Which of the following structures is lined with simple cuboidal epithelium with microvilli

2.4 Structure and Function of Simple Cuboidal Epithelium

Simple cuboidal epithelium consists of one layer of cells whose height roughly equals their width, so in sections perpendicular to the surface, cells resemble small box-like cubes. Cells in horizontal section appear to be a mosaic of polygonal tiles. As in other epithelia, cells rest on abasement membrane that firmly attaches to underlying connective tissue. Each cell has one spherical, centrally placed nucleus. This epithelium provides protection, forms conduits for gland ducts, and may be specialized for active secretion and absorption. On the surface of the ovary, it isovarian surface epithelium. It also lines renal tubules and small collecting ducts of the kidney, which engage in ion transport. The thyroid—an endocrine gland—contains spherical follicles of these cuboidal cells. The parenchyma of mostexocrine glands, such as salivary glands and pancreas, consists of cuboidal to columnar epithelial cells in grape-like clusters calledacini. In the eye, cells of pigmented epithelium of the retina and epithelium of the ciliary body are simple cuboidal and specialized for ion transport and secretion. Free surfaces of these cuboidal cells often havemicrovilli, which are best seen by electron microscopy. Their cytoplasm has more organelles than that of simple squamous epithelial cells, with more mitochondria and endoplasmic reticulum, which are evidence of high metabolic and functional activities.

Lens epithelium.

This is a simple cuboidal epithelium (Fig. 1-24A,D) restricted to the anterior surface of the lens. The cells become more columnar at the equator. As they elongate, the apical portion comes to lie deeper to other, more anteriorly positioned, lens cells. These elongated lens cells are known as lens ‘fibres’ (Fig. 1-24D). The manner in which equatorial lens epithelial cells are transformed into lens fibres is depicted in Figure 1-24A. The cell nucleus and cell body sink deeper into the lens as further cells are laid down externally. Mitotic activity is maximal in the pre-equatorial and equatorial lens epithelium, known as the germinative zone (Fig. 1-24A).

Simple Epithelia

Simple epithelia are defined as surface epithelia consisting of a single layer of cells. Simple epithelia are almost always found at interfaces involved in selective diffusion, absorption and/or secretion. They provide little protection against mechanical abrasion and thus are not found on surfaces subject to such stresses. The cells comprising simple epithelia range in shape from flattened to tall columnar, depending on their function. For example, flattened simple epithelia are ideally suited to diffusion and are therefore found in the air sacs of the lung (alveoli), the lining of blood vessels (endothelium) and lining body cavities (mesothelium). In contrast, highly active epithelial cells, such as the cells lining the small intestine, are generally tall since they must accommodate the appropriate organelles. Simple epithelia may exhibit a variety of surface specialisations, such asmicrovilli andcilia, which facilitate their specific surface functions.

BM basement membrane C collagenous supporting tissue M mesothelial lining cells N nucleus SM smooth muscle

BM basement membrane C cilia

Thick Loop (or Limb of the Loop)

The thick part of the ascending limb is lined by a simple cuboidal epithelium. These cells pump chloride ions from the urine; sodium moves with the chloride ions. In addition to the absorption of sodium, chloride and potassium ions; the thick limb is a major location of magnesium and calcium ion resorption. Given the impermeability of this segment to water, and the large amount of solute resorption that occurs, the tubular fluid becomes more dilute as it passages the thick ascending loop, which has given rise to the description to it as the ‘Diluting Segment’ of the nephron.

Given the requirement for active transport of Na+ and Cl− and other ions. The cells of the thick loop are rich in mitochondria and have a high ATP requirement, which makes them vulnerable to hypoxic damage due to high oxygen demand and a relatively poor blood supply.

Review

FIG. 16.26. Summary of major activities of different parts of the renal tubule

The function of the renal tubule is to transform an ultrafiltrate of plasma into a concentrated solution of waste products such as urea, creatinine, excess H+ and K+ and many other substances. At the same time, the tubule conserves essential water, Na+, bicarbonate, amino acids, glucose and low molecular weight proteins. This complex procedure is carried out by a variety of mechanisms in different segments of the tubule, including active transport, co-transport, passive diffusion, facilitated diffusion (seeCh. 1) and differential permeability of different parts of the tubule.

The ability of the tubule to produce concentrated urine is dependent on the high osmolarity of the renal medulla, which is created by the unique structure of the loops of Henle and vasa recta dipping down into the medulla. This is known as thecounter-current multiplier mechanism. In the presence of ADH, which renders the collecting tubule and duct permeable to water, the high osmolarity of the interstitium of the renal medulla draws water passively out of the tubule and into the medulla where it is carried away by the vasa recta. The counter-current multiplier mechanism is set up by the ability of the thick ascending limb of the loop of Henle to pump large amounts of NaCl into the interstitium against a concentration gradient while remaining impermeable to water. The thin descending limb is permeable to water but not NaCl, and water is reabsorbed into the medulla, resulting in hyperosmolar urine reaching the hairpin bend of the loop. This water, however, is removed by the vasa recta. The hyperosmolarity of the medulla is also partly due to the high concentrations of urea resulting from passive diffusion of urea from the medullary collecting duct into the interstitium along its concentration gradient.

This diagram outlines the major movements of solutes and water into and out of the different parts of the renal tubule. For further detail of these processes the reader is referred to current physiology texts.

TABLE 16.1. Review of the urinary system

Ureteric Bud Outgrowth

After specification and elongation, the nephric duct reaches the cloaca as a simple cuboidal epithelium. Shortly afterwards, the epithelium becomes pseudostratified and will soon give rise to the ureteric bud. At this point, the expression of Ret and its coreceptor Gfrα-1 becomes restricted to the caudal portion of the nephric duct, and Gdnf expression is restricted to the nephrogenic mesenchyme.85,90–93 The binding of Gdnf to Gfrα-1 (facilitated by heparan sulphate glycosaminoglycans)78,94 activates Ret, which in turn elicits a number of intracellular pathways that promote cell adhesion, proliferation, and migration. Among these are phosphatidylinositol 3-kinase (PI3K)/AKT, p38 mitogen-activated protein kinase (MAPK), RAS/extracellular signal-related kinase (ERK), and phospholipase Cγ (PLCγ)/Ca+ (see reference 95). A critical step in the Ret/Gdnf signaling pathway is the activation (via PI3K) of the ETS transcription factor genes, Etv4 and Etv5, which drive the expression of a number of transcripts required for ureteric bud outgrowth.96

An elegant study by Chi et al. elucidated the cellular basis of Ret/Gdnf-mediated ureteric bud outgrowth. Using time-lapse imaging and chimeric embryos containing both Ret+/+ and Ret−/− cells, they demonstrated that Ret+/+ cells contribute preferentially to form the ureteric bud tip, whereas the Ret−/− cells form the ureteric trunk. This preferential positioning of Ret+/+ cells in the nascent ureteric bud tip facilitates their response to Gdnf signals to proliferate and branch and prevents an indiscriminate ureteric bud induction site.97 A similar scenario occurs in chimeric embryos containing Etv4- or Etv5-deficient cells, confirming a critical role for these ETS transcription factors in ureteric bud outgrowth and branching.98

A complex signaling network is necessary for controlling the correct spatiotemporal execution of ureteric bud outgrowth and its precise positioning on the nephric duct (Fig. 8.2). In this regard, Six1, Pax2, Sall1, Hox11, and Eya1 act in concert to positively modulate the expression of Gdnf in the nephrogenic mesenchyme (see reference 99). Mutations in these genes result in failure of ureteric bud outgrowth, as would be expected.79,100–103 Conversely, Gdnf/Ret feedback inhibitors, such as Sprouty1 (Spry1), Foxc1, Bmp4, and Slit2 (and its receptor Robo2), restrict Gdnf/Ret-mediated ureteric bud outgrowth. If mutated, these aforementioned genes lead to the development of multiple ureters and multiplex kidneys due to the formation of ectopic ureteric buds.104–108

Mutations that disrupt Gdnf/Ret signaling also cause renal developmental abnormalities. Ret−/−, GFRα-1−/,− and Gdnf−/− mice have absent kidneys due to failure of ureteric bud formation.84,85,93,109–112 The same kidney phenotypes occur in Etv4/5−/− mice96 and mice lacking heparan sulfate 2-sulfotransferase (HS2ST), a key enzyme in heparan sulfate biosynthesis.113 Moreover, Ret mutations in the critical tyrosine residues Y1062 (activates MAPK and PI3K pathways) or Y1015 (activates PLCγ/Ca+) result in absent kidneys or nonfunctional kidneys with megaureters, respectively.114,115

Although Gdnf/Ret signaling is critical to the induction of ureteric bud outgrowth, other signaling pathways also have roles. This is supported by the observation that occasionally Ret−/−, Gfrα-1−/−, and Gdnf−/− mice form some kidney tissue, albeit nonfunctional. Subsequent studies have demonstrated that Fgf signaling (likely Fgf10) can compensate for the combined loss of Ret, Gdnf, and Spry. This occurs because Fgfs can activate the same downstream signaling pathways stimulated by Gdnf/Ret (e.g., PI3K-AKT and RAS/MAPK), which are normally negatively regulated by Spry.99,116,117

Ependyma

The ventricles of the brain and the central canal of the spinal cord are lined by a simple cuboidal epithelium, the ependyma. Ependymal cells contain abundant mitochondria and are metabolically active. Their luminal surfaces are ciliated and have microvilli, and the bases contact the subependymal layer of astrocytic processes. There is not a continuous basal lamina between ependymal cells and the subjacent glial cell processes (Fig. 6.12). Ependymal cells are attached to each other by zonulae adherens (desmosomes).

In some regions, particularly the third ventricle, there are patches of specialized ependymal cells called tanycytes (Fig. 6.12). Tanycytes have basal processes that extend through the layer of astrocytic processes to form end-feet on blood vessels and in the neuropil. They may function to transport substances between the ventricles and the blood. In contrast to ependymal cells, tanycytes are attached to each other and to immediately adjacent ependymal cells by tight junctions. Desmosomes are also present between tanycytes.

Adenomas

Alveolar adenomas are rare and typically occur in the lung periphery. They are recognized as solitary tumors with a network of spaces lined by simple cuboidal epithelium and a spindle cell stroma. Although considered neoplasms, adenomas are not recognized as having malignant potential. Papillary adenomas also typically occur in the periphery of the lung and also appear to have no malignant potential. Mucous gland adenomas more often occur in the central airways and may be difficult to distinguish from low-grade mucoepidermoid carcinomas, although adenomas do not appear to be a malignant precursor. Pleomorphic adenomas have features of both epithelial and connective tissue differentiation; they occur in the airway or the lung periphery and may exhibit malignant behavior. Mucinous cystadenomas are localized cystic masses filled with mucin and lined by columnar mucinous epithelium; they are usually peripheral and are benign, without malignant progression.

Cellular Composition

The basic unit of the gland is an acinus, a rounded secretory portion composed of a group of acinar cells that empty into an intercalated duct composed of simple cuboidal epithelia. Intercalated ducts merge to form striated ducts, whose epithelia are composed of simple columnar or stratified columnar epithelia (Tandler, 1993b). The striated appearance is due to basal accumulation of vertically oriented mitochondria (Tandler, 1993a,b). Several acini compose a lobule, where their respective intercalated and striated ducts drain into an intralobular duct. Lobules of the gland are separated by connective tissue. Intralobular ducts drain into interlobar ducts, which lead to the primary ducts that carry secretions to oral cavity (Marino and Gorelick, 2009; Tandler, 1993b). Myoepithelial cells surround acini and their respective intercalated ducts. These cells are thought to have contractile ability, as they possess morphological similarities to contractile cells, like myofilaments and gap junctions. It is believed that gap junctions are present in myoepithelial cells to allow for the coordinated contraction around the acinus (Pinkstaff, 1993).

Apocrine Sweat Glands

Apocrine sweat glands are not found in rodents. In humans, they are predominantly restricted to the human axillae and anogenital region. Apocrine sweat glands are tubular, coiled secretory glands lined by simple cuboidal epithelium that surround a larger lumen than eccrine sweat glands. Within the basal region, they contain myoepithelial cells with contractile properties that assist in the movement of secretory products upward and outward. Apocrine sweat gland ducts have the same histologic features as do the ducts of eccrine sweat glands. However, the intraepidermal portion of the apocrine sweat gland is straight and not coiled as is the eccrine duct (acrosyringium). Their decapitation secretions are thought to be propelled through the lumen by myoepithelial cells around the periphery of the secretory segment. Secretions and cellular detritus move most commonly through the apocrine duct into the pilosebaceous follicle in the infundibulum, but can be found opening directly onto the epidermal surface close to the hair follicle ostia.

Modified apocrine sweat glands also vary between rodents and humans. Ceruminous glands are found within the human, but not rodent, external ear canal and are responsible for wax secretion. Ciliary glands (also called the glands of Moll) are found at the margins of the eyelids, produce secretions that lubricate the eyeball, and have ducts that open into the follicles of the eyelashes in humans but not in rodents. Finally, mammary glands are considered apocrine sweat glands that and secrete milk. Due to the large size of rodent litters, enormous volumes of milk must be produced. As such, lactating rodents have mammary glands that extend over most of their bodies, including the back and leg regions. Raised areas, sometimes misinterpreted as hyperplasia or papillomas, are in fact the teats. See Chapter 23, Mammary Gland.