Vasopressins(1)

7/28/2019 Vasopressins(1)

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Oxytocin, Antidiuretic

hormone

Dr KeliLevel III lectures


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Posterior pituitary hormones:ADH (AVP) and Oxytocin

(hypothalamic hormones)Both are synthesized in the cell bodies of

hypothalamic neurons

ADH: supraoptic nucleus

Oxytocin: paraventricular nucleus

Both are synthesized as preprohormones andprocessed into nonapeptides (nine amino acids).

They are released from the termini in response toan action potential which travels from the axon

body in the hypothalamus


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Hypothalamus and posteriorpituitary


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Structures of ADH and oxytocin


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In uterus during labour

In mammary gland during lactation

Oxytocin: stimulates

myoepithelial contractions


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Oxytocin: milk ejection from

lactating mammary glandsuckling is major stimulus for release.

sensory receptors in nipple connect with

nerve fibers to the spine, then impulses

are relayed through brain to where

cholinergic synapses fire on oxytocin

neurons and stimulate release.


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Oxytocin: uterine contractions

Reflexes originating in the cervical, vaginal

and uterus stimulate oxytocin synthesis and

release via neural input to hypothalamus

Increases in plasma at time of ovulation,

parturition, and coitus

Estrogen increases synthesis and lowersthreshold for release


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Synthesis of ADH

It is synthesized as pre-prohormone and processedinto a nonapeptide (nine amino acids).

Six of the amino acids form a ring structure, joined bydisulfide bonds.

It is very similar in structure to oxytocin, differing onlyin amino acid #3 and #8.

ADH synthesized in the cell bodies of

hypothalamic neurons in the supraoptic nucleus

ADH is stored in the neurohypophysis (posteriorpituitary)forms the most readily released ADHpool


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Hypothalamus and posteriorpituitary


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Structure of ADH


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Antidiuretic Hormone: ADH

ADH is also known as arginine vasopressin

(AVP = ADH) because of its vasopressive

activity, but its major effect is on the kidneyin preventing water loss.


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ADH: conserve body water and

regulate tonicity of body fluids

Regulated by osmotic and volume stimuli

Water deprivation increases osmolality of

plasma which activates hypothalmic

osmoreceptors to stimulate ADH release


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ADH increases renal tubularabsorption of water


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Primary action of ADH: antidiuresis

ADH binds to V2 receptors on the peritubular(serosal) surface of cells of the distal convolutedtubules and medullary collecting ducts.

Via adenylate cyclase/cAMP induces productionand insertion of AQUAPORIN into the luminalmembrane and enhances permeability of cell towater.

Increased membrane permeability to water permitsback diffusion of solute-free water, resulting inincreased urine osmolality (concentrates urine).


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Secretion of ADH

The biological action of ADH is to conservebody water and regulate tonicity of body

fluids. It is primarily regulated by osmotic and

volume stimuli.

Water deprivation increases osmolality ofplasma which activates hypothalmicosmoreceptors to stimulate ADH release.


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Conversely, water ingestion suppresses

osmoreceptor firing and consequently shuts

off ADH release. ADH is initially suppressed by reflex neural

stimulation shortly after water is swallowed.

Plasma ADH then declines further afterwater is absorbed and osmolality falls

Secretion of ADH


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Pathway by whichADH secretion is

lowered and waterexcretion raisedwhen excess water is

ingested


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If plasma osmolality is directly increased byadministration of solutes, only those solutes thatdo not freely or rapidly penetrate cell membranes,such as sodium, cause ADH release.

Conversely, substances that enter cells rapidly,such as urea, do not change osmotic equilibriumand thus do not stimulate ADH release.

ADH secretion is exquisitely sensitive to changesin osmolality.

Changes of 1-2% result in increased ADH

secretion.

Secretion of ADHosmolality control


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ADH andplasma

osmolality


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ADH is stimulated by a decrease in blood volume,

cardiac output, or blood pressure.

Hemorrhage is a potent stimulus of ADH release. Activities, which reduce blood pressure, increase

ADH secretion.

Conversely, activities or agents that increase blood

pressure, suppresses ADH secretion.

Secretion of ADH

hemodynamic control


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ADH and

bloodpressure


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Pathway by which ADHsecretion and tubular

permeability to water is

increased when plasmavolume decreases


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Hypovolemia is perceived by pressure receptors-- carotid and aortic baroreceptors, and stretchreceptors in left atrium and pulmonary veins.

Normally, pressure receptors tonically inhibit

ADH release. Decrease in blood pressure induces ADH secretionby reducing input from pressure receptors.

The reduced neural input to baroreceptors relievesthe source of tonic inhibition on hypothalamiccells that secrete ADH.

Sensitivity to baroreceptors is less thanosmoreceptorssenses 5 to 10% change in volume

Secretion of ADH


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Hypovolemia also stimulates the generation ofrenin and angiotensin directly within the brain.

This local angiotensin II enhances ADH release inaddition to stimulating thirst.

Volume regulation is also reinforced by atrialnaturetic peptide (ANP).

When circulating volume is increased, ANP isreleased by cardiac myocytes, this ANP alongwith the ANP produced locally in the brain, acts toinhibit ADH release.

Secretion of ADH


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The two major stimuli of ADH secretion

interact.

Changes in volume reinforce osmolarchanges.

Hypovolemia sensitizes the ADH response

to hyperosmolarity.

Secretion of ADH


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Plasma Osmolality vs. ADH

The set point of the system

is defined as the plasma

osmolality value at which

ADH secretion begins to

increase. Above this point

slope is steep reflecting

sensitivity of system. Set

point varies from 280 to290 mOsm/kg H2O


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Blood volume vs. ADH

When blood volume or

arterial pressure

decreases, inhibitoryinput from baroreceptors

is over ridden and ADH

secretion is stimulated.

Normally, signals frombaroreceptors tonically

inhibit ADH secretion.


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Actions of ADH

The major action of ADH is on renal cells that are

responsible for reabsorbing free (osmotically

unencumbered) water from the glomerular filtrate.

ADH responsive cells line the distal convoluted tubules

and collecting ducts of the renal medulla.

ADH increases the permeability of these cells to water.

The increase in membrane permeability to water permits

back diffusion of water along an osmotic gradient.

ADH significantly reduces free-water clearance by the

kidney


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Actions of ADH

ADH action in the kidney is mediated by itsbinding to V2 receptors, coupled to adenylatecyclase and cAMP production.

cAMP activates protein kinase A which promptsthe insertion of water channels into the apicalmembrane of the cell.

When ADH is removed, the water channelswithdraw from the membrane and the apicalsurface of the cell becomes impermeable to wateronce again. .


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Actions of ADH

This mechanism of shuttling water channels into

and out of the apical membrane provides a very

rapid means to control water permeability The basolateral membrane of the ductal cells are

freely permeable to water, so any water that enters

via the apical membrane exits the cell across the

basolateral membrane, resulting in the netabsorption of water from the tubule lumen into the

peritubular blood.


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Water deprivation stimulates ADH

secretion, decreases free-water clearance,

and enhances water conservation. ADH and water form a negative feedback

loop.

Actions of ADH


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Inputs reflexly controlling thirst.


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ADH deficiency is caused by destruction or

dysfunction of the supraoptic and

parventricular nuclei of the hypothalamus.Inability to produce concentrated urine is a

hallmark of ADH deficiency and is referred

to as diabetes insipidus. ADH also acts on the anterior pituitary to

stimulate the secretion of ACTH.

Actions of ADH

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