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Chapter II: The Urine (3)

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(1) Small, round, or polyhedral cells are about the size of pus-corpuscles, or a little larger, with a single round nucleus. Such cells may come from the deeper layers of any part of the urinary tract. They are uncommon in normal urine. When they are dark in color, very granular, and contain a comparatively large nucleus, they probably come from the renal tubules, but their origin in the kidney is not proved unless they are found embedded in casts. Renal cells are abundant in parenchymatous nephritis, especially the acute form. They are nearly always fatty--most markedly so in chronic parenchymatous nephritis, where their {122} substance is sometimes wholly replaced by fat-droplets ("compound granule cells") (see Figs. 44, 48, 60, and 61).

(2) Irregular cells are considerably larger than the preceding. They are round, pear-shaped, or spindle-shaped, or may have tail-like processes, and are hence named large round, pyriform, spindle, or caudate cells respectively. Each contains a round or oval distinct nucleus. Their usual source is the deeper layers of the urinary tract, especially of the bladder. Caudate forms come most commonly from the pelvis of the kidney (see Figs. 49, _b_, 50, 62, and 63).

(3) Squamous or pavement cells are large flat cells, each with a small, distinct, round or oval nucleus (Fig. 49, _a_). They are derived from the superficial layers of the ureters, bladder, urethra, or vagina. Those from the bladder are generally rounded, while those from the vagina are larger, thinner, and more angular. Great numbers of these vaginal cells, together with pus-corpuscles, may be present when leukorrhea exists.

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3. Pus-corpuscles.--A very few leukocytes are present in normal urine. They are more abundant when mucus is present. An excess of leukocytes, mainly of the polymorphonuclear variety, with albumin, constitutes _pyuria_--pus in the urine.

When at all abundant, pus forms a white sediment resembling amorphous phosphates macroscopically. Under the microscope the corpuscles appear as very granular cells, about twice the diameter of a red blood-corpuscle (Figs. 51 and 63). In freshly voided urine many exhibit ameboid motion, assuming irregular outlines. Each contains one irregular nucleus or several small, rounded nuclei. The nuclei are obscured or entirely hidden by the granules, but may be brought clearly into view by running a little acetic acid under the cover-glass. This enables one to easily distinguish pus-corpuscles from small round epithelial cells, which resemble them in size, but have a single, rather large, round nucleus.

Pyuria indicates suppuration in some part of the urinary {124} tract--urethritis, cystitis, pyelitis, etc.--or may be due to contamination from the vagina, in which case many vaginal epithelial cells will also be present. In general, the source of the pus can be determined only by the accompanying structures (epithelia, casts) or by the clinical signs.

A fairly accurate idea of the quantity of pus from day to day may be had by shaking the urine thoroughly and counting the number of corpuscles per cubic millimeter upon the Thoma-Zeiss blood-counting slide.

4. Red Blood-corpuscles.--Urine which contains blood is always albuminous. Very small amounts do not alter its macroscopic appearance. Larger amounts alter it considerably. Blood from the kidneys is generally intimately mixed with the urine and gives it a hazy reddish or brown color. When from the lower urinary tract, it is not so intimately mixed, and settles more quickly to the bottom, the color is brighter, and small clots are often present.

Red blood-corpuscles are not usually difficult to recognize with the microscope. When very fresh, they have a normal appearance, being yellowish discs of uniform size (normal blood). When they have been in the urine any {125} considerable time, their hemoglobin may be dissolved out, and they then appear as faint colorless circles or "shadow cells" (abnormal blood), and are more difficult to see (Fig. 52; see also Figs. 45 and 60). They are apt to be swollen in dilute and crenated in concentrated urines. The microscopic findings may be corroborated by chemic tests for hemoglobin, although the microscope may show a few red corpuscles when the chemic tests are negative.

When not due to contamination from menstrual discharge, blood in the urine, or _hematuria_, is always pathologic. Blood comes from the kidney tubules in severe hyperemia, in some forms of nephritis, and in renal tuberculosis and malignant disease. The finding of blood-casts is the only certain means of diagnosing the kidney as its source. Blood comes from the pelvis of the kidney in renal calculus (Fig. 62), and is then usually intermittent, small in amount, and accompanied by a little pus and perhaps crystals of the substance forming the stone. Considerable hemorrhages from the bladder may occur in vesical calculus, tuberculosis, and newgrowths. Small amounts of blood generally accompany acute cystitis.

5. Spermatozoa are generally present in the urine of men after nocturnal emissions, after epileptic convulsions, and in spermatorrhea. They may be found in the urine of both sexes following coitus. They are easily recognized {126} from their characteristic structure (Fig. 53). The one-sixth objective should be used, with subdued light and careful focusing.

6. Bacteria.--Normal urine is free from bacteria in the bladder, but becomes contaminated in passing through the urethra. Various non-pathogenic bacteria, notably _Micrococcus ureæ_ (Fig. 54), are always present in decomposing urine. In suppurations of the urinary tract pus-producing organisms may be found. In many infectious diseases the specific germs may be eliminated in {127} the urine without producing any local lesion. Typhoid bacilli have been known to persist for months and even years after the attack.

Bacteria produce a cloudiness which will not clear upon filtration. They are easily seen with the one-sixth objective in the routine microscopic examination. Ordinarily, no attempt is made to identify any but the tubercle bacillus and the gonococcus.

Tubercle bacilli are nearly always present in the urine when tuberculosis exists in any part of the urinary tract, but are often difficult to find, especially when the urine contains little or no pus.

* * * * *

Detection of Tubercle Bacilli in Urine.--The urine should be obtained by catheter after careful cleansing of the parts.

(1) Centrifugalize thoroughly, after dissolving any sediment of urates or phosphates by gentle heat or acetic acid. Pour off the supernatant fluid, add water, and centrifugalize again. Addition of one or two volumes of alcohol will favor centrifugalization by lowering the specific gravity.

(2) Make thin smears of the sediment, adding a little egg-albumen if necessary to make the smear adhere to the glass; dry, and fix in the usual way.

(3) Stain with carbol-fuchsin, steaming, for at least three minutes.

(4) Wash in water, and then in 20 per cent. nitric acid until only a faint pink color remains.

(5) Wash in water.

(6) Soak in alcohol fifteen minutes or longer. This decolorizes the smegma bacillus (p. 35), which is often present in the urine, and might easily be mistaken for the tubercle bacillus. It is unlikely, however, to be present in catheterized specimens. It is always safest to soak the smear in alcohol for several {128} hours or over night, since some strains of the smegma bacillus are very resistant.

(7) Wash in water.

(8) Apply Löffler's methylene-blue solution one-half minute.

(9) Rinse in water, dry between filter-papers, and examine with the one-twelfth objective.

When the bacilli are scarce, the following method may be tried. It is applicable also to other fluids. If the fluid is not albuminous, add a little egg-albumen. Coagulate the albumen by gentle heat and centrifugalize. The bacilli will be carried down with the albumen. Separate the albumen, mix with artificial gastric juice (for preparation of which see test for pepsin, p. 222), and set in an incubator or warm place until digested. Finally, centrifugalize and stain as described above. The bacilli do not stain so well as in the ordinary methods.

A careful search of many smears may be necessary to find the bacilli. They usually lie in clusters (see Plate V). Failure to find them in suspicious cases should be followed by inoculation of guinea-pigs; this is the court of last appeal, and must also be sometimes resorted to in order to exclude the smegma bacillus.

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In gonorrhoea gonococci are sometimes found in the sediment, but more commonly in the "gonorrheal threads," or "floaters." In themselves, these threads are by no means diagnostic of gonorrhea. Detection of the gonococcus is described later (p. 264).

7. Animal parasites are rare in the urine. Hooklets and scolices of _Tænia echinococcus_ (Fig. 55) and embryos of _Filaria sanguinis hominis_ have been met. In Africa the ova, and even adults, of _Distoma hæmatobium_ are common, accompanying "Egyptian hematuria."

Other parasites, most of which are described in Chapter VI, may be present from contaminations. A worm {129} which is especially interesting is _Anguillula aceti_, the "vinegar eel." This is generally present in the sediment of table vinegar, and may reach the urine through use of vinegar in vaginal douches, or through contamination of the bottle in which the urine is contained. It has been mistaken for _Strongyloides intestinalis_ and for _Filaria sanguinis hominis_. It closely resembles the former in {130} both adult and embryo stages. The young embryos have about the same length as filaria embryos, but are nearly twice as broad and the intestinal canal is easily seen (compare Figs. 56 and 107).

C. EXTRANEOUS STRUCTURES

The laboratory worker must familiarize himself with the microscopic appearance of the more common of the numerous structures which may be present from accidental contamination (Fig. 57).

_Yeast-cells_ are smooth, colorless, highly refractive, spheric or ovoid cells. They sometimes reach the size of {131} a leukocyte, but are generally smaller (see Fig. 88, _l_). They might be mistaken by the inexperienced for red blood-corpuscles, fat-droplets, or the spheric crystals of calcium oxalate, but are distinguished by the facts that they are not of uniform size; that they tend to adhere in short chains; that small buds may often be seen adhering to the larger cells; and that they do not give the hemoglobin test, are not stained by osmic acid or Sudan but are colored brown by Lugol's solution, and are insoluble in acids and alkalis. Yeast-cells multiply rapidly in diabetic urine, and may reach the bladder and multiply there.

_Mold fungi_ (Fig. 58) are characterized by refractive, jointed, or branched rods (hyphæ), often arranged in a network, and by highly refractive, spheric or ovoid spores. They are common in urine which has stood exposed to the air.

_Fibers_ of wool, cotton, linen, or silk, derived from towels, the clothing of the patient, or the dust in the air are present in almost every urine. _Fat-droplets_ are most frequently derived from unclean bottles or oiled catheters. _Starch-granules_ may reach the urine from towels, the {132} clothing, or dusting-powders. They are recognized by their concentric striations and their blue color with iodin solution. _Lycopodium granules_ (Fig. 59) may also reach the urine from dusting-powders. They might be mistaken for the ova of parasites. _Bubbles of air_ are often confusing to beginners, but are easily recognized after once being seen. _Scratches_ and _flaws_ in the glass of slide or cover are likewise a common source of confusion to beginners.

IV. THE URINE IN DISEASE

In this section the characteristics of the urine in those diseases which produce distinctive urinary changes will be briefly reviewed.

1. Renal Hyperemia.--_Active hyperemia_ is usually an early stage of acute nephritis, but may occur independently as a result of temporary irritation. The urine is generally decreased in quantity, highly colored, and strongly acid. Albumin is always present--usually in traces only, but sometimes in considerable amount for a day or two. The sediment contains a few hyaline and finely granular casts and an occasional red blood-cell. In very severe hyperemia the urine approaches that of acute nephritis.

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_Passive hyperemia_ occurs most commonly in diseases of the heart and liver and in pregnancy. The quantity of urine is somewhat low and the color high, except in pregnancy. Albumin is present in small amount only. The sediment contains a very few hyaline or finely granular {134} casts. In pregnancy the amount of albumin should be carefully watched, as any considerable quantity, and especially a rapid increase, strongly suggests approaching eclampsia.

2. Nephritis.--The various degenerative and inflammatory conditions grouped under the name of nephritis have certain features in common. The urine in all cases contains albumin and tube-casts, and in all well-marked cases shows a decrease of normal solids, especially of urea and the chlorids. The characteristics of the different forms are well shown in the table on opposite page, modified from Hill.

{135} THE URINE IN NEPHRITIS

PHYSICAL. CHEMIC. MICROSCOPIC.
---------------------+---------------------+------------------------
Acute nephritis.
| |
Quantity diminished, | Urea and chlorids | Sediment abundant, red
often very greatly. | low. Much albumin: | or brown. Many casts,
Color dark; may be | up to 1.5 per cent. | chiefly granular, blood
red or smoky. | Reaction acid. | and epithelial
Specific gravity, | | varieties. Red
1.020 to 1.030. | | blood-cells abundant.
| | Numerous renal
| | epithelial cells and
| | leukocytes.
---------------------+---------------------+------------------------
Chronic parenchymatous nephritis.
| |
Quantity usually | Urea and chlorids | Sediment rather
diminished. Color | low. Largest | abundant. Many casts of
variable, often pale | amounts of albumin: | all varieties: fatty
and hazy. Specific | up to 3 per cent. | casts and casts of
gravity, 1.010 to | Reaction acid. | degenerated epithelium
1.020. | | most characteristic.
| | Blood present in
| | traces: abundant only
| | in acute exacerbations.
| | Numerous fattily
| | degenerated renal
| | epithelial cells, often
| | free globules of fat,
| | and a few leukocytes.
---------------------+---------------------+------------------------
Chronic interstitial nephritis.
| |
Quantity markedly | Urea and chlorids | Sediment very slight.
increased, | low in well-marked | Few narrow hyaline and
especially at night. | cases. Albumin | finely granular casts.
Color pale, clear. | present in traces | No blood except in
Specific gravity, | (often overlooked), | acute exacerbations.
1.005 to 1.015. | increasing in late | Very few renal cells.
| stages. Reaction | Uric acid and
| acid. | calcium-oxalate
| | crystals common.
---------------------+---------------------+------------------------
Amyloid degeneration of kidney.
| |
Quantity moderately | Slight decrease of | Sediment slight.
increased. Color | urea and chlorids. | Moderate number of
pale, clear. | Variable amounts of | hyaline, finely
Specific gravity, | albumin and | granular, and sometimes
1.012 to 1.018. | globulin. | waxy casts.
---------------------+---------------------+------------------------

3. Renal Tuberculosis.--The urine is pale, usually cloudy. The quantity may not be affected, but is apt to be increased. In early cases the reaction is faintly acid and there are traces of albumin and a few renal cells. In advanced cases the urine is alkaline, has an offensive odor, and is irritating to the bladder. Albumin in varying amounts is always present. Pus is nearly always present, though frequently not abundant. It is generally intimately mixed with the urine, and does not settle so quickly as the pus of cystitis. Casts, though present, are rarely abundant, and are obscured by the pus. Small amounts of blood are common. Tubercle bacilli are nearly always present, although animal inoculation may be necessary to detect them.

4. Renal Calculus.--The urine is usually somewhat concentrated, with high color and strongly acid reaction. Small amounts of albumin and a few casts may be present as a result of kidney irritation. Blood is frequently present, especially in the daytime and after severe exercise. Crystals of the substance composing the calculus--uric {136} acid, calcium oxalate, cystin--may often be found. The presence of a calculus generally produces pyelitis, and variable amounts of pus then appear, the urine remaining acid in reaction.

5. Pyelitis.--In pyelitis the urine is slightly acid, and contains a small or moderate amount of pus, together with many spindle and caudate epithelial cells. Pus-casts may appear if the process extends up into the kidney tubules (see Fig. 62). Albumin is always present, and its amount, in proportion to the amount of pus, is decidedly greater than is found in cystitis.

6. Cystitis.---In _acute_ and _subacute_ cases the urine is acid and contains a variable amount of pus, with many epithelial cells from the bladder--chiefly large round, pyriform, and rounded squamous cells. Red blood-corpuscles are often numerous.

In _chronic_ cases the urine is generally alkaline. It is {137} pale and cloudy from the presence of pus, which is abundant and settles readily into a viscid sediment. The sediment usually contains abundant amorphous phosphates and crystals of triple phosphate and ammonium urate. Vesical epithelium is common. Numerous bacteria are always present (see Fig. 63).

7. Vesical Calculus, Tumors, and Tuberculosis.--These conditions produce a chronic cystitis, with its characteristic urine. Blood, however, is more frequently present and more abundant than in ordinary cystitis. With neoplasms, especially, considerable hemorrhages are apt to occur. Particles of the tumor are sometimes passed with the urine. No diagnosis can be made from the presence of isolated tumor cells. In tuberculosis tubercle bacilli can generally be detected.

8. Diabetes Insipidus.--Characteristic of this disease is the continued excretion of very large quantities of pale, watery urine, containing neither albumin nor sugar. The {138} specific gravity varies between 1.001 and 1.005. The daily output of solids, especially urea, is increased.

9. Diabetes Mellitus.--The quantity of urine is very large. The color is generally pale, while the specific gravity is nearly always high--1.030 to 1.050, very rarely below 1.020. The presence of glucose is the essential feature of the disease. The amount of glucose is often very great, sometimes exceeding 8 per cent., while the total elimination may exceed 500 gm. in twenty-four hours. It may be absent temporarily. Acetone is generally present in advanced cases. Diacetic acid may be present, and usually warrants an unfavorable prognosis.

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A Manual of Clinical DiagnosisChapter II: The Urine (3)

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