Chapter 19: The Urinary System PDF

VetBooks.ir C H A P T E R 19 The Urinary System KIDNEYS 393 BLOOD CIRCULATION 394 RENAL FUNCTION: FILTRATION, SECRETION, & REABSORPTION Renal Corpuscles & Blood Filtration Proximal Convoluted Tubule Loop of Henle 395 396 400 402 T he urinary system consists of the paired kidneys and ureters, the bla...

VetBooks.ir C H A P T E R 19 The Urinary System KIDNEYS 393 BLOOD CIRCULATION 394 RENAL FUNCTION: FILTRATION, SECRETION, & REABSORPTION Renal Corpuscles & Blood Filtration Proximal Convoluted Tubule Loop of Henle 395 396 400 402 T he urinary system consists of the paired kidneys and ureters, the bladder, and the urethra. This system’s primary role is to ensure optimal properties of the blood, which the kidneys continuously monitor. This general role of the kidneys involves a complex combination of renal functions: Regulation of the balance between water and electrolytes (inorganic ions) and the acid-base balance; Excretion of metabolic wastes along with excess water and electrolytes in urine, the kidneys’ excretory product which passes through the ureters for temporary storage in the bladder before its release to the exterior by the urethra; Excretion of many bioactive substances, including many drugs; Secretion of renin, a protease important for regulation of blood pressure by cleaving circulating angiotensinogen to angiotensin I; Secretion of erythropoietin, a glycoprotein growth factor that stimulates erythrocyte production in red marrow when the blood O2 level is low; Conversion of the steroid prohormone vitamin D, initially produced in the skin, to the active form (1,25-dihydroxyvitamin D3 or calcitriol); and Gluconeogenesis during starvation or periods of prolonged fasting, making glucose from amino acids to supplement this process in the liver. ››KIDNEYS Approximately 12-cm long, 6-cm wide, and 2.5-cm thick in adults, each kidney has a concave medial border, the hilum—where nerves enter, the ureter exits, and blood and lymph vessels enter and exit—and a convex lateral surface, Distal Convoluted Tubule & Juxtaglomerular Apparatus Collecting Ducts URETERS, BLADDER, & URETHRA 404 405 406 SUMMARY OF KEY POINTS 411 ASSESS YOUR KNOWLEDGE 412 both covered by a thin fibrous capsule (Figure 19–1). Within the hilum the upper end of the ureter expands as the renal pelvis and divides into two or three major calyces. Smaller branches, the minor calyces, arise from each major calyx. The area surrounding the renal pelvis and calyces contains adipose tissue. The parenchyma of each kidney has an outer renal cortex, a darker stained region with many round corpuscles and tubule cross sections, and an inner renal medulla consisting mostly of aligned linear tubules and ducts (Figure 19–1). The renal medulla in humans consists of 8-15 conical structures called renal pyramids, all with their bases meeting the cortex (at the corticomedullary junction) and separated from each other by extensions of the cortex called renal columns. Each pyramid plus the cortical tissue at its base and extending along its sides constitutes a renal lobe. Parallel ducts and tubules extending from the medulla into the cortex comprise the medullary rays; these plus their associated cortical tissue are considered renal lobules. The tip of each pyramid, called the renal papilla, projects into a minor calyx that collects urine formed by tubules in one renal lobe (Figure 19–1). Each kidney contains 1-4 million functional units called nephrons (Figure 19–2), each consisting of a corpuscle and a long, simple epithelial renal tubule with three main parts along its length. The following are the major divisions of each nephron: Renal corpuscle, an initial dilated part enclosing a tuft of capillary loops and the site of blood filtration, always located in the cortex. Proximal tubule, a long convoluted part, located entirely in the cortex, with a shorter straight part that enters the medulla. Loop of Henle (or nephron loop), in the medulla, with a thin descending and a thin ascending limb. 393 19_Mescher_ch19_p393-412.indd 393 26/04/18 11:50 am VetBooks.ir 394 CHAPTER 19 FIGURE 19–1 The Urinary System Kidney. Renal cortex Renal medulla Renal column Renal pyramid Minor calyx Major calyx Renal pelvis Corticomedullary junction Renal papilla Renal artery Renal vein Renal lobe Ureter Fibrous capsule Each kidney is bean-shaped, with a concave hilum where the ureter and the renal artery and vein enter. The ureter divides and subdivides into several major and minor calyces, around which is located the renal sinus containing adipose tissue. Attached to each Distal tubule, consisting of a thick straight part ascend ing from the loop of Henle back into the cortex and a convoluted part completely in the cortex. Connecting tubule, a short minor part linking the nephron to collecting ducts. Connecting tubules from several nephrons merge to form collecting tubules that then merge as larger collecting ducts. These converge in the renal papilla, where they deliver urine to a minor calyx. Cortical nephrons are located almost completely in the cortex while juxtamedullary nephrons (about one-seventh of the total) lie close to the medulla and have long loops of Henle. › ›› MEDICAL APPLICATION Polycystic kidney disease is an inherited disorder in which normal cortical organization of both kidneys is lost due to the formation of multiple, large, fluid-filled cysts. The cysts may arise from any epithelial cells of the nephron and can lead to gross kidney enlargement and loss of renal function. ››BLOOD CIRCULATION As expected for an organ specialized to process the blood, the kidney vasculature is large, well-organized, and closely associated with all components of the nephron. Blood vessels of 19_Mescher_ch19_p393-412.indd 394 minor calyx is a renal pyramid, a conical region of medulla delimited by extensions of cortex. The cortex and hilum are covered with a fibrous capsule. the kidneys are named according to their locations or shapes (Figure 19–3). Each kidney’s renal artery divides into two or more segmental arteries at the hilum. Around the renal pelvis, these arteries branch further as the interlobar arteries, which extend between the renal pyramids toward the corticomedullary junction (Figure 19–3). Here the interlobar arteries divide again to form the arcuate arteries, which run in an arc along this junction at the base of each renal pyramid. Smaller interlobular arteries (or cortical radial arteries) radiate from the arcuate arteries, extending deeply into the cortex. From the interlobular arteries arise the microvascular afferent arterioles, which divide to form a plexus of capillary loops called the glomerulus, each of which is located within a renal corpuscle where the blood is filtered (Figures 19–3 and 19–4). Blood leaves the glomerular capillaries, not via venules, but via efferent arterioles, which at once branch again to form another capillary network, usually the peritubular capillaries profusely distributed throughout the cortex. From the juxtaglomerular corpuscles near the medulla, efferent arterioles do not form peritubular capillaries, but instead branch repeatedly to form parallel tassel-like bundles of capillary loops called the vasa recta (L. recta, straight), which penetrate deep into the medulla in association with the loops of Henle and collecting ducts. Collectively, the cortex receives over 10 times more blood than the medulla. 26/04/18 11:50 am 395 FIGURE 19–2 A nephron and its parts. C H A P T E R VetBooks.ir Renal Function: Filtration, Secretion, & Reabsorption Macula densa 1 9 Proximal convoluted tubule Glomerulus Glomerular capsule: Renal Visceral layer corpuscle Parietal layer Distal convoluted tubule Capsular space Loop of Henle: Proximal straight tubule Cortex Thin descending limb Medulla Renal tubule Thin ascending limb Connecting tubules Thick ascending limb Collecting duct Each kidney contains 1-4 million functional units called nephrons. Each nephron originates in the cortex, at the renal corpuscle surrounding a small tuft of glomerular capillaries. Extending from the corpuscle is the long PCT which leads to the short proximal straight tubule that enters the outer medulla. This tubule continues as the thin descending limb and the thin ascending limb of the nephron’s loop of Henle in the medulla. The loop of Henle Blood leaves the kidney in veins that follow the same courses as arteries and have the same names (Figure 19–3). The outermost peritubular capillaries and capillaries in the kidney capsule converge into small stellate veins that empty into the interlobular veins. › ›› MEDICAL APPLICATION There are many different glomerular diseases involving the renal corpuscles, with different causes calling for different treatments. Accurate diagnoses of such disorders by pathologists require sampling of the cortex and may involve examination of the renal corpuscles by immunofluorescence light microscopy or even by TEM. 19_Mescher_ch19_p393-412.indd 395 ends with a thick ascending limb, a straight tubule that reenters the cortex and ends at its thickened macula densa area where it contacts the arterioles entering the glomerulus. Beyond the macula densa this tubule is the distal convoluted tubule, the end of which is the short connecting tubule. Connecting tubules from many nephrons merge into cortical collecting tubules and a collecting duct that transports urine to the calyx. The Urinary System Renal Function: Filtration, Secretion, & Reabsorption Connecting tubule ››RENAL FUNCTION: FILTRATION, SECRETION, & REABSORPTION All the major functions of the kidneys—the removal of metabolic wastes and excess water and electrolytes from blood— are performed by various specialized epithelial cells of the nephrons and collecting systems. Renal function involves the following specific activities: Filtration, by which water and solutes in the blood leave the vascular space and enter the lumen of the nephron. Tubular secretion, by which substances move from epithelial cells of the tubules into the lumens, usually 26/04/18 11:50 am VetBooks.ir 396 CHAPTER 19 FIGURE 19–3 The Urinary System Blood supply to the kidneys. Interlobar artery Arcuate artery Afferent arteriole Interlobular artery Nephron Segmental artery Glomerulus Interlobular vein Renal PCT corpuscle DCT Renal artery Efferent arteriole Cortex Arcuate vessels Medulla Peritubular capillaries (associated with convoluted tubules) Vasa recta (associated with loop of Henle) Renal vein Loop of Henle Interlobar vein Arcuate vein A coronal view of a kidney (left) shows the major blood vessels, with their names. An expanded diagram (right) includes the microvascular components extending into the cortex and medulla from the interlobular vessels. Pink boxes indicate vessels with arterial after uptake from the surrounding interstitium and capillaries. Tubular reabsorption, by which substances move from the tubular lumen across the epithelium into the interstitium and surrounding capillaries. Along the length of the nephron tubule and collecting system, the filtrate receives various secreted molecules, while others are reabsorbed and then enters the minor calyces as urine and undergoes excretion. The number of nephrons decreases slightly in older adults, a process accelerated by high blood pressure. If a kidney is donated for transplant (unilateral nephrectomy), the remaining kidney undergoes compensatory growth with cellular hypertrophy in the proximal parts of the nephron tubules and an increase in the rate of filtration, which allow normal renal function to continue. 19_Mescher_ch19_p393-412.indd 396 Interlobular vein blood and light blue indicates the venous return. The intervening lavender boxes and vessels indicate capillaries where specific reabsorbed substances reenter the blood. › ›› MEDICAL APPLICATION Inflammation within the glomeruli, or glomerulonephritis, which can range from acute or chronic, usually stems from humoral immune reactions. Varieties of this condition involve the deposition of circulating antibody-antigen complexes within glomeruli or circulating antibodies binding to either glomerular antigens or extraneous antigens deposited in the glomeruli. Regardless of the source the accumulating immune complexes can then elicit a local inflammatory response. Renal Corpuscles & Blood Filtration At the beginning of each nephron is a renal corpuscle, about 200 μm in diameter and containing a tuft of glomerular capillaries, surrounded by a double-walled epithelial capsule called the glomerular (Bowman) capsule (Figures 19–2 and 19–5). 26/04/18 11:50 am FIGURE 19–4 Microvasculature of the renal cortex. G I G G A I PT Cortical vasculature is revealed in a section of the kidney with the renal artery injected with carmine dye before fixation. Small interlobular arteries (I) branch from the arcuate arteries and radiate out through the cortex giving off the afferent arterioles (A) that bring blood to the glomerular capillaries. Each glomerulus (G) contains a mass of capillary loops that drain into an efferent arteriole. These then branches as a large, diffuse network of peritubular capillaries (PT) throughout the cortex. (X125) The Urinary System Renal Function: Filtration, Secretion, & Reabsorption G A the visceral layer. Each renal corpuscle has a vascular pole, where the afferent arteriole enters and the efferent arteriole leaves, and a tubular pole, where the proximal convoluted tubule (PCT) begins (Figure 19–5). The outer parietal layer of a glomerular capsule consists of a simple squamous epithelium supported externally by a basal lamina. At the tubular pole, this epithelium changes to the simple cuboidal epithelium that continues and forms the proximal tubule (Figure 19–5). The visceral layer of a renal corpuscle consists of unusual stellate epithelial cells called podocytes (Figures 19–5c and 19–5d), which together with the capillary endothelial cells compose the apparatus for renal filtration. From the cell body of each podocyte several primary processes extend and curve around a length of glomerular capillary. Each primary process gives rise to many parallel, interdigitating secondary processes or pedicels (L. pedicellus, little foot; Figures 19–5c and 19–5d). The pedicels cover much of the capillary surface, in direct contact with the basal lamina (Figures 19–5c and 19–6). Between the interdigitating pedicels are elongated spaces, or filtration slit pores, 25- to 30-nm wide (Figures 19–5c and 19–6). Spanning adjacent pedicels and bridging the slit pores are zipper-like slit diaphragms (Figure 19–6). Slit diaphragms are modified and specialized occluding or tight junctions composed of nephrins, other proteins, glycoproteins, and proteoglycans important for renal function. Projecting from the cell membrane on each side of the filtration slit, these polyanionic glycoproteins and proteoglycans interact to form a series of openings within the slit diaphragm, with a surface that is negatively charged. Between the highly fenestrated endothelial cells of the capillaries and the covering podocytes is the thick (300-360 nm) glomerular basement membrane (GBM) (Figure 19–6). This membrane is the most substantial part of the filtration barrier that separates the blood from the capsular space and forms by fusion of the capillary- and podocyte-produced basal laminae. Laminin and fibronectin in this fused basement membrane bind integrins of both the podocyte and endothelial cell membranes, and the meshwork of cross-linked type IV collagen and large proteoglycans restricts passage of proteins larger than about 70 kDa. Smaller proteins that are filtered from plasma are degraded, and the amino acids reabsorbed in the proximal tubule. Polyanionic GAGs in the glomerular membrane are abundant and their negative charges, like those of the slit diaphragms, tend to restrict filtration of organic anions. Filtration, therefore, occurs through a structure with three parts: 1 9 PT 397 C H A P T E R VetBooks.ir Renal Function: Filtration, Secretion, & Reabsorption The fenestrations of the capillary endothelium, which blocks blood cells and platelets The thick, combined basal laminae, or GBM, which restricts large proteins and some organic anions The internal or visceral layer of this capsule closely envelops the glomerular capillaries, which are finely fenestrated. The outer parietal layer forms the surface of the capsule. Between the two capsular layers is the capsular (or urinary) space, which receives the fluid filtered through the capillary wall and 19_Mescher_ch19_p393-412.indd 397 The filtration slit diaphragms between pedicels, which restrict some small proteins and organic anions Normally about 20% of the blood plasma entering a glomerulus is filtered into the capsular space. The initial glomerular filtrate has a chemical composition similar to that of plasma except 26/04/18 11:50 am VetBooks.ir 398 CHAPTER 19 FIGURE 19–5 The Urinary System Renal corpuscles. Parietal layer of glomerular capsule Capsular space Afferent arteriole Vascular pole Tubular pole Flow of blood Flow of filtrate PL Juxtaglomerular apparatus: Juxtaglomerular cell Macula densa Proximal convoluted tubule Glomerulus Podocyte of visceral layer of glomerular capsule CS G Distal tubule Efferent arteriole Pedicel Endothelium of glomerulus DCT MD PCT (a) Renal corpuscle Visceral layer of glomerular capsule Pedicels (b) Histology of renal corpuscle Filtration slits Podocyte cell body Podocyte Capillary lumen Glomerular capillary Pedicels Filtration membrane Endothelium of fenestrated capillary Basement membrane of capillary Glomerular capillary covered by podocytes with pedicels Filtration slits of visceral layer (c) Filtration membrane (d) Podocytes (a) The renal corpuscle consists of a small mass of capillaries called the glomerulus, housed within a bulbous glomerular capsule. The visceral layer of the capsule is composed of complex epithelial cells called podocytes, which cover each capillary, forming slit-like spaces between interdigitating processes called pedicels. Blood enters and leaves the glomerulus through the afferent and efferent arterioles, respectively. macula densa (MD) and sections of proximal convoluted tubules (PCT) and distal convoluted tubules (DCT). (H&E; X300) (b) The micrograph shows the major histologic features of a renal corpuscle. The glomerulus (G) of capillaries is surrounded by the capsular space (CS) covered by the simple squamous parietal layer (PL) of Bowman capsule. Near the corpuscle is that nephron’s (d) The scanning electron microscopy (SEM) shows the distinctive appearance of podocytes and their pedicel processes that cover glomerular capillaries. (X800) 19_Mescher_ch19_p393-412.indd 398 (c) Filtrate is produced in the corpuscle when blood plasma is forced under pressure through the capillary fenestrations, across the filtration membrane or GBM surrounding the capillary, and through the filtration slit diaphragms located between the podocyte pedicels. 26/04/18 11:50 am FIGURE 19–6 399 Glomerular filtration barrier. C H A P T E R VetBooks.ir Renal Function: Filtration, Secretion, & Reabsorption C 1 9 P FS PC E BM P CS F PC FS SD a C F b Glomerular filter Fenestrated capillary endothelium Small protein The glomerular filtration barrier consists of three layered components: the fenestrated capillary endothelium, the GBM, and filtration slit diaphragms between pedicels. The major component of the filter is formed by fusion of the basal laminae of a podocyte and a capillary endothelial cell. (a) TEM shows cell bodies of two podocytes (PC) and the series of pedicels on the capillary (C) basement membrane separated by the filtration slit diaphragms. Around the capillaries and podocytes is the capsular space (CS) into which the filtrate enters. The enclosed area is shown in part (b). (X10,000) (b) At higher magnification, both the fenestrations (F) in the endothelium (E) of the capillary (C) and the filtration slits (FS) separating the pedicels (P) are clearly seen on the two sides of the thick, fused basement membrane (BM). Thin slit diaphragms (SD) bridge the slits between pedicels. (X45,750) (c) Diagram shows the three parts of the glomerular filter and their major functions. 19_Mescher_ch19_p393-412.indd 399 Glomerular basement membrane (blocks large proteins) Filtration slits diaphragms between pedicels (Regulate passage of many small proteins) The Urinary System Renal Function: Filtration, Secretion, & Reabsorption C Leukocyte Large protein Platelet Filtrate includes water, glucose, amino acids, ions, urea, many hormones, vitamins B and C, ketones, and very small amounts of protein Erythrocyte Not filtered Filtered ( ) Substances filtered by (c) y filtration membrane 26/04/18 11:50 am VetBooks.ir 400 CHAPTER 19 The Urinary System that it contains very little protein. The glomerular filter blocks filtration of most plasma proteins, but smaller proteins, including most polypeptide hormones, are removed into the filtrate. › ›› FIGURE 19–7 Podocyte Podocyte process MEDICAL APPLICATION 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). Proteinuria is an indicator of many potential kidney disorders. Unlike the shifting pressures affecting most capillary beds which drain into a venule (see Figure 5–18), the capillaries of each glomerulus (each totaling approximately 1 cm in length) are uniquely situated between the two arterioles, afferent and efferent. Importantly, contractile activity of these arterioles causes hydrostatic pressure in the glomerular capillaries to remain higher than the osmotic pressure exerted by their contents, resulting in the constant filtration of plasma by the glomerular filter along its total length, with no reabsorption of the filtrate. The glomerular filtration rate (GFR) is regulated continuously by neural and hormonal inputs affecting the degree of constriction in two arterioles. The total glomerular filtration area of an adult has been estimated at 500 cm2 and the average GFR at 125 mL/min or 180 L/d. Because the total amount of circulating plasma averages 3 L, it follows that the kidneys typically filter the entire blood volume 60 times every day. In addition to capillary endothelial cells and podocytes, renal corpuscles also contain mesangial cells (Gr. mesos, in the midst + angion, vessel), most of which resemble vascular pericytes in having contractile properties and producing components of an external lamina. Mesangial cells are difficult to distinguish in routine sections from podocytes, but often stain more darkly. They and their surrounding matrix comprise the mesangium (Figure 19–7), which fills interstices between capillaries that lack podocytes. Functions of the mesangium include the following: Physical support of capillaries within the glomerulus Adjusted contractions in response to blood pressure changes, which help maintain an optimal filtration rate Phagocytosis of protein aggregates adhering to the glo Mesangium. merular filter, including antibody-antigen complexes abundant in many pathological conditions Secretion of several cytokines, prostaglandins, and other factors important for immune defense and repair in the glomerulus Proximal Convoluted Tubule Cells in many parts of the nephron tubule and collecting system reabsorb water and electrolytes, but other activities are restricted mainly to specific tubular regions. Table 19–1 summarizes major functions of parts within nephrons and collecting ducts, along with the histologic features involved in these activities. 19_Mescher_ch19_p393-412.indd 400 Capillary Basal lamina Cytoplasm of endothelial cell Capillary Podocyte process Capillary Basement membrane Cytoplasm of endothelial cell Capillary Mesangial cell a US EC P L BM PD E MM MC * * MM b MM (a) Diagram shows that mesangial cells in renal corpuscles are located between capillaries and cover those capillary surface not covered by podocyte processes. (b) The TEM shows one mesangial cell (MC) and the surrounding mesangial matrix (MM). This matrix appears similar to and in many places continuous with basement membrane (BM) and supports capillaries where podocytes are lacking. Mesangial cells extend contractile processes (arrows) along capillaries that help regulate blood flow in the glomerulus. Some mesangial processes appear to pass between endothelial cells (EC) into the capillary lumen (asterisks) where they may help remove or endocytose adherent protein aggregates. The capillary at the left contains an erythrocyte (E) and a lymphocyte (L). Podocytes (P) and their pedicels (PD) open to the urinary space (US) and associate with the capillary surfaces not covered by mesangial cells. (X3500) At the tubular pole of the renal corpuscle, the simple squamous epithelium of the capsule’s parietal layer is continuous with the simple cuboidal epithelium of the proximal convoluted tubule (PCT) (Figures 19–8 and 19–9). These long, tortuous tubules fill most of the cortex. PCT cells are specialized for both reabsorption and secretion. Over half of the water and electrolytes, and all of the organic nutrients (glucose, amino 26/04/18 11:50 am 401 TABLE 19–1   Histologic features and major functions of regions within renal tubules. Locations Major Functions PCT Simple cuboidal epithelium; cells well-stained, with numerous mitochondria, prominent basal folds and lateral interdigitations; long microvilli, lumens often occluded Cortex Reabsorption of all organic nutrients, all proteins, most water, and electrolytes; secretion of organic anions and cations, H+, and NH4+ Thin limbs Simple squamous epithelium; few mitochondria Medulla Passive reabsorption of Na+ and Cl− TAL Simple cuboidal epithelium; no microvilli, but many mitochondria Medulla and medullary rays Active reabsorption of various electrolytes Simple cuboidal epithelium; cells smaller than in PCT, short microvilli and basolateral folds, more empty lumens Cortex Reabsorption of electrolytes Principal cells Most abundant, cuboidal to columnar; pale-staining, distinct cell membranes Medullary rays and medulla Regulated reabsorption of water & electrolytes; regulated secretion of K+ Intercalated cells Few and scattered; slightly darker staining Medullary rays Reabsorption of K+ (low-K+ diet); help maintain acid-base balance Loop of Henle DCT Collecting system DCT, distal convoluted tubule; PCT, proximal convoluted tubule; TAL, thick ascending limb. acids, vitamins, etc), filtered from plasma in the renal corpuscle are normally reabsorbed in the PCT. These molecules are transferred directly across the tubular wall for immediate uptake again into the plasma of the peritubular capillaries. Transcellular reabsorption involves both active and passive mechanisms, with the cells having a large variety of transmembrane ion pumps, ion channels, transporters, enzymes, and carrier proteins. Water and certain solutes can also move passively between the cells (paracellular transport) along osmotic gradients through leaky apical tight junctions. Small proteins in the filtrate are either reabsorbed by receptor-mediated endocytosis and degraded in the cuboidal cells, or degraded by peptidases on the luminal surface. In both cases the amino acids are released at the basolateral cell surfaces for uptake by capillaries. Conversely, organic anions and cations not filtered in the renal corpuscle (because of the polyanions in the filter or binding to plasma proteins) may be released in the peritubular capillaries, taken up by the cells of the proximal tubules and undergo secretion into the filtrate (Table 19–1). Organic anion and cation transporters allow the kidneys to dispose of such substances at a higher rate than by glomerular filtration alone. Because these molecules include important substances (such as bile salts and creatinine) and many antibiotics and other drugs, this process of tubular secretion is of great pharmacologic importance as a key mechanism of drug clearance. The cells of the proximal tubules have central nuclei and very acidophilic cytoplasm (Figures 19–8 and 19–9) because of 19_Mescher_ch19_p393-412.indd 401 the abundant mitochondria. The cell apex has very many long microvilli that form a prominent brush border in the lumen that facilitates reabsorption (Figures 19–8 through 19–10). Because the cells are large, each transverse section of a PCT typically contains only three to five nuclei. In routine histologic preparations, the long brush border may be disorganized and give the lumens a fuzz-filled appearance. Peritubular capillaries are abundant in the sparse surrounding connective tissue interstitium, which fills only about 10% of the cortex (Figure 19–8). Ultrastructurally the apical cytoplasm of these cells has numerous pits and vesicles near the bases of the microvilli, indicating active endocytosis and pinocytosis (Figure 19–10). These vesicles contain the small, reabsorbed proteins that will be degraded in lysosomes, with the amino acids released to the circulation. Proximal tubular cells also have many long basal membrane invaginations and lateral interdigitations with neighboring cells (Figure 19–10). Both the brush border and the basolateral folds contain the many types of transmembrane proteins that mediate tubular reabsorption and secretion. Long mitochondria concentrated along the basal invaginations (Figure 19–10) supply ATP locally for the membrane proteins involved in active transport. Because of the extensive interdigitations of the lateral membranes, discrete limits between cells of the proximal tubule are difficult to see with the light microscope. Besides their major roles in reabsorption and secretion, cells of the proximal tubule also perform hydroxylation of vitamin D and release to the capillaries. Moreover, fibroblastic The Urinary System Renal Function: Filtration, Secretion, & Reabsorption Histologic Features 1 9 Region of Tubule C H A P T E R VetBooks.ir Renal Function: Filtration, Secretion, & Reabsorption 26/04/18 11:50 am VetBooks.ir 402 CHAPTER 19 FIGURE 19–8 The Urinary System Renal cortex: proximal and distal convoluted tubules. D P P P P U D TP P D P G P P P P U D D P D a (a) The micrograph shows the continuity at a renal corpuscle’s tubular pole (TP) between the simple cuboidal epithelium of a proximal convoluted tubule (P) and the simple squamous epithelium of the capsule’s parietal layer. The urinary space (U) between the parietal layer and the glomerulus (G) drains into the lumen of the proximal tubule. The lumens of the proximal tubules appear filled, because of the long microvilli of the brush border interstitial cells in cortical areas near the proximal tubules produce erythropoietin, the growth factor secreted in response to a prolonged decrease in local oxygen concentration. › ›› MEDICAL APPLICATION Diabetic glomerulosclerosis, the thickening and loss of function in the GBM produced as part of the systemic microvascular sclerosis in diabetes mellitus, is the leading cause of (irreversible) end-stage kidney disease in the United States. Treatment requires either a kidney transplant or regular artificial hemodialysis. 19_Mescher_ch19_p393-412.indd 402 b and aggregates of small plasma proteins bound to this structure. By contrast, the lumens of distal convoluted tubules (D) appear empty, lacking a brush border and protein. (b) Here the abundant peritubular capillaries and draining venules (arrows) surrounding the proximal (P) and distal (D) convoluted tubules are clearly seen. (Both X400; H&E) Loop of Henle The PCT continues with the much shorter proximal straight tubule, which enters the medulla and continues as the nephron’s loop of Henle (Figure 19–2). This is a U-shaped structure with a thin descending limb and a thin ascending limb, both composed of simple squamous epithelia. The straight part of the proximal tubule has an outer diameter of about 60 μm, but it narrows abruptly to about 30 μm in the thin limbs of the loop. The wall of the thin segments consists only of squamous cells with few organelles (indicating a primarily passive role in transport) and the lumen is prominent (Figures 19–9 and 19–11). The thin ascending limb of the loop becomes 26/04/18 11:50 am 403 FIGURE 19–9 Convoluted tubules, nephron loops, and collecting ducts. C H A P T E R VetBooks.ir Renal Function: Filtration, Secretion, & Reabsorption RC Renal corpuscle PCT DCT (b) Renal cortex Nephron loop Tall microvilli Nucleus Mitochondria Basement Proximal convoluted tubule membrane (a) Nephron components T (a) Diagram of a nephron shows levels of the sections in the photos. (b) A section of cortical tissue shows one renal corpuscle (RC), the wide, eosinophilic proximal convoluted tubules (PCT) with the smaller, less well-stained distal convoluted tubules (DCT). (X160; H&E) T CD A (d) Cross section of renal medulla the thick ascending limb (TAL), with simple cuboidal epithelium and many mitochondria again, in the outer medulla and extends as far as the macula densa near the nephron’s glomerulus. The loops of Henle and surrounding interstitial connective tissue are involved in further adjusting the salt content of 19_Mescher_ch19_p393-412.indd 403 Distal convoluted tubule (c) Convoluted tubule epithelia A CD Short, sparse microvilli The Urinary System Renal Function: Filtration, Secretion, & Reabsorption Distal convoluted tubule Afferent arteriole Collecting duct Proximal convoluted tubule 1 9 Efferent arteriole (c) Diagram shows the major structural differences between the cuboidal cells of proximal and distal tubules. Cells of both tubules have basal membrane invaginations associated with mitochondria. (d) A cross section through a medullary renal pyramid shows the simple squamous epithelium of the thin descending and ascending limbs of loops of Henle (T) and its thick ascending limbs (A), as well as the pale columnar cells of collecting ducts (CD). Note also the homogeneous interstitium with capillaries smaller than the thin limbs. (X160; Mallory trichrome) the filtrate. Cuboidal cells of the loops’ TALs actively transport sodium and chloride ions out of the tubule against a concentration gradient into the hyaluronate-rich interstitium, making that compartment hyperosmotic. This causes water to be withdrawn passively from the thin descending part of the loop, thus concentrating the filtrate. The thin ascending 26/04/18 11:51 am VetBooks.ir 404 CHAPTER 19 The Urinary System › ›› MEDICAL APPLICATION FIGURE 19–10 Ultrastructure of proximal convoluted tubule cells. Sickle cell nephropathy, one of the most common problems caused by sickle cell disease, occurs when the affected erythrocytes sickle in the vasa recta, because of the low oxygen tension there. The nephropathy results from renal infarcts, usually within the renal papillae or pyramids. MV V V L Distal Convoluted Tubule & Juxtaglomerular Apparatus L L L L M M M M F C TEM reveals important features of the cuboidal cells of the proximal convoluted epithelium: the long, dense apical microvilli (MV), the abundant endocytotic pits and vesicles (V) in the apical regions near lysosomes (L). Small proteins brought into the cells nonspecifically by pinocytosis are degraded in lysosomes and the amino acids released basally. Apical ends of adjacent cells are sealed with zonula occludens, but the basolateral sides are characterized by long invaginating folds of membrane along which many long mitochondria (M) are situated. Water and the small molecules released from the PCTs are taken up immediately by the adjacent peritubular capillaries (C). Between the basement membranes of the tubule and the capillary shown here is an extension of a fibroblast (F). (X10,500) limbs reabsorb sodium chloride (NaCl) but are impermeable to water. The countercurrent flow of the filtrate (descending, then immediately ascending) in the two parallel thin limbs establishes a gradient of osmolarity in the interstitium of the renal pyramids, an effect that is “multiplied” at deeper levels in the medulla. Countercurrent blood flow in the descending and ascending loops of the vasa recta helps maintain the hyperosmotic interstitium. The interstitial osmolarity at the pyramid tips is about four times that of the blood. The countercurrent multiplier system established by the nephron loop and vasa recta is an important aspect of renal physiology in humans. 19_Mescher_ch19_p393-412.indd 404 The ascending limb of the nephron is straight as it enters the cortex and forms the macula densa, and then becomes tortuous as the distal convoluted tubule (DCT) (Figure 19–2). Much less tubular reabsorption occurs here than in the proximal tubule. The simple cuboidal cells of the distal tubules differ from those of the proximal tubules in being smaller and having no brush border and more empty lumens (Figure 19–9). Because distal tubule cells are flatter and smaller than those of the proximal tubule, more nuclei are typically seen in sections of distal tubules than in those of proximal tubules (Figure 19–8). Cells of the DCT also have fewer mitochondria than cells of proximal tubules, making them less acidophilic (Figure 19–9). The rate of Na+ absorption here is regulated by aldosterone from the adrenal glands. Where the initial, straight part of the distal tubule contacts the arterioles at the vascular pole of the renal corpuscle of its parent nephron, its cells become more columnar and closely packed, forming the macula densa (L. thicker spot). This is part of a specialized sensory structure, the juxtaglomerular apparatus (JGA) that utilizes feedback mechanisms to regulate glomerular blood flow and keep the rate of glomerular filtration relatively constant. The JGA is shown in Figures 19–5 and 19–12. Cells of the macula densa typically have apical nuclei, basal Golgi complexes, and a more elaborate and varied system of ion channels and transporters. Adjacent to the macula densa, the tunica media of the afferent arteriole is also modified. The smooth muscle cells are modified as juxtaglomerular granular (JG) cells, with a secretory phenotype including more rounded nuclei, rough ER, Golgi complexes, and granules with the protease renin (Figures 19–5 and 19–12). Also at the vascular pole are lacis cells (Fr. lacis, lacework), which are extraglomerular mesangial cells that have many of the same supportive, contractile, and defensive functions as these cells inside the glomerulus. Basic functions of the JGA in the autoregulation of the GFR and in controlling blood pressure include the following activities. Elevated arterial pressure increases glomerular capillary blood pressure, which increases the GFR. Higher GFR leads to higher luminal concentrations of Na+ and Cl– in the TAL of the nephron, which are monitored by cells of the macula densa. Increased ion levels in the lumen cause these cells to release ATP, adenosine, and other vasoactive compounds that trigger contraction of the afferent 26/04/18 11:51 am FIGURE 19–11 405 Renal medulla: nephron loops and collecting ducts. C H A P T E R VetBooks.ir Renal Function: Filtration, Secretion, & Reabsorption T I C C A T H T CD T I CD C A I I a C CD (a) A micrograph of a medullary renal pyramid cut transversely shows closely packed cross sections of the many nephron loops’ thin descending and ascending limbs (T) and thick ascending limbs (A), intermingled with parallel vasa recta capillaries containing blood (C) and collecting ducts (CD). All these structures are embedded in the interstitium (I), which contains sparse myofibroblast-like cells in a matrix very rich in hydrophilic hyaluronate. The specialized nature of the interstitial tissue helps maintain the osmolarity gradient established by differential salt and water transport across the wall of the nephron loop, which is required arteriole, which lowers glomerular pressure and decreases the GFR. This lowers tubular ion concentrations, which turns off the release of vasoconstrictors from the macula densa. Decreased arterial pressure leads to increased autonomic stimulation to the JGA as a result of baroreceptor function, including local baroreceptors in the afferent arteriole, possibly the JG cells themselves. This causes the JG cells to release renin, an aspartyl protease, into the blood. There renin cleaves the plasma protein angiotensinogen into the inactive decapeptide angiotensin I. Angiotensin-converting enzyme (ACE) on lung capillaries clips this further to angiotensin II, a potent vasoconstrictor that directly raises systemic blood pressure and stimulates the adrenals to secrete aldosterone. Aldosterone promotes Na+ and water reabsorption in the distal convoluted and connecting tubules, which raises blood volume to help increase blood pressure. 19_Mescher_ch19_p393-412.indd 405 b to concentrate urine and conserve body water. (X400; Mallory trichrome) (b) The TEM reveals the slightly fibrous nature of the interstitium (I) and shows that the simple squamous epithelium of the thin limbs (T) is slightly thicker than that of the nearby vasa recta capillaries (C). (X3300) (Figure 19–11b, used with permission from Dr Johannes Rhodin, Department of Cell Biology and Anatomy, University of South Florida College of Medicine, Tampa.) The Urinary System Renal Function: Filtration, Secretion, & Reabsorption T 1 9 A The return of normal blood pressure turns off secretion of renin by JG cells. Collecting Ducts The last part of each nephron, the connecting tubule, carries the filtrate into a collecting system that transports it to a minor calyx and in which more water is reabsorbed if needed by the body. As shown in Figures 19–13, a connecting tubule extends from each nephron and several join together in the cortical medullary rays to form collecting ducts of simple cuboidal epithelium and an average diameter of 40 μm. In the medulla these merge further, forming larger and straighter collecting ducts with increasingly columnar cells and overall diameters reaching 200 μm (Figures 19–11 and 19–14). Approaching the apex of each renal pyramid, several medullary collecting ducts merge again to form each papillary duct (or duct 26/04/18 11:51 am VetBooks.ir 406 CHAPTER 19 FIGURE 19–12 The Urinary System Juxtaglomerular apparatus. US G EA L AA P JG MD D P The JGA forms at the point of contact between a nephron’s distal tubule (D) and the vascular pole of its glomerulus (G). At that point cells of the distal tubule become columnar as a thickened region called the macula densa (MD). Smooth muscle cells of the afferent arteriole’s (AA) tunica media are converted from a contractile to a secretory morphology as juxtaglomerular granule cells (JG). Also present are lacis cells (L), which are extraglomerular mesangial cells adjacent to the macula densa, the afferent arteriole, and the efferent arteriole (EA). In this specimen the lumens of proximal tubules (P) appear filled and the urinary space (US) is somewhat swollen. (X400; Mallory trichrome) of Bellini), which deliver urine directly into the minor calyx (Figure 19–13). Running parallel with the descending and ascending limbs of the loops of Henle and vasa recta, medullary collecting ducts lie in the area with very high interstitial osmolarity (Figures 19–2 and 19–11). Collecting tubules and ducts are composed mainly of palestaining principal cells with few organelles, sparse microvilli, and unusually distinct cell boundaries (Figure 19–14). Ultrastructurally the principal cells can be seen to have basal membrane infoldings, consistent with their role in ion transport, and a primary cilium among the microvilli. The medullary collecting ducts are the final site of water reabsorption from the filtrate. Principal cells are particularly rich in aquaporins, the integral membrane pore proteins functioning as specific channels for water molecules, but here most aquaporins are sequestered in membranous cytoplasmic vesicles. 19_Mescher_ch19_p393-412.indd 406 Antidiuretic hormone (ADH), released from the posterior pituitary gland as the body becomes dehydrated, makes collecting ducts more permeable to water and increases the rate at which water molecules are pulled osmotically from the filtrate. Upon binding, ADH receptors on the basolateral cell surface stimulate the movement and insertion of vesicles with aquaporins into the apical (luminal) membranes, increasing the number of membrane channels and water movement through the cells. The high osmolarity of the interstitium draws water passively from the collecting ducts, concentrating the filtrate. The water thus saved immediately enters the blood in the vasa recta. Scattered among the principal cells are variably darker intercalated cells with more abundant mitochondria and projecting apical folds. Intercalated cells, some of which also occur in the DCTs, help maintain acid-base balance by secreting either H+ (from type A or α intercalated cells) or HCO3– (from type B or β intercalated cells). Histologic features and major functions of the nephron’s parts and collecting ducts are summarized in Table 19–1. › ›› MEDICAL APPLICATION A common problem involving the ureters is their obstruction by renal calculi (kidney stones) formed in the renal pelvis or calyces, usually from calcium salts (oxalate or phosphate) or uric acid. While urate stones are usually smooth and small, calcium stones can become large and irritate the mucosa. Most kidney stones are asymptomatic, but besides causing an obstruction that can lead to renal problems, movement of stones from the renal pelvis into the ureter can cause extreme pain on the affected side of the body. Problems caused by such stones can be corrected by either surgical removal of the stone or its disintegration using focused ultrasonic shock waves in a procedure called lithotripsy, although this treatment can cause significant renal damage. ››URETERS, BLADDER, & URETHRA Urine is transported by the ureters from the renal pelvis to the urinary bladder where it is stored until emptying by micturition via the urethra. The walls of the ureters are similar to that of the calyces and renal pelvis, with mucosal, muscular, and adventitial layers and becoming gradually thicker closer to the bladder. The mucosa of these organs is lined by the uniquely stratified urothelium or transitional epithelium introduced in Chapter 4 (Figures 19–15 and 19–16). Cells of this epithelium are organized as three layers: A single layer of small basal cells resting on a very thin basement membrane, An intermediate region containing from one to several layers of cuboidal or low columnar cells, and 26/04/18 11:51 am 407 FIGURE 19–13 Fluid transport in the urinary system. FIGURE 19–14 Collecting ducts. C H A P T E R VetBooks.ir Ureters, Bladder, & Urethra Filtrate 1 Capsular space 5 3 Descending limb of nephron loop VR 4 Ascending limb of nephron loop 3 5 Distal convoluted tubule (DCT) 4 6 6 Connecting tubules 7 Collecting duct 7 CD a 8 Urine 8 Papillary duct 9 9 Minor calyx 10 Major calyx 10 11 12 The Urinary System Ureters, Bladder, & Urethra 2 1 9 Tubular fluid 2 Proximal convoluted tubule (PCT) 1 11 Renal pelvis 12 Ureter Pale-staining columnar principal cells, in which ADH-regulated aquaporins of the cell membrane allow more water reabsorption, are clearly seen in these transversely sectioned collecting ducts (CD), surrounded by interstitium with vasa recta (VR). (X600; PT) A superficial layer of large bulbous or elliptical umbrella cells, sometimes binucleated, which are highly differentiated to protect the underlying cells against the potentially cytotoxic effects of hypertonic urine. 13 14 b 19_Mescher_ch19_p393-412.indd 407 13 Urinary bladder 14 Urethra The thick muscularis of the ureters moves urine toward the bladder by peristaltic contractions and produces prominent mucosal folds when the lumen is empty (Figure 19–16). (Left) (a) Diagram of a nephron and collecting system shows the flow of filtrate. (b) Upon delivery at a minor calyx, filtrate is no longer modified by reabsorption or secretion and is called urine. It flows passively into the renal pelvis but moves by peristalsis along the ureters for temporary storage in the urinary bladder, which is emptied through the urethra. 26/04/18 11:51 am VetBooks.ir 408 CHAPTER 19 FIGURE 19–15 and minor calyx. The Urinary System Renal papilla, collecting ducts, MC RP A CD I U T A sagittal section of a renal papilla shows numerous collecting ducts (also called the ducts of Bellini at this level) converging at the end of the renal papilla (RP) where they empty into the minor calyx (MC). The mucosa of the calyx contains dense connective tissue stained blue here and adipose tissue (A). The ducts are embedded in interstitial tissue, which also contains thin limbs of the nephron loops (X50; Mallory trichrome). Inset: An enlarged area shows the columnar epithelium of the collecting ducts (CD), the interstitium (I) and thin limbs (T), and the protective urothelium (U) that lines the minor calyx. (X200; Mallory trichrome) › ›› MEDICAL APPLICATION Bacterial infections of the urinary tract can lead to inflammation of the renal pelvis and calyces, or pyelonephritis. In acute pyelonephritis, bacteria often move from one or more minor calyx into the associated renal papilla, causing accumulation of neutrophils in the collecting ducts. Umbrella cells are especially well developed in the bladder (Figure 19–17) where contact with urine is greatest. These cells, up to 100 μm in diameter, have extensive intercellular junctional complexes surrounding unique apical membranes. Most of the apical surface consists of asymmetric unit membranes in which regions of the outer lipid layer appear 19_Mescher_ch19_p393-412.indd 408 ultrastructurally to be twice as thick as the inner leaflet. These regions are composed of lipid rafts containing mostly integral membrane proteins called uroplakins that assemble into paracrystalline arrays of stiffened plaques 16 nm in diameter. The abundant membranous plaques, together with the tight junctions, allow this epithelium to serve as an osmotic barrier protecting its cells and the cells of surrounding tissues from hypertonic urine and preventing dilution of the stored urine. Plaques are hinged together by more narrow regions of typical membrane. When the bladder is emptied, not only does the mucosa fold extensively, but individual umbrella cells decrease their apical surface area by folding the membrane at the hinge regions and internalizing the folded plaques in discoidal vesicles. As the bladder fills again these vesicles rejoin the apical membrane, increasing its surface area as the tight junctions are reorganized and the cells become less bulbous. The thickness of the full bladder’s urothelium is half that of the empty bladder (2-3 cell layers vs 5-7 layers), apparently the result of the intermediate cells being pushed and pulled laterally to accommodate the increased volume of urine. Urothelium is surrounded by a folded lamina propria and submucosa, followed by a dense sheath of interwoven smooth muscle layers and adventitia (Figures 19–16 and 19–17). Urine is moved from the renal pelvises to the bladder by peristaltic contractions of the ureters. The bladder’s lamina propria and dense irregular connective tissue of the submucosa are highly vascularized. The bladder in an average adult can hold 400-600 mL of urine, with the urge to empty appearing at about 150-200 mL. The muscularis consists of three poorly delineated layers, collectively called the detrusor muscle, which contract to empty the bladder (Figure 19–17). Three muscular layers are seen most distinctly at the neck of the bladder near the urethra (Figure 19–17). The ureters pass through the wall of the bladder obliquely, forming a valve that prevents the backflow of urine into the ureters as the bladder fills. All the urinary passages are covered externally by an adventitial layer, except for the upper part of the bladder that is covered by serous peritoneum. › ›› MEDICAL APPLICATION Cystitis, or inflammation of the bladder mucosa, is the most frequent problem involving this organ. Such inflammation is common during urinary tract infections, but it can also be caused by immunodeficiency, urinary catheterization, radiation, or chemotherapy. Chronic cystitis can cause an unstable urothelium, with benign urothelial changes involving hyperplasia or metaplasia. Bladder cancer is usually some form of transitional cell carcinoma arising from unstable urothelium. The urethra is a tube that carries the urine from the bladder to the exterior (Figure 19–18). The urethral mucosa has prominent longitudinal folds, giving it a distinctive appearance in cross section. In men, the two ducts for sperm transport during ejaculation join the urethra at the prostate gland 26/04/18 11:51 am 409 FIGURE 19–16 Ureters. C H A P T E R VetBooks.ir Ureters, Bladder, & Urethra Mucosa Lamina propria Transitional epithelium 1 9 M Mucosa Muscularis Mu Lumen Adventitia (a) Ureter cross section (b) (a) Diagram of a ureter in cross section shows a characteristic pattern of longitudinally folded mucosa, surrounded by a thick muscularis that moves urine by regular waves of peristalsis. The lamina propria is lined by a unique stratified epithelium called transitional epithelium or urothelium that is resistant FIGURE 19–17 to the potentially deleterious effects of contact with hypertonic urine. (b) Histologically the muscularis (Mu) is much thicker than the mucosa (M) and adventitia (A). (X18; H&E) The Urinary System Ureters, Bladder, & Urethra A Bladder wall and urothelium. U LP S LP S IL U U ML OL a A (a) In the neck of the bladder, near the urethra, the wall shows four layers: the mucosa with urothelium (U) and lamina propria (LP); the thin submucosa (S); inner, middle, and outer layers of smooth muscle (IL, ML, and OL); and the adventitia (A). (X15; H&E) 19_Mescher_ch19_p393-412.indd 409 b c (b) When the bladder is empty, the mucosa is highly folded and the urothelium (U) has bulbous umbrella cells. (X250; PSH) (c) When the bladder is full, the mucosa is pulled smooth, the urothelium (U) is thinner, and the umbrella cells are flatter. (X250; H&E) 26/04/18 11:51 am VetBooks.ir 410 CHAPTER 19 FIGURE 19–18 The Urinary System Urethra. E L a The urethra is a fibromuscular tube that carries urine from the bladder to the exterior of the body. (a) A transverse section shows that the mucosa has large longitudinal folds around the lumen (L). (X50; H&E) b epithelial lining varies between stratified columnar in some areas and pseudostratified columnar elsewhere, but it becomes stratified squamous at the distal end of the urethra. (X250; H&E) (b) A higher magnification of the enclosed area shows the unusual stratified columnar nature of the urethral epithelium (E). This thick (see Chapter 21). The male urethra is longer and consists of three segments: The prostatic urethra, 3-4 cm long, extends through the prostate gland and is lined by urothelium. The membranous urethra, a short segment, passes through an external sphincter of striated muscle and is lined by stratified columnar and pseudostratified columnar epithelium. The spongy urethra, about 15 cm in length, is enclosed within erectile tissue of the penis (see Chapter 21) and is lined by stratified columnar and pseudostratified columnar epithelium (Figure 19–18), with stratified squamous epithelium distally. In women, the urethra is exclusively a urinary organ. The female urethra is a 3- to 5-cm-long tube, lined initially 19_Mescher_ch19_p393-412.indd 410 with transitional epithelium which then transitions to nonkeratinized stratified squamous epithelium continuous with that of the skin at the labia minora. The middle part of the urethra in both sexes is surrounded by the external striated muscle sphincter. › ›› MEDICAL APPLICATION Urinary tract infections, usually involving coliform bacteria or Chlamydia, often produce urethritis and in women often lead to cystitis because of the short urethra. Such infections are usually accompanied by a persistent or more frequent urge to urinate, and urethritis may produce pain or difficulty during urination (dysuria). 26/04/18 11:51 am The Urinary System 411 SUMMARY OF KEY POINTS Renal Vasculature Renal arteries branch to form smaller arteries between the renal lobes, with interlobular arteries entering the cortex to form the microvasculature; venous branches parallel the arterial supply. In the cortex afferent arterioles enter capillary clusters called glomeruli, which are drained by efferent arterioles, instead of venules, an arrangement that allows higher hydrostatic pressure in the capillaries. The efferent arterioles from cortical glomeruli branch diffusely as peritubular capillaries, while those from juxtamedullary glomeruli branch as long microvascular loops called vasa recta in the medulla. Nephrons Functional units of the kidney are the nephrons, numbering about 1 million, each with a renal corpuscle and a long renal tubule, and a system of collecting ducts. The renal corpuscle has a simple squamous parietal layer of the glomerular (Bowman) capsule, continuous with the proximal tubule, and a specialized visceral layer of podocytes surrounding the glomerular capillaries. Podocytes extend large primary processes that curve around a capillary and extend short, interdigitating secondary processes or pedicels, between which are narrow spaces called slit pores. The elevated pressure in the capillaries forces water and small solutes of blood plasma through the glomerular filter into the capsular (or urinary) space inside the glomerular capsule. In each glomerulus the filter has three parts: the finely fenestrated capillary endothelium; the thick (330 nm) fused basal laminae of type IV collagen and other proteins produced by the endothelial cells and podocytes; and the slit pores between the pedicels, covered by thin filtration slit diaphragms. From the renal corpuscle, filtrate enters the long nephron tubule that extends through both the cortex and medulla, with epithelial cells for both reabsorption and secretion of substances into the filtrate. 19_Mescher_ch19_p393-412.indd 411 dal cells with long microvilli in the lumen, abundant mitochondria, and large, interdigitating basolateral folds. In the PCT, all glucose and other organic nutrients, all small proteins and peptides (which are degraded to amino acids), and much water and electrolytes are reabsorbed from the filtrate and transferred to the peritubular capillaries. From the PCT filtrate flows into the loop of Henle, located in the medulla, which has squamous thin descending and ascending limbs; the latter extends as a TAL back into the cortex. In the cortex the TAL (also known as the distal straight tubule) contacts the arterioles at the vascular pole of its parent renal corpuscle and there thickens focally as the macula densa. Tall epithelial cells of the macula densa and specialized smooth muscle cells in the adjacent afferent arteriole called juxtaglomerular cells, which secrete renin, comprise a JGA that is an important regulator of blood pressure. Beyond the macula densa, the tubule continues as the DCT, where electrolyte levels of the filtrate are adjusted further and which lead to short connecting tubules. Connecting tubules from several nephrons join to form the cortical collecting ducts, of simple cuboidal epithelium, which enter the medulla in parallel with the loops of Henle and vasa recta and become larger with more columnar cells. Urinary Tract Principal cells of the collecting ducts are pale-staining, with relatively few mitochondria and distinct cell membranes that are rich in aquaporins (water channels) for passive water reabsorption. The largest collecting ducts deliver filtrate into the minor calyces, where it undergoes no further modification and is called urine. The calyces, renal pelvis, ureters, and urinary bladder are lined by urothelium, or transitional epithelium, which protects underlying cells from hypertonic, potentially toxic effects of urine. Large, bulbous superficial cells of the urothelium, called umbrella cells, have apical membranes consisting of hinged regions with dense plaques of uroplakin proteins that protect the cytoplasm. As the urinary bladder fills its highly folded mucosa unfolds, the urothelium gets somewhat thinner by cell movements, and the hinged membrane plaques of umbrella cells partially unfold. The urethra drains the bladder and in both genders is lined initially by urothelium, followed (in males) by alternating stratified columnar and pseudostratified columnar epithelium and distally by stratified squamous epithelium. In males the urethra has three regions: the prostatic urethra in the prostate gland, the short membranous urethra passing through the urogenital diaphragm, and the long penile urethra. The Urinary System Ureters, Bladder, & Urethra The first tubular part, the PCT, is mainly cortical, has simple cuboi- 1 9 Kidney Each kidney has a thick outer cortex, surrounding a medulla that is divided into 8-12 renal pyramids; each pyramid and its associated cortical tissue comprises a renal lobe. The apical papilla of each renal pyramid inserts into a minor calyx, a subdivision of two or three major calyces extending from the renal pelvis. The ureter carries urine from the renal pelvis and exits the renal hilum, where the renal artery and vein are also located. C H A P T E R VetBooks.ir Ureters, Bladder, & Urethra 26/04/18 11:51 am