I will be periodically posting medical quizzes followed by answers and brief explanations. These quizzes represent medical problems and conditions that may be encountered by medical professionals. They are mainly intended as quick educational tips for medical students and residents, in addition to nephrology fellows. Although, I will make every effort to ensure the accuracy of the information presented, I am not responsible for any unintended mistakes or inappropriate use or application of the information presented. You should always consult with your supervising attending when you are taking care of your patients.
You are evaluating a patient who was admitted yesterday with cellulitis. The first year resident, who evaluated the patient yesterday, ordered urinary electrolytes as part of evaluating mild hyponatremia.
You are reviewing patient’s data with the medical student. The laboratory results are as follows:
Serum: Na 130, K 4.5, Cl 96, HCO3 24, BUN 15, Creatinine 1.3, Glucose 110.
Urine: Na 110Meq/l, K 40Meq/l, Cl 120Meq/l.
The medical student calculates the urinary anion gap (AG) (110+40-120=30) and gets a positive value of 30. He tells you that the patient must have a urinary acidification defect, since his urinary AG is positive and his ammonia excretion is only about 30Meq/l.
Which of the following is correct in regards to the student’s statement?
1-The medical student in correct, a positive urinary AG indicates a urinary acidification defect.
2-An ammonia concentration of 30meq/l is normal in patients with normal serum HCO3.
3-The patient does not have urinary acidification defect, since his serum HCO3 is normal and this urinary electrolyte results likely belong to another patient with renal tubular acidosis.
4-It is normal for individuals without acidemia to have a positive urinary AG.
Please scroll down to read the answer
The correct answer is number 4
Few points about urinary anion gap:
1-Urinary AG does not correlate with measured urinary ammonia
2-Urinary AG has no diagnostic value in patients without acidemia
3-Urinary AG in normal subject is positive indicating normal or low ammonia production (UpToDate in Medicine).
4-To understand the concept of urinary AG and how it relates to ammonia, it important to know the followings:
-Body fluids are electrically neutral , so positive ions should equal negative ions .
-Major urinary cations are: Na, K, NH4, Ca, Mg.
-Major urinary anions are: Chloride, Phosphate, Sulfate, in addition to a variety of organic anions (citrate, urate,creatinine,hippurate, ketones, pyruvate and others).
-Urinary concentrations of cations and anions in the urine can vary with diet . For example, high protein diet will lead to increase in sulfate excretion (normal less than 30 mmol or less than 60 meq), and eating sweet potatoes will increase the excretion of hippurate. Normally, GI absorption of Na and K exceeds that of chloride, so the sum of urinary K and Na exceeds chloride (UpToDate)
-In normal subjects urinary cations represented mainly by Na, K and NH4 are balanced by chloride and other anions, so when you subtract chloride from the sum of Na and K, you get a positive value since the concentration of NH4 in normal subject is relatively small ( and in general correlates with and approximates sulfate excretion), and urinary cations are balanced by chloride in addition to phosphate and numerous other urinary organic anions. However, when you develop acidosis that is not caused by renal tubular defects, NH4 generation and excretion increases markedly and this increase in cations has to be balanced by anions . Compensatory increase in the excretion of anions other than chloride is limited ( limited increase in phosphate in acidosis, sulfate excretion is diet-dependent, acidosis decreases citrate excretion, acidemia inhibits the production of organic acids).
-So chloride is the main anion that increases to balance NH4 (I am not sure of the mechanism, one explanation that is given in uptodate, states that when you have acidosis induced by diarrhea, you lose more Na and K than chloride, so you excrete more chloride in the urine).
-This large increase in NH4 and chloride, will lead to a negative value when you subtract chloride from the sum of K and Na.
5-The conclusion is that the urinary AG is a qualitative and not a quantitative method that we can use to show an appropriate renal response to acidosis by increasing NH4 production, and this will differentiate renal from non-renal causes of acidosis. It is not a quantitative method due to the fact that chloride is not the only anion that balances NH4 (in addition to not including Ca and Mg in the calculaton).
To illustrate these points further, the followings are actual 24 urine values of a patient who is being worked up for kidney stones. These values were converted to meq/l, in addition, the degree of dissociation of organic acids was calculated using the Henderson Hasselbalch equation , reported patient's urine pH, and specific organic acid pK:
As you can see, the total cations exceed total anions by 14 meq/l and this likely represent other unmeasured anions such as hippurate, pyruvate, lactate and other anions.
If you calculate the AG from the above values : Na+K minus Cl= 54.06. This value is not equal to the measured NH4 (32.43). The implied assumption in the classic AG calculation is that the only additional cation present is NH4 and the only quantitatively important anion is chloride. However, as you can see, there are other cations (Ca and Mg) and other anions ( especially phosphate and sulfate).