Objectives

* Describe the histologic features of the kidneys, and bladder. * Describe the structures that comprise the renal filtration barrier and their role in formation of glomerular filtrate (provisional urine). * Describe the role of the in concentrating urine. * Describe how aldosterone and antidiuretic hormone (ADH) affect the renal tubules. * Trace the pathway of urine flow along the and urinary tract. OVERVIEW OF THE URINARY SYSTEM * The urinary system consists of - The paired kidneys; - Paired ureters, which lead from the kidneys to - The ; and - The , which leads from the bladder to the exterior of the body. Functions of the Urinary System

* Filtration & excretion of cellular wastes from blood * Regulation of fluid and electrolyte balance by selective reabsorption and excretion of water and solutes * Production of the hormones renin and erythropoietin Extend from the 12th thoracic to the 3rd , Reddish, bean-shaped organs

Renal hilum The Urinary System Organization Kidney Organization

Parenchyma * Cortex - - Renal corpuscles - Major and minor calyces - Medullary rays - Nerves and vessels * Medulla - Connective tissues - Renal pyramids * Renal columns Kidney Organization Kidney Organization Kidney Cortex

Medullary Rays Kidney Cortex

A labyrinth of tubules Kidney Medulla and Renal Papillae Photomicrograph of human kidney capsule. This photomicrograph of a Mallory- Azan–stained section shows the capsule (cap) and part of the underlying cortex. The outer layer of the capsule (OLC ) is composed of dense connective tissue. The fibroblasts in this part of the capsule are relatively few in number; their nuclei appear as narrow, elongate, red-staining profiles against a blue background representing the stained collagen fibers. The inner layer of the capsule (ILC ) consists of large numbers of myofibroblasts whose nuclei appear as round or elongate, red-staining profiles, depending on their orientation within the section. Note that the collagen fibers in this layer are relatively sparse and that the myofibroblast nuclei are more abundant than those of the fibroblasts in the outer layer of the capsule. X180. Cortex

Medulla Kidney Cortex

Medullary Rays Kidney Cortex

Medullary Rays (Collect tubules) Diagram showing standard nomenclature for structures in the kidney. The two types of in the kidney are shown with their associated duct systems. A long-looped nephron is shown on the left, and a short-looped nephron is shown on the right. The relative position of the cortex, medulla, papilla, and capsule are indicated (not drawn to scale). The inverted cone-shaped area in the cortex represents a . The parts of the nephron are indicated by number: 1, including the and Bowman’s capsule; 2, proximal convoluted tubule; 3, proximal straight tubule; 4, descending thin limb; 5, ascending thin limb; 6, thick ascending limb (distal straight tubule); 7, located in the final portion of the thick ascending limb; 8, ; 9, connecting tubule; 9*, connecting tubule of the juxtamedullary nephron that forms an arch (arched connecting tubule); 10, cortical collecting duct; 11, outer medullary collecting duct; and 12, inner medullary collecting duct. (Modified from Kriz W, Bankir L. A standard nomenclature for structures of the kidney. The Renal Commission of the International Union of Physiological Sciences (IUPS). Kidney Int 1988;33:1–7.) * The renal columns represent cortical tissue contained within the medulla. - The caps of cortical tissue that lie over the pyramids are sufficiently extensive that they extend peripherally around the lateral portion of the pyramid, forming the renal columns (of Bertin). . Renal columns contain the same components as the rest of the cortical tissue, they are regarded as part of the medulla. Kidney Lobes and Lobules * The number of lobes in a kidney equals the number of medullary pyramids. - Each medullary pyramid and associated cortical tissue at its base an sides (one half of each adjacent ) constitute a lobe of the kidney. - The lobar organization of the kidney is conspicuous in the developing fetal kidney. . Each lobe is reflected as a convexity on the outer surface of the organ, but they usually disappear after birth. . The surface convexities typical of the fetal kidney may persist, however, until the teenage years and, in some cases, into adulthood. - Each human kidney contains 8 to 18 lobes. - Kidneys of some animals possess only one pyramid; these kidneys are classified as unilobar, in contrast to the multilobar kidney of the human. Photomicrograph of fetal kidney. This photomicrograph of an H&E–stained human fetal kidney shows the cortex, the medulla, and two associated pyramids. Note each surface convexity corresponds to a kidney lobe. During postnatal life, the lobar convexities disappear and the kidney then exhibits a smooth surface. X30. * A lobule consists of a collecting duct and all the nephrons that it drains. - The lobes of the kidney are further subdivided into lobules consisting of a central medullary ray and surrounding cortical material. - the center or axis of a lobule is readily identifiable, the boundaries between adjacent lobules are not obviously . - The concept of the lobule has an important physiologic basis; the medullary ray containing the collecting duct for a group of nephrons.

The Urinary System Kidney Circulation Blood Supply to the Kidney

Most important for you to know

. Approximately 90% to 95% of the blood passing through the kidney is in the cortex; 5% to 10% is in the medulla. Efferent arterioles

Afferent arterioles LM – injected kidney vascular system SEM - Ilu, intralobular Af, afferent arteriole; Ef, ; Gl, glomerulus Blood Flow in the Kidney Afferent arteriole

Glomerular capillaries

Efferent arteriole

or Supply cortical nephrons and Supply juxtamedullary nephrons, proximal and distal structures in the medulla, and then convoluted tubules loop back to cortex-medullary boundary Blood Supply to a Renal Corpuscle The Nephron * The nephron is the structural and functional unit of the kidney. - The nephron is the fundamental structural and functional unit of the kidney. - Both human kidneys contain approximately 2 million nephrons. - Nephrons are responsible for the production of urine.

- A nephron includes:

. The renal corpuscle . Tubules - proximal convoluted tubule - loop of Henle - distal convoluted tubule General Organization of the Nephron * The nephron consists of the renal corpuscle and a tubule system. - The renal corpuscle represents the beginning of the nephron. - It consists of the glomerulus, . a tuft of capillaries composed of 10 to 20 capillary loops, surrounded by a double-layered epithelial cup, the renal or Bowman’s capsule. . Bowman’s capsule is the initial portion of the nephron, where blood flowing through the glomerular capillaries undergoes filtration to produce the glomerular ultrafiltrate. - The glomerular capillaries are supplied by an afferent arteriole and are drained by an efferent arteriole that then branches, forming a new capillary network to supply the kidney tubules. - The site where the afferent and efferent arterioles penetrate and exit from the parietal layer of Bowman’s capsule is called the vascular pole. - Opposite this site is the urinary pole of the renal corpuscle, where the proximal convoluted tubule begins.

Efferent arteriole Bowman’s capsule

Afferent arteriole Glomerulus

Interlobular artery

Arcuate v & a Ascending & descending loops (Henle)

Collecting tubule Renal Corpuscle

A renal corpuscle consists of three things: Glomerulus - A tuft of capillaries Bowman’s capsule - The container that surrounds the glomerulus - Two layers: visceral (inner) and parietal (outer) Urinary space - The space between the two layers of Bowman’s capsule (where urine collects). Distal tubule Macula densa of distal tubule

Afferent arteriole

Efferent arteriole

Juxtaglomerular cells (modified smooth muscle) Vascular pole Bowman’s capsule (parietal layer) Bowman’s capsule (visceral layer of )

Parietal layer

Urinary space Urinary pole

Brush border (microvilli) Proximal convoluted tubule Glomerulus

Bowman’s capsule (parietal layer)

Urinary space

Renal corpuscle

Vascular and urinary poles Capillaries (blue) and podocytes (green) Podocytes

* Podocytes have a central cell body with primary processes. * Each primary process gives rise to secondary processes called pedicels (foot processes) that embrace the glomerular capillaries. * Foot processes from different podocytes interdigitate. * Spaces between pedicels are called filtration slits - A little diaphragm covers each filtration slit. Primary processes

Interdigitating secondary foot processes Foot processes

Glomerular capillaries & podocyte Mesangial Cells

* In addition to podocytes and glomerular capillary endothelial cells, mesangial cells are a third cell type present in the glomerulus. * Functions of mesangial cells: - Physical support for glomerulus. - Phagocytosis of proteins and other debris from the glomerular basal lamina. - Secretion of cytokines and other substances for immune defense and repair. Diagram and photomicrograph showing the relationship between the intraglomerular mesangial cells and the glomerular capillaries. a. The mesangial cell and its surrounding matrix are enclosed by the glomerular basement membrane (GBM) of the glomerular capillaries. The mesangial cells are in the same compartment as the endothelial cells and can be intimately associated with the GBM, as well as with the endothelial cells without the intervening GBM. Note that a mesangial cell produces extracellular mesangial matrix, which provides support for the glomerular capillaries. b. Photomicrograph of a glomerulus stained by the PAS method. Note that GBM is well visible within the glomerulus and surrounds the glomerular capillaries. The GBM reflects at the vascular pole to become the basal lamina of the epithelial cells that form the parietal layer of the Bowman’s capsule. The nuclei of the PAS-positive mesangial cells are positioned between the loops of capillaries more toward the center of the glomerulus. Specimen was counterstained with hematoxylin. X360. TEM of glomerulus (Mc, mesengial cells; Ca, capillaries) The Renal Filtration Barrier

The three things that comprise the filter are:

- Fenestrated endothelial cells of the glomerular capillaries - Glomerular basal lamina - Filtration slits between foot processes (covered with a diaphragm) Urinary space

Filtration slits

Glomerular basal lamina

Capillary lumen Fenestrated endothelial cells

Filtration barrier The Glomerular Basal Lamina * Made from fused basal laminae of endothelial cells and podocytes. * Lamina densa is a physical barrier (particles larger than 10 nm can’t easily cross). * Lamina rara is a charge barrier (negatively charged proteins with a molecular weight greater than albumin can’t easily cross). * The GBL is composed of . a network consisting of type IV collagen (mainly 3, 4, and 5 chains), . laminin, . nidogen, and . entactin, together with . heparin sulfate proteoglycans such as agrin and perlecan, as well as . multiadhesive glycoproteins. Urinary space

Filtration slits

Glomerular basal lamina

Lamina densa

Lamina Capillary rara lumen

Filtration barrier Schematic diagram of filtration barrier. The arrow indicates movement of plasma fluid across the glomerular filtration barrier, forming the glomerular ultrafiltrate (primary urine) that accumulates in the urinary space of the Bowman’s capsule. Note the layers of the filtration barrier that include fenestrated glomerular endothelial cells, glomerular basement membrane, and podocytes with filtration slit diaphragms spanned between their foot processes. In addition, the endothelial surface layer of glycoproteins and subpodocyte spaces are shown on this diagram. Scanning electron micrograph of the interior surface of a glomerular capillary. The wall of the capillary shows horizontal ridges formed by the cytoplasm of the endothelial cell. Elsewhere, fenestrations are seen as numerous dark oval and circular profiles. X5,600. (Courtesy of Dr. C. Craig Tisher.) * Nephrin is an important structural protein of the filtration slit diaphragm. - the filtration slit diaphragm revealed its complex protein structure as a zipper-like sheet configuration with a central density. - A transmembrane protein, nephrin is a key structural and functional component of the slit diaphragm. - Nephrin molecules emerging from opposite foot processes interact in the center of the slit (homophilic interactions), forming a central density with pores on both sides. - This intercellular protein sheet also contains other adhesion molecules, such . as Neph-1, Neph-2, P-cadherin, FAT1, and FAT2. - The filtration slit diaphragm is firmly anchored to numerous actin filaments within the foot processes of podocytes. . Regulation and maintenance of the actin cytoskeleton of podocytes has emerged as a critical process for regulating size, patency, and selectivity of the filtration slits. - Mutations in the nephrin gene (NPHS1) are associated with congenital nephrotic syndrome, a disease characterized by massive proteinuria and edema. Diagram of the filtration slit diaphragm. Filtration slit diaphragm is a complex zipper-like sheet structure formed by a transmembrane protein nephrin. The extracellular domains of nephrins emerge from the opposite foot processes of neighboring podocytes and interdigitate in the center of the slit forming a central density with pores on both sides. The intracellular domains of nephrins interact with actin cytoskeleton within the cytoplasm of foot processes. The sheet of nephrin molecules is reinforced near its attachment to the foot processes by Neph1 and Neph2 proteins that interact with each other and with nephrin. The other adhesion molecules such as P-cadherin, FAT1, and FAT2 are also found in this region. Note that foot processes of podocytes are separated by the glomerular basement membrane (GBM) from fenestrated endothelial cells lining glomerular capillaries. (Redrawn from Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med 2006;354:1387–401.) The filtration

- Hydrostatic pressure within the capillaries pushes water (and particles of the proper size, weight, and charge) from blood through the GBL into the urinary space. - Whatever enters the urinary space becomes provisional or temporary urine. - It will be excreted as urine unless it is reabsorbed in the nephron. Juxtaglomerular apparatus juxtaglom cells (JG Cells) Reabsorption vs. Secretion

- Reabsorption means a substance moves from the provisional urine into the blood. - Secretion means a substance moves from blood into urine. The tubules

- Proximal convoluted tubule and proximal straight tubule ( thick segment of descending limb) - Thin segment of loop of Henle - Distal straight tubule (= thick segment of ascending limb) - Distal convoluted tubule Proximal convoluted Distal convoluted tubule tubule Glomerulus

Cortex

Collecting tubule from Thick descending limb adjacent nephron

Loop of Henle Medulla

Thick ascending limb

Collecting duct

Thin limb

Papilla Proximal Tubules - Proximal convoluted tubule merges with Bowman’s capsule, is super long and winds extensively - Tons of mitochondria (so cells look more eosinophilic than other tubular cells) - Brush border (microvilli): lumen looks “fuzzy” - Main job: . reabsorption of water, NaCl, glucose and amino acids. - Proximal tubular cells have numerous mitochondria and a basal plasma membrane with many deep invaginations. - Important general principle: . numerous mitochondria + invaginations of basal plasma membrane suggest a cell is involved in active ion transport. Proximal convoluted tubules Proximal straight tubule TEM of Proximal Convoluted Tubules (PCT) Electron micrograph of a cell. The apical surface of the cell shows the closely packed microvilli (Mv) that collectively are recognized as the brush border in the light microscope. Many vesicles (V) are evident in the apical cytoplasm. Also present in the apical region of the cell are lysosomes (L). The nucleus has not been included in the plane of section. Extensive numbers of longitudinally oriented mitochondria (M) are present in the cell within the interdigitating processes. The mitochondria are responsible for the appearance of the basal striations seen in the light microscope, particularly if the extracellular space is enlarged. The electron micrograph also reveals a basal lamina (BL) and a small amount of connective tissue and the fenestrated endothelium (En) of an adjacent peritubular capillary. 15,000. Upper inset. This higher magnification of the microvilli shows the small endocytotic vesicles that have pinched off from the plasma membrane at the base of the microvilli. 32,000. Lower inset. A higher magnification of the basal portion of the interdigitating processes (IP) below the reach of the mitochondria. The extreme basal aspect of these processes reveals a dense material (arrows) that represents bundles of actin filaments (see Fig. 20.16). X30,000. Microvilli

Mitochondria The Loop of Henle

- Loop of Henle is in the medulla and is composed of thick and thin descending and ascending limbs. - Important because it actively pulls ions out of the urine, creating high osmotic pressure in the connective tissue surrounding the loop. - With this high osmotic pressure gradient, water passively leaves the urine as it goes through the medulla, creating a concentrated urine and preventing dehydration. - The excess water is pulled into the vasa recta (smart). Proximal convoluted Distal convoluted tubule tubule Glomerulus

Cortex

Collecting tubule from Thick descending limb adjacent nephron

Loop of Henle Medulla

Thick ascending limb

Collecting duct

Thin limb

Papilla Different Nephrons have Different Loops

Juxtamedullary nephrons - Close to the border of the cortex and medulla - Have very long loops of Henle - They make the connective tissue of the medulla hypertonic (so there’s high osmotic pressure and urine gets concentrated). Cortical nephrons - Located higher in the cortex - Have very short loops of Henle. Juxtamedullary nephron (long loop)

Cortical nephron (piddly loop) Thin Segment of Loop of Henle

- Transition from proximal tubule to thin segment is abrupt. - Brush border pretty much ends - Simple squamous epithelium - Nuclei bulge a little into lumen - Surrounded by capillaries (vasa recta) Proximal convoluted Distal convoluted tubule tubule Glomerulus

Cortex

Collecting tubule from Thick descending limb adjacent nephron

Loop of Henle Medulla

Thick ascending limb

Collecting duct

Thin limb

Papilla Schematic diagram of loop of Henle thin limb epithelial cells. This diagram shows the various types of epithelia and the region where they are found in the thin limb of the short and long loops of Henle. The diagrams of the epithelium do not include nuclear regions of the epithelial cells. (Modified from Madsen KM, Tisher CC. Physiologic anatomy of the kidney. In: Fisher JW (Ed). Kidney Hormones, London, UK: Academic Press 1986;3:45–100.)

Vasa recta Vasa recta

Thin limbs Distal Straight Tubule - Transition from thin segment to distal straight tubule is abrupt. - Simple cuboidal epithelium; - cells smaller - Brush border gone - Re-enters cortex, returns to renal corpuscle and attaches to afferent arteriole at macula densa (function unclear) - Juxtaglomerular apparatus cells are here too (make the hormone renin, which helps control blood pressure). Proximal convoluted Distal convoluted tubule tubule Glomerulus

Cortex

Collecting tubule from Thick descending limb adjacent nephron

Loop of Henle Medulla

Thick ascending limb

Collecting duct

Thin limb

Papilla Distal straight tubule Distal convoluted tubule

Macula densa Proximal convoluted tubule

Efferent Cortex arteriole

Visceral leaf of glomerular capsule (podocytes)

Renal glomerulus

Parietal leaf of glomerular (Bowman’s) capsule Interlobular Afferent vein arteriole

Interlobular artery Ascending limb

Medulla Descending limb Henle’s loop

Straight tubules

Thin segment

Collecting tubule Arcuate artery Macula densa Juxtaglomerular apparatus (makes renin) and macula densa (who knows what it does) Distal Convoluted Tubule

- Begins at vascular pole of renal corpuscle - Looks like distal straight tubule - Function: . finish concentrating urine - Aldosterone (a hormone made by the adrenal glands) increases sodium reabsorption by the distal convoluted tubular cells. - Water follows (in the collecting duct), and the urine becomes even more concentrated. Proximal convoluted Distal convoluted tubule tubule Glomerulus

Cortex

Collecting tubule from Thick descending limb adjacent nephron

Loop of Henle Medulla

Thick ascending limb

Collecting duct

Thin limb

Papilla Distal convoluted tubules Distal Convoluted Tubules

No brush border Less acidophilic cytoplasm Nuclei relatively close Larger lumen Electron micrograph of a distal convoluted tubule cell. The apical surface of the cell displays some microvilli (Mv), but they are not sufficiently long or numerous to give the appearance of a brush border (compare with Fig. 20.15). The nucleus and Golgi apparatus (G) are in the upper portion of the cell. Mitochondria (M) are chiefly in the basal region of the cell within the interdigitating processes (IP). As in the proximal tubule cell, the mitochondria account for the appearance of basal striations in the light microscope. A basal lamina (BL) is seen adjacent to the basal surface of the cell. X12,000. Collecting Tubules

- Lined by simple cuboidal epithelium - Cool-looking apical membrane bulges into lumen - Sensitive to antidiuretic hormone (ADH), which is made by the hypothalamus and stored in the posterior pituitary. - When there’s ADH around, special aquaporin channels (water channels) open up and allow water to pass through the cells. - This helps concentrate urine. * Cortical and Medullary Collecting Ducts - The cortical and medullary collecting ducts determine final urine osmolality by reabsorbing water. - The outer medullary collecting duct is also the site of urea reabsorption by facilitated transport utilizing urea transporter A1 (UT-A1). - The collecting ducts are composed of simple epithelium. - The cortical collecting ducts have flattened cells, somewhat squamous to cuboidal in shape. - The medullary collecting ducts have cuboidal cells, with a transition to columnar cells as the ducts increase in size. - The collecting ducts are readily distinguished from proximal and distal tubules by virtue of the cell boundaries . - Two distinct types of cells are present in the collecting ducts: • Light cells, also called principal cells or collecting duct (CD) cells, are the predominate cell type of collecting ducts. - They are pale-staining cells with true basal infoldings rather than processes that interdigitate with those of adjacent cells. - They possess a single primary cilium and relatively few short microvilli . - They contain small, spherical mitochondria. - These cells possess an abundance of antidiuretic hormone (ADH)–regulated water channels, aquaporin-2 (AQP-2), which are responsible for water permeability of the collecting ducts. - In addition, aquaporins AQP-3 and AQP-4 are present within the basolateral membrane of these cells. - Principal cells also express abundance of cytoplasmic mineralocorticoid receptors (MRs); . they are the primary target for aldosterone action. • Dark cells, also called intercalated (IC) cells, smaller numbers. - They have many mitochondria, and their cytoplasm appears denser. - , cytoplasmic folds, are present on their apical surface, as well as microvilli. - They do not show basal infoldings but have basally located interdigitations with neighboring cells. - Numerous vesicles are present in the apical cytoplasm. - The intercalated cells are involved in the secretion of H) or bicarbonate, depending on the whether the kidneys need to excrete acid or alkali. - The -intercalated cell actively secretes H into the collecting duct lumen via ATP- dependent pumps and releases HCO3 via Cl/HCO3 exchangers located in their basolateral cell membrane. - The cells of the collecting ducts gradually become taller as the ducts pass from the outer to the inner medulla and become columnar in the region of the renal papilla. - The number of dark cells gradually decreases until there are none in the ducts as they approach the papilla. Collecting ducts Kidney Medulla (Collect tubules and loops) kidney Collecting duct Scanning electron micrograph of a collecting duct. This micrograph shows dark cells (asterisks), with numerous short lamellipodia or microridges on their surface, and light (principal) cells, each with a primary cilium on its free surface along with small microvilli. The terms light and dark refer to the staining character of sectioned cells and not to the density differences reflecting charge characteristics of the coated surface of the specimen. (Courtesy of Dr. C. Craig Tisher.) * INTERSTITIAL CELLS - The connective tissue of the kidney parenchyma, called interstitial tissue, surrounds the nephrons, ducts, and blood and lymphatic vessels. - in the cortex it constitutes approximately 7% of the volume, where it may constitute more than 20% of the volume in medulla). - Two types of interstitial cells are recognized in the cortex : . cells that resemble fibroblasts, and . occasional macrophages.

- In the medulla, the principal interstitial cells resemble myofi broblasts. . They are oriented to the long axes of the tubular structures and may have a role in compressing these structures. HISTOPHYSIOLOGY OF THE KIDNEY

Diagram showing movement of substances into and out of the nephron and collecting system. The symbols indicate the mode of transport as well as specific molecule- dependent transporters that act on the nephron and collecting ducts (as noted in the key). - Urine flows from collecting ducts in renal into the minor calyx, to the major calyx and to the renal pelvis. - The minor and major calyces and renal pelvis are lined by transitional epithelium. Urine flow 1 Collecting ducts in renal papilla from collecting ducts out to 2 Minor calyx 3 Major calyx

4 Renal pelvis 5 Ureter Ureters What happens after urine leaves the kidney? Ureters

- Ureters are paired ducts which conduct urine from the kidney to the bladder. - Transitional epithelium lines the ureters which is cool, because it’s impermeable to water and ions. - Two layers of smooth muscle are present in the wall; - Peristaltic contraction of the smooth muscle moves urine along the ureter. Ureter: super low-power view Ureter – transitional epithelium Ureters have three and smooth muscle coats: 1) a consisting of transitional epithelium (4-5 cells thick) in longitudinal folds supported by a lamina propria of dense connective tissue, 2) a muscle coat with inner longitudinal and outer circular muscle fibers (an outermost layer of longitudinal fibers may also be present), and 3) an adventitial layer of fibroelastic connective tissue Ureter: Umbrella cells Urinary bladder Bladder

- Expandable vessel for the storage of urine. - Transitional epithelium lines the bladder (impermeable to water!) - Composed of four layers, like ureters. - Large bundles of smooth muscle in the wall. Bladder: transitional epithelium and lamina propria 1

2 3

Bladder: muscularis externa (3 layers) Bladder: umbrella cells Bladder – Transitional Epithelium Transmission electron micrograph of urinary bladder epithelium. The mucous membrane of the urinary bladder consists of transitional epithelium (TEp) with an underlying lamina propria (LP). The superficial layer (SupL) contains dome-shaped cells with unique fusiform vesicles (FV), which are evident here at this relatively low magnification. These are seen at higher magnification in Figure 20.27. The intermediate layer (IntL) of variable thickness contains cells that can differentiate and replace lost dome-shaped cells. The basal layer (BasL) contains stem cells of the transitional epithelium. X5,000. Transmission electron micrograph of the apical portion of a dome- shaped cell. a. The cytoplasm displays small vesicles, filaments, and mitochondria, but the most distinctive feature of the cell is its fusiform vesicles (FV). Note that the apical plasma membrane is covered by the rigid-looking concave urothelial plaques (UP) separated by intervening narrow hinge regions (HR). 27,000. b. The higher magnification shows that the membrane forming the fusiform vesicles (arrow) is similar to the apical plasma membrane of the urothelial plaque (UP). Both membranes are thickened and represent asymmetric unit membrane (AUM) in which the outer leaflet of the lipid bilayer is twice as thick as the inner leafl et. Uroplakins (transmembrane proteins called uroplakins (UPIa, UPIb, UPII, UPIIIa, and UPIIIb), the specific proteins of the urothelial plaque, are produced in the rER and then transported to the Golgi apparatus, where they undergo oligomerization into 16-nm particles with the final assembly into a crystalline array. The trans-Golgi network packages AUMs into the fusiform vesicles for delivery to the apical cell membrane. X60,000 Diagrams of the luminal surface of domeshaped cells. a. This drawing depicts a luminal surface of dome-shaped cells in a relaxed bladder. Note the apical plasma membrane of each cell is covered by the ridged concave urothelial plaques that are separated by intervening narrow hinge regions. The fusiform vesicles (drawn in different color) containing additional plaque membranes accumulate in the upper part of the cell. Most of them are vertically oriented and some are attached to hinge regions of the apical cell membrane. b. This diagram depicts the same cell in above diagram as it would appear in a stretched bladder. Note the additional plaques were added to the surface from the fusiform vesicles. The remaining vesicles in this stage are visible in more horizontal position. c. The urothelial plaque on a cross-section exhibits features of the asymmetric unit membrane (AUM) in which the outer leaflet of the lipid bilayer is twice as thick as the inner leaflet. The AUM is present in both, the urothelial plaques and fusiform vesicles. d. The thicker outer leaflet of the urothelial plaque contains a crystalline array of hexagonally arranged 16-nm in diameter proteins that are composed of a family of transmembrane proteins called uroplakins. Urethra Urethra - The urethra conveys urine from the bladder to the exterior. - Epithelium is variable along its length. Urethra: Epithelium varies from stratified or pseudostratified columnar to stratified squamous