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Jaundice
Definition: Jaundice is the clinical condition characterized by yellow coloration of the skin, sclera and mucous membrane due to increased concentration of bilirubin in the blood
Serum bilirubin levels between 1.0-3.0 mg/dL is regarded latent jaundice (subclinical jaundice).
When the serum bilirubin level exceeds 3.0 mg/dL, it is called jaundice (icterus) Jaundice is not a disease, it is a symptom of many diseases.
Classification:
1. Hemolytic jaundice (pre-hepatic jaundice)
2. Hepatic jaundice (hepatocellular jaundice)
3. Obstructive jaundice (post-hepatic jaundice)
> Hemolytic jaundice/pre-hepatic jaundice
a) Hemolytic jaundice is caused by anything which causes excessive breakdown (hemolysis) if red blood cells. Most of the bilirubin in blood is unconjugated(অধাতব)
b) The increased production of bilirubin leads to the increased production of urine-urobilinogen.
c) Bilirubin is not usually found in the urine because unconjugated bilirubin is not water- soluble
d) So the combination of increased urine-urobilinogen and no bilirubin in urine is suggestive of hemolytic jaundice.
>Hepatic/Hepatocellular jaundice
a) Hepatic (hepatocellular) jaundice is caused due to diminished functional capacity of liver due to various causes
b) Both the conjugated and unconjugated bilirubins are present in the blood
c) Bilirubin is also found in the urine (bilirubinuria). The urine-urobilinogen level may be normal or decressed
> Obstructive jaundice
a) Obstructive jaundice, also called post-hepatic jaundice, is caused by an interruption to the drainage of the bile due to obstruction of the intratherapatic or extrahepatic bile duct
b) Conjugated bilirubin level rises in the blood, and it is excreted through urine/ Therefore. in obstructive jaundice bile pigments can be detected in urine. The urine appears yellow-brown in color.
c) Urinary urobilin and fecal stercobilin excerets fall and in total obstruction of biliary tree these pigments may be totally absent
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The Chemical Examination

To perform the chemical examination, most clinical laboratories use commercially prepared test strips. These are narrow plastic strips that hold small squares of paper called test pads, arranged in a row. The test pads have chemicals impregnated into them. When a strip is briefly, but completely, dipped into urine, the test pads absorb the urine and a chemical reaction changes the color of the pad within seconds to minutes.

The laboratorian compares the color change for each reaction pad to a color chart provided with the test strips to determine the result for each test. Each reaction pad must be evaluated at the appropriate time for that chemical. If too little time or too much time has passed since the reaction, the laboratorian may get incorrect results. To reduce timing errors and eliminate variations in color interpretation, automated instruments are frequently used to “read” the reaction color on each test pad.

The degree of color change on a test pad can also give an approximation of the amount of substance present. For example, a slight color change in the test pad for protein may indicate a small amount of protein present in the urine whereas a deep color change may indicate a large amount.

The most frequently performed chemical tests using reagent test strips are:

Specific gravity
pH
Protein
Glucose
Ketones
Blood
Leukocyte esterase
Nitrite
Bilirubin
Urobilinogen
Some reagent test strips also have a test pad for ascorbic acid [vitamin C].

Specific Gravity (SG)
The first test, specific gravity, is actually a physical characteristic of the urine, a measure of urine concentration that can be determined using a chemical test.

There are no "abnormal" specific gravity values. This test simply indicates how concentrated the urine is. Specific gravity measurements are actually a comparison of the amount of solutes (substances dissolved) in urine as compared to pure water. If there were no solutes present, the SG of urine would be 1.000 – the same as pure water. Since all urine has some solutes a urine SG of 1.000 is not possible. If a person drinks excessive quantities of water in a short period of time or gets an intravenous (IV) infusion of large volumes of fluid, then the urine SG may be as low as 1.002. The upper limit of the test pad, an SG of 1.035, indicates a concentrated urine, one with many solutes in a limited amount of water.

Knowing the urine concentration helps health care providers decide if the urine specimen they are evaluating is the best one to detect a particular substance. For example, if they are looking for very small amounts of protein, a concentrated morning urine specimen would be the best sample.

pH
As with specific gravity, there are typical but not "abnormal" pH values. The kidneys play an important role in maintaining the acid-base balance of the body. Therefore, any condition that produces acids or bases in the body such as acidosis or alkalosis, or the ingestion of acidic or basic foods, can directly affect urine pH.

Diet can be used to modify urine pH. A high-protein diet or consuming cranberries will make the urine more acidic. A vegetarian diet, a low-carbohydrate diet, or the ingestion of citrus fruits will tend to make the urine more alkaline.

Some of the substances dissolved in urine will precipitate out to form crystals when the urine is acidic; others will form crystals when the urine is basic. If crystals form while the urine is being produced in the kidneys, a kidney stone or “calculus” can develop. By modifying urine pH through diet or medications, the formation of these crystals can be reduced or eliminated.

Protein
The protein test pad measures the amount of albumin in the urine. Normally, there will not be detectable quantities. When urine protein is elevated, a person has a condition called proteinuria; this can be an early sign of kidney disease. Albumin is smaller than most other proteins and is typically the first protein that is seen in the urine when kidney dysfunction begins to develop. Other proteins are not detected by the test pad but may be measured with a separate urine protein test. Other conditions that can produce proteinuria include:

Disorders that produce high amounts of proteins in the blood, such as multiple myeloma
Conditions that destroy red blood cells
Inflammation, malignancies (cancer), or injury of the urinary tract - for example, the bladder, prostate, or urethra
Vaginal secretions that get into urine
Glucose
Glucose is normally not present in urine. When glucose is present, the condition is called glucosuria. It results from either:

An excessively high glucose concentration in the blood, such as may be seen with people who have uncontrolled diabetes mellitus
A reduction in the "renal threshold." When blood glucose levels reach a certain concentration, the kidneys begin to excrete glucose into the urine to decrease blood concentrations. Sometimes the threshold concentration is reduced and glucose enters the urine sooner, at a lower blood glucose concentration.
Some other conditions that can cause glucosuria include hormonal disorders, liver disease, medications, and pregnancy. When glucosuria occurs, other tests such as blood glucose are usually performed to further identify the specific cause.

Ketones
Ketones are not normally found in the urine. They are intermediate products of fat metabolism. They can form when a person does not eat enough carbohydrates (for example, in cases of starvation or high-protein diets) or when a person's body cannot use carbohydrates properly. When carbohydrates are not available, the body metabolizes fat instead to get the energy it needs to keep functioning.

Ketones in urine can give an early indication of insufficient insulin in a person who has diabetes. Severe exercise, exposure to cold, and loss of carbohydrates, such as with frequent vomiting, can also increase fat metabolism, resulting in ketonuria.

Blood (Hemoglobin)
This test is used to detect hemoglobin in the urine (hemoglobinuria). Hemoglobin is an oxygen-transporting protein found inside red blood cells (RBCs). Its presence in the urine indicates blood in the urine (known as hematuria). The small number of RBCs normally present in urine (see microscopic examination) usually result in a "negative" test. However, when the number of RBCs increases, they are detected as a "positive" test result.

Even small increases in the amount of RBCs in urine can be significant. Numerous diseases of the kidney and urinary tract, as well as trauma, medications, smoking, or strenuous exercise can cause hematuria or hemoglobinuria.

This test cannot determine the severity of disease nor be used to identify where the blood is coming from. For instance, contamination of urine with blood from hemorrhoids or vaginal bleeding cannot be distinguished from a bleed in the urinary tract. This is why it is important to collect a urine specimen correctly and for women to tell their health care provider that they are menstruating when asked to collect a urine specimen.

Sometimes a chemical test for blood in the urine is negative, but the Microscopic Exam shows increased numbers of RBCs. When this happens, the laboratorian may test the sample for ascorbic acid (vitamin C), because vitamin C has been known to interfere with the accuracy of urine blood test results, causing them to be falsely low or falsely negative.

Leukocyte Esterase
Leukocyte esterase is an enzyme present in most white blood cells (WBCs). Normally, a few white blood cells (see microscopic examination) are present in urine and this test is negative. When the number of WBCs in urine increases significantly, this screening test will become positive.

When the WBC count in urine is high, it means that there is inflammation in the urinary tract or kidneys. The most common cause for WBCs in urine (leukocyturia) is a bacterial urinary tract infection (UTI), such as a bladder or kidney infection.

Nitrite
This test detects nitrite and is based upon the fact that many bacteria can convert nitrate to nitrite in the urine. Normally the urinary tract and urine are free of bacteria. When bacteria find their way into the urinary tract, they can cause a urinary tract infection (UTI). A positive nitrite test result can indicate a UTI. However, since not all bacteria are capable of converting nitrate to nitrite, someone can still have a UTI despite a negative nitrite test.

Bilirubin
Bilirubin is not present in the urine of normal, healthy individuals. Bilirubin is a waste product that is produced by the liver from the hemoglobin of RBCs that are removed from circulation. It becomes a component of bile, a fluid that is secreted into the intestines to aid in food digestion.

In certain liver diseases, such as biliary obstruction or hepatitis, bilirubin leaks back into the blood stream and is excreted in urine. The presence of bilirubin in urine is an early indicator of liver disease and can occur before clinical symptoms such as jaundice develop.

Urobilinogen
Urobilinogen is normally present in urine in low concentrations. It is formed in the intestine from bilirubin, and a portion of it is absorbed back into the bloodstream. Positive test results help detect liver diseases such as hepatitis and cirrhosis and conditions associated with increased RBC destruction
The Microscopic Examination

A microscopic examination may or may not be performed as part of a routine urinalysis. It will typically be done when there are abnormal findings on the physical or chemical examination. It is performed on urine sediment – urine that has been centrifuged to concentrate the substances in it at the bottom of a tube. The fluid at the top of the tube is then discarded and the drops of fluid remaining are examined under a microscope. Cells, crystals, and other substances are counted and reported either as the number observed "per low power field" (LPF) or "per high power field" (HPF). In addition, some entities, if present, are estimated as "few," "moderate," or "many," such as epithelial cells, bacteria, and crystals.

Red Blood Cells (RBCs)
Normally, a few RBCs are present in urine sediment. Inflammation, injury, or disease in the kidneys or elsewhere in the urinary tract, for example, in the bladder or urethra, can cause RBCs to leak out of the blood vessels into the urine. RBCs can also be a contaminant due to an improper sample collection and blood from hemorrhoids or menstruation.

White Blood Cells (WBCs)
The number of WBCs in urine sediment is normally low. When the number is high, it indicates an infection or inflammation somewhere in the urinary tract. WBCs can also be a contaminant, such as those from vaginal secretions.

Epithelial Cells
Normally in men and women, a few epithelial cells from the bladder (transitional epithelial cells) or from the external urethra (squamous epithelial cells) can be found in the urine sediment. Cells from the kidney (kidney cells) are less common. In urinary tract conditions such as infections, inflammation, and malignancies, more epithelial cells are present. Determining the kinds of cells present helps the health care provider pinpoint where the condition is located. For example, a bladder infection may result in large numbers of transitional epithelial cells in urine sediment. Epithelial cells are usually reported as "few," "moderate," or "many" present per low power field (LPF).

Microorganisms (bacteria, trichomonads, yeast)
In health, the urinary tract is sterile; there will be no microorganisms seen in the urine sediment. Microorganisms are usually reported as "none," "few," "moderate," or "many" present per high power field (HPF). Bacteria from the surrounding skin can enter the urinary tract at the urethra and move up to the bladder, causing a urinary tract infection (UTI). If the infection is not treated, it can eventually move to the kidneys and cause pyelonephritis. Less frequently, bacteria from a blood infection (septicemia) may move into the urinary tract. This also results in a UTI. Special care must be taken during specimen collection, particularly in women, to prevent bacteria that normally live on the skin or in vaginal secretions from contaminating the urine. A urine culture may be performed if a UTI is suspected.

In women (and rarely in men), yeast can also be present in urine. They are most often present in women who have a vaginal yeast infection, because the urine has been contaminated with vaginal secretions during collection. If yeast are observed in urine, then tests for a yeast (fungal) infection may be performed on vaginal secretions.

Trichomonads
Trichomonads are parasites that may be found in the urine of women or men (rarely). As with yeast, the trichomonads are actually infecting the vaginal canal and their presence in urine is due to contamination. If these are found during a urinalysis, then follow-up testing for Trichomonas vaginalis may be performed to look for a vaginal infection.

Casts
Casts are cylindrical particles sometimes found in urine that are formed from coagulated protein secreted by kidney cells. They are formed in the long, thin, hollow tubes of the kidneys known as tubules and usually take the shape of the tubule (hence the name). Under the microscope, they often look like the shape of a "hot dog" and in healthy people they appear nearly clear. This type of cast is called a "hyaline" cast.

When a disease process is present in the kidney, other things such as RBCs or WBCs can become trapped in the protein as the cast is formed. When this happens, the cast is identified by the substances inside it, for example, as a red blood cell cast or white blood cell cast. Different types of casts are associated with different kidney diseases, and the type of casts found in the urine may give clues as to which disorder is affecting the kidney. Some other examples of types of casts include granular casts, fatty casts, and waxy casts.

Normally, healthy people may have a few (0–5) hyaline casts per low power field (LPF). After strenuous exercise, more hyaline casts may be detected. Cellular casts, such as RBC and WBC casts, indicate a kidney disorder.

Crystals
Urine contains many dissolved substances (solutes) – waste chemicals that the body needs to eliminate. These solutes can form crystals, solid forms of a particular substance, in the urine if:

The urine pH is increasingly acidic or basic;
The concentration of dissolved substances is increased; and
The urine temperature promotes their formation.
Crystals are identified by their shape, color, and by the urine pH. They may be small, sand-like particles with no specific shape (amorphous) or have specific shapes, such as needle-like. Crystals are considered "normal" if they are from solutes that are typically found in the urine. Some examples of crystals that can be found in the urine of healthy individuals include:

Amorphous urates
Crystalline uric acid
Calcium oxalates
Amorphous phosphates
Calcium carbonate
If the crystals are from solutes that are not normally in the urine, they are considered "abnormal." Abnormal crystals may indicate an abnormal metabolic process. Some of these include:

Cystine
Tyrosine
Leucine
When crystals form as urine is being made in the kidney, they may group together to form kidney "stones" or calculi. These stones can become lodged in the kidney itself or in the ureters, tubes that pass the urine from kidney to the bladder, causing extreme pain.

Medications, drugs, and x-ray dye can also crystallize in urine. Therefore, the laboratorian must be familiar with and trained in the identification of urine crystals.(hemolytic anemia). When urine urobilinogen is low or absent in a person with urine bilirubin and/or signs of liver dysfunction, it can indicate the presence of hepatic or biliary obstruction.
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Bilirubinuria

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