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.
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.
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 or pressure falls by >10–20%. This baroregulatory system is probably of minor importance in the physiology of AVP secretion because the hemodynamic changes required to effect it usually do not occur during normal activities. However, the baroregulatory system undoubtedly plays an important role in AVP secretion in patients with large, acute disturbances of hemodynamic function.
AVP secretion also can be stimulated by nausea, acute hypoglycemia, glucocorticoid deficiency, smoking, and, possibly, hyperangiotensinemia. The emetic stimuli are extremely potent since they typically elicit immediate, 50- to 100-fold increases in plasma AVP even when the nausea is transient and is not associated with vomiting or other symptoms. They appear to act via the emetic center in the medulla and can be blocked completely by treatment with antiemetics such as fluphenazine. There is no evidence that pain or other noxious stresses have any effect on AVP unless they elicit a vasovagal reaction with its associated nausea and hypotension.
The most important, if not the only, physiologic action of AVP is to reduce water excretion by promoting concentration of urine. This antidiuretic effect is achieved by increasing the hydroosmotic permeability of cells that line the distal tubule and medullary collecting ducts of the kidney (Fig. 340-2). In the absence of AVP, these cells are impermeable to water and reabsorb little, if any, of the relatively large volume of dilute filtrate that enters from the proximal nephron. This results in the excretion of very large volumes (as much as 0.2 mL/kg per min) of maximally dilute urine (specific gravity and osmolarity ∼1.000 and 50 mosmol/L, respectively), a condition known as water diuresis. In the presence of AVP, these cells become selectively permeable to water, allowing the water to diffuse back down the osmotic gradient created by the hypertonic renal medulla. As a result, the dilute fluid passing through the tubules is concentrated and the rate of urine flow decreases. The magnitude of this effect varies in direct proportion to the plasma AVP concentration and, at maximum levels, approximates a urine flow rate as low as 0.35 mL/min and a urine osmolarity as high as 1200 mosmol/L. This action is mediated via binding to G protein–coupled V2 receptors on the serosal surface of the cell, activation of adenyl cyclase, and insertion into the luminal surface of water channels composed of a protein known as aquaporin 2 (AQP2). The V2 receptors and aquaporin 2 are encoded by genes on chromosomes Xq28 and 12q13, respectively.
Antidiuretic effect of arginine vasopressin (AVP) in the regulation of urine volume. In a typical 70-kg adult, the kidney filters ∼180 L/d of plasma. Of this, ∼144 L (80%) is reabsorbed isosmotically in the proximal tubule and another 8 L (4–5%) is reabsorbed without solute in the descending limb of Henle's loop. The ...
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