Increase In Extracellular Fluid Volume Research Articles

Properties of body fluids influencing salt gland secretion in Pekin ducks.

Pekin ducks were reared and maintained on 620 mosmol NaCl/kg H2O to enhance the secretory capability of their salt glands. When a control solution of 1,000 mosmol NaCl/kg H2O was infused intravenously at 0.2, 0.4, or 0.6 ml/min for 60-90 min, the infused loads were secreted in approximately equal quantities, indicating that the amount of NaCl in the extracellular fluid (ECF) before and after each infusion did not change. Salt and water secreted in response to experimental infusions of hyposmotic saline or blood were less than the solute and water infused. Thus, ECF volume increased and the Na+ concentration decreased. Infusions of control solution followed these experimental infusions. The salt and water secreted again equaled the amounts infused, indicating that the threshold concentration of Na+ ([Na+]th) for salt gland secretion was decreased by the increase in ECF volume. When the colloid dextran was added to the control solution, its infusion increased the colloid osmotic pressure of the blood and decreased nasal secretion. Because dextran increased the intravascular volume while the interstitial fluid volume (ISFV) decreased, we conclude that the [Na+]th was inversely correlated with ISFV.

17α-HYDROXYLASE DEFICIENCY. A COMBINATION OF HYDROXYLATION DEFECT AND REVERSIBLE BLOCKADE IN ALDOSTERONE BIOSYNTHESIS

We have studied the hormonal secretion and excretion patterns in a patient with the XX type of 17 alpha-hydroxylase deficiency. In the untreated state, the patient's urine contained only those steroids which do not require 17-hydroxylation in their biosynthesis. Aldosterone was not produced in the patient and the metabolic product of its immediate precursor, 18-hydroxy-11-dehydro-tetrahydrocorticosterone, was excreted in markedly elevated amounts. This apparent complete block in 18 oxidation was reversible upon long-term ACTH suppression within 27 days. Direct in vitro incubation of the patient's adrenal gland removed at operation demonstrated, 1) the complete lack of 17 alpha-hydroxylase activity, 2) the functional block in the ability to oxidize the hydroxyl group at the 18 methyl side chain. The addition of physiological concentrations of angiotensin to the incubation medium further showed, 3) angiotensin mildly stimulated the entire aldosterone biosynthetic pathway, 4) angiotensin directly stimulated the conversion of 18-hydroxycorticosterone to aldosterone. We propose that in this patient, 17-hydroxylase deficiency produced a decreased plasma concentration of cortisol, followed by stimulation of deoxycorticosterone production by ACTH. The resultant increase in extracellular fluid volume suppressed plasma renin activity. This resulted in a low plasma concentration of angiotensin II which directly suppressed oxidation of 18-hydroxycorticosterone to aldosterone. This defect has been called corticosterone methyl oxidase defect type 2.

Comparative study on development of corticosterone and DOCA hypertension in rats

The administration of corticosterone for 5 consecutive days to normal rats on a standard sodium intake induced negative sodium and water balance. These effects were opposite those observed under DOCA treatment. However, not only under DOCA but also under corticosterone treatment extracellular fluid volume (ECFV) and plasma volume (PV) increased, and blood pressure (BP) rose in parallel. Plasma renin and angiotensin II concentrations declined under the influence of both steroids. Plasma arginine vasopressin concentrations increased under DOCA, whereas they transiently decreased under corticosterone administration. These data suggest that the common mediator for BP elevation due to steroid excess would be an increase in ECFV and PV. The pathways by which this increase is achieved seem to be different. Under DOCA treatment ECFV and PV increased subsequent to renal sodium and water retention. Under corticosterone, however, sodium and water were shifted from intra- to extracellular compartments, and a fraction of this shifted sodium and water was conserved in extracellular space, most likely because corticosterone also affected renal sodium handling.

Diurnal pattern of water and electrolyte excretion and body weight in idiopathic orthostatic hypotension: The effect of three treatments

The diurnal pattern of water and solute excretion and body weight were examined in five control subjects and in a patient with idiopathic orthostatic hypotension before and during treatment. The patient had a reversed diurnal pattern of excretion of sodium, urea and water but not of potassium and creatinine, and there was an excessive diurnal variation in body weight. The effects of three treatments, high salt diet alone and then with the addition of head-up tilt, and later fludrocortisone, were studied. Fludrocortisone caused marked clinical improvement and retention of sodium and water. Once a steady state was achieved none of the treatments had any significant effect either on the diurnal variation in weight or on the water and solute excretion pattern except for a small reduction in sodium excretion at night when the patient slept with a head-up tilt. It is concluded that these treatments cause symptomatic improvement in idiopathic orthostatic hypotension through an increase in extracellular fluid volume rather than through any change in the abnormal diurnal pattern of water and salt excretion.

Separate roles of sodium ion concentration and fluid volumes in salt-loading hypertension in sheep.

The goal of these studies was to determine whether the hypertension caused by excessive salt loading results from sodium-induced expansion of the extracellular fluid volume or whether the salt increases the pressure in some other way, such as by causing vascular constriction. In one group of sheep, a combination of total nephrectomy and hemodialysis was used to produce and maintain step increases in extracellular fluid volume for 1 wk without a significant change in sodium ion concentration. In a 2nd group, unilateral nephrectomy, dialysis, and DOCA administration were used to cause step increases in sodium ion concentration while the extracellular fluid volume was held as close to normal as possible. The results showed a 41% increase in arterial pressure in the high-volume sheep and only a 4% increase in pressure in the high-sodium sheep. In both instances the total exchangeable sodium increased almost equally--a 21% increase in the high-sodium sheep. The data support the concept that sodium retention causes hypertension almost entirely because of sodium-induced expansion of the extracellular fluid volume.

Human growth hormone in myopathy: myotonic dystrophy, duchenne muscular dystrophy, and limb-girdle muscular dystrophy.

Abstract: Human growth hormone (HGH) produces an anabolic response in striated muscle. Since muscular dystrophy is characterized by a deterioration of muscle, studies were done to evaluate the response of these disorders to exogenous HGH. Four patients with myotonic dystrophy, seven with Duchenne muscular dystrophy and five with limb-girdle dystrophy were treated with HGH. Three dosage levels of HGH were used for each subject, and each subject was studied under metabolic balance procedures for 14 days. Patients with myotonic dystrophy and limb-girdle dystrophy, all adults, showed positive sodium, potassium and nitrogen balances and body weight increases far in excess of matched control subjects. These data were interpreted to represent c deposition of protoplasm and an increase in extracellular fluid volume. In contrast, negative balances of nitrogen and potassium were seen in six of the seven boys with Duchenne muscular dystrophy on the largest dose of HGH. Control subjects showed the expected positive metabolic responses. HGH is now being studied as a potential form of treatment of adult dystrophies. HGH is considered now not only to be of no value in the treatment of Duchenne muscular dystrophy, but must be suspected of playing a role in the pathophysiology of the disorder.

Plasma volume and extracellular fluid volume during long-term treatment with propranolol in essential hypertension.

1. In ten patients with essential hypertension treated with propranolol (320 mg daily for 4 months) plasma volume and extracellular fluid volume were determined. 2. A significant increase in extracellular fluid volume (ECFV) was found, but there was no significant change in plasma volume. 3. The genesis of the increase found in ECFV is briefly discussed.

A steady-state control analysis of the renin-angiotensin-aldosterone system.

This communication develops a steady-state block diagram about the configuration of the renin-angiotensin-aldosterone system in relation to the mineralocorticoid-dependent reabsorption of sodium. Two principal mechanisms appear to be involved in the control of renin secretion. The baroreceptor hypothesis suggests that decreased stretch of the afferent glomerular arteriole produces increased renin secretion. The macula densa theory, on the other hand, suggests that renin secretion responds to alterations either in sodium load or in sodium concentration at the macula densa. These two receptors are presented as parallel feedback pathways which are independently capable of altering renin secretion. This concept of independent receptor function is supported by literature in which one of the receptor pathways was eliminated. The system configuration for the renin-angiotensin-aldosterone system suggests the hypothesis that the vascular receptor controls renin secretion in the autoregulatory range of blood pressure and that macula densa control dominates at pressures below the autoregulatory range. The control system diagram also calls attention to certain unique features of the renin-angiotensin-aldosterone system; it indicates that (1) a chronic low-sodium diet involves changes in both input variables (extracellular fluid volume) and parameters (hepatic blood flow) to maximize sodium reabsorption, (2) thoracic inferior vena cava constriction opens the feedback loop so that the renal receptors do not perceive increases in extracellular fluid volume, (3) congestive heart failure reduces the overall gain of the system, and (4) a small nonhypotensive hemorrhage primarily increases renin secretion through renal sympathetic nerve stimulation.

Studies on the control of sodium excretion in experimental uremia.

A study of the mechanisms governing the high rate of sodium excretion per nephron characteristic of patients with chronic renal disease has been made in dogs. A "remnant kidney" was produced by 85% infarction of the left kidney while the right kidney was left intact. A bladder-splitting procedure allowed simultaneous measurement of glomerular filtration rate and the rate of sodium excretion by each kidney. The animals were fed a constant known amount of sodium chloride and 0.1 mg of 9 alpha-fluorohydrocortisone twice daily throughout the study. In a group of dogs fed 3 or 5 g of salt per day, sodium excretion by the remnant kidney averaged 6.5 muEq/min while the intact kidney was present and 53.7 muEq/min when the animals became uremic after the intact kidney was removed. The increased sodium excretion per nephron by the remnant organ often occurred within 18 hr after contralateral nephrectomy and persisted despite experimentally induced acute reductions in the glomerular filtration rate to below prenephrectomy levels. A second group of animals studied in the same manner but receiving 1 g of salt per day or less failed to develop a natriuresis after contralateral nephrectomy despite high grade uremia. Thus an increased impermeable solute load per nephron was not a regulatory factor in the production of the natriuresis. The increased rate of sodium excretion per nephron in uremia resembles that after saline loading in that it may occur without an increase in glomerular filtration rate or a reduction in mineralocorticoid stimulation. It follows that an additional factor or factors must be involved in the genesis of the natriuresis. In contrast to the natriuresis that is seen in normal animals subjected to saline loading, these uremic animals were found not to have a detectable increase in extracellular fluid volume or blood volume in the presence of high fractional sodium excretion rates. Sodium excretion in response to a small salt load by the remnant organ in uremia was 30% greater than the response of both kidneys in the preuremic state despite a markedly reduced total GFR. These data are consistent with the view that the volume control mechanism becomes more responsive in uremia.

Volume and composition of the body fluid compartments in severe infantile malnutrition

The following observations were made in infants and children suffering from malnutrition of different causes: 1.A percentage increase in extracellular fluid volume in relation to the actual body weight was the only consistent change in the extracellular fluid compartment. 2.The occurrence of edema (i.e., absolute volume expansion of extracellular fluid) was associated only with malnutrition due to low protein intake. In patients with edema, hypoproteinemia and reduced enzymatic activity of the duodenal juice were invariably observed. 3.The important factors leading to formation of edema in malnourished infants and children were a decrease in plasma colloid osmotic pressure and a loss of skin elasticity. Ineffective cardiac and perhaps renal compensatory capacities in these malnourished children were thought to contribute to formation of edema when there was too rapid expansion of the intravascular volume by infusions of plasma, intercurrent infections, or overfeeding. 4.The occurrence of diarrheal disease in patients with malnutrition may cause hyponatremia or cerebral anoxia from circulatory shock. These alterations were, however, less common than in normal infants suffering from diarrhea. Because of lower body metabolism in malnutrition, such infants were better able to withstand the circulatory stasis and anoxia. These patients had an accelerated wasting of body substance in diarrhea because they had no caloric reserves from which to draw during a period of decreased food assimilation. Malnourished infants were subject to death from sudden hypoglycemia resulting in respiratory paralysis. The following observations were made in infants and children suffering from malnutrition of different causes: 1.A percentage increase in extracellular fluid volume in relation to the actual body weight was the only consistent change in the extracellular fluid compartment. 2.The occurrence of edema (i.e., absolute volume expansion of extracellular fluid) was associated only with malnutrition due to low protein intake. In patients with edema, hypoproteinemia and reduced enzymatic activity of the duodenal juice were invariably observed. 3.The important factors leading to formation of edema in malnourished infants and children were a decrease in plasma colloid osmotic pressure and a loss of skin elasticity. Ineffective cardiac and perhaps renal compensatory capacities in these malnourished children were thought to contribute to formation of edema when there was too rapid expansion of the intravascular volume by infusions of plasma, intercurrent infections, or overfeeding. 4.The occurrence of diarrheal disease in patients with malnutrition may cause hyponatremia or cerebral anoxia from circulatory shock. These alterations were, however, less common than in normal infants suffering from diarrhea. Because of lower body metabolism in malnutrition, such infants were better able to withstand the circulatory stasis and anoxia. These patients had an accelerated wasting of body substance in diarrhea because they had no caloric reserves from which to draw during a period of decreased food assimilation. Malnourished infants were subject to death from sudden hypoglycemia resulting in respiratory paralysis.

Renal hemodynamics and antidiuretic hormone release associated with volume regulation.

Following the general reduction of extracellular fluid volume by hemorrhage, or the selective reduction of this volume in the thorax by positive pressure breathing, the volume regulating mechanism of the dog is implicated as part of the over-all compensatory mechanism to such stress situations, and appears to be dominant over any regulation via the osmoreceptors. Both these experimental procedures produce characteristic compensatory cardiovascular reactions, depressed renal function and highly significant increases in the circulating level of antidiuretic hormone. Following the isotonic expansion of the extracellular fluid volume with dextran, or selective expansion of the vascular capacity of the thorax by negative pressure breathing, the volume regulating mechanism appears to be subdominant to the control of body fluid volume via the osmoreceptors. In the case of an increase in extracellular fluid volume, reflex responses directed at volume regulation have no statistically significant action on renal hemodynamics, and any action on the release or inhibition of antidiuretic hormone could not be detected with certainty because of the limiting sensitivity of the bio-assay.

OBSERVATIONS OF A METABOLIC LESION IN COW'S-MILK ALLERGY

Clinical and metabolic studies of two infants allergic to cow's milk are described. In both babies episodes of clinical deterioration culminating in a cyanotic, peripheral circulatory shock-like state were repeatedly observed upon exposure to cow's milk. Despite clinical evidence of diminished circulatory volume, chloride space measurements suggesting increase in extracellular fluid volume at the expense of intracellular fluid were associated with the allergic reaction. Balance data indicate that external losses of sodium and water were small, and internal accumulation of potassium large, at the height of development of the metabolic disturbances. The metabolic responses are discussed with reference to possible mechanisms of production. It is evident that further experimental work is required for their elucidation. However, these studies indicate that allergy should be considered in the differential diagnosis in infants who show metabolic derangements which may superficially suggest primary renal or adrenal disease.