General aspects of build-up and functioning of an organism II

(Histology, Embryology)

Urinary system
Histology

Associated Prof: Irina Modebadze

TSU
The urinary system

The urinary system consists of the

paired kidneys and ureters and the
unpaired bladder and urethra.
This system contributes to the
maintenance of homeostasis by a
complex process that involves filtration,
active absorption, passive absorption,
and secretion.
The result is the production of urine, in
which various metabolic waste products
are eliminated.
 Renal Functions
■ Regulation of the balance between water and
electrolytes (inorganic ions) and the acid-base
balance;
■ Excretion of metabolic wastes along with
excess water and electrolytes in urine;
■ Excretion of many bioactive substances,
including many drugs;
■ Regulation of arterial blood pressure by
secretion of renin.
■ Secretion of erythropoietin, a glycoprotein growth factor that stimulates erythrocyte
production in red marrow when the blood O2 level is low;
■ Conversion of the steroid prohormone vitamin D, initially produced in the epidermis,
to the active form (1,25-dihydroxyvitamin D 3 or calcitriol);
■ Gluconeogenesis during starvation or periods of prolonged fasting, making glucose
from amino acids to supplement this process in the liver.
Kidney
Concave medial border, the hilum
— where nerves enter, the ureter
exits, and blood and lymph
vessels enter and exit — and a
convex lateral surface, both covered
by a thin fibrous capsule.
Within the hilum the upper end of
the ureter expands as the renal
pelvis and divides into two or
three major calyces. Smaller
branches, the minor calyces, arise
from each major calyx. The area
surrounding the renal pelvis and
calyces contains adipose tissue.
 Kidney cortex and medulla
1. cortex; 2. medulla; 3. calyx;
4. collecting ducts and Henle`s loops
The kidney has an outer cortex, a
darker region with many corpuscles
and cross sections of tubules, and an
inner medulla consisting of straight,
aligned structures.
In humans, the renal medulla
consists of 8-12 conical structures
called renal pyramids, which are
separated by extensions from the cortex
called renal columns.
Each pyramid plus the cortical tissue at
its base constitutes a renal lobe. The tip
of each pyramid, called the renal
papilla, projects into a minor calyx that
collects urine formed by tubules in the
pyramid.
 Renal lobule Kidney lobule
Striations extending from the
medulla into the cortex are called
medullary rays, parallel arrays of
tubules; these plus the attached
cortical tissue are considered
lobules. Renal lobule consists of
the nephrons grouped around a
single medullary ray, and draining
into a single collecting duct.
Each kidney contains around 1
million functional units called
nephrons that consist of simple,
Kidney cortex in light microscope (H&E x25). single layered epithelium along
1. Capsule; 2. Medullary ray (connecting, collecting, ascending their entire lengths.
and descending tubes) ; 3. Convoluted tubes (cortical labyrinth);
4. Vein; 5. Renal corpuscle.
Kidney cortex.
The major divisions of each nephron are the following:
■ Renal corpuscle, an initial dilated part
enclosing a tuft of capillary loops and the
site of blood filtration, always located in
the cortex;
■ Proximal tubule, a long convoluted
part, located entirely in the cortex, with
a shorter straight part that enters the
medulla;
■ Loop of Henle (or nephron loop), in
the medulla, with a thin descending and
a thin ascending limb. The last becomes
the thick ascending limb (TAL);
■ Distal tubule, continues from TAL of
Henle back into the cortex and a
convoluted part completely in the cortex;
■ Connecting tubule, a short final part
linking the nephron to collecting ducts.
 Nephron
Cortical nephron Juxtamedullary nephron
Two types of nephrons:
Cortical nephrons are located almost
completely in the cortex while
juxtamedullary nephrons (about 1/7 of
the total) lie close to the medulla and
have long loops of Henle.

All nephrons connecting tubules

merge to form collecting tubules that
then merge as larger collecting ducts.
These converge in the renal papilla,
where they deliver urine to a minor
calyx.

Renal parenchyma along with nephron

consist of collecting tubules and ducts.
 Blood supply of Nephron
From the interlobular arteries arise the
microvascular afferent arterioles, which divide to
form a plexus of capillary loops called the
glomerulus, each of which is located within a renal
corpuscle where the blood is filtered. Blood leaves
the glomerular capillaries, not via venules, but via
efferent arterioles, which at once branch again
to form another capillary network, usually the
peritubular capillaries that will nourish the
proximal and distal tubules and carry away
absorbed ions and low-molecular-weight materials.

Cortical nephrons afferent arteriole has a larger

diameter than the efferent arteriole. The differences in
luminal diameters of the arterioles result in a positive
filtration pressure within the renal corpuscle.
 All the major functions of the kidneys involve specific activities:

■ Filtration, by which water and solutes in the blood leave the vascular space and enter the
lumen of the nephron.
■ Tubular secretion, by which substances move from epithelial cells of the tubules into the
lumens, usually after uptake from the surrounding interstitium and capillaries.
■ Tubular reabsorption, by which substances move from the tubular lumen across the
epithelium into the interstitium and surrounding capillaries.
 Renal Corpuscles
Renal corpuscle, about 200 μm in diameter and containing a tuft of glomerular capillaries, surrounded by a
double-walled epithelial capsule called the glomerular (Bowman) capsule. The internal or visceral layer of
this capsule closely envelops the glomerular capillaries, which are fenestrated. The outer parietal layer
forms the surface of the capsule. Between the two capsular layers is the capsular (or urinary) space, which
receives the fluid filtered through the capillary wall and visceral layer. Each renal corpuscle has
a vascular pole, where
the afferent arteriole
enters and the efferent
arteriole leaves, and a
tubular or urinary pole,
where the proximal
convoluted tubule
(PCT) begins.
PCT - proximal convoluted
tubules; DCT - distal convoluted
tubules; CS – capsular space;
MD – macula densa; PL -
parietal layer; G – glomerulus.
The outer parietal layer of a glomerular capsule consists of a simple squamous epithelium supported externally
by a basal lamina. At the tubular pole, this epithelium changes to the simple cuboidal epithelium that continues
and forms the proximal tubule.
 Podocytes
The visceral layer of a renal corpuscle consists of epithelial cells podocytes, which together with the capillary
endothelial cells compose the apparatus for renal filtration. From the cell body of each podocyte several
primary processes extend. Each primary process gives rise to many parallel, interdigitating secondary processes
or pedicels. The pedicels cover the capillary surface. Between the interdigitating pedicels are elongated spaces,
or filtration slit pores, 25 to 30 nm wide. Spanning adjacent pedicels and bridging the slit pores are zipper-like
slit diaphragms. Slit diaphragms are modified occluding junction composed of nephrins, other proteins,
glycoproteins, and proteoglycans. The polyanionic glycoproteins and proteoglycans interact to form a series of
openings within the slit diaphragm, with a surface that is negatively charged.
SEM
 1. Endothelium, which blocks blood cells and platelets; Filtration barrier
2. Basement membrane, which restricts large proteins and some organic anions.
3. Slit diaphragms between pedicels, which restrict some small proteins and organic anions.
TEM Between the endothelial cells and the
podocytes is the thick (300-360 nm)
glomerular basement membrane. This
membrane forms by fusion of the
capillary- and podocyte-produced basal
laminae. Laminin and fibronectin in
this fused basement membrane bind
integrins of both cell membranes, and
the meshwork of cross-linked type IV
collagen and large proteoglycans
restricts passage of proteins larger than
about 70 kDa.
C – capillary; CS – capsular space; PC – podocyte;
E – endothelium; P – pedicels; FS - filtration slits;
F - fenestrations; SD - slit diaphragms; BM -
basement membrane.
Smaller proteins that are filtered from plasma are degraded, and the amino acids reabsorbed in the proximal
tubule. Polyanionic GAGs in the glomerular membrane are abundant and their negative charges, like those of
the slit diaphragms, tend to restrict filtration of organic anions.
Mesangial cell
Renal corpuscles also contain
mesangial cells, most of which
resemble vascular pericytes in
having contractile properties and
producing components of an
external lamina. Mesangial cells are
difficult to distinguish in routine
sections from podocytes, but often
stain more darkly. They and their
surrounding matrix comprise the
mesangium, which fills interstices
between capillaries.
 Functions of the mesangium:
TEM ■ Physical support of capillaries within
the glomerulus;
■ Adjusted contractions in response to
blood pressure changes, which help
maintain an optimal filtration rate;
■ Phagocytosis of protein aggregates
adhering to the glomerular filter.
■ Secretion of several cytokines,
prostaglandins, and other
factors important for immune defense
and repair in the glomerulus.

C – capillary; CS – capsular space; P – podocyte; EC – endothelial cell; L – lymphocyte;

PD – pedicels; US – urinary space; BM - basement membrane; MC – mesangial cell; MM – mesangial matrix.
 Proximal Convoluted Tubule
At the tubular pole of the renal corpuscle, the simple
squamous epithelium of the capsule’s parietal layer is
continuous with the simple cuboidal epithelium of the proximal
convoluted tubule (PCT). These long tubules fill most of the
cortex. PCT cells are specialized for both reabsorption and
secretion.
Over half of the water and electrolytes, and all of the organic
nutrients (glucose, amino acids, vitamins, etc), filtered from
plasma are normally reabsorbed in the PCT. These molecules are
transferred directly across the tubular wall (transcellular and
paracellular transport) for immediate uptake again into the
plasma of the peritubular capillaries.
Small proteins in the filtrate are either reabsorbed by
receptor-mediated endocytosis and degraded in the cuboidal
cells, or degraded by peptidases on the luminal surface.
P – proximal convoluted tubule; D - distal convoluted tubule; G –
glomerulus; U – urinary space; TP – tubular pole. (H&E)

PT staining
The cells have central nuclei and very acidophilic
cytoplasm, because of the abundant mitochondria. The
cell apex has long microvilli that form a prominent
brush border. Because the cells are large, each
transverse section of a PCT typically contains only three
to five nuclei.
Ultrastructurally the apical cytoplasm of these cells
has numerous pits and vesicles near the bases of the
microvilli, indicating active endocytosis and
pinocytosis.
TEM
MV – microvilli;
M – mitochondria;
L – lysosomes;
V - endocytosis vesicle;
F – fibroblast;
C – capillary.
Proximal tubular cells also have many long basal plasma
membrane invaginations (basal striation) and lateral
interdigitations with neighboring cells. Along the basal
invaginations long mitochondria are concentrated supply
ATP locally.
Organic anions and cations not filtered in the renal
corpuscle (because of the polyanions in the filter or binding
to plasma proteins) may be released in the peritubular
capillaries, taken up by the cells of the proximal
tubules and undergo secretion into the filtrate.
Henle's Loop
The PCT continues with the tubule that
enters the medulla and continues the
nephron’s loop of Henle. This is a U-shaped
structure with a thin and thick descending
limbs and a thin and thick ascending limbs.
The thick limbs are very similar in structure
to the distal convoluted tubule It has an
outer diameter of about 60 μm, but it thin
part to about 30 μm. The wall of the thin
segments consists only of squamous cells
and the lumen is prominent. Juxtamedullary
nephrons, however, are of prime
importance in establishing the gradient of
hypertonicity in the medullary interstitium,
he basis of the kidneys' ability to produce
hypertonic urine.
1 2
1. Cross section of medulla (Mallory trichrome, x 40). 2. TEM.
T – thin limbs; A – thick limbs; CD – collecting ducts; C – vasa
recta capillary; I – interstitium.

Kidney cortex (H&E).
p – proximal convoluted tubule; d - distal convoluted tubule.
Distal Convoluted Tubule
The ascending limb of the nephron is straight as
it enters the cortex and forms the macula densa,
and then becomes tortuous as the distal
convoluted tubule (DCT). Much less tubular
reabsorption occurs here than in the proximal
tubule. The simple cuboidal cells of the distal
tubules differ from those of the proximal tubules
in being smaller and having no brush border
and more empty lumens. Because of these
differences more nuclei are typically seen in
sections of distal tubules than in those of
proximal tubules. Cells of the DCT also have
fewer mitochondria than cells of proximal
tubules, making them less acidophilic. The rate
of Na+ absorption here is regulated by
aldosterone from the adrenal glands.
Where the initial, straight part of the distal tubule contacts the
afferent arterioles of its parent nephron, its cells become more
columnar and closely packed, forming the macula densa (L.
thicker spot). Cells of the macula densa typically have apical
nuclei, basal Golgi complexes, and a more complex and varied
system of ion channels and transporters.

Picrosirius-hematoxylin - macula

Adjacent to the macula densa, the tunica media of the

afferent arteriole is also modified. The smooth muscle
cells are modified as juxtaglomerular granular (JG)
cells, with a secretory phenotype including more
rounded nuclei, rough ER, Golgi complexes, and
zymogen granules with renin. Also at the vascular pole
are lacis cells, which are extraglomerular mesangial
cells that have many of the same supportive,
contractile and defensive functions as these cells inside
the glomerulus.
All these cells are part of a specialized sensory structure, the juxtaglomerular apparatus (JGA) that utilizes
feedback mechanisms to regulate glomerular blood flow and keep the rate of glomerular filtration relatively
constant.
 Collecting Ducts
Kidney medulla (H&E).
cd – collecting ducts; dt - distal convoluted tubules.
The last part of each nephron, the connecting
tubule, carries the filtrate into a collecting
system that transports it to a minor calyx. A
connecting tubule join together in the cortical
medullary rays to form collecting ducts of
simple cuboidal epithelium (diameter 40 μm).
In the outer medulla these merge further as
larger, straight collecting ducts (of Bellini),
which run to the tips of the medullary
pyramids with increasingly columnar cells
and overall diameters reaching 200 μm. In the
apex of the pyramid, several collecting ducts
merge further as a papillary duct which
delivers urine to the minor calyx.

Running parallel with the descending and ascending limbs of the loops of Henle and vasa recta, medullary
collecting ducts lie in the area with very high interstitial osmolarity.

Antidiuretic hormone (ADH, Vasopressin),
released from the pituitary gland as the body
becomes dehydrated, makes collecting ducts
more permeable to water and increases the rate at membranous cytoplasmic vesicles.
which water molecules are pulled osmotically
from the filtrate. Upon binding, ADH receptors
on the basolateral cell surface stimulate the
movement and insertion of vesicles with
aquaporins into the apical (luminal)
membranes, increasing the number of
membrane channels and water movement
through the cells.
Collecting ducts are composed mainly of pale-staining
principal cells with few organelles, sparse microvilli,
and unusually distinct cell boundaries. Ultrastructurally
the principal cells can be seen to have basal membrane
infoldings, consistent with their role in ion transport,
and a primary cilium among the microvilli. The
medullary collecting ducts are the final site of water
reabsorption from the filtrate. Principal cells are
particularly rich in aquaporins, the integral membrane
pore proteins that function as specific channels for water
molecules, but here most aquaporins are sequestered in
Scattered among the principal cells are variably
darker intercalated cells, or IC cells, with more
abundant mitochondria and projecting apical folds.
Intercalated cells, a few of which also occur in the DCTs,
help maintain acid-base balance by secreting either H+
or HCO3−.
The urinary passages
Urine is transported by the ureters from
the renal pelvis to the urinary bladder
where it is stored until emptying by
urination via the urethra. The calyces,
renal pelvis, ureter, and bladder have
somewhat similar histologic structure,
with the walls becoming gradually
thicker closer to the bladder.
Wall of urinary passages consist of
mucosa, no well seen muscularis mucosa,
submucosa, muscularis externa and
external (adventitia or some part with
serosa) layers.
 Urothelium
The mucosa of these organs is lined by the unique stratified transitional epithelium or
urothelium cells of which are organized as three layers:
■ A single layer of small basal cells resting on a very thin basement membrane;
■ An intermediate region containing from one to several layers of more columnar cells;
■ A superficial layer of very large, bulbous cells called umbrella cells that are occasionally
bi- or multinucleated and are highly differentiated to protect underlying cells against the
cytotoxic effects of hypertonic urine.
Umbrella cell
 Umbrella cells
Umbrella cell

The transitional epithelium of the bladder in the

undistended state is five or six cells in thickness;
the superficial cells are rounded and bulge into
the lumen. When the epithelium is stretched, as
when the bladder is full of urine, the epithelium
is only three or four cells in thickness, the result
of the intermediate cells being pushed and
pulled laterally and the superficial cells become
squamous.

Umbrella cells are especially well developed in the bladder where contact with urine is
greatest. These cells, up to 100 μm in diameter, have extensive intercellular junctional
complexes surrounding unique apical membranes.
 Walls of urinary passages
The lamina propria (loose connective tissue)
of mucosa continues in dense irregular
connective tissue of submucosa, and are
highly vascularized. It is followed by a dense
sheath of interwoven smooth muscle layers.
Urine is moved from the renal pelvises to the
bladder by peristaltic contractions of the
ureters. The muscular layers in the calyces,
renal pelvis, and ureters have a helical
arrangement. As the ureteral muscle cells
reach the bladder, they become longitudinal.

Bladder wall (H&E). U – urothelium; LP – lamina propria; S – submucosa -dens connective tissue;
IL, ML, OL - inner, middle, and outer layers of smooth muscle; A – adventitia.
 Renal calyx

Collecting ducts

All the urinary passages are

covered externally by an
adventitial layer, except for the
upper part of the bladder that is
covered by serous peritoneum.

Interstitium of medulla
 Ureter
H&E Lamina propria,
submucosa

Adventitia

Length 15 cm, diameter – 5 mm. Muscular has helical arrangement, but can distinguish two layer -
inner longitudinal and outer circular.
 Bladder end Urethra The muscularis of the bladder consists of three poorly
Serous delineated layers, collectively called the detrusor
peritoneum muscle, which contract to empty the bladder. Three
muscular layers are seen most distinctly at the neck
of the bladder near the urethra. The ureters pass
through the wall of the bladder obliquely, forming a
valve that prevents the backflow of urine into the
ureters as the bladder fills.
Muscularis: the internal longitudinal layer,
becomes circular around the prostatic
urethra and the prostatic parenchyma in
men. Its fibers form the true involuntary
internal urethral sphincter.
The middle layer ends at the bladder neck, and the outer longitudinal layer continues to the end of the
prostate in men and to the external urethral meatus in women. The female urethra is a tube 4-5 cm
long, lined initially with transitional epithelium with stratified squamous epithelium and some areas
of pseudostratified columnar epithelium. The mid part of the female urethra is surrounded by an
external striated voluntary sphincter.
 Male Urethra

The urethra is a tube that carries the urine from the bladder to the exterior. The urethral mucosa
has prominent longitudinal folds, giving it a distinctive appearance in cross section. In men, the
two ducts for sperm transport during ejaculation join the urethra at the prostate gland. The male
urethra is longer and consists of three segments:
■ The prostatic urethra, 3 to 4 cm long, extends through the prostate gland and is lined by
urothelium.
■ The membranous urethra, a short
segment, passes through an external
sphincter of striated muscle lined by
stratified columnar and
pseudostratified epithelium.
■ The spongy urethra, about 15 cm in
length, is lined by stratified columnar
and pseudostratified columnar
epithelium with stratified squamous
epithelium distally.