The effects of chronic hypoxemia on electrolyte and acid-base equilibrium: an examination of normocapneic hypoxemia and of the influence of hypoxemia on the adaptation to chronic hypercapnia.

We have carried out balance studies in normal dogs in order to appraise the effects of chronic hypoxemia on acid-base and electrolyte equilibrium. During the first phase of observation we produced a state of "pure" hypoxemia by reducing the oxygen concentration (utilizing nitrogen as a diluent) and by adding carbon dioxide to the environment in a concentration sufficient to keep arterial CO(2) tension (PCO(2)) within normal limits. The data demonstrate that such a 9-day period of normocapneic hypoxemia has no effect on electrolyte excretion and is virtually without effect on plasma composition. During the second phase of observation we subjected the hypoxemic dogs to stepwise increments in arterial carbon dioxide tension in order to evaluate the effects of the low oxygen tension on the acid-base adjustments to a chronic state of hypercapnia. At least 6 days was allowed for extracellular composition to reach a new steady state at each level of inspired carbon dioxide. The data demonstrate a rise in both plasma bicarbonate concentration and renal acid excretion that was not significantly different from that which has been described previously for hypercapnia without hypoxemia. Just as in these earlier studies, plasma hydrogen ion concentration rose with each increment in carbon dioxide tension, each millimeter Hg increment in PCO(2) leading to an increase in hydrogen ion concentration of 0.32 nmole per L. It thus appears that the chronic"carbon dioxide response curve" is not significantly influenced by moderately severe hypoxemia.

Nitrogen sparing induced by leucine compared with that induced by its keto analogue, alpha-ketoisocaproate, in fasting obese man.

We measured the effects of seven consecutive daily infusions of alpha-ketoisocaproate (the alpha-keto analogue of leucine) or leucine itself on urinary urea and total nitrogen excretion during fasting. Two study protocols were undertaken. In protocol I, subjects underwent three separate 14-d fasts: one during which 34 mmol/d of leucine were infused on days 1--7; a second during which 34 mmol/d of alpha-ketoisocaproate were infused on days 1--7; and a third control fast during which no infusions were given. Infusions of alpha-ketoisocaproate significantly reduced daily urine urea nitrogen excretion compared with both the control fasts and the fasts in which leucine was infused (P less than 0.001). This nitrogen-sparing effect of alpha-ketoisocaproate persisted during days 8--14 even though no further infusions were given. Daily urinary urea nitrogen excretion during fasts when leucine was administered did not differ from values observed during control fasts. In protocol II, subjects were starved on two occasions for 14 d. During one fast, infusions of 11 mmol/d of alpha-ketoisocaproate were given on days 1--7; during the control fast, no infusions were given. Daily urine urea nitrogen excretion was lower (P less than 0.001) on days 1--7 and also on days 8--14 of the fast during which alpha-ketoisocaproate was given. The nitrogen-sparing effect of alpha-ketoisocaproate could not be related to changes in circulating levels of amino acids, ketone bodies, or insulin in either protocol. We conclude that alpha-ketoisocaproate infusions decrease the nitrogen wasting of starvation, whereas leucine, studied under identical conditions, does not.

Nitrogen sparing induced by a mixture of essential amino acids given chiefly as their keto-analogues during prolonged starvation in obese subjects.

11 normal obese subjects were fasted for 33 days. In five, who served as controls, urine urea nitrogen excretion remained constant for 2 wk thereafter. The other six were given seven daily infusions containing 6-8 mmol each of the alpha-keto-analogues of valine, leucine, isoleucine, phenylalanine, and methionine (as sodium salts) plus 3-4 mmol each of the remaining essential amino acids (lysine, threonine, tryptophan, and histidine). Rapid amination of the infused ketoacids occurred, as indicated by significant increases in plasma concentrations of valine, leucine, isoleucine, alloisoleucine, phenylalanine, and methionine. Glutamine, glycine, serine, glutamate, and taurine fell significantly. Blood glucose, ketone bodies, plasma free fatty acids, and serum immunoreactive insulin concentrations were unaltered. Urine urea nitrogen fell from 1.46 to 0.89 g/day on the last day of infusions; 5 days later it was still lower (0.63 g/day) and in two subjects studied for 9 and 17 days postinfusion it remained below preinfusion control values. Urine ammonia, creatinine, and uric acid were unaltered. Nitrogen balance became less negative during and after infusions. The results indicate that this mixture of essential amino acids and their keto-analogues facilitates nitrogen sparing during prolonged starvation, in part by conversion of the ketoacids to amino acids and in part by altering mechanisms of nitrogen conservation. The latter effect persists after the ketoacids are metabolized.

The effect of carbohydrates on ammonium and ketoacid excretion during starvation.

The metabolic effects of oral ingestion of minute quantities of carbohydrate during prolonged starvation were studied in nine obese subjects. Measurements were made during a control period of total starvation, during the ingestion of 7.5 g carbohydrate daily, and finally during the ingestion of 15.0 g carbohydrate daily. Daily ketoacid excretion fell after carbohydrate ingestion and was significantly correlated (r = 0.62, P < 0.01) with the amount of carbohydrate administered. Despite this fall in ketoacids, the concentration of blood ketoacids, plasma free fatty acids, and serum insulin remained constant throughout the study. Urinary ammonium excretion, closely correlated with ketoacid output (r = 0.95, P < 0.001), also fell significantly after carbohydrate ingestion. No significant changes were present in extracellular or urinary pH. Urea nitrogen excretion did not change when urinary ammonium output fell. These results indicate that: the excretion of ketoacids and ammonium in starving man is exquisitely sensitive to minute amounts of ingested carbohydrate; the change in ketonuria appears to be due to increased renal ketoacid reabsorption after carbohydrate ingestion; and the nitrogen-sparing effect of reducing renal ammonium output in starvation can be dissociated from nitrogen sparing occurring because of changes in urine urea excretion.

Renal glomerular function and long-term lithium therapy.

Recently published studies vary widely in the quantitative assessment of glomerular filtration rate (GFR) in lithium-treated patients. Therefore, the authors tested 99 lithium-treated manic-depressive patients using several techniques to measure GFR. Ten of 86 patients who had no history of renal disease had mildly low creatinine clearance values. Significant correlations, which were not age-related, between the serum creatinine, Cockroft creatinine clearance, and duration of lithium therapy suggest a relationship between chronic lithium therapy and declining GFR. Since serum creatinine alone was insensitive, the authors recommend the use of duplicate classical creatinine clearances confirmed by Cockroft values to monitor GFR during lithium treatment.

Renal function and lithium: a longitudinal study.

Forty lithium-treated manic-depressive patients underwent two renal function assessments 6 to 18 months apart to assess the course of renal function changes associated with lithium therapy. No change in glomerular filtration rate was noted. Although the average 24-hour urine volume increased significantly, large increases occurred in few patients. Most patients had no substantial urine volume change, and a few had decreases. The changes were correlated with serum lithium levels. The results suggest that the majority of patients develop little renal concentrating impairment, while a small proportion of patients become more polyuric with further lithium treatment.

Indoor air quality and acute lower respiratory infection in Indian urban slums.

The present prospective study was conducted at two urban slums of Delhi, Kusumpur Pahari and Kathputly Colony, in the peak winter season from November 1994 through February 1995. We studied 642 infants to determine the incidence of acute lower respiratory infection (ALRI) and its relationship to indoor air pollution due to fuel used for cooking (wood or kerosene). In Kusumpur Pahari, there were 317 children (142 wood and 175 kerosene), including 64 controls and 78 cases of ALRI in the wood fuel group and 81 controls and 94 ALRI cases in the kerosene group (p > 0.05). Out of 316 children in Kathputly Colony (174 wood and 142 kerosene), there were 33 and 45 ALRI cases in the wood and kerosene groups, respectively (p < 0.05). Controls were children without ALRI and were used as controls in different groups. The demographic data and risk factors, namely, nutritional and immunization status, were comparable in ALRI cases and controls in both study areas. Pneumonia was the most common ailment in all the groups. Bronchiolitis was reported in 22.5% of the wood group and 27.1% of the kerosene group in Kathputly Colony versus 13.7% in the wood group and 12.1% in the kerosene group in Kusumpur Colony. Only one case of croup was reported from Kusumpur Pahari among wood users. The duration of illness was longer in the Kusumpur Pahari due to poor compliance, feeding, and child rearing habits. In conclusion, a higher incidence of ALRI was reported in kerosene users in Kathputly Colony, a high pollution area; however, the reasons for the differences observed need further elucidation.

Low-dose captopril in mild to moderate geriatric hypertension.

The safety and efficacy of captopril in geriatric patients with mild to moderate hypertension was examined in an eight-week multicenter study of 99 patients. Following a placebo period, patients were treated with captopril 25 mg twice daily. Patients who were uncontrolled after two weeks of active therapy were randomized to either captopril 25 mg plus hydrochlorothiazide 15 mg or captopril 50 mg twice daily. The average decrease in blood pressure at study completion was--16.9/11.9 mmHg. At the conclusion of the trial, 75.8% of patients responded to therapy. Captopril was well tolerated and believed to be a good therapeutic alternative for treating hypertension in the elderly population.

Nitrogen sparing induced early in starvation by infusion of branched-chain ketoacids.

The alpha-ketoanalogues of the branched-chain amino acids were administered to fasting subjects to determine whether or not they promoted nitrogen sparing. Two fasting studies were carried out in each subject. During the first week of one of the two fasts 4.7 g of a mixture of the alpha-ketoanalogues of valine, leucine, and isoleucine were infused daily. No infusions were administered during the other fast, which served as a control. Urinary urea and calculated total urinary nitrogen were significantly lower during both the week of infusions and the ensuing week of fasting after the infusions were discontinued. Immediately after ketoacid infusions, plasma branched-chain amino acids, including allosioleucine, rose, while alanine and several other amino acids (but not glutamine) fell. There were no differences between the two fasts with respect to ketone bodies, free fatty acids, glucose, insulin, or glucagon concentrations. We conclude that branched-chain ketoacids spare nitrogen early in fasting and that this effect persists after they are metabolized.

Renal conservation of ketone bodies during starvation.

Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.

The role of potassium in the control of ammonium excretion during starvation.

Administration of KC1 0.5 mmol/kg/day to subjects undergoin prolonged starvation reduced daily urinary ammonium and beta-hydroxybutyrate excretion by one-third. These changes were accompanied by an improvement in potassium balance and an increased rate of chloride excretion. A similar fall in ammonium excretion occurred in a second group of subjects after administration of KHCO3 0.5 mmol/kg/day. Ketone body and bicarbonate excretion remained unchanged in this group while potassium balance improved. In both the first and second groups urine pH fell significantly as the rate of excretion of urinary buffer (ammonium) decreased. When the dose of KHCO3 was increased to 1.5-2.0 mmol/kg/day in fasting subjects, the urine was alkalinized, and ammonium excretion fell to negligible levels, resulting in nitrogen sparing of 2.0 g/day. The results indicate that one-half of the increase in ammonium excretion observed in starvation is due to potassium deficiency. Nitrogen wastage caused by losses of urinary ammonium during starvation can be virtually eliminated by potassium supplementation and urinary alkalinization. The decrease in beta-hydroxybutyrate excretion after potassium chloride administration was not caused by a fall in the rate of nonionic diffusion of this organic acid related to the reduction in urine pH. The reason for the fall in beta-hydroxybutyrate excretion is not apparent, though it was associated with an increase in chloride excretion.

Case report. Unilateral renal vein thrombosis without proteinuria.

Unilateral renal vein thrombosis occurred in a patient who was found to have an adenocarcinoma and who had previously been subjected to trauma. Proteinuria was absent throughout the patient's entire clinical course, despite its well known association with renal vein thrombosis. However, other findings suggestive of renal vein thrombosis, including back pain and tenderness, hematuria and an enlarged kidney were present. It is clear that proteinuria need not be the only signal to occasion a search for renal thrombosis. This case probably constitutes the second report of absent proteinuria when thrombus forms within renal vein.

Natural and man-made disasters: the vulnerability of women-headed households and children without families.

Since 1980, over 2 million people have died as an immediate result of natural and man-made disasters and by 1992, the refugee population registered nearly 16 million people. This article reviews the human impact of disasters as a composite of two elements: the catastrophic event itself and the vulnerability of people. It also examines the specific case of women and children in the current world emergency context. It identifies four broad policy areas that affect women and children in disaster situations and discusses them with examples and field evidence. The first policy area addresses humanitarian assistance and armed conflicts, and armed conflict and international humanitarian law, the use of food as instrument of war, mines and civilian disability, and rape and sexual violence are discussed within this context. The second problem discussed is the issue of unaccompanied and abandoned children in terms of its magnitude and implications for relief response. Thirdly, the article examines the differential risks in emergencies for mortality and morbidity, specifically for women and children. Finally, it addresses certain policies and approaches to disaster rehabilitation which effectively mirror and reinforce inherent inequities in the affected society. The article notes that: (i) the largest proportion of disaster victims today arise from civil strife and food crises and that the majority of those killed, wounded and permanently disabled are women and children; and (ii) the ability of any country to respond effectively to disasters depends on the strength of its health and social infrastructure, and its overall developmental status. It concludes by identifying seven areas where concrete measures could be taken to improve the current situation.

PIP: Women and children are the people most affected by civil strife and food crises. A country's successful response to crises will depend on its preexisting infrastructure in the health and social sectors and its development status. The 1992 world refugee population was 16 million, which was a growth of about 500% since 1970. Another 1.2 million have been internally displaced. Over 300 million people in 1992 had homes or livelihoods destroyed by disaster. About 60% of disasters requiring external assistance have been due to floods and winds. Famines and drought do not occur as frequently, but have more long lasting effects on land and population; most recently, famines and droughts have stemmed from armed conflicts. Civil conflicts have claimed the most victims: almost 3 times as many civilians as soldiers. Food recently has been used as a weapon of war. The use of landmines in civil conflicts has resulted in growing numbers of civilian disabled. Millions of children have been abandoned or separated from their families due to armed conflicts. Sexual violence as a weapon of war against civilians results in high rates of pregnancy, sexually transmitted diseases and HIV, as well as psychological traumas. The mental illness or stress disorders from armed conflicts or refugee and abandonment status have been neglected as outcomes. Natural and civil disasters engender malnutrition and disruptions of breast feeding. Early immunization may not be possible under crisis conditions.

Acute renal failure. Community hospital experience with hemodialysis as intensive care adjunct.

A 3-year experience with 50 acute renal failure patients managed by hemodialysis in a 417-bed community hospital is reviewed. The 58% survival rate was better than that reported in other recent series. Possible reasons for our favorable mortality experience include: (1) Hemodialysis was performed within the ICU facility by the ICU staff. Continuity of total care was thereby maintained and hemodialysis problems, such as maintenance of circulating volume, were managed in the context of continued assessment of the patient's cardiopulmonary status. (2) In contrast to previous reports, the presence of sepsis did not influence recovery rates from acute renal failure. Early administration of specific antibiotics, mainly gentamicin, rapid drainage of abdominal abscesses, and early and frequent dialysis were all utilized in spetic patients and may have contributed to their high recovery rate. (3) The use of agressive dialysis may also have lessened other uremic complications, notably gastrointestinal bleeding. Our dialysis organization and procedures are described.

Evaluation of reduced dialysis frequency using nutritional therapy.

This study was carried out in seven patients being treated by intermittent hemodialysis. Each had some residual renal function. In protocol 1, when the patients were dialyzed weekly and the dietary protein intake was 0.96 g/kg/day, the nitrogen balance corrected for changes in the urea pool was positive during the days between dialysis; the serum urea concentration (SUN) before dialysis was 109 +/- 7 mg/dl. In protocol 2, when dietary protein was reduced to 0.4 g/kg/day and supplemented with essential amino acids (10 g/day), the corrected nitrogen balance on days between weekly dialyses was positive; the SUN before dialysis was lower than it was in protocol 1 (-33 +/- 7 mg/dl, P less than 0.01). The nonurea space (body weight minus body water) increased in six of seven patients during protocol 2. Two patients were then treated with the dietary regimen of protocol 2 and dialyzed every 2 weeks. The corrected nitrogen balance on nondialysis days was positive, and there was a further increase in nonurea space. This study suggests that dialysis frequency may be reduced in some patients with residual renal function by means of nutritional therapy.

Acute renal failure after ruptured abdominal aortic aneurysm: an improved clinical prognosis.

Eleven cases of renal failure associated with resection of ruptured abdominal aortic aneurysm and requiring hemodialysis are reported. Previously described series have emphasized the extremely high mortality rate in such patients. In our clinical experience, however, 8 of 11 consecutively treated patients with this clinical problem survived and recovered adequate renal function. We believe that these favorable results can be largely explained by the low incidence of pulmonary infection in our patients as opposed to the frequent occurrence of pulmonary sepsis in other reported series. The reduction in the incidence of pulmonary infection can probably be attributed to the early discontinuance of artificial ventilation after prompt removal of pulmonary edema fluid by intensive hemodialysis ultrafiltration. These survival figures demonstrate that, with appropriate intensive management, full recovery is possible in the majority of patients with acute renal failure complicating ruptured aortic abdominal aneurysm. Our experience serves as a stimulus to render full intensive care support to such patients.

The role of alanine and glutamine in steroid-induced nitrogen wasting in man.

1. Administration of dexamethasone, 8 mg/day (0-02 mmol/day), for 5 days to normal subjects produced negative nitrogen balance, due to early and sustained increases in urinary urea nitrogen excretion 2. In eight subjects ingesting 0-9--1-6 g of protein day-1 kg-1 body weight the cumulative increment in urea nitrogen excretion averaged + 12-5 g (SEM 2-8, P less than 0-01) over the 5 days of glucocorticoid administration. 3. Increases in urinary urea nitrogen excretion could be related to both plasma alanine and blood glutamine changes by using a multiple regression equation. 4. These results suggest that corticosteroids induce increased release of alanine and glutamine by peripheral tissues, which may augment urea formation and negative nitrogen balance. 5. The correlation between increments in urea nitrogen excretion and increases in plasma arginine remains unexplained.

Modulation of plasma aldosterone by physiological changes in hydrogen ion concentration.

To assess the effect of extracellular hydrogen ion concentration (PH+) on aldosterone secretion, studies in which other known modulators could be controlled were performed on 13 patients undergoing hemodialysis. High (35 mM) or low (14-17 mM) dialysate bicarbonate concentrations were utilized on separate days to either decrease or increase PH+, while plasma potassium concentrations (PK) were held at constant levels and changes in plasma renin activity (PRA) were minimized by avoiding changes in body weight. Changes in PH+ were associated with concordant changes in plasma aldosterone concentration (Pa) in both high- and low-bicarbonate studies. When these changes in Pa in high- and low-bicarbonate studies were analyzed together as a function of corresponding changes in PH+, a significant correlation could be demonstrated (r = 0.659, P less than 0.001). There was no correlation between changes in Pa and changes in PK, plasma sodium, plasma adrenocorticotropic hormone (ACTH), or PRA. Using the same methods to control PH+ and other variables during hemodialysis, the effects of altered PH+ on ACTH-stimulated aldosterone and cortisol secretion were evaluated in studies on six patients who received incremental infusions of ACTH after pretreatment with dexamethasone. In these studies, there was no demonstrable effect of PH+ on Pa or plasma cortisol concentration. We conclude that physiological changes in PH+ have a weak modulating effect on basal aldosterone secretion that may not be evident in the presence of other acutely applied stimuli.