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The Urinary System

The urinary system consists of the paired kidneys, the paired ureters, which lead from the kidneys to the bladder, the urinary bladder, which temporarily stores the urine, and the urethra, which leads from the bladder to the exterior of the body.

The Kidneys

General function

The kidneys are highly vascular, receiving about 25% of the cardiac output. They produce urine, in which various metabolic waste products are eliminated. Urine arises as an ultrafiltrate of blood which is modified by selective resorption and specific secretion by cells in the kidney. It contains water, electrolytes, waste products such as urea, uric acid and creatinine, and the breakdown products of various substances. The kidneys also keep the body's extracellular water content and ionic composition almost constant, even though the dietary intake of water and salt may vary.

Endocrine function

In addition to their activities in waste removal and homeostasis, the kidneys function as an endocrine organ. Several compounds, listed below, are produced by the kidneys and released into the blood.

The Structure of the Kidney

The kidneys are large, reddish organs located on either side of the spinal column on the posterior abdominal wall. They are covered with a thin but strong capsule of dense connective tissue. The medial border of each kidney is concave with a deep vertical fissure, the hilum, through which renal vessels and nerves pass. The expanded, funnel-shaped origin of the ureter, called the renal pelvis, also leaves through the hilum.

The renal pelvis is made of two or three divisions called the major calyses. Each major calyx branches into several cup-shaped minor calyces. The apical portion - called the papilla- of each renal pyramid projects into a minor calyx. (Renal pyramids are medullary structures which contain nephric tubules. They are described in more detail below.) The tip of the papilla is perforated with the openings of 10-25 papillary ducts, the final collecting ducts of the uriniferous tubules, and is therefore called the area cribrosa (Latin for sieve-like).

The renal pelvis is surrounded by a space called the renal sinus. The capsule, which passes inward at the hilum, forms the connective tissue covering of the sinus and becomes continuous with the connective tissue forming the walls of the renal pelvis and minor calyces. The sinus itself is largely filled with loose connective tissue and adipose tissue.

When a kidney is hemisected and viewed with the naked eye, two distinct regions can be seen. The outer part, called the cortex, is a dark reddish brown color. The inner part, called the medulla, is lighter-colored. The difference in color reflects the distribution of blood. About 90-95% of the blood passing through the kidney is in the cortex, the remaining 5-10% is in the medulla.

The following brief description of the nephron, the functional unit of the kidney, will make it easier to follow the discussion of the appearance of the cortex and medulla.

The Nephron and its Collecting Ducts

Each kidney has about two million nephrons. The components of the nephron are:

1) the renal corpuscle, which consists of a special arterial capillary bed called the glomerulus, and Bowman's capsule, which surrounds the glomerulus and holds the fluid exuded from it. The arteriole leading to the glomerulus is called the afferent arteriole, and the one draining it is called the efferent arteriole.

2) the proximal thick segment, consisting of the proximal convoluted tubule (PCT, also known as pars convoluta) and proximal straight tubule (pars recta). The proximal convoluted tubule arises from Bowman's capsule and remains in the proximity of the renal corpuscle. It continues into the proximal straight tubule, which forms the thick descending limb of the loop of Henle - the loop's first segment.

3) the thin segment, which makes up the thin limb of the loop of Henle-the second segment of the loop.

The loop of Henle is a U-shaped structure. Some distance down the descending limb of the U, the proximal thick segment gives way to the thin segment. The bottom of the U, which is in the form of a hairpin turn, may -depending on the nephron - consist of thin segment (in long loops of Henle) or be the beginning of the thick ascending limb (in short loops). In long loops of Henle, the thin segment continues for some distance up the ascending limb of the loop. The parallel arms (descending and ascending) of long loops are responsible for creating the countercurrent exchange mechanism essential for the formation of urine. (Described in more detail below.)

4) the distal thick segment, consisting of the distal straight tubule (pars recta) and the distal convoluted tubule (DCT or pars convoluta). The distal straight tubule makes up the third and final segment of the loop of Henle-the thick ascending limb. It continues into the distal convoluted tubule which returns to the vicinity of its own renal corpuscle.

The components of the nephron constitute the secretory portion of the uriniferous tubules. The distal convoluted tubule will connect to the excretory portion of the uriniferous tubules, the collecting tubules or ducts. The collecting ducts run alongside the straight segments of the nephron. The secretory (= nephron) and excretory portions originate from separate embryonic primordia which later become connected.

The Cortex

The cortex contains renal corpuscles as well as convoluted and straight parts of nephric tubules. It also has collecting tubules and an extensive vascular supply.

The cortex is not uniform in appearance. The renal corpuscles, barely discernable with the naked eye, are surrounded by their convoluted tubules, both proximal and distal. The areas of the cortex containing renal corpuscles and convoluted tubules are called cortical labyrinths. The straight portions of nephric tubules (proximal and distal) as well as collecting tubules, which are also straight, are found in areas called medullary rays. These are a series of vertical striations that appear to emanate from the medulla (hence the name). There are 400-500 medullary rays projecting into the cortex from the medulla.

The Medulla

The medulla is made up of 8 to 18 conical subdivisions called renal pyramids. The pyramids contain the straight segments of the nephrons and the collecting ducts, continuous with those in a group of medullary rays of the cortex. Each pyramid has its base toward the cortex and its apex, or papilla, projecting into a minor calyx. Each pyramid can be divided into an outer and inner zone. The outer zone (adjacent to the cortex) can be divided into an outer and inner stripe. The zones and stripes reflect the location of distinct segments of nephric tubules at specific levels within the pyramid, and are readily recognized in fresh specimens. The pyramids are accompanied by a capillary network called the vasa recta that runs in parallel with the various tubules and constitutes the vascular part of the countercurrent exchange mechanism.

The lateral boundaries of each pyramid are defined by inward extensions of the darker cortical tissue forming the renal columns (of Bertin). Although they contain the same components as the cortex, the renal columns are considered to be part of the medulla. A renal pyramid together with the cortical tissue overlying its base and covering its sides constitutes a renal lobe.

Different Types of Nephrons

Several types of nephrons have been identified, depending upon the location of their renal corpuscles within the cortex.

The part of the outer medulla containing the thick segments of both the descending and ascending limbs is called the outer stripe. The inner stripe of the outer medulla contains thin segments of the descending limb, and thick segments of the ascending limb. The inner medulla contains only thin segments, descending and ascending. These differences in the proportion of thick and thin segments account for the color differences of the zones and stripes that can be seen in sagittal sections of fresh specimens.

There is a much greater number of shorter loops than of longer loops. Only about one in seven nephrons are of the juxtamedullary kind with long loops of Henle.

Interstitial Tissue

The connective tissue of the kidney parenchyma is called interstitial tissue. It increases in amount from the cortex, where it constitutes about 7% of the volume, to the inner region of the medulla, where it constitutes about 20% of the volume. Two kinds of interstitial cells are found in the cortex. The first kind is found between the basement membrane of the tubules and the adjacent peritubular capillaries. It resembles fibroblasts and secretes the collagen and glycosaminoglycans of the extracellular matrix of the interstitium. The second type of cell is a macrophage.

The principal interstitial cells in the medulla resemble myofibroblasts. They may have a role in compressing the tubular structures. They contain prominent bundles of actin filaments, abundant rough ER, well-developed Golgi, lysosomes and lipid droplets. Prostaglandin and prostacyclin have been reported to be synthesized in the interstitium.

Kidney Lobes and Lobules

Lobulation in the post-natal kidney is not evident externally. A lobe is defined as a single medullary pyramid and the associated cortical tissue at its base, and at its sides (one-half of each adjacent renal column of Bertin). A lobule is defined as a papillary duct (the final collecting duct) and all the cortical collecting ducts and associated nephrons that empty into it. Thus, a central medullary ray and the surrounding cortical material constitutes a lobule. The boundaries between adjacent lobules is not clearly demarcated with connective tissue.

The Blood Supply of the Kidney

Each kidney is supplied by a branch of the aorta called the renal artery. In the renal sinus, it branches into a number of large interlobar arteries. The interlobar arteries pass between the pyramids to the boundary zone of the medulla and cortex. Here they bend sharply and form short arches, the arcuate or arciform arteries, which run along the base of the pyramid between the medulla and cortex. The arcuate arteries divide into a large number of finer branches, the interlobular arteries, which ascend perpendicularly through the cortical labyrinth to the surface, about midway between adjacent medullary rays.

The interlobular arteries give off numerous short, lateral branches, each of which enters a renal corpuscle as an afferent arteriole. A single afferent arteriole may spring directly from an interlobular artery or a common stem from an interlobular artery may branch to form several afferent arterioles. Some interlobular arteries enter the kidney capsule to provide its arterial supply.

The afferent arteriole branches into a tuft of capillaries with 10-20 loops, called the glomerulus. The glomerulus is an entirely arterial capillary bed. It is drained by the efferent arteriole, which leaves the glomerulus near the point at which the afferent arteriole enters. The point at which the two arterioles penetrate Bowman's capsule is called the vascular pole of the renal corpuscle. Opposite it is the urinary pole, where the proximal convoluted tubule arises. Bowman's capsule itself is a double-layered epithelial cup.

The efferent arterioles give rise to another network of capillaries called the peritubular capillaries. The arrangement of these capillaries differs according to whether they arise from glomeruli near the outer surface of the cortex or from the deeper, juxtamedullary glomeruli.

The arteriolae rectae also give rise to long-meshed capillary nets lined by fenestrated endothelium. They supply the tubular structures at the various levels of the medullary pyramids. (Note that the medulla does not have a direct arterial blood supply: all the blood it receives has first been through the glomeruli in the cortex.)

The venous flow of the kidney follows a reverse course to arterial flow, with the veins running in parallel to the corresponding arteries. In the cortex, peritubular capillaries drain into interlobular veins, which drain into arcuate veins, interlobar veins and the renal vein. In the medulla, the peritubular vessels (vasa recta) drain into the arcuate veins, and so on. Capillaries from the capsule and peritubular capillaries near the surface drain into stellate veins that enter interlobular veins.


The kidney has two major networks of lymphatic vessels, which are generally not seen in routine histological preparations. One is located in the capsule and outer region of the cortex and drains into larger lymph vessels of neighboring organs. The other arises between the uriniferous tubules, especially in the cortex, and enters lymphatics that accompany the larger blood vessels, and leaves through the hilum. There are anastomoses between the two networks.

Functional Histology of the Kidney Tubules

The Renal Corpuscle

The renal corpuscle consists of the glomerulus and the Bowman's capsule that surrounds it. As described above, the glomerulus is a tuft of arterial capillaries composed of 10-20 loops, supplied by an afferent arteriole and drained by an efferent arteriole. This arrangement produces a relatively high filtration pressure. The cytoplasm of glomerular endothelial cells is thin and has numerous fenestrations. The fenestrations are larger, more numerous and more irregular in outline than those of other fenestrated capillaries. They also lack a diaphragm.

Bowman's capsule is an epithelial cup with a visceral (or glomerular) layer and parietal (or capsular) layer. The visceral layer is intimately associated with the glomerular capillaries. It is made of specialized cells called podocytes ("foot cells"). The parietal layer is made of simple squamous epithelium. A space, called Bowman's space or the urinary space, lies between the two layers. The ultrafiltrate of blood emanating from the glomerulus is collected in this space.

When viewed with the light microscope, the nuclei of the simple squamous epithelial cells forming the parietal layer of Bowman's capsule can easily be identified. The urinary space between the glomerulus and the parietal layer is also obvious. However, the glomerulus itself appears as a large cellular mass. It is not possible to distinguish podocytes from glomerular endothelial cells or other cells called mesangial cells. The description of podocytes and mesangial cells which follows below is based on observations with the electron microscope.


Podocytes cover the glomerular capillaries. Their cell bodies are usually not found in extensive contact with the basement membrane. They stand off by one or two micrometers, but are attached to it via their primary processes, which ramify tentacle-like over its surface. Each primary process has numerous secondary processes, which in turn give rise to pedicels or foot processes. The pedicels interdigitate with those of neighboring podocytes. The spaces between the interdigitating pedicels, called filtration slits, are about 25 nm wide and are spanned by an electron dense membrane called the filtration slit membrane. The pedicels contain numerous actin microfilaments, which may have a role in regulating the size and patency of filtration slits.

The endothelial cells of the glomerulus share a basement membrane with the podocytes (visceral layer of Bowman's capsule). The filtration apparatus thus consists of:

The filtration apparatus can be described as a semi-permeable barrier. The two cellular layers are discontinuous, while the basement membrane, which is relatively thick, forms a continuous extracellular layer and is the principal component of the filtration barrier. Because of its thickness, it is prominent in histological sections stained with the periodic acid-Schiff (PAS) procedure and therefore also called the glomerular basement membrane (GBM).

The GBM restricts the movement of particles larger than 70,000 daltons, such as proteins like albumin or hemoglobin. Though albumin is not a usual constituent of urine, its occasional presence indicates that it is close to the effective pore size of the filtration barrier. Though the filtration barrier restricts the movement of protein, several grams pass through it each day. This protein is reabsorbed by endocytosis in the proximal convoluted tubule. Polyanionic glycosaminoglycans in the basement membrane restrict the movement of cationic molecules, even those smaller than 70,000 daltons. The narrow slit pores and the filtration slit membranes also act as physical barriers to bulk flow and free diffusion. The fenestrae of the endothelial cells restrict the movement of blood cells and other formed elements of the blood. In addition to structural barriers, the flow rate and pressure of the blood in the glomerulus also have an effect on the filtration function.

The mesangium

Another group of cells found in the renal corpuscle are mesangial cells, which together with the extracellular matrix they produce constitute the mesangium. The mesangium is most obvious at the vascular stalk of the glomerulus and in the interstices of adjoining glomerular capillaries. Mesangial cells are irregularly shaped, modified smooth muscle cells. One function of the mesangium is to provide structural support for the podocytes and glomerular capillaries. Mesangial cells are also phagocytic, removing trapped residues, aggregated proteins and immune complexes from the GBM. (Atypical for phagocytes, they do not arise from the mononuclear phagocytic system.) Since mesangial cells are capable of contraction, they are thought to be involved in local regulation of glomerular blood flow. They respond to, and release, a number of growth factors and can produce vasoactive and immunoregulatory inflammatory mediators, such as prostaglandins and interleukin 1. Mesangial cells are capable of dividing, and in some disease conditions, mesangial proliferation is stimulated.

The Proximal Thick Segment

The proximal thick segment includes the proximal convoluted tubule (PCT) and the proximal straight tubule. The proximal convoluted tubule arises at the urinary pole of the renal corpuscle. Its lumen is continuous with the urinary space. The simple squamous epithelum of Bowman's capsule changes abruptly to the simple cuboidal epithelium of the PCT. The PCT is the longest and widest part of the nephron, and constitutes the majority of tubular sections seen in the cortical labyrinth. It follows a tortuous course, then terminates by straightening out and passing into the nearest medullary ray to become the thick descending limb of the loop of Henle. The PCT is about 15 mm long, and the entire proximal thick segment can be up to 25 mm long.

The convoluted and straight parts of the proximal tubule have an essentially similar structure and function. The epithelium consists of a single layer of cuboidal cells. The cells of the simple cuboidal epithelium contain a single spherical nucleus in an eosinic cytoplasm. Not all the cells in a given section will have a visible nucleus, because the cells are considerably greater in width than the thickness of the sections.

On their luminal surface, the cells have a conspicuous brush border, which consists of numerous relatively long microvilli. A terminal bar apparatus, consisting of a narrow tight junction and a zonula adherens, seals off the intercellular space from the lumen. Long rodlike mitochondria in the basal half of the cells, oriented parallel to the cell axis, often give this part of the cell a faint striated appearance in the light microscope. The lateral limits of the cell cannot be discerned with the light microscope because their sides are elaborately fluted and interdigitate deeply with complementary ridges and grooves of neighboring cells. Near the cell base, the electron microscope reveals an even greater number of slender lateral processes extending under adjacent cells. They contain longitudinally-oriented microfilaments which may play a role in regulating the movement of fluid from the basolateral extracellular space across the basement membrane toward the adjacent peritubular capillaries.

Sections of the PCT in the cortical labyrinth often appear irregular in profile (eg. U-, J- or S-shaped) and the lumen is often star-shaped (as opposed to rounded). Within the medullary rays, the tubular profiles of the straight segments are rounded, but many display a star-shaped lumen. Their larger diameter, brush border and usually more eosinophilic staining help to distinguish them from other components of the ray. The straight segment is not as active as the PCT and contains fewer microvilli and fewer, randomly distributed mitochondria.

The PCT reabsorbs about 80% of the primary filtrate. The pump enzyme, sodium-potassium-activated ATPase, actively transports sodium into the lateral intercellular space. This is followed by the passive diffusion of chloride. The accumulation of NaCl creates an osmotic gradient that draws water from the lumen into the intercellular space. The hydrostatic pressure that builds up in the distended intercellular compartments, presumably aided by the contractile activity of the actin filaments at the base of the cell, drives an essentially isosmotic fluid through the basement membrane of the tubule into the renal connective tissue. Here it is reabsorbed into the vessels of the peritubular capillary network. Angiotensin II promotes the resorption of Na in the PCT, and also of HCO3. The PCT also reabsorbs amino acids, glucose and other sugars, and polypeptides. The microvilli of the brush border are covered with a well-developed glycocalyx that contains ATPases, peptidases and disaccharidases. Proteins and large peptides are reabsorbed by endocytosis.

The Thin Segment

The thin segment of the loop of Henle is recognized by its much lower epithelium, which is either simple squamous or low cuboidal. This segment is only about one-quarter the diameter of the proximal tubule. The transition from proximal thick to thin segment is abrupt. With the light microscope, some sections of the thin segment look flatter than others. With the electron microscope, four types of epithelial cells have been identified in the thin segment. (The detail below is for reference only. On your slides, you will only be required to identify a section as "thin segment.")

Type I is a thin simple epithelium with almost no interdigitations with neighboring cells and few organelles. It is found in short-looped nephrons.

Type II is a bit taller (low cuboidal). It has abundant organelles and many small, blunt microvilli. The extent of lateral interdigitation with neighboring cells shows species variation. It is found in the initial part of the thin descending limb of long-looped nephrons.

Type III epithelium is thinner and lacks interdigitations. The cell structure is simpler and with fewer microvilli than type II. It is found in the more distal part (within the inner medulla) of the thin descending limb of long-looped nephrons.

Type IV epithelium consists of low, flattened cells without microvilli and with few organelles. It is found at the bend of the loop and through the entire ascending limb of long-looped nephrons.

The function of the thin segment is discussed below in the section on the countercurrent multiplier mechanism.

The Distal Thick Segment

The distal thick segment consists of the distal straight tubule and the distal convoluted tubule (DCT). The straight tubule is the thick ascending limb of the loop of Henle. It passes through a pyramid (in the long loops) and continues into a medullary ray. From there, it enters the cortical labyrinth and makes contact with the vascular pole of its parent renal corpuscle. At this point, the epithelial cells of the tubule adjacent to the afferent arteriole are modified to form the macula densa (described below). The tubule then leaves the region of the corpuscle to become the distal convoluted tubule. The DCT is about 5 mm long, or one-third the length of the PCT (which is why you see many more profiles of PCT around the renal corpuscles), and follows a less tortuous course. The DCT ends in an arched collecting tubule or a shorter tubule called a connecting tubule, both of which lead to a straight collecting tubule in a medullary ray.

Distal tubules are lined with cuboidal cells that stain lightly with eosin but are less acidophilic than the cells of the proximal tubules. Because the cells are flatter and smaller than those of the proximal tubule, more cells and more nuclei are seen in a typical profile. The lateral margins of the cells are indistinct in the light microscope because the cells have extensive basolateral plications that interdigitate with those of other cells. Numerous large mitochondria associated with folds in the basal membrane sometimes gives the basal part of the cells a striated appearance (again not as prominent as in proximal tubules). The nucleus is located in the apical portion of the cell. Microvilli are present on the apical surface but they are much fewer in number and shorter than those of the proximal tubule. Consequently, no brush border is evident with the light microscope and the luminal surface of distal tubule sections appears cleaner and sharper than that of proximal tubules. The outside diameter of distal tubules is slightly smaller than that of proximal tubules. In the cortical labyrinth, profiles of DCTs are rounder than those of PCTs, which, as described above, are often irregular. In the medullary rays, where all the tubules are straight, all the profiles are round.

The distal tubule is responsible for the conservation of Na. Its cells have Na-K-ATPase on their basolateral surface, and Na resorption is coupled with K secretion. The luminal domain of the cell membrane has a cotransporter, driven by the inwardly directed Na gradient, that couples inward Cl transport to the Na and K transport. The resorption of Na and secretion of K is stimulated by aldosterone from the adrenal gland. The DCT also resorbs bicarbonate ion and concomitantly secretes hydrogen ion, causing an increase in urine acidification. In order to avoid the toxic effects of ammonia, it converts it to ammonium ion that can enter the urea cycle. The terminal portion of the DCT is sensitive to antidiuretic hormone (ADH, also called vasopressin), which increases the permeabiltiy of the tubule to water, to produce a more concentrated urine. (This effect also occurs in the collecting ducts, discussed below.) ADH is released from the posterior pituitary in response to increased plasma osmolality or decreased blood volume. The thick ascending limb is also involved in the countercurrent multiplier mechanism.

The Juxtaglomerular Apparatus

As the distal tubule contacts its parent corpuscle, it passes through a crevice between the afferent and efferent arterioles. The epithelial cells of the tubule adjacent to the afferent arteriole are modified to form the macula densa. The cells of the macula densa have a distinctive appearance. They are narrower and usually taller than other distal tubule cells, and their nuclei appear crowded, even superimposed (hence the name macula densa = dense spot). The cells of the afferent arteriole at this point are also modified, and are called juxtaglomerular cells (JG cells). The JG cells and the macula densa, as well as some associated mesangial cells, together constitute the juxtaglomerular (JG) apparatus.

The JG cells are modified smooth muscle cells of the tunica media of the afferent arteriole. They have ellipsoid nuclei and cytoplasm full of granules that stain with PAS. The electron microscope reveals that they have the characteristics of protein-secreting cells. They produce the enzyme renin. As described above, renin converts the blood protein angiotensinogen into an inactive decapeptide called angiotensin I (AI), which in turn is converted to the active octapeptide angiotensin II (AII) by endothelial cells in the lung.

Renin secretion increases if the NaCl concentration decreases. The cells of the macula densa monitor NaCl concentrations in the afferent arteriole, and regulate the release of renin from the JG cells in a paracrine manner. A significant blood loss or a drop in blood pressure from other causes also stimulates renin secretion, probably as a result of decreased tension in the wall of the JG cells. AII is a potent vasoconstrictor, and therefore directly increases blood pressure. The main physiological effect of AII appears to be to enhance the secretion of the adrenocortical hormone aldosterone. Aldosterone acts mainly on the distal tubules to increase the resorption of Na and Cl ions. This leads to the expansion of the extravascular fluid volume, and an increase in blood pressure. The increased blood pressure distends the JG cells and inhibits renin secretion, completing the negative feedback loop.

The cells of the macula densa also lie adjacent to some extraglomerular mesangial cells, called lacis cells, at the vascular pole of the renal corpuscle. Lacis cells are coupled to one another and to JG cells by gap junctions. They are believed to be involved in transmitting information from the macula densa to JG cells. The amount of renin released is probably determined through a functional cooperation of the macula densa, JG cells and lacis cells.

The Collecting Ducts

A distal convoluted tubule in the cortical labyrinth connects to a straight collecting tubule lying within the medullary ray either via an arched collecting tubule or a connecting tubule. A straight collecting tubule receives input from seven to ten nephrons. From the medullary ray, the collecting tubules pass inward through the outer zone of the medulla without further fusions. When they reach the inner zone, they join at acute angles with other tubules. There are about seven successive convergences in the inner medulla, which result in the formation of large, straight ducts called the papillary ducts of Bellini. The papillary ducts open on the area cribrosa at the apex of each papilla. (Note: Some people use the term "tubule" for the smaller structures, and "ducts" for the larger ones, other people use the terms interchangeably. We will accept either term. What is important is that you recognize a structure as a collector.)

The collecting ducts are lined with simple epithelium throughout their length. The arched collecting tubules and connecting tubules are lined with flattened cells, squamous to cuboidal in shape. (Do not spend time looking for them, concentrate on finding the collecting ducts in the medullary rays and medulla.) The epithelium of the straight collecting tubule in the cortex is cuboidal, but becomes taller as the duct progresses through the medulla. The papillary ducts have tall columnar epithelium. The diameter of the ducts increases as well, from 40 micrometers in the straight collecting tubules, to 100­200 micrometers in the papillary ducts.

Along the entire extent of the collecting duct, the principal cells stain only weakly with the usual stains. They have electron-lucent cytoplasm with few organelles and almost no invaginations of the basal cell membrane. They have a single cilium and relatively few, short microvilli (not visible with light microscope). They do not have processes that interdigitate with those of neighboring cells. As a result, the cell boundaries are often quite evident, which is not the case in the other thick tubules. This is a very useful criterion when trying to distinguish collecting ducts from distal straight segments in areas where they are found together (medullary rays, outer medulla), especially in cases where the staining of the two types of tubules is not markedly different. (The brush border of proximal straight tubules makes them easy to distinguish, and they also stain more darkly.) In the inner medulla, it is easy to distinguish the tall cuboidal or columnar collecting ducts from thin segments of the loop of Henle.

Several other criteria can sometimes be useful in distinguishing collecting ducts from distal tubule (DT) straight segments. In DTs, nuclei tend to be located closer to the lumen due to the presence of basal mitochondria, whereas the nuclei of collecting ducts tend to be more basally located. The cells of the (early) collecting ducts tend to be smaller and more cuboidal than those of the DT. However, the outer diameter of collecting tubules is larger than that of DTs. The luminal spaces of collecting ducts tend to be more regular than those of DTs.

In addition to the principal cells described above, another type of cell, the dark cell or intercalated cell, can sometimes be seen. Dark cells are found in much smaller numbers, and their frequency decreases as the duct progresses. None are found near the papilla. Microplicae (cytoplasmic folds) and microvilli are present on their apical surface, and the apical cytoplasm has numerous vesicles. These cells do not have basal infoldings but do have basally located interdigitations with neighboring cells. The function of dark cells is not known.

The permeability of the collecting ducts is regulated by antidiuretic hormone (ADH) from the posterior pituitary. In the absence of ADH, the principal cells are impermeable to water, and a dilute copious urine is produced. ADH promotes the permeability of the cells to water, which leaves the duct and enters the interstitial space. As a result, a small volume of hypertonic urine is produced. Excess water consumption inhibits the release of ADH. Inadequate consumption of water, or loss of fluid through sweating, vomiting or diarrhea stimulates the release of ADH. The inability to produce an adequate amount of ADH leads to diabetes insipidus.

Making Urine Hypertonic: The Countercurrent Multiplier Mechanism

All of the nephrons are involved in the filtering of blood, and the resoption and secretion of specific substances in the various segments of their tubules. Only the juxtamedullary nephrons with long loops of Henle are involved in the creation of a hypertonic urine. The manner in which this occurs is called the countercurrent multiplier mechanism. The long loops of Henle create a gradient of hypertonicity in the medullary interstitium that influences the concentration of the urine as it flows through the collecting ducts. The osmolarity of the interstitium increases from 300 mosm/L at the outer medulla adjacent to the cortex, to 1200 mosm/L in the deepest part of the inner medulla.

Recall that the thick descending (proximal) limb gives way to the thin descending limb near the outer part of the medulla. It is the thin descending limb and the entire ascending limb (thin and thick) that are involved in the countercurrent mechanism. The thin descending limb is freely permeable to Na, Cl and water, whereas both the thin and thick segments of the ascending limb are impermeable to water. Furthermore, the ascending limb actively transports Cl from the lumen to the interstitium, and Na passively follows to maintain electrochemical neutrality. Because water can't leave the ascending limb, the interstitium becomes hypertonic relative to the luminal contents. (Although some Na and Cl diffuse back into the nephron at the descending limb, these ions are transported out again at the ascending limb.) This produces the countercurrent multiplier effect, in which the concentration of NaCl increases in the interstitium down the length of the loop of Henle. The modified filtrate in the ascending limb that ultimately reaches the DCT becomes hypotonic.

In the absence of ADH, the DCT and the collecting tubules and ducts are also impermeable to water and a great quantity of hypotonic urine is formed. When ADH is present, they become highly permeable to water. Within the cortex, in which the interstitium is isotonic with blood, the modified filtrate equilibrates to isotonicity in the DCT, partly by loss of water to the interstitium and partly by addition of ions other than Na and Cl to the filtrate. In the medulla, increasing amounts of water leave the filtrate as the collecting duct progresses through the increasingly hypertonic interstitium. The filtrate (urine) becomes hypertonic.

The structure of the vasa recta that are closely associated with the loops of Henle is described above (under Blood Supply). In the medulla, these vessels form loops that closely parallel the loops of Henle. Because of this arrangement, these vessels can provide circulation to the medulla without disturbing the osmotic gradient that is established by the chloride pump in the ascending limb. Recall that both the arterial and venous limbs are very thin-walled and permeable. As the arterial vessels descend through the medulla, the blood loses water to the interstitium and gains salt from it, so that at the tip of the loop deep in the medulla, the blood is essentially in equilibrium with the hypertonic interstitial fluid. As the venous vessels ascend, the process is reversed, the hypertonic blood loses salt to, and gains water from, the interstitium. This passive countercurrent exchange of water and salt between the blood and interstitium occurs without the expenditure of energy. It is ultimately driven by the energy that drives the multiplier system: the active transport of Cl by the ascending limb of the loop of Henle.

List of Images




Figures for Kidney

Figure 1 shows a low power view of the human kidney. A large area of cortical labyrinth is seen bounded by two rays. The lower ray runs horizontally across the entire field of view; its boundary with labyrinth is shown by asterisks. The upper ray disappears toward the left of the field of view, blending into the surrounding cortical labyrinth. (This is a phenomenon of sectioning.) In the cortical labyrinth, glomeruli are seen as round solid structures. They are surrounded by the convoluted tubules, whose lumina are evident even at this magnification. It is not possible to distinguish proximal from distal tubules at this magnification.


Figure 2 shows another low power view of the cortex. The edge of the kidney, covered with the capsule, is seen on the left. Medullary rays are seen extending toward the medulla (not in view, toward the right), separated by areas of cortical labyrinth. The lowermost ray is the most prominent in this section. Within the labyrinth, the glomeruli are seen as solid round structures, whereas lumina are evident within the tubules.


Figure 3 shows a low power view of the junction between the cortex (at left) and the medulla (at right) of the human kidney. A large profile of an arcuate vessel lies between the two. The areas containing medullary rays and cortical labyrinth can be distinguished in the cortex. In the medulla, only profiles of tubules can be seen.



Figure 4 shows a low power view of the cortex of the monkey kidney. The monkey was perfused and, consequently, the preservation of many structures is better than in the human kidney. Glomeruli are seen among the kidney tubules. The cortex of the monkey kidney is not as neatly organized into medullary rays and cortical labyrinths as is the human kidney. (In some animals, for example rats, such an arrangement is absent.) The large spaces seen in the cortex are blood vessels that have been artifactually expanded by the perfusion process.


Figure 5 shows a high power view of a glomerulus surrounded by PCTs and DCTs in the human kidney. The structure of the glomerulus cannot be discerned with the light microscope, however, one can sometimes see capillaries within it (asterisks). The blue-staining nuclei of the different types of cells can be seen in the glomerulus, but there is no point in trying to distinguish them. The parietal (capsular) part of Bowman's capsule and Bowman's space are evident. Frequently it is possible to see nuclei of the simple squamous epithelium lining the capsular layer (arrowhead).

It is easy to distinguish the proximal from the distal convoluted tubules. The PCTs stain more deeply and have an obvious brush border. (In the slide of the human kidney, however, many of the PCTs are in very bad shape.) Profiles of PCTs tend to be larger in diameter and more irregular than those of DCTs. The DCTs are paler and the nuclei of their cells appear more regularly arranged. Contrary to what is seen in this figure, there are generally more profiles of PCTs than of DCTs, because the PCTs are significantly longer.


Figure 6 shows profiles of PCTs and DCTs in the cortex of the human kidney. Their distinguishing features are as described for Figure 5.





Figure 7 shows a high power view of a glomerulus surrounded by PCTs and DCTs in the monkey kidney. The histology is as described for the human kidney but the preservation is better. The brush border on the PCTs is much cleaner. Within the glomerulus, numerous profiles of capillaries can be seen, some of the larger ones are identified with asterisks in their lumina. Two downward-facing endothelial cells can be seen in the capillary identified by the lowermost asterisk. This section fortuitously captured the afferent arteriole entering the glomerulus. The afferent arteriole is quite expanded (probably as a result of the perfusion), and some endothelial cell nuclei can be seen bulging into its lumen. Unfortunately, the macula densa associated with it is not seen. Numerous nuclei can be seen within the glomerulus; they belong to podocytes and mesangial cells in addition to the endothelial cells. (Except for certain endothelial cells, the nuclei are not distinguishable.) The nuclei of some of the cells lining the capsular layer of Bowman's capsule can also be seen (arrowhead).


Figure 8 is similar to Figure 7 in showing a glomerulus surrounded by numerous tubules. In this figure, the macula densa is very clearly identifiable, with its pallisade arrangement of narrower, taller cells with more crowded nuclei. The arrangement of cells of the macula densa (MD) can be compared with that of the DCT seen to the right in longitudinal section (which is probably continuous with the section containing the MD). The afferent arteriole is visible but not easily distinguished, squeezed between the MD and the glomerulus. At the urinary pole of the renal corpuscle, a small segment of the emerging PCT has been sectioned (arrowhead).

Figure 9 shows another renal corpuscle in the monkey kidney. In this section, both the macula densa and afferent arteriole are identifiable (but not spectacular) at the vascular pole, and the beginning of the PCT can be seen at the urinary pole. Notice the abrupt transition from simple squamous to simple cuboidal epithelium. It is not common to see all these feature in a single section.



Figure 10 shows a high power view of a medullary ray in the human kidney. The straight segments of the proximal tubules can be identified by their deeper staining and their (unfortunately ill-preserved) brush border. A distal straight tubule lies between two collecting ducts. The cells of the distal tubule stain more darkly and are not as tall as those of the collecting ducts. The boundaries between individual cells can frequently be seen in the collecting ducts. Some of these areas are indicated by asterisks.


Figure 11 shows a high power view of the medulla of the human kidney. The tubules are seen in longitudinal section. This section is from the inner stripe of the outer medulla. Proximal straight tubules (thick descending limbs) are not present because they end in the outer stripe. Distal straight tubules (thick ascending limbs) are present (so you know it cannot be the inner medulla). If you were to scan the medulla at low power, you would see that the degree of staining within the tubules can be quite variable. Here, the distal straight tubules are quite darkly stained. Notice, however, that there is no brush border. In the collecting duct, notice that the cells are paler, taller, with nuclei at the same level, and with distinct cell boundaries (most obvious in the lower row of cells of the labelled collecting duct). The epithelium of the thin segments and of the blood vessels (vasa recta) is squamous. Red blood cells can frequently be seen in the blood vessels.

Figure 12 shows a high power view of the outer medulla of the monkey kidney. The section can be identified as being from the outer stripe because proximal thick segments (with a deep-staining brush border) can be seen. The identifying features of the tubules are similar to those described in the human kidney. (It will be harder to distinguish blood vessels from thin segments, however, because most of the blood was flushed out during perfusion.)



Figure 13, also from the monkey kidney, shows tubules cut in longitudinal section. This section is from the inner stripe of the outer medulla: thick ascending limbs (distal) but no thick descending limbs (proximal), are present.




The Excretory Passages

The urine that is excreted at the area cribrosa flows sequentially to: a minor calyx belonging to that papilla, a major calyx, the renal pelvis, through the ureter to the urinary bladder where it is stored, and through the urethra where it is voided.

All these passageways, except the urethra, have the same general structure:

There is no distinct submucosa. The lamina propria blends with the underlying smooth muscle of the muscularis.

Transitional Epithelium

The transitional epithelium that lines the excretory passages of the urinary system (except for the urethra) is unique to those regions. It is much thicker in the bladder and ureters (up to about 8 cells thick) than in the calyces ( 2 to 3 cell thick). It is essentially impermeable to salts and water. It is also able to become thinner and flatter, thereby allowing distensibility of the passageways. When the urinary bladder is empty (undistended), its transitional epithelium is about 5-8 cells in thickness. When it is full (distended), its epithelium is about 3-4 cells in thickness. The ability of transitional epithelium to distend is due to the structure of the surface cells.

In routine histological sections of transitional epithelium (where the tissue is not distended), the surface cells appear large and rounded, and bulge into the lumen. Many are binucleate. These large round surface cells become more or less squamous in the distended state. The basal cells of transitional epithelium are the smallest, and the nuclei appear crowded because of the minimal amount of cytoplasm in the cell. The cells in the intermediate layers are intermediate in size.

Examination of the surface cells with the transmission electron microscope shows thickened, more rigid areas of the plasma membrane, called plaques, on the luminal surface. Between the plaques are shorter areas where plasma membrane is not thickened- the interplaque regions. In the undistended state, the plaques fold inward into the apical cytoplasm. In sections, they appear as fusiform vesicles because their continuity with the apical surface is not evident. In the distended state, the clefts and fusiform vesicles are reinserted into into the cell surface as the mucosa unfolds and the cells flatten. Filaments attached to the undersurface of the plaque and extending into the apical cytoplasm may prevent undue stretching in the distended state. The luminal membrane of surface cells has an unusual chemical compostion: cerebroside is the major component of the polar lipid fraction.

The Ureters

The ureters convey the final urine to the bladder. They arise from the renal pelvis and follow an oblique path through the wall of the bladder. In histological sections, the mucosa is typically folded, having a star-shaped appearance, due to the contraction of the smooth muscle of the muscularis. The lamina propria is fairly wide, and consists of fibroelastic connective tissue, usually more dense and with more fibroblasts under the epithelium, and looser near the muscularis. Diffuse lymphatic tissue may be seen.

The muscularis consists of an inner longitudinal and an outer circular layer of smooth muscle. They are usually not clearly defined as two layers. They generally appear as loose, anastomosing strands of smooth muscle separated by abundant collagenous connective tissue. In the terminal part of the ureters, a thick outer layer of longitudinal muscle is described in addition to the other two, particularly in the portion of the ureter that passes into the bladder. Peristaltic contractions of the smooth muscle move the urine from the minor calyces through the ureter to the bladder.

As the bladder distends with urine, the openings of the ureters are compressed, reducing the possibility of reflux of urine into the ureters. Contraction of the smooth muscle of the bladder wall also compresses these openings. This is important in protecting the kidney from the spread of infections from the bladder and urethra, which are frequent sites of chronic infection, especially in the female.

The ureters are covered with an adventitia which is continuous with the surrounding fibroelastic connective tissue containing abundant adipose cells, numerous blood vessels and small nerves. A portion of the tube may be covered with a serosa.

Figures for Ureter

Figure 14 is a low power view of the layers forming the wall of the ureter. The mucosa consists of transitional epithelium overlying a lamina propria of moderately dense fibroelastic connective tissue. Lymphocytes and other cells, blood vessels, and nerves are found in the lamina propria. The mucosa seen here has the typical star-shaped appearance. Notice the debris in the lumen. The muscularis consists of loose, anastomosing strands of smooth muscle, separated by connective tissue. The smooth muscle bundles (some of which are identified by asterisks) stain a reddish color, while the CT separating them and that of the lamina propria stains an orange-yellow color. The adventitia is not in the field of view.


Figure 15 shows a high power view of the transitional epithelium of the ureter. The centre of the figure is at one of the arms of the star-shaped lumen, hence epithelium is seen on both sides. A few of the large, rounded surface cells are indicated by asterisks. The preservation of the epithelium is, unfortunately, not very good. Some of the lamina propria can be seen. The (purple) nuclei seen among the (orange) connective tissue fibres belong mainly to fibroblasts and lymphocytes.


Figure 16 shows a very low power view of the ureter (at the lower right) and the connective tissue that surrounds it. The adventitia of the ureter blends into the surrounding connective tissue, which contains much adipose tissue, many blood vessels and small nerves (not identifiable here).



The Bladder

Urine is temporarily stored in the bladder before it is eliminated to the outside. The size and shape of the bladder change as it fills. The bladder has three openings, two for the ureters and one for the urethra. The triangular region formed by these openings, called the trigone, is relatively smooth and constant in thickness. The rest of the bladder wall is thick and folded when the bladder is empty, and thin and smooth when it is full. The differences between the trigone and the rest of the bladder wall reflect their different embryological origins: the trigone originates from the embryonic mesonephric ducts, while the major portion of the wall originates from the cloaca.

The layers of the bladder wall are similar to those of the ureter. The mucosa looks similar to that of the ureter, but its thick muscularis is distinctive. The muscularis has three layers of muscle, an inner longitudinal, a middle circular or spiral layer and an outer longitudinal. The middle layer is the largest. However, the muscle layers are even less clearly defined than in the ureter, and appear as anastomosing bundles separated by loose connective tissue. In the region of the trigone, thin, dense bundles of smooth muscle form a circular mass around the internal opening of the urethra, forming the internal sphincter of the bladder. Contraction of the smooth muscle of the bladder forces the urine into the urethra.

The bladder has a serosa, covered with mesothelium, on its upper surface. Elsewhere, the outer layer of the wall consists of a fibrous adventitia.

Figures for Bladder

Figure 17 shows a very low power view of the bladder. The layers are the same as for the ureter. No detail can be seen at this magnification. The purpose of this image is to give some idea of the thickness of the muscular wall (muscularis). The epithelium is seen as a fairly thin line, whose slightly pink color is not very distinct from the orange of the underlying lamina propria. The muscularis appears as bundles of smooth muscle separated by connective tissue. Although it is organized into three layers, these are not very distinct.


Figure 18 shows a slightly higher power view of the bladder wall; the mucosa and some of the muscularis is seen. The histology of the mucosa is similar to that described for the ureter. (The relative thickness of the layers differs.)



Figure 19 shows a high power view of the mucosa of the bladder, with its transitional epithelium and lamina propria of fibroelastic connective tissue with abundant cells. Unfortunately, the condition of the epithelium is not perfect.




The Urethra

The urethra is the terminal part of the excretory passageway. In the male, it also serves to convey sperm to the outside.

Male urethra:

The male urethra is about 20 cm long and can be divided into three distinct segments. The first segment, the prostatic urethra, extends from the neck of the bladder through the prostate gland. The next segment, the membranous urethra, extends for about 1 cm from the apex of the prostate gland to the bulb of the corpus spongiosum of the penis. The last segment, the penile urethra, extends for about 15 cm through the length of the corpus spongiosum and opens to the outside at the glans. A loose, fibroelastic lamina propria underlies the epithelium of the urethra (described below for the various segments).

The prostatic urethra is lined by transitional epithelium. It is surrounded by the fibromuscular stroma of the prostate gland. It lies on a conical elevation of particularly dense stroma without glands called the colliculus seminalis. The colliculus protrudes into the lumen of the urethra and gives it a crescent shape. The prostatic utriculus, a remnant of the embryonic Mullerian duct, lies in the mass of the colliculus and opens into the urethra. Ejaculatory ducts (the continuations of the vasa deferentia into the prostate) course alongside the utriculus and finally open into the urethra. In addition, there are numerous small openings of the ducts of the prostatic glands into the urethra. (The prostatic glands are described in the Reproduction Block. The sections of the prostate on our slides do not contain the urethra.)

The membranous urethra is lined with pseudostratified or stratified columnar epithelium that more closely resembles the epithelium of the genital duct system. It is surrounded by the skeletal muscles of the pelvic and urogenital diaphragms, which form the external (voluntary) sphincter of the urethra.

The penile urethra, like the membranous part, is lined with pseudostratified or stratified columnar epithelium, but it can have patches of stratified squamous epithelium. Where the urethra opens at the tip of the glans, the lumen becomes dilated and star-shaped, and is called the fossa navicularis. The fossa navicularis has stratified squamous epithelium which is continuous with epidermis of the skin.

The surface of the mucosa of the urethra has many recesses (lacunae of Morgagni) which continue into deeper, branching mucous glands, the glands of Littre. These are best developed in the penile urethra. Mucous cells, singly or in groups, are also found along the surface epithelium.

The penile urethra is surrounded by the erectile tissue of the corpus spongiosum, which contains numerous large, irregular venous spaces separated from each other by trabeculae of fibroelastic connective tissue with numerous smooth muscle fibres.

Female urethra:

The female urethra is short, 3-5 cm in length, extending from the bladder to the vestibule of the vagina, where it terminates just below the clitoris. The mucosa has many longitudinal folds. Near the bladder, the epithelium may be transitional, but for most of the length of the urethra it is stratified squamous. Patches of stratified columnar and pseudostratified columnar epithelium may be seen. Mucus-secreting cells in the mucosal folds, similar to the glands of Littre, are present. Numerous small glands, the para- or periurethral glands, which are homologous to the prostate in the male, open into the urethra. The lamina propria is a highly vascularized layer of connective tissue with many venous sinuses; it resembles the corpus spongiosum. The muscularis has two poorly-defined layers: inner longitudinal and outer circular. Where the urethra penetrates the urogenital diaphragm, the striated muscle of this structure forms the external or voluntary urethral sphincter. The outer adventitia blends with that of the vagina.

Figures for Urethra

Figure 20 shows a low power view of part of the penile urethra. The mucosa has many recesses which continue into the glands of Littré. Several such glands can be seen here. Because they are mucus-secreting, they stain a little paler than the rest of the epithelium. Mucous cells can also be found, singly or in groups, right along the surface epithelium. Although it is hard to tell at this magnification, the area indicated by the asterisk probably contains mucous cells, as the staining is paler there. The penile urethra is surrounded by the erectile tissue of the corpus spongiosum.


Figure 21 shows a higher power view of the epithelium of the penile urethra. Part of the epithelium is stratified columnar. A group of mucous cells is indicated.




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