The Kidneys

Location and External Anatomy of the Kidneys

The Kidneys

The kidneys are the primary functional organ of the renal system. They are essential in
homeostatic functions such as the regulation of electrolytes, maintenance of acid–base
balance, and the regulation of blood pressure (by maintaining salt and water balance).
They serve the body as a natural filter of the blood and remove wastes that are excreted
through the urine.

They are also responsible for the reabsorption of water, glucose, and amino acids, and
will maintain the balance of these molecules in the body. In addition, the kidneys
produce hormones including calcitriol, erythropoietin, and the enzyme renin, which are
involved in renal and hemotological physiological processes.

Anatomical Location

The kidneys are a pair of bean-shaped, brown organs about the size of your fist. They
are covered by the renal capsule, which is a tough capsule of fibrous connective tissue.
Adhering to the surface of each kidney are two layers of fat to help cushion them.

The asymmetry within the abdominal cavity caused by the liver typically results in the
right kidney being slightly lower than the left, and left kidney being located slightly more
medial than the right. The right kidney sits just below the diaphragm and posterior to the
liver, the left below the diaphragm and posterior to the spleen.

Resting on top of each kidney is an adrenal gland (adrenal meaning on top of renal),
which are involved in some renal system processes despite being a primarily endocrine
organ. The upper parts of the kidneys are partially protected by lower ribs, and each
whole kidney and adrenal gland are surrounded by two layers of fat (the perirenal and
pararenal fat) and the renal fascia.

The kidneys are located at the rear wall of the abdominal cavity just above the waistline
and are protected by the ribcage. They are considered retroperitoneal, which means
that they lie behind the peritoneum, the membrane lining of the abdominal cavity.

There are a number of important external structures connecting the kidneys to the rest
of the body. The renal artery branches off from the lower part of the aorta and provides
the blood supply to the kidneys. Renal veins take blood away from the kidneys into the
inferior vena cava. The ureters are structures that come out of the kidneys, bringing
urine downward into the bladder.
Internal Anatomy of the Kidneys

The cortex and medulla make up two of the internal layers of a kidney and are
composed of individual filtering units known as nephrons.

There are three major regions of the kidney:

1. Renal cortex
2. Renal medulla
3. Renal pelvis

The renal cortex is a space between the medulla and the outer capsule. The renal
medulla contains the majority of the length of nephrons, the main functional component
of the kidney that filters fluid from blood. The renal pelvis connects the kidney with the
circulatory and nervous systems from the rest of the body.

Renal Cortex

The kidneys are surrounded by a renal cortex, a layer of tissue that is also covered by
renal fascia (connective tissue) and the renal capsule. The renal cortex is granular
tissue due to the presence of nephrons—the functional unit of the kidney—that are
located deeper within the kidney, within the renal pyramids of the medulla.

The cortex provides a space for arterioles and venules from the renal artery and vein,
as well as the glomerular capillaries, to perfuse the nephrons of the kidney.
Erythropotein, a hormone necessary for the synthesis of new red blood cells, is also
produced in the renal cortex.

Renal Medulla

The medulla is the inner region of the parenchyma of the kidney.

The medulla consists of multiple pyramidal tissue masses, called the renal pyramids,
which are triangle structures that contain a dense network of nephrons.

At one end of each nephron, in the cortex of the kidney, is a cup-shaped structure called
the Bowman’s capsule. It surrounds a tuft of capillaries called the glomerulus that
carries blood from the renal arteries into the nephron, where plasma is filtered through
the capsule.

After entering the capsule, the filtered fluid flows along the proximal convoluted tubule to
the loop of Henle and then to the distal convoluted tubule and the collecting ducts,
which flow into the ureter. Each of the different components of the nephrons are
selectively permeable to different molecules, and enable the complex regulation of
water and ion concentrations in the body.
Renal Pelvis

The renal pelvis contains the hilium. The hilum is the concave part of the bean-shape
where blood vessels and nerves enter and exit the kidney; it is also the point of exit for
the ureters—the urine-bearing tubes that exit the kidney and empty into the urinary
bladder. The renal pelvis connects the kidney to the rest of the body.

Supply of Blood and Nerves to the Kidneys

The renal veins drain the kidney and the renal arteries supply blood to the kidney.

Because the kidney filters blood, its network of blood vessels is an important component
of its structure and function. The arteries, veins, and nerves that supply the kidney enter
and exit at the renal hilum.

Renal Arteries

The renal arteries branch off of the abdominal aorta and supply the kidneys with blood.
The arterial supply of the kidneys is variable from person to person, and there may be
one or more renal arteries supplying each kidney.

Due to the position of the aorta, the inferior vena cava, and the kidneys in the body, the
right renal artery is normally longer than the left renal artery. The renal arteries carry a
large portion of the total blood flow to the kidneys—up to a third of the total cardiac
output can pass through the renal arteries to be filtered by the kidneys.

Renal blood supply starts with the branching of the aorta into the renal arteries (which
are each named based on the region of the kidney they pass through) and ends with the
exiting of the renal veins to join the inferior vena cava. The renal arteries split into
several segmental arteries upon entering the kidneys, which then split into several
arterioles.

These afferent arterioles branch into the glomerular capillaries, which facilitate fluid
transfer to the nephrons inside the Bowman’s capsule, while efferent arterioles take
blood away from the glomerulus, and into the interlobular capillaries, which provide
tissue oxygenation to the parenchyma of the kidney.

Renal Veins

The renal veins are the veins that drain the kidneys and connect them to the inferior
vena cava. The renal vein drains blood from venules that arise from the interlobular
capillaries inside the parenchyma of the kidney.
Renal Plexus

The renal plexus are the source of nervous tissue innervation within the kidney, which
surround and primarily alter the size of the arterioles within the renal cortex. Input from
the sympathetic nervous system triggers vasoconstriction of the arterioles in the kidney,
thereby reducing renal blood flow into the glomerulus.

The kidney also receives input from the parasympathetic nervous system, by way of the
renal branches of the vagus nerve (cranial nerve X), which causes vasodilation and
increased blood flow of the afferent arterioles. Due to this mechanism, sympathetic
nervous stimulation will decrease urine production, while parasympathetic nervous
stimulation will increase urine production.

Nephron, Parts, and Histology

The nephron of the kidney is involved in the regulation of water and soluble substances
in blood.

A Nephron

A nephron is the basic structural and functional unit of the kidneys that regulates water
and soluble substances in the blood by filtering the blood, reabsorbing what is needed,
and excreting the rest as urine. Its function is vital for homeostasis of blood volume,
blood pressure, and plasma osmolarity. It is regulated by the neuroendocrine system by
hormones such as antidiuretic hormone, aldosterone, and parathyroid hormone.

The Glomerulus

The glomerulus is a capillary tuft that receives its blood supply from an afferent arteriole
of the renal circulation. Here, fluid and solutes are filtered out of the blood and into the
space made by Bowman’s capsule.

A group of specialized cells known as juxtaglomerular apparatus (JGA) are located

around the afferent arteriole where it enters the renal corpuscle. The JGA secretes an
enzyme called renin, due to a variety of stimuli, and it is involved in the process of blood
volume homeostasis.

The Bowman’s capsule (also called the glomerular capsule) surrounds the glomerulus.
It is composed of visceral (simple squamous epithelial cells; inner) and parietal (simple
squamous epithelial cells; outer) layers. The visceral layer lies just beneath the
thickened glomerular basement membrane and only allows fluid and small molecules
like glucose and ions like sodium to pass through into the nephron.
Red blood cells and large proteins, such as serum albumins, cannot pass through the
glomerulus under normal circumstances. However, in some injuries they may be able to
pass through and can cause blood and protein content to enter the urine, which is a
sign of problems in the kidney.

Proximal Convoluted Tubule

The proximal tubule is the first site of water reabsorption into the bloodstream, and the
site where the majority of water and salt reabsorption takes place. Water reabsorption in
the proximal convoluted tubule occurs due to both passive diffusion across the
basolateral membrane, and active transport from Na+/K+/ATPase pumps that actively
transports sodium across the basolateral membrane.

Water and glucose follow sodium through the basolateral membrane via an osmotic
gradient, in a process called co-transport. Approximately 2/3rds of water in the nephron
and 100% of the glucose in the nephron are reabsorbed by cotransport in the proximal
convoluted tubule.

Fluid leaving this tubule generally is unchanged due to the equivalent water and ion
reabsorption, with an osmolarity (ion concentration) of 300 mOSm/L, which is the same
osmolarity as normal plasma.

The Loop of Henle

The loop of Henle is a U-shaped tube that consists of a descending limb and ascending
limb. It transfers fluid from the proximal to the distal tubule. The descending limb is
highly permeable to water but completely impermeable to ions, causing a large amount
of water to be reabsorbed, which increases fluid osmolarity to about 1200 mOSm/L. In
contrast, the ascending limb of Henle’s loop is impermeable to water but highly
permeable to ions, which causes a large drop in the osmolarity of fluid passing through
the loop, from 1200 mOSM/L to 100 mOSm/L.

Distal Convoluted Tubule and Collecting Duct

The distal convoluted tubule and collecting duct is the final site of reabsorption in the
nephron. Unlike the other components of the nephron, its permeability to water is
variable depending on a hormone stimulus to enable the complex regulation of blood
osmolarity, volume, pressure, and pH.

Normally, it is impermeable to water and permeable to ions, driving the osmolarity of

fluid even lower. However, anti-diuretic hormone (secreted from the pituitary gland as a
part of homeostasis) will act on the distal convoluted tubule to increase the permeability
of the tubule to water to increase water reabsorption. This example results in increased
blood volume and increased blood pressure. Many other hormones will induce other
important changes in the distal convoluted tubule that fulfill the other homeostatic
functions of the kidney.

The collecting duct is similar in function to the distal convoluted tubule and generally
responds the same way to the same hormone stimuli. It is, however, different in terms of
histology. The osmolarity of fluid through the distal tubule and collecting duct is highly
variable depending on hormone stimulus. After passage through the collecting duct, the
fluid is brought into the ureter, where it leaves the kidney as urine.

Physiology of the Kidneys

Overview of Urine Formation

Urine is formed in three steps: filtration, reabsorption, and secretion.

Urine is a waste byproduct formed from excess water and metabolic waste molecules
during the process of renal system filtration. The primary function of the renal system is
to regulate blood volume and plasma osmolarity, and waste removal via urine is
essentially a convenient way that the body performs many functions using one process.
Urine formation occurs during three processes:

1. Filtration
2. Reabsorption
3. Secretion

Filtration

During filtration, blood enters the afferent arteriole and flows into the glomerulus where
filterable blood components, such as water and nitrogenous waste, will move towards
the inside of the glomerulus, and nonfilterable components, such as cells and serum
albumins, will exit via the efferent arteriole. These filterable components accumulate in
the glomerulus to form the glomerular filtrate.

Normally, about 20% of the total blood pumped by the heart each minute will enter the
kidneys to undergo filtration; this is called the filtration fraction. The remaining 80% of
the blood flows through the rest of the body to facilitate tissue perfusion and gas
exchange.

Reabsorption

The next step is reabsorption, during which molecules and ions will be reabsorbed into
the circulatory system. The fluid passes through the components of the nephron (the
proximal/distal convoluted tubules, loop of Henle, the collecting duct) as water and ions
are removed as the fluid osmolarity (ion concentration) changes. In the collecting duct,
secretion will occur before the fluid leaves the ureter in the form of urine.

Secretion

During secretion some substances±such as hydrogen ions, creatinine, and drugs—will

be removed from the blood through the peritubular capillary network into the collecting
duct. The end product of all these processes is urine, which is essentially a collection of
substances that has not been reabsorbed during glomerular filtration or tubular
reabsorbtion.

Urine is mainly composed of water that has not been reabsorbed, which is the way in
which the body lowers blood volume, by increasing the amount of water that becomes
urine instead of becoming reabsorbed. The other main component of urine is urea, a
highly soluble molecule composed of ammonia and carbon dioxide, and provides a way
for nitrogen (found in ammonia) to be removed from the body. Urine also contains many
salts and other waste components. Red blood cells and sugar are not normally found in
urine but may indicate glomerulus injury and diabetes mellitus respectively.

Glomerular Filtration

Glomerular filtration is the renal process whereby fluid in the blood is filtered across the
capillaries of the glomerulus.

Glomerular filtration is the first step in urine formation and constitutes the basic
physiologic function of the kidneys. It describes the process of blood filtration in the
kidney, in which fluid, ions, glucose, and waste products are removed from the
glomerular capillaries.

Many of these materials are reabsorbed by the body as the fluid travels through the
various parts of the nephron, but those that are not reabsorbed leave the body in the
form of urine.
Glomerulus Structure

Glomerulus structure: A diagram showing the afferent and efferent arterioles bringing blood in and out of the
Bowman’s capsule, a cup-like sac at the beginning of the tubular component of a nephron.

Blood plasma enters the afferent arteriole and flows into the glomerulus, a cluster of
intertwined capillaries. The Bowman’s capsule (also called the glomerular capsule)
surrounds the glomerulus and is composed of visceral (simple squamous epithelial
cells—inner) and parietal (simple squamous epithelial cells—outer) layers.

The visceral layer lies just beneath the thickened glomerular basement membrane and
is made of podocytes that form small slits in which the fluid passes through into the
nephron. The size of the filtration slits restricts the passage of large molecules (such as
albumin) and cells (such as red blood cells and platelets) that are the non-filterable
components of blood.

These then leave the glomerulus through the efferent arteriole, which becomes
capillaries meant for kidney–oxygen exchange and reabsorption before becoming
venous circulation. The positively charged podocytes will impede the filtration of
negatively charged particles as well (such as albumins).
The Mechanisms of Filtration

The process by which glomerular filtration occurs is called renal ultrafiltration. The force
of hydrostatic pressure in the glomerulus (the force of pressure exerted from the
pressure of the blood vessel itself) is the driving force that pushes filtrate out of the
capillaries and into the slits in the nephron.

Osmotic pressure (the pulling force exerted by the albumins) works against the greater
force of hydrostatic pressure, and the difference between the two determines the
effective pressure of the glomerulus that determines the force by which molecules are
filtered. These factors will influence the glomeruluar filtration rate, along with a few other
factors.

Regulation of Glomerular Filtration Rate

Regulation of GFR requires both a mechanism of detecting an inappropriate GFR as

well as an effector mechanism that corrects it.

Glomerular Filtration Rate

Glomerular filtration rate (GFR) is the measure that describes the total amount of filtrate
formed by all the renal corpuscles in both kidneys per minute. The glomerular filtration
rate is directly proportional to the pressure gradient in the glomerulus, so changes in
pressure will change GFR.

GFR is also an indicator of urine production, increased GFR will increase urine
production, and vice versa.

The Starling equation for GFR is:

GFR=Filtration Constant × (Hydrostatic Glomerulus Pressure–Hydrostatic Bowman’s

Capsule Pressure)–(Osmotic Glomerulus Pressure+Osmotic Bowman’s Capsule
Pressure)

The filtration constant is based on the surface area of the glomerular capillaries, and
the hydrostatic pressure is a pushing force exerted from the flow of a fluid itself; osmotic
pressure is the pulling force exerted by proteins. Changes in either the hydrostatic or
osmotic pressure in the glomerulus or Bowman’s capsule will change GFR.

Hydrostatic Pressure Changes

Many factors can change GFR through changes in hydrostatic pressure, in terms of the
flow of blood to the glomerulus. GFR is most sensitive to hydrostatic pressure changes
within the glomerulus. A notable body-wide example is blood volume.
Due to Starling’s law of the heart, increased blood volume will increase blood pressure
throughout the body. The increased blood volume with its higher blood pressure will go
into the afferent arteriole and into the glomerulus, resulting in increased GFR.
Conversely, those with low blood volume due to dehydration will have a decreased
GFR.

Pressure changes within the afferent and efferent arterioles that go into and out of the
glomerulus itself will also impact GFR. Vasodilation in the afferent arteriole and
vasconstriction in the efferent arteriole will increase blood flow (and hydrostatic
pressure) in the glomerulus and will increase GFR. Conversely, vasoconstriction in the
afferent arteriole and vasodilation in the efferent arteriole will decrease GFR.

The Bowman’s capsule space exerts hydrostatic pressure of its own that pushes
against the glomerulus. Increased Bowman’s capsule hydrostatic pressure will decrease
GFR, while decreased Bowman’s capsule hydrostatic pressure will increase GFR.

An example of this is a ureter obstruction to the flow of urine that gradually causes a
fluid buildup within the nephrons. An obstruction will increase the Bowman’s capsule
hydrostatic pressure and will consequently decrease GFR.

Osmotic Pressure Changes

Osmotic pressure is the force exerted by proteins and works against filtration because
the proteins draw water in. Increased osmotic pressure in the glomerulus is due to
increased serum albumin in the bloodstream and decreases GFR, and vice versa.

Under normal conditions, albumins cannot be filtered into the Bowman’s capsule, so the
osmotic pressure in the Bowman’s space is generally not present, and is removed from
the GFR equation. In certain kidney diseases, the basement membrane may be
damaged (becoming leaky to proteins), which results in decreased GFR due to the
increased Bowman’s capsule osmotic pressure.

GFR Feedback

GFR is one of the many ways in which homeostasis of blood volume and blood
pressure may occur. In particular, low GFR is one of the variables that will activate the
renin–angiotensin feedback system, a complex process that will increase blood volume,
blood pressure, and GFR. This system is also activated by low blood pressure itself,
and sympathetic nervous stimulation, in addition to low GFR.

Tubular Reabsorption

Tubular reabsorption is the process by which solutes and water are removed from the
tubular fluid and transported into the blood.
Filtrate

The fluid filtered from blood, called filtrate, passes through the nephron, much of the
filtrate and its contents are reabsorbed into the body. Reabsorption is a finely tuned
process that is altered to maintain homeostasis of blood volume, blood pressure,
plasma osmolarity, and blood pH. Reabsorbed fluids, ions, and molecules are returned
to the bloodstream through the peri-tubular capillaries, and are not excreted as urine.

Mechanisms of Reabsorption

Tubular secretion: Diagram showing the basic physiologic mechanisms of the kidney and the three steps
involved in urine formation. Namely filtration, reabsorption, secretion, and excretion.

Reabsorption in the nephron may be either a passive or active process, and the specific
permeability of the each part of the nephron varies considerably in terms of the amount
and type of substance reabsorbed. The mechanisms of reabsorption into the peri-
tubular capillaries include:

 Passive diffusion—passing through plasma membranes of the kidney epithelial cells by

concentration gradients.
 Active transport—membrane-bound ATPase pumps (such as NA+/K+ ATPase pumps) with
carrier proteins that carry substances across the plasma membranes of the kidney
epithelial cells by consuming ATP.
 Cotransport—this process is particularly important for the reabsorption of water. Water
can follow other molecules that are actively transported, particularly glucose and sodium
ions in the nephron.

These processes involve the substance passing though the luminal barrier and the
basolateral membrane, two plasma membranes of the kidney epithelial cells, and into
the peri-tubular capillaries on the other side. Some substances can also pass through
tiny spaces in between the renal epithelial cells, called tight junctions.

Osmolarity Changes

As filtrate passes through the nephron, its osmolarity (ion concentration) changes as
ions and water are reabsorbed. The filtrate entering the proximal convoluted tubule is
300 mOsm/L, which is the same osmolarity as normal plasma osmolarity.

In the proximal convoluted tubules, all the glucose in the filtrate is reabsorbed, along
with an equal concentration of ions and water (through cotransport), so that the filtrate is
still 300 mOsm/L as it leaves the tubule. The filtrate osmolarity drops to 1200 mOsm/L
as water leaves through the descending loop of Henle, which is impermeable to ions. In
the ascending loop of Henle, which is permeable to ions but not water, osmolarity falls
to 100–200 mOsm/L.

Finally, in the distal convoluted tubule and collecting duct, a variable amount of ions and
water are reabsorbed depending on hormonal stimulus. The final osmolarity of urine is
therefore dependent on whether or not the final collecting tubules and ducts are
permeable to water or not, which is regulated by homeostasis.

Tubular Secretion

Hydrogen, creatinine, and drugs are removed from the blood and into the collecting duct
through the peritubular capillary network.

Tubular secretion is the transfer of materials from peritubular capillaries to the renal
tubular lumen; it is the opposite process of reabsorption. This secretion is caused
mainly by active transport and passive diffusion.
Usually only a few substances are secreted, and are typically waste products. Urine is
the substance leftover in the collecting duct following reabsorption and secretion.

Mechanisms of Secretion

The mechanisms by which secretion occurs are similar to those of reabsorption,

however these processes occur in the opposite direction.

 Passive diffusion—the movement of molecules from the peritubular capillaries to the

intersitial fluid within the nephron.
 Active transport—the movement of molecules via ATPase pumps that transport the
substance through the renal epithelial cell into the lumen of the nephron.

Renal secretion is different from reabsorption because it deals with filtering and cleaning
substances from the blood, rather than retaining them. The substances that are
secreted into the tubular fluid for removal from the body include:

 Potassium ions (K+)

 Hydrogen ions (H+)
 Ammonium ions (NH4+)
 Creatinine
 Urea
 Some hormones
 Some drugs (e.g., penicillin)
Tubular secretion: Diagram showing the basic physiologic mechanisms of the kidney and the three steps
involved in urine formation.

Many pharmaceutical drugs are protein-bound molecules thatDiagram showing the

basic physiologic mechanisms of the kidney and the three steps involved in urine
formation. amely filtration, reabsorption, secretion, and excretion. are easily secreted,
which is why urine testing can detect the exposure to many types of drugs. Tubular
secretion occurs throughout the different parts of the nephron, from the proximal
convoluted tubule to the collecting duct at the end of the nephron.

Hydrogen Ion Secretion

The tubular secretion of H+ and NH4+ from the blood into the tubular fluid is involved in
blood pH regulation. The movement of these ions also helps to conserve sodium
bicarbonate (NaHCO3). The typical pH of urine is about 6.0, while it is ideally 7.35 to
7.45 for blood.
pH regulation is primarily a respiratory system process, due to the exchange of carbon
dioxide (a component of carbonic acid in blood), however tubular secretion assists in pH
homeostasis as well.

Following Secretion

Urine that is formed via the three processes of filtration, reabsorption, and secretion
leaves the kidney through the ureter, and is stored in the bladder before being removed
through the urethra. At this final stage it is only approximately one percent of the
originally filtered volume, consisting mostly of water with highly diluted amounts of urea,
creatinine, and variable concentrations of ions.

Positive troponin test

Troponins are a group of proteins found in skeletal and heart (cardiac) muscle fibers
that regulate muscular contraction. Troponin tests measure the level of cardiac-specific
troponin in the blood to help detect heart injury.

There are three types of troponin proteins: troponin C, troponin T, and troponin I.
Troponin C initiates contraction by binding calcium and moves troponin I so that the two
proteins that pull the muscle fiber shorter can interact. Troponin T anchors the troponin
complex to the muscle fiber structure. There is little or no difference in troponin C
between skeletal and cardiac muscle, but the forms of troponin I and troponin T are
different. Measuring the amount of cardiac-specific troponin T or troponin I in the blood
can help identify individuals who have experienced damage to their heart.

Normally, troponin is present in very small to undetectable quantities in the blood. When
there is damage to heart muscle cells, troponin is released into the blood. The more
damage there is, the greater the concentration in the blood. Primarily, troponin tests are
used to help determine if an individual has suffered a heart attack. They may also be
helpful in evaluating someone for other forms of heart injury.

Many laboratories in the U.S. use high-sensitivity troponin tests since the Food and
Drug Administration (FDA) approved them in 2017. Because this version of the test is
more sensitive than previous, older versions, it becomes positive sooner and may help
detect heart injury and acute coronary syndrome earlier. The hs-troponin test may also
be positive in people with stable angina and even in people with no symptoms. When it
is elevated in these individuals, it indicates an increased risk of future heart events such
as heart attacks.

When a person has a heart attack, levels of cardiac-specific troponins I and T can
become elevated in the blood within 3 or 4 hours after injury and may remain elevated
for 10 to 14 days.