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CLS 1521 AND CLS 1531
URINALYSIS
(Part III)
Objectives with narrative and illustrations.
All objectives are cognitive, unless identified as being psychomotor. The
student, at the end of each instructional component, whether in the classroom or
lab, is responsible for meeting the objectives. All student that achieves a
cumulative score of 70% or better on all problem sets, case studies, major
exams, quizzes, and library assignments are deemed to have met the objectives of
this course.
3-200 DISCUSS THE GRANULAR CAST AND ITS CLINICAL SIGNIFICANCE.
Granular casts are acellular casts and are generally thought to be a stage in
the degeneration process of cellular casts. The size of the granules in this
cast varies resulting in two general categories: fine and coarse granular casts.
Neither is more significant than the other, therefore the size of granules are
not differentiated and these casts are simply reported out as granular casts per
lpf. It is not uncommon to find granular casts accompanying hyaline casts in
times of physical exertion, emotional stress, dehydration, or heat stress. It is
the second most commonly occurring cast in urine sediment. When viewed in the
brightfield microscope, these casts appear colorless or yellow in appearance. If
you observe a hyaline cast with several obvious granules, but the cast is
predominately hyaline, then report the cast as the hyaline type. This cast has a
high refractive index and is most often observed in the cigar shape. This cast
will take on a variety of colors dependent upon the staining material.
a. Sternheimer-Malbin stain causes dark blue coloration of the granules.
b. Bilirubin will stain the cast a yellow-orange color.
c. Phenazopyridium produces a orange-red color.
This cast can been reported to have been confused with the hemoglobin cast, see
Objective #199. It can be confused with the bacterial cast. The bacterial cast
can be differentiated with Gram's stain, see Objective #204. The granular cast
should be reported out as number per lpf. This cast is observed in all renal
disorders, stress, and during the recovery phase of acute kidney failure.
Note the following illustration of the granular cast.
3-201 DISCUSS THE FATTY CAST AND ITS CLINICAL SIGNIFICANCE.
This cast may contain fat oval bodies or fat globules or both (see Figure 21)
and when present is pathologically significant. It is characterized by a high
refractive index, stains with Sudan III or IV (if triglycerides are present) and
the polarized microscope demonstrates the Maltese cross phenomenon (if
cholesterol and its esters are present). The following may be observed when
fatty casts are present:
[1] variable size fat globules within the cast.
[2] will NOT take up Sternheimer-Malbin stain.
[3] cast matrix will be either hyaline or granular in type.
[4] proteinuria is present.
[5] variable size free-floating fat globules in the "neighborhood".
[6] strongly positive protein test on the reagent test strip or 3% SSA test.
[7] the urine strongly foams when shaken due to increased albuminuria.
The presence of these casts indicates the following type of renal pathology: (1)
nephrotic syndrome, (2) lipid necrosis, (3) diabetic neuropathy, (4) lupus
neuropathy, (5) any chronic renal disorder, and (6) renal tubular cell death.
Report out this cast as numbers per lpf. Refer to the following
illustration of a fatty cast.
3-202
DISCUSS THE WAXY CAST, HOW TO RECOGNIZE IT, AND ITS CLINICAL SIGNIFICANCE.
This is an acellular cast with a very high refractive index. Its presence in a
urine specimen is an indicator of renal tubular damage, severe stasis and is a
very serious pathological finding. These casts are associated with chronic renal
failure, nephrotic syndrome, diabetic neuropathy, renal allograft rejection, and
renal amyloidosis. In the brightfield microscope, the waxy cast is homogeneously
smooth in appearance, has parallel sides with sharp margins (in which cracks,
fissures, convolutions, and notches can be observed), ends that are often blunt
and a broken off appearance, and will appear to have thickened areas. The color
of the waxy cast in unstained sediment is from colorless to gray to yellowish.
If stained with Sternheimer-Malbin stain, the waxy cast appears pink. Because
waxy casts appear in urine specimens with a serious pathology, these casts are
often appear with diameter 2 to 6 times larger than the average casts. These
casts are broad casts or renal failure casts. See the following illustration.
3-203
DISCUSS THE "MIXED” CAST AND ITS CLINICAL SIGNIFICANCE.
A mixed cast is one that has more than one component, see Figure 22. It is not
unusual for more than one component to be incorporated into a Tamm-Horsfall
matrix. Clinical significance of finding mixed casts will correlate to that
described for a specific constituent. Mixed casts may be any one of the
following components as shown in the following examples.
WBC + renal tubular epithelial cell
WBC + granular
WBC + RBC
Other examples of mixed casts would be:
a. fatty + renal tubular epithelial cell
b. bacterial + renal tubular epithelial cell
c. bacterial + RBC
d. granular + WBC + renal tubular
epithelial cell
e. RBC + renal tubular epithelial cell
A hyaline matrix or pigmented matrix plus a component
not constitute a
mixed cast. |
3-204
DISCUSS THE BACTERIAL CAST AND ITS CLINICAL SIGNIFICANCE.
Bacterial casts may be expected to occur whenever a patient is diagnosed with
pyelonephritis. The bacteria are often difficult to discern within the cast
matrix and it is not unusual for a bacterial cast to be reported out as a
granular cast. The following information will help to identify the bacterial
cast.
a. Bacteria should be in the "neighborhood".
b. WBC should be in the "neighborhood" and may be present in the cast, in
which
case, the cast is a mixed cast. Because of the responsiveness of
neutrophils to
bacterial presence, few true bacterial casts are observed.
c. WBC casts may be present.
d. The protein, nitrite and leukocyte esterase pads on the reagent strip should
be positive.
Note: Performing a Gram stain may facilitate recognition of the bacterial cast.
3-205
DISCUSS THE PIGMENTED CAST AND ITS CLINICAL SIGNIFICANCE.
The pigmented cast is usually a hyaline cast that has a distinctive coloration
form (1) bilirubin, (2) hemoglobin, (3) myoglobin, (4) phenazopyridium, or (5)
any strongly colored medication. Ordinary urine pigments do not stain casts. If
the pigment is due the hemoglobin, this could be an indicator of a transfusion
reaction or hemolytic anemia. If the pigment is due to myoglobin, then muscle
trauma or acute renal failure may be the cause. If bilirubin is present, not
only will the casts be stained, but also the cellular elements. Bilirubin is an
indicator of hepatitis. Strongly colored medications such as phenazopyridium is
an indicator that a treatment process is in progress and may not be considered
to be clinically significant.
3-206
EXPLAIN WHAT IS MEANT BY "TELESCOPED” URINE SEDIMENT.
Telescoped urine is a term that describes the appearance of all types of casts
and any other pathological components in the urine sediment. It has been used to
describe the sediment of patients diagnosed with acute glomerulonephritis. Its
original meaning described the simultaneous appearance of WBC's and RBC's in
urine. The term now includes the appearance of casts, including broad casts,
waxy casts, and oval fat bodies.
3-207
EXPLAIN "ATHLETIC PSEUDO-NEPHRITIS".
This is a physiological, transient condition that occurs when strenuous activity
is followed by a release of hyaline and granular casts in the urine. Once the
stress is relieved, the condition disappears.
3-208
EXPLAIN THE SIGNIFICANCE OF "BROAD" CASTS.
Broad casts occur when the flow of urine in the lumen of the tubules becomes
very compromised. Formation usually occurs within dilated or atrophied distal
tubules and the larger collecting tubules. Their presence is an indicator of a
poor prognosis. They may be of any type of cast, but granular and waxy types are
more often observed. Broad casts will range from two to six times larger than
the typical cast. These
casts are sometimes called renal failure casts.
3-209
DISCUSS CRYSTAL CASTS AND THEIR CLINICAL SIGNIFICANCE.
Crystal casts occur when solutes precipitate in the lumen of the renal tubules
and become trapped in the hyaline cast matrix. It is the consensus of most
professionals that these casts have no clinical significance. The two most
commonly encountered crystal-type casts are calcium oxalates and sulfonamides,
with uric acid crystals in third place. Casts with amorphous urates have been
reported. Before reporting out a crystal cast, be sure that you confirm the
presence of a protein matrix and that these are not crystals aligned along a
sticky strand of mucus. Because crystal casts may cause irritation in the
tubules, bleeding may occur. Some degree of hematuria may accompany such casts
in urine.
3-210
DISCUSS MUCUS IN URINE AND ITS CLINICAL SIGNIFICANCE.
Mucus is a proteinaceous fibrous material produced and excreted by the glands in
the lower parts of the urinary tract and it also comes from the vagina as a
urine contaminant. Tamm-Horsfall protein is known to be a component of mucus and
renal tubular cells do contribute the presence of this formed element. Mucus is
not considered to be clinically significant. There may be clinical concern, if
there is an inflammatory condition that is characterized by excretion of larger
quantities of mucus. Mucus is most often seen as "threads" having a fine,
asymmetrical appearance. They vary in width and length, appearing ribbon-like
and often wavy. The ends are typically irregular, pointed, or frayed (split). Mucus can easily be overlooked in the urine specimen because of its low
refractive index. Sternheimer-Malbin stain enhances its appearance giving
it a pink or blue cast. Mucus has been confused with hyaline casts, but careful
observation will reveal the irregular nature of the mucus strands. Mucus can be
seen in clumps.
3-211
DISCUSS YEAST IN URINE AND ITS CLINICAL SIGNIFICANCE.
Yeast are fungi and the most common encountered species in urine is Candida
albicans. This species is observed most often in diabetic patients and women
with vaginal moniliasis. It is possible for a UTI to caused by yeast. Yeast are
oval to round, small to moderate size, refractile, colorless cells that resemble
erythrocytes. Yeast are easily differentiated from RBC's because they will not
dissolve in dilute acid nor take up vital stains. Other conditions in which
yeast may be found are pregnancy, immuno-compromised patients, and women on oral
contraceptives. Caution must be exercised in identify a yeast infection. Yeast
are present in the air and on the skin. Because of this, yeast can easily
contaminate a urine specimen.
Candida albicans is an oval yeast measuring 2 - 3 by 4 - 6 μM. This yeast is a
“normal” contaminant found on virtually all people. It stains gram-positive. It
produces budding cells that may be elongated and resembles hyphae. Such
elongations are called pseudohyphae. This organism has the potential to invade
the body producing sepsis, thrombophlebitis, endocarditis, or other infections
of body organs. Such invasions are not a problem to the normal and healthy
individual as the immune system readily destroys this yeast. Individuals with
predisposing factors as [1] diabetes mellitus, [2] general debility, [3]
immunodeficiency (AIDS or chemotherapy), [4] indwelling urinary catheters, and
[5] indwelling I.V. catheters may find this organism to be a problem.
Refer to the following illustrations.
yeast with hyphae
mycelial form of yeast
budding yeast
Two other yeast species can be found in urine, but on an infrequent basis.
Torulopsis glabrata are small yeast cells, do not form pseudohyphae, easily
phagotized by WBC's. Candida parapsilosis is usually found in patients with
indwelling catheters. They are commonly found on the skin and in the feces of
healthy patients.
3-212
DISCUSS THE POTASSIUM HYDROXIDE PREPARATION AND ITS ROLE IN URINE TESTING.
Potassium hydroxide (10% KOH solution) is added to a slide preparation of
vaginal secretions, slightly diluted with saline. The slide is warmed and
observed macroscopically. KOH enhances fungal elements by destroying other
cellular and formed elements. Bacteria are not affected by the KOH solution. The
procedure required that a vaginal swab be placed in 0.5 mL of saline and swirled
to mix. A drop of this combination is placed on a glass slide and a drop of KOH
is added, mixed, and a coverslip placed over the mixture. The specimen is then
examined under the microscope.
3-213
DISCUSS SPERMATOZOA IN URINE AND THEIR CLINICAL SIGNIFICANCE.
Sperm are commonly observed in the urine of males. They may be observed in the
urine of women in which case it will be the result of vaginal contamination.
Spermatozoa are easily recognized by their oval head and long narrow trail.
Urine is not a viable medium for sperm and most sperm observed in urine are
usually nonmotile. If motile sperm are encountered, it indicates a recent
ejaculation. The presence of sperm are in urine is of no clinical significance
unless the patient is undergoing fertility testing or it is a question of
forensic pathology.
3-214
DISCUSS PARASITES IN URINE AND THEIR CLINICAL SIGNIFICANCE.
A variety of parasites may be observed in urine. The most commonly encountered
parasite is Trichomonas vaginalis. Commonly called a "trich" or "trichomonas", when seen in
urine, it will be most often observed in women, usually the result of vaginal
contamination. "Trich" can be easily observed in fresh urine preparations. Look
for quick, flitting or jerky motions. Although it is responsible for vaginal
infections, it can also infect the urethra, prostate, periurethral glands and
bladder. It is a flagellated, pear-shaped protozoan, about the size of
leukocytes or renal tubular epithelial cells. Sizes have been reported from 5 μM
and up to 30 μM. It has single nucleus, four anterior flagella, an anterior
undulating membrane (ending half-way down the length of the parasite), and a
posterior axostyle. It is transmitted sexually, producing symptoms in women, but
is generally asymptomatic in men. The parasite is fragile and rapidly dies as
urine ages or if it is stored. A "dead trich" is difficult to identify because
it assumes a spherical form and appears as a degenerating leukocyte or renal
tubular epithelial cell. Staining does not enhance its morphology and
identification is best accomplished if a living "trich" can be observed in fresh
urine. See the following illustrations.
Trichomonas
dead 'trich'
living 'trich"
vaginalis
(as seen in old urine) (in fresh
urine)
he other true urinary parasite is Schistosoma haematobium, a trematode (fluke).
It is endemic to the middle east, Africa, and Portugal. It is seldom seen in the
United States. The fluke resides in the venous plexuses of the urinary bladder,
prostate gland, uterus, and vagina. Its eggs migrate through the bladder wall
and appear in the urine. When looking for ova, it is recommended that a late
morning urine specimen be collected and examined. See the following
illustration.
Another parasite occasionally found in urine is the Enterobius vermicularis
ovum. Refer to the following illustration If it is present it is due to fecal contamination. It is
occasionally seen in urine in the larval form.
At one time or another, intestinal parasites have been found in urine. This
would be due a vesicosigmoid fistula or fecal contamination. Examples include:
Entamoeba histolytica, Ascaris lumbricoides, and Giardia lamblia.
3-215
DESCRIBE TWO WAYS THAT FECAL CONTAMINATION CAN OCCUR IN URINE.
Vesicosigmoid fistula: A pathological occurrence when the urinary bladder and
sigmoid colon fuses and an abnormal opening (fistula) forms. The movement of
fecal material into the urinary bladder will then occur. To demonstrate this
anomaly may require ingesting an inert, indicator substance (as charcoal). The
presence of charcoal in the urine is diagnostic.
Improper collection technique and is seen most often in infants and physically
compromised patients. Proper care in cleaning and collecting the urine will
eliminate this problem.
3-216
DISCUSS BACTERIA IN URINE AND THEIR CLINICAL SIGNIFICANCE.
Normal, healthy urine is sterile and free of bacterial. Most bacteria observed
in urine is due to pollution that is a result of careless handling, use of
non-sanitized containers, vaginal contamination, or resultant of
gastrointestinal tract contamination. In the case of contamination, the presence
of bacteria is not clinically significant. The most commonly encountered
bacteria are the gram negative rods. If bacteria are observed and there are
leukocytes present in the sediment, and the chemistry tests for protein,
nitrate, and leukocyte esterase are positive, then a UTI is possible and a
culture and sensitivity should be performed.
Bacteria observed range for small cocci and rod forms to large forms. On
occasions large and long bacteria are observed with a large central swelling,
these are protoplasts and are the outcome of antibiotic therapy. If there is
difficulty in recognizing bacteria, the gram-stain technique may be helpful in
visualizing these microorganisms. If bacteria are found in a clean catch
specimen collected in a sterile container, a UTI is possible. If bacteria can be
readily observed in fresh “uncentrifuged” specimen, it may be a possible UTI. To
reliably identify bacteria in urine, use a clean-catch specimen collected in a
sterile container, centrifuge, and gram-stain. If bacteriuria is obvious, but
WBC's are absent, investigate the collection and handling methods to eliminate
contamination.
3-217
DISCUSS CRYSTAL FORMATION IN URINE.
Crystals precipitate in urine due to high concentrations of solutes. There are
four factors that enter into crystal formation:
[1] Solute concentration: factors include dehydration, dietary excesses, and
medications.
[2] pH: Solubility is pH dependent. Crystals that precipitate in neutral or
alkaline urine are less soluble than the crystals that precipitate in acidic
urine. As a rule, inorganic salts (calcium, phosphate, ammonium, and magnesium)
precipitate in alkaline urine. Organic solutes (uric acid, cystine, bilirubin,
and x-ray dye) tend to precipitate out in acidic urine.
[3] The rate of flow through the tubules affect crystal formation. A slow rate
of flow produces a concentrated urine and promotes crystal formation. A rapid
flow rate produced a more dilute urine and decreased crystal formation.
[4] Temperature: If warm, the solutes remain in solution better and
crystallization is retarded or does not occur. If cold, then solutes become less
soluble and crystallization occurs readily.
Normal, healthy urine seldom contains crystals. The presence of crystals in
urine may be called crystalluria. If crystals are present in the urine at the
time of voiding, it is possible that this may be clinically significant. Most
crystals observed in urine precipitate out after sitting (especially if the
urine is refrigerated before testing), because the solute concentration is high,
a super saturated solution, and the solubility threshold is exceeded as the
urine cools.
3-218
DISCUSS AMORPHOUS SEDIMENT IN URINE AND ITS CLINICAL SIGNIFICANCE.
There are three types of amorphous sediments. Each has the following details:
[1] precipitated salts,
[2] not clinically significant,
[3] are coarse granular in appearance.
If the amount of amorphous sediment is abundant, it can make the microscopic
evaluation difficult, hence they become a nuisance and hindrance. The term
"amorphous"
literally means "without any form". These crystals are shapeless and
formless, resembling sawdust or sand. Amorphous sediment is the most commonly
encountered types of crystals in urine. If urine is tested within the first hour
after collecting (without refrigeration), amorphous formation is minimized.
In neutral to alkaline urine, there are two types of amorphous crystals. The
most common type is "amorphous phosphates". As you observe urine specimens in
lab, a urine with a moderate amount (or larger) of amorphous phosphates present,
the macroscopic, cloudy appearance will be white. The are soluble in dilute
acids and will not dissolve when heated to 60 OC. These are made up of magnesium
and calcium phosphates. The other type of formless crystal is amorphous
carbonate. This type is found infrequently in urine and tends to be composed of
rod-shaped calcium carbonate. Because of their small shape, they have been
confused with bacteria. If large calcium carbonate crystals are present, they
will take on a dumbbell-like shape (see Objective #3-226). If a
dilute acid is added, effervescence will be observed as CO2 is given off. Both
of these crystals appear colorless when viewed with the microscope.
In neutral to acid urine, amorphous urates are observed. Macroscopically, these
crystals will appear as a pink, brick-like dust. Because of their chemical
nature, they readily absorb the urinary pigments. It is uroerythrin that imparts
the reddish color. In the microscope, they will appear colorless or sometimes a
brownish coloration. These crystals are uric acid salts of sodium, potassium,
magnesium, or calcium. If these crystals are warmed to body temperature or to 60
OC, they will dissolve. They will also dissolve in dilute alkali. If you add a
strong mineral acid like HCl or glacial acetic acid to the sediment, allow the
mixture to "sit" for a period of time. uric acid will crystallize out.
3-219
LIST THE NORMAL URINARY CRYSTALS AND THE pH AT WHICH THEY ARE FOUND.
► amorphous urates (pH: acid to neutral),
► calcium oxalate (pH: acid to neutral,
sometimes can be observed in a slightly
alkaline pH),
► uric acid (pH: acid to
neutral, sometimes can be observed in a slightly
alkaline pH),
► monosodium urate
(pH: acid to neutral),
► calcium oxalate, both di- and monohydrate forms, (pH:
acid to neutral,
sometimes can be observed in slightly alkaline pH),
► amorphous
phosphates (pH; neutral to alkaline),
► triple phosphate (pH: neutral to
alkaline),
► dicalcium phosphate (pH: neutral to alkaline),
► calcium phosphate (pH;
neutral to alkaline),
► calcium carbonate (pH: neutral to alkaline),
► ammonium biurate (neutral to alkaline),
► calcium sulfate (pH; acidic).
3-220
DISCUSS CALCIUM OXALATE CRYSTALS AND THEIR SIGNIFICANCE IN URINE.
Also called envelope crystals. They are colorless and do not absorb pigments
from the urine. The most common shape is the octahedral form which appears as
two pyramids joined at their bases. When focusing on this crystal, there is the
appearance of a refractile cross or star in the center of a cube. If there is an
increased number of these crystals, then it is called "oxaluria". The persistent
finding of numerous calcium oxalate crystals could be an indicator of small
bowel disease, urinary calculi, renal failure disease, diabetes mellitus, high
milk intake, bone fractures, CNS injuries, ethylene glycol poisoning, or
acetazolamide therapy. These crystals are formed from the calcium salts of
oxalic acid and other oxalates. Foods high in oxalic acid and oxalates are:
oranges, cabbage, rhubarb, asparagus, brussel sprouts, tomatoes, spinach,
broccoli, and berries.
There are two basic types of calcium oxalate crystals; dihydrate and monohydrate
forms. The dihydrate form tends to form squares and rectangles, whereas the
monohydrate form tends to form oval and dumbbell shapes. Biconcave disk forms
have been reported. Caution: Monohydrate may form long ovals and closely
resemble acetaminophen crystals. Because there is a variety of forms, these
crystals may be described as being pleomorphic. Regardless of the type, either
form is generally considered to be clinically insignificant. Calcium oxalate
crystals are soluble in dilute hydrochloric acid but not dilute acetic acid.
Refer to the following illustrations.
Dihydrate form of calcium oxylate
Monohydrate form of calcium oxylate
3-221
DISCUSS URIC ACID CRYSTALS AND THEIR SIGNIFICANCE.
This is the most pleomorphic of the crystals found in urine. Forms/patterns
include rhombic (diamond), cubes, rosettes (when multiple crystals cluster and
fuse), needles, wedge, dumbbells, hexagons, and irregular plates/shapes. Uric
acid crystals, when first formed are colorless, but because of their chemical
properties, will adsorb pigments from the urine. Uric acid crystals will appear
in varying shades of yellow or yellow-brown, dependent upon the amount of
pigment in the urine. This coloration is a key to their identification. Uric
acid crystals are quite variable in size. These crystals are soluble in alkali
but are insoluble in acids or alcohol. Generally, the presence of uric acid
crystals are considered to be clinically insignificant. In any condition
(examples: gout, leukemia, lymphoma) in which there is an increase in the
cellular turnover rate, uric acid crystals will be increased. If a patient is on
cytotoxin therapy, there will be an increase in cell destruction. This means
that purine metabolism will be increased and uric acid crystal formation will
occur. Examine the following illustration
3-222
DISCUSS SODIUM URATE CRYSTALS AND THEIR CLINICAL SIGNIFICANCE.
Sodium urates are a variant of uric acid crystals. These are colorless (most
often observed) to slightly yellow rods or slender prisms. Some laboratorians
call these uric acid spears. They are found singly or in clusters. They will
dissolved at 60 oC. They are clinically insignificant and may be reported as "urate
crystals". In the presence of hydrochloric acid, they will change to the uric
acid form. Note the following illustration.
3-223
DISCUSS TRIPLE PHOSPHATE CRYSTALS AND THEIR CLINICAL SIGNIFICANCE.
Also called ammonium, magnesium phosphate crystals, "coffin lids", and
"hip-roof" crystals, they are colorless and exhibit much variation in size. They
often appear as three- or six-sided prisms, colorless, and very refractile.
Other pattern variations are "feathery star-shapes" and fern-like forms, but
these forms are uncommon. There presence is generally non-significant, however
they are observed with chronic UTI, obstructive uropathy, and urinary calculi.
These crystals are characterized by imperfections (not perfectly formed). There
are very variable in size and are soluble in 10% acetic acid.
Examine the following illustrations.
3-224
DISCUSS DICALCIUM PHOSPHATE CRYSTALS AND THEIR SIGNIFICANCE.
This is a uncommon variation of calcium phosphate and may be found in slightly
acidic urine. The correct designation is dicalcium hydrogen phosphate. They tend
to be long slender prisms, with one end pointed. They are often found in
clusters and for this reason may be called "stellar phosphates". They are
colorless, soluble in dilute acetic acid, and are clinically insignificant.
Note the following example.
3-225
DISCUSS CALCIUM PHOSPHATE CRYSTALS AND THEIR SIGNIFICANCE.
These crystals are usually observed as large, colorless, irregular, thin plates
that are granular in appearance. They float on top of the urine and resemble a
type of "scum". They have been reported as wedge shaped prisms. These are
soluble in 10% acetic acid. CAUTION: Small plates may resemble a degenerate
squamous epithelial cell. Examine the following illustration.
3-226
DISCUSS CALCIUM CARBONATE CRYSTALS AND THEIR SIGNIFICANCE.
These crystals appear most often in an amorphous form (see Objective #3-212). On
occasions, they will appear in crystalline form and then they are dumbbell in
shape. It has been suggested that this shape is due to clumping and fusing of
the amorphous crystals. They are soluble in dilute acetic acid and will
effervesce. Note the following illustration.
3-227
DISCUSS AMMONIUM BIURATE CRYSTALS AND THEIR CLINICAL SIGNIFICANCE.
Synonyms are: thorn apple crystal and starfish crystal. Their shape is peculiar
for it fused spheres, tortuous shape, and the presence or absence of spiny
projections. They are yellow brown in color, rarely occurring in fresh urine. If
alkaline urine is allowed to stand, then these crystals may precipitate out.
They are not clinically significant and will dissolve at 60 0C, in acetic acid,
or sodium hydroxide. They have been confused with yeast cells and leucine
crystals. If concentrated HCl is added, these crystals can reform to uric acid
crystals. Examine the following illustrations.
[with and without spicules (thorns)]
3-228 DISCUSS CALCIUM SULFATE CRYSTALS AND THEIR CLINICAL SIGNIFICANCE.
This is a very rare crystal that occurs as long, thin needles and prisms. It is
found only in acidic urine. Most textbooks do not mention this crystal.
3-229
LIST THE ABNORMAL CRYSTALS THAT ARE OF METABOLIC ORIGIN.
Hippuric acid (pH: mostly alkaline, sometimes in acidic and neutral urine),
cystine (pH: acidic), tyrosine (pH: acidic), leucine (pH: acidic), cholesterol
(pH: acidic), bilirubin (pH: acidic), and hemosiderin (pH: acidic).
3-230
DISCUSS HIPPURIC ACID CRYSTALS AND THEIR SIGNIFICANCE.
This crystal is not discussed in most textbooks. It is considered to be an
abnormal, but non-pathogenic crystal. It is formed as a colorless crystal, and
like uric acid, it has an affinity for urinary pigments to take on a yellowish
color. It occurs most often as an elongated prism with variable lengths and
widths, the ends being triangular or pointed. Other shapes reported are needles
(which can arrange in clusters), and rhombic plates. Hippuric acid can be a uric
acid look-a-like. It is soluble in acetic acid (uric acid is not soluble), hot
water, alkali, and ether. It has been reported to be observed in the urine of
"glue-sniffers". Refer to the following
illustration.
3-231
DISCUSS CYSTINE CRYSTALS AND THEIR SIGNIFICANCE.
A rarely observed crystal that appears in the urine as a hexagonal plate and has
the tendency to laminate to other cystine plates. Sides of the hexagon may be of
unequal lengths and will vary greatly in size (measuring up to 100 μM). This
crystal is soluble in dilute HCl, ammonia, dilute bases; but is insoluble in
acetic acid, alcohol, boiling water and ether. Cystine can crystallize out in
the kidney to form stones and cause urinary blockage. It is rapidly destroyed by
bacteria. When searching for these crystals, use in fresh urine. Bacteria will
rapidly destroy cystine. Avoid letting the slide dry, crystals will wrinkle and
change shape as the urine evaporates. The presence is due to an inborn error of
metabolism in which there is a defect in the transport mechanisms for cystine,
ornithine, lysine and arginine. Cells cannot reabsorb these amino acids and thus
appear in the urine in large quantities and of these four, only cystine is
precipitates as crystals. The appearance of these crystals are clinically
significant and indicate some type of pathology. Cystine crystals are also
observed in pyelonephritis, heavy metal nephrotoxicity, Wilson's disease, and
renal tubule acidosis. Note the following illustration.
3-232
DISCUSS TYROSINE CRYSTALS AND THEIR CLINICAL SIGNIFICANCE.
Tyrosine crystals are fine, delicate needles that may be arranged in sheaves or
clumps. Sometimes these crystals may have a fine, silky appearance. They are
formed first as colorless crystals and will take on a pale yellow color if
bilirubin (or some other strong dye, Sternheimer-Malbin stain will dye the
crystals purple) is present. When focusing with a microscope, these crystals may
appear black. These crystals are soluble in alkali, mineral acids, acetic acid,
or heat; but insoluble in acetone, alcohol, or water. Because of their
insolubility in water, these crystals may be seen more often than others. These
crystals are observed with severe liver disease, Oasthouse urine disease,
hereditary tyrosinosis, bilirubinuria, or if leucine crystals are present.
Note the following illustrations.
| Oasthouse Urine Disease is a metabolic disease of methionine and
it produces increased amounts of alpha-hydroxybutyric
acid. |
3-233
DISCUSS LEUCINE CRYSTALS AND THEIR CLINICAL SIGNIFICANCE.
Often describes as yellow to brown, oily appearing spheres; with variable sizes,
having the appearance of concentric rings (with or without radial striations),
and a central nidus. Their presence is a serious prognosis. These crystals may
be observed in severe liver disease, but more likely to be found associated with
metabolic disorders. These crystals are soluble in hot alkali, hot alcohol, and
boiling glacial acetic acid. They are insoluble in dilute HCl and warm dilute
acetic acid. They may be found in urine with tyrosine crystals. Examine the
following illustration.
3-234
DISCUSS CHOLESTEROL CRYSTALS AND THEIR CLINICAL SIGNIFICANCE.
If observed in urine, it is pathologically significant. Cholesterol crystallizes
out as broad, flat plates, often characterized by a notched corner. These
crystals will appear colorless or take on a pale-green to yellow coloration.
They are soluble in chloroform, ether, and boiling alcohol; but insoluble in
warm alcohol. If cholesterol crystals are truly present, look for a specific
gravity < 1.035 and a positive protein test along with the presence of fat
globules, oval fat bodies, and/or fatty casts. If these are not present then
another crystal should be considered. Be cautious in identifying these crystals
since they can resemble radiographic dye crystals, see Objective #3-241. It is
recommended that cholesterol crystals should not be reported if the confirmatory
findings are not present. Cholesterol crystals are observed in lymph gland
disorders, chyluria, severe UTI, and nephrotic syndrome. See the following
illustration.
3-235
DISCUSS BILIRUBIN CRYSTALS AND THEIR SIGNIFICANCE.
Bilirubin crystals have been reported in a variety of forms: fine needles (that
may form clusters), rhombic plates, cubes, and granules. Colors range from
yellow-brown to reddish-brown. These crystals are soluble in alkali, acetone,
chloroform, and acids; but insoluble in alcohol and ether. Bilirubin is a strong
dye and if present in urine, will stain other crystals (especially uric acid)
along with cells and casts. The appearance of precipitated bilirubin has the
same significance as a positive reagent strip test or Ictotest. Refer to
Learning Objectives #112, #114, #115, and #116. Note the
following illustrations.
3-236
DISCUSS HEMOSIDERIN CRYSTALS AND THEIR SIGNIFICANCE.
Hemosiderin, if it precipitates out, will appear as amorphous urates. If
hemosiderin crystals are present, they may be confirmed with a Prussian blue
stain. The presence of hemosiderin in the urine, either free or crystalline
form, is an indicator of an intravascular hemolytic episode.
3-237
LIST THE ABNORMAL CRYSTALS OF IATROGENIC OR DRUG ORIGIN AND INDICATE THE pH
AT WHICH THEY ARE FOUND.
Sulfonamides (pH: acid to neutral), radiographic (pH: acid to neutral),
penicillin (pH: acid to neutral), and acyclovir (pH: acid to neutral).
3-238
DISCUSS SULFONAMIDE CRYSTALS AND THEIR SIGNIFICANCE.
Sulfa's or sulfonamides are important findings in urine specimens. The crystal
that is encountered is determined by the drug administered. When sulfa's were
first discovered and prescribed, they tended to be insoluble and could
precipitate out in kidney, posing a risk for renal damage. Current manufacturing
technology has essentially eliminated this problem and such crystals are seldom
observed in the urine, however a potential risk is
still present if the patient is allowed to become dehydrated. Crystal formation
in the tubules may cause hematuria or oliguria (by blockage). The variety of
shapes for sulfa's include: dumbbells, rosettes, sheaves (with central or
lateral bindings), fans, hexagonal plates, rectangular plates, arrowheads,
rhomboids, and spheres. The following are four examples of sulfa's that have
been prescribed.
A. Sulfadiazine:
a. appears as spheres with irregular striations, but may look like a dense
brown
spheres or bundles of needles similar to sheaves of wheat.
b. it has been reported as a look-a-like to the ammonium biurate crystal.
B. Sulfamethoxazole:
a. Also called "Gantrisin", this is a very soluble sulfa and is rarely seen.
b. When observed as a crystal, it appears as a brown sphere that may be
unevenly
divided or rosettes.
C. Sulfasalazine:
a. A poorly absorbed sulfa that is used to treat enteric diseases. If there
is
tissue damage in the intestine, it may be absorbed into the blood
stream.
b. It is excreted as sulfapyridine or acetylsulfapyridine.
c. Crystals will appear as rhomboids.
D. Acetylsulfadiazine"
a. This is a seldom used medication.
b. Its crystals appear as yellow-brown sheaves of wheat with eccentric
bindings.
Sulfa's are soluble in acetone. They precipitate out as colorless crystals, but
have an affinity to absorb urinary pigments and which will contribute to a
yellow coloration. If a urine is allowed to stand and the pH becomes alkaline,
sulfa crystals tend to dissolve. Fresh urine should be used to look for these
crystals. To help identify suspected sulfa crystals, review the patients
medication charts. Note the illustrations of other sulfa crystals.
sulfisoxazole
3-239
DISCUSS PENICILLIN CRYSTALS AND THEIR CLINICAL SIGNIFICANCE.
Penicillin-type antibiotics are seldom observed in urine. If they should be
present, it will be due to a high dosage when the physician is aggressively
treating for an infection (example: meningitis, septicemia). Ampicillin crystals
are long, thin, colorless prisms or needles that may appear singly or in
clusters. Penicillin-G crystals tend to be rectangular, oblong, and with pointed
ends. These types of crystals tend to form when refrigerated. See the following
example of ampicillin crystals.
3-240
DISCUSS ACYCLOVIR CRYSTALS AND THEIR CLINICAL SIGNIFICANCE.
Acyclovir is an anti-viral medication. When given high doses of this drug, the
urine may demonstrate fine, slender needles that closely resemble sodium urate
crystals. These crystals are most likely to be observed in neutral or slightly
alkaline urine.
NOTE
When medications are administered in high doses, there is a chance that crystals
may appear in urine. When encountering unknown crystals in a sediment
examination, refer to the patients chart as a strategy to identify the crystal. |
3-241
DISCUSS RADIOGRAPHIC DYE CRYSTALS AND THEIR CLINICAL SIGNIFICANCE.
These are water soluble radio-opaque chemicals that are readily excreted by the
kidney. These dyes are derived from triiodobenzoic acid. If the dye is
designated as a meglumine, it is a triiodobenzoic acid conjugated with a
synthetic organic compound to form a more water-soluble and less-toxic chemical.
Triiodobenzoic acid based dyes are a variety of mixtures (with different
inorganic anions) and are known by trade names as Hypaque, Renograffin,
Cystograffin, and Renovist. Crystals of Renograffin (meglumine diatrizoate) will
appear in urine shortly after injection and may be mistaken for cholesterol
crystals, see Objective 3-234. One characteristic of the presence these
radio-opaque chemicals in urine is a positive sulfosalicylic acid test. The
importance of recognizing radiographic dye crystals is that of false
identification. Things to remember about these type of crystals are (1) they may
appear in urine for up to four hours after injection, (2) the strip reagent test
for protein is negative, but the 3% SSA test is likely to be positive, and (3)
specific gravity will be elevated, usually over 1.040.
There is usually no clinical significance associated with these crystals. If a
patient has a kidney disorder or is dehydrated, then the patient may experience
a problem. If the crystals are unusually abundant, the appearance of the urine
specimen may be cloudy.
Note the following illustrations of x-ray dye crystals.|
renograffin
hypaque
3-242
EXPLAIN WHAT IS MEANT WHEN SOMETHING IS OF IATROGENIC ORIGIN.
Iatrogenic means (1) physician induced or (2) caused by treatment or
medications. The implication is that an adverse mental, chemical, or physical
condition was induced by the effects of treatment. This means that the effects
could have been avoided by proper care on the part of the physician.
3-243
EXPLAIN WHAT IS MEANT BY QUALITY ASSURANCE (Q.A.).
It is a program of checks and balances to assure the quality of laboratory
services. It is a mechanism to detect problems and improve services that
includes plans, policies, and procedures. Q. A. encompasses every ancillary
service of the institution. The following components are part of the Q. A.
process in the laboratory; (1) how tests are ordered, (2) the quality of the
request forms, (3) identification of patients, (4) how specimens are procured,
(5) how specimens are labeled, (6) how specimens are transported to the lab, (7)
how specimens are processed, (8) how tests are performed and if there is an
established procedure for each test, (9) laboratory procedure manuals for every
department, (10) laboratory instruments, (11) quality of reagents, (12)
turnaround time, (13) accuracy of results that are reported, (14) how is quality
control in the laboratory conducted, (15) procedures for going about to solve
problems, (16) how are patient's records kept, (17) are critical values
established, and (18) what proficiency test procedures are in place to assure
accuracy of results.
Q. A. is a process that included the interaction between the patient, the
laboratory, other departments, and the physicians. Included in this process is
included evaluation, monitoring, documentation, and communication to remove
obstacles to appropriate patient care. Its intent is to give self confidence to
the laboratory staff performing the tests.
3-244
DEFINE QUALITY CONTROL (Q. C.) IN THE LABORATORY AND DESCRIBE HOW IT IS
AFFECTED IN THE CLINICAL LABORATORY.
Q. C. is a system that ensures reliable test results in the clinical laboratory.
This system monitors the facilities, test methods, test equipment, reagents,
supplies, procedures, equipment maintenance, calibration strategies, control
procedures, remedial actions, and maintains a record book.
3-245
EXPLAIN HOW RELIABILITY, ACCURACY,
PRECISION, AND VARIANCE ARE PART OF THE QUALITY CONTROL PROGRAM.
Reliability is dependent upon the accuracy and precision of test results. An
accurately performed test describes how close the test results are to the actual
value of the test. A test that can be repeated over and over, still obtaining
the same results describes the precision of the test procedure. If test results
can be obtained that are statistically close to the actual value and when
repeated and the same results are obtained, then the test is reliable. Accuracy
and precision of a test depends upon the laboratory using standardized
procedures, control standards, reputable reagents and supplies, and precise
equipment. Variance is a statistical term that describes how much fluctuation
occurs when a specimen is tested repeatedly. The smaller the fluctuation the
smaller the variance and the more reliable the test.
3-246
DISCUSS HOW CONTROL SPECIMENS CONTRIBUTES TO THE Q. C. PROGRAM.
A control specimen is an sample specimen that resembles the patient's test
specimen, but the constituents are known. Generally control specimens consists
of low abnormal, normal, and high abnormal values. The control specimens are
entered into the testing procedure and treated as a patient specimen. In this
way, by knowing the expected outcome of a control specimen, any variable that
would affect the patient specimen will also affect the control. Through the
control specimen; the parameters of reliability, precision, accuracy, and
variance are monitored and the results of the testing procedure assured.
3-247
IDENTIFY SEVEN FACTORS THAT MAY CAUSE A TEST RESULT TO BE UNACCEPTABLE.
[1] The reagents or controls have deteriorated.
[2] Defect in equipment/instrument.
[3] Glassware improperly cleaned or is contaminated.
[4] Failure in correctly timing the incubation temperatures.
[5] Failure to use a method appropriate for the equipment/instruments.
[6] Carelessness/indifference by the laboratory staff performing the test.
[7] Murphy's law. If something can go wrong it will and you
won't know why.
Statistically for some unknown reason a test result will be in error.
3-248
EXPLAIN HOW Q. C. IS A PART OF SPECIMEN EVALUATION FOR ACCEPTABILITY OF A
URINE SPECIMEN FOR TESTING.
Specimens must be received into the laboratory that are suitable for testing.
The laboratorian must be able to recognize whether or not a specimen will be
able to provide the kind of results that a physician can use in the care of a
patient. The following seven points address this process.
[1] Incorrect preservative used in the urine. If a urine is preserved with
formalin and a leukocyte esterase test is requested, the results will be a
false
positive.
[2] An insufficient volume of urine for the requested test. If procedure calls
for 1.0 mL of urine and the lab receives 0.5 mL, another specimen should
be
collected.
[3] The specimen is not labeled. It is impossible for the laboratory to
guarantee that the results are for a specific patient.
[4] The specimen or requisition form is improperly labeled. Same reason as
#3.
[5] The specimen is inappropriate for the test requested. If a random
specimen
is brought in for a culture and sensitivity in an unclean
container, the results
would be invalid and unnecessary costs to the
Patient.
[6] Visibly contaminated urine. If the urine contains fecal material, it is
invalid for tests.
[7] Specimen not collected properly for transportation to a reference lab. The
preservative may not be correct or the amount in container is wrong. The
lab
cannot guaranteed reliable results.
3-249
DESCRIBE TEN ERRORS THAT CAN OCCUR IN URINE TESTING IF A LABORATORY FAILS TO
HOLD TO Q. A. PRINCIPLES.
[1] Inadequate care of reagents (failure to replace bottle cap or improper
temperature storage).
[2] Testing urine that is not fresh (usually more than 1 - 2 hours old).
[3] Failure to mix urine before testing (this is the most common error in the
lab).
[4] Failure to follow directions, tends to use short cuts, poor technique.
[5] Not able to recognize false positive or false negative results. The
laboratorian
does not understand what substances can interfere with a test.
[6] Using chemically unclean containers. There may be residual cleaning
materials present.
[7] Failure to recognize critical values or when values are inconsistent with
each other.
[8] Failure to recognize when a test must be repeated. The tech has a
disregard
for test results.
[9] Recording wrong results. 2.22 mg/dL is different from 22.2 mg/dL.
[10] Lack of understanding of the importance of incorporating test data from
several tests to make a clinical diagnosis. The laboratorian can use such
data
to verify his/her results.
3-250
WHEN A GIVEN A LIST OF EQUIPMENT ITEMS, STATE HOW FREQUENTLY PERFORMANCE
TESTS SHOULD BE PERFORMED.
[1] Thermometers: Test when received into the department and test once
annually
using a National Bureau of Standards certified thermometer.
[2] Temperature devices (refrigerators, dry-block baths, etc.): Test daily by
recording the temperature and recording in a log.
[3] Reagent strip readers: Test daily by using standard reagent strips and
control urine.
[4] Microscopes: Perform daily. Perform maintenance as prescribed in the
procedure manual.
[5] Centrifuges: Clean daily with disinfectant. Check r.p.m. with a tachometer
and timer with a stop watch on an annual basis.
[7] Automatic pipettes: Test when received into the laboratory and then
annually
per the laboratory procedure manual.
3-251
USING Q. A. TECHNIQUE, DESCRIBE HOW TO CORRECTLY HANDLE MISLABELED OR
NON-LABELED URINE SPECIMENS.
[1] If unlabeled or mis-labeled, set the specimen and its requisition aside in
a
container
[2] Obtain an "incident sheet" and record responses and actions.
[3] Notify the collection source (nursing station, clinic, etc.). State the
problem
and request that a new specimen be collected. Record the name of the
person talked to, date, time, and any other data.
[4] Do not discard the specimen. Retain until the matter is resolved and
determined to be completed.
[5] If the specimen cannot be re-collected, then one of the following must
occur:
a. The physician must contact the laboratory and request testing on the
questionable sample. He must also signature the incident document.
b. The person responsible for collecting the specimen must come to the
laboratory and identify the specimen, properly label the specimen
and/or
requisition form. They must also sign off on the incident form.
[6] Perform the test and report results after signatures are secured.
[7] Dependent upon the circumstances, the report may need to contain the
following comment, "This specimen was improperly labeled (or whatever
the
problem), but was approved for testing. The laboratory cannot
otherwise
guarantee that the reported values are from this patient.
[8] Forward a copy of the incident report to the Q. A. committee and the
unit
which sent the specimen.
3-252
DISCUSS GLOMERULONEPHRITIS IN GENERAL TERMS.
This is a disorder that involves the structure and function of the glomerulus.
There are five major renal syndromes that are designated as glomerulonephritis.
These are:
1. Acute Glomerulonephritis.
2. Rapidly Progressive Glomerulonephritis.
3. Chronic Glomerulonephritis.
4. Nephrotic Syndrome.
5. Asymptomatic urinary abnormality.
There are four basic anomalies that are common to glomerulonephritis and when
present, are clinically diagnostic of this disorder. First: hematuria, second:
proteinuria, third: decreased glomerular filtration rate, fourth: hypertension.
3-253
DISCUSS THE CLINICAL FEATURE OF ACUTE GLOMERULONEPHRITIS (AGN).
This is a generalized glomerulopathy is characterized by a swift onset of
symptoms and can be subdivided into the following variations of syndromes:
[1] Post-streptococcal glomerulonephritis (PSGN).
[2] Non-poststreptococcal glomerulonephritis (NPSGN).
[3] Acute glomerulonephritis caused my a multi-system disease (ex: SLE).
[4] Membranoproliferative glomerulonephritis (MPGN)
[5] Berger's disease.
[6] Serum sickness.
These six types of acute glomerulonephritic syndromes will be characterized by
the following basic clinical laboratory findings: (1) hematuria, (2) proteinuria,
(3) reduced glomerular filtration rate (GFR), (4) Azotemia, (5) salts and water
retention (causes hypertension), and (6) oliguria. Other laboratory findings
that the laboratorian should look for are:
[1] In the event of hematuria, note the clarity and color. Gross hematuria will
produce a smoky or coffee-colored urine. This is different from a
hemorrhage
which will produce a urine specimen that has so much blood
in it that it looks
like blood.
a. The reagent strip test for blood will be positive.
b. If the specific gravity is low and the urine alkaline, then most of the
RBC's
may be hemolyzed, yet the strip test should be positive for
blood (hemoglobin).
c. Always perform a microscopic and look for RBC/Hgb casts.
d. RBC's are often dysmorphic.
[2] Examine the sediment for the presence of WBC's and WBC casts. If RBC
casts
are present then expect to find WBC casts. Also present should be
granular casts
and occasional renal tubular epithelial cell casts.
*NOTE: If WBC casts are present, this is an indicator that there is a glomerular
and/or interstitium inflammation.
[3] Note the protein test results. These should be positive, ranging from 1+ to
4+. In most cases, the protein loss will range between 0.2 gram/day to 3.0
grams/day. If the loss is >3.0 grams/day, the disorder may be designated
as nephrotic syndrome instead of glomerulonephritis.
[4] Oliguria is the rule.
[5] The specific gravity reading is usually elevated because of oliguria and
proteinuria. Normal specific gravity value are 1.002 to 1.035.
[6] The Erythrocyte Sedimentation Rate (ESR) is usually increased. Normal
ESR
values (Westergren method) are 7-15 mm/hour for men and 12-17
mm/hour for
women).
[7] A non-laboratory clinical feature that may be present is edema.
3-254
REVIEW POST-STREPTOCOCCAL GLOMERULONEPHRITIS (PSGN) AND PRESENT THE TYPICAL
CLINICAL FINDINGS.
This is a disorder that if it appears will do so about 1-2 weeks after a
streptococcal throat infection or may take longer if a cutaneous infection.
Although it can affect any age or gender group, it most often occurs in children
and young adults. PSGN is considered to the archetype or basic form of acute
glomerulonephritis. The microorganism involved is designated as a Group A
Streptococcus (S. pyogenes) and is thought to be stimulus that results in the
production of an immune complex that attaches to and damages the glomerulus.
This makes this an immune mediated disease. If you were culture the blood or
urine for the microorganism, there would be no success. Two things must be
demonstrated for this disorder to be diagnosed PSGN.
[1] Beta-hemolytic streptococcus (Group A) must be cultured from a throat
or
skin lesion.
[2] An anti-streptolysin O (ASO) titer (>200 Todd units) must be evident.
NOTE: The following tests (if performed co-currently) should be positive:
a. anti-streptokinase (ASK)
b. anti-hyaluronidase (AN)
c. anti-deoxyribonuclease (ADNAase)
Prognosis: In children and young adults, it is good. Mortality rate is <1%. In
adults, the prognosis is poorer. The reason is not understood. The outlook
worsens if proteinuria and/or hematuria is marked/severe. There are case studies
in which PSGN has progressed to Rapidly Progressive Glomerulonephritis or
Chronic Glomerulonephritis.
Urinalysis laboratory findings include:
[1] Proteinuria: usually <3.5 gm loss/day. In 20% of patients loss may
exceed
3.5 gm/day. If loss >0.5 gm/day, then is an indicator of loss
of renal function
and the condition becomes more serious for the patient.
[2] Oliguria with increased turbidity.
[3] Marked hematuria. This is the hallmark feature for PSGN.
[4] Examine sediment for (1) RBC, (2) WBC, (3) hyaline casts, (4) granular
casts, (5) RBC casts, (6) WBC casts, (7) RTEC casts, and (8) waxy casts
[should
not be a common finding].
Other laboratory findings that should be examined for correlation.
[1] Increased ASO titer
[2] Increased ESR
[3] Mild anemia
[4] Hypoalbuminemia
[5] If tested for CPR or RF, then expect tests to be negative.
[6] Decreased sodium and increased potassium
3-255
REVIEW NON-POSTSTREPTOCOCCAL GLOMERULONEPHRITIS (NPSGN) AND PRESENT THE
TYPICAL CLINICAL FINDINGS.
This is a pathogen induced glomerulonephritis and is similar to PSGN. This
disorder occurs less frequently. Its prognosis is generally good, however in
some instances, this disease has progressed to Rapidly Progressive
Glomerulonephritis or Chronic Glomerulonephritis. Bacterial conditions known to
cause NPSGN are: sepsis, infective endocarditis, typhoid fever, syphilis,
pneumococcal pneumonia, and meningococcemia. Viral conditions that have been
implicated are: hepatitis B, mumps, measles, infectious mononucleosis, varicella
(chicken pox), vaccinia (cowpox), and echovirus induced infections (30 known
viruses known to cause meningitis, pneumonia, myocarditis, and enteritis).
Parasites connected with NPSGN are the malarial parasites, in particular
Plasmodium falcaparium and Toxoplasma gondii (toxoplasmosis). Each of
these causative organism produces their own unique symptoms. Immunological
testing can identify most organisms. Culture and sensitivity testing is very
effective if the problem is due to a bacterial pathogen.
Urinalysis laboratory findings are basically the same as for PSGN. Other
laboratory findings will differ in the following parameters:
(1) Absence of an ASO titer, (2) RF test is usually positive and elevated, and
(3) Anti-streptokinase (ASK) test is negative.
3-257 REVIEW ACUTE GLOMERULONEPHRITIS (ASSOCIATED WITH MULTI-SYSTEM DISEASE) AND
PRESENT THE TYPICAL CLINICAL FINDINGS.
This third type of acute glomerulonephritis is secondary to a multi-systemic
disease. Examples of the primary diseases are:
[1] Systemic Lupus Erythematosus... a chronic inflammatory disease of
connective
tissue of unknown etiology. Every organ and/or structure
can be involved. In the
case of the kidney's, renal damage can occur.
[2] Schonlein-Henoch Purpura... a vasculitis characterized by skin lesions
and
hidden visceral lesions. The kidney's may demonstrate such lesions,
which may be
severe. Other symptoms are erythema, urticaria,
gastrointestinal distress, and
joint pain.
[3] Goodpasture syndrome... a type of progressive glomerulonephritis that
eventually becomes renal failure. Other problems are pulmonary
hemorrhage, hemosiderosis, and development of antibodies to
basement membrane antigens. This
is a rare disease and death usually
occurs to renal failure.
Note: In this acute type of glomerulonephritis, when secondary to a
multisystemic disease, the clinical findings in urinalysis are essentially the
same as for NPSGN. See Objective #3-254.
3-257
REVIEW MEMBRANOPROLIFERATIVE OR MEMBRANE PROLIFERATIVE GLOMERULONEPHRITIS (MPGN)
AND PRESENT THE TYPICAL CLINICAL FINDINGS.
This disorder is also known as mesangiocapillary glomerulonephritis or lobular
glomerulonephritis. MPGM is characterized by the proliferation of mesangial
cells (a flat epithelial cell) associated with the basal membranes of the
glomerular capillaries. The net effect is that the glomerulus becomes more
permeable. There are two variations of this disorder.
[1] Type I is characterized by immune complex pathogenesis and is secondary
to a
primary disorder such as systemic lupus erythematosus, chronic
hepatitis B, and
(in some cases) transplant rejection.
[2] TYPE II is a more severe form and is usually associated only with
transplant
rejection. This second variation of MPGM is also known as
"dense deposit
disease".
This is a progressive disease and 50% of the
patients will die within a ten year
period because it develops into an
"end-stage" renal disease.
Urinalysis clinical findings are hematuria and proteinuria.
Plasma clinical findings is a decrease in C3 complement levels. In the patient
with Type II MPGN, the BUN and creatinine levels are increased.
3-258
BRIEFLY REVIEW BERGER’S DISEASE AND PRESENT THE TYPICAL CLINICAL FINDINGS.
This disease is also known as Idiopathic Renal Hematuria or IGA Neuropathy. The
disease has a predilection for young adult males. It is a slow progressive
disease and may take up to 25 years to run it course. For 50% of the patients,
it will develop into "end-stage" renal disease. It is an immune-complex mediated
disease.
Typical urinalysis clinical findings are proteinuria, hematuria, and RBC casts.
Blood evaluation will demonstrate azotemia and hypertension. The best way to
diagnose this disorder is a renal biopsy of the glomeruli.
3-259
DISCUSS SERUM SICKNESS AND ITS RELATIONSHIP TO GLOMERULONEPHRITIS.
Serum sickness is an immune-complex disease in which glomerulonephritis is
frequently observed. A patient injected with a foreign protein to which he had
been previously sensitized will develop a sequence of symptoms that include
pyrexia, myalgia, skin lesions, arthralgia (arthritis), gastrointestinal
distress, nausea, and vomiting. This patient is susceptible to an anaphylactic
reaction. If a patient presents symptoms of arthritis, skin eruptions, and
glomerulonephritis; then serum sickness is suspect.
Significant urinalysis laboratory findings are proteinuria, hematuria, and RBC
casts. Other clinical laboratory test results include decreased serum
compliment, increased ESR, anemia, mild leukocytosis, and possibly eosinophilia.
3-260
DISCUSS RAPID PROGRESSIVE GLOMERULONEPHRITIS (RPGN) AND THE TYPICAL CLINICAL
FINDINGS.
Other synonyms for this disorder is crescentic glomerulonephritis,
extracapillary glomerulonephritis, or diffuse glomerulonephritis. This disorder
can develop suddenly and without warning and progress into renal failure. This
disease can develop after an infection, become secondary to a systemic disease
(occurs in 40% of the cases), or following flu-like symptoms. Prognosis is poor
with 90% of the patients developing chronic glomerulonephritis, then renal
failure. It affects all age groups and has a predilection for males. One
distinctive feature of this disease is the formation of cellular proliferation
in Bowman's capsule which affects the permeability of the glomerulus. Immune
complexes will form on the glomerular capillaries as a result of another
disorder. Macrophages will damage the capillary walls. Twenty percent of the
RPGN cases are associated with Goodpasture Syndrome, an autoimmune disorder.
NOTE: prognosis is improved is RPGN can be caught early.
Urinalysis lab findings include:
[1] Proteinuria, with losses up to 1.5 gm albumin/day.
[2] Oliguria in 50% of the patients.
[3] Hematuria.
[4] Acidic pH
[5] Specific gravity ranging from 1.020 to 1.030.
[6] Decreased glomerular filtration rate.
[7] Microscopic analysis features WBC's, RBC's, and
casts (hyaline, granular,
RBC, and RTEC)
[8] Fibrin Degradation Products (FDP) are found.
Other laboratory findings are: increased BUN, increased creatinine,
increased uric acid, and anemia.
NOTE: Best way to diagnose this disorder is the renal biopsy.
3-261 BRIEFLY DISCUSS FOCAL GLOMERULONEPHRITIS AND ITS CLINICAL FINDINGS.
Also known as "idiopathic nephritic syndrome". This is a disorder that arises
because of IgA immunocomplexes that affect the glomerulus. The number of
glomeruli that are affected are variable and often suffer minimal damage. The
clinical course of this disease is mild with a good prognosis. Typical urinary
laboratory findings are proteinuria and hematuria. The
microscopic sediment should be examined for hyaline, granular, and RBC casts.
3-262
DISCUSS CHRONIC GLOMERULONEPHRITIS AND ITS CLINICAL FINDINGS.
Chronic glomerulonephritis (CGN) is a syndrome characterized by persistent
urinary abnormalities. It is a slow, progressive impairment (taking up to 20
years) of the renal function with permanent damage to the glomeruli. A majority
of the patients will demonstrate lesions. About 80% of the patients diagnosed
with CGN were previously diagnosed with another form of glomerulonephritis. The
systematic loss of renal tissue will result in renal failure requiring either
dialysis or a renal transplant. CGN is usually diagnosed by (1) an incidental
finding of abnormal urine when the physician is examining a asymptomatic
patient, (2) result of an insidious onset of progressively worsening symptoms
that indicates a renal problem, or (3) an bacterial or viral illness with an
associated glomerulonephritic symptoms.
Urinary laboratory findings in the early stages of the disease are (1) acidic
pH, (2) proteinuria (low values), (3) hematuria (low values), and (4) hyaline
and granular casts (there are on occasions broad casts observed). The patient
will experience polyuria and nocturia.
Urinary laboratory findings in the late stage of the disease
are:
1. Specific gravity fixed at 1.010. 5. Oliguria or anuria
2. Abnormal creatinine clearance test. 6. Hematuria with dysmorphic forms
3. PSP test = <25% (very low value) 7. All types of casts with broad forms
4. Proteinuria 8. Color = pale yellow
Other clinical laboratory findings are:
1. Azotemia 4. Decreased blood calcium levels
2. Anemia 5. Increased blood phosphate levels
3. Enlarged heart 6. hypertension
7. reversed A/G ratio
NOTE: If edema is present, then the following will be observed
1. elevated specific gravity
2. Oval fat bodies with free floating fat globules. WBC may ingest some of
the
lipids.
3. Markedly increased ESR
4. Very pronounced proteinuria
5. Numbers of casts may be increased
6. Renal function may be difficult to interpret.
3-263 DISCUSS NEPHROTIC SYNDROME AND THE CLINICAL FINDINGS.
Nephrotic syndrome (NS) is characterized by four distinctive features: (1)
massive edema, (2) heavy proteinuria [with losses of ≥5 gm/day], (3)
hypoalbuminemia, and (4) increased sensitivity for infections. Some patient
diagnosed with NS will present with hyperlipidemia. NS is a group of clinical
characteristics that appear simultaneously. It is often the endpoint for a
number of diseases such as: Berger's disease, RPGN, MPGN, focal
glomerulonephritis, any toxic injury to the kidney, infections (examples:
hepatitis, malaria, endocarditis, infectious mononucleosis), multisystemic
diseases, diabetes mellitus, bee stings, allograph rejections, and pre-eclamptic
toxemia. Glomerular and tubular damage are typical. The prognosis is always
poor.
Urinary laboratory findings are proteinuria, hematuria, oval fat
bodies, all types of casts, free-floating fat globules, renal tubular epithelial
cells, WBC's, and increased turbidity. NOTE: there is a correlation between
protein loss and oval fat bodies, as proteinuria increases, so does the number
of oval fat bodies and lipid globules.
Other laboratory findings are (1) hypoalbuminemia [<4.0 gm/dL], (2)
hyperlipidemia with cholesterol >200 mg/dL and triglycerides >200 mg/dL, (3)
plasma oncotic pressure <300 mOsm/kG, (4) hypocalcemia, and (5) edema.
3-264 DISCUSS MINIMAL CHANGE DISEASE (MCD) AND ITS CLINICAL FINDINGS.
MCD is also called (1) lipoid nephrosis, (2) nil lesion disease, (3) foot
process disease, and (4) minimal change nephrotic syndrome. There is little or
no morphological changes in the glomerulus, however there is an abnormality with
the podocyte processes that allows for greater filtration. Immunocomplexes are
usually not demonstrated. The cause of this disorder is not known. There is a
loss of the negative charge of polyanions which will allow for greater protein
loss. MCD is observed most often in children with 80% of the cases occurring
before eight years of age and it tends to occur more often in males. Renal
failure rarely occurs and there is a high remission rate. Some patients have
progressed into Mesangial Proliferative Glomerulonephritis and this is a poor
prognosis as it may continue to worsen and develop into renal failure.
Urinary laboratory findings are (1) marked proteinuria, (2) hematuria, (3) oval
fat bodies, (4) free fat droplets, (5) predominately hyaline and granular casts,
however RBC casts and fatty casts have been reported. Crystals may be present in
fresh urine. Other clinical laboratory findings include decreased in blood
protein, hypoalbuminemia, increased cholesterolemia, and a reversed A/G ratio.
3-265 EXPLAIN THE MEANING OF "TELESCOPED" URINE.
The term actually means to "slide past one another". In urinalysis, it
originally meant that WBC's and RBC's along with their respective casts were
present in the urine. Its current usage (when it is used) implies that just
about "everything" can be found in the urinary sediment.
3-266 DISCUSS LOWER URINARY TRACT INFECTIONS AND THE CLINICAL FINDINGS.
There are four types of lower urinary tract infections (UTI): prostatitis (only
in males), urethritis, cystitis, and ureteritis. UTI's occur most often in women
and does not become a recurring problem for men until after their 45th birthday.
Most UTI begin by pathogen invasion of the urethra and migration to any part of
the urinary system. Most lower UTI's are asymptomatic. The most common symptoms
are dysuria, frequency of urination, and a sense of urgency to urinate. There
are no reliable signs/symptoms for lower UTI's. The most common pathogen in
lower UTI's is Escherichia coli (cause up to 90% of these infections). Other
causative microorganisms are Proteus penneri, Klebsiella pneumonia,
Enterobacter
aerogenes, Serratia marcescens, and Pseudomonas aeruginosa. These five
microorganisms are often observed in nosocomial infections involving indwelling
catheters. All of the afore mentions bacteria are gram-negative bacteria. Gram
positive bacteria are only occasionally involved in UTI's.
Urine laboratory findings are increased turbidity with no change
in urine volume. An offensive or foul odor is often the rule. Other findings are
(1) proteinuria [loss <0.5 gm/day in which the reagent strip test would never be
higher than a 1+], (2) alkaline pH, (3) positive nitrate test, and (4) positive
leukocyte test. The microscopic sediment should demonstrate (1) slight hematuria,
(2) significant increase in WBC's [known as pyuria], (3) clumping of WBC, (4)
absence of casts, (5) transitional epithelial cells, and (6) bacteriuria. If the
bacteria count is <103/μL, then is designated as being contaminated. If the
count is ≥105/μL, then is a UTI is very probable.
NOTE
Casts are not an expected finding lower UTI's. WBC clumping is not to be
confused with casts. WBC clumps will be irregular in shape and absent of a
matrix. |
3-267
DISCUSS CYSTITIS AND THE CLINICAL LAB FINDINGS.
If cystitis is present, then also most likely is urethritis. Cystitis is
characterized by dysuria, frequency of urination, urgency to urinate, and
suprapubic pain. Urine lab findings are the same as identified in OBJECTIVE
#3-266. If the bacterial count is <105/μL when cultured should consider the
possibility of “candida”, “trichomonas” or gonorrhea.
3-268
DISCUSS UPPER URINARY TRACT INFECTIONS AND THE CLINICAL LAB FINDINGS.
Also called pyelonephritis, this infection is observed most often in women which
probably begins as an untreated case of cystitis or urethritis. The causative
bacteria are the same as for the lower UTI's. The onset of this infection is
characterized by flank pain, nocturia, frequency of urination, urgency of
urination accompanied by nausea, cephalalgia, pyrexia, and an overall malaise.
This disorder, with proper treatment will run it course in <2 weeks and will be
benign.
Urine laboratory findings are the same as for a lower UTI with the following differences: urine volume is decreased, proteinuria is larger [2+ or higher], hyaline, granular, and WBC casts may be
found, and hematuria is of a greater magnitude. The specific gravity may be
lower values and macrophages may be observed.
3-269 DISCUSS CHRONIC PYELONEPHRITIS AND ITS CLINICAL LAB FINDINGS.
This chronic inflammatory disorder is caused by obstruction, vesicourethral
reflux, or a neurogenic bladder. A reflux problem is where urine is allowed to
flow backward into the renal pelvis and/or renal tubules. This allows bacteria
to invade the interstitium producing a persistent infection that produces
fibrosis and scarring of parenchymal tissue. Up to 15% of these patients will
progress to renal failure.
Urine lab findings may be non-existent for infection. Usual lab findings include
proteinuria, positive leukocyte esterase test, positive nitrate test, pyuria,
and bacteriuria. Polyuria and nocturia usually develop. Specific gravity may be
low and a variety of cast may be observed (hyaline, granular, WBC, RTEC, waxy,
and broad).
3-270 DESCRIBE RENAL TUBULOINTERSTITIAL PATHOLOGIES AND THEIR CLINICAL LABORATORY
FINDINGS.
These are pathological abnormalities that involve the tubules and/or
interstitial tissues. A dysfunction can occur any where in the tubule or any
region of the kidney. These pathologies are referred to as Acute Interstitial
Nephritis. There are three general modes of renal injury:
[1] An allergic response that occurs in the interstitium and is caused by
antibiotics
(Gentamycin, Amphotericin B, Rifampin, Cephalosporin, Methicillin,
or
sulfonamides).
a. These drugs when removed by the tubules induce an immunogenic
response that
produces antibodies that complex with renal tubular
epithelium and induces
damage.
b. Inflammatory responses causes invasive phenomenon with
lymphocytes, monocytes, eosinophils, neutrophils, and macrophages;
compounding the problem.
c. The increase in inflammation leads to lesions, damage, and impairment
of
renal function.
[2] Damage to the tubules through heavy metal or metabolic toxins (lead,
cadmium, mercury, copper, hydroxyurea, aminoglycosides, uric acid, etc.)
[3] Slow and insidious destruction of tubular function (abuse of medications
as:
aspirin, phenacetin, ibuprofen, fenoprofen, etc.).
Clinical symptoms include: fever, skin rash, polyuria, and nocturia. Removal of
the offending cause usually restores normal functioning abilities.
Urine laboratory findings are: acidic pH, proteinuria, hematuria, leukocyturia,
glycosuria, amino aciduria, natriuresis (causes excess water loss), phosphaturia,
uricosuria, and bicarbonaturia (contributes to metabolic acidosis). Unless the
problem is corrected there will be a progressive decrease in the glomerular
filtration rate (GFR).
3-271 DESCRIBE HOW URIC ACID ACTS AS A METABOLIC TOXIN AND THE EXPECTED CLINICAL
LABORATORY FINDINGS.
Gout is characterized by hyperuricemia (increased uric acid in the blood) and is
a form of arthritis that affects the joints. This elevation of uric acid induces
a chronic interstitial neuropathy. In addition there is the tendency to form
uric acid kidney stones. The presence of uric acid crystals in the interstitial
tissues induces fibrosis, tubular atrophy, and glomerular sclerosis. The
vascular system in the kidney is also affected (arterio-nephrosclerosis). Renal
disease associated with gout begins as mild and is slowly progressive. This
patient is at risk for developing pyelonephritis.
Urine laboratory findings are: (1) increased urates and uric acid crystals, (2)
strongly acidic pH, (3) bacteriuria (25% of the cases), (4) occasional oliguria,
(5) WBC's, and (6) variable hematuria.
3-272 DISCUSS ACUTE RENAL FAILURE AND ITS CLINICAL LABORATORY FINDINGS.
Acute renal failure (ARF) is where the renal system ceases to function. This
disorder can result from any glomerular, vascular, or tubular disease. ARF
begins suddenly with a decrease in glomerular filtration rate (GFR), azotemia,
and oliguria or anuria. There are three type os ARF: pre-renal, renal, and
postrenal. Pre-renal is associated with any cause that results in a decrease in
renal blood flow and causes a decreased GFR. Causes for decreased blood flow
are: decreased cardiac output, burns, hemorrhage, and surgical procedures. Renal
ARF may arise form any disease process or abnormality that affects the kidney
and is characterized by renal destruction. Post-renal ARF is induced by
obstruction (tumors or stones) in urine flow. The increase in hydrostatic
pressure within the tubules and Bowman's capsule results in tubular damage.
Prognosis is poor with about a 60% mortality rate.
Urine laboratory findings do not distinguish between the three types of ARF. The
cardinal feature of ARF is oliguria and progressive azotemia. pH becomes more
alkaline and metabolic acidosis is likely to occur. There is possible
proteinuria, RBC's and RBC casts. Waxy casts may be observed. If there is anuria,
urinalysis testing cannot be performed.
3-273
DISCUSS CHRONIC RENAL FAILURE (CRF) AND ITS CLINICAL LABORATORY FINDINGS.
This is a disorder characterized by a progressive loss of renal function. The
course of this disease is silent and does not express itself until about 80% of
the renal function is compromised. During the course of the disease as tubular
damage and loss occurs, the healthy nephrons function normally and mask out any
problems. When the GFR drops to 15 to 20% of normal, overt renal failure becomes
obvious. CRF begins to present with azotemia, acid-base imbalances, water
imbalance, electrolyte imbalance, anemia, and other organ system disturbances.
Once the diagnosis is made, the outcome for the patient is without hope.
Urine laboratory findings are: (1) decrease GFR, (2) fixed specific gravity of
1.010, marked proteinuria, (4) hematuria, and (5) oliguria.
3-274
DISCUSS RENAL ALLOGRAPH REJECTION AND THE CLINICAL LABORATORY FINDINGS.
Renal transplant rejections can be divided into three areas: immunological,
surgical, or medical. If the rejection process sets up immediately (within a few
hours), it is a hyperacute rejection. If rejection begins after about 12 hours
and within 12 days, it is designated as acute renal rejection. If rejection
onsets between 12 days and up to 18 months later, it is delayed rejection. If
rejection occurs between six months to 6 years, it is designated as chronic
renal rejection. The distinguishing urinary characteristic for allograph
rejection is a decrease in the GFR.
Urine laboratory findings for acute renal rejection are: (1)
renal cells with abnormal nuclear shapes, (2) casts, (3) RBC's, (4) WBC's, (5)
amorphous material in the background, (6) bacteria, (7) oliguria (or possibly
anuria), (8) renal tubular epithelial cells, and (9) proteinuria (primary
feature).
Other clinical findings are: (1) azotemia, (2) anemia, (3) hypophosphatemia, (4) hyperlipidemia, (5) hypertension (primary feature), and (6) hypoproteinemia.
3-275 DEFINE A RENAL FUNCTION TEST.
Also referred to as a renal clearance test, it is a testing procedure that
evaluates the filtering capacity of glomeruli.
3-276
EXPLAIN WHAT INFORMATION A RENAL FUNCTION TEST IS SUPPOSE TO PROVIDE.
[1] Measure the filtering capacity of the glomeruli.
[2] It must be able to assess the degree of renal damage, that is estimate the
number of
functional nephrons that are available.
[3] ability to monitor the effectiveness of treatment.
[4] determine if antibiotics can be administered (If the glomerular filtration
rate (GFR) is reduced, then antibiotics may not be effectively eliminated
which
results in a toxic buildup and would be detrimental to the patient.
[5] To determine if a decrease is present and if so, is it progressive.
3-277
DEFINE THE GLOMERULAR FILTRATION RATE (GFR).
It is the rate at which the kidney's can remove a substance from the blood as
measured in mLs per minute.
3-278 LIST FIVE FACTORS WHICH AFFECT THE GLOMERULAR FILTRATION RATE (GFR).
[1] The hydrostatic and osmotic pressures that exist across the walls of the
glomerular capillaries.
[2] Total surface area represented by the capillary walls.
[3] The permeability of the capillary walls.
[4] Number of nephrons (in a normal kidney, there are
around one million).
[5] The flow rate of blood of blood entering the capillaries.
3-279 LIST EIGHT ADVANTAGES AND DISADVANTAGES FOR USING CREATININE AS A RENAL
FUNCTION TEST.
[1] (A) Creatinine is a waste product of muscle metabolism and is easily
measured.
[2] (A) It is present in the blood at a constant level, it fluctuates very
little.
[3] (A) It has a low rate of reabsorption in the kidney tubules.
[4] (A) It closely approximate the inulin test (the standard for renal testing).
[5] (D) What you eat may affect the results.
[6] (D) Tubules will produce creatinine during advanced stages of renal disease.
[7] (D) It requires testing both the blood and urine levels of creatinine
simultaneously.
[8] (D) If you use the Jaffe reaction to measure creatinine levels, interfering
substances may be a problem. Glucose, ascorbic acid, protein, pyruvic
acid,
cephalosporins, and acetone are known to alter the results.
(A = advantage, D = disadvantage)
3-280
EXPLAIN WHAT IS REQUIRED FOR THE CREATININE CLEARANCE TEST, STATE THE NORMAL
RANGE FOR MALES AND FEMALES, AND CITE THE FORMULA FOR THIS EVALUATION PROCEDURE.
The following information is required to calculate rate of clearance to
determine if the kidney is effectively eliminating waste products.
[1] The volume of urine flow. This is expresses in mLs/minute and is "V" in the
formula.
a. To calculate, collect urine during a strictly timed interval. Divide the
volume collected (mLs) by the time in minutes. The answer will be in
mLs/minute.
[2] Creatinine concentration in the urine, "U" in the formula. This is performed
in chemistry and is expressed as mg/dL. Normal values are not expressed
in mg/dL,
but in grams/day. Males = 1.0 - 2.0 grams/day and females =
0.8 - 1.8 grams/day.
[3] Creatinine concentration in the blood/plasma, "P" in the formula. This is
performed in chemistry. Normal values: males = 0.64 mg/dL and females
=
0.57-0.92 mg/dL.
[4] To have a standardized test, the results must be normalized by dividing
the
body surface area of an typical individual (1.73 M2) by the body
surface area of
the patient. This step requires knowing the height (in
inches) and the weight
(in pounds).
[5] "C" is unknown and after mathematical manipulation of the formula, "C"
is
the amount of creatinine cleared from the blood into the urine. It is
expressed
as mLs/minutes which describes how many mLs of plasma is
being cleared of creatinine.
The formula is as follows:
U (×) V 1.73
C = ------------- (×) -------
P A
Normal values for this test are:
men: 107 - 139 mL/min
women: 87 - 107 mL/min
children: similar values as men
Note: values tend to decrease with age.
3-281 DESCRIBE AND EXPLAIN HOW TO USE A NOMOGRAM.
A nomogram is a mathematical conversion mechanism for
calculating the body surface of an individual using height and weight
determinations. It is a three column figure that requires the use of a straight
edge. The straight edge is placed against the weight (in pounds) and the height
(in feet) and then the body surface area is determined by observing the value of
the middle column in square meters. If the straight edge is placed so that it
aligns on the 185 pound point and the 6.0 feet point, the edge will fall on the
1.90 point. The answer is 1.90 square meters. Note the following example
of the nomogram.
3-282 CALCULATE A CREATININE CLEARANCE PROBLEM WHEN GIVEN DATA AND INTERPRET THE
RESULTS.
A 12 hour (500 mL) urine specimen is sent to the lab from a 25 y/o patient who
is six feet tall and weighs 185 pounds. Plasma creatinine was calculated to be
1.1 mg/dL and the urine creatinine was calculated at 175 mg/dL. The calculation,
using the formula in OBJECTIVE #3-274, is as follows:
1. Convert 500 mLs of urine collected over 12 hours to mLs/minute. 12 hours
=
720 minutes. Divide 500 by 720. The answer is 0.694 mLs per minute.
This becomes
"V" in the formula.
2. Convert 6.0 foot height and 185 pounds to square meters of body surface.
See
Objective #3-281 on how to use the nomogram. The answer is 1.90
square meters of
body surface.
3. Plasma creatinine is 1.1 mg/dL and is "P" in the formula.
4. Urine creatinine is 175 mg/dL and is "U" in the formula.
5. Solving for the answer:
175 mg/dL (×) 0.694 mLs/min 1.73
C = ------------------------------------- (×) --------
1.1 mg/dL 1.90
121.45 mLs/min
C = -------------------- (×) .91
1.1
C = 110.4 mLs/min (×) .91
C = 100.47 mLs/min (the amount of glomerular filtrate being produced/minute.
It appears that GFR is lower than expected for men. The plasma value for
creatinine is 1.1 mg/dL or 0.011 mg/mL. Notice that each mL of urine contains
1.75 mg creatinine/mL. In order for transfer 0.011 mg creatinine/mL of plasma to
urine so that it contains 1.75 mg creatinine/mL, it requires the blood flow rate
be such that 100.47 mLs of plasma filtrate is produce per minute. Since the
normal (expected) rate of production of plasma filtrate for a man is from 107 to
139 mLs per minute, this patient is producing at a rate less normal and is an
indicator that there is some type of glomerular abnormality and may be an
indicator of early renal disease.
NOTE
The glomerular filtration rate is an indicator of the number of functional
nephrons and also of their functional capacity. If a sufficient number of these
nephrons are healthy, a change in the GFR may not occur because the healthy
nephrons are compensating for the non-functioning nephrons. This is why a person
can survive with only one kidney. |
3-283 LIST FIVE SOURCES OF ERROR REGARDING THE CREATININE CLEARANCE TEST.
[1] Allowing the patient to be active/exercise, [2] not drinking water [the
patient needs to have a good urine formation flow rate], [3] incorrect timing,
[4] incorrectly collecting the urine, and [5] conducting the test on a patient
who has a significant renal disorder.
3-284 EXPLAIN WHAT IS MEANT BY A TUBULAR SECRETION TEST.
This is a test that assesses renal blood flow and measuring the tubular
secretion of non-filtered substances (penicillin, hippuric acid, phenobarbital,
ammonia). The test that provides the best clinical data is the p-aminohippuric
acid (PAH) test. The test that is the easiest to perform is the
phenylsulfophthalein (PSP) dye test. The portion of blood that enters the
glomerular capillaries is filtered. The portion of blood that does not enter the
capillaries enters the peritubular capillaries and selected waste products are
removed by renal tubular secretion. Tubular secretion is an active process. The
tubules must be functionally normal in order to provide an accurate renal blood
flow results and the renal blood flow must be normal to provide accurate tubular
secretion results. The PAH test is a measurement of the blood flow through the
entire nephron, which is designated as renal blood flow, and it is an indicator
of the state of health of the tubular secretory function. The secretion of the
dye is hindered in chronic glomerulonephritis, chronic pyelonephritis, and
congenital polycystic kidney disease.
3-285
BRIEFLY DISCUSS THE PAH TEST.
PAH (p-aminohippuric acid) is a low toxicity, weak organic acid that loosely
bind with plasma proteins and is totally secreted from the peritubular
capillaries and directly into the nephron. The test is not routinely performed
in hospitals, but in specialized renal centers. The patient must be continuously
infused with PAH to maintain constant plasma concentration and carefully timed
to provide accurate results. 90% of the dye is excreted in one pass through the
kidney. 100% of the dye will be removed by the tubular secretion mechanism and
none through the filtration process of the kidney.
3-286 BRIEFLY DISCUSS THE PSP TEST.
The phenylsulfophthalein (PSP) or phenol red test is becoming obsolete. About
94% of the PSP dye will bind to proteins which prevents the dye from being
removed by the glomeruli. The protein bound dye is removed by tubular secretion.
The test is simple to perform. After collecting a pre-injection urine, 6.0 mg of
PSP dye is injected into a well hydrated patient. Urine is collected at 15, 30,
60 and 120 minutes. The urine is made alkaline with NaOH and the color produced
measured in a spectrophotometer. The pre-injection urine contains 0% dye. The 15
minute specimen is the most important specimen and provides the most
information. In a normally functioning kidney, 25 to 50% of the dye will be
excreted in the 15 minute specimen, 15 to 25% of the dye is excreted in the 30
minute specimen, 10 to 15% in the 60 minute specimen, and 5% of the dye in the
120 minute specimen. Over a two hour period, 60 to 85% of the dye will be
excreted. Any reduction in the amount of dye secreted implies a reduction in
renal blood flow. About 6% of the dye is removed by glomerulus because PSP is
not bound to protein. This test has an error risk, the liver can remove up to
20% of the dye which may invalidate the test.
3-287 DEFINE AMINOACIDURIA AND BRIEFLY DESCRIBE ITS THREE TYPES.
It simply means that there is an excess of amino acids in the urine. There are
three type of aminoacidurias:
[1] Overflow: The plasma levels of amino acids are increased and results in
more
amino acids being filtered at the glomeruli. This excess in amino acids
exceed
the threshold rate and increased amounts of amino acids are
excreted in the
urine.
[2] No-threshold: This involves those amino acids that are not normally
recovered by the tubules. When there is an increase in the plasma
concentration
there will be a corresponding in an increase of these amino
acids in the urine.
[3] Renal aminoacidurias: These are due to a primary metabolic disorder as
phenylketonuria, cystinosis, and 5-hydroxyindoleacetic acid. Secondary
disorders
are where amino acids are spilled into the urine because of an
existing problem
such as a severe liver disease (hepatitis) or a generalized
tubular disorder
resultant of an existing disease as Fanconi's syndrome.
3-288 LIST FOUR DISORDERS THAT INVOLVE THE RENAL SYSTEM THROUGH DEFECTIVE TUBULAR REABSORPTION MECHANISMS.
Fanconi's syndrome: A congenital hypoplastic anemia with a fatal prognosis,
death occurring before puberty. It is characterized by aminoaciduria, glycosuria,
phosphaturia, bicarbonaturia, uricaciduria. Bence Jones proteinuria can be
frequently found in these patients. A patient who presents with this disorder
could also have been previously diagnosed with cystinosis, multiple myeloma,
Wilson's disease, Amyloidosis, heavy metal poisoning, or Lowe's syndrome. If a
previous diagnosis is the case, then Fanconi's syndrome is acquired.
Cystinosis: An inborn error of metabolism which may be benign or fatal.
Cystinosis is characterized by the deposition of cystine in the lysosomes of all
the cells. When cystine deposits in the tubular cells, there is a loss in the
ability to reabsorb a number of metabolites or to acidify urine. Glucosuria,
polyuria, aminoaciduria, phosphoruria, and other urinary anomalies result. It
can progress to renal failure.
Wilson's disease: An autosomal recessive disease characterized by cirrhosis of
the liver, splenomegaly, degenerative changes in the brain, accumulation of
copper in the renal cortex, decrease in tubular function, proteinuria,
aminoaciduria, phosphaturia, hypercalciuria, glucosuria, and uricaciduria. There
is loss of the ability to acidify the urine. It has been found that if the
accumulation of copper can be controlled, then renal functions can return to
normal.
Galactosemia: A disorder in which galactose cannot be metabolized. There are two
types of galactosemia; (1) galactose-1-phosphate uridyl transferase deficiency
and (2) galactokinase deficiency. Galactose-1-phosphate uridyl transferase
deficiency galactosemia is the classic form and most serious. Untreated infants
will survive only a few weeks, rarely a few months. Clinical findings include
jaundice, hepatosplenomegaly, cataracts, hemolytic anemia, proteinuria,
aminoaciduria, and galactosuria. This condition can be detected by screening for
the presence of a reducing sugar in urine with the clinitest tablet when the
glucose oxidase test is negative. Diet restrictions prevent the disease.
3-289 DISCUSS PHENYLKETONUIRA AND HOW TO SCREEN FOR ITS PRESENCE.
Phenylketonuria (PKU) is the best known of the aminoaciduria's. It is due to a
deficiency of the enzyme "phenylalanine hydroxylase", which when present
converts phenylalanine to tyrosine. PKU causes other amino acids to appear in
urine in abnormal amounts, inhibition of the transport of tyrosine, and has an
inhibitory effect upon the absorption of amino acids across the intestinal wall.
PKU is a disorder which must be caught early. If left untreated, mental
retardation sets in by the third week and the maximal effects are accomplished
by the eighth or ninth month. Initial screening for PKU is a blood test and does
not require urine. A blood specimen should be collected on the third day to
allow the infants metabolism to stabilized. To collect blood soon (approximately
four hours) will identify a number of PKU disorders but will miss some. A
popular and widely used test is the Guthrie test. Once the PKU disorder has been
identified, treatment consists of maintaining the child on a phenylalanine free
diet until about it for the first decade of its life or longer if medically
required.
Screening urine for PKU does have some value as a follow-up test for:
[1] follow up on a questionable diagnosis.
a. Girls are slower to develop diagnostic phenylalanine levels than boys
and may
escape detection of the disorder with an early blood test..
b. late detection with treatment can prevent further mental retardation.
[2] Monitor diet to see if the patient is "cheating".
[3] Monitoring the dietary intake of pregnant PKU females. If a pregnant PKU
woman allows her phenylalanine levels to escalate, it will have a detrimental
effect upon the developing fetal brain.
The urine of a PKU patient contains phenylpyruvic acid which give it a mousy or
barnyard-like odor. The 10% ferric chloride test is a quick screening method to
detect the presence of PKU. A positive test is indicated by a transient,
transparent blue to blue-green color.
3-290
DISCUSS THE ADVANTAGES AND DISADVANTAGES OF THE FERRIC CHLORIDE TEST.
The ferric chloride test is a non-specific test and will react with any chemical
that will form complex with the ferric ion. Its advantage lies in the ease in
which the test can be performed and its disadvantage is due to it
non-specificity.
3-291 DISCUSS THE GUTHRIE TEST.
This is a bacterial inhibition test that depends upon the germination of spores
of Bacillus subtilis enhanced by the presence of phenylalanine. A culture plate
containing an inhibitor in the agar is plated with the spores. Separate paper
disks containing the patient's blood, a standard amount of phenylalanine, and
without phenylalanine; are placed on the plate and incubated. If growth occurs
around the patient's disk and that of the phenylalanine standard, then the test
is positive for PKU. No growth will occur around the negative control disk. The
Guthrie test is a reasonably accurate test.
3-292 DISCUSS NEWBORN SCREENING FOR INHERITED DISORDERS FROM A NATIONAL
PERSPECTIVE.
All states are required to do newborn screening for inherited disorders, but not
all states do the same tests. A table was devised by the American Academy of
Pediatricians that gives the requirements of each state. Eleven diseases are
listed in the table which are [1] phenylketonuria (PKU), [2] hypothyroidism, [3]
galactosemia, 8[4] hemoglobinopathy, [5] maple-syrup urine disease, [6]
homocystinuria, [7] biotinidase deficiency, [6] adrenal hyperplasia, [9]
tyrosinemia, [10] cystic fibrosis, and [11] toxoplasmosis. PKU and
hypothyroidism testing is done in all 50 states, Washington D.C., the Virgin
Islands, and Puerto Rico. Galactosemia is tested for in 46 states and
hemoglobinopathies in 45 states. Testing rates after these four diseases are
very limited. Twenty states test for maple-syrup urine disease, twenty-two test
for homocystinuria, twenty-one test for biotinidase deficiency, eleven test for
adrenal hyperplasia, seven test for tyrosinemia, four test for cystic fibrosis,
and two test for toxoplasmosis. The state of Arkansas only tests infants for
three of the eleven disorders as of 2001, these being (PKU, hypothyroidism, and
hemoglobinopathies).
Current laws that regulate newborn screening give up to three weeks for
completing the screening tests. This time period allows too much time, since
damage can occur in the brain tissue within three days, causing irreversible
mental retardation in affected infants. All newborn screenings are taken to the
State Health Department. The volume of testing required is such that
rapid-turn-around-time (TAT) is not possible. Advocates for quicker TAT’s
suggest that updated equipment can improve laboratory efficiency, TAT, and
increase the number and types of screens that can be performed. The recommended
testing procedure is Tandom Mass Spectroscopy. This procedure still utilizes the
heel stick for the method of collection and it is advantageous because it can
test over twenty-five metabolic disorders.
3-293 DISCUSS THE IMPORTANCE OF URIC ACID IN URINE TESTING.
Uric acid is an end product of nucleoprotein metabolism. The amount that appears
in urine is dependent upon the amount of endogenous and exogenous purines
metabolized. Uric acid will be excreted in the urine as uric acid crystals, as a
solute, and as sodium, potassium, or ammonium salts of uric acid (urates). The
average mixed diet will produce from 0.5 to 1.0 grams of uric acid in a 24 hour
urine specimen. In renal disorders, uric acid values in urine does not
fluctuate, therefore this data is not clinically significant. Urine testing for
uric acid is simply not done. Urine values for uric acid will increase in
polycythemia vera, leukemia, cytotoxic drug medication, liver disease, and
febrile illness.
3-294
DISCUSS HOMOCYSTINURIA AND HOW TO SCREEN FOR THIS DISORDER.
Homocystinuria is a biochemical abnormality due to a homozygous, autosomal
recessive trait, not a specific disease. There are several variants of this
abnormality, but the most common is due to a deficiency in the enzyme "cystathionine
β-synthase. Many patients will die from thromboembolic problems. Clinical
manifestations are ectopia lentis, osteoporosis, scoliosis, and sometimes
kyphosis, and mental retardation in a significant number of patients. Normally,
homocysteine is not detected in plasma, but in this disorder it is readily
detected in urine. The urinary cyanide-nitroprusside or silver-nitroprusside
test is positive (red-purple color). Fresh urine is recommended for testing and
if the urinary tests are positive, they should be followed up with more
specific/sensitive spectrophotometric procedures. Urine with this chemical may
have a sulfur-like odor
3-295 DISCUSS CYSTINOSIS AND HOW TO SCREEN FOR THIS DISORDER.
See also Objective #288. There are three clinical forms of cystinosis. The
infantile (in first decade of life) and juvenile forms (second decade of life)
will lead to renal involvement and insufficiency. The third form, the adult
form, is benign and is not included in this objective. Diagnosis is confirmed by
quantitatively determining the cystine concentration in leukocytes or cultured
fibroblasts. Urinary findings in the laboratory are polyuria, pyelonephritis,
decreased GFR, aminoaciduria, hyperphosphaturia, glucosuria, and kaliuresis.
Urine odor resembles that of sulfur.
3-296 DISCUSS 5-HYDROXYINDOLEACETIC ACID (5-HIAA) AND HOW TO SCREEN FOR THIS
DISORDER.
5-HIAA is a metabolite in the metabolic pathway of tryptophan. In the healthy
individual, any 5-HIAA in urine is the natural metabolic by-product of serotonin
degradation. If a carcinoid tumors (contains argentaffin cells) are present,
then also is the enzyme "tryptophan hydroxylase" which catalyzed the formation
of 5-hydroxytryptophan (5-HPT). This 100 fold increase in 5-HPT is in turn is
oxidized to 5-HIAA, which is rapidly excreted into the urine. Patients who are
to be tested for 5-HIAA will collect a 24-hour urine (use HCL as a preservative)
and are to be instructed to NOT eat bananas, pineapples, or tomatoes (have high
levels of serotonin). Such patients are to be medication free for 72 hours. The
urinary screening tests; ferric chloride (blue-green color produced),
nitroso-naphthol (dark violet or purple color produced),
3-297
DISCUSS MELANURIA AND HOW TO SCREEN FOR THIS DISORDER.
Melanin is a metabolite out of an alternate pathway of tyrosine that produces
melanin, protein, thyroxine, and tyrosine sulfate. Melanin is produced by cells
called melanocytes. If melanin is deficient, albinism is resultant. If melanin
is being overproduced, the increased amounts will be excreted in the urine. Over
production may be due to a melanoma. If a urine specimen (containing melanin) is
allowed to sit in the lab, it will darken to a black or brown color. The
following are urinary screening test. If they are positive, further patient
evaluation is necessary.
[1] Ferric chloride: gray-black (possibly with precipitate)
[2] Acetest tablet (sodium nitroprusside): red
[3] Ehrlich's test: red
3-298 DISCUSS TYROSYLURIA AND HOW TO SCREEN FOR THIS DISORDER.
Tyrosyluria simply means that there is an increased quantity of tyrosine derived
metabolites in the urine. If there is tyrosyluria, then tyrosinemia is present.
Tyrosinuria is the consequence of excess amino acids spilling in the urine from
tyrosinemia. The most common form of tyrosinemia a transitory condition observed
in infants and is due to the lack of development of the liver. As the liver
mature, the disorder disappears. If a patient has a severe liver disease,
tyrosinemia may be resultant. There are two hereditary forms of tyrosinemia and
in either case, the patient usually dies in the first decade of life. Tyrosine
can be screened for in the urinary lab with the following:
[1] Ferric chloride test: transient green color
[2] Nitroso-naphthol test: red color
[3] Millon's test: red color produced
3-299 DISCUSS INDICANURIA AND HOW TO SCREEN FOR THIS DISORDER.
Indicanuria is associated with an increased intestinal absorption of indole,
which is converted to indican in the liver. Indican is secreted in its colorless
form into the urine. Air oxidation will covert the indican to indigo blue which
can stain diapers and clothing. Early diagnosis can be made if blue stains are
noted in the diapers. This phenomenon is associated with Hartnup's disease.
Hartnup's disease is an autosomal recessive trait characterized by pellagra-like
skin lesions, neural disorders, 10 fold loss of monoaminomonocarboxylic amino
acids in the urine along with the an intestinal defect that prevents the
absorption of these amino acids. This disease can be treated with a high protein
diet and nicotinamide supplement. Urine can be screened for indican using ferric
chloride. A blue-violet color is produced that can be extracted into chloroform.
3-300 DISCUSS ALKAPTONURIA AND HOW TO SCREEN FOR THIS DISORDER.
Alkaptonuria is a rare disorder of tyrosine metabolism with a deficiency in the
enzyme "homogentisic acid oxidase". The consequence of this disease is the
accumulation of homogentisic acid in the connective tissue leaving the tissue
darkly pigmented. This pigmented condition is called "ochronosis" and the
patient will develop degenerative arthritis. Homogentisic acid (dihydroxyphenylacetic
acid) accumulates and is excreted in the urine. Urine will readily darken with
standing and exposure to air or sunlight. It is easy to miss the urine changes
and "ochronosis" may be identified through x-rays, intermittent but acute
arthritis, brown scleral pigment, or thickened ears. Urine screening procedures
include:
[1] ferric chloride: transient blue color
[2] clinitest tablet: orange-red
[3] silver nitrate: black
[4] ammonium hydroxide: will alkalinize the urine, turning it black.
This disorder is usually not diagnosed until middle-age. If dark stains are
noted in the diapers of neonates, then the disorder may be diagnosed earlier. At
this present time there is no satisfactory treatment for alkaptonuria.
3-301
DISCUSS MUCOPOLYSACCHARIDOSES AND HOW TO SCREEN FOR THIS DISORDER.
Mucopolysaccharidoses lysosomal storage diseases and are inherited disorders of
connective tissue. There are seven types (I - VII), with 13 subtypes, and each
is due to a deficiency in an enzyme that cannot effectively degrade dermatin
sulfate, keratan sulfate, heparan sulfate, and/or chondroitin sulfate (mucopolysaccharides).
The affected mucopolysaccharides will accumulate in the organs and tissues,
affecting their function. Urinary screening tests include:
[1] Cetyltrimethylammonium bromide (CTAB): Add 1.0 mL of 5% citrate buffered
CTAB to 5.0 mL centrifuge urine. If positive, the white flocculation will occur.
[2] A filter paper may be prepared by soaking in 2% Azure A dye. Add a drop of
urine to the dried paper. If positive, a blue spot will appear. Confirm the test
by soaking the paper in a solution of 0.5% acetic acid in 100% methanol. If mucopolysaccharides are present, the spot will remain.
Only Types MPS I-S, MPS II (mild), MPS-IV B, MPS VI (mild), and possibly MPS VII
have a good prognosis. The other eight types/subtypes have very poor prognosis.
3-302 DISCUSS CYSTINURIA AND HOW TO SCREEN FOR THIS DISORDER.
Cystinuria is an inherited autosomal recessive disorder and is characterized by
increased amounts of cystine in the urine. This is because the renal tubules
cannot reabsorb this amino acid from the glomerular filtrate. Other amino acids
affected by this disorder are ornithine, lysine, and arginine. Cystine has low
solubility in urine, hexagonal crystals are routinely observed and kidney stones
are a constant concern. Urinary screening tests for cystine are:
[1] cyanide-nitroprusside: red-purple color
[2] clinitest tablet: red-orange
False positive can occur if ketones or homocystine are present. If a patient is
suspected of having cystinuria, look for RBC's in the sediment. This may
indicate irritation from kidney stones. Chromatography tests will confirm the
presence of the amino acids associated with this disorder.
3-303 DISCUSS MAPLE SYRUP URINE DISEASE (MSUD) AND HOW TO SCREEN FOR THIS
DISORDER.
This rare autosomal recessive disorder is also called "branched-chain ketonuria"
or "branched-chain aminoaciduria. Leucine, isoleucine, and valine accumulate in
the blood and a keto-acidosis results. The ketoacids are excreted in the urine
and give the urine its characteristic "maple syrup" odor. Infants with this
disorder demonstrate problems one week after birth. The disorder, once
identified, can be controlled by diet and monitoring the production of ketoacids.
This disease should be confirmed by liquid chromatography technology. Urine
screening tests include:
[1] ferric chloride: green-gray color
[2] nitroso-naphthol: red color
[3] 2,4-dinitrophenylhydrazine: yellow
[4] Acetest: purple
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