03 September 2016

Lecture #3: THE PITUITARY GLAND: THE NEUROHYPOPHYSIS




THE NEUROHYPOPHYSIS

A.    The Oxytocin

Function of oxytocin

1.      Causes the milk ejection from the lactating breast; regulated by positive feedback mechanism; PRL cooperates with oxytocin.

2.      Stimulates contraction of uterine muscles that occurs during childbirth; regulated by positive feedback mechanism.

3.      Aids in fertilization by promoting fertilization of the ovum causing uterine propulsion of the male semen upward the fallopian tubes (escalator effects of oxytocin)


Regulation of secretion

1.      Stimulation of the nipple by the sucking infant–oxytocin release stimulates the myoepithelium of the ductulas if the infant is unable to obtain milk by sucking.

2.      Dilatation of the cervix and stimulation of other generative organs – oxytocin release plays a role in the initiation and maintenance of uterine contractions during labor. Uterine muscle is responsible to oxytocin only if it has previously been exposed to estrogen.


B.     The Antidiuretic Hormone (ADH): Vasopressin

Function of ADH

1.      Increase water permeability of the luminal membrane of the collecting duct epithelium.

2.      The V1 receptors mediate vascular smooth muscle contraction and stimulate prostaglandin synthesis and liver glycogenolysis. Activation of these receptors increases phosphatidylinositol breakdown, thus causing cellular calcium mobilization.

3.      The V2 receptors, which produce the renal actions of vasopressin, activate G proteins and stimulate the generation of cyclic AMP.

Regulation of secretion

ADH stimulation starts with its binding to the V2 receptor located on the distal convoluted tubules and collecting ducts. Adenyl cyclase is activated, and cAMP is generated. The second messenger (cAMP) probably initiates a phosphorylation of a membrane protein or proteins, causing an increase in the luminal membrane permeability to the water. In addition to regulating water balance in the body, the action of ADH has a concentrating effect on the urine. The primary stimulus for ADH secretion is an increase in the plasma osmolality as detected by the osmoreceptors in the brain. Patients with an ADH deficiency have a polydipsia (increased thirst) and polyuria (increased urine output). The name arginine vasopressin is also applied to this hormone, since it can cause generalized vasoconstriction and may help in maintaining blood pressure during traumatic injuries.

Clinical significance of ADH

1.      Hypersecretion

a.      Diabetes insipidus (D.I.) – a disorder resulting from deficient ADH action and is characterized by the passage of copious amounts of very dilute urine. This disorder must be distinguished from other polyuric states such as primary polydipsia and osmotic diuresis.

Classification of D.I.

(1)   Central or Neurogenic D.I. – cause by hypophysectomy (complete or partial), surgical removal of suprasellar tumors, histiocytosis, granulomas, infections, interruption of blood supply.

(2)   Nephrogenic D.I. – cause by chronic renal disease (any renal disease that interferes with collecting duct or medullary function, e.g. chronic pyelonephritis), hypokalemia, protein starvation, hypercalcemia, sickle cell anemia, Sjogren’s syndrome, drugs (e.g., lithium, fluoride, methoxyflurane anesthesia, demecycline, colchicine), congenital effect.

b.     Primary polydipsia – a disorder of thirst that is either due to psychogenic causes or to altered osmotic and non–osmotic regulation of thirst, which involves greatly increased drinking, usually in excess of 5L of water per day, leading to dilution of the ECF, inhibition of vasopressin secretion and water diuresis.

2.      Hyposecretion

a.      Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH)

Conditions associated with SIADH

(1)   Malignant lung disease, particularly bronchogenic carcinoma.

(2)   Non–malignant lung disease, e.g. tuberculosis

(3)   Tumors at other sites (especially lymphoma, sarcoma), e.g., duodenum, pancreas, brain, prostate, thymus.

(4)   CNS trauma and infections

(5)   Drugs that stimulate vasopressin release, e.g., clofibrate, chlorpropamide and other drugs such as thiazides, carbamazepine, phenothiazine, vincristine, cyclophosphamide.

(6)   Endocrine diseases: adrenal insufficiency, myxedema, anterior pituitary insufficiency.

Laboratory diagnosis of ADH

1.      Vasopressin test

Give 5 units of aqueous vasopressin subcutaneously or 1 ug of desmopressin acetate intravenously, intramuscularly or subcutaneously and measure urine osmolality after 1 hour.

Patients with complete central diabetes insipidus will show an increase of >50% in urine osmolality, while patients with nephrogenic diabetes insipidus show an increase of <50%.

Patients with partial central diabetes insipidus also show increases of <50% and patients with primary polydipsia have responses <9%. In these cases, measurement of ADH levels is particularly helpful.

CONCEPT OF PANHYPOPITUITARISM

Panhypopituitarism is a generalized hypofunction of the pituitary gland with resulting decreases in all pituitary hormone levels. Generally, panhypopituitarism is seen after severe damage has occurred in the pituitary. These patients have thyroid and adrenal insufficiency as well as absence of gonadal function. Most often, the treatment for this syndrome is replacement of the deficient hormone.

1.      Simmond’s disease – is a form of panhypopituitarism that develops after destruction of the pituitary by surgery, infection, injury or tumor. The symptoms may vary in intensity and include extreme weight loss, general debility, dry skin, bradycardia, hypotension, atrophy of the genitalia and breasts and premature senility.

2.      Sheehan’s syndrome – another form of panhypopituitarism, often with an insidious onset. This syndrome is caused by a pituitary infarction after complications of postpartum hemorrhage. It is thought that the infarction may be caused by vascular spasms of the hypophyseal arteries, resulting in a decreased blood flow to the pituitary, tissue hypoxia and necrosis.

During pregnancy, the pituitary is slightly enlarged from an increased demand of hormones, causing an increased need for nutrients and oxygen to the pituitary cells. This may make it more susceptible to the hypoxia induced by the vascular spasms. The first symptom of Sheehan’s syndrome is failure of lactation (decreased PRL) and postpartum amenorrhea (decreased FSH and LH). The number of symptoms and the severity depend on the actual amount of pituitary tissue destroyed. Decreased TSH results in hypothyroidism (dry skin, coarse hair, bradycardia, hypotension). Mineralocorticoids from the adrenal cortex are usually not affected by decreased ACTH, so plasma sodium is generally normal. If the posterior as well as the anterior pituitary is damaged, the patient may also have diabetes insipidus. Sheehan’s syndrome is more likely to develop in women with poor prenatal care. This syndrome is becoming a rare disorder largely because of improved prenatal care.





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