Salt depletion

Since the discovery of renin over 100 years ago, the RAAS has been extensively studied as a prime target or site of action for many effective antihypertensives.15 Renin is produced and stored in the juxtaglomerular cells of the kidney, and its release is stimulated by impaired renal perfusion, salt depletion, and pr adrenergic stimulation. The release of renin is the rate-limiting... 

High-risk patients Hypertensive patients at risk of excessive hypotension include those with the following concurrent conditions or characteristics Heart failure, hyponatremia, high-dose diuretic therapy, recent intensive diureses or increase in diuretic dose, renal dialysis, or severe volume or salt depletion of any etiology. Single doses of enalaprilat as low as 0.2 mg have produced excessive hypotension in normotensive patients with these diagnoses. Because of the potential for an extreme hypotensive response in these patients, initiate therapy under very close medical supervision. The... 

Volume- and salt-depleted patients - A lower initial dose of 75 mg is recommended in patients with depletion of intravascular volume or salt (eg, patients treated vigorously with diuretics or on hemodialysis). 

Hypotension/Votume- or salt-depleted patients In patients who are intravascularly volume-depleted (eg, those treated with diuretics), symptomatic hypotension may occur. Correct these conditions prior to administration. 

Heat illness is traditionally divided into heat exhaustion and heat stroke. Heat exhaustion is the condition in which the casualty collapses from hypo-volaemia due to salt and water depletion. This is probably compounded by physiological cutaneous vasodilatation, which causes shifts in blood volume from the core of the body to the skin. People who are unacclimatised to the environment are more likely to suffer heat exhaustion, especially if there is a lack of access to water. Where a person replenishes fluid losses from sweating with water alone, salt depletion predominates and this can cause insidious symptoms of exhaustion before the final collapse. 

Patients who present with heat exhaustion require fluid resuscitation. An attempt should be made to assess the amount of salt depletion and dehydration. This may be difficult clinically although the presence of symptoms such as muscle cramps in sodium depletion, and signs such as loss of tissue turgor may help. Laboratory measurement of sodium, urea, creatinine and haematocrit are the best guide. Pre-renal renal impairment is common. Treatment usually requires 5-10 1 of oral or intravenous isotonic fluids in the first 24 hours. In severe hyponatraemia the rapid correction of sodium should be carefully monitored with frequent sodium measurements and a reduction in fluid infusion rate if necessary to reduce the risk of osmotic demyelination (central pontine myelinol-ysis). 

In case of severe salt depletion when rapid electrolyte restoration is essential. 

In severe salt depletion resulting from excessive fluid loss due to sweating, vomiting, diarrhoea, etc. 

Cell DC-2. Earlier demineralization studies by Lyon (9) employed cell DC-2. This was a sandwich-type cell with Lucite side plates bolted together with two epoxy resin-gasketed graphite electrodes separated by an anion-permeable membrane. The membrane was necessary because a suitable anion-responsive electrode was not then known. The principle of operation is that in the cathode compartment, after several current reversal conditioning cycles, sodium ions are removed by the cathode while chloride ions migrate from the cathode through the membrane to the anion chamber. In the anode chamber, sodium ions, from the previous half cycles, are rejected from the anode. The net result was salt depletion in the cathode chamber and a similar concentration increase in the anode chamber. 

If an electrical current is passed across a cation-exchange membrane, salt depletion takes place in the surface layer facing the anode. Supply of salt occurs by diffusion across the unstirred film. Maximum diffusion flow occurs if the salt concentration near the membrane equals zero. 

Symptomatic hypotension due to the withdrawal of angiotensin 11-mediated vasoconstrictor tone can occur, especially after the first dose of an ACE-inhibitor, and particularly in patients with high plasma renin activity (e.g., patients with salt depletion due to high doses of diuretics, or with CHF). 

Electrodialysis — Figure. The electro dialysis cell (a) [i] (a = anion-permeable membrane c = cation-permeable membrane o = positive ion = negative ion ion migration under action of electrical current (b), causes salt depletion in alternate compartments and salt enrichment in adjacent ones (c))... 

Rossat J, Maillard M, Nussberger J, Brunner HR, Burnier M. Renal effects of selective cyclooxygenase-2 inhibition in normotensive salt-depleted subjects. Clin Pharmacol Ther 1999 66(l) 76-84. 

An additional physical explanation for salt depletion from the surface of sea ice is that upon freezing of sea ice most of the salt is trapped in the form of concentrated brine droplets that slowly melt their way through the ice due to a lowered freezing point and greater density than the surrounding ice (see Open University Course Team, 1999). 

Avoidance of salt depletion and a salt load (500-1000 ml of 0.9% saline) reduce the renal toxicity of DAMB (120-126). Also the maintenance of adequate serum potassium concentrations by replacement therapy may be important and may contribute to kidney sparing (127). Other preventive measures, including dopamine infusion, are of no value (128). 

Animal experiments have shed more light on Chinese herb nephropathy (29). Salt-depleted male Wistar rats were regularly injected with two different doses of aristolochic acid or with vehicle only for 35 days. The histological signs of Chinese herb nephropathy were demonstrated only in animals that received the high dose of 10 mg/kg. The authors presented this as an animal model for studying the pathophysiology of Chinese herb nephropathy. 

Debelle FD, Nortier JL, De Prez EG, Garbar CH, Vienne AR, Salmon IJ, Deschodt-Lanckman MM, Vanherweghem JL. Aristolochic acids induce chronic renal failure with interstitial fibrosis in salt-depleted rats. J Am Soc Nephrol 2002 13(2) 431-6. 

These findings are in accordance with Chua et al study in the volume depleted female Sprague-Dawley rat [106]. Rats were injected intramuscularly with five times the human dose of TMP-SMZ (100/500 mg/kg/ day) for nine days. Prior to treatment, the animals were placed in a low sodium diet for seven days and salt depleted by means of administration of furosemide (2 mg/kg/day) for the first three days. At baseline, experimental and control (glucose given instead of TMP-SMZ) groups have similar GFR, serum creatinine, and hematocrit and were conserving sodium maximally. Nine days of TMP-SMZ did not affect GFR, serum creatinine or electrolyte levels. Loss of body weight and anemia only developed in the rats treated with TMP-SMZ. In this study performed in female rats, known to have a lower tubular secretion of creatinine [107,108], TMP did not appear to decrease the tubular secretion of creatinine. 

Swan et al. [127] conducted a multi-center that involved both a randomized, single-dose crossover study and a randomized, parallel group, multidose study involving elderly, salt-depleted subjects. The single dose study involved 15 subjects who where crossed... 

Collectively, these studies suggest that COX-2 plays a dominate role in the regulation of salt and water excretion in prostaglandin dependent patient, while the role of COX-1 seems to involve the regulation of renal hemodynamics, including GFR. The Swan et al. [127] study suggests that COX-2 may also play a role in regulating GFR however, the combination of elderly patients who are salt depleted may have provided a more severe hemodynamic stress than was present in the other three studies. 

AndreucciVE,ConteG, Dal Canton A, DiMinnoG,Usberti M.The causal role of salt depletion in acute renal failure due to captopril in hypertensive patients with a single functioning kidney and renal artery stenosis. Renal Failure 1987 10 9-20. 

As previously stated, there is abundant evidence that CSA markedly increases endothelin production and endothehn up-regulates TGF-(3 expression, which in its turn is clearly involved in CSA chronic nephrotoxicity. Therefore, the existence of an endothehn-TGF- (3 pathway in CSA-induced fibrosis was proposed [511]. Supporting this hypothesis, increased tubular cells endothelin mRNA expression was found in human biopsies with chronic CSA nephrotoxicity [488] and Ramirez et al found dramatic elevations in endothelin system components in CSA-treated rats that strongly correlate with renal structural lesions [446]. In contrast, experimental use of an endothelin receptor antagonist did not prevent interstitial fibrosis in the salt-depleted chronic CSA nephrotoxicity model [442, 443]. 

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