URINARY SYSTEM Part I (Top and Bottom)
Roger Bick.
Reading: Gartner and Hiatt Chapter 16, pp. 335-352; Klein and McKenzie pp301-310
Learning Objectives:
Name components of functioning renal parenchyma versus passive collecting system.
Be able to describe the flow of blood through the kidneys from the renal artery back to
the renal vein via either a superficial or a juxtamedullary glomerulus.
Recognize the main divisions of the nephron with light microscopy and know their main
functions.
Name the components of the juxtaglomerular apparatus.
List the components of the glomerular filtration barrier.
Be able to identify the following components of the renal corpuscle with light
microscopy: parietal/visceral epithelium, mesangium, capillaries, urinary pole, vascular
pole, and Bowman's capsule.
Be able to identify the following components of the renal corpuscle by electron
microscopy: epithelial, endothelial, and mesangial cells; mesangium; basement
membrane.
Understand the zones of the kidney and the locations of various parts of the nephron
within those zones.
Key Words: Cortex, medulla, nephron, transitional epithelium, ureter, Renal corpuscle,
glomerular filtration barrier and bladder.
GROSS FEATURES
A. KIDNEY
1. Location- The kidneys are located in the retroperitoneal space with the upper
pole at the level of T12 and the lower at L3.
2. Fetal Features - In fetal life, the kidneys are composed of 7-18 pyramid-shaped
lobes (bases externally oriented, apices pointing inward) giving them a lumpy external
appearance. The demarcation between the lobes is obscured in time, so that the kidney
ultimately has a smooth appearance. It is important to be aware of the early lobar composition
of the kidneys to understand the internal architecture and nomenclature.
3. Adult Features -Each kidney weighs 120 to 170 gm and is 11-12 cm in length.
a. Functional parenchyma
(1) Cortex: This occupies the outermost rim of tissue grossly, being about 1 cm in
thickness. Large vessels can be seen and delineate the cortex from the next zone inward, the
medulla.
(2) Medulla: This zone is medial to the cortex and contains 7-18 conical masses
called renal pyramids. The base of each pyramid is at the corticomedullary boundary, while
the apex of each extends inward to the renal pelvis, forming a nipple-like protrusion called a
papilla. Sometimes several pyramids terminate in a common papilla, so that there are fewer
papillae than there are pyramids. Urine is released from small holes in the papillae into a
passive collecting system. Extensions of the cortex between adjacent pyramids are called
renal columns (of Bertin). Each pyramid and the surrounding cortical tissue in the renal
column comprises a lobe, the total number corresponding to the number of lobes in the fetal
kidney.
1
b. Intrarenal Collecting System
(1) Minor Calyx: Each minor calyx is a cup-like structure that surrounds 1-2
papillae and collects the released urine.
(2) Major Calyx: The minor calyces funnel into 2-3 larger major calyces.
(3) Pelvis: The major calyces funnel into this large atrium-like area deep within
the kidney.
c. EXTRARENAL COLLECTING SYSTEM
(1) Ureter: The pelvis gradually narrows into this tube-like conduit which runs from the
kidney to the bladder. The proximal part of the ureter begins in the renal hilum, defined as
the medial aspect of the kidney where the renal artery and vein, ureter, and fat are found.
(2) Bladder
(3) Urethra
ARTERIAL SYSTEM
Blood enters the kidney at the hilus via a renal artery, branching into interlobar arteries
perpendicular to the surface, between the renal lobes.
From these, arcuate arteries branch off at right angles, running parallel to the surface
between the cortex and medulla. (They are very useful landmarks since they define the border
between cortex and medulla.) Smaller branches are then given off into the cortex, again
running perpendicular to the surface, called interlobular arteries. Circulation distal to these
arteries will be considered with other histologic features.
2
INNERVATION
The kidney is richly supplied with sympathetic nerves that follow the course of the renal
arteries and arterioles and innervate the smooth muscle in their walls to contract. Strong
sympathetic stimulation constricts these vessels, increasing their resistance and decreasing
renal blood flow. Sympathetic nerves are also found on tubules and can directly cause
increases in sodium absorption.
HISTOLOGIC FEATURES
A. COLLECTING SYSTEM
1. Minor Calyx to Bladder
The calyces, renal pelvis, ureter and bladder have the same basic histologic structure.
a. Mucosa
(1) Epithelium: Transitional; increase from 3 cell layers deep at the minor calyx to 6 in the
bladder
(2) Lamina Propria: Loose to dense connective tissue.
NOTE: More than 90% of urinary bladder tumors originate in the epithelial lining.
b. Muscularis
Begins with the minor calyces, and consists of 2 layers of smooth muscle, with the innermost
being longitudinal and the one external to this being circular. As the ureter approaches the
bladder, a third outer longitudinal layer is added, which is constant throughout the bladder.
c. Adventitia or Serosa
Only the dome of the bladder is covered by serosa (peritoneum). The wall of the rest of the
bladder and ureter phase into the surrounding tissues without a defined serosa.
2. Transitional Epithelium Dynamics
This epithelium is unique in the necessity for it to be able to expand and contract rapidly.
This is accomplished by the presence in the apical cytoplasm of discoid vesicles, the
membranes of which serve as reservoirs for apical membrane expansion as follows. When the
bladder is empty (A), the apical cytoplasm of the innermost cells is filled with discoid
vesicles underneath the plasmalemma. As the bladder fills and the epithelium stretches (B),
these vesicles fuse with the apical membranes, providing increased surface area.
Compare the structure of the transitional epithelium when the urinary bladder is empty (A) or
full (B). When the bladder is full, the capacity of epithelial cells to slide upon one another
reduces the thickness of the epithelium. As a result, the interior surface of the bladder
increases. In B, note the thin strands of collagen fibers separating bundles of smooth muscle
cells. PSH stain. Medium magnification
3
3. Urethra
Near the bladder, the urethra has transitional epithelium. Adjacent to the "external world", the
epithelium is stratified squamous. Between the zones, the epithelium may be stratified
columnar or pseudostratified columnar. The female urethra is mostly lined with stratified
squamous epithelium. Glands may empty into the lumen of the urethra of the male or female.
There are abundant elastic fibers in the lamina propria. The muscularis proximally consists of
inner longitudinal and outer circular smooth muscle. At the urogenital diaphragm, voluntary
striated muscle fibers are mixed with the outer layer of smooth muscle.
Beyond this, the muscularis begins to disappear and ceases to exist as one of the layers. There
is no serosa. In the female, the connective tissue, of the adventitia fuses with the vaginal
canal. More details regarding the male urethra will be provided in a later lecture.
B. THE NEPHRON - Main Divisions
This is the functional unit of the kidney, with 1,300,000 comprising each kidney. Each
nephron is further subdivided into areas that differ structurally and functionally. A relatively
small amount of connective tissue containing abundant capillaries, some cells and matrix
separates the tubules. This connective tissue space is called the interstitium.
1. Renal corpuscle
a. Glomerulus
b. Bowman's capsule
c. Bowman's space
2. Proximal tubule
a. Proximal convoluted tubules
b. Thick descending limb
3. Thin limb
a. Thin descending limb
b. Thin ascending limb
4. Distal tubule
a. Distal straight tubule (thick ascending limb)
b. Distal convoluted tubule
5. Collecting tubule/duct
NOTE: Loop of Henle - Includes the straight, or last portion of the proximal tubule, the
thin limb, and the distal straight tubule or thick ascending limb that lie in the medulla.
4
THE RENAL CORPUSCLE (Malpighian Corpuscle)
1. Structure
This is a complex structure which absolutely requires both a two and three dimensional
conceptualization for complete understanding. The adult glomeruli measure approximately
200 µm in diameter.
a. Vascular Component - The Glomerulus (plural: glomeruli)
We last left circulation at the level of the small cortical interlobular arteries. Branching off
these are afferent arterioles. Each afferent arteriole subdivides into a brain-like convolution
of capillaries. Each ball of capillaries constitutes a glomerulus (glomerular capillaries;
glomerular tuft). The capillaries merge back into a single efferent arteriole that carries blood
away. The fate of the circulation from this point will be continued later. At this point it will
be noted that some cells within the walls of the afferent and efferent arterioles, in addition to
being of smooth muscle origin typical of other arterioles, also contain granules of renin. They
are called juxtaglomerular cells or granular cells. The significance of this feature will also
be subsequently discussed.
The glomerular capillaries are characterized by an inner simple squamous fenestrated
endothelium in which there are no diaphragms across the fenestrae. This layer is thus very
leaky and presents little barrier to the movement of plasma. The endothelial cells rest on a
glomerular basement membrane (GBM), which is an amorphous extracellular, gel-like
layer. It is thought to be the major barrier to the movement of plasma.
b. Glomerular basement membrane (GBM)
Major components of the GBM include Type IV collagen and laminin which both contribute
to adhesion of the epithelia to the GBM, and proteoglycans such as heparan sulfate, which
contribute an overall negative charge to the GBM. The GBM is not totally homogeneous, but
can be seen with transmission electron microscopy to have the following layers:
Lamina Rara Interna: An electron-lucid layer directly under the endothelium.
Lamina Densa: An internal electron-dense layer.
Lamina Rara Externa: Electron-lucid layer found under the visceral epithelium.
The foot processes or pedicels of the visceral epithelium or podocytes (see below) rest
directly on the GBM. Like the endothelium, the visceral epithelium contributes to the
formation of this extracellular layer. The GBM is thus sandwiched tightly between the
5
visceral epithelium on one side and the glomerular endothelium on the other side. The GBM,
interestingly, represents a fusion of the basal laminae, specifically the laminae densa, of two
epithelia, a unique arrangement in the body. (Review the portion of the connective tissue
lecture on basement membranes to better visualize this recalling that, since there is no
underlying connective tissue, there will not be a lamina reticularis).
c. Epithelial Component
(1) Visceral Epithelium:
This epithelium closely invests the glomerular capillaries. It is unique in the body in that it
consists of octopus-like cells called podocytes (visceral epithelial cells). The "arms" of these
cells encircle the capillaries and are called foot processes or pedicels. The foot processes or
pedicels rest directly on the GBM. The pedicels of neighboring cells interdigitate, but do not
actually touch. They are separated by narrow spaces called filtration slits. Each slit is bridged
by a thin membrane called a filtration slit diaphragm, which in turn is penetrated by a
zipper-like array of rectangular pores. It is through these pores that plasma is able to pass
through the visceral epithelial layer, and they provide little resistance to flow. Since each pore
is slightly smaller than an albumin molecule, macromolecules of this size and larger are
normally retained within the vasculature and do not filter.
(2) Parietal Epithelium; Parietal Layer of Bowman's Capsule:
The visceral epithelium coats the glomerular capillaries, but where they merge with the
arterioles, called the vascular pole, this layer reflects away and transitions immediately into a
simple squamous epithelium. It forms a thin veil around the glomerular tuft and is separated
from the tuft by a space, called Bowman's space. On the opposite side of the tuft from the
vascular pole the parietal layer transitions into a tall columnar type of epithelium that forms
the beginning of the tubular system. This is the urinary pole of the renal corpuscle.
In summary, the visceral and parietal epithelial layers both compose the Bowman's
capsule, but have very different appearances and functions and are separated by Bowman's
space (urinary space).
d. The Glomerular Mesangium
Connective tissue cells are found between the afferent and efferent arterioles -
Extraglomerular mesangial cells, and the bases of the capillary loops - Intraglomerular
mesangial cells. They are surrounded by an amorphous matrix. Mesangial cells and matrix
are collectively referred to as the mesangium. Aside from a supportive role, the function of
the mesangium is unclear but under intensive investigation. It is known that the cells contain
myosin and have contractile properties. They also play a role in uptake and elimination of
small particles and antigen-antibody complexes. Other functions are speculated.
6
e. The Glomerular Filtration Barrier
Plasma must filter out of the glomerular capillaries through various layers of the renal
corpuscle into Bowman's space, where it is then called the filtrate. The layers traversed in
this passage are:
(1) Glomerular capillary endothelium
(2) Glomerular basement membrane
Lamina rara interna
Lamina densa
Lamina rara externa
(3) Pores in filtration slit diaphragms of the visceral epithelium
1. Function
In 24 hours, 180 liters (48 gallons) of plasma filter out of the glomerular capillaries into
Bowman's space where it is then called the filtrate. Subsequent processing of this filtrate by
the tubules will result in reabsorption of 179 L, and elimination from the body of 1 L as urine.
7
LABORATORY GUIDE FOR URINARY SYSTEM - PART I
I. EXTRARENAL COLLECTING SYSTEM
Slide 72 was taken from a human kidney that underwent autolysis and is less than ideal
for learning histologic features. It is useful to view this section grossly holding the slide
against a white background to distinguish the lobated pattern of the human kidney. Note
several papillae and minor calyces. Check to see if the layers described in lecture are
present in the minor calyx.
Slide 73 shows proximal and distal sections of a ureter. Identify the layers, noting
especially the transitional epithelium. How can you tell which one was nearest the kidney
and which one was nearest the bladder? Also, do you see a serosa?
Slide 11 is a section of bladder with a piece of ureter included in the lumen. Review all
layers of both structures. The bladder epithelium appears better preserved than that of the
ureter. Note the dense irregular connective tissue of the lamina propria, and in the
bladder, its vascularity. How many muscle layers are there in the muscularis? Is there a
serosa present?
II. ZONES OF THE KIDNEY
This is best performed on the perfused unilobate rat kidney found on Slide 74. First
examine the kidney grossly and then with an inverted ocular to locate cortex, outer
medulla (outer zone), and inner medulla (inner zone). This will be fun and challenging
8
since the sections distributed through the class have many different orientations and, in
some cases, don't have all zones included. If you find you have been deprived of a zone,
harass your immediate neighbors for their kidneys. The ideal section is shown below in
cut A. Less ideal sections occur with cuts that are superficial or oriented strangely, shown
in cut B.
Arcuate veins will appear as large, empty circular profiles and serve to delineate cortex
from medulla which can't be distinguished grossly on the basis of texture or color. The
medulla is subdivided into several zones and stripes. The outer zone of the medulla is
clearly distinguishable from the inner zone, which is light and has a fine texture. The
inner zone is the portion referred to grossly as the papilla. The outer zone is further
subdivided into stripes. The outer stripe is very eosinophilic due to the presence of large,
eosinophilic proximal tubules. The inner stripe is paler due to the absence of proximal
tubules. Thus, while the outer medulla is two-toned with its two stripes, the inner medulla
appears as a more homogenous area.
The medullary zones are ill-defined in the human kidney and need not be studied at this
time today. Instead, use the rest of this period to identify, in both rat and human, the
cortex and detailed features of glomerular architecture.
III. THE RENAL CORPUSCLE
Slide 74 - rat kidney, H&E
Slide 75 - perfused human kidney, H&E
Slide 76 - perfused human kidney, PAS
Features of the renal corpuscle are easy to find in either rat or human. Distinguish the
approximate inner limit of the cortex by the presence of arcuate veins and arteries. The
former have extremely thin walls for their size. Can you find interlobular vessels coming
off these arcuates at right angles to the surface? At low magnifications you will see the
cortex to be occupied by renal corpuscles appearing as large circular profiles interspersed
among the tubules. It will necessary to look at quite a few to locate all necessary features
not usually present in one cross section. Be sure you can identify:
1. Bowman's space
2. Bowman's capsule - Parietal and visceral epithelium
3. Capillaries - lumens easy to distinguish, endothelial cells and walls less so
4. Vascular pole
a. Afferent/efferent arterioles
b. Extraglomerular mesangial cells
5. Urinary pole with proximal tubule
6. Intraglomerular mesangial cells
If a specific stain for renin were used, in which of these structures would you predict a
positive reaction?
What's the difference between podocytes and visceral epithelium? Or is there any?
To save yourself wear and tear in Part II, be sure you have recognized 4a and b,
components of the juxtaglomerular apparatus (JGA) to be described in the second lecture.
In a few lucky places, you will also be able to see another feature of the JGA, the macula
densa. Look for a tubule in close apposition to this region, and if you can see cells on the
glomerular side of this tubule where the nuclei are very close together forming a "dense
spot", you have identified the macula densa. In your next lab session, this feature will be
valuable for you to give positive identification to the thick ascending limb.
9
Once you have studied renal corpuscles with H&E, repeat the procedure, using slide 106,
human kidney stained with PAS, which highlights basement membranes and glycoprotein
in connective tissue. This stain highlights the GBM, the mesangial matrix (which is
otherwise difficult to see normally), and the Bowman's capsule.
10