Last edited: 10/2/2021

5. ANTIDIURETIC HORMONE
Endocrinology | Antidiuretic Hormone (ADH) Medical Editor: Ilia-Presiyan Georgiev

o Proximal convoluted tubule (PCT)

OUTLINE o Loop of Henle
o Distal convoluted tubule (DCT)
I) SYNTHESIS
II) STIMULI AND INHIBITORS Many nephrons empty their filtrate into one collecting
III) EFFECT ON THE KIDNEYS duct
IV) EFFECT ON THE VESSELS o The collecting duct is made of principal cells which
V) HYPERSECRETION are the target of ADH
VI) HYPOSECRETION o On the cell membrane there are vasopressin type 2
VII) APPENDIX receptors that trigger an intracellular cascade when
VIII) REVIEW QUESTIONS activated
IX) REFRENCES
(2) It activates a G stimulatory protein
that goes to an effector enzyme on the cell membrane –
I) SYNTHESIS
Adenylate cyclase
The antidiuretic hormone (ADH), also known as o The effector enzyme has a specific point of
Vasopressin is produced in the Supraoptic nucleus attachment for the Gs protein
(SON) in the hypothalamus and secreted by the o The effector enzyme becomes very active
neurohypophysis
(3) Adenylate cyclase
After it’s created it is transported down the axons in
synaptic vesicles by specific motor proteins has a specific enzyme – GTPase
The vesicles need certain stimuli to release the ADH o GTPase cuts the GTP and turns it into GDP (removes
o ↓ blood volume and ↓ blood pressure a phosphate)
o ↑ plasma osmolality  G protein is turned off
o Energy is produced and used to convert ATP to
cAMP
 cAMP activates protein kinase A (pkA)
(4) The activated pKA
goes to the cell nucleus and stimulates specific genes
o They undergo transcription and translation and
produce specific proteins
o They go to the endoplasmic reticulum, then to the
Golgi apparatus and are packed into vesicles
Figure 1 Synthesis of ADH. o The specific proteins are called aquaporin type 2
Aquaporin type 3 and 4 are located on the cell
membrane and are always open
II) STIMULI AND INHIBITORS (5) Aquaporin 2
(1) Low blood volume → low blood pressure is phosphorylated by pkA
o Vesicle merge with the cell membrane
↓ blood pressure causes the hormone Angiotensin II to
o Water located in the collective duct goes into the
be secreted
principal cell and into the blood
o Angiotensin II binds to certain receptors
o They signal the hypothalamus to release the ADH When the water goes to the blood, the plasma volume
rises
(2) High plasma osmolality o ↑ plasma volume → ↑ blood pressure
Osmolality refers to the concentration solutes and water o ↑ water in circulation → ↓ plasma osmolality drops
inside the plasma o Plasma becomes isotonic (about 300 milliosmoles
o High plasma osmolality - ↓ water, ↑ solutes per liter)

o Low plasma osmolality - ↑ water, ↓solutes

(3) Inhibitors
↑ blood volume
↓ plasma osmolality
Alcohol

III) EFFECT ON THE KIDNEYS

(1) The nephron consists of

Renal corpuscles
o Glomerulus Figure 2 Effect of ADH on the kidneys.
o Bowman’s capsule
Kidney tubules

Antidiuretic Hormone ENDOCRINE PHYSIOLOGY: Note #5. 1 of 3

 o Bacterial infection
IV) EFFECT ON THE VESSELS  Destroys different tissues causing a rise in the
ADH levels.
(1) There are ADH receptors (type V1) o Meningitis
on the smooth muscle cells in any systemic blood vessel ↑ ADH → ↑ water remain
ADH binds to the receptors and activates a Gq protein
mechanism → ↑ Ca++ levels in the cells
o The cells contract If the water remains higher than the solutes (especially
o The vessels decrease their perimeter sodium and chlorine) water will start leaking out the blood
(vasoconstriction) vessels
 ↑peripheral resistance o There are not enough salts to keep it inside
 ↑the blood pressure If it leaks into the brain it can cause cerebral edema
o Very dangerous
o Can be treated with mannitol to pull the water out

VI) HYPOSECRETION

(1) Diabetes Insipidus

Causes
o Severe trauma to the head
Figure 3 Effect of ADH on the vessels.
 Damages the hypothalamus/ posterior pituitary
 Prevents ADH secretion

V) HYPERSECRETION ↓ ADH
o Great water losses through the urine – polyuria
(1) Syndrome of inappropriate ADH secretion (SIADH) o Persisting feeling of thirst – polydipsia
Causes
Back in the days they tasted urine to diagnose diabetes
o Tumors
 Hypothalamus Sweet urine → diabetes mellitus
 Posterior pituitary Bitter and watery urine → diabetes insipidus

VII) APPENDIX

Effects of ADH
Location of the
Target organ Receptors Mechanism Effects
receptors
Water located in the collective duct
Kidneys Vasopressin type 2 Principal cells Gs goes into the principal cell and into the
blood
Smooth muscle
Vessels Vasopressin type 1 Gq Vasoconstriction
cells

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 VIII) REVIEW QUESTIONS IX) REFRENCES
When bound to __________ specific receptors
● Le T, Bhushan V, Sochat M, Chavda Y, Zureick A. First Aid for
signal the hypothalamus to release the ADH? the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017
a. Angiotensin I ● Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ:
b. Angiotensin II Pearson; 2020.
c. Angiotensin III ● Boron WF, Boulpaep EL. Medical Physiology.; 2017.
● Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL,
d. Angiotensin IV Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth
Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical; 2018
● Hall JE, Hall ME. Guyton and Hall Textbook of Medical
Which stimuli activate the release of ADH? Physiology. Philadelphia, PA: Elsevier; 2021.
a. ↓ blood volume, ↓ blood pressure, ↓ plasma
osmolality
b. ↑ blood volume, ↑ blood pressure, ↓ plasma
osmolality
c. ↓ blood volume, ↑ blood pressure, ↑ plasma
osmolality
d. ↓ blood volume, ↓ blood pressure, ↑ plasma
osmolality

On the cell membrane of which cells are type 2

vasopressin receptors located??
a. Principal cells on the collecting duct
b. Principal cells on the proximal convoluted tubule
c. Principal cells on the loop of Henle
d. Principal cells on the distal convoluted tubule

Which enzyme is need for energy so that pkA is

activated?
a. UTPase
b. ATPase
c. ADPase
d. GTPase

Which proteins are produced as an effect of pkA?

a. Gs protein
b. Aquaporin 3
c. Aquaporin 2
d. Gi protein

What happens to the plasma when the plasma

osmolality drops??
a. Becomes hypotonic
b. Becomes isotonic
c. Becomes hypertonic
d. Becomes watery

What is the effect of ADH on blood vessel?

a. Relax
b. Contract
c. Clog
d. Rupture

Hyposecretion of ADH leads to?

a. Diabetes mellitus
b. Syndrome of inappropriate ADH secretion
c. Diabetes insipidus
d. Acromegaly

Symptoms of diabetes insipidus are:

a. Polyuria
b. Cerebral edema
c. Night sweats
d. General edema

What is the usual cause of SIADH?

a. Kidney disease
b. Diabetes mellitus
c. Trauma
d. Tumor

CHECK YOUR ANSWERS

Antidiuretic Hormone ENDOCRINE PHYSIOLOGY: Note #5. 3 of 3