Review of Literature Chapter 2

Urine Analysis
Urine Analysis:
The urine analysis is one of the most commonly ordered clinical
tests in pediatrics. This frequency is partly due to the ease of urine
collection and testing. Urine testing has been a part of medicine for many
centuries, with Hippocrates having written about urine examination as
early as 400 bc (Liao and Churchill, 2001).
Advances in chemistry allowed significant progress in urine
testing during the nineteenth century, and the modern era of reagent strip
(dipstick) testing began in 1956 (Voswinckel, 1994).
Urinary tract diseases are often diagnosed in patients with no
symptom (Ahmed and Lee, 1997). An abnormal urine test may be the
earliest warning of a significant renal disease. Because of its simplicity,
routine urine analysis is the best way in early detection of most frequent
conditions like proteinuria, hematuria or glycosuria at a very low cost
(Murphy, 2004). This is useful in selecting asymptomatic patients with
renal diseases who may benefit from early treatment, counseling or who
require long term follow up (Cho et al., 2001).

Urine Dipstick Test:

A urinalysis is a urine test best performed on a full bladder first thing
in the morning. A urinalysis checks appearance, concentration and
content of urine and is used to detect and/or manage a wide range of
medical disorders, such as urinary tract infections (UTI's), kidney disease
and diabetes. A dipstick, usually a thin, plastic stick with strips of
chemicals on it, is coated with urine, the chemical strips will change color
if certain substances are present or if certain levels are above, or below,

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normal which can indicate the presence of compounds like proteins,

ketones, hemoglobin, nitrites, glucose, bilirubin, urobilinogen, leukocyte
and leukocyte esterase, as well as harmful pathogens. Dipstick urinalysis
is convenient, but false-positive and false-negative results can occur
(Strasinger et al., 2014).

A urine dipstick test is a test of urine, using a special strip of paper

that is dipped into a sample of urine. The result is available almost
immediately. It is sometimes called a rapid urine test (Loo et al., 1984).

Urine is normally sterile - this means it's completely free of germs

(bacteria) - and only has in it waste chemicals from all of the millions of
chemical reactions that go on in the body all of the time. But in some
conditions chemicals that shouldn't normally be there get through the
filtering systems in the kidney and get into urine. This is where urine
dipstick testing comes in (Simerville et al., 2005).

A urine dipstick test is the quickest way to test urine. It involves

dipping a specially treated paper strip into a sample of urine. The results
are usually available within 60-120 seconds. The sample doesn't need to
be sent to a laboratory for a urine dipstick test, although if the test is
abnormal one might need to do another sample to be sent for further
testing in a laboratory (Strasinger et al., 2014). .

There are several different kinds of urine testing strips that test for
different things in the urine. The strip has squares on it that change colour
in the presence of certain substances. The strip will then be compared to a
chart on the side of the urine testing strip package. Often the more intense

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the colour change, the more of the substance there is in the urine
(Strasinger et al., 2014).

A urine dipstick test is done for lots of different reasons, such as:
 To screen for diabetes.
 If patient might have a urine infection.
 If patient have tummy (abdominal) pain.
 If patient have back pain.
 If patient have seen blood in his urine (hematuria).
 Some people with diabetes will do their own urine dipstick testing.

Normal urine varies in colour from colourless to dark yellow.

Various things can affect the way the urine looks, from how much patient
have been drinking to what patient have eaten recently. The smell can
also vary widely and is not a good gauge of illness (Mundt and
Shanahan, 2010).
A urine dipstick test can look for the following:
 Blood
o Not normally found in the urine.
o May be present if there is an infection.
o Can be due to significant underlying disease, such as cancer, in the
bladder or kidney.
o Will always need to be confirmed by sending the sample for a full
laboratory test, as the dipstick test can be positive when there's
nothing wrong (Kitamoto et al., 1992).
 Protein
o Protein is normally found in the urine in tiny amounts but these
tiny amounts aren't usually picked up on a urine dipstick test.

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o Can be the first sign of kidney disease (Patel, 2006)

 Glucose
o Glucose, a type of sugar, is never normally found in the urine.
o Glucose in the urine may be the first sign of diabetes (Marsenic,
2009)
 Ketones
o Ketones are chemicals made by the body when it's breaking down
fat for energy, which is what we do when we are starving and have
used up all, or nearly all, of our stores of sugar (glucose). This is
normal.
o Ketones are not usually found in the urine.
o Ketones may be present if patient has diabetes and it's out of
control and the levels of sugar in the blood are very high (Meyer,
1994)
 Bilirubin and urobilinogen
o Bilirubin and urobilinogen are chemicals produced by the liver.
They are not normally found in the urine.
o If bilirubin is found in the urine it usually means there's a problem
with the liver.
o Small amounts of urobilinogen may be found in the urine but large
amounts suggest a problem with the liver or with red blood cells
being destroyed too quickly (Patel, 2006)
 Leukocyte esterase and nitrite
o These are both tests for the presence of infection.
o Leukocyte esterase test looks for a reaction that only happens if
there are lots of white cells in the urine. White cells get into the
urine when there is an infection.

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o Nitrite is not normally found in the urine but will appear there if
there are lots of germs (bacteria) in the urine.
Nitrite test can be negative even if there are lots of bacteria in the urine if
the urine hasn't been in the bladder for long. For example it will be
negative if you do your urine sample soon after having passed urine.
Ideally you should wait at least four hours from the last time you had a
pee before doing your urine sample (Semeniuk and Church, 1999).
The urine dipstick test also measures how concentrated the urine is and
how acidic it is (Chadha et al., 2001).

Urine Screening:
The merits of mass screening of asymptomatic healthy children
have been debated for some time (Linshaw and Gruskin, 1997). The
American Academy of Pediatrics previously recommended a screening
urinalysis at four time points during childhood, but the current
recommendation is to obtain a screening urine analysis only at the
preschool physically, and yearly in sexually active adolescents to look for
leukocyte esterase (American Academy of Pediatrics, 2000).
Many pediatricians obtain screening urine analysis more frequently.
It is common to find abnormalities on urine screening tests, but in most
cases, these are transient or due to a false positive reading (Plamer et al.,
1997).
Screening can also identify individuals who have subclinical
chronic kidney disease who may potentially benefit from early
identification. Mass urine screening is thought to be of benefit in a
number of Asian countries (Murakami et al., 2005).

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Abnormal Urine Analysis

Color and Appearance:
The normal appearance of a freshly voided urine sample is clear and
pale to dark yellow. A number of medications and foods can alter the
appearance of urine .Urine may have a cloudy appearance from sitting at
room temperature for a prolonged period (> 1 hour), triphosphate
crystals, increased urates, urinary tract infection (UTI), pyuria, or high
concentration (Liao and Churchill, 2001).
Specific Gravity and pH:
The specific gravity (SG) is a measure of urine concentration.
Usually, it simply reflects recent fluid intake but should be interpreted
with the clinical situation in mind. A low urine SG in a patient clinically
euvolemic is likely non-significant. Low urine SG in someone who
appears dehydrated can result from a renal concentrating defect. A high
urine SG may reflect lack of recent fluid intake in an otherwise healthy-
appearing child or dehydration in someone who has been ill (London et
al., 2003)
Urine pH varies with acid–base balance and can range from 5 to 8
in healthy individuals. The urine pH is primarily of interest in limited
clinical situations such as metabolic acidosis and with certain types of
kidney stones. A low urine pH promotes the formation of uric acid and
cystine stones, whereas high urine pH promotes calcium phosphate
precipitation. Urine pH is reliable only on a freshly voided specimen
(Patel, 2006).

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Cells:
Red blood cells
In most cases, two or less RBCs per high-power field are considered
normal, although some laboratories may have a slightly different
reference range. Urine microscopy may be useful in determining the
etiology of hematuria. The presence of dysmorphic RBCs (may have
membrane blebs, an irregular surface, or other membrane defects) and
RBC casts suggests a renal source of the hematuria, most likely
glomerular disease. Normal-appearing RBCs and the lack of casts suggest
lower–urinary tract bleeding (Kitamoto et al., 1992).

White blood cells

Greater than five white blood cells per high-power field is generally
considered abnormal. Pyuria usually signifies urinary tract infection
(UTI), although it is not specific for UTI. Other conditions that can result
in pyuria include fever, glomerulonephritis, and other inflammatory
processes, whether in the bladder or pelvic region (Gorelick and shaw,
1999).

Epithelial cells
Epithelial cells that may be observed on microscopic examination
include renal tubular cells, transitional cells, and squamous epithelial
cells. All three cells types may be observed in normal urine. Increased
numbers of renal tubular cells may be seen with acute tubular necrosis
and exposure to nephrotoxic agents. Squamous epithelial cells line the
distal third of the urethra. In female patients, squamous cells may
originate from the vagina or vulva. Large amounts of squamous epithelial
cells in the urine suggest a contaminated urine sample (Patel, 2006).

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Bacteria
The presence of bacteria in an asymptomatic patient is most likely
due to contamination with normal flora from the external urethral meatus
or vagina. When the urine has been centrifuged, the bacteria clump and
are more easily seen. When bacteria are observed in unspun urine, the
patient may have significant bacteriuria. It is generally recommended,
however, that asymptomatic bacteriuria not be treated because it has not
been shown to have benefit and may increase the risk for pyelonephritis
(Kemper and Avner, 1992).

Casts
Casts are formed in the lumen of distal convoluted tubules and
collecting ducts and consist of an organic matrix composed of Tamm-
Horsfall mucoprotein with or without additional elements. There are
many different types of urinary casts that may be observed on urine
microscopy (hyaline, granular, waxy, fatty, red blood cell, white blood
cell, epithelial cell). Hyaline casts are the most common and can be seen
in normal individuals. They consist primarily of mucoproteins and may
be increased with concentrated urine, diuretics, renal disease, fever, and
exercise. The presence of cellular casts is of greater significance (Patel,
2006).

Crystals
It is common to find crystals on microscopic examination of the
urine. Crystal formation depends on a number of factors, and the presence
of crystals may or may not be pathologic. Usually, the presence of
crystals in the urine is of limited clinical significance (Patel et al., 2006).
Super saturation of the solute components of the crystals must occur for

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crystallization to initiate. A number of factors affect super saturation,

including solute concentration, ionic strength, urine pH, and the presence
of promoters or inhibitors. These factors vary during the day depending
on fluid intake, dietary intake, and body metabolism. Urine in normal
individuals is often supersaturated with calcium oxalate, calcium
phosphate, and sodium urate (Gambaro et al., 2016).

Protein
Under normal circumstances, low molecular weight proteins and a
small amount of albumin are filtered through the glomerular capillary
wall. Most of the low molecular weight proteins are reabsorbed in the
tubules, whereas Tamm- Horsfall protein is secreted. As a result, up to
150 mg/d (in adults) or 4 mg/m2/h (in children) of protein in the urine is
considered to be within normal limits. In glomerular disease, the primary
protein excreted is albumin, whereas in tubular disease, low molecular
weight proteins, which would usually be reabsorbed, are excreted in the
urine (Patel, 2006).

Glucose
Glucose is freely filtered at the glomerulus but is almost completely
reabsorbed in the proximal tubule. The appearance of glucose in the urine
may reflect high plasma glucose, resulting in a glucose load in the filtrate
that exceeds the proximal tubule’s ability to reabsorb glucose. Typically,
glucose does not appear in the urine until the plasma level exceeds 180 to
200 mg/dL. Alternatively, glycosuria may reflect a defect in the proximal
tubule cells ability to reabsorb a normal filtered glucose load. When this
defect is an isolated one, it is termed renal glycosuria and is due to a
mutation in the SGLT2 transporter (Santer et al., 2003).

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Ketones
Ketone production is increased when there is altered glucose
metabolism.The increased breakdown of fatty acids generates ketones.
Ketones in the urine are most commonly seen in patients whose
nutritional intake has been compromised by illness or starvation. Ketones
can also be seen with uncontrolled diabetes mellitus, a high-fat/low-
carbohydrate diet, liver disease, and certain forms of glycogen storage
disease (Reed et al., 1991).

Bilirubin and Urobilinogen

Bilirubin is a breakdown product of hemoglobin formed in the
reticulo- endothelial cells. Unconjugated bilirubin such as that observed
with hemolysis is not water soluble, remains tightly bound to albumin,
and is not filtered at the glomerulus. After bilirubin is conjugated to
bilirubin glucuronide by the liver, it is water soluble and can appear in the
urine. In the normal individual, the amount of bilirubin in the urine is
below the threshold of detection of most reagent test strips. Most
conjugated bilirubin is eliminated in bile into the gastrointestinal tract.
The appearance of bilirubin in the urine suggests obstruction to bile
outflow or hepatitis (Patel, 2006).
Urobilinogen is formed in the colon when bacterial glucuronidases
hydrolyze conjugated bilirubin followed by reduction of free bilirubin to
urobilinogen. Most urobilinogen is excreted in the feces, but up to 20% is
reabsorbed and enters the portal circulation. The liver then re-excretes
most of this urobilinogen into the bile, and a small amount of
urobilinogen is usually seen in the urine. Patients who have liver
dysfunction may have decreased hepatic uptake with resulting increased
urobilinogen in the urine. With biliary obstruction, the amount of

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urobilinogen is more variable, but with severe obstruction, urobilinogen

can be negative due to the absence of bilirubin in the intestines. Unlike
bilirubin, urobilinogen is increased in the urine following hemolysis
(Patel, 2006).

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