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The human being is truly a remarkable organism. Did you know that on
average your bone marrow secretes into circulation about 2 million red blood
cells per second. That means that the spleen has to disassemble about 2
million red cells per second. The average human being has about 80,000 to
140,000 heart beats per day and will have about 25,000 to 32,000 breaths
per day. You lose about 1 million skin cells every time you shower. An
average person with normal kidney function will have 140 to 180 liters of
blood flow through their kidneys per day to get cleansed. Out of this you
will make 1 to 3 lilters of urine per day.
The kidneys are remarkable also. They perform
many different functions for your body. They cleanse the blood of metabolic
byproducts and impurities and eliminate drugs and other compounds from the
blood. They help maintain the blood pressure and manage your fluid balance.
They also help manage your electrolytes and make hormones that help regulate
your blood volume and absorb calcium from your diet and maintain bone
health.
Most people have two kidneys located in
your back under the diaphragm (your breathing muscle). Every time that you
breathe your kidneys move up and down. Some people may be born with only one
kidney (solitary kidney) and some people may have kidneys joined at the
bottom (horseshoe kidneys).
Each kidney is fed by a large renal artery
that branches off of the abdominal aorta. The blood enters the
kidney to get cleansed and to also nourish the kidney. The cleansed blood is
carried out of the kidney and back into circulation by the renal vein.
Each kidney has about 1 million filtering
units called nephrons. Each nephron is made up of an afferent arteriole
carrying blood into the glomerulus to get rinsed and an efferent arteriole
carrying the cleansed blood out of the glomerulus (the actual filtering
unit). The filtered blood is carried by the efferent arteriole to the vasa
recta capillaries that feed the loop of henle cells. The cleansed blood is
then carried back to central circulation.
Scanning colorized electron micrograph of
the glomerulus.
The capillary in the glomerulus is
permeable and allows certain items to be filtered out of the blood into the
capsular space making urine. The urine is carried out of the glomerulus by
the proximal convoluted tubule (4,1 and 2 above) into the loop of henle and
then into the renal pelvis (E above) where it drains into the ureter and
then into the bladder where it is stored.
If you look closely at the cortex and
medulla, you can see many tiny, tubular structures that stretch across both
regions perpendicular to the surface of the kidney. In each kidney, there
are one million of these structures, called nephrons. The nephron is the
basic unit of the kidney. It is a long thin tube that is closed at one end,
has two twisted regions interspaced with a long hair-pin loop, ends in a
long straight portion and is surrounded by capillaries.
The parts of the nephron are as follows:
Bowman's capsule - This closed end at the beginning of
the nephron is located in the cortex.
Proximal convoluted tubule or proximal tubule - The first twisted region
after the Bowman's capsule; it is in the cortex.
Loop of Henle - A long, hairpin loop after the proximal tubule, it extends
from the cortex down into the medulla and back.
Distal convoluted tubule or distal tubule - This second twisted portion of
the nephron after the loop of Henle is located in the cortex.
Collecting duct - This long straight portion after the distal tubule that is
the open end of the nephron extends from the cortex down through the
medulla.
Each part of the nephron has different types of cells with different
properties -- this is important in understanding how the kidney regulates
the composition of the blood.
The nephron has a unique blood supply compared to other organs:
Afferent arteriole - connects the renal artery with
the glomerular capillaries
Glomerular capillaries - coiled capillaries that are inside the Bowman's
capsule
Efferent arteriole - connects the glomerular capillaries with the
peritubular capillaries
Peritubular capillaries - located after the glomerular capillaries and
surrounding the proximal tubule, loop of Henle, and distal tubule
Interlobular veins - drain the peritubular capillaries into the renal vein.
The kidney is the only organ of the body in which two capillary beds, in
series, connect arteries with veins. This arrangement is important for
maintaining a constant blood flow through and around the nephron despite
fluctuations in systemic blood pressure.
Regulating the composition of the blood involves the following:
> Keeping the concentrations of various ions and other important substances
constant
> Keeping the volume of water in your body constant
> Removing wastes from your body
> Keeping the acid/base concentration of your blood constant
The kidney does this by a combination of three processes:
It filters 20 percent of the plasma and non-cell elements from the blood
into the inside of the nephron (the lumen).
It reabsorbs the components that the body needs from the lumen back into the
blood.
It secretes some unwanted components from the blood into the lumen of the
nephron.
Anything (fluid, ions, small molecules) that has not been reabsorbed from
the lumen gets swept away to form the urine, which ultimately leaves the
body. Through these processes, the blood is maintained with the proper
composition, and excess or unwanted substances are removed from the blood
into the urine.
Kidney
Processes: Filtration
The filtrate only includes small molecules and water. No red blood cells get
filtered. Therefore, no blood appears in the urine under normal conditions.
If you find blood in your urine, you should contact your physician as soon
as possible because it could be a sign of kidney problems.
In the nephron, approximately 20 percent of the blood gets filtered under
pressure through the walls of the glomerular capillaries and Bowman's
capsule. The filtrate is composed of water, ions (e.g. sodium, potassium,
chloride), glucose and small proteins (less than 30,000 daltons -- a dalton
is a unit of molecular weight). The rate of filtration is approximately 125
ml/min or 45 gallons (180 liters) each day. Considering that you have 7 to 8
liters of blood in your body, this means that your entire blood volume gets
filtered approximately 20 to 25 times each day! Also, the amount of any
substance that gets filtered is the product of the concentration of that
substance in the blood and the rate of filtration. So the higher the
concentration, the greater the amount filtered or the greater the filtration
rate, the more substance gets filtered.
Kidney Processes: Reabsorption
Once inside the lumen of the nephron, small molecules, such as ions, glucose
and amino acids, get reabsorbed from the filtrate:
Specialized proteins called transporters are located on the membranes of the
various cells of the nephron.
These transporters grab the small molecules from the filtrate as it flows by
them.
Each transporter grabs only one or two types of molecules. For example,
glucose is reabsorbed by a transporter that also grabs sodium.
Transporters are concentrated in different parts of the nephron. For
example, most of the Na transporters are located in the proximal tubule,
while fewer ones are spread out through other segments.
Some transporters require energy, usually in the form of adenosine
triphosphate (active transport), while others do not (passive transport).
Water gets reabsorbed passively by osmosis in response to the buildup of
reabsorbed Na in spaces between the cells that form the walls of the nephron.
Other molecules get reabsorbed passively when they are caught up in the flow
of water (solvent drag).
Reabsorption of most substances is related to the reabsorption of Na, either
directly, via sharing a transporter, or indirectly via solvent drag, which
is set up by the reabsorption of Na.
Two major factors affect the reabsorption process:
Concentration of small molecules in the filtrate - the higher the
concentration, the more molecules can be reabsorbed. Like our children in
the fish pond game, if you increase the number of fish in the stream, the
children will have an easier time catching them.
In the kidney, this is true only to a certain extent because:
There is only a fixed number of transporters for a given molecule present in
the nephron.
There is a limit to how many molecules the transporters can grab in a given
period of time.
Rate of flow of the filtrate - flow rate affects the time available for the
transporters to reabsorb molecules. As with our fish pond, if the stream
moves by slowly, the children will have more time to catch fish than if the
stream were moving faster.
To give you an idea of the quantity of reabsorption across the nephron,
let's look at the sodium ion (Na) as an example:
Proximal tubule - reabsorbs 65 percent of filtered Na. In addition, the
proximal tubule passively reabsorbs about 2/3 of water and most other
substances.
Loop of Henle - reabsorbs 25 percent of filtered Na.
Distal tubule - reabsorbs 8 percent of filtered Na.
Collecting duct - reabsorbs the remaining 2 percent only if the hormone
aldosterone is present.
Kidney
Processes Working Together
Some
substances are secreted from the plasma into the lumen by the cells of the
nephron. Examples of such substances are ammonia (NH3). As in reabsorption,
there are transporters on the cells that can move these specific substances
into the lumen.
Now let's put all of these processes -- filtration, reabsorption and
secretion -- together to understand how the kidneys maintain a constant
composition of the blood. Let's say that you decide to eat several bags of
salty (NaCl) potato chips at one sitting. The Na will be absorbed into your
blood by your intestines, increasing the concentration of Na in your blood.
The increased Na in the blood will be filtered into the nephron. While the
Na transporters will attempt to reabsorb all of the filtered Na, it is
likely that the amount will exceed their ability. Therefore, excess Na will
remain in the lumen; water will also remain, due to osmosis. The excess Na
will be excreted into the urine and eliminated from the body. So whether a
substance remains in the blood depends on the amount filtered into the
nephron and the amount reabsorbed or secreted by various transporters.
Let's look at an another example: Why do you have to keep taking repeated
doses of any given medicine? Well, once you take the medicine, it gets
absorbed by the intestine into the blood. The medicine in the blood acts on
its target cell and also gets filtered into the nephron. Most medicines do
not have transporters in the nephron to reabsorb them from the filtrate. In
fact, some transporters actively secrete medicines into the nephron.
Therefore, the medicine gets eliminated in the urine and you must take
another dosage later.
Kidneys: Maintaining Water Volume
Your kidneys have the ability to conserve or waste water. For example, if
you drink a large glass of water, you will find that you will have the urge
to urinate within an hour or so. In contrast, if you do not drink for a
while, such as overnight, you will not produce much urine and it will
usually be very concentrated (i.e. darker). How does your kidney know the
difference? The answer to this question involves two mechanisms:
The structure and transport properties of the loop of Henle in the nephron.
The anti-diuretic hormone (ADH), also called vasopressin, secreted by the
pituitary gland.
Loop of Henle
The loop of Henle has a descending limb and an ascending limb. As filtrate
moves down the loop of Henle, water is reabsorbed, but ions (Na,Cl) are not.
The removal of water serves to concentrate the Na and Cl in the lumen. Now,
as the filtrate moves up the other side (ascending limb), Na and Cl are
reabsorbed, but water is not. What these two transport properties do is set
up a concentration difference in NaCl along the length of the loop, with the
highest concentration at the bottom and lowest concentration at the top. The
loop of Henle can then concentrate NaCl in the medulla. The longer the loop,
the bigger the concentration gradient. This also means that the medulla
tissue tends to be saltier than the cortex tissue.
Now, as the filtrate flows through the collecting ducts, which go back down
through the medulla, water can be reabsorbed from the filtrate by osmosis.
Water moves from an area of low Na concentration (high water concentration)
in the collecting ducts to an area of high Na concentration (low water
concentration) in the medullary tissue. If you remove water from the
filtrate at this final stage, you can concentrate the urine.
Anti-Diuretic Hormone (ADH)
ADH, which is secreted by the pituitary gland, controls the ability of water
to pass through the cells in the walls of the collecting ducts. If no ADH is
present, then no water can pass through the walls of the ducts. The more ADH
present, the more water can pass through.
Specialized nerve cells, called osmoreceptors, in the hypothalamus of the
brain sense the Na concentration of the blood. The nerve endings of these
osmoreceptors are located in the posterior pituitary gland and secrete ADH.
If the Na concentration of the blood is high, the osmoreceptors secrete ADH.
If the Na concentration of the blood is low, they do not secrete ADH. In
reality, there is always some very low level of ADH secreted from the
osmoreceptors.
Kidneys: Maintaining Water Balance
Why You Urinate Soon After Drinking a Large Glass of Water
When you drink a large glass of water, the water gets absorbed into the
blood and the following happens:
The absorbed water increases the amount of water filtered in the glomerulus.
The absorbed water in the blood reduces the Na concentration a little.
The reduced Na concentration lowers the amount of Na filtered in the
glomerulus.
The nephron reabsorbs all of the reduced Na load and some of the
accompanying water, leaving excess water in the filtrate.
The reduced Na concentration is sensed by the osmoreceptors.
The osmoreceptors do not secrete as much ADH.
Because the collecting ducts do not see as much ADH, they do not allow much
water to be reabsorbed in response to the Na concentration gradient set up
by the loop of Henle.
The excess water gets excreted in the urine.
When the excess water is excreted, the Na concentration of the blood returns
to normal.
Why You Have Concentrated Urine in the Morning
Typically, we do not drink water overnight when we sleep. So, our intestines
are not absorbing water:
Decreased water absorption by the intestine reduces the amount of water in
the blood.
Decreased water in the blood reduces the amount of water filtered in the
glomerulus.
Decreased water in the blood increases the Na concentration in the blood.
Increased Na concentration in the blood increases the amount of Na filtered
in the glomerulus.
The nephron does not reabsorb all of the filtered Na, and some water remains
with it in the filtrate.
The increased Na concentration in the blood is sensed by the osmoreceptors.
The osmoreceptors secrete ADH.
The collecting ducts see more ADH and allow water to be reabsorbed in
response to the Na concentration gradient set up by the loop of Henle.
More water gets reabsorbed from the collecting ducts, producing a
concentrated urine. A little water is lost in the urine because of the Na;
we cannot excrete solid urine.
The removal of Na and increased reabsorption of water help return the blood
concentration of Na to normal.
So, the loop of Henle sets up the Na concentration gradient across the
medulla, allowing for water to be reabsorbed from the collecting ducts, and
ADH allows the water to pass through those collecting ducts.
Your blood maintains a constant concentration of hydrogen ion (pH) by a
chemical mixture of hydrogen ions and sodium bicarbonate. The sodium
bicarbonate is produced by the carbon dioxide (CO 2) formed in the cells as
a byproduct of many chemical reactions. The CO2 enters the blood in the
capillaries, where red blood cells contain an enzyme called carbonic
anhydrase that helps combine CO 2 and water (H 2O) to form carbonic acid (H
2 CO3 ) quickly. The carbonic acid formed then rapidly separates into
hydrogen ions (H+ ) and bicarbonate ions (HCO3-). This reaction can also
proceed in the reverse direction, whereby sodium bicarbonate plus hydrogen
ion yields carbon dioxide and water.
Carbonic
Anhydrase
CO 2 + H 2 O <---------> H 2 CO3 <---------> H+ + HCO 3 -
The correct pH is maintained by keeping the ratio of hydrogen ion to
bicarbonate in the blood constant. If you add acid (hydrogen ion) to the
blood, then you will reduce the bicarbonate concentration and alter the pH
of the blood. Similarly, if you reduce the hydrogen ion by adding alkali,
you will increase the bicarbonate concentration and alter the pH of the
blood.
Now, the acid/base balance of our blood changes in response to many things
including:
Diet - diets rich in meats provide acids to the bloods when digested. In
contrast, diets rich in fruits and vegetables make our blood alkaline
because they are rich in bicarbonates.
Exercise - exercising muscles produce lactic acid that must be eliminated
from the body or metabolized.
Breathing - high altitude causes rapid breathing that makes our blood
alkaline. In contrast, certain lung diseases that block the diffusion of
oxygen can cause the blood to be acidic.
Regulating Blood Composition
The kidney can correct any imbalances by removing excess acid (hydrogen ion)
or bases (bicarbonate) in the urine and restoring the bicarbonate
concentration in the blood to normal. The kidney cells produce a constant
amount of hydrogen ion and bicarbonate because of their own cellular
metabolism (production of carbon dioxide). Through a carbonic anhydrase
reaction similar to the red blood cells, hydrogen ions get produced and
secreted into the lumen of the nephron. Also, bicarbonate ions get produced
and secreted into the blood. In the lumen of the nephron, filtered
bicarbonate combines with secreted hydrogen ions to form carbon dioxide and
water (carbonic anhydrase is also present on the luminal surface of the
kidney cells). Whether the kidney removes hydrogen ions or bicarbonate ions
in the urine depends upon the amount of bicarbonate filtered in the
glomerulus from the blood relative to the amount of hydrogen ions secreted
by the kidney cells. If the amount of filtered bicarbonate is greater than
the amount of secreted hydrogen ions, then bicarbonate will be lost in the
urine. Likewise, If the amount of secreted hydrogen ion is greater than the
amount of filtered bicarbonate, then hydrogen ions will be lost in the urine
(i.e. acidic urine).
Let's consider a few examples:
Acid Diet
Hydrogen ions added to the blood by breaking down a meat-rich diet combine
with bicarbonate in the blood and form carbon dioxide and water.
This reaction reduces the bicarbonate concentration and the pH in the blood.
The decreased bicarbonate concentration in the blood reduces the amount of
bicarbonate filtered in the glomerulus.
All of the filtered bicarbonate combines with the hydrogen ion secreted by
the kidney cells in the lumen to form carbon dioxide and water.
Because the filtered load of bicarbonate was less than the amount of
hydrogen ion secreted by the kidney cells, there is an excess of hydrogen
ion in the urine.
The amount of bicarbonate secreted from the kidney cells into the blood was
equal to the hydrogen ion secreted into the lumen and greater than the
filtered load of bicarbonate from the blood -- therefore, the blood has a
net gain of bicarbonate.
This process continues to lose hydrogen ions in the urine and gain
bicarbonate in the blood until the concentrations of hydrogen (pH) and
bicarbonate ions in the blood are restored to normal.
Alkaline Diet
Bicarbonate added to the blood from the fruit or vegetable-rich diet
combines with hydrogen ions to form carbon dioxide and water.
This reaction reduces the hydrogen ion concentration and increases the pH.
The increased bicarbonate concentration increases the amount of bicarbonate
filtered in the glomerulus.
The filtered bicarbonate exceeds the amount of hydrogen ion secreted by the
kidney cell, and excess bicarbonate is lost in the urine.
The amount of bicarbonate secreted from the kidney cells into the blood was
equal to the hydrogen ions secreted into the lumen and less than the
filtered load of bicarbonate from the blood -- therefore, the blood has a
net loss of bicarbonate.
This process continues to lose bicarbonate in the urine and reduce the
bicarbonate in the blood until the concentrations of hydrogen (pH) and
bicarbonate ions in the blood are restored to normal.
How Kidneys Influence Blood Pressure
The blood pressure in your body depends upon the following conditions:
The force of contraction of the heart - related to how much the heart muscle
gets stretched by the incoming blood.
The degree to which the arteries and arterioles constrict - increases the
resistance to blood flow, thus requiring a higher blood pressure.
The circulating blood volume - the higher the circulating blood volume, the
more the heart muscle gets stretched by the incoming blood.
The kidney influences blood pressure by:
Causing the arteries and veins to constrict.
Increasing the circulating blood volume.
How the Kidney Causes Blood Vessels to Constrict
Diuretics
People with chronic high blood pressure (hypertension) often take a class of
drugs called diuretics to control their blood pressure. Diuretics reduce Na
reabsorption from the lumen of the nephron. Water reabsorption is also
reduced. Therefore, Na and water are lost in the urine, which increases
urine flow. The decreased reabsorption of Na and water from the nephron
reduces blood volume, thereby reducing blood pressure.
Specialized cells are located in a portion of the distal tubule located near
and in the wall of the afferent arteriole. The distal tubule cells (macula
densa) sense the Na in the filtrate, and the arterial cells (juxtaglomerular
cells) sense the blood pressure. When the blood pressure drops, the amount
of filtered Na also drops. The juxtaglomerular cells sense the drop in blood
pressure and the decrease in Na is relayed to them by the macula densa
cells. The juxtaglomerular cells then release an enzyme called renin. Renin
converts angiotensinogen (a peptide, or amino acid derivative) into
angiotensin I. Angiotensin I is then converted to angiotensin II by an
angiotensin-converting enzyme (ACE), which is found mainly in the lungs.
Angiotensin II causes blood vessels to contract -- the increased blood
vessel constrictions elevate the blood pressure.
How the Kidney Increases the Circulating Blood Volume
Angiotensin II also stimulates the adrenal gland to secrete a hormone called
aldosterone. Aldosterone stimulates more Na reabsorption in the distal
tubule, and water gets reabsorbed along with the Na. The increased Na and
water reabsorption from the distal tubule reduces urine output and increases
the circulating blood volume. The increased blood volume helps stretch the
heart muscle and causes it to generate more pressure with each beat, thereby
increasing the blood pressure.
The actions taken by the kidney to regulate blood pressure are especially
important during traumatic injury, when they are necessary to maintain blood
pressure and conserve the loss of fluids.
Bone metabolism is
influenced by the kidneys:
Your body stores calcium in the bones, but also maintains a constant level
of calcium in the blood. If the blood calcium level falls, then the
parathyroid glands in your neck release a hormone called parathyroid
hormone. Parathyroid hormone increases calcium reabsorption from the distal
tubule of the nephron to restore the blood calcium level. Parathyroid
hormone also stimulates calcium release from bone and calcium absorption
from the intestine.
In addition to parathyroid hormone, your body also requires vitamin D to
stimulate calcium absorption from the kidney and intestine. Vitamin D is
found in milk products. A precursor to vitamin D (cholecalciferol) is made
in the skin and processed in the liver. However, the final step that
converts an inactive form of cholecalciferol into active vitamin D occurs in
the proximal tubule of the nephron. Once activated, vitamin D stimulates
calcium absorption from the proximal tubule and from the intestine, thereby
increasing blood calcium levels.
Kidney stones are often caused by problems in the kidney's ability to handle
calcium. In addition, the kidney's role in maintaining blood calcium is
important in the bone disease osteoporosis that afflicts many elderly
people, especially women.
As you can see, the kidneys perform many functions that are important to
your body:
Controlling the composition of your blood and eliminate wastes - filtration/reabsorption/secretion
method
Influencing blood pressure - renin secretion
Helping to regulate your body's calcium - vitamin D activation
If the kidneys fail to function, then renal dialysis methods (artificial
filtration methods) can be used to help you survive by cleansing the blood.
This is especially necessary when both kidneys fail. Although you have two
kidneys, it is possible to live with only one. One healthy kidney can be
donated and transplanted into a compatible person with total kidney failure.
Kidney transplants are a common way to help those people survive and live a
normal life.
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