A woman with hyponatraemia, acidosis, aneuria and terminal ileostomy

(Section Editor: K. Kühn)

Simon Desmeules, Paul René de Cotret and Paul Isenring

Groupe de Néphrologie de L'Hôtel-Dieu de Québec, Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada G1R 2J6

Keywords: acidosis; azotaemia; conduit; fistula; hyponatraemia

Introduction

It is not uncommon for more than one electrolyte and/or acid base disorder to be present simultaneously. In such a setting, determining the aetiological and pathophysiological factors involved can represent a real challenge. Failure to identify these factors thoroughly may lead to a disastrous outcome either from improper fluid and electrolyte management or from the ongoing consequence of an underlying illness left untreated. Here, we report the case of a patient who developed pronounced hyponatraemia, metabolic acidosis and hyperazotaemia. These manifestations were associated with true volume depletion and a severe decline in urine output. Rapid correction of plasma Na (PNa) was avoided by recognizing the important role played by hypovolaemia and high plasma urea (Purea) in free water excretion. In addition, a definitive cure could be offered to the patient after identifying the underlying illness responsible for the clinical manifestations.

Case

On March 21, 2000, a nephrological evaluation was requested for a 53-year-old woman with hyponatraemia and decreased consciousness. Her main past medical history consisted of: (i) an adenocarcinoma of the uterus in 1994, treated by hysterectomy and radiotherapy; (ii) a Dukes 2A adenocarcinoma of the colon in 1998, treated by total colectomy with terminal ileostomy; and (iii) a rectocutaneous fistula that closed spontaneously in 1999.

The patient was evaluated for cloudy urine, dysuria and suprapubic pain in another centre on March 10, 2000. Ciprofloxacin was initiated after obtaining a voided urine specimen. Three days later the patient was re-evaluated because of ongoing urinary symptoms. Analyses of the urine specimen collected on March 10 were consistent with contamination and, accordingly, the antibiotic was discontinued. An abdominal ultrasound later revealed mild hydronephrosis that was more pronounced on the left side. On March 16, 2000 the patient was transferred to the L'Hôtel-Dieu de Québec Hospital for further evaluation.

On March 21, 2000 she developed clouding of consciousness. Physical examination showed a body weight of 45.3 kg (normally 47 kg), a blood pressure of 114/65 mmHg supine and 80/30 mmHg standing, and an increased skin turgor. The jugular veins were non-distended, the heart and lungs were normal, and no abdominal mass or pain were noted. Review of hospital charts showed that the patient was oligeuric between March 16 and March 20, and that she was aneuric by March 21. Blood and/or urine tests were obtained between March 10 and March 21. As shown in Table 1Go, Purea increased several-fold between March 16 and March 21, and PNa decreased concomitantly from 128 to 110 mM. Plasma creatinine (Pcreat) values were also higher in March 2000 compared with a value obtained in November 1999.


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Table 1.  Blood and urine tests obtained between November 1999 and March 21, 2000

 
1. What is the cause of the abnormally high urea-to-creatinine ratio seen in this patient on 21 March 2000?
Several conditions can lead to a high urea-to-creatinine ratio, as listed in Table 2Go. Our patient has clear evidence for dehydration. However, the 3-fold increase in Purea between March 15 and March 21 (Table 1Go), accompanied by a decrease in Pcreat while the patient was oligoaneuric, indicates that other factors probably account for the very high urea-to-creatinine ratio (480) on March 21.


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Table 2.  Causes of high urea-to-creatinine ratio

 

2. How would you classify the patient's hyponatraemia?
As mentioned above, physical examination suggests dehydration. Thus, hyponatraemia occurred in the setting of hypovolaemia. A urinary osmolality (Uosm) of 463 mOsM on March 13 (see Table 1Go), indicating high levels of antidiuretic hormone (ADH) at the collecting duct, and a urinary [Na] (UNa) <5 mM, which is consistent with hyperaldosteronism, both confirm that the effective circulating volume is reduced—presumably by >10% considering non-osmotic stimulation of ADH release.

It is pertinent to note that even if the patient has normoosmolar hyponatraemia (calculated plasma osmolality (Posm) 291 mOsM) she should be treated for hypoosmolar hyponatraemia. Here, the Posm is normal because of high Purea, which is an ineffective osmole. Thus, the patient has true hyponatraemia and rapid correction of this condition would place her at risk for centropontine myelinolysis.

3. What is the cause of the aneuria?
Aneuria is often caused by urinary tract obstruction and is then usually associated with hydronephrosis. Here, interestingly, the progression to aneuria occurred without any fall in the glomerular filtration rate (GFR); Pcreat even declined slightly during the same period. Hence, hydronephrosis in our patient could have only occurred in the setting of mild urinary tract obstruction and preserved diuresis; the symptom of ‘aneuria’ in such a context must indicate that urine is not being excreted through the normal collecting system. It appears very likely, therefore, that the patient had a fistula between the urinary tract and a hollow organ, e.g. the gut. Previous abdominal irradiation for uterine carcinoma is a major risk factor for internal fistulæ.

4. How would you demonstrate the fistula?
The hypothesis of an enteric fistula can be verified by determining whether the volume of the ileostomy drainage has changed, and by analysing its content. The presence of creatinine in the stools, for example, would suggest the presence of an enterourinary fistula. A radionuclide scan of the kidney showing partially preserved renal function with abnormal urine distribution would also suggest a fistula.

Review of the patient's chart revealed that the ileostomy bag had to be emptied more frequently in the past week, and laboratory studies indicated that creatinine was excreted in the gastrointestinal tract (see Table 3Go). A radionuclide scan (shown in Figure 1Go) and a retrograde cystography (Figure 2Go) confirmed the presence of a fistula between a segment of the small intestine (somewhere from the proximal jejunum to the proximal ileum) and the bladder.


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Table 3.  Tests performed on bladder urine and on ileostomy drainage fluid

 


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Fig. 1.  Radionuclide scan of the kidney using mercapto-acetyl-(glycine)3. A fast and intense uptake of the radioisotope is observed (a and b), followed by a rapid transit from cortex to medulla (b–g). Tracer also appears precociously in the pelvis (b) and the bladder (c); the collecting system, however, appears slightly dilated and there is stagnation of the isotope in the upper urinary tract, suggesting mild or partial obstruction. From (d) to (f), an abnormal shadow appears in the region of the vesical dome (see white arrows). From (f) to (g), an intensifying dark spot is seen on the right side of the bladder dome (see black arrow) and probably indicates a site of fistulization. From (e) to (h), another shadow (see open arrows) shows that an increasing amount of urine follows a ‘paraureteral’ route.

 


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Fig. 2.  Retrograde cystography. Note the significant amount of contrast material in the small intestine. The site of probable fistulization is marked with an arrow.

 
During the afternoon of March 21, an indwelling bladder catheter and double J ureteral stents were inserted by retrograde canulation. A perfusion of isotonic saline (154 mM NaCl) was also started at 100 ml/h, providing a means of restoring the extracellular volume. After these treatments, the amount of urine excreted through the bladder increased greatly. Serum and urine tests were obtained on repeated occasions during the following 24 h (see Table 4Go).


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Table 4.  Blood and urine tests obtained between March 21 and March 23, 2000

 

5. What is your main concern regarding the correction of hyponatraemia?
The main concern is correcting PNa too rapidly (>0.5 mM/h). In this particular case, there are two reasons why the risk for rapid correction is high. First, the patient has non-osmotic ADH secretion due to volume depletion. Once this stimulus is no longer present as a result of proper rehydration, suppression of ADH will lead to aqueous diuresis. Secondly, the patient has high Purea(~60 mM before treatment) with partially preserved GFR. As the circulating volume is re-established, the increase in urine output will lead to a higher than expected loss of free water because of urea-induced osmotic diuresis.

6. How would you prevent a rapid correction of the PNa?
The key to managing the water disorder in this patient is to administer free water or prevent excessive water diuresis as the effective circulating volume is being restored. Based on the data in Table 4Go, the saline perfusion led to loss of volume-mediated ADH secretion, sometimes before 6 p.m. when Uosm fell to 355 mOsM (had the patient not been azotemic, Uosm would have been <100 mOsM).

Free water can be administered as dextrose 5% but high infusion rates may lead to dextrose-induced osmotic diuresis. Free water can also be administered as enteric tap water, which is safe and effective. The initial rate of administration is estimated by calculating the ongoing free water loss by the kidney, which is equal to the urinary volumex(1–((UNa+K)/(PNa+Pk))). Once a target PNa is reached (maximum rise in PNa 10–12 mM/day and 0.5 mM/h), the equation used to calculate the rate of free water administration will have to include all of the active osmoles given to the patient; this equation represents the net free water loss and is equal to the urinary volume x(1-((UNa+K-OralNa+K-IVNa+K)/(PNa+Pk))).

Another means of preventing rapid PNa correction is, as mentioned above, to decrease free water diuresis. This may be done by administering desmopressin, which is safe and will effectively counteract water loss induced by urea and decreased ADH secretion. Free water diuresis can also be abated by using a loop diuretic to promote osmole excretion. This type of intervention would only be effective if Uosm is >350 mOsM.

To prevent rapid PNa correction in our patient on March 21, it was decided to administer enteric tap water, furosemide and desmopressin all together because of very high Purea and urinary urea (Uurea) at 2 p.m. (see Table 4Go) and at 6 p.m.; here, an osmolar gap of +216 mM, including only 11 mM of unmeasured cations (see Appendix 1), suggests that Uurea was very elevated. This treatment effectively prevented a rapid correction of the hypoosmolar disorder; as illustrated in Table 4Go, PNa increased from 108 to 115 mM (+7 mM or approximately 1 mM/h) in the first 6 h and remained stable for the next 20 h.

7. How would you interpret and explain the acid–base disorder in this case?
After the nephrological evaluation on March 21, blood gas and urinary measurements were ordered (the result is shown in Table 4Go, line 1). Clearly, the patient has hyperchloraemic metabolic acidosis. The calculated plasma anion gap, assuming normal albumin levels, is 15 mM, and the urinary anion gap is -12 mM. These calculated values suggest that NH4 is being excreted in the urine and that the cause of acidosis is extrarenal (see Appendix 1).

8. Is it possible to determine how the gut modified the urine to bring about the electrolyte and acid–base disorder?
To do so, one can compare the composition of the urine in the bladder with that of the urine in the ileostomy drainage bag. One is then comparing the urine before it enters the intestine and after it exits the intestine. Consequently, change in urine composition will result from transport processes between the entry and the exit sites. These assumptions, however, are only valid if minimum back leak of urine occurs from gut to bladder and if there is minimum contamination from fluid formed above the level of the fistula. Here, it was possible to obtain simultaneous measurements on both bladder and ileostomy specimens when the patient had had empty stomach for several hours (see Table 3Go). In addition, aneuria at the time the specimens were collected suggests that significant gut-to-bladder back leak is unlikely.

9. What was the effect of the small intestine on urine composition with regard to water handling?
A 63% increase in creatinine (see Table 3Go) probably indicates that water is reabsorbed through the intestine's epithelium. However, because the gut is also able to reabsorb creatinine [1], water reabsorption must have been higher than that predicted by the change in creatinine from bladder to ileum. Based also on the increase in [Na]+[K] from bladder to ileum (69 vs 78 mM, respectively), it can be said that more water is being reabsorbed than effective osmoles. Interestingly therefore, the gut is able to extract additional free water from that formed by the kidney.

10. What was the effect of the small intestine on electrolyte handling?
After partial correction for water loss, it is seen in Table 3Go (line 3) that [Na] and [Cl] decreased by >40% in the ileostomy drainage, indicating partial reabsorption of these solutes. Therefore, the gut is not causing net salt wastage at this particular time. It is important to note, however, that 50% more Cl is reabsorbed compared with Na, indicating that an unmeasured anion is secreted in the intestinal lumen and/or that an unmeasured cation other than K is reabsorbed along with Cl. A positive anion gap of 21 in the stools confirms that an unmeasured anion is being secreted. High levels of urea in the ileostomy drainage also indicate that an unmeasured cation, namely NH4 generated by urea-splitting bacteria, could be present in the intestinal lumen and partially reabsorbed with Cl. All these changes in the electrolyte composition of the urine are consistent with NH4-Cl/H-HCO3 exchange.

Another abundant urinary solute, urea, is being reabsorbed as it comes into contact with the intestinal mucosa. In Table 3Go, for instance, a marked decrease in [urea] from bladder to small intestine (82% reduction) is observed. In interpreting this result, however, it is important to remember that some urea is probably reabsorbed as NH3 following degradation by intestinal ureases, and that water reabsorption may have been underestimated (as mentioned above). In this patient, therefore, it appears that the gut avidly reabsorbed urea, thereby contributing to hyperazotaemia.

The last important urinary solute, K, remained at the same concentration after its passage down the small intestine. Although incomplete correction for water reabsorption may have also overestimated [K] in the ileostomy drainage, relatively normal PK between March 16 and March 21 suggests that the gut had a minimal effect on net K transport.

11. What are the main electrolyte and acid–base disorders resulting from urinary diversions?
Ureteroileostomies commonly cause an increase in urinary acidification with or without mild hyperchloremic acidosis. The pathophysiology of this complication has been reviewed by McDougal et al. [3] and it appears to involve the Na/H and the HCO3/Cl antiporters, which enable the parallel reabsorption of NH4 and Cl in exchange for H and HCO3 [411]. Severe metabolic acidosis is infrequent because rapid drainage of urine into a collecting bag limits the contact time between urine and intestine.

Hyperazotaemia has not been described frequently with urinary diversions using ileal segments; this may also have to do with the relatively small surface of intestinal mucosa to which urine is exposed with this type of diversion. For example, animal models in which long ileal diversions are performed do tend to accumulate urea in their plasma, presumably from hepatic detoxification of the reabsorbed ammonium [5].

Jejunal conduits are now seldom used because of an unacceptably high frequency of complications. Indeed, 40–65% of the patients develop hyponatraemia, hyperkalaemia, acidosis and azotaemia, the so-called ‘jejunal conduit syndrome’. The severity of the abnormalities in this syndrome also appears to correlate with the length of the conduit [12,13]. The pathophysiological basis of this syndrome has not been rigorously determined but there is some evidence for NaCl wasting leading to a reduction in the extracellular volume and for high levels of potassium reabsorption [13,14]. Transport systems that may be involved include K channels, K–Cl symporters and the Na pump.

12. Can you identify the site of fistulization: proximal ileum or jejunum?
Our patient underwent a fistulectomy within the following weeks. During surgery, cement-like adhesions were found throughout the abdominal cavity and around the posterior wall of the bladder dome. These retroperitoneal adhesions were probably responsible for the mild urinary tract obstruction seen in this patient. Because of the distorted anatomy, it was not possible to identify the exact site of fistulization, although the surgeons felt that the enteric opening was in the middle part of the small intestine.

Based on the preoperative evaluation, and because the phenotype of electrolyte complications did not fit that of either type of urinary diversion described earlier, it is possible that our patient had a mixed jejunal and ileal ‘conduit-like’ syndrome. Such a syndrome may have occurred from fistulization of the bladder into the jejunum, forcing urine to come into contact with the mucosæ of both jejunum and ileum. Presumably, the very large surface of mucosa to which the patient's urine was exposed would account for the severity of the hyperazotaemia.

13. Based on the available information, can you propose a pathophysiological chain of events that led to the complications presented by the patient?
To explain the electrolyte disorders in our case, the following scenario can be proposed: NH4Cl and urea excreted by the kidney were reabsorbed throughout the jejunum and the ileum; NH4-Cl/H-HCO3 countertransport led to hyperchloraemic metabolic acidosis, stimulating renal NH4 excretion further, while pure urea absorption (and also hepatic NH4 production) led to hyperazotaemia. High Purea, in turn, caused osmotic diuresis with secondary dehydration, accentuating azotaemia further. Dehydration led to increased thirst and ADH hypersecretion, causing dilution of the extracellular fluid and hyponatraemia. It is also interesting to point out that in this case, the gut was able to extract additional free water from that formed in the kidney, which probably contributed to the hypoosmolar disorder. To explain the absence of hyperkalaemia in our case, we propose that the effect of a jejunal diversion was counteracted by the effect of an ileal diversion.

Several lessons can be drawn from this unique case:

(1) An increase in the urea-to-creatinine ratio is not always caused by prerenal azotaemia.
(2) Normoosmolar hyponatraemia in the presence hyperazotaemia should be treated as hypoosmolar hyponatraemia.
(3) If associated with hypovolaemia, the latter condition carries a high risk for overly rapid correction of PNa.
(4) Administration of desmopressin or urinary electrolyte enrichment with furosemide are two options to prevent excessive water diuresis.
(5) Patients with intestinal conduit and vesicointestinal fistulæ are prone to electrolyte disorders, the severity of which varies according to the length of the gut exposed to urine.
(6) NH4-Cl reabsorption in exchange for H-HCO3, and urea reabsorption are important mechanisms for the development of acidosis and dehydration in patients with urinary diversions.
(7) The small intestine has high capabilities for net free water reabsorption.

Conclusion

The case presented here offers unique insights into the role of the gut in water and electrolyte handling, and into the pathophysiology of complications related to urinary conduits. To our knowledge, a combined jejunoileal conduit-like syndrome resulting from an acquired vesicojejunal fistula has not been described previously, although a similar case without hyponatraemia was published recently [15].

Appendix 1

The urine anion gap and the osmolar gap are often used as surrogate measures of urine NH4 [16]. They may also indicate the presence of HCO3, which is another unmeasured urinary solute that can be excreted in substantial quantities under specific circumstances. It is important to mention, however, that these indirect determinations may represent poor substitutes for direct measurements. Indeed, a recent study by Kirschbaum et al. [16] showed that in addition to NH4, SO4 and PO4 urinary excretion could also be quite variable in patients with metabolic acidosis. Thus, the difference between [Na+K] and [Cl] may not correspond only to the difference between [HCO3] (as the unmeasured anions) and [NH4] (as the unmeasured cations). The results of the urine anion gap and the osmolar gap must be interpreted with caution.

Acknowledgments

The authors wish to thank Dr Raymonde Gagnon of the Montreal General Hospital (McGill University) for excellent advice. They are also grateful to members of the Radiology Department, as well as to Drs Antoine Kibrité and Louis Lacombe of the L'Hôtel-Dieu de Québec Hospital (Laval University) for their expertise.

Notes

Correspondence and offprint requests to: Paul Isenring, L'Hôtel-Dieu de Québec Research Centre, 10 McMahon Street (Room 3852), Québec, Canada G1R 2J6. Email: paul.isenring{at}crhdq.ulaval.ca Back

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