Transcellular Shift Research Articles

Hyperkalemia With High-Dose Trimethoprim-Sulfamethoxazole Therapy

In a patient with the acquired immunodeficiency syndrome, a progressive increase in the serum potassium concentration occurred with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) therapy for Pneumocystis carinii pneumonia. In this patient, factors known to alter transcellular potassium shifts to induce hyperkalemia were not present. There was no evidence of glucocorticoid or mineralocorticoid insufficiency at the time of hyperkalemia, while the transtubular potassium gradient decreased. The hyperkalemia resolved spontaneously on discontinuation of TMP-SMX therapy, suggesting that this electrolyte abnormality is related to altered renal tubular secretion of potassium as a consequence of the high-dose TMP-SMX therapy.

Assessment of Hyperphosphatemia and Hypophosphatemia

Methodologic aspects including causes of factitious hyperphosphatemia and hypophosphatemia are summarized. The differential diagnosis of hyperphosphatemia is reviewed under its three broad causes: decreased glomerular filtration rate, increased exogenous or endogenous phosphate load, and increased renal tubular phosphate reabsorption. The differential diagnosis of hypophosphatemia is reviewed under its three broad causes: inadequate gastrointestinal input, excess phosphate losses, and transcellular shifts. The consequences of hyperphosphatemia and hypophosphatemia are outlined with a focus on pathophysiologic and clinicochemical sequelae. A laboratory perspective is emphasized in outlining management strategies.

Transcellular urea gradients cause minimal depletion of extracellular volume during hemodialysis.

Concern exists that increasingly high-efficiency dialysis will result in large urea gradients between intracellular and extracellular compartments (VI, VE) leading to large amounts of extracellular volume depletion (delta VE) and hemodynamic instability induced by rapid water flow from VE to VI. The authors investigated this question with a two-compartment model that provided estimates of VI, VE, and osmotically active intracellular and extracellular urea and nonurea concentrations during hemodialysis. The authors found that the urea gradient-induced transcellular water shift is only a very small fraction of VE, even with high urea clearance and short hemodialysis time. The net water shift was small because the urea and nonurea transcellular osmolar gradients were of similar magnitudes but in offsetting directions.

Serum β<sub>2</sub> Microglobulin and Extracellular Fluid Volume During Haemodialysis

Conflicting results have been published concerning serum beta 2 microglobulin (beta 2-M) kinetics during dialysis with a cuprophane membrane which is not permeable for the protein. We have investigated the hypothesis that the apparent increase of free serum beta 2-M could result from extracellular fluid volume (ECV) contraction. Using inulin, ECV was measured before and 1 h after a dialysis session with a sodium dialysate concentration of 145 mmol/l. Dialysis was performed either with a cuprophane or a high-flux membrane. Transcellular water shift and changes in beta 2-M concentration were calculated from total body water changes (ultrafiltration) and ECV. ECV decreased from a predialysis value of 16.6 +/- 3.51 (mean +/- SD) (24.9% bodyweight) to a postdialysis value of 11.9 +/- 2.11 (19.8% bodyweight). Ultrafiltration was only 3.1 +/- 1.01, indicating concomitant water shift from ECV to intracellular fluid space. A significant decrease in corrected beta 2-M concentration was found for high-flux membranes. However, postdialysis beta 2-M did not change significantly after dialysis with cellulosic membranes. In conclusion, the apparent increase of serum beta 2-M concentration measured during dialysis with cellulosic membranes may be explained by ECV contraction. These results have to be taken into account for any pathogenic mechanism of the beta 2-M-associated amyloidosis occurring in long-term haemodialysed patients.

A Case of Hyperkalemia discovered immediately after the Induction of General Anesthesia

Acute hyperkalemia may result from many causes, i.e. excessive load, transcellular shift, decreased renal excretion, and so on, and may be associated with irreversible and fatal cardiac manifestations, muscle weakness, ventilatory and adrenal insufficiency, etc. We experienced a case of acute hyperkalemia probably due to red cell lysis whoch ws evident immediately after the induction of general anesthesia with thiopental sodium and succinylcholine in a 33 year-old female patient with common bile duct obstructive jaundice. In spiote of active management during anesthesia and posoperative period, eventually she died of cardiac arrest. For the successful management of the acute hyperkalemia, the anesthesiologist should be aware of oits etiologies, pathophysiology, diagnosis & treatment.

Dynamic changes in serum phosphorus levels in diabetic ketoacidosis

The dynamic changes in serum phosphorus levels in 69 episodes of ketoacidosis in 48 diabetic patients were retrospectively evaluated. The mean age was 41 ± 2 years (mean ± SEM), and the duration of diabetes mellitus was 7 ± 1 years. The serum phosphorus levels determined within the first six hours of admission were analyzed. Before initiation of therapy, the incidence of hyperphosphatemia was 94.7 percent. At the end of 12 hours, the mean serum phosphorus level fell from 9.2 ± 0.6 to 2.8 ± 0.3 mg/dl. Before therapy, the serum phosphorus level correlated positively with the serum glucose level, the effective plasma osmolality, and anion gaps, and correlated negatively with the serum chloride level. It is concluded that hyperphosphatemia is common in diabetic ketoacidosis before therapy. The increase in serum phosphorus is likely to be due to a transcellular shift. Potential factors responsible for the shift are serum glucose, through its osmotic effect, and the organic anions.

Hypophosphatemia.

Hypophosphatemia, defined as serum phosphate levels less than 2.5 mg%, is a relatively common disorder that can affect virtually every organ system. Phosphate deficiency can result from decreases in phosphate intake or absorption, increased loss from renal and nonrenal pathways, and transcellular phosphate shifts. Optimum therapy is directed at recognizing patients at greatest risk, correcting the underlying abnormality, and supplementing phosphate intake. Intravenous phosphate therapy is indicated for severe hypophosphatemia (serum phosphate less than 1 mg%) with close monitoring of serum phosphate, calcium, potassium, and magnesium levels. Indications for phosphate therapy and suggestions for empirical iv therapy in severe hypophosphatemia are presented.

Hypokalemia After Resuscitation

To the Editor.— The recent article by Thompson and Cobb in the Dec 3, 1982, issue ofThe Journaldescribing the frequent observation of hypokalemia ([K + ] ≤3.6 mEq/L) following resuscitation from ventricular fibrillation was most interesting. The authors were probably correct in their assumption that the observed decrement in serum potassium concentration was too rapid to be attributable to renal or gastrointestinal losses. Presumably, transcellular shift of potassium from the extracellular to intracellular compartment occurred during the administration of sodium bicarbonate. The authors state the resultant hypokalemia did not occur in the classic manner in that hypokalemia was not confined to the alkalotic patients but was also observed in patients with normal or decreased systemic pH. The elegant study of Fraley and Adler 1 in 1977 clearly demonstrates that exogenous bicarbonate administration can induce a significant reduction in serum potassium concentration independent of systemic pH. Although the Fraley and Adler

Water metabolism in diabetes mellitus

Transcellular shifts of water and changes in the physiology of water excretion are common in diabetes mellitus and its treatment. Recent evidence indicates that hyperglycemia in diabetic patients, but not in normal subjects, is characterized by elevations of circulating levels of arginine vasopressin (AVP; antidiuretic hormone, ADH). The role arid importance of these observations remain to be defined since elevations of plasma AVP levels do not decrease water excretion in diabetic patients. Certain oral sulfonylureas, notably chlorpropamide and tolbutamide, are known to decrease renal free water clearance (CH 2O), whereas insulin increases C H 2O ; the insulin and tolbutamide effects may be clinically trivial, whereas that of chlorpropamide is important. The hyponatremic effect of chlorpropamide may be exaggerated in diabetic patients by concomitant diuretic therapy. Euglycemia during chlorpropamide therapy appears to allow full expression of the action of chlorpropamide ob C H 2O ; hyperglycemia with attendant osmotic diuresis protects chlorpropamide-treated patients against hyponatremia. Inhibition of prostaglandin synthesis with nonsteroidal anti-inflammatory agents enhances expression of the ADH effect on the kidney, but it does not appear to potentiate chlorpropamide hyponatremia. Two other oral sulfonylurea agents, tolazamide and glyburide, increase C H 2O . Diazoxide is an antihypertensive thiazide which is antidiuretic as well as hyperglycemic. Thus, abnormalities of water metabolism are common in diabetes mellitus. Whether certain of these abnormalities are clinically important depends upon the presence of the osmotic diuresis of hyperglycemia and the pharmacology of diabetic management.

Tolazamide hepatotoxicity — a case report

Transcellular shifts of water and changes in the physiology of water excretion are common in diabetes mellitus and its treatment. Recent evidence indicates that hyperglycemia in diabetic patients, but not in normal subjects, is characterized by elevations of circulating levels of arginine vasopressin (AVP; antidiuretic hormone, ADH). The role arid importance of these observations remain to be defined since elevations of plasma AVP levels do not decrease water excretion in diabetic patients. Certain oral sulfonylureas, notably chlorpropamide and tolbutamide, are known to decrease renal free water clearance (CH2O), whereas insulin increases CH2O; the insulin and tolbutamide effects may be clinically trivial, whereas that of chlorpropamide is important. The hyponatremic effect of chlorpropamide may be exaggerated in diabetic patients by concomitant diuretic therapy. Euglycemia during chlorpropamide therapy appears to allow full expression of the action of chlorpropamide ob CH2O; hyperglycemia with attendant osmotic diuresis protects chlorpropamide-treated patients against hyponatremia. Inhibition of prostaglandin synthesis with nonsteroidal anti-inflammatory agents enhances expression of the ADH effect on the kidney, but it does not appear to potentiate chlorpropamide hyponatremia. Two other oral sulfonylurea agents, tolazamide and glyburide, increase CH2O. Diazoxide is an antihypertensive thiazide which is antidiuretic as well as hyperglycemic. Thus, abnormalities of water metabolism are common in diabetes mellitus. Whether certain of these abnormalities are clinically important depends upon the presence of the osmotic diuresis of hyperglycemia and the pharmacology of diabetic management.

Response of serum Mg and K to glucose and insulin infusion in uremic dogs

The effect of glucose and insulin infusion on serum levels of Mg and K was studied in nonuremic and uremic circumstances. Fifty cubic centimeters of 50 per cent dextrose containing 8 units regular insulin were infused intravenously into 18 dogs: Group I=intact control (7 dogs), Group II=sham-operated (5 dogs) and Group III=bilateral nephrectomy (6 dogs). Statistically significant decreases in serum K were observed in each of the groups studied. In contrast, no changes were seen for serum Mg. These observations indicate that while glucose and insulin infusion effectively ameliorates uremic hyperkalemia in the dog, no such influence is exerted on the hypermagnesemia. This divergent response observed in the present study, is consistent with the view that in transcellular shifts the mobility of K exceeds that of Mg.