interlobar arteries form the arcuate arteries. Interlobular arteries branch off at right angles from the arcuate arteries and follow a course in the cortex perpendicular to the renal capsule. Interlobular arteries form the boundaries of the renal lobules, which consist of a medullary ray and the adjacent cortical labyrinth. From the interlobular arteries arise the afferent arterioles, which supply blood to the capillaries of the glomeruli. Blood passes from these capillaries into the efferent arterioles, which at once branch again to form a peritubular capillary network that will nourish the proximal and distal tubules and carry away absorbed ions and low-molecular-weight materials. The efferent arterioles that are associated with juxtamedullary nephrons form long, thin capillary vessels. These vessels, which follow a straight path into the medulla and then loop back toward the corticomedullary boundary, are called vasa recta (straight vessels). The descending vessel is a continuous-type capillary, whereas the ascending vessel has a fenestrated endothelium. These vessels, containing blood that has been filtered through the glomeruli, provide nourishment and oxygen to the medulla. Because of their looped structure, they do not cany away the high osmotic gradient set up in the interstitium by Henle’s loop.

The capillaries of the outer cortex and the capsule of the kidney converge to form the stellate veins (so called because of their configuration when seen from the surface of the kidney), which empty into the interlobular veins.

Veins follow the same course as arteries. Blood from interlobular veins flows

into arcuate veins and from there to the interlobar veins. Interlobar veins converge to form the renal vein through which blood leaves the kidney.

 

Juxtaglomerular Apparatus of kidney

 

Juxtaglomerular Apparatus consists of such components:

Juxtaglomerular (JG) cells

juxtavascular cells

macula densa

mesangial cells.

Adjacent to the renal corpuscle, the tunica media of the afferent arteriole has modified smooth muscle cells. These cells, called Juxtaglomerular (JG) cells, have ellipsoid nuclei and a cytoplasm full of secretory granules that stain with periodic acid-Schiff. Secretions of Juxtaglomerular cells play a role in the maintenance of blood pressure.

When examined with the electron microscope, Juxtaglomerular cells show characteristics of protein-secreting cells, including an abundant rough endoplasmic reticulum, a highly developed Golgi complex, and secretory granules measuring approximately 10-40 nm in diameter. Juxtaglomerular cells produce the hormone renin, which acts on a plasma protein—angiotensinogen—io produce an inactive decapeptide, angiotensin I. As a result of the action of a converting enzyme present in high concentration in lung endothelial cells, this substance loses two amino acids and becomes an active octapeptide, angiotensin II.

After a significant hemorrhage, there is an increase in renin secretion. Angiotensin II is produced, enhancing blood pressure by both constricting arterioles and stimulating the secretion of the adrenocortical hormone aldosterone. Aldosterone acts on cells of the renal tubules (mostly the distal tubules) to increase the absorption of sodium and chloride ions from the glomerular apparatus. This increase in sodium and chloride ions, in turn, expands the fluid volume, leading to an increase in blood pressure.

Decreased blood pressure caused by other factors (e.g., sodium depletion, dehydration) also activates the renin-angiotensin II-aldosterone mechanism that contributes to the maintenance of blood pressure.

Juxitavascular cells are lying in the vascular pole between the macula densa and afferent and efferent arterioles. Cells are oval-shaped and have a lot of processes which contact with mesangial cells. They produce rennin in case when juxtaglomerular cells cannot produce it.

The macula densa of the distal convoluted tubule is usually located near the renal corpuscle between the afferent and efferent arterioles. Experimental evidence suggests that ceils of the macula densa are sensitive to the chloride ion content of tubular fluid, producing molecular signals that promote constriction of the glomerular afferent arteriole. This mechanism enables the macula densa to regulate the rate of glomerular filtration.

 

Renal Interstitium

 

Both the cortex and the medulla contain specialized cells in the spaces between uriniferous tubules and the blood and lymph vessels. These interstitial cells are more frequent in the medulla, where cells containing cytoplasmic lipid droplets and implicated in the synthesis of a hypotensor hormone are found. These cells may be the source of medullipin I, a substance that is converted in the liver to medullipin II, a potent vasodilator that lowers blood pressure.

 

HISTOPHYSIOLOGY

 

The kidney regulates the chemical composition of the internal environment by a complex process that involves filtration, active absorption, passive absorption, and secretion. Filtration takes place in the glomerulus, where an ultrafiltrate of blood plasma is formed. The tubules of the nephron, primarily the proximal convoluted tubules, absorb from this filtrate the substances that are useful for body metabolism, thus maintaining the homeostasis of the internal environment. They also transfer from blood to the tubular lumen certain waste products that are eliminated with the urine. Under certain circumstances, the collecting ducts are permeable to water, contributing to the concentration of urine—which is usually hypertonic in relation to blood plasma. In this way, the organism controls its water, intercellular fluid, and osmotic balance.

The two kidneys produce about 125 mL of filtrate per minute; of this amount, 124 mL is absorbed and only 1 mL is released into the calyces as urine. About 1500 mL of urine is formed every 24 hours.

Filtration

The blood flow in the two kidneys of an adult amounts to 1.2-1.3 L of blood per minute. This means that all the circulating blood in the body passes through the kidneys, ever) 4—5 minutes. The glomeruli are composed of arterial capillaries in which the hydrostatic pressure—about 45 mm Hg— is higher than that found in other capillaries.

The glomerular filtrate is formed in response to the hydrostatic pressure of blood, which is opposed by the osmotic (oncotic) pressure of plasma colloids (20 mm Hg), and the hydrostatic pressure of the fluids in Bowman’s capsule (10 mm Hg), The net filtration pressure at the afferent end of glomerular capillaries is 15 mm Hg.

The glomerular filtrate has a chemical composition similar to that of blood plasma but contains almost no protein, because macromolecules do not readily cross the glomerular wall. The largest protein molecules that succeed in crossing the glomerular filter have a molecular mass of about 70 kDa, and small amounts of plasma albumin appear in the filtrate.

Because endothelial cells of glomerular capillaries are fenestrated with numerous openings (70-90 nm in diameter) without diaphragms, the endothelium is easily permeated.

Proximal Convoluted Tubule

The glomerular filtrate formed in the renal corpuscle passes into the proximal convoluted tubule, where the processes of absorption and excretion begin. The proximal convoluted tubule absorbs all the glucose and amino acids and about 85% of the sodium chloride and water contained in the filtrate, in addition to phosphate and calcium. Glucose, amino acids, and sodium are absorbed by these tabular cells through an active process involving Na⁺/K⁺-ATPase (sodium pump) located in the basolateral cell membranes. Water diffuses passively, following the osmotic gradient. When the amount of glucose in the filtrate exceeds the absorbing capacity of the proximal tubule, urine becomes more abundant and contains glucose.

Absorption of the small amount of protein present in the filtrate takes place by pinocytosis. The proteins are digested by lysosomes, and the amino acids are reused by local cells.

In addition to these activities, the proximal convoluted tubule secretes creatinine and substances foreign to the organism, such as paraaminohippuric acid, penicillin, and iodopyracet (an iodinated organic compound used as an x-ray contrast medium), from the interstitial plasma into the filtrate. This is an active process referred to as tubular secretion. Study of the rates of secretion of these substances is useful in the clinical evaluation of kidney function.

Henle’s Loop

Henle s loop is involved in water retention; only animals with such loops in their kidneys are capable of producing hypertonic urine and thus maintaining body water. Henle’s loop creates a gradient of hypertonicity in the medullary interstitium that influences the concentration of the urine as it flows through the collecting ducts.

Although the thin descending limb of the loop is freely permeable to water, the entire ascending limb is impermeable to water. In the thick ascending limb, sodium chloride is actively transported out of the tubule to establish the gradient of hypertonicity in the medullary interstitium that is necessary for urine con­centration. The osmolarity of the interstitium at the tips of the medullary pyramids is about four times that of blood.

Distal Convoluted Tubule

In the distal convoluted tubule, there is an ion-exchange site at which—if aldosterone is present in high enough concentration—sodium is absorbed and potassium ions are secreted. This is the site of the mechanism that controls the total salt and water content of the body. The distal tubule also secretes hydrogen and ammonium ions into tubular urine. This activity is essential for maintenance of the acid-base balance in the blood.

 

Collecting Ducts

The epithelium of collecting ducts is responsive to arginine vasopressin, or antidiuretic hormone (ADH), secreted by the posterior pituitary. If water intake is limited, ADH is secreted and the epithelium of the collecting ducts becomes permeable to water, which is absorbed from the glomerular filtrate, transferred to blood capillaries, and thus retained in the body. In the presence of ADH, intramembrane particles in the luminal membrane aggregate to form what may be channels for water absorption.

 

Hormonal Effects

 

As explained above, water balance is controlled in part by the posterior lobe of the pituitary, which secretes antidiuretic hormone (ADH). A high intake of water inhibits production of ADH; the walls of the collecting ducts become impermeable to water, and water is not absorbed. The result is the formation of large amounts of hypotonic urine; water is eliminated, while the ions necessary for osmotic balance are retained. When small amounts of water are ingested or when a great loss of water occurs (e.g., from excessive sweating or diarrhea), the walls of collecting ducts become permeable to water, which is absorbed, and the urine becomes hypertonic.

 

Diagram of capillary loops in glomerulus and location of point of contact with distal convoluted tubule at base of loops. A histological section would show a closely packed portion of epithelial cells lining the distal tubule – the macula densa. Juxtaglomerular cells (J-G) would lie nearby in the wall of the afferent arteriole. The wedge-shaped space just above the distal tubule is called the polar cushion and would be filled with mesangial cells which are sometimes called Polkissen or Lacis cells in this location. Other mesangial cells extend up among the capillary loops of the glomerulus. By definition, the term juxtaglomerular apparatus includes the J-G cells, macula densa, and polar cushion.

 

 

Diagram (top) of relation of juxtaglomerular (JG) cells to macula densa. Both areas sense the concentration of urine being produced, and by their action can alter it.

 

 

At lower right pole of glomerulus, note a triangular wedge of Polkissen cells just to the left of the straight row of macula densa cells. The latter are part of the epithelial wall of the distal tubule.

 

 

EM photo showing dark particles, which are secretory granules in the cytoplasm of juxtaglomerular cells. These cells are modified smooth muscle cells and secrete the hormone renin. Steroid hormones of the adrenal cortex, mainly aldosterone, increase distal tubular absorption of sodium from the filtrate and thus decrease sodium loss in the urine. Aldosterone also facilitates the elimination of potassium and hydrogen ions. This hormone is crucial in maintaining electrolyte balance in the body.

Aldosterone deficiency in adrenalectomized animals and in humans with Addison disease results in an excessive loss of sodium in the urine

 

BLADDER & URINARY PASSAGES

 

The bladder and the urinary passages store the urine formed in the kidneys and conduct it to the exterior. The calyces, renal pelvis, ureter, and bladder have the same basic histologic structure, with the walls of the ureters becoming gradually thicker as proximity to the bladder increases.

 

 

Ureter, with typically stellate lumen. The transitional epithelium rests on a blue c.t. lamina propria. There is no boundary between lamina propria and the deeper c.t. submucosa. The muscularis externa stains a grayer blue in this slide; there are inner lonlitudinal and outer circular muscle layers visible here. On the outside is the blue c.t. adventitia with quite a bit of fat. (Mallory stain)

 

The mucosa of these organs consists of transitional epithelium and a lamina propria of loose-to-dense connective tissue. Surrounding the lamina propria of these organs is a dense woven sheath of smooth muscle.

The transitional epithelium of the bladder in the undistended state is five or six cells in thickness; the superficial cells are rounded and bulge into the lumen. These cells are frequently polyploid or binucleate. When the epithelium is stretched, as when the bladder is full of urine, the epithelium is only three or four cells in thickness, and the superficial cells become squamous.

 

 

Transitional epithelium – diagnostic for urinary tract. The surface cells are characteristically dome-shaped and puffy.

 

The superficial cells of the transitional epithelium have a special membrane of thick plates separated by narrow bands of thinner membrane that are responsible for the osmotic barrier between urine and tissue fluids. When the bladder contracts, the membrane folds along the thinner regions, and the thicker plates invaginate to form fusiform cytoplasmic vesicles. These vesicles represent a reservoir of these thick plate:; that can be stored in the cytoplasm of the cells of the empty bladder and used to cover the increased cell surface in the full bladder. This luminal membrane is assembled in the Golgi complex and has an. unusual chemical composition—cerebroside is the major component of the polar lipid fraction.

 

 

Transitional epithelium from a distended urinary bladder; compare with the contracted wall in the preceding slide. When stretched, the epithelium becomes very thin, with fewer layers of cells, and the surface cells tend to be flattened. There’s only the one layer of flatter cells, however, which is quite different from the appearance of stratified squamous epithelium (with which this might be confused.)

 

The muscular layers in the calyces, renal pelvis, and ureters have a helical arrangement. As the ureteral muscle cells reach the bladder, they become longitudinal. The muscle fibers of the bladder run in every direction (without distinct layers) until they approach the bladder neck, where three distinct layers can be identified: The internal longitudinal layer, distal to the bladder neck, becomes circular around the prostatic urethra and the prostatic parenchyma in men. It extends to the external meatus in women. Its fibers form the true involuntary urethral sphincter. The middle layer ends at the bladder neck, and the outer longitudinal layer continues to the end of the prostate in men and to the external urethral meatus in women.

The ureters pass through the wall of the bladder obliquely, forming a valve that prevents the backflow of urine. The intravesical ureter has only longitudinal muscle fibers.

The urinary passages are covered externally by an adventitial membrane — except for the upper part of the bladder, which is covered by serous peritoneum.

 

Urethra

 

The urethra is a tube that carries the urine from the bladder to the exterior. In men, sperm also pass through it during ejaculation. In women, the urethra is exclusively a urinary organ.

Male Urethra: The male urethra consists of four parts: prostatic, membranous, bulbous, and pendulous. The initial part of the urethra passes through the prostate, which is situated very close to the bladder, and the ducts that transport the secretions of the prostate open into the prostatic urethra.

In the dorsal and distal part of the prostatic urethra, there is an elevation, the verumontanum (from Latin, meaning mountain ridge), that protrudes into its interior. A closed tube called the prostatic utricle opens into the tip of the verumontanum; this tube has no known function. The ejaculatory ducts open on the sides of the verumontanum. The seminal fluid enters the proximal urethra through these ducts to be stored just before ejaculation. The prostatic urethra is lined with transitional epithelium.

The membranous urethra extends for only 1 cm and is lined with stratified or pseudostratified columnar epithelium. Surrounding this part of the urethra is a sphincter of striated muscle, the external sphincter of the urethra, The voluntary external striated sphincter adds further closing pressure to that exerted by the involuntary urethral sphincter. The latter is formed by the continuation of the internal longitudinal muscle of the bladder.

The bulbous and pendulous parts of the urethra are located in the corpus spongiosum of the penis. The urethral lumen dilates distally, forming the fossa navicularis. The epithelium of this portion of the urethra is mostly pseudostratified and columnar, with stratified and squamous areas.

Littre’s glands are mucous glands found along the entire length of the urethra but mostly in the pendulous part. The secretory portions of some of these glands are directly linked to the epithelial lining of the urethra; others have excretory ducts.

Female Urethra: The female urethra is a tube 4-5 cm Ions, lined with stratified, squamous epithelium and areas of pseudostratified columnar epithelium. The mid part of the female urethra is surrounded by an external striated voluntary sphincter.

 

Students’ Practical Activities:

Students must know and illustrate such histologic specimens:

Specimen 1. Trachea.

Haematoxylin and Eosin.

The respiratory epithelium of the trachea is tall, pseudostratified and ciliated and contains goblet cells. The tracheal epithelium is supported by a thick basement membrane. Beneath the basement membrane, the lamina propria consists of loose, highly vascular, connective tissue which becomes more condensed at its deeper aspect to form a band of fibro-elastic tissue. Underlining the lamina propria is the loose submucosa containing numerous mixed sero-mucous glands which decrease iumber in the lower parts of the trachea. The submucosa merges with the perichondrium in the underlining hyaline cartilage rings or with the external adventitial layer between the rings.

 

Trachea at higher magnification showing pseudostratified ciliated columnar epithelium lining the lumen. A wide blood vessel lies in the lamina propria below. Hyaline cartilage is at the bottom of the picture.

 

Illustrate and indicate: 1. Respiratory mucosa: a) pseudostratified columnar ciliated epithelium; b) lamina propria of the mucosa; 2. Submucosa; 3. Hyaline cartilage: a) C-shaped rings; 4. Adventitia.

Specimen 2. Lungs with bronchi.

Haematoxylin and Eosin.

As the bronchi diminish in diameter the structure progressively changes to more closely resemble that of large bronchioles. The respiratory epithelium is tall columnar but not pseudostratified, and goblet cells have diminished iumber. The lamina propria is thin and completely encircled by smooth muscle which is disposed in a spiral manner. This arrangement of smooth muscle permits contraction of the bronchi in both length and diameter during expiration. Sero-mucous glands are sparse in the submucosa and are rarely found in smaller airways. The framework is reduced to a few irregular plates; cartilage also does not usually extend belong the tertiary bronchi. Note that the submucosa merges with the surrounding adventitia and thence with the lung parenchyma. A small lymphoid aggregation is seen in the adventitia.

 

Illustrate and indicate: I. Middle sized bronchus. 1. respiratory mucosa: a) respiratory epithelium; b) lamina propria of the mucosa; c) smooth muscle layer; 2. Submucosa; 3. Islands of elastic cartilages; 4. Adventitia.

II. Small bronchus. 1. Respiratory mucosa: a) simple columnar ciliated epithelium; b) lamina propria of the mucosa; c) smooth muscle layer; 2. Adventitia.

III. Terminal portion of the respiratory tree.

Illustrate and indicate: 1. Terminal bronchiole; 2. Respiratory bronchioles; 3. Alveolar ducts; 4. Alveolar sacs; 5. Alveoli; 6. Pulmonary vessels.

Specimen 3. Kidney.

Haematoxylin and Eosin.

This specimen of a kidney illustrates the gross features of the kidney. The substance of the kidney may be divided into an outer cortex and an inner medulla. In histological section of the cortex, numerous renal corpuscles are just visible.

The collecting ducts are easily recognised by their large diameter and columnar, pale-stained epithelial lining.

Detail of renal corpuscle. Dark pink epithelium = proximal tubule. Lighter pink (as at upper top left) = distal tubule.

Illustrate and indicate: 1.Capsule of the kidney; 2. Cortex: a) renal corpuscle; b) glomerulus; c) Bowman’s capsule; d) Bowman’s space; 3. Proximal convoluted tubule; 4. Renar medulla: a) loop of Henle; b) medullary rays; 5. Arcuate artery.

 

Specimen 4. Ureter.

Haematoxylin and Eosin.

The ureter is muscular organ, whose wall contains 4 tunics: mucosa, submucosa, muscularis and adventitia

The lumen of the ureter is lined by urinary epithelium (also called transitional epithelium) which is thrown up into folds in the relaxed state.

Urinary epithelium (also called transitional epithelium or urothelium) is especially adapted. Urinary epithelium rests on a basement membrane which is often too thin to be resolved by light microscopy and was formely thought to be absent. The basal layer is irregular and may be deeply indented by strands of underlying connective tissue containing capillaries.

Muscularis has two layers of smooth muscle arranged into an inner longitudinal layer and an outer circular layer. Another outer longitudinal layer is present in the lower third of the ureter.

 

Illustrate and indicate: 1.Mucosa: a) transitional epithelium; b) lamina propria of the mucosa; 2.Submucosa; 3.Smooth muscle layers: a) inner longitudinal layer; b) outer circular layer; 4.Adventitia.

 

Specimen 5. Urinary bladder.

Haematoxylin and Eosin.

The general structure of the bladder wall resembles that of the lower third of the ureters. The wall of the bladder consists of three loosely arranged layers of smooth muscle and elastic fibres which contract during micturition. Note the inner longitudinal, outer circular and outermost longitudial layers of smooth muscle. The urinary epithelium lining the bladder is thrown into many folds in the relaxed state. The outer adventitial coat contains arteries, veins and lymphatics.

 

 

Illustrate and indicate: 1.Mucosa: a) transitional epithelium; b) lamina propria of the mucosa; 2.Submucosa; 3.Smooth muscle layer; 4.Adventitia.

REFERENCES:

A-Basic:

1.     Practical classes materials

http://intranet.tdmu.edu.ua/data/kafedra/internal/histolog/classes_stud/English/medical/III%20term/20%20Respiratory%20system.%20Urinary%20system.htm

2.     Lecture presentations

http://intranet.tdmu.edu.ua/ukr/kafedra/index.php?kafid=hist&lengid=eng&fakultid=m&kurs=2&discid=Histology, cytology and embryology

3.  Stevens A. Human Histology / A. Stevens, J. Lowe. – [second edition]. –Mosby, 2000. – P. 159-176

4.     Wheter’s Functional Histology : A Text and Colour Atlas / [Young B., Lowe J., Stevens A., Heath J.]. – Elsevier Limited, 2006. – P. 234-251, 302-328

5.     Inderbir Singh Textbook of Human Histology with colour atlas / Inderbir Singh. – [fourth edition]. – Jaypee Brothers Medical Publishers (P) LTD, 2002. – P. 207-216, 258-272

6.     Ross M. Histology : A Text and Atlas / M. Ross W.Pawlina. – [sixth edition]. – Lippincott Williams and Wilkins, 2011. – P. 664-740

 

B – Additional:

1.     Eroschenko V.P. Atlas of Histology with functional correlations / Eroschenko V.P. [tenth edition]. – Lippincott Williams and Wilkins, 2008. – P. 333-381

2.     Junqueira L. Basic Histology / L. Junqueira, J. Carneiro, R. Kelley. – [seventh edition]. – Norwalk, Connecticut : Appleton and Lange, 1992. – P. 358-377, 392-409

3.     Charts:

http://intranet.tdmu.edu.ua/index.php?dir_name=kafedra&file_name=tl_34.php#inf3

4.     Disk:

http://intranet.tdmu.edu.ua/data/teacher/video/hist/  

5.     Volkov K. S. Ultrastructure of the main components of body / K. S. Volkov. – Ternopil : Ukrmedknyha, 1999. – P. 78-84, 88-94

http://intranet.tdmu.edu.ua/data/books/Volkov(atlas).pdf

http://en.wikipedia.org/wiki/Circulatory

http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html

http://www.udel.edu/biology/Wags/histopage/histopage.htm