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91

▪ Both are polypeptides, each containing nine amino acids
▪ Vasopressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-ArgGlyNH2
▪ Oxytocin: Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH2
▪ The similarity of the molecules explains their partial functional similarities

ADH and Oxytocin

92

▪ Injection (as small as 2 nanograms) can cause decreased excretion of water by the kidneys
▪ Without this hormone, the collecting tubules and ducts become almost impermeable to water and allows extreme loss of water into the urine
▪ causes insertion of aquaporins which causes absorption of water from the collecting tubules and ducts by osmosis

Anti-diuretic Hormone (ADH)

93

Vasoconstrictor Effect of ADH

▪ Low concentrations of ADH cause water reabsorption
▪ Higher concentrations of ADH have a potent effect of constricting the arterioles throughout the body
▪ Stimulus: decreased blood volume
▪ Decreased stretch signal from atrial stretch receptors, baroreceptors of the carotid, aortic, and pulmonary regions

94

Regulation of ADH

▪ Secretion of ADH primarily regulated by osmotic & volume stimuli
▪ Most important physiologic stimulus for ADH secretion: ↑ plasma osmolarity
▪ Hypovolemia or volume contraction also potent stimulus
▪ H2O is conserved in the body while Na & other solute continue to be excreted in the urine → causes dilution of the solutes in the ECF → correcting the initial excessively concentrated ECF

95

- State of excess free water excretion

Manifested by :
- Excretion of excessive amounts of dilute urine
- Excessive thirst
- Reduction of fluid intake will not affect the concentration of the urine

Diabetes Insipidus (DI)

96

▪ Total or partial loss of the ability to synthesize or release AVP
▪ Causes: brain tumor; head trauma and brain surgery that damages the posterior pituitary or hypothalamus
▪ Loss of free water leads to an ↑ in plasma osmolality

Central Diabetes Insipidus

97

▪ Hyperosmolality cannot increase AVP sufficiently but usually results in a large increase in thirst

▪ In many patients with this disease, the patient has:
a. high water intake and output
b. normal plasma osmolality

▪ It is only when water intake is restricted that the severe hyperosmolality becomes apparent

Central Diabetes Insipidus

98

▪ Levels of ADH is normal or elevated but the renal tubules cannot respond appropriately to ADH

Nephrogenic Diabetes Insipidus

99

Nephrogenic Diabetes Insipidus: Causes

- Failure of the countercurrent mechanism to form a hyperosmotic medullary interstitial
- ADH receptors in distal tubules and collecting ducts maybe non-functional or kidneys damaged
- Drugs : lithium (drug for bipolar disorder) and tetracyclines

100

Treatment of Diabetes Insipidus

1. Central DI: Synthetic analog of ADH like desmopressin (subcutaneous or nasal spray)

2. Nephrogenic DI:
- Correct the underlying renal disorder for hypernatremia: low Na diet
- Diuretic that enhances sodium excretion: Thiazides

101

▪ Overproduction of ADH not accounted for by hyperosmolality or non-osmotic stimuli to ADH
▪ Excessive secretion of ADH → reduces urine output
→ retention of water and increase in volume of ECF
→ secondary increase in urine output
→ urine formed is concentrated
→ Na+ and other ions excreted in urine
→ low Na+ in ECF

Syndrome of Inappropriate Anti-diuretic Hormone (SIADH)

102

Low Sodium in the blood can lead to

Brain swelling, seizures, coma and eventually Death

103

Treatment of SIADH

▪ Aimed towards correcting hyponatremia and its symptoms
- Loop diuretic (furosemide): promotes free water excretion
- Isotonic and sometimes, hypertonic saline
- Fluid intake restriction to 0.5 to 1.0 L/day
- Aquaretics/vaptans: agents that competitively block ADH action and increase water excretion
- Demelocycline (an older tetracycline)

104

▪ Powerfully stimulates contraction of the pregnant uterus
▪ Facilitates bonding or attachment between mother and infant
▪ Causes milk to be expressed from the alveoli into the ducts of the breast
▪ Psychogenic factors and sympathetic activation can inhibit OTC secretion and depress milk ejection

OXYTOCIN

105

▪ This hormone is at least partially responsible for causing birth of the baby:
- In a hypophysectomized animal, the duration of labor is prolonged
- Amount of oxytocin in the plasma increases during labor, especially during the last stage
- Stimulation of the cervix in a pregnant animal elicits nervous signals that pass to the hypothalamus and cause increased secretion of oxytocin

OXYTOCIN

106

▪ Brand names: Syntocinon®, Pitocin ®
▪ Used therapeutically to decrease immediate postpartum bleeding
▪ Used to induce labor
▪ OTC assists in ovulation & in the termination of the corpus luteum

OXYTOCIN as a Drug

107

More Reasons to Breastfeed

▪ Oxytocin is not only extensively interconnected to the cortisol, noradrenaline and several neurotransmitter systems to produce long-term effects
▪ It is also highly correlated to resilience to stress, growth, healing and well-being.

108

- Central 20% of the adrenal gland
- Neuroectodermal in origin
- Functionally related to ANS
- Secretes catecholamines in response to sympathetic stimulation
- An enlarged specialized sympathetic ganglion

Adrenal medulla

109

- Discharge catecholamines into the bloodstream
- Composed of chromaffin cells
- Catecholamines are secreted into the blood to act as hormones
- Source of ALL circulating epinephrine and ~30% of circulating norepinephrine

Adrenal medulla

110

- Innervated by cholinergic preganglionic sympathetic neurons
- Contains granules

chromaffin cells

111

Adrenal medulla: Vascularity

- Blood is carried from cortex to medulla
Few medullary arterioles (oxygen- and nutrient-rich blood)
Numerous cortical sinusoids (rich with cortical hormones)

- Medullary arterioles and cortical sinusoids >> medullary plexus of vessels >> single suprarenal vein

112

(Adrenal Medulla: Vascularity)
Consequence of high concentration of cortisol from cortex bathe chromaffin cells

- Cortisol inhibits neuronal differentiation of the medullary cells
- Cortisol induces expression of PNMT (converts NE to epinephrine)

113

- Outer 80% of the adrenal gland
- Mesodermal in origin
- Secretes CORTICOSTEROIDS which are all synthesized from cholesterol

Adrenal cortex

114

- Thin layer underneath the capsule
- Secretes ALDOSTERONE because it contains aldosterone synthase
- Controlled mainly by ECF concentrations of angiotensin II and potassium (Both stimulate aldosterone secretion)

Zona glomerulosa

115

- Middle and widest layer
- Straight cords of large cells with "foamy" cytoplasm
filled with lipid droplets
- Secretes CORTISOL AND CORTICOSTERONE, and small amounts of androgen and estrogen
- Controlled by hypothalamo-pituitary-adrenal axis ACTH

Zona fasciculata

116

- Deep layer
- Secretes ADRENAL ANDROGENS DEHYDROEPIANDROSTERONE (DHEA) AND ANDROSTENEDIONE, and small amounts of estrogen and glucocorticoids
- Controlled by ACTH and cortical androgen-stimulating hormone*

Zona reticularis

117

MNEMONICS for the ADRENAL MEDULA LAYERS

“It gets sweeter as you go deeper”
Glomerulosa - Salt (Mineralocorticoid)
Fasciculate - Sugar (glucocorticoid)
Reticular - Sex (androgens)

118

Principal corticosteroids

1. Aldosterone (principal mineralocorticoid)
2. Cortisol (principal glucocorticoid)
3. Adrenal cortex also produce small amounts of sex hormones (androgenic hormones)

119

Affects the electrolyes (“minerals”) of the ECF sodium and potassium

Aldosterone (principal mineralocorticoid)

120

- Exhibits important effects that increase blood glucose concentration
- Protein and fat metabolism

Cortisol (principal glucocorticoid)