2. THE POSTERIOR PITUITARY GLAND
The posterior pituitary gland, also called neurohypophysis, is composed mainly of glial-like supporting cells called pituicytes.
These do not produce hormone but receive terminal nerve endings of large magnocellular neurons that originate in the hypothalamus.

3. The posterior pituitary gland hormones
Posterior pituitary gland releases 2 hormones:
1. Antidiuretic hormone (ADH), or arginine vasopressin
(AVP).
2. Oxytocin
Both hormones are produced in hypothalamic nuclei:
- Supraoptic nucleus  (ADH + 1/6 oxytocin)
- Paraventricular nucleus  (Oxytocin + 1/6 ADH)

4. The posterior pituitary hormones – 1. ADH (vasopressin):
ADH activates (2) second messenger systems:
1. cAMP
2. IP3/Ca2+

5. 1) Antidiuretic hormone (ADH) or vasopressin 2) Oxytocin
Nerve tracts originate in the supraoptic and paraventricular nuclei of the hypothalamus. These tracts pass to the neurohypophysis through the pituitary or hypophyseal stalk.
The nerve endings are bulbous knobs that contain many secretory granules called herring bodies. These endings lie on the surfaces of the capillaries onto which they secrete two posterior pituitary hormones
1) Antidiuretic hormone (ADH) or vasopressin
2) Oxytocin

6. Neurophysin I carries oxytocin and
Vasopressin and oxytocin, each has a characteristic binding polypeptide called neurophysin associated with it, in the granules of the neurons that secrete them. These are thought to be:
Neurophysin I carries oxytocin and
Neurophysin II carries vasopressin.

7. When nerve impulses are transmitted downward along the fibers, the hormone is released from the secretory granules by Ca-dependant exocytosis and is absorbed into adjacent capillaries.
As hormone is loosely bound to neurophysin, it immediately separates while neurophysin has no known functions afterwards.

8. VASOPRESSIN RECEPTORS
VIA, VIB and V2.
All are G protein-coupled.
The VIA and VIB act through phosphotidylinositol hydrolysis to increase the intracellular Ca conc.
The V2 act through c-AMP formation.

9. Location V in the luminal membranes of renal collecting duct system VIA---- in the vascular smooth muscle, liver and brain

10. Action of ADH ADH has 2 main effects:
1.  water re-absorption (retention) by distal tubules & collecting ducts of the kidneys.
* This effect is regulated by V2 receptors, through the
action of cAMP.
2. Contraction of vascular smooth muscles  generalized vasoconstriction.
* This effect is regulated by V1 receptors, through the action
of IP3/Ca2+.

12. PHYSIOLOGIC FUNCTIONS OF ADH Principal effect is retention of water by the kidney, hence, often called Antidiuretic hormone (ADH). It greatly increases the permeability of the collecting ducts & collecting tubules to water and allows it’s reabsorption. In this way it conserves water and produces a very conc. urine. In the absence of ADH , the tubules are impermeable to water and cause extreme dilution of urine.

13. The Effects of ADH on the distal collecting tubules and Collecting Ducts
Figure 26.15a, b

14. Mechanism of antidiuresis When ADH acts, it combines with membrane receptors that form c-AMP. It phosphorylates the protein channels aquaporins and insert them in the apical portions of cells, thus providing high water permeability.

15. Formation of Water Pores: Mechanism of Vasopressin Action

16. Facultative water reabsorption

17. All this occurs in 5 to 10 minutes
All this occurs in 5 to 10 minutes. Movement of water is by simple diffusion. At least 5 types of aquaporins have been identified. 1,2 &3 are found in the kidneys, 4 is found in the brain and 5 is found in the salivary and lacrimal glands and in the resp. tract.

18. REGULATION OF ADH
Near the hypothalamus are modified neuron receptors called osmoreceptors. When the ECF becomes too conc., fluid is pulled by osmosis out of the osmoreceptor cell decreasing it’s size and sending signal to the hypothalamus to secrete ADH. Vice versa.

19. A second neuronal area important in controlling osmolarity and ADH secretion is located along the anteroventral region of the third ventricle, called the AV3V region. At the upper part of this region is a structure called the subfornical organ, and at the inferior part is another structure called the organum vasculosum of the lamina terminalis (OVLT). Between these two organs is the median preoptic nucleus, which has multiple nerve connections with the two organs as well as with the supraoptic nuclei and the blood pressure control centers in the medulla of the brain.

20. Control of ADH release
1. Increased plasma osmolality,  arterial blood pressure, due to  blood volume   ADH.
2. Age:   ADH secretion  water retention & hyponatremia.
3. Pain, nausea, emotional stress & physical trauma   ADH secretion.
4. Drugs, e.g. morphine, barbiturates, & nicotine   ADH
secretion.
5. Alcohol   ADH secretion.
6. Hypoxia increases ADH secretion

21. Dr. Bolliger Kanas University Medical Center 1999
The basic feedback loop is shown in this slide. An increase in ECF osmolality stimulates the osmoreceptive cells in the two hypothalmic nuclei. The cell bodies of these neurons respond to stretch and their firing rate is directly proportional to it.
As we will see soon, these neuroendocrine cells are also innervated by nerve tracks coming from the medulla. These nerve tracks receive input from the baroreceptors in and around the great vessels of the heart.
When firing rate of the neuroendocrine cells increase, ADH is released from the post synaptic nerve terminals in the posteriour pituitary. The half life of ADH is only about 20 min. This allows the effect of the hormone to be rapidly present and rapidly cease when it is no longer needed. This is a very tightly regulated hormone. The figure implies that ADH acts on the CCD and Medullary collecting ducts to increase water reaborption. As ADH levels increase, urine volume decreases and urine osmolality increases.
Dr. Bolliger Kanas University Medical Center 1999

22. ADH hormone is a small 9 amino acid peptide hormone that shares tremendous similarity with oxytocin (necessary for uterine contactions and milk ejection during breast feeding). These two hormones are produced by cells located in the same regions of the hypothalmus and they differ by only 2 amino acids in their structure. They can occupy each others receptors if the concentrations in blood rise out of the normal range. This needs to be kept in mind in obstetrics since ocytocin (called pitocin) is adminstered to speed up labour and if the amounts given are too high will cause water retention in the mother. This can be an extremely serious problem which causes CNS swelling- neurons swell, expand into the ventricles, and cause irreversible brain damage. Physicians are far more aware of this now and vigilante in using oxytocin.
Getting back to ADH also called vasopressin, or AVP is produced by osmosensitive neuroendocrine cells in the hypothalmus. As ECF osmolality increases, the cells shrink and their rate of firing increases. This is associated with the release of ADH from the nerve endings which reside in the posterior pituituary. The osmotic shrinkage also stimulates ADH synthesis and transport of the hormone to the nerve endings. There is always sufficient ADH in the nerve endings to respond to osmotic drive. ADH receptors are expressed in the kidney cells that are responsible for water conservation. As shown above
ADH causes pure water to be conserved by the kidney which can be seen in an increase in urine osmolality and a reduction in urine volume. The water that is retained helps restore Body fluid osmolality back to normal.

24. Vasoconstrictor effect of ADH
Higher conc. of ADH have a potent effect of constricting the arterioles , thus increasing the blood pressure. For this reason ADH is also called Vasopressin.
Decreased blood volume esp. up to %, strongly stimulates ADH secretion, the secretory rate may rise to as high as 50 times normal.

25. Mechanism of vasoconstriction
The atria, esp. right atrium, have stretch receptors which are stimulated by overfilling. When they are excited, they send signals to brain to inhibit ADH secretion.
Conversely when unexcited due to under filling, greatly increased secretion of ADH occurs.

26. Decreased stretch of baroreceptors of the carotid, aortic and pulmonary regions participate in increased ADH secretion.

27. Receptors in hypothalamus
Control of ADH release
1.  in plasma osmolality, as in dehydration which will stimulate osmoreceptors in the hypothalamus   ADH.
Hyperosmolarity of ECF
-ve feedback
Receptors in hypothalamus
More ADH release
Thirst
Collecting ducts of kidneys
 Water intake
Reabsorption of water
Dilution of ECF

28. Control of ADH release … cont.
2.  blood volume ( 10%)  stimulate mechanoreceptors in the great arteries (aorta & carotids) & right atrium   ADH.
Loss of ECF volume
Less pressure in Rt. atrium & great vessels
Less nerve impulse to the hypothalamus
Thirst
More ADH release
 Water intake
More water reabsorption by kidneys
Maintains ECF volume

29. Abnormalities of ADH release – Hyposecretion:
Lack of ADH  Diabetes insipidus.
2 types of DI: a. Neurogenic (central, or cranial) …
Problem in Hypothalamus or Post pituitary
gland.
b. Nephrogenic …resistance of V2 receptors
in collecting ducts of the kidneys.
- No ADH is needed as treatment.
Symptoms: Polyuria  20 L/day (N  1.5 L/d)
 specific gravity of urine (diluted urine),
 plasma osmolality.

30. Primary Polydypsia
Patient drinks too much water that continuously suppresses ADH

31. What happens if we give ADH?
Disorder
AQP2 expression
Urine osmolality
Urine volume
Central Diabetes Insipidus
Yes
Will increase
Will decrease
Nephrogenic Diabetes Insipidus No
No response
No change
Primary Polydypsia
Have to stop patient from drinking- the ADH would increase on its own
Central DI can be treated with the administration of a stable ADH analogue- 8-D-desaminoADH. ADH itself as a half life of about 20 minutes. It is rapidly destroyed by plasma peptidases.
Nephrogenic DI is not easily managed since normal responsiveness to ADH can not be restored. Paradoxically, the strategy for treatment is to reduce the volume of fluid that is delivered to the CCD thus reducing volume losses. This is accomplished by giving the patient a thiazide diuretic. This causes a decrease in effective circulating volume, which slightly reduces GFR, enhances proximal reabsoption thus reducing delivery to the distal nephron. This has been found to be helpful for many patient.
Primary polydipsia has to be carryully diagnosed to determine if the water intake is a primary problem or the normal response to high water loss. A period of water deprivation will easily reveal the answer. Water output will begin to decline and the patient’s plasma osm will start to return to normal. In contrast a person with Central DI if deprived of water will continue producing the large volume of low osm urine and plasma osm will rapidly increase about normal e.g. like Sam in our initial case.

32. Abnormalities of ADH release – Hypersecretion:
 ADH, ‘Schwartz-Bartter Syndrome’:
 - occurs after surgery.
- adenoma.
- Bronchial carcinoma.
Signs & Symptoms:
- Hyponatremia
- Mental confusion.
- Coma.

33. Is it Christmas yet...