Chapter 19:

Urinary System

Color Textbook of Histology, 3rd ed.

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Gartner & Hiatt

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Hemisected Kidney
Each kidney has a cortex and a medulla. The cortex presents (1) renal corpuscles; (2) cortical labyrinth; and (3) longitudinal striations, medullary rays, whereas the medulla contains the renal pyramids, whose bases form the corticomedullary border. The apex of a renal pyramid, the renal papilla, is perforated by 20 or so openings of the ducts of Bellini. The apex is surrounded by a cup-like minor calyx, two or three of which drain into a major calyx. These, in turn, empty into the renal pelvis. Neighboring pyramids are separated from each other by material resembling the cortex, the cortical columns (of Bertin). A renal pyramid, with its associated cortical arch and cortical columns, represents a lobe of the kidney. Each medullary ray with part of the cortical labyrinth surrounding it is considered a kidney lobule, which continues into the medulla as a coneshaped structure. The functional unit of the kidney is the uriniferous tubule, a highly convoluted structure that modifies the fluid passing through it to form urine as its final output. Uriniferous tubules are densely packed so that the connective tissue stroma of the kidney is scant. The entire uriniferous tubule is epithelial in nature and is, therefore, separated from the connective tissue stroma by an intervening basal lamina. This tubule consists of two parts, each with a different embryological origin, the nephron and the collecting tubule. There are approximately 1.3 million nephrons in each kidney. Several nephrons are drained by a single collecting tubule.
For more information see Overview of Kidney section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Figure 191 A, Hemisected kidney illustrating morphology and circulation. B, Arrangement of cortical and juxtamedullary nephrons. Copyright 2007 by Saunders/Elsevier. All rights reserved.

Nephron
Two types of nephrons are found in the human kidney: shorter cortical nephrons and longer juxtamedullary nephrons, whose renal corpuscle is located in the cortex and whose tubular parts are located in the medulla. The specific locations of the two types of nephrons, the cellular composition of their various regions, and the specific alignments of these regions in register with one another permit the subdivision of the medulla into an outer zone and an inner zone. The outer zone of the medulla is further subdivided into an outer stripe and an inner stripe. Unless otherwise noted, all of the descriptions in this textbook refer to juxtamedullary nephrons, even though they constitute only 15% of all nephrons. Each juxtamedullary nephron is about 40 mm long. The constituent parts of the nephron are modified to perform specific physiological functions. The renal corpuscle, with its attendant glomerulus, filters the fluid expressed from the bloodstream. The subsequent tubular portions of the nephron (i.e., the proximal tubule, the thin limbs of Henles loop, and the distal tubule) modify the filtrate to form urine.
For more information see the Nephron section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Figure 192 Light micrograph of the kidney cortex in a monkey, illustrating renal corpuscles (R), medullary ray (M), and cross-sectional profiles of the uriniferous tubules (132). A portion of the urinary space (S) is clearly evident at the periphery of the renal corpuscle and is bound by the simple squamous epithelium composing the parietal layer (P) of Bowmans capsule. Copyright 2007 by Saunders/Elsevier. All rights reserved.

Renal Corpuscle

Figure 194 A renal corpuscle and its juxtaglomerular apparatus.

The renal corpuscle is composed of a tuft of capillaries, the glomerulus, which is invaginated into Bowmans capsule, the dilated, pouch-like, proximal end of the nephron. The glomerulus contacts the visceral layer of Bowmans capsule, composed of modified epithelial cells called podocytes. The outer wall surrounding Bowmans space, is the parietal layer. The glomerulus is supplied by the short, straight afferent glomerular arteriole and drained by the efferent glomerular arteriole. Filtrate leaking out of the glomerulus enters Bowmans space through a complex filtration barrier composed of the endothelial wall of the capillary, the basal lamina, and the visceral layer of Bowmans capsule. The glomerulus is formed as several tufts of anastomosing capillaries that arise from branches of the afferent glomerular arteriole. The connective tissue component does not enter Bowmans capsule, and is replaced by a specialized cell type known as mesangial cells. There are two groups of mesangial cells: Extraglomerular mesangial cells are located at the vascular pole, and pericyte-like intraglomerular mesangial cells are situated within the renal corpuscle.
For more information see the Renal Corpuscle and Glomerulus sections in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007. Copyright 2007 by Saunders/Elsevier. All rights reserved.

Filtration Barrier
Podocytes bear numerous long, tentacle-like cytoplasmic extensions, primary (major) processes, which follow the longitudinal axes of the glomerular capillaries. Each primary process bears many pedicels, which completely envelop most of the glomerular capillaries by interdigitating with pedicels from neighboring major processes of different podocytes. Pedicels rest on the lamina rara externa of the basal lamina. Interdigitation occurs in such a fashion that narrow clefts,, known as filtration slits, remain between adjacent pedicels. Filtration slits are not completely open; instead, they are covered by a thin (6 nm thick) slit diaphragm, which extends between neighboring pedicels and acts as a part of the filtration barrier. Fluid leaving the glomerular capillaries through the fenestrae is filtered by the basal lamina. The lamina densa traps larger molecules (>69,000 Da), whereas the polyanions of the laminae rarae impede the passage of negatively charged molecules and molecules that are incapable of deformation. The fluid that penetrates the lamina densa and enters Bowmans space, is the glomerular ultrafiltrate.
Figure 197 The interrelationship of the glomerulus, podocytes, pedicels, and basal laminae.

Because the basal lamina traps larger macromolecules, it would become clogged were it not continuously phagocytosed by intraglomerular mesangial cells and replenished by both the visceral layer of Bowmans capsule (podocytes) and glomerular endothelial cells.
For more information see the Glomerulus section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Glomerular Filtration
Each primary process bears many pedicels, which completely envelop most of the glomerular capillaries by interdigitating with pedicels from neighboring major processes of different podocytes. Pedicels rest on the lamina rara externa of the basal lamina. Interdigitation occurs in such a fashion that narrow clefts,, known as filtration slits, remain between adjacent pedicels. Filtration slits are not completely open; instead, they are covered by a thin (6 nm thick) slit diaphragm, which extends between neighboring pedicels and acts as a part of the filtration barrier. Fluid leaving the glomerular capillaries through the fenestrae is filtered by the basal lamina. The lamina densa traps larger molecules (>69,000 Da), whereas the polyanions of the laminae rarae impede the passage of negatively charged molecules and molecules that are incapable of deformation. The fluid that penetrates the lamina densa and enters Bowmans space, is the glomerular ultrafiltrate. Because the basal lamina traps larger macromolecules, it would become clogged were it not continuously phagocytosed by intraglomerular mesangial cells and replenished by both the visceral layer of Bowmans capsule (podocytes) and glomerular endothelial cells.
Figure 1910 Electron micrograph of pedicels (P) and diaphragms bridging the filtration slits of a glomerulus in a rat (86,700). BS, Bowmans space; CL, capillary lumen. Note the laminae rara externa (short arrow) and the filtration slit diaphragm (long arrow). (From Brenner BM, Rector FC: The Kidney, 4th ed, Vol 1. Philadelphia, WB Saunders, 1991.) For more information see the Glomerulus section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Proximal Tubule
The proximal tubule, constituting much of the renal cortex, consists of a highly tortuous region, the pars convoluta (proximal convoluted tubule), located near renal corpuscles, and a straighter portion, the pars recta (descending thick limb of Henles loop), which descends in medullary rays within the cortex and then in the medulla to become continuous with the loop of Henle. About 67% to perhaps as much as 80% of sodium, chloride (Cl), and water is resorbed from the glomerular ultrafiltrate and transported into the connective tissue stroma by cells of the proximal tubule. Sodium is actively pumped out of the cell at the basolateral cell membranes by a sodium pump associated with sodium-potassium adenosine triphosphatase (Na+-K+ ATPase). The sodium (Na+) is followed by chloride to maintain electrical neutrality and by water to maintain osmotic equilibrium. In addition, all of the glucose, amino acids, and protein in the glomerular ultrafiltrate are resorbed by cells of the proximal tubule.
For more information see the Proximal Tubule section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Figure 1911 A drawing of the uriniferous tubule and its cross-sectional morphology.

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Thin limbs of Henles loop

The thin limbs of the loop of Henle have three regions: the descending thin limb, Henles loop, and the ascending thin limb. Juxtamedullary nephrons have much longer thin segments, 9 to 10 mm in length, and they form a hairpin-like loop that extends deep into the medulla as far down as the renal papilla. The region of the loop continuous with the pars recta of the proximal tubule is called the descending thin limb (of Henles loop), the hairpin-like bend is Henles loop, and the region that connects Henles loop to the pars recta of the distal tubule is known as the ascending thin limb (of Henles loop). The descending thin limb is highly permeable to water and reasonably permeable to urea, sodium, chloride, and other ions. The major difference between the ascending and descending thin limbs is that the ascending thin limb is only moderately permeable to water.
For more information see the Thin Limbs of Henles Loop section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Figure 1911 A drawing of the uriniferous tubule and its cross-sectional morphology.

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Distal Tubule
The distal tubule is subdivided into the pars recta, which, as the continuation of the ascending thin limb of Henles loop, is also known as the ascending thick limb of Henles loop, and the pars convoluta (distal convoluted tubule). Interposed between the ascending thick limb and the distal convoluted tubule is a modified region of the distal tubule called the macula densa. The ascending thick limb of Henles loop joins the ascending thin limb and ascends through the medulla to reach the cortex. The low cuboidal epithelial cells composing the ascending thick segment are not permeable to water or urea. In addition, its cells have chloride (and perhaps sodium) pumps that function in the active transport of chloride (and sodium) from the lumen of the tubule. As the ascending thick limb of the Henle loop passes near its own renal corpuscle. This region of the distal tubule is called the macula densa. The distal convoluted tubule is impermeable to water and urea. But, in response to aldosterone, these cells can actively resorb all of the remaining sodium (and, passively, chloride) from the lumen of the tubule into the renal interstitium.
For more information see the Distal Tubule section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Figure 1911 A drawing of the uriniferous tubule and its cross-sectional morphology.

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Juxtaglomerular Apparatus
The juxtaglomerular apparatus consists of the macula densa of the distal tubule, juxtaglomerular cells of the adjacent afferent (and, occasionally, efferent) glomerular arteriole, and the extraglomerular mesangial cells. The juxtaglomerular (JG) cells are modified smooth muscle cells located in the tunica media of afferent (and, occasionally, efferent) glomerular arterioles. They contain granules housing the proteolytic enzyme renin. The absence of basal lamina permits intimate contact between cells of the macula densa and the JG cells. The extraglomerular mesangial cells occupy the space bounded by the afferent arteriole, macula densa, efferent arteriole, and vascular pole of the renal corpuscle. These cells may contain occasional granules and are probably contiguous with the intraglomerular mesangial cells.
For more information see the Juxtaglomerular Apparatus section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Figure 1914 The juxtaglomerular apparatus. Copyright 2007 by Saunders/Elsevier. All rights reserved.

Collecting Tubules
Collecting tubules (collecting ducts) are not part of the nephron. They have different embryological origins, and it is only later in development that they meet the nephron and join it to form a continuous structure. The distal convoluted tubules of several nephrons join to form a short connecting tubule that leads into the collecting tubule. The glomerular ultrafiltrate that enters the collecting tubule is modified and delivered to the medullary papillae. Collecting tubules are about 20 mm long and have three recognized regions: cortical, medullary, and papillary. Collecting tubules are impermeable to water. However, in the presence of antidiuretic hormone (ADH) they become permeable to water (and, to a certain extent, urea). Thus, in the absence of ADH, urine is copious and hypotonic, and in the presence of ADH the volume of urine is low and concentrated.
For more information see the Collecting tubules section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Figure 191 A, Hemisected kidney illustrating morphology and circulation. B, Arrangement of cortical and juxtamedullary nephrons.

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Formation of Urine
The osmolality of the glomerular ultrafiltrate is the same as that of circulating blood. This osmolality is not altered by the proximal tubule because water has left its lumen in response to the movement of ions. However, the osmotic pressure of formed urine is different from that of blood. The osmotic pressure differential is established by the remaining regions of the uriniferous tubule. Interestingly, the osmolarity and volume of urine vary, indicating that the kidneys can modulate these factors. A gradient of osmolarity, increasing from the corticomedullary junction to deep into the medulla, is maintained in the renal medullary interstitium. The long loops of Henle of juxtamedullary nephrons aid the creation and the maintenance of this osmotic gradient via a countercurrent multiplier system . The cells of the thin descending limb of Henles loop are freely permeable to water and salts. Therefore, the movement of water reacts to the osmotic forces in its microenvironment. The thin ascending limb is relatively impermeable to water, but salts can enter or leave the tubule, depending on conditions in the interstitium. It is important to understand, at this point (to be explained later), that urea enters the lumina of the thin limbs of Henles loop.
For more information see the Formation of Urine section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Figure 1920 Histophysiology of the uriniferous tubule. B, Antidiuresis (in the presence of ADH). Numbers indicate milliosmoles per liter. Areas outlined by a thick line indicate that the tubule is impermeable to water. In the presence of ADH, the collecting tubule changes so that it becomes permeable to water and the concentration in the interstitium of the inner medulla increases. The vasa recta is simplified in this drawing because it encompasses the entire uriniferous tubule (see Fig. 19-1).

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Formation of Urine (cont.)

The thick ascending limb of Henles loop is completely impermeable to water; however, a chloride pump actively removes chloride ions from the lumen of the tubules and these ions enter the interstitium. Sodium ions follow passively (although some suggest the presence of a sodium pump also) to preserve electrical neutrality. As the filtrate ascends, it contains fewer and fewer ions; hence, the amount of salts that may be transferred out into the interstitium decreases. Thus, a gradient of salt concentration is established in which the highest interstitial osmolarity is deep in the medulla and the osmolarity of the interstitium decreases toward the cortex. Because the medulla is tightly packed with thick and thin (ascending and descending) limbs of Henles loop and collecting tubules, the gradient of osmolarity that is established is pervasive and affects all the tubules equally
For more information see the Formation of Urine section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Figure 1920 Histophysiology of the uriniferous tubule. B, Antidiuresis (in the presence of ADH). Numbers indicate milliosmoles per liter. Areas outlined by a thick line indicate that the tubule is impermeable to water. In the presence of ADH, the collecting tubule changes so that it becomes permeable to water and the concentration in the interstitium of the inner medulla increases. The vasa recta is simplified in this drawing because it encompasses the entire uriniferous tubule (see Fig. 19-1).

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Formation of Urine (cont.)

Therefore, keeping the foregoing in mind, we can recap the formation of urine the movement of ions and water, once again starting as the ultrafiltrate, which, as the student should recall, is isotonic with blood as it leaves the pars recta of the proximal tubule. As the ultrafiltrate descends in the thin descending limb of Henles loop, it loses water (reducing volume and increasing osmolarity), reacting to the osmotic gradient of the interstitium, so that the intraluminal filtrate more or less becomes equilibrated with that of the surrounding connective tissue. This fluid of high osmolarity now ascends in the thin ascending limb of Henles loop, which is mostly impermeable to water but not to salts. Thus, the volume of the ultrafiltrate does not change (i.e., the volume is the same when the ultrafiltrate leaves the ascending thick limb as when it entered it), but the osmolarity of the ultrafiltrate inside the tubule adjusts to the osmolarity of the interstitium. The fluid entering the ascending thick limb of Henles loop passes a region that is impermeable to water but has a chloride pump, which removes chloride ions from the lumen, followed passively (or perhaps also actively) by sodium ions. Because water cannot leave the lumen, the ultrafiltrate becomes hypotonic but its volume remains constant as it ascends to the cortex in the ascending thick limb. The chloride and sodium that were transferred from the lumen of the ascending thick limb into the connective tissue are responsible for the establishment of a concentration gradient in the renal interstitium of the outer medulla.
Figure 1920 Histophysiology of the uriniferous tubule. B, Antidiuresis (in the presence of ADH). Numbers indicate milliosmoles per liter. Areas outlined by a thick line indicate that the tubule is impermeable to water. In the presence of ADH, the collecting tubule changes so that it becomes permeable to water and the concentration in the interstitium of the inner medulla increases. The vasa recta is simplified in this drawing because it encompasses the entire uriniferous tubule (see Fig. 19-1).

For more information see the Formation of Urine section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Copyright 2007 by Saunders/Elsevier. All rights reserved.

Formation of Urine (cont.)

The filtrate that leaves the distal convoluted tubule to enter the collecting tubule is hypotonic. As the collecting tubule passes through the medulla to reach the area cribrosa, it is also subject to the same osmotic gradients as the ascending and descending limbs of Henles loop. In the absence of antidiuretic hormone (ADH), the cells of the collecting tubule and, to a lesser extent, of the distal convoluted tubule are completely impermeable to water . Therefore, the filtrate, or urine, is not modified in the collecting tubule and the urine remains dilute (hypotonic). Under the influence of ADH, however, the cells of the collecting tubule (and, in animals other than humans and monkeys, the distal convoluted tubules) become freely permeable to water and urea. As the filtrate descends through the renal medulla in the collecting tubule, it is subject to the osmotic pressure gradients established by the hairpin-like loops of Henle and the vasa recta, and water leaves the lumina of the collecting tubules to enter the interstitium. Hence, the urine, in the presence of ADH, becomes concentrated and hypertonic. In addition, the concentration of urea becomes extremely high in the lumen of the collecting tubule, and in the presence of ADH it passively enters the interstitium of the inner medulla. Thus, much of the concentration gradient of the renal interstitium in the inner medulla is due to the presence of urea rather than sodium and chloride.
For more information see the Formation of Urine section in Chapter 19 of Gartner and Hiatt: Color Textbook of Histology, 3rd ed. Philadelphia, W.B. Saunders, 2007.

Figure 1920 Histophysiology of the uriniferous tubule. B, Antidiuresis (in the presence of ADH). Numbers indicate milliosmoles per liter. Areas outlined by a thick line indicate that the tubule is impermeable to water. In the presence of ADH, the collecting tubule changes so that it becomes permeable to water and the concentration in the interstitium of the inner medulla increases. The vasa recta is simplified in this drawing because it encompasses the entire uriniferous tubule (see Fig. 19-1).

Copyright 2007 by Saunders/Elsevier. All rights reserved.