Chapter 340

The neurohypophysis, or posterior pituitary, is formed by axons that originate in large cell bodies in the supraoptic and paraventricular nuclei of the hypothalamus. It produces two hormones: (1) arginine vasopressin (AVP), also known as antidiuretic hormone, and (2) oxytocin. AVP acts on the renal tubules to reduce water loss by concentrating the urine. Oxytocin stimulates postpartum milk letdown in response to suckling. AVP deficiency causes diabetes insipidus (DI), which is characterized by the production of large amounts of dilute urine. Excessive or inappropriate AVP production predisposes to hyponatremia if water intake is not reduced in parallel with urine output.

### Synthesis and Secretion

AVP is a nonapeptide composed of a six-member disulfide ring and a tripeptide tail (Fig. 340-1). It is synthesized via a polypeptide precursor that includes AVP, neurophysin, and copeptin, all encoded by a single gene on chromosome 20. After preliminary processing and folding, the precursor is packaged in neurosecretory vesicles, where it is transported down the axon, further processed to AVP, and stored in neurosecretory vesicles until the hormone and other components are released by exocytosis into peripheral blood.

###### Figure 340-1

Primary structures of arginine vasopressin (AVP), oxytocin, and desmopressin.

AVP secretion is regulated primarily by the "effective" osmotic pressure of body fluids. This control is mediated by specialized hypothalamic cells known as osmoreceptors, which are extremely sensitive to small changes in the plasma concentration of sodium and certain other solutes but normally are insensitive to other solutes such as urea and glucose. The osmoreceptors appear to include inhibitory as well as stimulatory components that function in concert to form a threshold, or set point, control system. Below this threshold, plasma AVP is suppressed to levels that permit the development of a maximum water diuresis. Above it, plasma AVP rises steeply in direct proportion to plasma osmolarity, quickly reaching levels sufficient to effect a maximum antidiuresis. The absolute levels of plasma osmolarity/sodium at which minimally and maximally effective levels of plasma AVP occur, vary appreciably from person to person, apparently owing to genetic influences on the set and sensitivity of the system. However, the average threshold, or set point, for AVP release corresponds to a plasma osmolarity or sodium of about 280 mosmol/L or 135 meq/L, respectively; levels only 2–4% higher normally result in maximum antidiuresis.

Though it is relatively stable in a healthy adult, the set point of the osmoregulatory system can be lowered by pregnancy, the menstrual cycle, estrogen, and relatively large, acute reductions in blood pressure or volume. Those reductions are mediated largely by neuronal afferents that originate in transmural pressure receptors of the heart and large arteries and project via the vagus and glossopharyngeal nerves to the brainstem, from which postsynaptic projections ascend to the hypothalamus. These pathways maintain a tonic inhibitory tone that decreases when blood volume ...

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