Anti Diuretic hormone (ADH) –

Vasopressin

DR.ERIC MAYO DAGRADI

LABORATORIUM ILMU FAAL
FAKULTAS KEDOKTERAN
UNIVERSITAS HANG TUAH
 Anti Diuretic hormone (ADH) – the definition
Arginine Vasopressin(AVP)

• ADH is a peptide hormone from the Hypothalamic nuclei

and stored in the posterior pituitary gland.
• It prevents the formation of dilute urine and promotes
water retention in the body
• Also called vasopressin
• www.medinenet. Com – www.vivo.colostate.edu
ADH – the background
regulates ECF

• ADH conserve body water and ECF by :

• Reduction in the formation of dilute urine
• Promotion of renal reabsorption of water and
Na+
• Maintains blood volume and BP by peripheral
vasoconstriction in response to severe drop in
blood volume
• ADH is used in the treatment of Diabetes
Insipidus
• www.medicaldictionary.com -
www.vivo.colostate.edu
 Vasopressin – the structure

• Vasopressin is a Nona peptide hormone having 9 AAs

acids including Arginine. Hence called AVP
• 2 Cysteine AAs form a Sulfahydryl bond and a ring
• Neurophysin is a carrier protein that helps to carry AVP
along the axons to be stored in Posterior Pituitary
• Is released in response to an appropriate stimulus
Structure of AVP/ADH – A Nona peptide
 Types of Vasopressin - 2
AVP and LVP

• There are 2 types of Vasopressin depending upon

the presence of Arginine or Lysine
• Arginine Vasopressin(AVP) has AA Arginine in
mammals
• Lysine Vasopressin (LVP) has AA Lysine and is
present in Pigs
 ADH – the Target organs
Kidneys/ blood vessels /CNS

These are the tissues/organs with ADH receptors like :

1. Renal : Distal Collecting tubules and Collecting ducts
2. CVS : vascular muscles/atria/ Baro Recept./carotid
sinus/aortic arch.
3. Hypothalamus : Osmo Receptors/major vessels
4. Hypothalamus : Angio II Receptors
5. Myometrium and platelets
 ADH Receptors - designation with actions
V1,V2 ,V3 and Angio11

Receptors for the ADH are designated as :

q V1 - CVS/ Baro receptors. Maintain blood volume/BP
by vasoconstriction
q V2 - Renal Tubules / ↑ water reabsorption/
Aquaporins/↓ urine formation
q V3 - Hypothalamus/Osmo receptors. Maintain Plasma
Osmolarity
q Hypothalamic Angio II Receptors – located near
Hypothalamic Osmo receptors
Activated during Hypotension to ↑ angio II and
Adosterone secretion from adrenal cortex to↑ Blood
volume and BP
Synthesis of ADH
Supra optic and PVN

• ADH is synthesized as Pro hormone in the RER of large

neurons of the Hypothalamic Nuclei :
• Supra optic and Para Ventricular
• It is bound to a carrier protein -Neurophysin that
transports AVP to the Posterior pituitary via axons
• Stored as secretary vesicles in Posterior Pitutary and
released in response to a physiological stimulus
Biosynthesis of ADH
Regulation of ADH synthesis

• ADH is regulated by the following pathways

• Changes in the ECF/plasma Osmolarity - Osmorecptors
• Low ECF volume and BP – Baro receptors
• Hypotension and Hypovolemia - Angio II Receptors
• Rennin – angio II – Aldosterone system
 Changes in ECF/plasma Osmolarity
VR2 - Osmorecptors

• Hypothalamic Osmo receptors detect changes in ECF

Osmolarity
• When ECF Osmolarity is high (↑Na), it stimulates ADH
secretion
• High ADH promotes renal reabsorption of water and
prevent the formation of dilute urine
• It lowers the ECF/plasma Osmolarity
• Opposite is true when Osmolarity of ECF is low
Regulation of ADH – hypothalamic Osmo
recptors
 Hypovolemia /Hypotension
VR1 +VR2

Hypovolumia/hypotension is sensed by the Baro receptors in the carotid

sinus and aortic arch/trunks
Baro receptors get activated to ↑ ADH secretion
↑ ADH promotes renal water reabsorption by insertion of solute free
water channel – Aquaporins 2
It restores blood volume and BP by vasoconstriction also
Opposite is true when blood volume/ BP is high
Reduction in blood volume/ BP stimulates the Baro receptors in the large
veins/arteries/(Carotid sinus) and atria to ↑ADH
A drop of 15 to 20% in BP and blood volume is required
Both promote ADH synthesis to↑ BP by vasoconstriction and Restore blood
volume by ↑ renal reabsorption
Major causes of Hypovolumia/hypotension are: Bleeding from trauma
/surgery, dehydration from diarrhea and vomiting
Regulation of ADH synthesis
Causes of Hypovolumia and hypotension

• Major causes of Hypovolumia are bleeding from

trauma/surgery , dehydration from diarrhea and
vomiting
• A drop of 15 - 20% in blood /fluid loss is required to
promote/↑ the secretion of ADH and to compensate
for :
• fluid/blood loss by peripheral vasoconstriction and ↑renal reabsorption
• Opposite is true for hypertension and hyper volumia
Rennin- angio II- Adosterone system
alternate mechanism
• Hypovolemia/hypotension is also sensed by the Angio. 11
receptors in hypothalamus
• Angio II receptors are also located near the
hypothalamic Osmo receptors which also get activated
• It promotes ADH and Aldo. secretion from Adrenal cortex
• Aldo. promotes renal reabsorption of Na+, excretion of
potassium K+ and water – sympathetic stimulation ↑ ADH
Renin- ango II- Aldosterone system
Mechanism of action – V2 R
2nd messenger system

• ADH is a peptide hormone with mechanism of like ones

• It binds to the external domain of the GPCR and
activates its Cytoplasmic Trimeric G- protein
• Causes the binding of α – GDP to α – GTP, further to
Adenylate Cyclase and release of cAMP from ATP
• cAMP is a 2nd messenger
Mechanism of action – V2 R cont.
cAMP/Insertion of Aquaporins

• cAMP stimulates the insertion of free water channels,

Aquaporins- 2 in the membranes of renal tubules
• These channels transport solute free water through the
Renal tubular cells back to blood
• It ↓ plasma Osmolarity and ↑ the Conc. of urine
Mechanism of Action - V2 R.
Insertion of AQ2
 Mechanism of action - V1R
IP3 and DAG as 2nd messenger

• Stimulation of V1 R at the vascular muscles causes the

activation of the enzyme, Phospholipase C8, in the plasma
membrane
• It cleaves PIP2 to Inositol Tri Phosphate (IP3) and Diacyglycerol
(DAG)
• These are 2nd messengers that releases intracellular Calcium
• Calcium promotes vasoconstriction, peripheral resistance and
BP
• Further, it compensates blood volume
V1R – Vascular smooth muscles
Metabolic actions of ADH

• Major action of ADH is to conserve body water via its

action on the :
• Kidneys to prevent its loss through dilute urine
formation and :
• promotion of renal reabsorption (Aquaporins)
• CVS to maintain the blood volume and BP by increasing
the vasoconstriction after blood/fluid loss through :
• bleeding; diarrhea dehydration, vomiting and trauma
ADH - Secretion abnormalities

• ADH may be secreted in excess or there can

be the deficiency of ADH secretion
• Both of the secretion abnormalities lead to
certain important clinical conditions that :
• Disturbs the normal life comforts
 Deficiency of ADH - Diabetes Insipidus (DI)
2 types

• Deficiency of ADH secretion is the most common in

human and animals that produces excessive urine
• Renal tubules lose their ability to reabsorb especially
of water
• Urinary output may be ˃ 16 L/day in some patients
• The condition is Diabetes Insipidus(DI)
• DI may be Hypothalamic/ central or
Nephrogenic/peripheral
 Types of Diabetes Insipidus

1. Hypothalamic Diabetes Insipidus is the most common

• and is due to gene mutation.
• Genetic mutation may be of ADA receptor gene or
Aquaporins gene – responsive to treatment

2. Nephrogenic DI: It is due to Renal pathology that have

lost their ability of reabsorption- non responsive to
treatment
Diabetes Insipidus – A life threatening
disease

• Diabetes mellitus is life threatening disease that give

rise
• To massive hypo volumemia / hypotension
• It is a life threatening condition If Hypovolumia is not
compensated by adequate water intake
• Desmopressin is an ADH analogue used to treat DI
• Excess is called syndrome of inappropriate ADH
secretion.
• There is Hyopnatremia and hypoosmolarity – cells swell
up and Na level is less than 135 mEq/L