Fluid and Electrolyte Losses

Fluid and electrolyte abnormalities are virtually universal in patients with DKA, and, if unrecognized or mismanaged, contribute significantly to the morbidity and mortality of DKA (1-6). Fluid and electrolyte losses in DKA vary so that the extent of these losses is unpredictable in any given patient. However, estimates of losses that form the basis of the initial management of DKA have been formulated (see Table 2). It is emphasized that these recommendations are only guidelines, that each patient should be closely monitored, and that the response to the initial therapy dictates any subsequent changes.

Water and electrolyte losses from the extracellular compartment occur via osmotic diuresis brought about by hyperglycemia, via the respiratory tract because of hyperventilation as a result of metabolic acidosis and via the gastrointestinal tract because of vom-

Dka Metabolic Pathways

Fig. 3. Key metabolic pathways of intermediary metabolism. Disruption of the elements of these pathways may be pathogenetic in the development of hypoglycemia. Not shown is the hormonal control of these pathways: 1, glucose-6-phosphatase; 2, glucokinase; 3, amylo-1,6-glucosidase; 4, phosphory-lase; 5, phosphoglucomutase; 6, glycogen synthetase; 7, galactokinase; 8, galactose-1-phosphate uridyl transferase; 9, uridine diphosphogalactose-4-epimerase; 10, phosphofructokinase; 11, fructose-1,6-diphosphatase; 12, fructose-1,6-diphosphate aldolase; 13, fructokinase; 14, fructose-1-phosphate aldolase; 15, phosphoenolypyruvate carboxykinase; 16, pyruvate carboxylase. [From Pagliara AS, et al. Hypoglycemia in infancy and childhood. J Pediatr 82:365 (Pt 1), 558, (Pt 2), 1973.]

Fig. 3. Key metabolic pathways of intermediary metabolism. Disruption of the elements of these pathways may be pathogenetic in the development of hypoglycemia. Not shown is the hormonal control of these pathways: 1, glucose-6-phosphatase; 2, glucokinase; 3, amylo-1,6-glucosidase; 4, phosphory-lase; 5, phosphoglucomutase; 6, glycogen synthetase; 7, galactokinase; 8, galactose-1-phosphate uridyl transferase; 9, uridine diphosphogalactose-4-epimerase; 10, phosphofructokinase; 11, fructose-1,6-diphosphatase; 12, fructose-1,6-diphosphate aldolase; 13, fructokinase; 14, fructose-1-phosphate aldolase; 15, phosphoenolypyruvate carboxykinase; 16, pyruvate carboxylase. [From Pagliara AS, et al. Hypoglycemia in infancy and childhood. J Pediatr 82:365 (Pt 1), 558, (Pt 2), 1973.]

iting. In DKA, there is an osmotically driven shift of water from the intracellular to the extracellular compartment. This phenomenon results in a clinical underestimation of the extent of dehydration and is responsible for the unusual laboratory finding of hyponatremia despite dehydration and hyperosmolarity. It is estimated that for every 3 mM increase in glucose, there will be a 1 mM fall in plasma sodium concentration. Spurious hyponatremia may also result from lipemic plasma because sodium is distributed only in water, but the volume of the sample taken into account for the calculation of sodium concentration includes the space occupied by lipids and other solids. This artifact can be avoided if special electrodes are used for the estimation of serum or plasma sodium concentration. Serum potassium levels in DKA are variable but tend to be at the upper limits of normal in the majority of patients at initial presentation. However, even when serum potassium is normal, there is almost always depletion of total-body potassium stores. Several factors contribute to these alterations of potassium balance. Serum potassium tends to be elevated because insulin deficiency per se will reduce the Na+/K+-ATPase activity with a decrease in sodium-potassium exchange across the cell membrane. In

Table 2

Fluid and Electrolyte Maintenance and Losses in Diabetic Ketoacidosis

Table 2

Fluid and Electrolyte Maintenance and Losses in Diabetic Ketoacidosis

Element

Maintenance requirementsa

Lossesb

Water

15GG mL/m2

100 mg/kg (range: 60-100)

Sodium

45 meq/m2

6 meq/kg (range: 5-13)

Potassium

35 meq/m2

5 meq/kg (range: 4-6)

Chloride

3G meq/m2

4 meq/kg (range: 3-9)

Phosphate

1G meq/m2

3 meq/kg (range: 2-5)

a Maintenance is epxressed in surface area to permit uniformity because fluid requirements change as weight increases.

b Losses are expressed per unit of body weight because the losses remain relatively constant as a function of total body weight. Source: From ref. 2.

a Maintenance is epxressed in surface area to permit uniformity because fluid requirements change as weight increases.

b Losses are expressed per unit of body weight because the losses remain relatively constant as a function of total body weight. Source: From ref. 2.

addition, acidosis will cause a movement of intracellular potassium to the extracellu-lar-intravascular compartment in exchange for hydrogen ions moving into the cell along a concentration gradient. Hyperglycemia per se and impairment of renal function also tend to keep the serum potassium levels elevated. The potassium entering the intravascular compartment is then lost in part via osmotic diuresis and vomiting and in part via the actions of aldosterone, elevated in response to volume depletion.

Initiation of therapy may result in a rapid decrease in serum potassium levels with disastrous consequences if adequate potassium supplementation is not instituted, making hypokalemia one of the avoidable causes of fatality in DKA. Correction of acido-sis, restoration of intravascular volume, administration of insulin, and improvement in renal function all tend to decrease extracellular concentration of potassium. In addition, if bicarbonate is provided, the hypokalemic effects of the above-mentioned factors are compounded (12). It is estimated that about one-quarter to one-half of the potassium administered during fluid replacement therapy is lost in the urine. Patients with urinary losses greatly exceeding these estimates (potassium sink) have been described; such patients are at a serious risk of hypokalemia. Hence, potassium supplements should be provided early in the course of therapy; contrary to the usual practice of avoiding potassium infusion in patients with renal failure, patients with DKA and compromised renal function may need careful potassium supplementation because insulin therapy will promote cellular uptake of extracellular potassium and favor the development of hypokalemia. These considerations about potassium balance in DKA emphasize the need for frequent and meticulous monitoring of serum potassium concentrations, with adjustments in the therapeutic regimen tailored to each individual patient's response rather than reliance on a "standard" protocol (1-6,12,13).

Disturbances in phosphorus homeostasis must also be considered during the management of patients with DKA. Because DKA is a catabolic state, it is accompanied by a shift of intracellular phosphate into the extracellular compartment, with subsequent loss via urine, leading to depletion of total-body phosphorus. As in the case of potassium, serum phosphate concentrations do not provide an accurate estimate of the total-body phosphate stores. Also, as with potassium, institution of insulin and fluid replacement therapy results in a shift of extracellular phosphate into the intracellular compartment and, therefore, frequently leads to a hypophosphatemic state (1-4,13,14).

Hypophosphatemia impairs insulin action and will result in a decrease in synthesis of ATP and other energy intermediates. Phosphate deficiency will also result in a depletion of 2,3-diphosphoglycerate (2,3-DPG). Depletion of 2,3-DPG leads to a shift in the oxygen-hemoglobin dissociation curve to the left; that is, it increases the affinity of hemoglobin for oxygen and hence decreases the amount of oxygen released to the tissues. Concurrent acidosis shifts the oxygen-hemoglobin dissociation curve to the right (Bohr effect) so that the effect of 2,3-DPG deficiency is offset by DKA. However, after institution of treatment, the amelioration of the acidotic state may unmask the deleterious effect of hypophosphatemia on tissue oxygen supply. Inclusion of phosphate in the therapeutic regimen is therefore recommended and has been shown to lead to the normalization of 2,3-DPG levels within 24 h, whereas without phosphate supplementation, this process may take 3-4 d (13). Phosphate is recommended and usually provided as potassium phosphate. This form of replacement confers an additional advantage in that it facilitates a reduction in the amount of chloride administered as potassium chloride to replace potassium losses and thus helps to avoid the development of hyperchloremic acidosis. Despite these theoretical reasons for phosphate supplementation, clinical studies have, by and large, failed to substantiate an unequivocal advantage of phosphate therapy in terms of either decreased morbidity and mortality or shortened recovery time (14). Hence, the decision to administer phosphate must be made on an individual basis and not as a routine measure, especially as there exists a danger of precipitating hyperphosphatemia and hypocalcemia (14,15).

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Responses

  • GRINGAMOR
    How does dka cause metabolic acidosis?
    6 years ago

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