AN ALBUM OF URINARY MICROSCOPY IMAGES IN A CLINICAL CONTEXT
G.B. Fogazzi, Milan, Italy
S. Verdesca, Milan, Italy
Now the last case.
On March 25th, 2003, very unusual crystals were found in the urine of a 30-year-old woman who was in the 8th week of her first pregnancy. The patient was under medication with folic acid, iron sulphate and levothyroxine.
The day before urinalysis, the patient had eaten large amounts of vegetables, especially spinach and salad.
The urine by dipstick showed: pH 7.5, specific gravity 1.025; albumin, glucose, haemoglobin, leukocyte esterase, nitrites negative.
The urine sediment showed a ++ crystalluria without any other particles. The crystals were colorless with an appearance which I had never seen before.
In fact, the crystals, were a combination of triangles of different width separated by clear spaces whose apexes converged towards a roundish central structure. They had a mean diameter of about 28 µm and didn’t show any birefringence under polarized light. For this appearance we defined them as “daisies”.
Here they are the crystals, as seen by bright field microscopy (slide 135)
and by phase contrast microscopy (slide 136).
Daisies we said, but some months later we found that they were also very similar to a type of pumpkin…
So, what crystals were they? We didn’t have any idea at that time. Therefore, we decided to undertake two steps in order to achieve their identification.
1. We reviewed all the images of crystals which could find in our specialized library (since we do love urinary sediment, we have everything dealing with it in our lab); 2. We performed infrared spectroscopy.
Thus, we reviewed 58 books devoted to urinary sediment, urinalysis, or clinical microscopy. Of these, 43 books were historical ones, which covered the period 1844 (the year of the publication of the very first book on urinary sediment by Guy’s Hospital man Golding Bird) to 1960. Fifteen other books were recent books, which covered the period 1981 to 1999. In this way, we examined more than 1530 images of crystals, and in only two works crystals similar to ours were found.
One work was the French book, published in 1853, "Traité de chimie anatomique et physiologique normale et pathologique" by Charles Robin and his firend Verdeil. It showed a plate with crystals which were perfectly identical to ours. Interestingly, the crystals had been found in the saliva (not in the urine!!) of a dog. As to their composition, it was claimed that they were due to calcium carbonate.
The second historical book in which we found crystals identical to ours was an Atlas published in Vienna in 1871, which had been written by two Austrian gentlemen, the surgeon Robert Ultzmann and the professor of medical chemistry Karl B. Hofmann. The authors stated that those crystals were due to a combination of creatin and zinc chloride. In more recent books, no crystals similar to ours were found.
Thus after reviewing all the books of our specialized library we had the following information: our crystals: unknown composition; French treatise: calcium carbonate; Austrian Atlas: creatin plus zinc chloride.
At this point we had the result of infrared spectroscopy (again performed for us by Professor Michel Daudon, Paris).
Our crystals did contain calcium carbonate. However, the infrared spectrum did not correspond to calcium carbonate commonly found in biological fluids. They were somewhat atypical.
Thanks to this case we were able to publish another short paper in 2007.
After the publication of that paper, we decided to know more about calcium carbonate crystals. By reviewing the literature, we found that they:
- are rare in humans, while they frequent in the urine of horses and other herbivores
- precipitate in alkaline urine
- have a pleomorphic appearance (dumbels, four-leaved clovers, daisies, pumpkins, etc)
- are either birefringent or non birefringent under polarized light
- cause effervescence if acetic acid is added to the urine, due to the production of carbon dioxide
- may just be the result of the ingestion of large amounts of vegetables
- usually do not have clinical implications
In addition, we decided to examine the urine of horses, in which calcium carbonate crystals are common. In one horse we found many calcium carbonate crystals, whose nature was confirmed by infrared spectroscopy. Interestingly, some crystals were somewhat similar to the crystals we found in our lady (slide 147 by bright field; slide 148 by phase contrast; slide 149 by polarized light)
In our opinion, these findings in the urine of a horse confirmed in some way that the crystals we found in our lady contained a type of calcium carbonate.
At this point of the story we thought we could suggest the following take home message:
- in most instances urine contains crystals which can be identified with the combined knowledge of crystal morphology, birefringence features, and urinary pH
- however, in rare cases unusual crystals can be identified only by the means of infrared spectroscopy
- insights into the history of medicine and into the urine of animals can be useful to solve present medical problems
But a few days ago we discovered that the story was not yet finished. In fact, while I was in Amsterdam for the European Congress of Laboratory Medicine, I was contacted by a Croatian colleague, who told me that she had found crystals identical to ours by analyzing a urine sample with an automated sediment analyzer (slide 151). Interestingly, also this time the urine belonged to a pregnant woman who the day before had eaten a lot of spinach and other vegetables….
At this point, we are planning to prepare another paper, which might sound like this: Pumpkin crystals: rare but not so rare and why in pregnant women? And what is the role of spinach?
Now, the very last slide with the conclusions. We hope that we have been able to demonstrate that the urinary sediment examination is important in the management of the renal patients in a wide range of clinical situations. However an old tool, urine microscopy in the hands of us nephrologists still provides irreplaceable clinical information and can still stimulate our intellectual curiosity, as the last cases demonstrates very well. Why then we don’t we use such a useful, simple, quick, inexpensive test as we should?