MEDN2001: RENAL PHYSIOLOGY
LEARNING OBJECTIVES

Produce a diagram showing the structures and major functions of the nephron.

Explain the relationship between renal blood flow and glomerular filtration rate.

Discuss the role of the sympathetic nervous system in the regulation of renal blood flow.

Describe the role of the renin–angiotensin–system as it relates to renal blood flow.

List several factors that affect glomerular filtration rate.

Briefly explain the process of urine formation.

List specific transport mechanisms occurring in different parts of the nephron, including active transport,
osmosis, facilitated diffusion, and passive electrochemical gradients

Describe the processes which occur in the nephron to regulate fluid and electrolyte balance in the body

Identify the electrolytes reabsorbed and secreted by the proximal and distal tubes.

Describe the system of urine concentration.

Identify hormones activated or secreted by the kidney and describe their actions.
THE NEPHRON
The nephron is the functional unit of the kidney,
having the ability to form urine. The nephron is formed
of the outer cortex and inner medullar, however the
medulla only gets 2% of the blood flow (only the loop
of henle dips below the medulla). From the renal
artery we have different arterials feeding into
different nephrons. The nephron is a tubule that is
convoluted at some parts and consists of 6 main
structures.
Collecting ducts: collects the urine from multiple functional units. Consists of intercalated and principal cells.
Bowman’s capsule: the expand ends of the tubule (C shape part of tubule) which consists of a glomerular membrane
across which happens the filtration. There is a basement membrane onto which we have epithelium cells; they also
have podocytes with large slits in between allowing for the movement of particles. Under the basement membrane,
we have the lining of the capillaries (endothelium cells). The size of slit and fenestrae regulate what can pass through
the glomerular membrane.
Glomerulus: expanded ends of the tubule with the capillaries, and is surrounded by the bowman’s capsule
Proximal convoluted tubule: the first part which is convoluted. The proximal convoluted tubule cells are rich in
mitochondria and microvilli which allows the cell to have a very large surface area for transport. This tubule is
responsible for reabsorbing substances such as glucose, amino acids and sodium back into the bloodstream.
Distal convoluted tubule: second part which is convoluted. The distal convoluted tubule cells have less mitochondria
and microvilli than the proximal tubule – as it has the same function but to a lesser extent. This tubule is responsible
for regulating the balance of electrocytes in the urine
Loop of Henle: it is U shaped between the proximal convoluted tubule and consists of a thin descending part and thick
ascending part. It helps concentrate urine by creating a concentration gradient in the kidney.
The blood that enters the nephron from the renal artery afferent arteriole is filtered at the Bowman’s capsule; the
blood is filtered to remove waste products such as urea. The important nutrients (such as glucose) are reabsorbed
back into the blood at the proximal convoluted tubule (can sometimes occur in the distal); the loop of Henle helps
concentrate urine by reabsorbing water. Some substances are secreted from the blood to be added to the urine (e.g.,
excess electrolytes) and this occurs in the distal convoluted tubule. The collecting duct then carries the urine from
multiple nephrons and excretes it out of the body; urine excretion rate = filtration – reabsorption rate + secretion
rate
RENAL BLOOD FLOW AND GLOMERULAR FILTRATION RATE
Renal blood flow determines the rate at which blood is filtered through the glomeruli in the kidney; the glomeruli is a
network of small blood vessels that are responsible for filtering blood and producing urine. The renal blood flow is the
amount of blood that flows through the kidneys per unit time, regulated by local and systemic factors such as blood
pressure. The glomerular filtration rate is the amount of blood that is filtered through the glomeruli per unit time,
reflecting the ability of the kidneys to remove waste products from the blood.
Thus, renal blood flow affects the glomerular filtration rate by regulating the amount of blood that flows through the
glomeruli and ultimately the filtration pressure in the glomeruli. An increase in renal blood flow will cause an increase
in the glomerular filtration rate, and any decrease in renal blood flow will decrease the glomerular filtration rate.
SYMPATHETIC NERVOUS SYSTEM AND RENAL BLOOD FLOW REGULATION
The sympathetic nervous system regulates renal blood through a complex interplay of neural, hormonal and local
factors; being involved in the control of the constriction and dilation of renal blood vessels. When the sympathetic
nervous system is activated, the neurotransmitter norepinephrine is released from the sympathetic nerve terminals,
and the renin-angiotensin-aldosterone system (RAAS) is also activated.
Norepinephrine acts on alpha-adrenergic receptors on the smooth muscle cells in the renal blood vessels, causing
vasoconstriction (constriction of vessels) of the afferent arterioles and reducing renal blood flow; vasoconstriction
decreases pressure in the vessels and thus decreases glomerular filtration rate (GFR) and urine output.
Activation of the renin-angiotensin-aldosterone system (RAAS) also regulates renal blood flow through the action of
the hormone Angiotensin II. Angiotensin II acts on angiotensin receptors on the smooth muscle cells of the renal
blood vessels, causing moderate vasoconstriction of the efferent arterioles and reducing blood flow. Angiotensin II
also stimulates the release of aldosterone, promoting sodium retention and water reabsorption which increases blood
volume and pressure, and hence renal blood flow.
RENIN-ANGIOTENSIN-SYSTEM
The renin-angiotensin-system is a hormonal system that plays an important role in the regulation of blood flow.
Receptors in the kidney will detect a decrease in blood pressure or blood volume and as a result will secrete renin.
Renin acts on its substrate, angiotensinogen, to cleave it into angiotensin I, which is then converted to angiotensin II
when it reaches the lungs by the action of the angiotensin-converting enzyme (ACE).
Angiotensin II can directly act on the kidney to constrict vessel walls in the efferent arterioles (vasoconstriction) –
these are the blood vessels that carry blood away from the glomeruli. This results in a decrease in glomerular filtration
rate and an decrease in renal blood flow.
Angiotensin II can also stimulate the secretion of aldosterone from the adrenal glands. Aldosterone promotes sodium
retention and water reabsorption, which leads to an increase in blood volume and blood pressure – aldosterone is
the king of salt and water retention.
Drugs that target the RAAS system, such as ACE inhibitors and angiotensin receptor blockers, work by inhibiting the
production/effects of angiotensin II – reducing vasoconstriction and increasing renal blood flow.
GLOMERULAR FILTRATION RATE
Glomerular filtration rate (GFR) is the rate of filtration against the glomerular membrane, the volume which will be
filtered within unit time. The forces across the membrane affects the rate of filtration.
GFR = Kf (glomerular hydrostatic pressure + Bowman’s colloidal osmotic pressure) – (Bowman’s hydrostatic
pressure + glomerular colloidal osmotic pressure)
Factors that can affect the GFR include:

Glomerular hydrostatic pressure: this can be effect by the diameter of afferent and efferent arterioles and
arterial blood pressure.

Glomerular colloidal pressure: increased pressure (e.g., dehydration) decreases GFR, decreased pressure
(e.g., hypoproteinemia) increases GFR

Bowman’s hydrostatic pressure: e.g., stone in the ureter, increases pressure and decreases GFR

Bowman’s colloidal osmotic pressure

Ultrafiltration coefficient: permeability of the membrane (increases thickness, reduces Kf and GFR), surface
area of membrane (increase surface area, increases Kf and increases GFR)

Surface area can be affected by the relaxation of mesangial cells e.g., cAMP and dopamine which will
increase surface area. The contraction of mesangial cells e.g., norepinephrine and histamine will
reduce surface area. A decrease in the number of glomerular capillaries will decrease surface area.

Renal blood flow: an increase in renal blood flow will increase GFR

Blood pressure: an increase in blood pressure can lead to an increase in GFR

Hormonal factors: hormones such as angiotensin II and aldosterone can affect GFR (through the regulation of
renal blood flow and sodium/water reabsorption)
URINE FORMATION
The process of urine formation takes place in the nephrons of the kidneys. The first process in urine filtration is
glomerular filtration, where the blood enters the glomerulus (a network of capillaries in the nephron) through the
renal artery afferent arteriole and is filtered through a semi-permeable membrane. The filtrate is filtered in the
Bowman’s capsule and contains water, electrolytes and small molecules such as glucose, amino acids and urea – due
to the semi-permeable nature of the membrane.
The filtrate then moves into the renal tubules, where important nutrients such as glucose and amino acids are
reabsorbed into the blood in the proximal convoluted tubule in the processes of tubular reabsorption. Sodium and
water are also reabsorbed to maintain fluid balance in the body.
Next, tubular secretion occurs in the distal convoluted tubule. Substances, such as hydrogen ions, are secreted into
the renal tubules by active transport to be added to the urine (e.g., excess electrolytes)
As the filtrate moves through the Loop of Henle, water is reabsorbed to concentrate the urine. The concentrated urine
is then collected in the renal pelvis and transported to the bladder for storage and eventual excretion.
TRANSPORT MECHANSIMS IN THE NEPHRON
The different areas of the nephron use a variety of transport mechanisms in the formation of urine.
The mechanisms of tubular transport in the proximal and distal tubule uses active transport and passive transport to
achieve their respective functions. Active transport requires energy in the form of ATP and follows the chemical and
electrical gradient. There are two types of active transport, and this includes primary active transport and secondary
active transport (can be co-transport or counter-transport). Actively transported substances have a tubular transport
maximum (Tm) which is the maximum rate at which a substance can be transported by the renal tubules due to the
saturation of specific carrier and enzyme systems involved in active transport (e.g., glucose, PAH). Passive transport
requires no energy and moves with the chemical electrical gradient. The moving of a substance from the lumen to the
interstitial fluid can be done by transcellular transport (the substance passes through the cell) or paracellular
transport through the middle of the cells. For example, sodium is actively transported out of the tubular lumen by the
sodium-potassium pump, and when this occurs chlorine CI- can be transported paracellular. Water and urea also be
transported paracellular – when other substances are actively transported into the fluid through osmosis. Water and
electrolytes are reabsorbed by peritubular capillaries by bulk flow.
The kidney reabsorbs filtered glucose through the sodium-glucose cotransporters; essentially cotransport is driven by
the active sodium transport out of the cell through the sodium-potassium pump which allows for the glucose uptake
following the concentration gradient. 100% of glucose is reabsorbed in the proximal convoluted tubule with sodium.
Water reabsorption occurs through the process of osmosis and can be obligatory or facultative. Obligatory
reabsorption is independent of ADH and will result in the maximum amount of water excreted if we do not reabsorb
more under the effect of ADH – this accounts for 87% of filtered water. Under obligatory reabsorption, the proximal
tubule accounts for 65% of reabsorption, 15% of reabsorption occurs in the thin loop of Henle as it is not permeable
to any solutes (increases osmolarity), and 5% of reabsorption occurs in the distal tubules. In comparison, facultative
reabsorption is dependent on the effects of ADH and accounts for 12.5% of filtered water. The action of ADH relocates
more water channels to the membrane to increase the permeability of the membrane to water, which results in an
extra 8% reabsorbed from the late distal tubule and cortical collecting duct, and 4.5% more from the medullary
collecting duct.
Sodium is an important substance in the reabsorption of water, thus 99% or more of filtered sodium ions are
reabsorbed along the renal tubule. The thin descending loop of the loop of Henle does not allow for the reabsorption
of any ions, including sodium, so the majority of sodium ions (65%) are reabsorbed in the proximal convoluted tubule.
Sodium is important for reabsorptions of other substances through secondary active transport, such as glucose and
amino acids, which rely on the sodium-potassium pump. Hydrogen relies on the sodium-potassium pump in the
mechanism of counter transport; in that for every hydrogen ion secreted, there is one bicarb ion reabsorbed. In the
thick ascending loop of Henle, we have a channel that allows one sodium ion and two chloride ions will be reabsorbed
secondary to the active reabsorption of sodium. The potassium will leak into the lumen urine to ensure that the
channel keeps working; this leaking also creates a positive potential allowing magnesium and calcium to enter the
interstitium blood. The distal convoluted tubule is the site of sodium and chloride reabsorption.
The collecting duct is the site of the action of epithelial sodium channels, as they have cells which have receptors for
the hormone aldosterone. Aldosterone will enter the cell and stimulates the nucleus to form proteins that form the
epithelial sodium channels; the availability of these channels makes sodium reabsorption easier.
REGULATION OF BODY FLUID AND ELECTROYTE BALANCE
Filtration: this occurs in the glomerulus where the blood is filtered through a semipermeable membrane, allowing for
the passage of water, electrolytes, and small molecules such as glucose, amino acids, and urea.
Reabsorption: this occurs in the proximal convoluted tubule where important nutrients such as glucose, amino acids
and electrolytes are transported back into the blood – this can be through active transport, facilitated diffusion and
diffusion. Sodium ions are actively transported out of the tubular fluid into the surrounding blood vessels which creates
a concentration gradient that drives the pass transport of other solutes, such as glucose and amino acids. Water will
follow the solutes through osmosis. Water and electrolytes are also reabsorbed by peritubular capillaries by bulk flow.
Secretion: this occurs in the distal convoluted tubule where the nephron secretes certain substances into the tubular
fluid through active transport mechanisms. These substances may include excess ions or toxins that need to be
eliminated from the body.
Regulation: the rate of filtration and reabsorption in the nephron is regulated by hormones such as aldosterone and
antidiuretic hormone (ADH). These hormones can alter the permeability of the nephron to water and solutes which
change the rate at which they can be reabsorbed or secreted – e.g., aldosterone promotes the reabsorption of sodium
ions and water. The Loop of Henle creates a concentration gradient in the medulla which allows for the concentration
of the urine; the collecting duct will respond to ADH which allows for the regulation of permeability to water, leading
to the reabsorption of water back into the body and produces more concentrated urine.
ELECTROCYTLE BALANCE BY PROXIMAL AND DISTAL TUBES
Proximal tubule
Sodium: the proximal tubules reabsorbs approx. 2/3s of filtered sodium through active transport of sodium ions out
of the tubular lumen by the sodium-potassium pump – this creates a concentration gradient that drives the
reabsorption of other solutes.
Chloride: chloride ions are reabsorbed along with sodium through passive transport, when sodium is transported
through the sodium-potassium pump
Potassium: potassium ions are reabsorbed through a combination of passive transport and active transport
mechanisms. This occurs in the thick ascending limb of the loop of Henle, if you are potassium deficient than in the
distal tubule you will reabsorb 5% of potassium.
Magnesium: magnesium ions are reabsorbed through passive transport mechanisms
Calcium: calcium ions are reabsorbed through passive transport mechanisms – will only reabsorb 50% because the
other 50% is bound to protein.
Distal tubule
Sodium: the distal tubule fine-tunes the amount of sodium reabsorbed /secreted depending on the body’s needs
Chloride: can be reabsorbed or secreted depending on the body’s needs
Potassium: fine-tunes the regulation of the potassium ion balance, can either secrete or reabsorb potassium
depending on the body’s needs. If you are high in potassium, then the aldosterone hormone will instead reabsorb
sodium and water and secretes potassium
Hydrogen: regulation of the acid-base balance in the body is maintained by secreting hydrogen ions to maintain a
proper pH balance. H+ ions are secreted in all segments of the renal tubule, except the descending and thin ascending
limbs of the loop of Henle. For each H+ secreted, one HCO3- is reabsorbed.
SYSTEM OF URINE CONCENTRATION
The aim of urine concentration is to produce urine with a high concentration of solutes (such as urea, sodium and
potassium) and a low volume of water to conserve water in the body and maintain proper fluid balance. In order to
produce concentrated urine, there must be enough ADH which increases the permeability of the late distal convoluted
tubule, collecting tubule and medullary duct to water.
The main mechanism in the system of urine concentration is the counter current exchange. The blood is first filtered
in the glomeruli of the nephron and then water and electrolytes are reabsorbed in the proximal tubules. The function
of the loop of Henle in the counter current exchange mechanism is as the counter current multiplier.
The loop of Henle consists of one descending limb and one ascending limb, each of which has a distinct permeability
to water and solutes – descending limb is highly permeable to water (but impermeable to solutes) while the ascending
limb is impermeable to water (but permeable to solutes). As fluid flows through the descending limb water is passively
reabsorbed out of the tubule into the surrounding interstitial fluid due to the high concentration of solutes in the
interstitial fluid (equilibrate by osmosis). The ascending limb is impermeable to water but can actively transport ions
such as sodium and chloride into the interstitial fluid – results in dilute tubular fluid. The interstitial fluid becomes
increasingly concentrated as solutes are transported out of the ascending limb establishing a concentrated gradient.
As the fluid advances, it creates a gradient where water is passively reabsorbed out of the tubule and into the
interstitial fluid – concentrating the urine. The vasa recta then acts as a counter current exchanger which maintains
the gradient created by the loop of Henle. In the presence of ADH, urea is also reabsorbed into the interstitium through
passive diffusion (from the medullary duct) which helps with the concentration of urine.
The antidiuretic hormone (ADH) also plays a role in the concentration of urine. ADH is released from the pituitary gland
in response to changes in blood osmolarity, increasing the permeability of the collecting ducts to water through the
relocation of more water channels in the membrane. This allows for the reabsorption of water back into the
bloodstream and thus makes the urine more concentrated.
Counter current mechanism: as urine flows downwards in the collecting tubule, it encounters higher concentrations
of solutes in the interstitium and hence loses water due to osmosis.
HORMONES OF THE KIDNEY
Renin: an enzyme secreted by juxtaglomerular cells and is involved in the regulation of blood pressure by catalysing
the conversion of angiotensinogen into angiotensin I. Angiotensin I is then converted into angiotensin II by the action
of the enzyme ACE. Angiotensin II causes vasoconstriction, increasing sodium reabsorption in the kidneys and
stimulates the release of aldosterone from the adrenal gland which promotes sodium and water retention.
Erythropoietin (EPO): a hormone secreted by the kidneys in response to low oxygen levels in the blood. It stimulates
the production of red blood cells in bone marrow, increasing oxygen-carrying capacity and improving tissue
oxygenation
Calcitriol: also known as vitamin D3 which helps to regulate calcium and phosphorus metabolism. It increases
calcium and phosphorus absorption in the small intestine and promotes calcium reabsorption in the kidneys.
Prostaglandins: group of lipid compounds that play a role in regulating blood pressure by causing vasodilation and
inhibiting sodium and water reabsorption in the kidneys. Also aids the regulation of kidney function by modulating
blood flow, glomerular filtration rate and electrolyte balance.