Author: Xu Yisheng
Unit: Department of Clinical Laboratory, Second Affiliated Hospital of Gannan Medical College
As one of the three major routines of the laboratory department, the urine routine examination is a project that tests people who are no longer familiar with it. At the same time, it is also the simplest, fastest and most affordable test for clinicians to judge patients' urinary system diseases, which can be called a "good quality and low price" dry goods.
But behind these indicators of urinary routine, how much meaning is hidden, and what are the true and false results? Take a recent case of negative red and white blood cells in urine dry chemistry, and talk about the things that are routine in the urine.
Case after
On November 20, colleagues informed that urinary routine specimen No. 24 was quite interesting, and found that the results of the red and white cells of the urine dry chemical and the urine sediment analyzer were inconsistent, and the microscope microscopy results were consistent with the results of the urine sediment analyzer, as shown in Figure 1.
Figure 1
Patient information, female, 51 years old, clinical diagnosis: dyspnea, pelvic malignancy.
Dry chemical test strips: urine protein +1, vitamin C +3, PH 5.0, SG 1.030, the rest is normal.
Urinary sediment analyzer: 109.5 leukocytes/uL, 70.8 erythrocytes/uL, 11.0/uL cast.
Urine centrifugation microscopy: leukocytes +2/HP, erythrocytes +1/HP, clear cast±.
How do I analyze this urine routine result?
Erythrocytes are falsely negative
Urine sediment cells have formed sub-counts, centrifugal microscopy can find the presence of red blood cells, naturally can think of dry chemical occult blood negative as false negative, the root cause, is caused by vitamin C.
Looking at the patient's urine dry chemical instrument test results, as shown in Figure 2, the vitamin C concentration is 5.6mmol/L.
Figure 2
Flipping through the instructions of the 11 urine test strips shows that when the vitamin C concentration exceeds 1.4mmol/L, the low concentration occult blood measurement will cause false negative results. The concentration of vitamin C in the patient's urine has far exceeded the minimum concentration on the test strip that can affect the occult blood outcome.
White blood cells are falsely negative
Dry chemical determination of leukocytes is to detect leukocyte esterase, and neutrophils contain the most esterase in leukocytes, followed by monocytes, and lymphocytes do not contain this enzyme. Therefore, if the urine is dominated by monocytes and lymphocytes (such as rejection after kidney transplantation), the dry chemical leukocyte test band membrane mass can be falsely negative.
Based on the diagnosis of pelvic malignancy, a review of the electronic medical record found that the patient underwent laparoscopic exploration under general anesthesia + bilateral adnexal with resection + pelvic mass resection + abdominal pelvic tumor implant inactivation + intestinal adhesion release + pelvic adhesion separation and release + intravenous port implantation on the afternoon of November 19, with intraoperative bleeding of about 1600 mL. On the morning round of November 20, the urine output was 2150 mL, the abdominal drainage tube ejected 300 mL of light bloody fluid, and the pelvic drainage tube elicited 400 mL of bloody fluid.
The patient's urine was sent for test on the morning of November 20, and there is no history of kidney transplantation, and yesterday's self-surgery did not cause self-rejection. Because colleagues have discarded the urine sediment, it is impossible to stain to distinguish whether it is neutrophils, lymphocytes, or monocytes.
Questions are reborn
Given the high concentration of vitamin C, will dry chemical white blood cells be disturbed by vitamin C?
Flipping through the test textbook, as shown in Figure 3, the urine dry chemical analyzer detects white blood cells, and the false negative causes are: protein, vitamin C, glucose, and cephalexin [1].
Figure 3
In the 4th edition of the "National Clinical Laboratory Practice", the factors affecting the results of urine test strips are also mentioned, and the false negatives of leukocyte esterase are: high concentration of tetracycline in the urine, vitamin C, mercury salts, trypsin inhibitors, oxalates; 1% boric acid; mucus-containing specimens and lymphocyte-containing specimens. Leukocyte esterase sensitivity decreases as concentrations of glucose (> 30 g/L), bimi, and oxalate increase, and leukocyte esterase is also interfered with by nitrofurantoin, gentamicin, cefotaxin, and high concentrations of albumin (>5 g/L)[2].
The patient's urine protein was shown on the dry chemical instrument as PRO +1,0.3g/L, which was much smaller than the high concentration protein (>5g/L), so the WBC false negative caused by the high concentration of albumin was excluded.
Since textbooks and operating procedures say that vitamin C can cause false negatives of white blood cells in the urine, and the concentration of vitamin C in the urine of patients is so high, will the "real culprit" be vitamin C? We continue to analyze
Drug factors?
Since the patient was an ICU patient, an idea flashed: Is it possible that the drug factor is possible?
We know that patients in ICU wards are generally more serious patients, and they use more drugs than patients in ordinary wards, and it is understandable to consider drug factors.
One drug is mentioned in both the test textbooks and the protocols: cefolix. It is a semi-synthetic first-generation oral cephalosporin antibiotic drug that inhibits the synthesis of cell walls, causing cell contents to swell to rupture and dissolve, killing bacteria.
The patient's urine routine was sent to 10:18 on November 20, taking this as the time node to check the doctor's instructions, enter the doctor's workstation to browse, and sure enough, it was found that the clinical use of cefoperazone sulbactam, vitamin C injection, and cefoperazone sulbactam drug is the third generation of cephalosporin.
Use cefoperazone sulbactam at 16:11 on November 18, as shown in Figure 4.
Figure 4
On January 19 at 19:45 use vitamin C injection, as shown in Figure 5.
Figure 5
Use cefoperazone sulbactam on November 20 at 09:00, as shown in Figure 6.
Figure 6
A thousand turns
It can be seen that cefoperazone sulbactam is used more often than vitamin C injection, is it really cefoperazone sulbactam? This needs to start with the metabolic pathway of the drug.
Why do textbooks and protocols say that cefolix can cause WBC to be falsely negative? This is because cephalexin (the first generation of cephalosporin) is metabolized from urine at a rate of 90% (indicating that its main route of excretion is the kidneys). As a third-generation cefoperazone sulbactam, although the antibacterial range is wider than that of the first generation, its main excretion route is hepatobiliary, not the kidneys.
Therefore, even if it is calculated from the time, the use time and frequency of cefoperazone are close to the time of urine routine detection, but because it is not excreted in the kidneys, it will not appear in the urine, so it is excluded that the WBC false negative in the urine is caused by cefoperidone sulbactam.
The metabolic process and conversion of vitamin C in the body are still inconclusive, but it can be determined that the last metabolite of vitamin C is excreted by the urine. Combined with the patient's use of vitamin C injections the night before, this seems to turn the problem back to square one: vitamin C.
The truth is revealed
When I browsed the medical orders again, I suddenly found that in addition to the vitamin C medical orders issued by the clinic on November 19, there were also urine bags to apply for medical orders, as shown in Figure 7, that is to say, the urine received by the laboratory department on November 20 was urine bag urine, all of which could make sense.
Figure 7
On the evening of the 19th, the clinical prescription of vitamin C and urine bag doctors, the patient's urine is excreted into the urine bag, and the metabolic pathway of vitamin C is exactly the kidney, that is to say, between the evening of the 19th and the morning of the 20th, the urine in the urine bag has been mixed with vitamin C and red and white cells. From Figure 5, it can be seen that vitamin C injection 0.5g: 2mL * 1 stick / stick, a total of 3g was applied, that is, 6 sticks. It can be imagined how high the concentration of vitamin C in the urine should be if this vitamin C is metabolized by the kidneys.
In the end, it can be considered that the patient's urine dry chemical red and white blood cells are false negative, and the "black hand" behind the scenes is vitamin C, and he is highly suspicious that the vitamin C concentration in the patient's urine is far more than 5.6mmol/L, because the vitamin C of the urine dry chemical test strip can only be measured at most +3 (5.6mmol/L).
Inadequacies
The shortcoming of this case is that the laboratory was unable to quantitatively measure how high the amount of vitamin C in the patient's urine was. The concentration of dry chemical vitamin C in the urine can only be used as qualitative, and its concentration can only be regarded as a semi-quantitative quantity. In addition, a positive dimension C can only reach +3 at most. Looking at the 11 urine dry chemical test strips, the positive values for vitamin C are: ± (0.6mmol/L), +1 (1.4mmol/L), +2 (2.8mmol/L), +3 (5.6mmol/L), as shown in Figure 8.
Figure 8
Case studies
It is more common for vitamin C in the urine to cause pseudo-negative chemoecyptemia in the urine, but it is still relatively rare to cause a false-negative chemoecynossible blood and white blood cells at the same time.
The reason why the patient can have negative red and white cells is due to the clinical use of vitamin C injection and urine bag retention of urine, resulting in long-term contact with cells in the urine bag, and the concentration of vitamin C is also very high.
When analyzing urine routine reports, it is important to pay attention to the effects of vitamin C as an indicator. In particular, when the five indicators of urine vitamin C are positive, urine dry chemical occult blood, white blood cells, glucose, bilirubin, and nitrite are negative, it is necessary to carefully consider whether the negative is false negative.
Some teachers may ask: Is it possible that the source of vitamin C in food is possible? The answer is: look at the patient's condition. Although the source of vitamin C is mostly food, especially citrus fruits, vegetables, etc., the patient is more seriously ill, and the influence of food factors can be ignored. Clinical doctors ordered that 6 vitamin C injections were applied for, so the factor of considering the drug of vitamin C accounted for the main factor.
summary
The significance of vitamin C in the urinary routine is not to suggest certain diseases, but to help clinicians and examiners determine whether other indicators in urine dry chemistry are credible and whether they are disturbed by vitamin C.
【Reference】
Xu Wenrong,Lin Donghong. Clinical basic laboratory technology[M].Beijing, People's Medical Publishing House, 2015:147
[2] Shang Hong,Wang Yusan,Shen Ziyu. National Clinical Laboratory Operating Procedures 4th Edition[M].Beijing, People's Medical Publishing House, 2015:163
Source: Inspection Horizon Network
Edited by: Yeah Reviewer: Xiao Ran