Chapter 17
There’s A Lot to Making Pee Pee
The urinary system in a nutshell—not a lot of anatomy but lots of physiology. Those little ole
kidneys may look simple but they are packed with complex systems for making urine. This
system can be the downfall of many a student, at least if they don’t get the big picture first.
Anatomy of the Urinary System (Fig. 17.1)
Hey, how hard can it be? Kidneys, ureters, urinary bladder, urethra and that’s it? Well, there’s a
bit more detail to go over. Let’s start with the kidneys.
The kidneys are bean shaped (you know, kidney beans) organs located behind the abdominal
cavity. We say they are retroperitoneal. The peritoneum is the membrane that lines the
abdominal cavity so they are behind the abdominal cavity (watch out for those kidney
punches).
They are located on the sides of the low back around the twelfth rib and extend to about the
third lumbar vertebra. The kidneys are surrounded by fat (perirenal fat) and a tough fibrous
membrane (renal capsule).
If we look inside we will see two major divisions. The outer portion is called the renal cortex
and the inner portion is called the medulla. Some cortical tissue extends into the medulla (renal
columns). The medulla contains triangular structures called renal pyramids (where’s the
Pharoh?). At the tip of each pyramid is a structure called the renal papilla. Urine drains from the
renal papilla to the minor and major calyces to the renal pelvis and finally to the ureter.
Blood enters the kidney at a dent called the renal hilus. The renal artery brings blood in and the
renal vein brings it out. The renal artery branches upon entering the kidney. The branches
include:
Renal artery—segmental—interlobar—arcuate—interlobular
If you need to memorize these branches use the following mnemonic:
Read Several Interesting Articles Indeed
Fig. 17.1. Urinary system.
Fig. 17.2. Kidney.
1. Renal pyramid 2. Interlobular artery 3. Renal artery 4. Renal vein 5. Renal hilum 6. Renal pelvis 7.
Ureter 8. Minor calyx 9. Renal capsule 10. Inferior border 11. Superior border 12. Interlobar vein 13.
Nephron 14. Renal sinus 15. Major calyx 16. Renal papilla [Link] column
Getting down to the microscopic structures we see one all-important structure in the kidney.
This is the nephron which is the structure that makes urine (Fig. 17.3). There are around one
million nephrons in one kidney and they do a great job making urine. Some nephrons lie near
the medulla and are called juxtamedullary nephrons. These nephrons extend deep into the
medulla. Other nephrons reside in the cortex and only minimally extend into the medulla.
These are known as cortical nephrons.
The afferent arteriole brings blood to the nephron and the efferent arteriole brings blood out.
Between the afferent and efferent arterioles is a tuft of capillaries called the glomerulus. The
glomerulus is surrounded by a fibrous capsule called the glomerular capsule (Bowman’s
capsule). The glomerular capsule connects with the proximal convoluted tubule which connects
with the nephron loop (loop of Henle). The nephron loop connects with the distal convoluted
tubule which in turn connects with the collecting duct which transports urine to the renal
papilla.
The ureters carry the urine from the kidney to the bladder. The ureters have a smooth muscle
layer that is capable of producing peristaltic contractions that occur once every two to three
minutes. The parasympathetic nervous system increases these contractions and the
sympathetic nervous system inhibits them.
The urinary bladder is a hollow organ that resides in the pelvic cavity (Fig. 17.4). The area on the
inside of the bladder between the two ureter connections and the urethra is called the trigone.
The urinary bladder and ureters are internally lined with transitional epithelium. The bladder
also has a thick smooth muscle layer sometimes called the detrusor muscle. Contraction of the
detrusor muscle increases the internal pressure of the bladder and causes urine to be expelled.
Male bladders contain an area of smooth muscle and elastic tissue called the internal urinary
sphincter. This area is not present in females. The function of this structure is to keep semen
from entering the urinary bladder during intercourse. Both males and females have an external
urinary sphincter located in the urethra that controls the flow of urine.
The male urethra consists of three parts. The prostatic urethra exits the bladder and extends to
the inferior prostate gland. It then becomes the membranous urethra until it enters the penis
where it becomes the penile urethra.
Fig. 17.3. Nephron.
1. Glomerulus, 2. Efferent arteriole, 3. Bowman's capsule, 4. Proximal tube, 5. Cortical collecting tube, 6.
Distal tube, 7. Loop of Henle, 8. Collecting duct, 9. Peritubular capillaries, 10. Arcuate vein, 11. Arcuate
artery, 12. Afferent arteriole, 13. Juxtaglomerular apparatus.
Fig. 17.4. Urinary bladder.
Urinary Physiology
The Big Picture: Urinary Physiology
There are 3 primary processes of urine formation:
1. Filtration
2. Tubular reabsorption (move stuff from kidney to blood)
3. Tubular secretion (move stuff from blood to kidney)
So we have a good idea of how the system is put together so now it’s time to get into some of
that physiology I told you about earlier.
We can gain a good deal of insight into how the kidneys work by examining the inputs and
outputs. Blood flows into the kidney and urine and blood flow out. So the kidneys must
somehow make urine from blood. The blood enters via the renal artery and exits via the renal
vein. The urine exits by way of the ureters and flows to the bladder, urethra, and out of the
body.
One of the simplest ways to make urine from blood is to filter the blood. This is actually the first
stage of urine formation (filtration). Filters work by the movement of substances from areas of
higher to lower pressure across a filtration membrane. The filtration membrane sorts
substances based on size. You could think of it as being filled with holes. Smaller substances
pass through the holes while larger substances do not. Smaller substances that are filtered
include water, electrolytes and glucose.
There would be a problem if filtration were the only mechanism of urine formation. Our bodies
need many of the filtered substances and they would be lost in the urine. So there must be
some other mechanisms that help to maintain the balance. Fortunately there are and these
include tubular reabsorption and secretion.
Tubular reabsorption and secretion work together to reclaim substances like water, glucose and
electrolytes after they have been filtered. Tubular reabsorption employs a number of
mechanisms in order to move filtered substances back into the blood. Tubular secretion also
uses a number of mechanisms to move substances from the blood to the urine. Besides
reclaiming filtered substances, both of these processes fine tune electrolyte, water and pH
balance.
Besides maintaining fluid, electrolyte and pH balance, the kidneys monitor blood oxygen levels.
They secrete the hormone erythropoietin in response to low oxygen levels. The hormone
travels to the bone marrow to stimulate the production of red blood cells. The kidneys also
work to control vitamin D synthesis.
Urine Formation Process #1: Filtration
The kidneys make a heck of a lot of filtrate each day. They typically produce about 123 ml of
filtrate per minute which adds up to about 180 liters per day. If all of this filtrate ended up as
urine you would spend your days in the bathroom and drinking water! Fortunately most of that
filtrate is reabsorbed leaving around one to two liters of urine per day (which allows you some
time away from the bathroom).
In order to move substances through the filter there must be a pressure gradient (oh no, here
we go again). Substances must move from an area of higher pressure to lower pressure. The
pressure gradient is called filtration pressure or net filtration pressure. Net filtration pressure is
directly proportional to the glomerular filtration rate. So if for some reason net filtration
increases or decreases, so does glomerular filtration rate, and so does the amount of filtrate
produced.
Net filtration pressure is the combination of a series of pressures that exist in the renal
corpuscle. These include glomerular capillary hydrostatic pressure, glomerular capsular
hydrostatic pressure and colloid osmotic pressure.
Glomerular capillary hydrostatic pressure is the blood pressure inside the capillaries. It is
usually about 50 mm Hg and must be greater that the pressure inside the glomerular capsule
known as glomerular capsular hydrostatic pressure. This one is the main pressure and must be
greater than the total of the other pressures in order for the filter to work.
The glomerular capillary hydrostatic pressure is controlled in part by the diameter of the
afferent and efferent arterioles. The efferent arterioles have a smaller diameter than the
afferent arterioles. The smaller diameter works to decrease blood flow through the efferent
arterioles increasing the pressure inside the glomerular capillaries. Changing the diameter of
the afferent and efferent arterioles changes the glomerular capillary hydrostatic pressure. For
example, increasing the diameter of the afferent arteriole or decreasing the diameter of the
efferent arteriole increases the capillary pressure.
The pressure inside the glomerular capsule is called the glomerular capsular hydrostatic
pressure. This pressure is created by fluid inside the capsule as well as downstream in the
tubules. It is usually about 10 mm Hg. The glomerular capsular hydrostatic pressure works
against filtration.
Colloid osmotic pressure is produced by the presence of plasma proteins in the blood called
colloids. The colloids produce a pulling force causing water to move back into the glomerular
capillaries. This pressure is usually about 30 mm Hg (Fig. 17.5).
We can calculate the net filtration pressure by the following:
Net Filtration Pressure = Glomerular capillary hydrostatic pressure – Glomerular capsular
hydrostatic pressure – Colloid osmotic pressure
If we plug in the normal values:
NFP = 50 mm Hg – 10 mm Hg – 30 mm Hg
NFP = 10 mm Hg
So the net filtration pressure is about 10 mm Hg.
The kidneys are constantly working to keep the amount of filtrate relatively constant despite
changes in mean arterial pressure. For example as systemic blood pressure increases the
afferent arterioles vasoconstrict keeping the glomerular capillary hydrostatic pressure constant.
Likewise when blood pressure decreases the afferent arteriole dilates.
The sympathetic nervous system affects the afferent arteriole by causing it to vasoconstrict
under intense sympathetic activity such as when exercising strenuously or when in shock.
Fig. 17.5. Glomerular filtration. 1. Glomerular capillary hydrostatic pressure. 2. Glomerular
capsular hydrostatic pressure. 3. Colloid osmotic pressure
Urine Formation Process #2: Tubular Reabsorption
During filtration substances were just sorted based on size. This means that lots of stuff moves
through the filter that our bodies need, like glucose and water for example. There must be
some other process that works to reclaim these important substances. There is and it’s called
tubular reabsorption (Figs.17.6-17.12).
One important thing to remember is that in tubular reabsorption substances move from the
tubule to the blood.
Substances move by various ways in tubular reabsorption and we will cover a few.
Symporters
Big Picture: Symporters
Symporters are like mooching friends.
Some cells lining the kidney tubules contain special transport proteins called symporters. To
describe the action of symporters I like to use my analogy of the mooching friend. Let’s say my
friend and I went to the movies. When it came time to pay my friend stated that he forgot his
wallet and asked if I could “spot” him some money to get in. So I provided the energy (money)
to get into the movie. My friend (who needs friends like him) just went along for the ride.
This is how the sodium glucose symporter works. Sodium provides the energy in the form of a
gradient. There’s lots of sodium coming out of the filter and moving into the tubules compared
to inside the cells lining the tubules. So sodium moves through the transport protein and
glucose (the mooching friend) goes along for the ride (Fig. 17.6).
So, what would happen if lots and lots of glucose was produced by the filter and moved into the
tubules? Well, the amount of glucose would exceed the number of symporters. This would
cause glucose to flow into the urine and out of the body in a condition called glucosuria. This
happens in diabetes.
Other substances are transported back into tubular cells via symporters. These include amino
acids and vitamins.
Fig. 17.6. Sodium-glucose symporter.
Fig. 17.7. The sodium-potassium pump has a role in tubular reabsorption. Amino acids also
move from tubule to blood via symporters.
Passive Movement of Substances
Other substances move passively from the tubules to the blood. Sodium is again one of these as
well as calcium, magnesium, potassium. Since so much sodium moves into the interstitium
surrounding the tubules water also follows sodium via good ole osmosis. This is how much of
the water is reabsorbed (Fig. 17.8).
Fig. 17.8. Some electrolytes are reabsorbed via diffusion.
Urine Formation Process #3 Tubular Secretion
Tubular secretion involves moving substances from the blood to the tubules. Unlike tubular
reabsorption that moves substances in order to maintain fluid and electrolyte balance, tubular
secretion primarily works to eliminate toxic substances or byproducts of metabolism.
Antiporters
Big Picture: Antiporters
Antiporters are like revolving doors.
Tubular secretion can involve active or passive transport. An example of passive transport is the
sodium hydrogen antiporter. This transport protein uses the sodium gradient to move sodium
from the tubule to inside the cell while at the same time moving excess hydrogen ions out of
the cell and into the tubule.
In describing the antiporter I like to use the analogy of the revolving door. Let’s say that I am
staying in one of those fancy hotels with a big revolving door. I enter the door and push on the
glass to move the door. At the same time someone is exiting the hotel and moves through the
door going in the opposite direction and not pushing at all. I am providing the energy while the
other person moves in the opposite direction getting a free ride. In the case of the antiporter,
sodium provides the energy in the form of a gradient while hydrogen goes along for the ride
(Fig. 17.9).
Other examples of secreted substances include ammonia, potassium, penicillin, and para-
aminohippuric acid. These substances are not normally produced in the body.
Aldosterone
Big Picture: Aldosterone
Aldosterone tells the kidneys to ‘hang on’ to sodium.
Certain tubule cells are “leaky” to sodium and potassium. In other words when aldosterone
attaches to receptors on these cells it increases their permeability to sodium and potassium. So,
aldosterone causes more sodium to be reabsorbed, while at the same time causing potassium
to be secreted (Fig. 17.10).
Atrial Natriuretic Hormone
Big Picture: Atrial Natriuretic Hormone (ANH)
ANH tells the kidneys to ‘get rid’ of sodium.
Atrial Natriuretic Hormone (ANH) is secreted by the wall of the right atrium in the heart in
response to atrial stretch. ANH has the opposite action of aldosterone and inhibits sodium and
water reabsorption in the kidney tubules.
Bicarbonate Reabsorption
Big Picture: Bicarbonate Reabsorption
Bicarbonate is reabsorbed
Yes, it sounds pretty simple. Bicarbonate ions do move from the kidney tubules to the blood.
However, there are a few steps along the way that make it seem complicated.
So, here we go with good ole bicarbonate reabsorption. Remember that hydrogen is secreted
into the tubule by way of the sodium-hydrogen antiporter. Hydrogen runs into bicarbonate ions
to form carbonic acid. The carbonic acid dissociates into carbon dioxide and water (remember
this from the respiratory system?). The carbon dioxide then diffuses into cells lining the lumen
of the tubule and combines with water in the presence of carbonic anhydrase to form carbonic
acid (again). The carbonic acid once again dissociates into hydrogen and bicarbonate ions. The
hydrogen gets antiported back out to keep the process looping while the bicarbonate moves
out of the cell and into the blood and viola! Reabsorption!
Fig. 17.9. Sodium-hydrogen antiporter.
Fig. 17.10. Aldosterone increases tubular reabsorption of sodium and tubular secretion of
potassium.
Urea
Urea flows through the nephron loop, distal convoluted tubule and collecting duct. The
collecting duct is permeable to urea so some flows back into the medulla. Some urea makes its
way back to the descending limb of the nephron loop which is also permeable to urea allowing
urea to flow in. This creates a cycle of sorts that helps to maintain the high medullary
concentration gradient.
The Juxtaglomerular Apparatus
Big Picture: Juxtaglomerular Apparatus (JG apparatus)
The JG apparatus helps to control blood pressure and the amount of urine produced.
The juxtaglomerular apparatus is a group of cells residing at the junction of the afferent
arteriole and distal ascending limb of the nephron loop (Fig. 17.13). The juxtaglomerular
apparatus consists of two different types of cells. Juxtaglomerular cells are located on the
afferent arteriole side
So in a nutshell, the juxtaglomerular cells monitor blood pressure. When blood pressure
decreases the cells secrete something that will increase it. That something is renin. Renin then
triggers the renin-angiotensin system. The end result is the formation of a substance called
angiotensin II. Angiotensin II promotes vasoconstriction (which raises blood pressure) and
secretion of the adrenal cortex hormone aldosterone. Aldosterone promotes sodium
reabsorption and since water follows salt (osmosis again) we get fluid retention which also
raises blood pressure.
The other cells in the juxtaglomerular apparatus are the macula densa cells. These babies
monitor the filtrate in the kidney tubule. Usually they keep the afferent arteriole open by
secreting nitric oxide synthetase secretion which promotes nitric oxide secretion (a
vasodilator), but if too much filtrate is produced (oops, we’re making too much urine) nitric
oxide synthetase secretion is inhibited. The cells also secrete adenosine which promotes
vasoconstriction of the afferent arteriole. The vasoconstriction of the afferent arteriole causes a
subsequent decrease in the production of filtrate.
This one works like one of those lawn sprinklers. The water source is the hose (afferent
arteriole). If there is too much water flowing out of the sprinkler we could step on the hose
(vasoconstrict) to decrease the flow.
Fig. 17.13. Juxtaglomerular apparatus. . Juxtaglomerular apparatus. The juxtaglomerular cells
secrete renin while the macula densa cells secrete nitric oxide.
The Nephron Loop
Big Picture: Nephron Loop
The nephron loop contains two parts. These are the descending and ascending limbs.
In the descending limb water moves out but salt stays in (concentration increases).
In the ascending limb salt is pumped out and water stays in (concentration decreases).
The nephron loop consists of two segments including a descending and ascending limb each
with different characteristics (Fig. 17.14).
The descending limb contains a thin layer of epithelium that is more permeable to water than
the thick portion of the ascending limb. An isotonic fluid (about 300 mOsm) enters the
descending limb. As it progresses down the limb, water diffuses into the interstitium causing
the concentration to dramatically increase. The fluid concentration can increase to as high as
1200 mOsm (very hypertonic).
The thick segment of the ascending limb inhibits the passage of water by diffusion and contains
a series of active transport proteins that selectively move substances. Sodium and chloride are
moved out of the ascending limb and into the interstitium by way of these active transport
proteins. As fluid moves up the ascending limb the concentration decreases. A 100 mOsm
hypotonic solution exits the ascending limb and enters the distal convoluted tubule.
The countercurrent consists of the “current” of water moving in one direction and the “current”
of sodium chloride moving in the opposite direction. The high “salt” gradient is maintained by
the active transport of sodium and chloride in the ascending limb. Urea also diffuses into the
descending limb adding to the increased concentration.
Fig. 17.14. Nephron loop.
Antidiuretic Hormone (ADH)
Big Picture: Antidiuretic hormone (ADH)
ADH causes water retention by increasing permeability in the distal convoluted tubule.
ADH is secreted by the posterior pituitary gland in response to an increase in blood solute
concentration as senses by osmoreceptors in the hypothalamus (remember the endocrine
chapter?). ADH targets the kidney, particularly the distal convoluted tubule.
ADH affects the distal convoluted tubule by making it more permeable to water by increasing
the appearance of aquaporins (water channels). Remember that the fluid exiting the nephron
loop is hypotonic. The hypotonic fluid enters the distal convoluted tubule that is surrounded by
the interstitium and peritubular capillaries which are isotonic. If the tubule is impermeable to
water then dilute urine is produced. If the tubule is made more permeable to water, then water
moves to the more highly concentrated interstitium and blood. ADH then plays an important
role in maintaining fluid balance.
Urine Composition
Adults produce about one to two liters of urine daily. Pathologies such as diabetes or some
medications can produce a larger urine output known as polyuria. A urine output of less than
500 ml/day is known as oliguria and an output less than 100 ml is known as anuria.
Urine is the final product of the kidney. It is mostly water (95%) with a few other solutes
including nitrogenous wastes, electrolytes, pigments, and toxins. It can also contain abnormal
substances including glucose, albumin, bile and acetone.
Urine is usually clear or straw colored. An abnormal color may indicate presence of blood, bile,
bacteria, drugs, food pigments, or high-solute concentration. Urine will become cloudy after
standing due to a buildup of bacteria. Pus from problems such as kidney infections will also
make urine cloudy.
Urine has a slight odor. It will develop an ammonia odor after standing due the breakdown of
urea. An acetone odor may indicate diabetes. The pH of urine varies between 4.6 and 8.0. The
specific gravity is between 1.001 and 1.035.
Micturition (Peeing)
Urine continuously flows from the kidney to the bladder. The bladder acts as a storage reservoir
for urine and can store up to one liter. At about 300 ml the urge to urinate becomes evident.
Once the wall is stretched the micturition reflex is stimulated. Stretch of the bladder sends
impulses to sensory neurons in the pelvic nerves to the sacral segments of the spinal cord.
Micturition is under parasympathetic control and parasympathetic impulses cause the bladder
to contract. The motor impulses for micturition originate in a micturition center in the pons.
The center also receives input from the cerebral cortex (so one can decide whether or not to
micturate). Contraction of the bladder increases the internal pressure pushing urine into the
urethra.
The micturition reflex is an involuntary reflex in infants. Voluntary control of the reflex does not
occur until around age 2-3 years.
Renal Clearance
Big Picture: Renal Clearance
Renal clearance represents how much blood has to pass though the kidney to completely
remove a substance.
Renal clearance is used to determine kidney function. Renal clearance is the volume of blood
plasma from which a substance is completely removed in one minute. Renal clearance reflects
the three processes of urine formation which include glomerular filtration, tubular reabsorption
and tubular secretion. We can use an indirect method to determine renal clearance that
includes the rate of urine output and the concentration of the substance in blood plasma and
urine.
For example let’s say we are determining the renal clearance for a substance ‘X’. We know the
concentration of X in the urine is 5.0 mg/ml and the concentration of X is .3 mg/ml in the
plasma. We also know the rate of urine output equals 2 ml/min. The renal clearance can be
determined by the following:
Renal Clearance (C) = UV/P
U = concentration of substance in urine
V = rate of urine output
P= concentration of substance in plasma
For our example:
C = (5.0)(2)/.3
C = 33.33 ml/minute
This can be interpreted as 33.33 ml of blood plasma is cleared of substance X every minute.
Image Credits
Chapter 17
17.1 From: [Link]
17.2 From: [Link]
17.3 From: [Link] Author: Burton Radons
17.4 From: [Link]
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