Vasopressin pathophysiology

Vasopressin (AVP, ADH) is the principal hormone responsible for the body's narrow control of plasma osmolality (Baylis 2001). Vasopressin is synthesized in the supraoptic (SON) and paraventricular (PVN) nuclei in the hypothalamus. The synthesized hormone is released from the neurohypophysis (posterior pituitary gland). It is a nonapeptide derived from a 155 amino acid precursor encoded in chromosome 20 about 11 kilobases from the gene for oxytocin. Vasopressin is excreted in approximately equimolar amounts with its hypophysin and then circulates in the bloodstream with a half-life of 5—15 minutes.

Receptors for vasopressin have been identified (Baylis 2001, Preisser et al 2000). A vasopressin 1A receptor utilizes phospholipase C/G protein, inositol phosphates and diacylglycerol as intracellular messengers for vasopressin functions in smooth muscle, platelets, liver and some sites in the central nervous system (CNS). A vasopressin 1B receptor utilizes similar intracellular mechanisms and is primarily located in the pituitary corticotroph. A vasopressin 2 receptor utilizes adenylate cyclase and Gs protein through cAMP and protein kinase A to activate aquaporin 2 channel insertion in renal tubular cells.

Vasopressin release is powerfully stimulated by high osmolality, reduced blood pressure (stretch), by nausea/vomiting, and by a variety of visceral traction stimuli, but the correlation between plasma vasopressin and osmolality of blood is tightly and directly linked over the range 285—305 mOsmol/kg (Helderman et al 1978, Moses et al 1976). When osmolality is maintained, the effect of changes in blood pressure on plasma arginine vasopressin is also quite tight over the range 0—40 mm Hg fall in blood pressure.

A number of studies have been undertaken to explore abnormalities in vasopressin in ageing and in Alzheimer's disease (Robertson & Rose 1980, Hoogendijk et al 1985, Faull et al 1993, Frolkis et al 1999, Liu et al 2000). Not all these studies are in agreement, but the following changes seem to be reasonably well established. In ageing, the basal arginine vasopressin level in blood is normal or increased, the plasma arginine vasopressin level following stimulation is increased, the cerebrospinal fluid (CSF) arginine vasopressin level is normal and the renal response to arginine vasopressin is diminished.

In Alzheimer's disease, basal arginine vasopressin is normal or decreased, stimulated arginine vasopressin is decreased and CSF levels of arginine vasopressin are decreased. There are also changes with ageing in other hormones of relevance to volume homeostasis (Lesser et al 1963, Shoeller 1989). Plasma noradrenaline tends to increase with ageing, particularly in men, whereas there is a lesser change in plasma adrenaline changes. Plasma renin activity and plasma aldosterone decrease with age and plasma atrial natriuretic hormone is increased in ageing.

End-organ changes also occur. Anatomic changes in the ageing kidney include reduced size of the kidney, fewer glomeruli, a reduced tubular mass, and sclerosis of pre- and post-glomerular arterioles. At the functional level, there is decreased glomerular filtration rate, decreased renal blood flow, and a reduction in the maximum urine concentration capability and the maximum urine dilution capability. There are also sluggish responses to Na+ deprivation and to an acid load.

It is not uncommon for elderly subjects to have changes in fluid homeostasis related to low fluid intake (Miller 1995, Roth et al 2001). There are many reasons for this lower fluid intake, including limited access to fluids due to immobility, visual problems, or in some cases, restraints; fluid restriction (therapeutic, procedural, or preventive); altered mental status (CNS disease, infections, drugs); gastrointestinal disorders (swallowing problems, obstruction, drugs); and altered thirst mechanisms (impaired thirst, CNS disease, drugs). These situations may account for much of the hypernatraemia in the elderly. In one study, febrile illness was present in 70% of elderly subjects presenting with hypernatraemia, infirmity in 40%, surgery in 21%, nutritional supplementation in 20%, intravenous solutions in 18%, diabetes mellitus in 15%, diarrhoea in 11%, gastrointestinal bleed in 9% and diuretic use in 9%. Only 7% of such patients actually had diabetes insipidus as the cause of the hypernatraemia.

0 0

Post a comment