3. urinary regulation

URINARY REGULATION
PHYSIOLOGY: RENAL

ANTIDIURETIC HORMONE
OVERVIEW
‣ Antidiuretic hormone (ADH), also known as vasopressin, is
a small peptide hormone which regulates the body’s
retention of water
‣ It is one of only two hormones secreted by the posterior
pituitary gland
‣ Learning Goal
‣ To discuss the synthesis, storage, release and action of
ADH, and consider its clinical relevance

SYNTHESIS AND STORAGE
‣ The synthesis of ADH occurs in the supraoptic and
paraventricular nuclei in the hypothalamus
‣ It is then transported to the posterior pituitary gland via
the neurohypophysial capillaries
‣ In the posterior pituitary gland, its synthesis is completed
and it is stored here until it is ready to be secreted into the
circulation

RELEASE
‣ The release of ADH is controlled by several factors
‣ The two most influential factors are changes in plasma
osmotic pressure, and volume status
‣ Other factors that promote the release of ADH include
exercise, angiotensin II, and emotional states such as pain
‣ ADH release is inhibited by atrial natriuretic peptide (ANP),
which is released by stretched atria in response to increases
in blood pressure, as well as alcohol and certain medications

OSMOTIC PRESSURE
‣ Osmoreceptors in the hypothalamus regulate the amount
of ADH released in response to changes in the osmotic
pressure of plasma
‣ They are located in the organum vasculosum of the lamina
terminalis (OVLT) and the subfornical organ, which are two
of the sensory circumventricular organs of the brain
‣ Both organs lack a blood-brain barrier, allowing them to
directly detect the osmolarity of the blood

OSMOTIC PRESSURE
‣ Osmotic pressure is dependent on the plasma osmolality
‣ Plasma osmolality is in turn affected by the total body plasma volume
‣ Following a fall in plasma volume there is an increase in the plasma
sodium (Na+) concentration, and therefore the osmolarity is increased
‣ Subsequently water exits cells, and moves down its concentration
gradient into the plasma
‣ This stimulates the osmoreceptors cells to contract, which results in
afferent signals being sent from the hypothalamus to the posterior
pituitary gland to increase the release of ADH

OSMOTIC PRESSURE
‣ Alternatively, if there is an increase in the total body
volume then the osmolality of the plasma will reduce
‣ In this situation, water will move down its concentration
gradient from the plasma, into osmoreceptor cells, causing
them to expand
‣ As a result, afferent signals are sent from the
hypothalamus to the posterior pituitary gland
to decrease the release of ADH

VOLUME STATUS
‣ ADH secretion also occurs during states of hypovolemia
‣ Baroreceptors in the left atrium, carotid artery and aortic arch
detect changes in arterial blood volume
‣ If blood pressure reduces, baroreceptors relay this to the vagus
nerve, which sends afferent signals that directly stimulates the
release of ADH from the posterior pituitary
‣ Conversely, in a hypervolemic state, the release of ADH will be
reduced

ACTION
‣ The main action of ADH in the kidney is to regulate the volume and osmolarity of
the urine
‣ Specifically, it acts in the distal convoluted tubule (DCT) and collecting ducts (CD)
‣ During states of increased plasma osmolality, ADH secretion is increased
‣ ADH acts through a G-protein coupled receptor to increase the transcription and
insertion of Aquaporin–2 channels to the apical membrane of the DCT and CD
cells
‣ Consequently, the permeability of the DCT and CD cells to water increases
‣ This allows water to move down its concentration gradient, out of the nephron
and back into the blood stream, thus normalizing plasma osmolality and
increasing total blood volume

ACTION
‣ In response to decreased plasma osmolarity, ADH release is reduced
‣ This reduces the number of Aquaporin-2 channels being inserted into the
apical membrane of the DCT and CD cells
‣ In turn, there is a subsequent reduction in the amount of water
reabsorbed from the nephron back in the blood stream
‣ In high concentrations, ADH can also act on the blood vessels to
increase peripheral vascular resistance, the result of which is increased
blood pressure
‣ This mechanism is useful in restoring blood pressure during hypovolemic
shock

https://teachmephysiology.com/urinary-system/regulation/antidiuretic-hormone/

REVIEW QUESTIONS
‣ Where is ADH stored and released into the circulation?
‣ Hypothalamus
‣ Posterior pituitary gland
‣ Juxtaglomerular apparatus
‣ Macula densa

REVIEW QUESTIONS
‣ Where is ADH stored and released into the circulation?
‣ Hypothalamus
‣ Posterior pituitary gland
‣ Juxtaglomerular apparatus
‣ Macula densa
‣ ADH is synthesized in the hypothalamus, but stored and
released by the posterior pituitary gland.

REVIEW QUESTIONS
‣ Where are osmoreceptors located in the brain?
‣ Subfornical terminalis
‣ Subfornical vasculosum of the lamina terminalis
‣ Organum vasculosum of the lamina temporalis
‣ Organum vasculosum of the lamina terminalis

REVIEW QUESTIONS
‣ Where does ADH exert its effect?
‣ Proximal Convoluted Tubule
‣ Loop of Henle
‣ Ascending limb
‣ Collecting duct

REVIEW QUESTIONS
‣ Which channel does ADH increase the number of?
‣ Aquaporin 1
‣ Aquaporin 2
‣ Aquaporin 3
‣ Aquaporin 4

REVIEW QUESTIONS
‣ How will an increase of ADH impact sodium
concentration?
‣ Directly increase
‣ Decrease
‣ No change
‣ Indirectly increase

REVIEW QUESTIONS
‣ How will an increase of ADH impact sodium concentration?
‣ Directly increase
‣ Decrease
‣ No change
‣ Indirectly increase
‣ An increase of ADH will increase water reabsorption, and therefore
decrease sodium concentration. This can happen in dehydrated states,
but can also happen under normal conditions. This is then called
syndrome of inappropriate antidiuretic hormone secretion (SIADH).

THE RENIN-ANGIOTENSIN-
ALDOSTERONE SYSTEM

THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
OVERVIEW
‣ The Renin-Angiotensin-Aldosterone System (RAAS) is a hormone
system within the body that is essential for the regulation of blood
pressure and fluid balance
‣ The system is mainly comprised of the three hormones renin,
angiotensin II and aldosterone
‣ Primarily it is regulated by the rate of renal blood flow
‣ Learning Goal
‣ To describe the system, discuss how the system is regulated and
outline some clinically relevant points around it

https://teachmephysiology.com/urinary-system/regulation/the-renin-angiotensin-aldosterone-system/

RAAS - RENIN RELEASE
‣ The first stage of the RAAS is the release of the enzyme renin
‣ Renin released from granular cells of the renal juxtaglomerular
apparatus (JGA) in response to one of three factors:
‣ Reduced sodium delivery to the distal convoluted tubule detected
by macula densa cells
‣ Reduced perfusion pressure in the kidney detected by baroreceptors in
the afferent arteriole
‣ Sympathetic stimulation of the JGA via β1 adrenoreceptors
‣ The release of renin is inhibited by atrial natriuretic peptide (ANP), which is
released by stretched atria in response to increases in blood pressure

RAAS - PRODUCTION OF ANGIOTENSIN II
‣ Angiotensinogen is a precursor protein produced in the
liver and cleaved by renin to form angiotensin I
‣ Angiotensin I is then converted to angiotensin II
by angiotensin converting enzyme (ACE)
‣ This conversion occurs mainly in the lungs where ACE is
produced by vascular endothelial cells, although ACE is
also generated in smaller quantities within the renal
endothelium

RAAS - BINDING OF ANGIOTENSIN II
‣ Angiotensin II exerts its action by binding to various
receptors throughout the body
‣ It binds to one of two G-protein coupled receptors, the
AT1 and AT2 receptors
‣ Most actions occur via the AT1 receptor
‣ The following table outlines its effect at different points

Site Main Action
Arterioles Vasoconstriction
Kidney Stimulates Na+ reabsorption
Sympathetic nervous system Increased release of noradrenaline (NA)
Adrenal cortex Stimulates release of aldosterone
Hypothalamus
Increases thirst sensation and stimulates
anti-diuretic hormone (ADH) release
ANGIOTENSIN II

EFFECTS OF ANGIOTENSIN II - CARDIOVASCULAR EFFECTS
‣ Angiotensin 2 acts on AT1 receptors found in the
endothelium of arterioles throughout the circulation to
achieve vasoconstriction
‣ This signalling occurs via a Gq protein, to activate
phospholipase C and subsequently increase intracellular
calcium
‣ The net effect of this is an increase in total peripheral
resistance and consequently, blood pressure

EFFECTS OF ANGIOTENSIN II - NEURAL EFFECTS
‣ Angiotensin II acts at the hypothalamus to stimulate the
sensation of thirst, resulting in an increase in fluid consumption
‣ This helps to raise the circulating volume and in turn, blood
pressure
‣ It also increases the secretion of ADH from the posterior
pituitary gland – resulting in the production of more
concentrated urine to reduce the loss of fluid from urination
‣ This allows the circulating volume to be better maintained until
more fluids can be consumed

EFFECTS OF ANGIOTENSIN II - NEURAL EFFECTS
‣ It also stimulates the sympathetic nervous system to increase
the release of noradrenaline (NA)
‣ This hormone is typically associated with the “fight or flight”
response in stressful situations and has a variety of actions
that are relevant to the RAAS:
‣ Increase in cardiac output
‣ Vasoconstriction of arterioles
‣ Release of renin

EFFECTS OF ANGIOTENSIN II - RENAL EFFECTS
‣ Angiotensin II acts on the kidneys to produce a variety of effects,
including afferent and efferent arteriole constriction and
increased Na+ reabsorption in the proximal convoluted tubule
‣ (These effects and their mechanisms are summarized in the table
on the next slide)
‣ Angiotensin II is also an important factor in tubuloglomerular
feedback, which helps to maintain a stable glomerular filtration rate
‣ The local release of prostaglandins, which results in a preferential
vasodilation to the afferent arteriole in the glomerulus, is also vital to
this process

Target Action Mechanism
Renal artery and afferent
arteriole
Vasoconstriction
Voltage-gated calcium
channels open and allow an
influx of calcium ions
Efferent arteriole
Vasoconstriction (greater
than the afferent arteriole)
Activation of AT1 receptor
Mesangial cells
Contraction, leading to a
decreased filtration area
Activation of Gq receptors
and opening of voltage-gated
calcium channels
Proximal convoluted tubule Increased Na+ reabsorption
Increased Na+/H+ antiporter
activity and adjustment of the
Starling forces in peritubular
capillaries to increase
paracellular reabsorption

ALDOSTERONE
‣ Finally, angiotensin II acts on the adrenal cortex to stimulate the release
of aldosterone
‣ Aldosterone is a mineralocorticoid, a steroid hormone released from
the zona glomerulosa of the adrenal cortex
‣ Aldosterone acts on the principal cells of the collecting ducts in the
nephron
‣ It increases the expression of apical epithelial Na+ channels (ENaC) to
reabsorb urinary sodium
‣ Furthermore, the activity of the basolateral Na+/K+/ATPase is increased

ALDOSTERONE
‣ This causes the additional sodium reabsorbed through ENaC
to be pumped into the blood by the sodium/potassium pump
‣ In exchange, potassium is moved from the blood into the
principal cell of the nephron
‣ This potassium then exits the cell into the renal tubule to be
excreted into the urine
‣ As a result, increased levels of aldosterone cause reduced
levels of potassium in the blood

REVIEW QUESTIONS
‣ What is the prime regulator of the RAAS?
‣ Serum sodium
‣ Renal blood flow
‣ Serum potassium
‣ Levels of cortisol

REVIEW QUESTIONS
‣ What is the prime regulator of the RAAS?
‣ Serum sodium
‣ Renal blood flow
‣ Serum potassium
‣ Levels of cortisol
‣ Reduced flow, reduced pressure and sympathetic
stimulation drive the RAAS

REVIEW QUESTIONS
‣ From where is renin released?
‣ Granular cells of renal juxtoglomerular apparatus
‣ Liver
‣ Adrenal glands
‣ Renal tubules

REVIEW QUESTIONS
‣ From where is renin released?
‣ Granular cells of renal juxtoglomerular apparatus
‣ Liver
‣ Adrenal glands
‣ Renal tubules
‣ Renin is released from the juxtaglomerular apparatus is
response to specific triggers

REVIEW QUESTIONS
‣ Where is ACE predominantly found?
‣ Kidneys
‣ Brain
‣ Skin
‣ Lungs

REVIEW QUESTIONS
‣ Where is ACE predominantly found?
‣ Kidneys
‣ Brain
‣ Skin
‣ Lungs
‣ ACE is predominantly produced by vascular endothelial
cells in the lungs

REVIEW QUESTIONS
‣ Which hormone is released from the adrenals following
the binding of angiotensin II?
‣ Cortisol
‣ Aldosterone
‣ ADH
‣ ACTH

REVIEW QUESTIONS
‣ Through which G protein does angiotensin 2 act in the
vasculature?
‣ Gs
‣ Gi
‣ Gq
‣ None of the above

REVIEW QUESTIONS
‣ From which structure is ADH released in response to
angiotensin 2?
‣ Anterior pituitary
‣ Hypothalamus
‣ Adrenal glands
‣ Posterior pituitary

REVIEW QUESTIONS
‣ Aldosterone causes which of the following electrolyte
changes?
‣ Increased serum sodium, increased serum potassium
‣ Increased serum sodium, reduced serum potassium
‣ Decreased serum sodium, decreased serum potassium
‣ Decreased serum sodium, increased serum potassium

REVIEW QUESTIONS
‣ Aldosterone causes which of the following electrolyte changes?
‣ Increased serum sodium, increased serum potassium
‣ Increased serum sodium, reduced serum potassium
‣ Decreased serum sodium, decreased serum potassium
‣ Decreased serum sodium, increased serum potassium
‣ By stimulating the Na/K pump, it causes increased sodium re-
absorption and increased potassium excretion

References
These slide reflect a summary of the contents of
TeachMePhysiology.com and are to be used for
educational purposes only in compliance with the terms of
use policy.
Specific portions referenced in this summary are as follows:
‣ https://teachmephysiology.com/urinary-system/regulation/antidiuretic-hormone/
‣ https://teachmephysiology.com/urinary-system/regulation/the-renin-angiotensin-
aldosterone-system/
Additional sources are referenced on the slide containing
that specific content.

3. urinary regulation

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