1. Anti Diuretic hormone (ADH) – Vasopressin Lecture NO : 2nd MBBS
Dr Muhammad Ramzan

2. Anti Diuretic hormone (ADH) – the definition Arginine Vasopressin(AVP)
ADH is a peptide hormone from Hypothalamic nuclei and stored in posterior pituitary gland as vesicles
It prevents the formation of dilute urine and promotes water retention in the body
Also called vasopressin for ↑ BP
Com –

3. ADH – the background regulates ECF
ADH conserve body water and ECF by preventing the formation of dilute urine and :
Promoting renal reabsorption of water and Na
Maintains blood volume/ BP by peripheral vasoconstriction in response to severe drop in blood volume
ADH is used in the treatment of Diabetes Insipidus

4. Vasopressin – the structure
Vasopressin is a Nona peptide hormone having 9 AAs 1. including AA. Arginine. Hence called AVP
2. Cysteine AA form a Sulfahydryl bond and a ring
Neurophysin, a carrier protein that helps to carry AVP along axons to be stored in Post. Pituitary
It Is released in response to an appropriate stimulus
↑ Osmolarity, ↓ BP

5. Structure of AVP/ADH – A Nona peptide

6. 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 in Pigs

7. ADH – the Target organs Kidneys/ blood vessels /CNS
These are the tissues/organs with ADH receptors like:
Renal : Distal Collecting tubules and Collecting ducts
CVS : Baro Receptors in Carotid sinus/aortic arch and vascular muscles/atria
CNS /Hypothalamus: Osmo Receptors/major vessels 3
Hypothalamus : Angio11 Receptors
Myometrium and platelets

8. ADH Receptors - designation with actions V1,V2 ,V3 and Angio11
Receptors for the ADH are designated as :
V1 - CVS/ Baro receptors. Maintain blood volume/BP
V2 - Renal Tubules: ↑ water reabsorption/ Aquaporins
V3 – Hypothalamus Osmo receptors. Maintain Plasma Osmolarity
4. Hypothalamic Anglo 11 Receptors – located near Hypothalamic Osmo receptors
Activated during Hypotension to ↑ angio11 and Aldosterone secretion from adrenal cortex to↑ Blood volume and BP

9. Synthesis of ADH Supra optic and PVN
ADH is synthesized as Pro hormone in RER of :
Supra optic and Para Ventricular nuclei
It is bound to a carrier protein - Neurophysin that transports AVP to Post. Pitu. via axons
Stored as secretary vesicles in Post. Pituitary and released in response to a physiological stimulus
↑Osmolarity, and ↓ BP

10. Biosynthesis of ADH

11. Regulation of ADH synthesis
ADH is regulated by the following 3 pathways
Changes in ECF/plasma Osmolarity: Osmorecptors 1
Changes in ECF volume and BP : Baro receptors 2
Renin - angio11 – Aldo system : Angio11 receptors 3

12. Regulation of ADH synthesis

13. Regulation of ADH synthesis

14. Causes of Hypovolumia and hypotension - 2
Major causes of Hypovolumia are:
1. Bleeding from trauma/surgery 2. dehydration from diarrhea and vomiting
A drop of % in blood /fluid loss is required for ↑ in ADH secretion to compensate for fluid loss
Opposite is true for hyper volumia and hypertension

15. Changes in ECF Osmolarity VR3 – hypothalamic Osmorecptors
Changes in the Osmolarity of ECF are detected by the Hypothalamic Osmo receptors
High Osmolarity (↑Na), stimulates ADH secretion that promotes renal reabsorption of H2O
It , thus lowers Osmolarity of ECF/plasma
Opposite is true when Osmolarity of ECF is low (↓ADH)

16. Regulation of ADH – hypothalamic Osmo recptors

17. Changes in ECF volume and BP VR1 +VR2
↓BP/blood volume is sensed by the Baro receptors in the carotid sinus and aortic arch/Trunks
Baro receptors get activated to ↑ ADH secretion that
promotes renal water reabsorption
It restores blood volume and ↑BP by vasoconstriction
Opposite is true when blood volume/ BP is high

18. Renin- angio11- Adosterone system alternate mechanism
↓ BP/blood volume is also sensed by hypothalamic Angio.11 receptors that are located near to:
Hypothalamic Osmo receptors
Get activated to promote ADH and Aldo. secretion
Both promote renal reabsorption of Na+ and water,
Aldo also promote excretion of K+
Both ↑ vasoconstriction and ↑ BP’ /Sympathetic NS

19. Renin- ango11- Aldo. system

20. Mechanism of action – V2 R 2nd messenger system
ADH is a peptide hormone with mechanism of like ones
It binds to the GPCR; activates G- Protein,α- GTP which stimulates Adenylate Cyclase for cGMP, 2nd messenger
It inserts Aquaporins 2 to ↑ free water renal reabsorption Thus, ↑ blood volume that lowers Osmolarity
Further it ↑ urinary conc.

21. Mechanism of Action - V2 R. Insertion of AQ2

22. Mechanism of action - V1R IP3 and DAG as 2nd messenger
Stimulation of V1 R at the vascular muscles causes the activation of membranous enzyme:
Phospholipase C8 that cleaves PIP2 to :
IP3 (Inositol Tri Phosphate) and Diacyglycerol (DAG)
Both 2nd messengers release intracellular Calcium
Ca++ promotes vasoconstriction and ↑BP
Further, it increases venous return

23. V1R – Vascular smooth muscles

24. Metabolic actions of ADH
Major action of ADH is to conserve body water via its action on the Kidneys to ↓dilute urine formation and:
↑ urinary reabsorption (Aquaporin2)
To maintain the blood volume/ BP by ↑ing vasoconstriction after blood or fluid loss

25. ADH - Secretion abnormalities
ADH may be secreted in excess or there can be the deficiency of ADH secretion
Both abnormalities lead to certain important clinical conditions that :
Disturbs normal life comforts

26. Deficiency of ADH - Diabetes Insipidus (DI) 2 types
ADH deficiency is common in human and animals that produces excessive urine
Urinary output may be ˃ 16 L/day in some patients
The condition is called Diabetes Insipidus(DI)
DI may be Hypothalamic/ central and :
Nephrogenic or peripheral

27. Types of Diabetes Insipidus 2
1.Hypothalamic DI is commonly due to gene mutation
Genetic mutation may be of ADA receptor gene or Aquaporins gene – is responsive to treatment
2.Nephrogenic DI: It is due to Renal pathology that have lost their ability of reabsorption
It is non responsive to treatment

28. Diabetes Insipidus – A life threatening disease
Diabetes Insipidus, is a life threatening disease that give rise to massive hypo volumemia / hypotension
If Hypovolumia is not compensated by adequate water or fluid intake it may be fatal
Desmopressin is an ADH analogue, used to treat DI

29. ADH excess – Reduction in Sodium level
Excess is called syndrome of :
Inappropriate ADH secretion.
There is Hyopnatremia and hypo - Osmolarity
Cells may swell up if Na level is less than 135 mEq/L