C:\COOPER\Anat118\urinary98.htm

ANATOMY 118/158 = General Histology
Fall Quarter, 1998
URINARY SYSTEM
Dr. Douglas Cooper

1. Know the organization, histological appearance, and basic functions of the following:

The urinary system is comprised of the paired kidneys and ureters, bladder, and urethra. The kidneys have evolved a fairly complex structure to accomplish their primary function of maintaining a relatively constant composition of ions and other small solutes (e.g. amino acids, sugars, waste products) in the interstitial tissue fluid bathing cells. This is important for allowing normal cell function and survival. Interstitial fluid composition closely reflects blood plasma composition, because capillaries are highly permeable for ions, other small solutes, and water. Therefore, the kidneys can regulate interstitial fluid composition by regulating blood plasma composition, removing accumulated waste and compensating for changes induced by drinking, eating, exercise, etc. Basically, the kidneys act as a filtering system for the blood, retaining proteins or anything larger, while allowing the rest of the plasma to pass into a system of tubules lined by cells able to specifically reabsorb from the filtrate valuable small solutes and water as needed. Anything left passes out of the body as urine through the plumbing system of ureters, bladder, and urethra.

In addition, the kidneys have also evolved several endocrine functions, responding to changes in blood composition by secreting hormones that regulate blood pressure (renin) and red cell production (erythropoietin).

The kidneys are rounded bean-shaped organs situated retroperitoneally on either side of the vertebral column. Where the renal artery, vein, and ureter access the kidney, there is a concave area, the hilus. Each kidney is covered by a thin, but strong, capsule of dense connective tissue. Progressively smaller branches of the renal artery radiate toward the capsule. In the outer portion of the kidney parenchyma, the cortex, individual arterioles form small capillary knots, glomeruli, that filter blood. The filtrate fluid flows through a series of tubules down through the inner portion of the kidney parenchyma, the medulla, into a collecting area at the hilus, the renal pelvis. The kidney parenchyma wraps around this funnel-shaped cavity that collects urine and drains it into the ureter. Smaller funnel-shaped branches of the main cavity that drain into the renal pelvis are called major and minor calyces.

The medulla is composed of approximately a dozen conical divisions called renal pyramids, each with its apex or papilla projecting (toward the hilus) into the lumen of one of the minor calyces. Each renal pyramid with the cortical tissue overlying its cone (grouping the glomeruli that eventually drain together into one minor calyx) is called a renal lobe. The tip of each papilla has a perforated appearance at the area cribrosa, where many tubules empty into a minor calyx. There is a fairly clear boundary between the medulla and cortex, the corticomedullary boundary, but extensions of medullary tissue extend into the cortex in places as medullary rays.

In the cortex, individual arterioles form small capillary knots, glomeruli, that filter blood. Each knot is surrounded by a spherical layer of epithelial cells, Bowman's capsule, to collect the filtered plasma. Each glomerulus with its investing Bowman's capsule is called a renal corpuscle. The region of the renal corpuscle where the arterioles enter and leave is called the vascular pole. At the opposite side, the urinary pole, a tubule drains filtrate fluid out of each corpuscle and conducts it through a series of tubules down through the medulla.

Each kidney contains approximately 1 million functional units called nephrons composed of a renal corpuscle (glomerulus and Bowman's capsule), draining into a proximal tubule, flowing into a loop of Henle which dives into the medulla and then returns to the cortex, where it continues as a distal tubule. Distal tubules from many nephrons drain into a collecting duct which returns through the medulla to drain at the area cribrosa into a minor calyx. A uriniferous tubule is one nephron and its collecting tubule.

Medullary rays occur where collecting tubules from many nephrons in a single cortical lobule flow together into larger collecting ducts passing down to the medulla. Also in the medullary rays are descending and ascending thick limbs of Henle's loop and blood vessels.

This is accomplished by collecting a protein-free plasma filtrate in Bowman's space, and then reabsorbing almost all of the amino acids and sugar and secreting or reabsorbing given ions and water as needed as the filtrate passes through the rest of the nephron. The remaining fluid with metabolic waste, the ion and water content adjusted, is excreted as urine. An adult human has a total plasma volume of about 3L. Approximately 20% of the plasma flowing through the kidneys is passed into the glomerulus as a filtrate. Blood flow to the kidneys is very high, about 1.2L per minute, enough to form a filtrate equivalent to approximately 60 times the total plasma volume per day. Obviously, this has to be efficiently reabsorbed.

The renal corpuscle functions to form the protein-free plasma filtrate. Capillary hydrostatic (blood) pressure forces fluid through the fenestrations in the glomerular capillary endothelium, through the underlying basement membrane, and so into Bowman's space. The basement membrane of the glomerulus is especially thick, essentially a double basement membrane fusing that of the capillary endothelium and that of the underlying visceral epithelium of Bowman's capsule. One can think of a glomerulus as like a fist of capillaries punched into a the balloon-like blind end of a uriniferous tubule. Bowman's capsule is composed of both a visceral layer of epithelium closely investing the glomerular capillaries and a smooth squamous parietal layer forming a cup-like space around the rest. This double basement membrane between the endothelium and the visceral epithelium is negatively charged (rich in heparin sulfate proteoglycans) and excludes plasma proteins (generally slightly negatively charged) on the basis of both size and charge repulsion.

The visceral epithelium does not form a major barrier, because it is composed of a special type of epithelial cell, the podocyte, which wraps the glomerular capillaries in non-continuous sheath of interdigitating finger like cellular processes. The plasma filtrate fairly easily passes through the filtration slits between podocyte processes. These processes function to support the basement membrane and endocytose some of the small amount of plasma protein that passes through.

Another cell type, the intraglomerular mesangial cells, located between the capillary endothelial cells and basement membrane, serve to endocytose protein and other material that passes through endothelial fenestrae but collects on the blood side of the basement membrane.

The proximal tubule, as the name implies, is the first tubule portion following the renal corpuscle. It is the longest segment and highly convoluted (also called the "proximal convoluted tubule"). Its lining cuboidal cells have a prominent apical brush border, highly interdigitated lateral membranes, and basal infoldings lined with mitochondria, all reflecting a very high level of transcellular transport. The proximal tubule epithelium recovers about 100% of the amino acids and glucose from the glomerular filtrate, 65% of the salt and water, and most of the small remaining amount of protein. Sodium is pumped out of the cells at the basal side at the expense of ATP (produced by the mitochondria). Water diffuses across the cells in response to ionic and osmotic gradients via water channels called aquaporins. Glucose and amino acids are pumped into the cells at the apical surface against a concentration gradient and leave the cells at the basal surface by symporter channels. Proteins are endocytosed, transferred to lysosomes, hydrolyzed to amino acids, and diffuse out of the cells into the general circulation.

Appearance of protein or glucose in the urine are clinical signs of metabolic or kidney disease. Protein in the urine (proteinuria) is indicative of damage to the glomerular basement membrane, allowing plasma protein to escape and overwhelming the limited ability of podocytes and proximal tubule cells to recover it. Similarly, appearance of glucose in the urine (glucosuria) is a sign that abnormally high blood glucose levels (e.g. due to insulin insufficiency, diabetes mellitus) have exceeded the renal resorptive capacity. Proteinuria and glucosuria could also be signs that damage to proximal tubule cells has reduced their resorptive capacity.

The loop of Henle continues from the cortical proximal tubule as a so-called thick descending limb, thin (squamous) loop, and thick ascending limb. Nephrons can be divided into two general types, the cortical nephrons, which have very little if any thin loop, and the juxtamedullary nephrons, which have long thin loops running deep into the medulla. Shifting blood flow between these two nephron types helps regulate the degree of urine salt concentration, because the long loops of Henle play the major role concentrating urine by a process called "countercurrent exchange". Their primary function is to transport NaCl from the lumen to the interstitium. The lining epithelium of either type of thick descending limb is basically a straight portion of the proximal convoluted tubule, as is the thick ascending limb basically a straight portion of the distal convoluted tubule. The really distinguishing features and functions of the loops of Henle are in the simple squamous lined thin limb which runs deep into the medulla. The key to remember here is that the descending thin limb is permeable to water, but impermeable to NaCl, whereas the ascending thin limb is impermeable to water, but permeable to NaCl. Therefore, water leaves the descending thin limb in response to osmotic pressure, while NaCl is extruded from the ascending thin limb to maintain that osmotic gradient at 4X the osmolarity of plasma. Countercurrent exchange is further explained below in relation to the renal vasculature.

The distal tubule continues from the thick ascending limb of Henle in the medulla as a straight segment passing back into the cortex next to the originating renal corpuscle for that nephron and then on as a convoluted segment continuing on to the collecting duct. The lining epithelium is simple cuboidal with few a microvilli, but no well organized brush border. As in the proximal tubule, lateral cell interdigitations prevent paracellular fluid transport and basal infoldings with mitochondria reflect the presence of ATPase dependent sodium pumps. The primary function of the distal tubule is to reabsorb NaCl. The epithelial cells are impermeable to water, so it cannot follow NaCl into the interstitium here, and the distal tubule lumen contents are generally hypotonic. These cells also resorb bicarbonate while excreting nitrogen as ammonia. The return of each distal tubule to pass beside the vascular pole of its originating renal corpuscle is important for endocrine kidney function of the juxtaglomerular apparatus described below.

Several distal convoluted tubules drain together into a collecting tubule which conducts urine through the cortex to converge into collecting ducts descending towards the medulla as medullary rays and then through the medulla into the minor calyces. The simple cuboidal lining of the collecting ducts and tubules is easily distinguished from the proximal and distal tubules due to its clearly visible intercellular boundaries (i.e. lack of lateral interdigitations). Tight junctional complexes still restrict paracellular transport.

The collecting ducts do not just function to conduct urine, but also participate ion the final steps of renal regulation of salt and water balance. They secrete H⁺via a proton pump to acidify the urine, and resorb Na⁺ in exchange for K⁺ under the regulation of an adrenal hormone, aldosterone. Another hormone, anti-diuretic hormone (ADH), secreted by the pituitary when CNS receptors indicate sense increased blood tonicity, regulates water permeability of the collecting duct cells. Typically urine entering the collecting ducts is hypotonic. ADH can increase water resorption by inducing apical vesicles containing water channels (aquaporins) to fuse with the apical duct cell membranes. Water permeability of the collecting duct epithelium increases causing water resorption and urine concentration. If needed, greater than 99% of the filtered water can be resorbed.

The renal artery enters the kidney at the hilus and branches to form several interlobar arteries that course radially towards the capsule, passing between the pyramids in the medulla. Perpendicular branches arise at the level of the corticomedullary border and these arcuate arteries follow that arcing border. From the arcuate arteries arise perpendicular interlobular branches that again course radially now marking the boundaries of cortical lobules. Branching off from these throughout the cortex are the afferent glomerular arterioles which end in renal glomeruli.

The glomeruli are examples of portal circulatory systems, meaning that the arterial blood passes from an arteriole through a system of capillaries which then merge to form another arteriole, not a venule, which eventually branches to form capillaries again. The efferent glomerular arterioles emerging from cortical (short) nephrons subsequently give rise to a peritubular capillary network that surrounds the ascending and descending limbs of the short loops of Henle. Efferent arterioles from the juxtamedullary (long) nephrons give rise to long, thin, straight, capillary vessels, the vasa recta, that plunge deep into the medulla, form hairpin loops, and return back toward the cortex. The ascending vasa recta follow closely parallel to the descending portion of the same vessel, so forming an important part of the renal countercurrent system. The descending arterial side of these capillary vessels has a continuous endothelium, but the ascending venous portion has a very thin fenestrated endothelium. Vasa recta penetrate to various medullary depths before turning back. At the corticomedullary border, the ascending vasa recta flow into interlobular and arcuate veins. The large renal veins accompany the arteries (i.e. interlobar, arcuate, and interlobular veins).

Two of the most basic of kidney functions are to maintain a homeostatic balance of NaCl and water. It is easy to understand how NaCl can be regulated by active transport in or out of the body, but since water transport depends on its osmotic flow, largely along NaCl gradients, a problem arises in developing a system to independently regulate NaCl and water balance. One of the key physiological principles used in the kidney that allows us to excrete a hypertonic urine, conserving water, is countercurrent exchange, and it is this principle which dictates many of the complex aspects of kidney organization. Renal countercurrent exchange depends on the close antiparallel association of the ascending and descending portions of the loop of Henle and vasa recta and the collecting ducts, which promotes rapid molecular transport from one to the other. A true explication of renal countercurrent exchange is beyond our goals for this chapter, but the basics are outlined below.

To begin to grasp countercurrent exchange (a fancy name for a fairly simple idea), first consider a simpler example than found in the kidney. Think of a penguin standing on ice, faced with the need to provide blood flow to his frigid feet while maintaining his internal body temperature. The problem is to keep as high a gradient of temperature as possible down his legs. This is accomplished by close antiparallel arrangement of the vertically passing arterial and venous systems. Warm blood starting its journey down the legs passes next to cold blood returning from the feet and the oppositely flowing (countercurrent) systems equilibrate (exchange) heat between them. By the time the arterial blood reaches the feet it has lost its heat to the venous blood.. By the time the venous blood reaches the body, it has been warmed to body temperature by heat flow from the passing arterial blood. If the arterial and venous systems did not flow intimately antiparallel, warm blood would arrive at the feet where a lot of heat would be lost due to the high temperature gradient, and cold blood would return to the body. Instead, countercurrent exchange keeps a steep temperature gradient from body to feet, minimizing heat loss.

In the kidney, countercurrent exchange of NaCl and urea allows a high concentration gradient to be maintained between the outer and inner medulla. Establishing this concentration gradient depends on the following steps. 1) The ascending limb of Henle is impermeable to water, but permeable to NaCl. NaCl is also actively transported out of the thick ascending limb, creating a hypertonic interstitium in the medulla. NaCl transport is regulated by aldosterone secreted from the adrenal gland. Low levels of aldosterone allow serious loss of sodium in the urine. 2) High levels of NaCl and urea in the medullary interstitium allow water to be osmotically reabsorbed (under control of ADH) out of the now hypotonic urine in the collecting ducts, increasing the concentration of urea left behind in the collecting duct lumen. 3) In the inner medulla, the collecting duct becomes permeable to urea and it passively diffuses out down its concentration gradient, so also reaching a high concentration in the inner medulla interstitium. The high urea concentration means that some will diffuse into the loop of Henle, but some of this will then recycle out of the collecting duct again, countercurrent exchange. 4) The high medullary NaCl and urea concentration serves also to osmotically draw water out of the (water permeable, NaCl impermeable) descending limb of Henle's loop (concentrating NaCl in the lumen). 5) The reversed permeability properties of the ascending limb facilitate active NaCl transport out down its concentration gradient, countercurrent exchange. The key steps are active transport of NaCl out of the ascending loop and passive transport of urea out of the inner collecting duct, allowing ADH regulation of water channels to regulate osmotic resorption of water. About 50% of the urea and up to 99% or more of the water can be resorbed this way.

But resorbed water has to be removed from the medullary interstitium to prevent it from collapsing the medullary concentration gradient. That is accomplished by diffusion into the vasa recta, returning water to the circulation. Accepting that the above transport processes set up a situation where the interstitial concentrations of NaCl and urea rise progressively to quite high levels moving from the outer to inner medulla, how can the vasa recta supply blood to the medulla and remove water without capillary permeability also drawing off the concentrated materials? The answer again is countercurrent exchange. NaCl and urea enter the descending vasa recta, but exit the ascending vasa recta following their concentration gradients. Conversely, water diffuses out of the descending vasa recta increasing the plasma protein concentration, but diffuses back into the ascending vasa recta.

Renal countercurrent exchange can be considered as operating in three different loops: the loop of Henle passes through a steep concentration gradient of NaCl and urea. So, too, do the vasa recta. The third loop is formed by the ascending limb of Henle and the descending collecting duct, passing in the opposite direction through the NaCl and urea gradients. These loops are critical for establishing and maintaining the high medullary interstitial concentrations, which are critical for efficiently resorbing water. The concentration of urea allows water to be resorbed independently of NaCl.

Figure 3: Three different loops use countercurrent exchange to maintain steep osmotic gradients in the kidney. Note that for purposes of illustration these are drawn as stretched widely apart, when in fact it is important for their function that each loop runs very closely antiparallel. Relative solute concentrations are illustrated by type size.

Substance	Amount Filtered	Amount Reabsorbed	% Reabsorbed
Na⁺ (mEq)	26,000	25,850	99.4
K⁺ (mEq)	900	900	100
Cl^- (mEq)	18,000	17,850	99.2
H₂O (L)	180	179	99.4
Glucose (mmol)	800	800	100
Urea (mmol)	870	460	53

The kidney is not only regulated by various hormones secreted by other organs, but also has its own endocrine functions, especially regulating blood pressure and erythropoiesis.

Renal endocrine regulation of blood pressure occurs via a specialized portion of the renal corpuscle called the juxtaglomerular apparatus. Recall that the distal tubule derived from a given corpuscle passes in close proximity to the vascular pole of that same corpuscle. Specializations of the epithelial lining of the distal tubule and of the smooth muscle of the afferent glomerular arteriole occur in the small area where they make contact. The epithelial cells appear narrower with more closely packed nuclei that in other regions of the distal tubule. These modified epithelial cells are referred to the macula densa. The adjacent smooth muscle cells of the afferent arteriole appear fatter than normal and contain secretory granules containing the proteolytic enzyme renin. These modified smooth muscle cells are referred to as juxtaglomerular cells or JG cells.

The macula densa acts as a chemoreceptor monitoring sodium concentration in the distal tubule. In response to falling Na⁺ concentrations, the macula densa signals the JG cells to secrete renin. The JG cells themselves are pressor receptors. That is they monitor blood pressure and secrete renin in response to falling pressure. Renin secreted into the blood cleaves the protein angiotensinogen to yield angiotensin I, which can be cleaved to yield active angiotensin II by another enzyme, angiotensin-converting enzyme (ACE), on the surface of endothelial cells, primarily in the lung. Angiotensin II causes constriction of arteriolar smooth muscle, elevating arterial blood pressure, and it also stimulates secretion of aldosterone from the adrenal cortex, which induces the distal tubules to increase Na⁺ recovery, which then tonically holds more water in the circulation, so too increasing blood pressure.

Hypertension, increased blood pressure, is a prevalent and important health problem that can arise from a number of different causes, for instance decreased arterial elasticity (hardening of the arteries) due to atherosclerosis. In many cases, we do not yet understand the cause (essential hypertension), but genetic susceptibility is clearly important. Hypertension itself exacerbates atherosclerosis and greatly increases the risk of strokes (vascular accidents in the brain). Diuretics induce decreased renal water resorption and have long been used to treat high blood pressure (hypertension). ACE inhibitors are a relatively new class of drugs for this purpose, as are angiotensin II receptor inhibitors.

Renal endocrine regulation of erythropoiesis occurs by secretion of erythropoietin by specialized cells (probably mesangial cells) that respond to O₂ tension in the afferent arteriole. Recall that erythropoietin regulates red cell production by hematopoietic tissue. Kidneys are the major, but not sole, site of erythropoietin production.

The extrarenal system carries urine in the ureters from the renal pelvises to the bladder, where it is stored, and from the bladder through the urethra to the exterior. All parts of the extrarenal passages (except the urethra) have a similar structure with a mucosa, muscularis, and adventitia. The thickness of the wall of these passages gradually increases from the upper to lower parts. The lumen is lined by a mucosa consisting of transitional epithelium. When stretched, transitional epithelium assumes the appearance of a thin stratified squamous epithelium. In relaxed state, the surface cells are large and dome-shaped.

The epithelium is two to three cells thick in the renal calyces, three to four cells thick in the ureter, and five or more cells thick in the bladder.

The muscularis in the calyces, renal pelvis and ureter has a helical arrangement of smooth muscle cells, whereas the smooth muscle cells surrounding the bladder run in all directions as one thick layer. The ureters pass into of the bladder wall obliquely, forming a valve that prevents urine backflow.

The male's urethra (not shown) is substantially longer more complex than the female's. In the male, the urethra has three segments: 1) prostatic urethra, lying within the prostate and lined by transitional epithelium, 2) membranous urethra, extending from the prostate to the root of the penis and lined by stratified or pseudostratified columnar epithelium, and 3) penile urethra, lined by the same type of epithelium as the membranous urethra, but transitioning to stratified squamous epithelium. The female urethra is lined by stratified squamous epithelium but may have patches of stratified or pseudostratified columnar cells.

1. The light microscopic structure of each component of the nephron.
(Review its components as the basic unit of structure and function in the kidney.)

2. The vascular supply of the cortex and medulla.
(Review the adaptation of the vasa recta that prevents dissipation of the hypertonic gradient in the medullary interstitium.)

3. The juxtaglomerular apparatus.
(Review its role in the endocrine regulation of blood pressure and salt and water retention.)

4. The general structure of the urinary pelvis, ureter, and urinary bladder.
(Review the functional specialization of transitional epithelium.)

First study the cortical area on slide 81 (monkey kidney). Amongst the many cross-sectioned tubules are scattered renal corpuscles. Examine a number of these trying to find examples of vascular and urinary poles, good images of Bowman's capsule and space, and the juxtaglomerular apparatus.

The renal corpuscles are the most distinctive components of the cortex. The center of each corpuscle consists of a cluster of capillary loops (the renal glomerulus) coated with a layer of epithelial cells (visceral layer of Bowman's capsule). These two layers are too difficult for you to distinguish from one another by light microscopy. The wall of the corpuscle is lined with simple squamous epithelium (parietal layer of Bowman's capsule), a layer you can identify. The glomerular basement membrane may be barely visible as blue lines in the shape of loops within the renal corpuscle. Recall that it is interposed between the capillary endothelium and the visceral layer of Bowman's capsule.

Examine the afferent and efferent glomerular arterioles of the renal corpuscles. The two are difficult to distinguish and we don't expect you to do so. However, part of the smooth muscle coat of the afferent arteriole is specialized to form the juxtaglomerular cells (JG cells). These are larger than the other smooth muscle cells and store the endocrine secretory product, renin. The epithelial cells lining the region of the distal tubule adjacent to the juxtaglomerular cells are narrower with their nuclei noticeably more closely packed than elsewhere in the tubule. This area of the distal tubule is the macula densa and signals the JG cells to secrete renin when sodium concentration in the distal tubule falls. Together, the juxtaglomerular cells and the macula densa are referred to as the juxtaglomerular apparatus.

Next learn to differentiate sections of proximal and distal convoluted tubules and collecting tubules surrounding the renal corpuscles. The proximal convoluted tubules are the most numerous cross-section, because this is the longest segment of the nephron. They have a fairly dark staining cuboidal epithelium. The nuclei of the lining cells are relatively widely spaced; the lining cells are fairly broad. Lateral cell borders are highly interdigitated so not visible by light microscopy. The apical borders have a well developed brush border, but this does not fix well and so the lumenal aspect of these cells appears indistinct with a lot of granular material occluding the lumen. The distal convoluted tubules also have cuboidal epithelium, but this appears somewhat lower and lighter staining than the proximal tubule and has only a few microvilli, no brush border. The nuclei appear more closely spaced. The collecting tubules have a high cuboidal epithelium with distinct lateral and apical cell boundaries (no lateral interdigitations and no microvilli). The transition from distal tubule to collecting tubule is gradual; therefore, you will see tubules that have intermediate characteristics.

As you scan around you will also notice bundles of straight parallel tubules in the cortex. These are medullary rays and contain the thick descending limbs of Henle's loop (the straight portion of the proximal tubule), thick ascending limbs of Henle's loop (the straight portion of the distal tubule), and cortical collecting ducts. They are a particularly good place to compare tubule types. Try to find rays cut in both cross and longitudinal sections. Each medullary ray is the core of a cortical renal lobule. The surrounding periphery of the lobule contains the remaining components of the nephrons whose Henle's loops lie in the medullary ray, i.e., the renal corpuscles and the proximal and distal convoluted tubules. Between lobules, parrallel to the medullary rays, run the interlobular arteries. You can think of each renal lobule as being roughly cylindrical in shape and extending from the corticomedullary junction to the capsule of the kidney.

Next study the medulla, which contains no corpuscles. The parenchymal components of the outer medulla consist of medullary collecting ducts and ascending and descending thick limbs of Henle's loop. In the outer medulla, the ascending and descending thick limbs of Henle's loop are lined by cuboidal epithelial cells. Cuboidal lining cells of the thick descending limb resemble cells of the proximal tubule, of which they form the terminal straight portion; those of the thick ascending limb resemble cells of the distal tubule, of which they form the initial straight portion. These thick portions of Henle's loop extend only a short distance in the medulla and should be identified close to the corticomedullary junction.

The majority of efferent glomerular arterioles end by emptying into the peritubular capillary plexus of the cortex. However, the efferent arterioles of renal corpuscles located near the corticomedullary border provide the capillary circulation for the medulla by giving rise to the vasa recta, long capillary loops which penetrate deep into the medulla in the same manner as Henle's loops. In the outer part of the medulla the ascending and descending limbs of the vasa recta are clustered together to form large vascular bundles that are easy to recognize.

The inner medulla contains collecting ducts and ascending and descending thin limbs of Henle's loop, which you should identify. Both thin limbs are lined by simple squamous epithelium similar to capillary endothelium. The two thin limbs can't be distinguished from one another. Identify the vasa recta capillaries of the inner medulla by the erythrocytes in their lumen.

The epithelial lining of the terminal collecting ducts becomes columnar where they empty urine into a renal calyx at the apex of a renal pyramid. You will only be able to see the openings of the collecting ducts and the renal pelvis, lined by transitional epithelium, if your section passes through the apex of a renal pyramid.

Examine various sections of the renal arteries and veins. Arcuate arteries and veins should be easy to recognize, because they are located at the corticomedullary border. From the arcuate vessels emerge interlobular arteries and veins which run perpendicularly from the corticomedullary border towards the periphery of the cortex. The interlobular arteries have the typical appearance of small arteries and are also easy to recognize, but the interlobular veins are atypical in structure. Although broad in diameter, they have a very thin wall that seems to consist only of endothelium. Both interlobular vessels, as you can tell from their name, run in the boundary between adjacent lobules. The vessels are generally located midway between two medullary rays. This makes sense because the center of each lobule is a medullary ray. Deep in the medulla you may also be able to see very large interlobar arteries and veins.

On slide 85, identify the transitional epithelium and the smooth muscle layer (muscularis) of the ureter. This epithelium also lines the pelvis of the kidney and the bladder. Also observe the abundant smooth muscle in the wall of the ureter. Peristalsis of the smooth muscle helps to move urine to the urinary bladder.

The thick wall of the bladder consists chiefly of large irregularly oriented bundles of smooth muscle. Autonomic nerves are scattered among them. This bladder was fixed in a contracted condition and consequently its transitional epithelium is highly infolded. Observe the characteristic broad, dome-shaped cells that form the superficial layer.