Excess Extracellular Fluid Research Articles

Balancing diuretic therapy in heart failure: loop diuretics, thiazides, and aldosterone antagonists.

In heart failure, sodium is retained by the kidneys despite increases in extracellular volume. There is activation of renin secretion, which culminates in the production of angiotensin II, causing vasoconstriction and aldosterone secretion. These synergistically produce an increase in tubular reabsorption of sodium and water. Diuretics are the mainstay of symptomatic treatment to remove excess extracellular fluid in heart failure. Diuretics that affect the ascending loop of Henle are most commonly used. Thiazide diuretics promote a much greater natriuretic effect when combined with a loop diuretic in patients with refractory edema. Recently, spironolactone, an aldosterone receptor blocking agent, has been recommended to attenuate some of the neurohormonal effects of heart failure. Regardless of the diuretic, patients need to be counseled on the importance of avoiding sodium in their diet

Regression of left ventricular hypertrophy after conversion to nocturnal hemodialysis

Left ventricular hypertrophy (LVH) is an independent risk factor for mortality in the dialysis population. LVH has been attributed to several factors, including hypertension, excess extracellular fluid (ECF) volume, anemia and uremia. Nocturnal hemodialysis is a novel renal replacement therapy that appears to improve blood pressure control. This observational cohort study assessed the impact on LVH of conversion from conventional hemodialysis (CHD) to nocturnal hemodialysis (NHD). In 28 patients (mean age 44 +/- 7 years) receiving NHD for at least two years (mean duration 3.4 +/- 1.2 years), blood pressure (BP), hemoglobin (Hb), ECF volume (single-frequency bioelectrical impedance) and left ventricular mass index (LVMI) were determined before and after conversion. For comparison, 13 control patients (mean age 52 +/- 15 years) who remained on self-care home CHD for one year or more (mean duration 2.8 +/- 1.8 years) were studied also. Serial measurements of BP, Hb and LVMI were also obtained in this control group. There were no significant differences between the two cohorts with respect to age, use of antihypertensive medications, Hb, BP or LVMI at baseline. After transfer from CHD to NHD, there were significant reductions in systolic, diastolic and pulse pressure (from 145 +/- 20 to 122 +/- 13 mm Hg, P < 0.001; from 84 +/- 15 to 74 +/- 12 mm Hg, P = 0.02; from 61 +/- 12 to 49 +/- 12 mm Hg, P = 0.002, respectively) and LVMI (from 147 +/- 42 to 114 +/- 40 g/m2, P = 0.004). There was also a significant reduction in the number of prescribed antihypertensive medications (from 1.8 to 0.3, P < 0.001) and an increase in Hb in the NHD cohort. Post-dialysis ECF volume did not change. LVMI correlated with systolic blood pressure (r = 0.6, P = 0.001) during nocturnal hemodialysis. There was no relationship between changes in LVMI and changes in BP or Hb. In contrast, there were no changes in BP, Hb or LVMI in the CHD cohort over the same time period. Reductions in BP with NHD are accompanied by regression of LVH.

Plasma clearance of polyfructosan and extracellular body fluid distribution in idiopathic dilated cardiomyopathy and after heart transplantation

The total extracellular fluid volume and distribution in plasma and interstitial spaces, and the microvascular permeability properties were studied in 16 nonedematous patients with congestive heart failure (CHF) due to idiopathic dilated cardiomyopathy and 17 such patients who underwent heart transplantation (HT) by analyzing the 3-hour plasma disappearance curve of polyfructosan. Eighteen healthy subjects served as controls. Polyfructosan (3.5 kD) is an extracellular marker and inulin analog transported almost solely by diffusion. The initial capillary membrane plasma clearance (i.e., the permeability-surface area product), the interstitial plasma clearance determined at 10 minutes (clearance[10]), and the extracellular volume were determined from the polyfructosan curves. I-131-albumin was used as a plasma volume reference. Permeability-surface area product was elevated in both patient groups (6.6 ± 1.9 ml/ kg/min in the CHF group and 6.7 ± 2.0 ml/kg/min in the HT group vs 5.1 ± 1.3 ml/kg/min in controls, p <0.01 for both), whereas clearance(10) was normalized in the HT group (4.5 ± 0.9 ml/kg/min in the HT group, 4.4 ± 0.7 ml/kg/min in controls vs 5.0 ± 0.9 ml/kg/min in the CHF group, p <0.1 and p <0.05, respectively). The normalization of interstitial plasma clearance of polyfructosan was associated with time since HT (r = 0.49, p <0.05). Plasma volumes were similar in all 3 groups (41 ± 8 ml/kg in controls, 44 ± 13 in the CHF group and 39 ± 8 in the HT group). In contrast, total extracellular volume was elevated in both patients groups (177 ± 27 ml/kg in the CHF group and 173 ± 27 in the HT group vs 152 ± 12 in controls, p <0.01). The results strongly suggest a microvascular permeability defect in both patient groups that perhaps plays a role in the extravascular distribution of the excess extracellular fluid volume.

Body composition in acromegaly: the effect of treatment.

Total body water (TBW) and total potassium (TBK) were measured in patients participating in a follow-up investigation of all acromegalic patients seen between 1956 and 1984. The results were compared with population-based estimates of TBK and TBW calculated from height (BH), weight (BW) age and sex, using data from a large number of healthy subjects (n = 476). The findings were compared with values obtained at diagnosis and were also related to growth hormone (GH) and IGF-I/SmC concentrations at follow-up. BW at follow-up was unchanged compared to BW at diagnosis and was 9.7 and 10.0 kg higher in males and females, respectively, than in healthy subjects of the same BH (BWnorm). Growth hormone concentration at follow-up correlated directly with excess extracellular fluid volume (ECW%) (P less than 0.001) and inversely with the ratio observed/predicted body fat (BF%) (P less than 0.001) as well as with BW/BWnorm (P less than 0.05). On the other hand, GH concentration did not correlate with excess body cell mass (BCM%) estimated from TBK. IGF-I/SmC concentration correlated with GH concentration at follow-up (P less than 0.001) and with ECW% (P less than 0.01) but not with BCM% or BF%. In 39 patients, data on body composition were also available at diagnosis. Of these, three males had developed gonadal insufficiency and their BCM had decreased markedly. One patient had suffered from hemiplegia. Five patients had not received any treatment. In the remaining 30 treated patients, those with a post-treatment GH concentration below 5 mU/l were normalized with respect to ECW and BF. BCM, however, was unchanged. In contrast, patients with GH concentration greater than or equal to mU/l displayed unchanged body composition. Furthermore, BH decreased significantly in successfully treated patients.

Circulating Inhibitors of Sodium Transport at the Prehypertensive Stage of Essential Hypertension

Alterations in cellular calcium metabolism are presumed to be the basis of the vasoconstrictive process that sustains elevations in arterial pressure. Altered membrane sodium transport can effect changes in intracellular free calcium concentration through changes in transmembrane sodium gradients and membrane depolarization. Thus, changes in membrane sodium transport could produce calcium accumulation in vascular smooth muscle, resulting in vasoconstriction and arterial hypertension. Multiple sodium transport abnormalities exist in tissues of genetically hypertensive rats, and blood cells of human essential hypertensives. Na+-K+ cotransport and Na+-Li+ countertransport abnormalities appear to be primary membrane defects, but a direct physiologic link of these to vasoconstriction remains to be established. Evidence for circulating Na,K-ATPase inhibitors in hypertension is now widely reported, and Na,K-ATPase inhibition provides a rationale for vasoconstriction through altered calcium and/or neurotransmitter metabolism. Na,K-ATPase inhibition in hypertensive disease appears to arise not as a primary abnormality in membrane transport, nor as a phenomenon secondary to hypertension per se, but as a physiological response to compensate for excess extracellular fluid volume accumulation.

Pathophysiological mechanisms of brain edema development: role of tissue factors.

In experiments carried out on adult rabbit "chest-head" preparations the volume changes of the exposed brain (BrV) were determined in repeated tests during a controlled increase of the systemic venous pressure (SVP) of about 13 mm Hg. The changes of both SVP and BrV were usually parallel at the onset of the experiments, but when the brains became preedematous hysteresis appeared in the plots of their relationships. The hysteresis increased gradually (sometimes with periods of partial decrease) thus indicating a delay in the draining of blood from the brain's venous system and in the removal of excess extracellular fluid from the cebral tissue. Evidence for water filtration through the capillary walls during increase of the SVP, and, thus, of brain intravascular pressure, was obtained by detecting the dynamics of [Na+] and [K+] in the extracellular fluid of the cerebral cortex by ion-selective electrodes. This process appeared reversible in normal brains while in the preedematous ones the excessive water filtration resulted in brain edema. The preedematous state of the brain is believed to be caused by changes of the mechanical properties of brain tissue and/or by changes in osmolarity.

Body Composition in Chronic Renal Failure&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;

In severe chronic renal failure loss of weight is common due to a reduction in body fat and fat-free solids. The lean body mass forms an increased proportion of body weight. Body water is relatively increased largely due to an excess extracellular fluid. Intracellular fluid is reduced relative to standard weight in the majority of patients. The exchangeable sodium is increased. The changes are not confined to patients with terminal uraemia but are most marked in those who have received prolonged treatment with low-protein diets. After the start of regular haemodialysis body weight falls because of losses of body water from both extracellular and intracellular spaces. Thereafter body weight increases, due to gains in body fat and fat-free solids. Changes in exchangeable sodium are variable. Intercurrent illness, poor dialysis, or fluid indiscretions rapidly induce a return of the original abnormalities and recovery is slow. Similar changes in body composition are observed after renal transplantation though these may be modified by large doses of prednisone. In general, transplantation is more effective in restoring body composition to normal than haemodialysis. These changes closely resemble those found in malnutrition and it is suggested that the abnormalities of body composition found in chronic renal failure are attributable to protein-calorie deficiency.