Here is a link to an interesting article about how latex gloves are made and why 17-18% of the population has an allergy to them. Not all allergies are the same and this article takes a look at what causes the different types of sensitive to our most important item of personal protective equipment.
http://www.immune.com/rubber/nr3.html
Wednesday, September 1, 2010
Tuesday, August 24, 2010
The history of the pregnancy tests
From early Egyption days to the "rabbit" test the pregnancy test has progressed a long way towards today's modern stick test.
Taken from Mental Floss @ http://www.mentalfloss.com/blogs/archives/14656
Dead Rabbits & Other Historical Pregnancy Tests
by Sara Newton - May 5, 2008 - 3:59 PM
In the ubiquitous Baby Mama trailer, Tina Fey looks at a used home pregnancy test that mocks her with a foreboding blue “NO” in the results box. Although the mock factor is optional, home pregnancy tests can lay it out straight: YES or NO. Whether the results are determined by blue lines, a plus or minus sign, or the plain words, the “pee on a stick” method is a popular way to discover if one is with child. Isn’t it interesting that one of life’s greatest achievements (new life) can be diagnosed by one of life’s most common routines (peeing, albeit on a prophetic stick)? Also as fascinating, this dichotomy existed long before the FDA approved the first home pregnancy test in the 1970s.
Knocked up like an Egyptian
The earliest recorded “peeing on a stick” test comes from those innovative Egyptians. In 1350 B.C., in between building pyramids and wrapping sarcophagi, someone produced a document describing how to determine pregnancy. You guessed it; a speculating woman must urinate on wheat and barley seeds, of course! The ancient papyrus read, “If the barley grows, it means a male child. If the wheat grows, it means a female child. If both do not grow, she will not bear at all.” In 1963, testing this theory found it 70 percent accurate, as the urine of pregnant women contains elevated levels of estrogen that may promote growth in these grains. As far as the gender guessing, that was Ra having a chuckle.
The Sample is in the Chamber Pot
Starting in the Middle Ages and up until the 17th century, “piss prophets” diagnosed many different conditions and diseases based on the color of urine. Since proven unscientific and often incorrect, this medical practice known as a “Uroscopy” often referred to a handy Uroscopy Wheel to help with diagnosis. A 1552 European document described pregnancy urine as a “clear pale lemon color leaning toward off-white, having a cloud on its surface.” The aptly named prophets employed another pregnancy test where they mixed urine and wine and watched the alcohol reacting with certain present proteins. In yet another dubious 17th-century test, a ribbon was dipped in a woman’s urine and burned. If the smell nauseated her, baby was on the way!
The Mouse Died
Fast-forward to the early 20th century, when scientists first discovered the role hormones played in female reproduction, they identified a specific hormone found only in pregnant woman, human chorionic gonadotropin (hCG). In the 1920s and 30s, to recognize the presence of hCG, which indicated pregnancy early on, doctors injected urine into an immature mouse, rat, frog, or even a rabbit. If a woman were pregnant, the test subject would go into heat despite its immaturity. To announce their status, women euphemized, “The mouse died” or “I killed the Easter bunny,” because killing and dissecting the lab animal confirmed the results. A common misconception arose that if the animal died after injection, it pointed to a positive pregnancy test. But in actuality, all tested specimens were disposed of, much to the chagrin of animal rights activists. This test was known as the A-Z test, named after the founding scientists, Selmar Ascheim and Bernhard Zondek.
To e.p.t.and Beyond
In the 1970s, as a result of the sexual revolution and the presence of reproductive choices, Wampole’s two-hour, urine-based pregnancy test became available only to doctors and technicians. The test could be done early on, but the packaging pictured an authoritative man wearing a lab coat, implying that this test was not intended for home use. Other intimidating tools in the box included: test tubes, a plastic rack, three bottles of chemical solutions, a small funnel, pipettes, and a saline solution. What a way to create an atmosphere encouraging relaxation and sample giving!
In 1977, the e.p.t. (which originally stood for “early pregnancy test,” and is now the more comforting “error proof test”) became the first home pregnancy test on the U.S. market. The test took two hours and was more accurate when dealing with positive results. In 1978, an issue of Mademoiselle described the original e.p.t.: “For your $10, you get pre-measured ingredients consisting of a vial of purified water, a test tube containing, among other things, sheep red blood cells…as well as a medicine dropper and clear plastic support for the test tube, with an angled mirror at the bottom.”
Home pregnancy tests evolved to the stick we know now and are still evolving. In 2003, Clearblue Easy’s digital pregnancy test ushered in a new generation of home pregnancy tests. In place of a thin blue line, the indicator screen says either “pregnant” or “not pregnant.” But if still skeptical, one can always go into a doctor’s office for a blood serum test for a definitive answer. Or maybe he has some barley or wheat that have a second opinion.
Sara Newton is an occasional contributor to mental_floss.
Taken from Mental Floss @ http://www.mentalfloss.com/blogs/archives/14656
Dead Rabbits & Other Historical Pregnancy Tests
by Sara Newton - May 5, 2008 - 3:59 PM
In the ubiquitous Baby Mama trailer, Tina Fey looks at a used home pregnancy test that mocks her with a foreboding blue “NO” in the results box. Although the mock factor is optional, home pregnancy tests can lay it out straight: YES or NO. Whether the results are determined by blue lines, a plus or minus sign, or the plain words, the “pee on a stick” method is a popular way to discover if one is with child. Isn’t it interesting that one of life’s greatest achievements (new life) can be diagnosed by one of life’s most common routines (peeing, albeit on a prophetic stick)? Also as fascinating, this dichotomy existed long before the FDA approved the first home pregnancy test in the 1970s.
Knocked up like an Egyptian
The earliest recorded “peeing on a stick” test comes from those innovative Egyptians. In 1350 B.C., in between building pyramids and wrapping sarcophagi, someone produced a document describing how to determine pregnancy. You guessed it; a speculating woman must urinate on wheat and barley seeds, of course! The ancient papyrus read, “If the barley grows, it means a male child. If the wheat grows, it means a female child. If both do not grow, she will not bear at all.” In 1963, testing this theory found it 70 percent accurate, as the urine of pregnant women contains elevated levels of estrogen that may promote growth in these grains. As far as the gender guessing, that was Ra having a chuckle.
The Sample is in the Chamber Pot
Starting in the Middle Ages and up until the 17th century, “piss prophets” diagnosed many different conditions and diseases based on the color of urine. Since proven unscientific and often incorrect, this medical practice known as a “Uroscopy” often referred to a handy Uroscopy Wheel to help with diagnosis. A 1552 European document described pregnancy urine as a “clear pale lemon color leaning toward off-white, having a cloud on its surface.” The aptly named prophets employed another pregnancy test where they mixed urine and wine and watched the alcohol reacting with certain present proteins. In yet another dubious 17th-century test, a ribbon was dipped in a woman’s urine and burned. If the smell nauseated her, baby was on the way!
The Mouse Died
Fast-forward to the early 20th century, when scientists first discovered the role hormones played in female reproduction, they identified a specific hormone found only in pregnant woman, human chorionic gonadotropin (hCG). In the 1920s and 30s, to recognize the presence of hCG, which indicated pregnancy early on, doctors injected urine into an immature mouse, rat, frog, or even a rabbit. If a woman were pregnant, the test subject would go into heat despite its immaturity. To announce their status, women euphemized, “The mouse died” or “I killed the Easter bunny,” because killing and dissecting the lab animal confirmed the results. A common misconception arose that if the animal died after injection, it pointed to a positive pregnancy test. But in actuality, all tested specimens were disposed of, much to the chagrin of animal rights activists. This test was known as the A-Z test, named after the founding scientists, Selmar Ascheim and Bernhard Zondek.
To e.p.t.and Beyond
In the 1970s, as a result of the sexual revolution and the presence of reproductive choices, Wampole’s two-hour, urine-based pregnancy test became available only to doctors and technicians. The test could be done early on, but the packaging pictured an authoritative man wearing a lab coat, implying that this test was not intended for home use. Other intimidating tools in the box included: test tubes, a plastic rack, three bottles of chemical solutions, a small funnel, pipettes, and a saline solution. What a way to create an atmosphere encouraging relaxation and sample giving!
In 1977, the e.p.t. (which originally stood for “early pregnancy test,” and is now the more comforting “error proof test”) became the first home pregnancy test on the U.S. market. The test took two hours and was more accurate when dealing with positive results. In 1978, an issue of Mademoiselle described the original e.p.t.: “For your $10, you get pre-measured ingredients consisting of a vial of purified water, a test tube containing, among other things, sheep red blood cells…as well as a medicine dropper and clear plastic support for the test tube, with an angled mirror at the bottom.”
Home pregnancy tests evolved to the stick we know now and are still evolving. In 2003, Clearblue Easy’s digital pregnancy test ushered in a new generation of home pregnancy tests. In place of a thin blue line, the indicator screen says either “pregnant” or “not pregnant.” But if still skeptical, one can always go into a doctor’s office for a blood serum test for a definitive answer. Or maybe he has some barley or wheat that have a second opinion.
Sara Newton is an occasional contributor to mental_floss.
Sunday, August 15, 2010
Rheumatoid Factor
Rheumatoid factor (RF) is an autoantibody that is produced by the body in response to certain disease states. Rheumatoid factor is usually an IgM antibody; however other classes of immunoglobulins can be produced. The antibody targets the Fc region of human IgG that is altered in protein structure. The RF autoantibodies attach themselves to healthy tissues throughout the body causing damage. The body can produce rheumatoid factor in response to various illnesses however it is most commonly measured to help diagnose potential cases of Rheumatoid Arthritis and Sjogren’s syndrome.
Rheumatoid factor can be present in a variety of illnesses. Around 75% of patients with Rheumatoid arthritis or Sjogren’s syndrome will present with a positive RF test. The remaining percentage of people with these two diseases will present with a negative level of RF or have very low levels. High RF levels can be found in patients with other autoimmune diseases such as lupus, scleroderma, and vasculitis. Positive RF tests can also be associated with diseases such as tuberculosis, malaria, hepatitis, endocarditis, and leukemia. Because RF levels may or may not be present in a patient with a specific illness RF is not used to definitively diagnose any disease.
Rheumatoid factor is measured in conjunction with other tests to help make a diagnosis. If Rheumatoid arthritis or Sjogren’s syndrome is suspected, a clinician might order other autoantibody tests such as an ANA (antinuclear antibody), anti-SS-A, or anti-SS-B to help differentiate between all possibilities. Performing a CRP level or a Sedimentation rate can help to determine if there is inflammation present. A newer test called the Cyclic Citrullinated Peptide Antibody (CCP) test can be ordered to detected early onset Rheumatoid Arthritis. This test can be performed in the event that RF levels are negative and the clinician still suspects Rheumatoid arthritis. Clinicians will use results from a variety of tests along with clinical findings to diagnose a patient with Rheumatoid arthritis.
Rheumatoid factor testing can be performed either by agglutination assays or through nephelometry. Here at BSHS we perform RF testing on the Dimension Vista system. The Vista uses nephelometry to measure levels of rheumatoid factor in a sample. The reagent includes polystyrene particles that are coated with anti-human IgG and a phosphate buffer. When the reagent is added to a patient’s sample any rheumatoid factor present will bind to the anti-human IgG. The aggregates that are formed scatter light in direct proportion to the concentration of RF present.
Normal values for rheumatoid factor can vary depending on testing methods. Agglutination methods will report results out as a titer. Nephelometric methods will report out rheumatoid factor as a unit of concentration. For the method utilized by the Dimension Vista, the normal range is less than 15 IU/mL. Factors that can affect results include excessively lipemic and icteric samples. Age can play a factor as well. High RF levels can be found in up to 10% of people over the age of 65 years. These potential false positive results should be taken into account when determining a diagnosis.
Rheumatoid factor is an autoantibody produced by the body for unknown reasons. It attaches to various tissues in the body causing damage and subsequent illness. Clinicians will measure levels of rheumatoid factor in the body in order to determine if a patient potentially has rheumatoid arthritis or Sjogern’s syndrome. While there is no definitive test to diagnosis rheumatoid arthrisis, testing for RF in conjunction with others assays and clinical findings can help clinicians in diagnosing potential cases of rheumatoid arthritis.
References
• SIEMENS Dimension Vista Flex reagent cartridge. (2008). RF. (REF K7068). Newark, DE: Siemens Healthcare Diagnostics Inc.
• Rheumatoid Factor. (2010). Rheumatoid Factor: The Test. Lab Tests Online. Retrieved on July 18, 2010 from http://www.labtestsonline.org/understanding/analytes/rheumatoid/test.html
• Arthritis Health Center: Rheumatoid Factor. (2008). Rheumatoid Factor. WebMD. Retrieved on July 18, 2010 from http://www.arthritis.webmd.com/rheumatoid-factor-rf
Rheumatoid factor can be present in a variety of illnesses. Around 75% of patients with Rheumatoid arthritis or Sjogren’s syndrome will present with a positive RF test. The remaining percentage of people with these two diseases will present with a negative level of RF or have very low levels. High RF levels can be found in patients with other autoimmune diseases such as lupus, scleroderma, and vasculitis. Positive RF tests can also be associated with diseases such as tuberculosis, malaria, hepatitis, endocarditis, and leukemia. Because RF levels may or may not be present in a patient with a specific illness RF is not used to definitively diagnose any disease.
Rheumatoid factor is measured in conjunction with other tests to help make a diagnosis. If Rheumatoid arthritis or Sjogren’s syndrome is suspected, a clinician might order other autoantibody tests such as an ANA (antinuclear antibody), anti-SS-A, or anti-SS-B to help differentiate between all possibilities. Performing a CRP level or a Sedimentation rate can help to determine if there is inflammation present. A newer test called the Cyclic Citrullinated Peptide Antibody (CCP) test can be ordered to detected early onset Rheumatoid Arthritis. This test can be performed in the event that RF levels are negative and the clinician still suspects Rheumatoid arthritis. Clinicians will use results from a variety of tests along with clinical findings to diagnose a patient with Rheumatoid arthritis.
Rheumatoid factor testing can be performed either by agglutination assays or through nephelometry. Here at BSHS we perform RF testing on the Dimension Vista system. The Vista uses nephelometry to measure levels of rheumatoid factor in a sample. The reagent includes polystyrene particles that are coated with anti-human IgG and a phosphate buffer. When the reagent is added to a patient’s sample any rheumatoid factor present will bind to the anti-human IgG. The aggregates that are formed scatter light in direct proportion to the concentration of RF present.
Normal values for rheumatoid factor can vary depending on testing methods. Agglutination methods will report results out as a titer. Nephelometric methods will report out rheumatoid factor as a unit of concentration. For the method utilized by the Dimension Vista, the normal range is less than 15 IU/mL. Factors that can affect results include excessively lipemic and icteric samples. Age can play a factor as well. High RF levels can be found in up to 10% of people over the age of 65 years. These potential false positive results should be taken into account when determining a diagnosis.
Rheumatoid factor is an autoantibody produced by the body for unknown reasons. It attaches to various tissues in the body causing damage and subsequent illness. Clinicians will measure levels of rheumatoid factor in the body in order to determine if a patient potentially has rheumatoid arthritis or Sjogern’s syndrome. While there is no definitive test to diagnosis rheumatoid arthrisis, testing for RF in conjunction with others assays and clinical findings can help clinicians in diagnosing potential cases of rheumatoid arthritis.
References
• SIEMENS Dimension Vista Flex reagent cartridge. (2008). RF. (REF K7068). Newark, DE: Siemens Healthcare Diagnostics Inc.
• Rheumatoid Factor. (2010). Rheumatoid Factor: The Test. Lab Tests Online. Retrieved on July 18, 2010 from http://www.labtestsonline.org/understanding/analytes/rheumatoid/test.html
• Arthritis Health Center: Rheumatoid Factor. (2008). Rheumatoid Factor. WebMD. Retrieved on July 18, 2010 from http://www.arthritis.webmd.com/rheumatoid-factor-rf
Sunday, August 8, 2010
Sickle Cell Disease
What Is Sickle Cell Disease?
By Rachael Rettner, LiveScience Staff Writer
posted: 30 July 2010 10:38 am ET
Sickle cell disease gets its name from the distorted shape of a patient's red blood cells, which are sometimes C-shaped rather than the normal doughnut shape. The cells' disfigurement comes from the presence of abnormal hemoglobin — a protein in red blood cells that carries oxygen throughout the body. Not all red blood cells are sickle shaped all the time — they take on the shape in response to a stressor, such as lack of oxygen, dehydration or infection.
The disease is hereditary. People who have two copies of the sickle cell gene, one from each parent, are said to have sickle cell anemia, the most severe form of the disease. People with one sickle cell gene are said to have sickle cell trait. They don't show symptoms, but can pass the gene on to their children.
Having just one copy of the gene confers protection against malaria. This protection is thought to be why the genetic mutation has stuck around over the course of evolution. It may also explain why the disease primarily affects those who descend from tropical or subtropical countries (where malaria is prevalent), including Africa, South America, Central America and India. In the United States, 70,000 to 100,000 African Americans are estimated to have sickle cell anemia, or 1 out of every 500 births in this population, according to the Centers for Disease Control and Prevention (CDC). About 1 in 12 African Americans has sickle cell trait. The condition occurs in 1 out of every 36,000 Hispanic American births. And around the world, the disease affects millions of individuals.
The abnormal sickle cells are less flexible than normal red blood cells and can also stick together and form clumps, which can cause a number of problems. The cells can block blood vessels and restrict blood flow, which can lead to pain, organ and nerve damage, and stroke.
"People can have problems in any part of their body," said Marsha Treadwell, a sickle cell disease researcher at Children's Hospital Oakland Research Institute (CHORI) in California. "Blood flows everywhere."
The sickle cells also don't live as long as normal red blood cells, lasting around 20 days instead of the usual three months. As a result, patients experience anemia.
Recent advances in pediatric care have led to a decrease in the mortality rate for the disease in children. From 1999 to 2002, sickle cell-related death among African-American children less than 4 years of age fell by 42 percent, according to the CDC. However, the average life expectancy for those with sickle cell disease in the United States is still 30 years shorter than the average lifespan of healthy adults.
By age 45, 24 percent of sickle cell patients have had a stroke, said Elliott Vichinsky, a hematologist at CHORI. But even without having a stroke, the condition may lead to cognitive problems.
In a recent study, Vichinsky found adult sickle cell patients with no history of brain problems performed worse on cognitive tests than controls matched from the community after adjusting for age, gender and education. The result suggests sickle cell patients may have problems with everyday tasks such as multitasking, remembering appointments and carrying out their jobs. The researchers suspect the cognitive problems might be due to a lack of oxygen being delivered to the brain, and so, in many cases, the problems could be reversible. The study was published May 12 in the Journal of the American Medical Association.
Current treatments involve blood transfusions to treat anemia and help prevent stroke, and pain medication for pain episodes. The only sickle cell-specific drug available, known as hydroxyurea, helps alleviate pain and can reduce the rate of mortality in patients.
A bone marrow transplant can cure the disease, but this option is not available for many people because the transplant needs to be matched exactly.
Full article @ http://www.livescience.com/health/what-is-sickle-cell-disease-100730.html
By Rachael Rettner, LiveScience Staff Writer
posted: 30 July 2010 10:38 am ET
Sickle cell disease gets its name from the distorted shape of a patient's red blood cells, which are sometimes C-shaped rather than the normal doughnut shape. The cells' disfigurement comes from the presence of abnormal hemoglobin — a protein in red blood cells that carries oxygen throughout the body. Not all red blood cells are sickle shaped all the time — they take on the shape in response to a stressor, such as lack of oxygen, dehydration or infection.
The disease is hereditary. People who have two copies of the sickle cell gene, one from each parent, are said to have sickle cell anemia, the most severe form of the disease. People with one sickle cell gene are said to have sickle cell trait. They don't show symptoms, but can pass the gene on to their children.
Having just one copy of the gene confers protection against malaria. This protection is thought to be why the genetic mutation has stuck around over the course of evolution. It may also explain why the disease primarily affects those who descend from tropical or subtropical countries (where malaria is prevalent), including Africa, South America, Central America and India. In the United States, 70,000 to 100,000 African Americans are estimated to have sickle cell anemia, or 1 out of every 500 births in this population, according to the Centers for Disease Control and Prevention (CDC). About 1 in 12 African Americans has sickle cell trait. The condition occurs in 1 out of every 36,000 Hispanic American births. And around the world, the disease affects millions of individuals.
The abnormal sickle cells are less flexible than normal red blood cells and can also stick together and form clumps, which can cause a number of problems. The cells can block blood vessels and restrict blood flow, which can lead to pain, organ and nerve damage, and stroke.
"People can have problems in any part of their body," said Marsha Treadwell, a sickle cell disease researcher at Children's Hospital Oakland Research Institute (CHORI) in California. "Blood flows everywhere."
The sickle cells also don't live as long as normal red blood cells, lasting around 20 days instead of the usual three months. As a result, patients experience anemia.
Recent advances in pediatric care have led to a decrease in the mortality rate for the disease in children. From 1999 to 2002, sickle cell-related death among African-American children less than 4 years of age fell by 42 percent, according to the CDC. However, the average life expectancy for those with sickle cell disease in the United States is still 30 years shorter than the average lifespan of healthy adults.
By age 45, 24 percent of sickle cell patients have had a stroke, said Elliott Vichinsky, a hematologist at CHORI. But even without having a stroke, the condition may lead to cognitive problems.
In a recent study, Vichinsky found adult sickle cell patients with no history of brain problems performed worse on cognitive tests than controls matched from the community after adjusting for age, gender and education. The result suggests sickle cell patients may have problems with everyday tasks such as multitasking, remembering appointments and carrying out their jobs. The researchers suspect the cognitive problems might be due to a lack of oxygen being delivered to the brain, and so, in many cases, the problems could be reversible. The study was published May 12 in the Journal of the American Medical Association.
Current treatments involve blood transfusions to treat anemia and help prevent stroke, and pain medication for pain episodes. The only sickle cell-specific drug available, known as hydroxyurea, helps alleviate pain and can reduce the rate of mortality in patients.
A bone marrow transplant can cure the disease, but this option is not available for many people because the transplant needs to be matched exactly.
Full article @ http://www.livescience.com/health/what-is-sickle-cell-disease-100730.html
Sunday, August 1, 2010
Credit-card sized microfluidics
Laboratory in microdrops: Credit card-size microflow system handles thousands of experiments
ScienceDaily (2010-07-29) -- Tens of thousands of chemical and biochemical experiments may be conducted daily with the use of a microflow system of the size of a credit card, developed by scientists in Poland. The device has already been tested in research on the effectiveness of antibiotic mixtures. ... > read full article
Sunday, July 25, 2010
Prealbumin
Prealbumin is a transport protein in the body that can be measured to determine if a patient is malnourished or needs nutritional support. The name prealbumin is actually a misnomer, as this protein is not related in structure to albumin. The formal name for prealbumin is transthyretin. This protein is made primarily in the liver and is used by the body to transport T3 and T4. While prealbumin contains both binding sites for T3 and T4 it usually only carries one of these molecules at a time.Prealbumin has a high proportion of essential to non-essential amino acids and a high content of tryptophan. Along with a half-life of two days, the proportion of amino acids inside prealbumin make it an ideal marker for nutritional status. Prealbumin is classified as an acute phase reactant. As such, concentrations will decrease naturally in the event of inflammation. Other acute phase reactants such as CRP can be run in tandem with prealbumin in order to rule out decreased concentrations due to inflammation.
The concentration of prealbumin in a patient’s serum will increase or decrease rapidly in response to a patient’s nutritional status. Increases in concentration can occur due to drug therapy with high-dose corticosteroids or high-dose nonsteroidal anti-inflammatory drugs. Increases in prealbumin can also be seen in Hodgkin’s disease and kidney failure. It is not typical to use prealbumin testing to monitor these conditions. Decreases in the concentration of prealbumin are more serious and are a sign of malnutrition. A decreased concentration of prealbumin can be found in chronic illnesses such as cancer or AIDS, in patients with hyperthyroidism, in sepsis, and in liver disease. Other conditions that can lead to malnutrition include protein-losing gastrointestinal illnesses, eating disorders such as anorexia, massive trauma, pancreatitis, and severe burn victims. All of these diseases and disorders can result in a decreased concentration of prealbumin.
Prealbumin levels can also be used to monitor the effectiveness of nutritional therapy. Physicians will order prealbumin levels on patients who are scheduled for surgery or hemodialysis in order to determine if a patient will have a negative or diminished outcome to treatment. Patients with a normal prealbumin level are better nourished and will recover more quickly from these types of treatments. Prealbumin levels can also be used to monitor the effectiveness of parenteral nutrition therapy. If a patient is responding to nutritional therapy then prealbumin levels should increase about 1 mg/dL per day.
Normal ranges for prealbumin concentration can vary slightly between laboratories however a general range is 20-40 mg/dL. Here at BSHS we are running prealbumin on the Dimension Vista system. This assay detects the concentration of prealbumin in serum using an antiserum. The antiserum combines with the prealbumin to form immune complexes that are detected via nephelometry. These immune complexes create light scatter that is directly proportional to the concentration of prealbumin in the sample.
Prealbumin is an ideal marker for nutritional status. It has a short half-life and reacts quickly to changes in a patient’s diet. It contains within it a wide variety of essential and non-essential amino acids that are used throughout the body. Because of its structure it is a better marker for nutritional status than albumin levels alone. When available it is the preferred test for determining the nutritional status of a patient.
References
· Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). 563-564.
· SIEMENS Dimension Vista Flex reagent cartridge. (2008). Prealbumin. (REF K7064). Newark, DE: Siemens Healthcare Diagnostics Inc.
· Prealbumin. (2009). Prealbumin: The Test. Lab Tests Online. Retrieved on July 24, 2010 from http://www.labtestsonline.org/understanding/analytes/prealbumin/glance.html#
· Prealbumin. (2010). Prealbumin. Clinlab Navigator. Retrieved on July 24, 2010 from http://www.clinlabnavigator.com/index.php?option=com_content&view=aritcle&id=473&letter=P
The concentration of prealbumin in a patient’s serum will increase or decrease rapidly in response to a patient’s nutritional status. Increases in concentration can occur due to drug therapy with high-dose corticosteroids or high-dose nonsteroidal anti-inflammatory drugs. Increases in prealbumin can also be seen in Hodgkin’s disease and kidney failure. It is not typical to use prealbumin testing to monitor these conditions. Decreases in the concentration of prealbumin are more serious and are a sign of malnutrition. A decreased concentration of prealbumin can be found in chronic illnesses such as cancer or AIDS, in patients with hyperthyroidism, in sepsis, and in liver disease. Other conditions that can lead to malnutrition include protein-losing gastrointestinal illnesses, eating disorders such as anorexia, massive trauma, pancreatitis, and severe burn victims. All of these diseases and disorders can result in a decreased concentration of prealbumin.
Prealbumin levels can also be used to monitor the effectiveness of nutritional therapy. Physicians will order prealbumin levels on patients who are scheduled for surgery or hemodialysis in order to determine if a patient will have a negative or diminished outcome to treatment. Patients with a normal prealbumin level are better nourished and will recover more quickly from these types of treatments. Prealbumin levels can also be used to monitor the effectiveness of parenteral nutrition therapy. If a patient is responding to nutritional therapy then prealbumin levels should increase about 1 mg/dL per day.
Normal ranges for prealbumin concentration can vary slightly between laboratories however a general range is 20-40 mg/dL. Here at BSHS we are running prealbumin on the Dimension Vista system. This assay detects the concentration of prealbumin in serum using an antiserum. The antiserum combines with the prealbumin to form immune complexes that are detected via nephelometry. These immune complexes create light scatter that is directly proportional to the concentration of prealbumin in the sample.
Prealbumin is an ideal marker for nutritional status. It has a short half-life and reacts quickly to changes in a patient’s diet. It contains within it a wide variety of essential and non-essential amino acids that are used throughout the body. Because of its structure it is a better marker for nutritional status than albumin levels alone. When available it is the preferred test for determining the nutritional status of a patient.
References
· Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). 563-564.
· SIEMENS Dimension Vista Flex reagent cartridge. (2008). Prealbumin. (REF K7064). Newark, DE: Siemens Healthcare Diagnostics Inc.
· Prealbumin. (2009). Prealbumin: The Test. Lab Tests Online. Retrieved on July 24, 2010 from http://www.labtestsonline.org/understanding/analytes/prealbumin/glance.html#
· Prealbumin. (2010). Prealbumin. Clinlab Navigator. Retrieved on July 24, 2010 from http://www.clinlabnavigator.com/index.php?option=com_content&view=aritcle&id=473&letter=P
Tuesday, July 20, 2010
Salad Spinner Centrifuge
Salad Spinner Centrifuge: A Cheap, Ingenious Health Care Tool user
by Tonic, on Tue Jul 13, 2010 5:45am PDT 1815
From Yahoo News Healthy Living
http://shine.yahoo.com/channel/health/salad-spinner-centrifuge-a-cheap-ingenious-health-care-tool-2019637/
We already know that we need to eat plenty of leafy greens to stay healthy, but who knew that a salad spinner itself could help save lives?
As we learn from EurekAlert, Rice University undergraduates Lila Kerr and Lauren Theis were presented with an assignment in their Introduction to Bioengineering and World Health class. As Theis explains:
"We were essentially told we need to find a way to diagnose anemia without power, without it being very costly and with a portable device."
In a solution short on cost but long on ingenuity, the duo modified a basic, everyday salad spinner into an easy to use and transport centrifuge that successfully separates blood to allow diagnosis of anemia with no electricity. The device costs about $30, can process 30 individual 15 microliter blood samples at a time, and can separate blood into its component red cells and plasma in about 20 minutes.
"Sally Centrifuge," as the innovation has been dubbed by its creators, is undergoing a series of field tests this summer in places that will benefit from the availability of effective but low-tech solutions and adaptations. As part of Rice University's Beyond Traditional Borders (BTB), a global health initiative focused primarily on developing countries, Kerr and Theis are traveling along with their device to Ecuador, Swaziland and Malawi, where rural clinics will provide real-world testing of the surprising diagnostic tool.
In rural, under-served and impoverished parts of the world, a positive diagnosis for anemia is a critically important clue when looking for other health problems such as malnutrition, or serious chronic infectious diseases such as malaria and HIV/AIDS. Until now, blood samples taken in the field would have to be sent to a distant location complete with expensive laboratory centrifuges and electricity, while patients would be left waiting for the results — a lapse in time that can be deadly. Being able to diagnose the condition in real time with "Sally Centrifuge" would allow appropriate treatment to begin before before an illness progresses and a patient's condition deteriorates too drastically.
Maria Oden, engineering professor and co-adviser to the team, reflects on how successfully the two young women approached the assignment by providing something that may literally save lives as it is brought to bear on pressing health challenges in rural and economically under-developed regions of the world:
"The students really did an amazing job of taking very simple, low-cost materials and creating a device their research shows correlates nicely with hematocrit levels in the blood. Many of the patients seen in developing world clinics are anemic, and it's a severe health problem. Being able to diagnose it with no power, with a device that's extremely lightweight, is very valuable."
Have an innovative idea for re-purposing a household gadget yourself? Share it in a comment below!
-David Bois
Photo by Jeff Fitlow/Rice University.
Read more Weird Science stories at Tonic!
by Tonic, on Tue Jul 13, 2010 5:45am PDT 1815
From Yahoo News Healthy Living
http://shine.yahoo.com/channel/health/salad-spinner-centrifuge-a-cheap-ingenious-health-care-tool-2019637/
We already know that we need to eat plenty of leafy greens to stay healthy, but who knew that a salad spinner itself could help save lives?
As we learn from EurekAlert, Rice University undergraduates Lila Kerr and Lauren Theis were presented with an assignment in their Introduction to Bioengineering and World Health class. As Theis explains:
"We were essentially told we need to find a way to diagnose anemia without power, without it being very costly and with a portable device."
In a solution short on cost but long on ingenuity, the duo modified a basic, everyday salad spinner into an easy to use and transport centrifuge that successfully separates blood to allow diagnosis of anemia with no electricity. The device costs about $30, can process 30 individual 15 microliter blood samples at a time, and can separate blood into its component red cells and plasma in about 20 minutes.
"Sally Centrifuge," as the innovation has been dubbed by its creators, is undergoing a series of field tests this summer in places that will benefit from the availability of effective but low-tech solutions and adaptations. As part of Rice University's Beyond Traditional Borders (BTB), a global health initiative focused primarily on developing countries, Kerr and Theis are traveling along with their device to Ecuador, Swaziland and Malawi, where rural clinics will provide real-world testing of the surprising diagnostic tool.
In rural, under-served and impoverished parts of the world, a positive diagnosis for anemia is a critically important clue when looking for other health problems such as malnutrition, or serious chronic infectious diseases such as malaria and HIV/AIDS. Until now, blood samples taken in the field would have to be sent to a distant location complete with expensive laboratory centrifuges and electricity, while patients would be left waiting for the results — a lapse in time that can be deadly. Being able to diagnose the condition in real time with "Sally Centrifuge" would allow appropriate treatment to begin before before an illness progresses and a patient's condition deteriorates too drastically.
Maria Oden, engineering professor and co-adviser to the team, reflects on how successfully the two young women approached the assignment by providing something that may literally save lives as it is brought to bear on pressing health challenges in rural and economically under-developed regions of the world:
"The students really did an amazing job of taking very simple, low-cost materials and creating a device their research shows correlates nicely with hematocrit levels in the blood. Many of the patients seen in developing world clinics are anemic, and it's a severe health problem. Being able to diagnose it with no power, with a device that's extremely lightweight, is very valuable."
Have an innovative idea for re-purposing a household gadget yourself? Share it in a comment below!
-David Bois
Photo by Jeff Fitlow/Rice University.
Read more Weird Science stories at Tonic!
Sunday, July 18, 2010
Many False-Positive HIV Test Results for Those in AIDS Vaccine Trials
Many False-Positive HIV Test Results for Those in AIDS Vaccine Trials
By Amanda Gardner
HealthDay Reporter by Amanda Gardner
healthday Reporter 13 mins ago
SUNDAY, July 18 (HealthDay News) -- Almost half of HIV-negative people who participate in clinical trials for HIV vaccines end up testing positive on routine HIV tests -- even though they're not actually infected, a new study shows.
The reason: They underwent what experts call "vaccine-induced seropositivity/reactivity" (VISP), meaning that they possess immune system antibodies to the virus but not the virus itself. That's an important distinction, since routine HIV screening looks for virus antibodies only.
Experts pointed out that the results are not new or surprising, but simply underline the delicacies of conducting trials into HIV/AIDS.
"You need to make sure to use other forms of testing for HIV, for example, viral load or p24 antigen, not just HIV antibodies. And people who've been in trials need to know their antibody status by the end of the trial," said Dr. Michael Horberg, director of HIV/AIDS at Kaiser Permanente in Santa Clara, Calif. "If it is a false positive but they do not have HIV infection, that would be very important for them to know, especially if they do repeat testing as part of good preventive health."
But a positive test can still carry stigma as well as insurance repercussions, noted Dr. Jerome F. Levine, an infectious diseases specialist with Hackensack University Medical Center in New Jersey, adding that "trials have had trouble recruiting people for this very reason."
The findings are simultaneously being presented Sunday at the International AIDS Conference in Vienna and published in the July 21 issue of the Journal of the American Medical Association (JAMA).
In this study of almost 2,200 people -- all participants in HIV vaccine trials -- 41.7 percent underwent VISP and tested positive for HIV antibodies. And those rates differed depending on the type of vaccine administered, ranging from 6.3 percent to 86.7 percent.
A second study, also being presented at the conference and published in JAMA, found that a screening program used in emergency departments where patients can "opt out" did not turn up very many new cases of HIV. These types of screening programs routinely test people entering the emergency room, regardless of their suspected level of risk or the presence or absence of symptoms.
The study compared the effectiveness of the test in turning up new cases of HIV infection versus tests ordered directly by a doctor.
The "opt-out" program started being recommended by the U.S. Centers for Disease Control and Prevention in 2006, but only in locales where the rate of undiagnosed cases of HIV infection rose above 0.1 percent.
Most health care facilities in the United States still don't use the opt-out method, said Levine.
This study took place in a Denver emergency department that annually sees about 55,000 patients. The hospital alternated from physician-directed testing to opt-out testing every four months over the course of two years.
First of all, the study found that only 25 percent of patients in the opt-out group actually agreed to a test.
Furthermore, close to 7,000 people were screened but only 0.15 percent turned out to be HIV-positive. Only 1 percent of the more than 21,000 patients who opted out were screened later and only 2.2 percent of those were found to be HIV-positive.
The small number of people who underwent HIV testing -- only one-quarter -- is a big limitation to the study, said Horberg, but that doesn't mean that such programs don't have value.
"Just because someone has a negative test, that doesn't mean that that testing wasn't successful," he said. "It may have raised the awareness of the patient. It may be prompting them to change their behavior and to really do an analysis of what good preventive health they need to follow."
A third paper in the journal recommended that all cancer patients be screened for HIV. This might sway cancer treatment decisions, for instance, helping doctors and patients avoid drugs that suppress the immune system, the authors noted.
More information
There's more on HIV/AIDS at the U.S. Centers for Disease Control and Prevention.
By Amanda Gardner
HealthDay Reporter by Amanda Gardner
healthday Reporter 13 mins ago
SUNDAY, July 18 (HealthDay News) -- Almost half of HIV-negative people who participate in clinical trials for HIV vaccines end up testing positive on routine HIV tests -- even though they're not actually infected, a new study shows.
The reason: They underwent what experts call "vaccine-induced seropositivity/reactivity" (VISP), meaning that they possess immune system antibodies to the virus but not the virus itself. That's an important distinction, since routine HIV screening looks for virus antibodies only.
Experts pointed out that the results are not new or surprising, but simply underline the delicacies of conducting trials into HIV/AIDS.
"You need to make sure to use other forms of testing for HIV, for example, viral load or p24 antigen, not just HIV antibodies. And people who've been in trials need to know their antibody status by the end of the trial," said Dr. Michael Horberg, director of HIV/AIDS at Kaiser Permanente in Santa Clara, Calif. "If it is a false positive but they do not have HIV infection, that would be very important for them to know, especially if they do repeat testing as part of good preventive health."
But a positive test can still carry stigma as well as insurance repercussions, noted Dr. Jerome F. Levine, an infectious diseases specialist with Hackensack University Medical Center in New Jersey, adding that "trials have had trouble recruiting people for this very reason."
The findings are simultaneously being presented Sunday at the International AIDS Conference in Vienna and published in the July 21 issue of the Journal of the American Medical Association (JAMA).
In this study of almost 2,200 people -- all participants in HIV vaccine trials -- 41.7 percent underwent VISP and tested positive for HIV antibodies. And those rates differed depending on the type of vaccine administered, ranging from 6.3 percent to 86.7 percent.
A second study, also being presented at the conference and published in JAMA, found that a screening program used in emergency departments where patients can "opt out" did not turn up very many new cases of HIV. These types of screening programs routinely test people entering the emergency room, regardless of their suspected level of risk or the presence or absence of symptoms.
The study compared the effectiveness of the test in turning up new cases of HIV infection versus tests ordered directly by a doctor.
The "opt-out" program started being recommended by the U.S. Centers for Disease Control and Prevention in 2006, but only in locales where the rate of undiagnosed cases of HIV infection rose above 0.1 percent.
Most health care facilities in the United States still don't use the opt-out method, said Levine.
This study took place in a Denver emergency department that annually sees about 55,000 patients. The hospital alternated from physician-directed testing to opt-out testing every four months over the course of two years.
First of all, the study found that only 25 percent of patients in the opt-out group actually agreed to a test.
Furthermore, close to 7,000 people were screened but only 0.15 percent turned out to be HIV-positive. Only 1 percent of the more than 21,000 patients who opted out were screened later and only 2.2 percent of those were found to be HIV-positive.
The small number of people who underwent HIV testing -- only one-quarter -- is a big limitation to the study, said Horberg, but that doesn't mean that such programs don't have value.
"Just because someone has a negative test, that doesn't mean that that testing wasn't successful," he said. "It may have raised the awareness of the patient. It may be prompting them to change their behavior and to really do an analysis of what good preventive health they need to follow."
A third paper in the journal recommended that all cancer patients be screened for HIV. This might sway cancer treatment decisions, for instance, helping doctors and patients avoid drugs that suppress the immune system, the authors noted.
More information
There's more on HIV/AIDS at the U.S. Centers for Disease Control and Prevention.
Cerebral Spinal Fluid
Cerebral Spinal fluid (CSF) is the fluid that protects and nourishes the brain and spinal cord. It is a filtrate of arterial blood that is produced by the choroid plexuses of the lateral and fourth ventricles of the brain. CSF flows inside all the ventricles, the central canal of the spinal cord, and throughout the subarachnoid space of the brain. The body produces up to a maximum of 150 mL of CSF for adults and 60 mL for neonates. This volume remains constant as the ventricles secrete and reabsorb CSF at a rate of approximately 840 mL a day. The blood-brain barrier refers to the structure and function of the capillaries inside the choroid plexuses of the ventricles. All pre and post capillary vessels in the brain are covered by an extension of the subarachnoid space called the perivascular space. The capillaries are not covered by the perivascular space. They make contact with the endothelial cells in the choroid plexuses and have a special structure that only allows for the movement of certain substances between the blood and the CSF. The result is that small lipophilic molecules such as oxygen and carbon dioxide can move freely between the two structures, whereas larger molecules such as glucose and amino acids require the help of transporters. The blood-brain barrier protects the brain from toxic substances, drugs, and other foreign materials. In the event that the blood-brain barrier is disrupted, materials that are normally kept out of the CSF can gain entry into the brain. Inflammatory mediators and malignant brain cells are examples of things that can cause disruptions of the structures in the blood-brain barrier.
CSF can be collected for both therapeutic and diagnostic purposes. In the event that intracranial pressure is increased CSF can be collected in order to relieve pressure inside the brain. CSF obtained for laboratory analysis can reveal the presence of inflammation, trauma, infections, or even malignancies. CSF can be collected from a variety of sites, however it is most often collected using a lumbar puncture. In this case a needle is inserted into the space between vertebrae in the lumbar portion of the spine in order to remove CSF. In the event that a lumbar puncture cannot be performed a cisternal puncture or a ventricular puncture can be used. A cisternal puncture is done with fluoroscopy, and involves placing the needle below the occipital bone of the skull in order to obtain a sample. A ventricular puncture is usually done in the operating room and involves inserting a needle directing into one of the ventricles of the brain. Lastly samples can be obtained from shunts that have been placed either in the spinal column or in the ventricles. Up to 20 mL of fluid can be obtained for analysis and is collected 2-4 mL at a time into three separate sterile tubes. Each tube should be labeled in the order that it is collected. The first tube collected is used for the analysis of chemistries, serology, and if needed a beginning cell count. The second tube is used for microbiological analysis. The third tube is used for a final cell count and morphology. Cell counts should be done within one hour of collection since cells degrade rapidly in CSF. Cell counts can also be paired (performed on tubes 1 & 3) in order to rule out the presence of contamination due to a traumatic tap.
In a normal healthy patient CSF is clear, colorless, and contains only a few cells. It can have up to five leukocytes per cmm but should not have any erythrocytes present. The leukocytes most often seen are lymphocytes and monocytes. Because the brain requires proteins and glucose for nourishment it is normal to find these molecules in CSF. A normal sample of CSF has a total protein level around 15-45 mg/mL and a glucose level around 40-70 mg/mL. These values can change in response to a disruption in the blood-brain barrier. There are several instances where CSF protein levels will be increased. Mild increases can occur due to inflammation caused by diseases such as meningitis, encephalitis, presence of tumors, hemorrhage, and stroke. Bacterial meningitis will cause a much larger increase in CSF protein concentration. Severe increases in protein concentration can be found in patients with Guillain-Barre syndrome. For patients with multiple sclerosis the increase in protein concentration is mild however there will be a specific elevation in IgG which can be quantified via separate testing. A decrease in CSF protein concentration is a sign that the body is producing CSF rapidly either due to illness or injury. Increases in CSF glucose are a reflection of high serum glucose levels. Most often CSF glucose concentrations will present as normal to decreased. A decrease in CSF glucose can be a sign of bacterial or fungal infection as these organisms utilize the glucose available to them. Tumors and leukocytes will also utilize glucose and increased concentrations of these cells can lead to a decrease in the concentration of CSF glucose. When performing a cell count and differential it is important to note the numbers and types of cells found in CSF. Increases in the amount of leukocytes present can be indicative of infection, stroke, or tumors. Neutrophils will be more abundant in bacterial infections while lymphocytes and monocytes will be more abundant in viral infections and malignancies. The presence of erythrocytes can be indicative of a bleed either in the brain or the spinal cord. However blood can be introduced into a CSF sample as the result of a traumatic tap. It is also important to note that high levels of erythrocytes can falsely increase the concentration of CSF protein. This can occur even when the sample is full of degraded erythrocytes and appears xanthochromic in color.
Cerebral spinal fluid analysis is an important tool available to doctors when diagnosing patients. The brain and spinal cord are well protected by the body; however in the event of illness or injury they can become compromised. It is imperative to perform analysis of samples quickly in order to gain the most accurate picture of a patient’s condition. This valuable analysis allows clinicians to properly treat patients and save lives.
References
*Turgeon, M. L., Clinical Hematology Theory and Procedures. Boston/Toronto/London: Little, Brown & Company (1993). p. 406.
*Cerebrospinal Fluid. (2008). Chapter Fourteen: Cerebrospinal Fluid. Neuropathology Web. Retrieved on May 29, 2010 from http://www.neuropathologyweb.org/chapter14/chapter14CSF.html
*Cerebral Spinal Fluid Collection. (2010). Cerebral Spinal Fluid Collection. Medline Plus. Retrieved on May 29, 2010 from http://www.nlm.nih.gov/medlineplus/ency/article/003428.htm
CSF can be collected for both therapeutic and diagnostic purposes. In the event that intracranial pressure is increased CSF can be collected in order to relieve pressure inside the brain. CSF obtained for laboratory analysis can reveal the presence of inflammation, trauma, infections, or even malignancies. CSF can be collected from a variety of sites, however it is most often collected using a lumbar puncture. In this case a needle is inserted into the space between vertebrae in the lumbar portion of the spine in order to remove CSF. In the event that a lumbar puncture cannot be performed a cisternal puncture or a ventricular puncture can be used. A cisternal puncture is done with fluoroscopy, and involves placing the needle below the occipital bone of the skull in order to obtain a sample. A ventricular puncture is usually done in the operating room and involves inserting a needle directing into one of the ventricles of the brain. Lastly samples can be obtained from shunts that have been placed either in the spinal column or in the ventricles. Up to 20 mL of fluid can be obtained for analysis and is collected 2-4 mL at a time into three separate sterile tubes. Each tube should be labeled in the order that it is collected. The first tube collected is used for the analysis of chemistries, serology, and if needed a beginning cell count. The second tube is used for microbiological analysis. The third tube is used for a final cell count and morphology. Cell counts should be done within one hour of collection since cells degrade rapidly in CSF. Cell counts can also be paired (performed on tubes 1 & 3) in order to rule out the presence of contamination due to a traumatic tap.
In a normal healthy patient CSF is clear, colorless, and contains only a few cells. It can have up to five leukocytes per cmm but should not have any erythrocytes present. The leukocytes most often seen are lymphocytes and monocytes. Because the brain requires proteins and glucose for nourishment it is normal to find these molecules in CSF. A normal sample of CSF has a total protein level around 15-45 mg/mL and a glucose level around 40-70 mg/mL. These values can change in response to a disruption in the blood-brain barrier. There are several instances where CSF protein levels will be increased. Mild increases can occur due to inflammation caused by diseases such as meningitis, encephalitis, presence of tumors, hemorrhage, and stroke. Bacterial meningitis will cause a much larger increase in CSF protein concentration. Severe increases in protein concentration can be found in patients with Guillain-Barre syndrome. For patients with multiple sclerosis the increase in protein concentration is mild however there will be a specific elevation in IgG which can be quantified via separate testing. A decrease in CSF protein concentration is a sign that the body is producing CSF rapidly either due to illness or injury. Increases in CSF glucose are a reflection of high serum glucose levels. Most often CSF glucose concentrations will present as normal to decreased. A decrease in CSF glucose can be a sign of bacterial or fungal infection as these organisms utilize the glucose available to them. Tumors and leukocytes will also utilize glucose and increased concentrations of these cells can lead to a decrease in the concentration of CSF glucose. When performing a cell count and differential it is important to note the numbers and types of cells found in CSF. Increases in the amount of leukocytes present can be indicative of infection, stroke, or tumors. Neutrophils will be more abundant in bacterial infections while lymphocytes and monocytes will be more abundant in viral infections and malignancies. The presence of erythrocytes can be indicative of a bleed either in the brain or the spinal cord. However blood can be introduced into a CSF sample as the result of a traumatic tap. It is also important to note that high levels of erythrocytes can falsely increase the concentration of CSF protein. This can occur even when the sample is full of degraded erythrocytes and appears xanthochromic in color.
Cerebral spinal fluid analysis is an important tool available to doctors when diagnosing patients. The brain and spinal cord are well protected by the body; however in the event of illness or injury they can become compromised. It is imperative to perform analysis of samples quickly in order to gain the most accurate picture of a patient’s condition. This valuable analysis allows clinicians to properly treat patients and save lives.
References
*Turgeon, M. L., Clinical Hematology Theory and Procedures. Boston/Toronto/London: Little, Brown & Company (1993). p. 406.
*Cerebrospinal Fluid. (2008). Chapter Fourteen: Cerebrospinal Fluid. Neuropathology Web. Retrieved on May 29, 2010 from http://www.neuropathologyweb.org/chapter14/chapter14CSF.html
*Cerebral Spinal Fluid Collection. (2010). Cerebral Spinal Fluid Collection. Medline Plus. Retrieved on May 29, 2010 from http://www.nlm.nih.gov/medlineplus/ency/article/003428.htm
Sunday, July 11, 2010
Antibodies against Influenza
Antibody may help treat and prevent influenza outbreaks
ScienceDaily (2010-07-10) -- Researchers have discovered a monoclonal antibody that is effective against "avian" H5N1, seasonal H1N1 and the 2009 "swine" H1N1 influenza. Scientists have shown that this antibody potently prevents and treats the swine H1N1 influenza in mouse models of the disease. ... > read full article
Saturday, July 3, 2010
Erythrocyte Inclusions
There are various types of erythrocyte inclusions that can be found when performing a peripheral smear. While some inclusions can be seen using a Wright’s stain, other inclusions can only be viewed with special staining. Each type of inclusion has its own unique properties and associated disease states. It is important for the purposes of a diagnosis that inclusions are noted when found while performing a differential.
Reticulocytes are the most common type of erythrocytes containing inclusions. A reticulocyte is a young erythrocyte that has extruded its nucleus leaving behind reticulum. This is a normal part of the maturation cycle of erythrocytes. This reticulum can appear an even bluish color or a patchy bluish-orange color under a Wright’s stain. This is referred to a polychromatophilia. In order to visualize the inclusions in reticulocytes a peripheral smear can be stained with new methylene blue. Under this stain the inclusions will appear either as filaments or as granules. It is normal for adults to have 0.5 to 1.5% reticulocytes. In general the amount of reticulocytes present is proportional to the production of erythrocytes. In cases of hemorrhage or severe red cell destruction the percentage of reticulocytes present will increase. In the case of chronic anemia or other diseases of defective erythrocyte production the percentage of reticulocytes will be decreased. Reticulocyte counts can be performed manually using new methylene blue stain and counting the cells on a hemocytometer. Most laboratories have instrumentation that will perform this count.
Basophilic stippling, Howell-Jolly bodies, and siderotic granules are common types of erythrocyte inclusions that can be visualized using Wright’s stain. Basophilic stippling is the aggregation of ribosomal material within the erythrocyte. The cell appears basophilic or blue to purple in color, with the presence of dark bluish granules spread throughout the cell. These granules are seen in cases of abnormal heme synthesis and in lead intoxication. Howell-Jolly bodies are composed of nuclear material that has remained inside the erythrocyte after the nucleus has been extruded. The granules are large, round, and are not refractile. These inclusions are very dark in color. Howell-Jolly bodies are usually found in cases of splenectomy and in some hemolytic anemias. They are not usually found in iron-deficiency anemia. Siderotic granules, also known as Pappenheimer bodies, are inclusions that contain iron. These inclusions stain a faint blue color. Siderotic granules are smaller than Howell-Jolly bodies and are usually found in clusters of two or more, often to the side of the cell. These granules are often found after a splenectomy, or whenever hemoglobin synthesis is impaired. They are absent in iron-deficiency anemia. While it is normal to see an occasional Howell-Jolly body in a peripheral smear, the presence of basophilic stippling and siderotic granules is abnormal.
It is important to take note of any type of erythrocytic inclusions when performing a peripheral smear. Each type of inclusion is composed of its own unique cellular material and can be associated with various disease states. While some inclusions may present with similar characteristics closer inspection of the entire peripheral smear can help clarify which inclusions if any are present.
References
• Miale, J. B., Laboratory Medicine: Hematology. St. Louis, Missouri: The C.V. Mosby Company (1982). p. 486-489.
• Carr, J. H., Rodak, B.F., Clinical Hematology Atlas. St. Louis, Missouri: Elsevier Saunders (2004). p. 111-115.
Reticulocytes are the most common type of erythrocytes containing inclusions. A reticulocyte is a young erythrocyte that has extruded its nucleus leaving behind reticulum. This is a normal part of the maturation cycle of erythrocytes. This reticulum can appear an even bluish color or a patchy bluish-orange color under a Wright’s stain. This is referred to a polychromatophilia. In order to visualize the inclusions in reticulocytes a peripheral smear can be stained with new methylene blue. Under this stain the inclusions will appear either as filaments or as granules. It is normal for adults to have 0.5 to 1.5% reticulocytes. In general the amount of reticulocytes present is proportional to the production of erythrocytes. In cases of hemorrhage or severe red cell destruction the percentage of reticulocytes present will increase. In the case of chronic anemia or other diseases of defective erythrocyte production the percentage of reticulocytes will be decreased. Reticulocyte counts can be performed manually using new methylene blue stain and counting the cells on a hemocytometer. Most laboratories have instrumentation that will perform this count.
Basophilic stippling, Howell-Jolly bodies, and siderotic granules are common types of erythrocyte inclusions that can be visualized using Wright’s stain. Basophilic stippling is the aggregation of ribosomal material within the erythrocyte. The cell appears basophilic or blue to purple in color, with the presence of dark bluish granules spread throughout the cell. These granules are seen in cases of abnormal heme synthesis and in lead intoxication. Howell-Jolly bodies are composed of nuclear material that has remained inside the erythrocyte after the nucleus has been extruded. The granules are large, round, and are not refractile. These inclusions are very dark in color. Howell-Jolly bodies are usually found in cases of splenectomy and in some hemolytic anemias. They are not usually found in iron-deficiency anemia. Siderotic granules, also known as Pappenheimer bodies, are inclusions that contain iron. These inclusions stain a faint blue color. Siderotic granules are smaller than Howell-Jolly bodies and are usually found in clusters of two or more, often to the side of the cell. These granules are often found after a splenectomy, or whenever hemoglobin synthesis is impaired. They are absent in iron-deficiency anemia. While it is normal to see an occasional Howell-Jolly body in a peripheral smear, the presence of basophilic stippling and siderotic granules is abnormal.
It is important to take note of any type of erythrocytic inclusions when performing a peripheral smear. Each type of inclusion is composed of its own unique cellular material and can be associated with various disease states. While some inclusions may present with similar characteristics closer inspection of the entire peripheral smear can help clarify which inclusions if any are present.
References
• Miale, J. B., Laboratory Medicine: Hematology. St. Louis, Missouri: The C.V. Mosby Company (1982). p. 486-489.
• Carr, J. H., Rodak, B.F., Clinical Hematology Atlas. St. Louis, Missouri: Elsevier Saunders (2004). p. 111-115.
Friday, July 2, 2010
Carbon Nanotubes Form Ultrasensitive Biosensor to Detect Proteins
ScienceDaily (June 27, 2010) — A cluster of carbon nanotubes coated with a thin layer of protein-recognizing polymer form a biosensor capable of using electrochemical signals to detect minute amounts of proteins, which could provide a crucial new diagnostic tool for the detection of a range of illnesses, a team of Boston College researchers report in the journal Nature Nanotechnology.
The nanotube biosensor proved capable of detecting human ferritin, the primary iron-storing protein of cells, and E7 oncoprotein derived from human papillomavirus. Further tests using calmodulin showed the sensor could discriminate between varieties of the protein that take different shapes, according to the multi-disciplinary team of biologists, chemists and physicists.
Molecular imprinting techniques have shown that polymer structures can be used in the development of sensors capable of recognizing certain organic compounds, but recognizing proteins has presented a difficult set of challenges. The BC team used arrays of wire-like nanotubes -- approximately one 300th the size of a human hair -- coated with a non-conducting polymer coating capable of recognizing proteins with subpicogram per liter sensitivity.
Central to the function of the sensor are imprints of the protein molecules within the non-conducting polymer coating. Because the imprints reduce the thickness of the coating, these regions of the polymer register a lower level of impedance than the rest of the polymer insulator when contacted by the charges inherent to the proteins and an ionized saline solution. When a protein molecule drops into its mirror image, it fills the void in the insulator, allowing the nanotubes to register a corresponding change in impedance, signaling the presence of the protein, according to co-author Dong Cai, an associate research professor of Biology at BC.
The detection can be read in real time, instead of after days or weeks of laboratory analysis, meaning the nanotube molecular imprinting technique could pave the way for biosensors capable of detecting human papillomavirus or other viruses weeks sooner than available diagnostic techniques currently allow. As opposed to searching for the HPV antibody or cell-mediated immine responses after initial infection, the nanotube sensor can track the HPV protein directly. In addition, no chemical marker is required by the lebel-free electrochemical detection methods.
"In the case of some diseases, no one can be sure why someone is ill," said Cai. "All that may be known is that it might be a virus. At that time, the patient may not have detectable serum antibodies. So at a time when it is critical to obtain a diagnosis, there may not be any traces of the virus. You've basically lost your chance. Now we can detect surface proteins of the virus itself through molecular imprinting and do the analysis."
In addition to Cai and Professor of Biology Thomas C. Chiles, the Boston College team included Assistant Professor Jeffrey Chuang and researchers Chenjia Xu and Lu Zhang of the Department of Biology; Professor Mary Roberts of the Department of Chemistry; Professor Michael Naughton, Professor Zhifeng Ren and researchers Yucheng Lan, Ying Yu and Hengzhi Wang, and Huaizhou Zhao of the Department of Physics; and researchers Lu Ren, and Ying Yu, also affiliated with the Institute of Nanoscience and Nanotechnology at Central China Normal University.
Reprinted from ScienceDaily @
http://www.sciencedaily.com/releases/2010/06/100627155118.htm
The nanotube biosensor proved capable of detecting human ferritin, the primary iron-storing protein of cells, and E7 oncoprotein derived from human papillomavirus. Further tests using calmodulin showed the sensor could discriminate between varieties of the protein that take different shapes, according to the multi-disciplinary team of biologists, chemists and physicists.
Molecular imprinting techniques have shown that polymer structures can be used in the development of sensors capable of recognizing certain organic compounds, but recognizing proteins has presented a difficult set of challenges. The BC team used arrays of wire-like nanotubes -- approximately one 300th the size of a human hair -- coated with a non-conducting polymer coating capable of recognizing proteins with subpicogram per liter sensitivity.
Central to the function of the sensor are imprints of the protein molecules within the non-conducting polymer coating. Because the imprints reduce the thickness of the coating, these regions of the polymer register a lower level of impedance than the rest of the polymer insulator when contacted by the charges inherent to the proteins and an ionized saline solution. When a protein molecule drops into its mirror image, it fills the void in the insulator, allowing the nanotubes to register a corresponding change in impedance, signaling the presence of the protein, according to co-author Dong Cai, an associate research professor of Biology at BC.
The detection can be read in real time, instead of after days or weeks of laboratory analysis, meaning the nanotube molecular imprinting technique could pave the way for biosensors capable of detecting human papillomavirus or other viruses weeks sooner than available diagnostic techniques currently allow. As opposed to searching for the HPV antibody or cell-mediated immine responses after initial infection, the nanotube sensor can track the HPV protein directly. In addition, no chemical marker is required by the lebel-free electrochemical detection methods.
"In the case of some diseases, no one can be sure why someone is ill," said Cai. "All that may be known is that it might be a virus. At that time, the patient may not have detectable serum antibodies. So at a time when it is critical to obtain a diagnosis, there may not be any traces of the virus. You've basically lost your chance. Now we can detect surface proteins of the virus itself through molecular imprinting and do the analysis."
In addition to Cai and Professor of Biology Thomas C. Chiles, the Boston College team included Assistant Professor Jeffrey Chuang and researchers Chenjia Xu and Lu Zhang of the Department of Biology; Professor Mary Roberts of the Department of Chemistry; Professor Michael Naughton, Professor Zhifeng Ren and researchers Yucheng Lan, Ying Yu and Hengzhi Wang, and Huaizhou Zhao of the Department of Physics; and researchers Lu Ren, and Ying Yu, also affiliated with the Institute of Nanoscience and Nanotechnology at Central China Normal University.
Reprinted from ScienceDaily @
http://www.sciencedaily.com/releases/2010/06/100627155118.htm
Sunday, June 27, 2010
Gamma-glutamyl Transferase
Gamma-glutamyl transferase, abbreviated GGT, is a sensitive indicator of liver disease. While an increased value of GGT can indicate the presence of liver damage it cannot be used to pinpoint a condition causing the damage. Because it is nonspecific for liver damage it is used in conjunction with other liver enzymes such as alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). In some instances it is used together with ALP to determine if an elevated ALP is due to liver or bone disease.
Gamma-glutamyl transferase is an enzyme found in cells that acts upon peptides and compounds that contain a gamma-glutamyl group. It transfers the gamma-glutamyl group from these peptides and compounds to a different acceptor. GGT is found in all cells throughout the body with the exception of myocytes. The highest concentration of GGT levels are found in the kidneys and the liver. A serum GGT level is reflective mainly of liver GGT and has a half life of around four days. Both GGT and ALP are enzymes bound to the membranes of cells. While ALP can be found in both liver and bone cells, GGT is found in its greatest concentration within hepatocytes. When a liver becomes diseased it begins to produce more GGT and ALP, thus they are both good indicators of hepatic dysfunction.
GGT serum levels rise during various disease states. The highest elevations can be found in the case of biliary obstructions. In order to determine whether or not the obstruction is intra-hepatic versus post-hepatic a serum bilirubin can be run in conjunction with the GGT. An intra-hepatic obstruction will have only a small rise in the serum bilirubin whereas a post-hepatic obstruction will have a greatly elevated serum bilirubin. High concentrations of serum GGT can also be present in liver cancer and the GGT might be elevated even before other liver enzymes become elevated. Moderate elevations of serum GGT can be found in infectious hepatitis. Small increases in GGT can be found in fatty liver disease and drug or alcohol intoxication. Some of the drugs that can cause an elevated serum GGT include phenytoin, carbamazepine, phenobarbitol, steroids, and erythromycin. The most common liver aliment that presents with an elevated GGT is alcoholism. Acute ingestion of alcohol will cause a small elevation in serum GGT. This level will fall again as the liver processes the alcohol. When it comes to chronic alcoholics, about 75% will present with an elevated GGT that persists. In some cases disease states other than actual liver disease can cause GGT to be elevated. In the case of myocardial infarction and congestive heart failure it is believed that the lack of sufficient blood flow to the liver is enough to cause damage and elevate GGT levels. Pancreatitis and pancreatic cancer can also present with occasional elevated levels of GGT. In all cases it is important to evaluate GGT levels in conjunction with other laboratory values in order to determine a patient’s disease state.
The lab in which I work currently runs GGT on the DADE Dimension system. This test is a colormetric test that uses the reagents gamma-glutamyl-3-carboxy-4-niranilide (GCNA) and glycylglycine. If GGT is present in serum it acts as a catalyst and transfers the glutamyl group from GCNA to the molecule glycylglycine. During this transfer a molecule called 5-amino-2-nitrobenzoate is released and the concentration of this molecule is read at an absorbance of 405 nm. The amount of 5-amino-2-nitrobenzoate released is proportional to the concentration of GGT present in the serum. GGT levels are prone to interferences from hemolysis due to the presence of GGT in red blood cell membranes. Hemolysis will cause a false increase in GGT. High levels of bilirubin will also cause a GGT level to be falsely increased. Finally triglyceride levels over 60 mg/dL can cause a false decrease in GGT concentration. Normal ranges are age dependent and infants and children have higher levels than adults. For adults the normal range is around 5-85 U/L.
Gamma-glutamyl transferase is used by clinicians as indicator of liver disease. Since it is nonspecific for liver damage it should be used along side other liver enzymes to determine the presence of liver disease. Comparing GGT results alongside other liver enzymes can help a clinician better pinpoint the origin of disease in a patient. For instance running an ALP along side a GGT can help a clinician determine if a patient has bone disease versus liver disease. Also running a bilirubin and liver panel alongside a GGT can help a clinician determine if an obstruction in the gastrointestinal tract is pre-hepatic or post-hepatic. Although it is a very little used test in the laboratory it is still a valuable tool that laboratory technicians can offer to clinicians for the purpose of diagnosing patients.
References
• Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p. 458, 612-613,1797.
• GGT. (2010). GGT: The Test. Lab Tests Online. Retrieved on March 21, 2010 from http://www.labtestsonline.org/understanding/analytes/ggt/test.html
• SIEMENS Dimension Flex reagent cartridge. (2008). GGT. (REF DF45A). Newark, DE: Siemens Healthcare Diagnostics Inc.
• GGT. (2000). SydPath: GGT. SydPath: The Institute of Laboratory Medicine. Retrieved on March 21, 2010 from http://www.sydpath.stvincents.com.au/ tests/GGT.htm
Gamma-glutamyl transferase is an enzyme found in cells that acts upon peptides and compounds that contain a gamma-glutamyl group. It transfers the gamma-glutamyl group from these peptides and compounds to a different acceptor. GGT is found in all cells throughout the body with the exception of myocytes. The highest concentration of GGT levels are found in the kidneys and the liver. A serum GGT level is reflective mainly of liver GGT and has a half life of around four days. Both GGT and ALP are enzymes bound to the membranes of cells. While ALP can be found in both liver and bone cells, GGT is found in its greatest concentration within hepatocytes. When a liver becomes diseased it begins to produce more GGT and ALP, thus they are both good indicators of hepatic dysfunction.
GGT serum levels rise during various disease states. The highest elevations can be found in the case of biliary obstructions. In order to determine whether or not the obstruction is intra-hepatic versus post-hepatic a serum bilirubin can be run in conjunction with the GGT. An intra-hepatic obstruction will have only a small rise in the serum bilirubin whereas a post-hepatic obstruction will have a greatly elevated serum bilirubin. High concentrations of serum GGT can also be present in liver cancer and the GGT might be elevated even before other liver enzymes become elevated. Moderate elevations of serum GGT can be found in infectious hepatitis. Small increases in GGT can be found in fatty liver disease and drug or alcohol intoxication. Some of the drugs that can cause an elevated serum GGT include phenytoin, carbamazepine, phenobarbitol, steroids, and erythromycin. The most common liver aliment that presents with an elevated GGT is alcoholism. Acute ingestion of alcohol will cause a small elevation in serum GGT. This level will fall again as the liver processes the alcohol. When it comes to chronic alcoholics, about 75% will present with an elevated GGT that persists. In some cases disease states other than actual liver disease can cause GGT to be elevated. In the case of myocardial infarction and congestive heart failure it is believed that the lack of sufficient blood flow to the liver is enough to cause damage and elevate GGT levels. Pancreatitis and pancreatic cancer can also present with occasional elevated levels of GGT. In all cases it is important to evaluate GGT levels in conjunction with other laboratory values in order to determine a patient’s disease state.
The lab in which I work currently runs GGT on the DADE Dimension system. This test is a colormetric test that uses the reagents gamma-glutamyl-3-carboxy-4-niranilide (GCNA) and glycylglycine. If GGT is present in serum it acts as a catalyst and transfers the glutamyl group from GCNA to the molecule glycylglycine. During this transfer a molecule called 5-amino-2-nitrobenzoate is released and the concentration of this molecule is read at an absorbance of 405 nm. The amount of 5-amino-2-nitrobenzoate released is proportional to the concentration of GGT present in the serum. GGT levels are prone to interferences from hemolysis due to the presence of GGT in red blood cell membranes. Hemolysis will cause a false increase in GGT. High levels of bilirubin will also cause a GGT level to be falsely increased. Finally triglyceride levels over 60 mg/dL can cause a false decrease in GGT concentration. Normal ranges are age dependent and infants and children have higher levels than adults. For adults the normal range is around 5-85 U/L.
Gamma-glutamyl transferase is used by clinicians as indicator of liver disease. Since it is nonspecific for liver damage it should be used along side other liver enzymes to determine the presence of liver disease. Comparing GGT results alongside other liver enzymes can help a clinician better pinpoint the origin of disease in a patient. For instance running an ALP along side a GGT can help a clinician determine if a patient has bone disease versus liver disease. Also running a bilirubin and liver panel alongside a GGT can help a clinician determine if an obstruction in the gastrointestinal tract is pre-hepatic or post-hepatic. Although it is a very little used test in the laboratory it is still a valuable tool that laboratory technicians can offer to clinicians for the purpose of diagnosing patients.
References
• Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p. 458, 612-613,1797.
• GGT. (2010). GGT: The Test. Lab Tests Online. Retrieved on March 21, 2010 from http://www.labtestsonline.org/understanding/analytes/ggt/test.html
• SIEMENS Dimension Flex reagent cartridge. (2008). GGT. (REF DF45A). Newark, DE: Siemens Healthcare Diagnostics Inc.
• GGT. (2000). SydPath: GGT. SydPath: The Institute of Laboratory Medicine. Retrieved on March 21, 2010 from http://www.sydpath.stvincents.com.au/ tests/GGT.htm
Kidney Disease
The kidneys are the main organs in the body responsible for filtering waste products out of the bloodstream. They are responsible for filtering out the waste that is not needed and reabsorbing the chemicals and water that can still be utilized by the body. On a daily basis the kidneys process approximately two hundred quarts of blood and filter out two quarts of waste material which becomes urine. If we did not have the kidneys to remove these waste products from the blood they would quickly build up and begin to severely damage the body.
The actual point where filtration occurs in the kidney is in units called nephrons. Inside the millions of nephrons in each kidney rest a glomerulus, which is a tiny cluster of blood vessels surrounding a urine collection tubule. The capillaries of the glomerulus are very permeable allowing wastes and water to pass into the urine tubules while keeping proteins and blood in the bloodstream. Most diseases of the kidneys attack this portion of the kidney. A healthy person has 100% kidney function and most people could live with 30-40% kidney function without noticing any ill health effects. Serious effects on health occur when kidney function falls below 25% and end stage renal disease is classified as renal function below 15%.
Kidney disease is caused by damage to either the vasculature inside the nephron or to the structure inside the organ. The two most common causes of chronic kidney disease are Diabetes and Hypertension. Diabetes causes glucose to build up in the blood and poison the kidney. Unused glucose gets filtered out by the kidney causing damage to the vessels in the glomeruli over time. Hypertension causes damage to the vessels in the glomeruli just as it causes damage to all the blood vessels in the body. In both cases, as the vessels are damaged the walls thicken and the nephrons can no longer filter wastes at full capacity. Other diseases attack the glomeruli such as infections, sclerotic diseases, and autoimmune diseases. Once again, the vessels harden up with damage and cannot filter blood properly. Polycystic kidney disease is a genetic disorder where cysts grow inside the kidney causing structural damage. The cysts grow and eventually replace the mass of the kidney causing kidney failure. Drugs and poisons can cause kidney damage by damaging the glomeruli. Physical trauma can cause structural damage as can obstructions like kidney stones and tumors. Even something like an enlarged prostate gland in men can cause kidney damage. Whether kidney failure is acute (AKF) or chronic (CKF) doctors rely on laboratory tests to help determine on how to diagnose and treat the patient.
There is no one test that can assess kidney function. The clinician uses a variety of tests on both serum and urine to assess a patient’s level of kidney function. The most commonly known test is serum creatinine. Creatinine is a waste product of various bodily processes, especially muscle activity. It is carried by the bloodstream to the kidneys where it is freely filtered by the glomerulus. Some creatinine gets reabsorbed by the tubules and reused by the body. Normal levels are age dependent and can range anywhere between 0.2-1.3 mg/dL depending on the laboratory. An elevation in serum creatinine is usually a sign that the kidneys are not functioning properly. However estimating kidney function based on old creatinine kidney function formulas is not entirely accurate. The Glomerular Filtration Rate (GFR) calculation was developed to increase the accuracy of accessing kidney function. The calculation is based on values for serum creatinine, age, gender, and race. A true Gomerular Filtration Rate test measures glomerular filtration by injecting the patient with a tracable form of insulin, collecting a twenty-four hour urine, and then testing the urine for the analyte to see how much is recovered. Based on this original test the estimated GFR calculation was developed. The calculation is a cost effective solution to collecting twenty-four hour urines and still measures the functioning renal mass and filtering capacity of the kidneys. GFR’s are said to be “normalized” for body surface area. Normalizing allows for the calculated GFR to be run on people of various body sizes by setting the body surface area (BSA) value in the equation at 1.73m2. In general the normal range for the GFR is >60 ml/min/1.73m2 for both African Americans (GRFAA) and non- African Americans (GFRNA). When assessing chronic kidney disease GFR values between 30 and 59 are indicative a moderate decrease in kidney function. GFR values between 15 and 29 are indicative of a severe reduction of kidney function, and a GFR less than 15 is labeled as kidney failure.
Another test to measure functioning renal mass and filtering capacity of the kidneys is the Creatinine Clearance. This test is also performed on at twenty-four hour urine collection and it approximates the rate that creatinine is filtered out by the glomeruli of the kidneys. However because creatinine is reabsorbed by the tubules this test is not as accurate as the GFR at assessing renal function. Normal range for a creatinine clearance is around 88-128 ml/min but can vary between laboratories. For a random urine creatinine the range is 30-125 mg/dL and for a twenty-four hour urine creatine the range is 600-2500mg/24hr. Checking for urine creatinine becomes more valuable when it can be compared with a urine protein.
Kidney disease is usually first detected by the presence of persistent proteinuria. Random spot checks for protein are done with every urinalysis. When a urinalysis comes back positive for protein a clinician will usually order a urine creatinine, a urine protein, and possibly a microalbumin. These three tests can help determine what level of kidney disease, if any, a patient is experiencing. Healthy kidneys do not release protein into the urine. When a glomerulus becomes damaged proteins can leak through causing even more damage. In early stages of kidney disease when damage is small only small proteins will leak through such as albumin. Once this occurs the patient is said to have microalbuminuria. This is usually seen in patients such as diabetics. The clinician will order a urine microalbumin level. Some doctors call the microalbumin test an albumin to creatinine ratio. This ratio compares the two values to determine the level of kidney function of the patient. In general a normal range for a random microalbumin is <30 mg Mcalb/g Creat. Microalbumin testing is also used to continuously monitor patients, such as diabetics, who are already known to have kidney disease. Because microalbumin testing is looking for such small amounts of protein one should take note that certain conditions can give false positives. Uncontrolled diabetes, uncontrolled hypertension, menstrual contamination, infection, and even strenuous exercise can elevate microalbumin results. These conditions should be taken into consideration before testing the patient. Once the glomeruli become moderately to severely damaged, larger proteins begin to pass through into the urine. The patient is said to have proteinuria. At this point there is no need to test just for small amounts of albumin. A urine total protein will test for all types of protein that are leaking into the urine. In general normal range for a random total urine protein is <11.9 mg/dL and the range for a twenty-four hour total urine protein is <149.1 mg/24hr. There is merit to running twenty-four hour urines in that they offer more accuracy in measurement than random urine testing. If the clinician wants to know what types of protein are in the urine, samples can be sent out for chromatographic and electrophoretic testing. The benefit of knowing what types of proteins are in the urine can help out in instances of autoimmune and hereditary kidney diseases. Once testing has confirmed the presence of kidney damage the clinician can take the best course of action to ensure that remaining kidney function is stabilized.
Even though a person can live a normal life with a significant reduction in kidney function, kidney damage is irreversible. Persons with known chronic diseases such as diabetes and hypertension should take care to have their clinician monitor their kidney function. The easiest way to detect kidney problems is with a spot urine protein test, a serum creatinine, and a calculated GFR. Diabetics should have their microalbumin/creatinine ratios checked yearly to monitor for the onset of kidney disease. For everyone the best way to ensure that the kidneys stay healthy is to control glucose levels, blood pressure, cholesterol levels, and not smoke. Having healthy blood vessels will ensure that you have a healthy heart and healthy kidneys.
References
• Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p.797-815.
• The Kidneys and How They Work. (2009).National Kidney and Urologic Diseases Information Clearinghouse: The Kidneys and How They Work. Retrieved on November 28, 2009 from http://kidney.niddk.nih.gov/Kudiseases/pubs/yourkidneys/
• FAQs About the Glomerular Filtration Rate. (2003). The IHS Provider: FAQs About the Glomerular Filtration Rate. Retrieved on November 28, 2009 from http://www.ihs.gov/medicalprograms/kidney/pro_clinicaltools/FAQsaboutGFR.pdf.
• Chronic Kidney Disease. (2009). National Kidney Foundation: Chronic Kidney Disease. Retrieved on November 28, 2009 from http://www.kidney.org/kidneydisease/ckd/index/cfm.
The actual point where filtration occurs in the kidney is in units called nephrons. Inside the millions of nephrons in each kidney rest a glomerulus, which is a tiny cluster of blood vessels surrounding a urine collection tubule. The capillaries of the glomerulus are very permeable allowing wastes and water to pass into the urine tubules while keeping proteins and blood in the bloodstream. Most diseases of the kidneys attack this portion of the kidney. A healthy person has 100% kidney function and most people could live with 30-40% kidney function without noticing any ill health effects. Serious effects on health occur when kidney function falls below 25% and end stage renal disease is classified as renal function below 15%.
Kidney disease is caused by damage to either the vasculature inside the nephron or to the structure inside the organ. The two most common causes of chronic kidney disease are Diabetes and Hypertension. Diabetes causes glucose to build up in the blood and poison the kidney. Unused glucose gets filtered out by the kidney causing damage to the vessels in the glomeruli over time. Hypertension causes damage to the vessels in the glomeruli just as it causes damage to all the blood vessels in the body. In both cases, as the vessels are damaged the walls thicken and the nephrons can no longer filter wastes at full capacity. Other diseases attack the glomeruli such as infections, sclerotic diseases, and autoimmune diseases. Once again, the vessels harden up with damage and cannot filter blood properly. Polycystic kidney disease is a genetic disorder where cysts grow inside the kidney causing structural damage. The cysts grow and eventually replace the mass of the kidney causing kidney failure. Drugs and poisons can cause kidney damage by damaging the glomeruli. Physical trauma can cause structural damage as can obstructions like kidney stones and tumors. Even something like an enlarged prostate gland in men can cause kidney damage. Whether kidney failure is acute (AKF) or chronic (CKF) doctors rely on laboratory tests to help determine on how to diagnose and treat the patient.
There is no one test that can assess kidney function. The clinician uses a variety of tests on both serum and urine to assess a patient’s level of kidney function. The most commonly known test is serum creatinine. Creatinine is a waste product of various bodily processes, especially muscle activity. It is carried by the bloodstream to the kidneys where it is freely filtered by the glomerulus. Some creatinine gets reabsorbed by the tubules and reused by the body. Normal levels are age dependent and can range anywhere between 0.2-1.3 mg/dL depending on the laboratory. An elevation in serum creatinine is usually a sign that the kidneys are not functioning properly. However estimating kidney function based on old creatinine kidney function formulas is not entirely accurate. The Glomerular Filtration Rate (GFR) calculation was developed to increase the accuracy of accessing kidney function. The calculation is based on values for serum creatinine, age, gender, and race. A true Gomerular Filtration Rate test measures glomerular filtration by injecting the patient with a tracable form of insulin, collecting a twenty-four hour urine, and then testing the urine for the analyte to see how much is recovered. Based on this original test the estimated GFR calculation was developed. The calculation is a cost effective solution to collecting twenty-four hour urines and still measures the functioning renal mass and filtering capacity of the kidneys. GFR’s are said to be “normalized” for body surface area. Normalizing allows for the calculated GFR to be run on people of various body sizes by setting the body surface area (BSA) value in the equation at 1.73m2. In general the normal range for the GFR is >60 ml/min/1.73m2 for both African Americans (GRFAA) and non- African Americans (GFRNA). When assessing chronic kidney disease GFR values between 30 and 59 are indicative a moderate decrease in kidney function. GFR values between 15 and 29 are indicative of a severe reduction of kidney function, and a GFR less than 15 is labeled as kidney failure.
Another test to measure functioning renal mass and filtering capacity of the kidneys is the Creatinine Clearance. This test is also performed on at twenty-four hour urine collection and it approximates the rate that creatinine is filtered out by the glomeruli of the kidneys. However because creatinine is reabsorbed by the tubules this test is not as accurate as the GFR at assessing renal function. Normal range for a creatinine clearance is around 88-128 ml/min but can vary between laboratories. For a random urine creatinine the range is 30-125 mg/dL and for a twenty-four hour urine creatine the range is 600-2500mg/24hr. Checking for urine creatinine becomes more valuable when it can be compared with a urine protein.
Kidney disease is usually first detected by the presence of persistent proteinuria. Random spot checks for protein are done with every urinalysis. When a urinalysis comes back positive for protein a clinician will usually order a urine creatinine, a urine protein, and possibly a microalbumin. These three tests can help determine what level of kidney disease, if any, a patient is experiencing. Healthy kidneys do not release protein into the urine. When a glomerulus becomes damaged proteins can leak through causing even more damage. In early stages of kidney disease when damage is small only small proteins will leak through such as albumin. Once this occurs the patient is said to have microalbuminuria. This is usually seen in patients such as diabetics. The clinician will order a urine microalbumin level. Some doctors call the microalbumin test an albumin to creatinine ratio. This ratio compares the two values to determine the level of kidney function of the patient. In general a normal range for a random microalbumin is <30 mg Mcalb/g Creat. Microalbumin testing is also used to continuously monitor patients, such as diabetics, who are already known to have kidney disease. Because microalbumin testing is looking for such small amounts of protein one should take note that certain conditions can give false positives. Uncontrolled diabetes, uncontrolled hypertension, menstrual contamination, infection, and even strenuous exercise can elevate microalbumin results. These conditions should be taken into consideration before testing the patient. Once the glomeruli become moderately to severely damaged, larger proteins begin to pass through into the urine. The patient is said to have proteinuria. At this point there is no need to test just for small amounts of albumin. A urine total protein will test for all types of protein that are leaking into the urine. In general normal range for a random total urine protein is <11.9 mg/dL and the range for a twenty-four hour total urine protein is <149.1 mg/24hr. There is merit to running twenty-four hour urines in that they offer more accuracy in measurement than random urine testing. If the clinician wants to know what types of protein are in the urine, samples can be sent out for chromatographic and electrophoretic testing. The benefit of knowing what types of proteins are in the urine can help out in instances of autoimmune and hereditary kidney diseases. Once testing has confirmed the presence of kidney damage the clinician can take the best course of action to ensure that remaining kidney function is stabilized.
Even though a person can live a normal life with a significant reduction in kidney function, kidney damage is irreversible. Persons with known chronic diseases such as diabetes and hypertension should take care to have their clinician monitor their kidney function. The easiest way to detect kidney problems is with a spot urine protein test, a serum creatinine, and a calculated GFR. Diabetics should have their microalbumin/creatinine ratios checked yearly to monitor for the onset of kidney disease. For everyone the best way to ensure that the kidneys stay healthy is to control glucose levels, blood pressure, cholesterol levels, and not smoke. Having healthy blood vessels will ensure that you have a healthy heart and healthy kidneys.
References
• Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p.797-815.
• The Kidneys and How They Work. (2009).National Kidney and Urologic Diseases Information Clearinghouse: The Kidneys and How They Work. Retrieved on November 28, 2009 from http://kidney.niddk.nih.gov/Kudiseases/pubs/yourkidneys/
• FAQs About the Glomerular Filtration Rate. (2003). The IHS Provider: FAQs About the Glomerular Filtration Rate. Retrieved on November 28, 2009 from http://www.ihs.gov/medicalprograms/kidney/pro_clinicaltools/FAQsaboutGFR.pdf.
• Chronic Kidney Disease. (2009). National Kidney Foundation: Chronic Kidney Disease. Retrieved on November 28, 2009 from http://www.kidney.org/kidneydisease/ckd/index/cfm.
Transudates vs. Exudates
There are various places in the body where fluids can accumulate. When fluids accumulate inside a cavity they are referred to as effusions. Effusions can occur in the pleural, pericardial, and peritoneal cavities of the body. Since it is not natural for fluids to accumulate in theses spaces it is important that they be tested by a laboratory in order to determine the cause of the accumulation. Effusions are classified as either transudates or exudates. Laboratory testing is performed in order to determine whether a fluid is a transudate or an exudate.
Classifying a fluid as a transudate or an exudate can help clinicians determine what disease process is causing fluid to accumulate and enables them to proceed with subsequent treatment. All organs in the body have their own linings that help to protect the organ and are filtered by the lymphatic system. In order for these linings to work properly they must be permeable and allow for the transfer of fluids, proteins, and other metabolites between them. A transudate is a fluid that accumulates in cavities due to a malfunction of the filtering membranes of cavity linings. A malfunction in a membrane can be caused by organ disease or by the back up of the lymphatic system. These systemic disease processes cause the fluid balance between the linings to become disrupted which in turn leads to the buildup of fluid on one side of the membrane. Transudates are usually found in conditions such as liver disease, pancreatic disease, and congestive heart failure. An exudate is a fluid that accumulates inside a cavity due to the presence of foreign materials such as bacteria, viruses, parasites, fungi, and tumor cells. The presence of infection or cancerous cells causes a response by the body that sends large numbers of leukocytes to respond to the site. An exudate forms as a result of all these cells (both leukocytes and foreign material) and their metabolites filling the cavity.
Several tests can be performed in the laboratory to determine if a fluid is either a transudate or an exudate. The results of these tests, specifically the chemistries, should be compared with baseline peripheral blood testing in order to determine the whether the results obtained from the fluid sample are normal or abnormal. This is done at the discretion of the clinician as most laboratories do not provide reference ranges for fluids. The major test used to differentiate between a transudate or an exudate is the concentration of total protein in a fluid. Transudates generally have total protein concentration less than 3.0 g/dL while exudates generally have a total protein greater than 3.0 g/dL. Another way of looking at this value is to compare it to the level of total protein found in the patient’s serum. A transudate will still have a low concentration of total protein while an exudate will generally have a concentration of total protein that is greater than half the concentration of total protein found in the serum. Other chemistry testing that can help to differentiate transudates from exudates includes lactate dehydrogenase (LDH), glucose, and amylase. Lactate dehydrogenase is an enzyme that is used by cells in metabolism and production of energy. When there is a large presence of cells and cell death such as in infection and inflammation the concentration of LDH in the area increases. Transudates will have LDH levels lower than 200 units/L while exudates will have LDH levels higher than 200 units/L. Another way of assessing the levels of LDH in fluid is to compare it to the concentration of LDH in serum. Transudates will have a fluid to serum ratio of LDH lower than 0.6 while exudates will have a ratio of fluid to serum LDH that is higher than 0.6. While the concentration of glucose in a fluid does not necessarily help to determine if a fluid is a transudate or an exudate, it can help determine what might be causing an exudate. Decreased values in the concentration of glucose in an exudate can occur in bacterial infections, malignancies, rheumatoid arthritis, and tuberculosis. The glucose levels in an exudate will be considerably lower in comparison with the serum glucose in these conditions. Like glucose, the purpose for measuring the concentration of amylase in a fluid is to help determine what might be causing an exudate. Concentrations of amylase can accumulate in an exudate in response to esophageal rupture, pancreatitis, and pancreatic cancer. No matter what chemistry testing is ordered on a fluid it is best to compare it in relation to serum levels to help assess whether a fluid is a transudate or an exudate.
Other testing that can help to differentiate between a transudate and an exudate includes noting the appearance of the fluid and performing a differentiated cell count. Transudates are generally clear and pale yellow in appearance as they are basically filtrates of plasma. These fluids contain very little cellular material. The leukocyte count is usually less than 1.0 X 109/L and the erythrocyte count is less than 100.0 X 109/L. The leukocytes that are present consist of monocytes and lymphocytes. On the other hand exudates have an opposite appearance. Exudates will generally appear cloudy or turbid. They can have a variety of colors; yellow, brown, greenish, and even bloody. In some instances they may even be clotted due to the presence of fibrinogen. Exudates will show an abundance of cellular material. The leukocyte count will usually be greater than 1.0 X 109/L and include neutrophils, lymphocytes, monocytes, eosinophils, and even basophils. The erythrocyte count will generally be greater than 100.0 X 109/L, however the count can be falsely increased in the event of a traumatic tap. In instances that an exudate is caused by infection it might be possible to visualize bacteria with a Wright’s stain; however it is more useful to perform a Gram Stain. Finally a cell count and differential can reveal the presence of cancer. Tumor cells can be seen in a peripheral smear and be sent for pathology review in order to determine what type of cancer is present in the patient. The results from both the hematology and chemistry testing of a fluid can help a clinician to determine what type of fluid is being produced by the body and why it is being produced.
Effusions that form within the body are classified as either transudates or exudates. Buildup of fluid most often occurs in the pleural, pericardial, and peritoneal cavities of the body. While it is natural to have a balance of fluid between these linings for the purpose of protection and lymphatic drainage, disease processes can upset this balance. Laboratory testing is performed in order to determine the cause for this buildup of fluid. Classifying a fluid as a transudate or and exudate allows clinicians to determine what disease processes might be occurring and how to subsequently treat them.
References
• Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p. 580.
• Ringsrud, K.M., Linne, J.J., Urinalysis & Body Fluids: A Colortext and Atlas. St. Louis, Missouri: Mosby-Year Book, Inc (1995). p. 202-203.
• Kjeldsberg, C.R., Knight, J.A., Body Fluids. Chicago: American Society of Clinical Pathologists (1986). p. 77-79, 92-93.
Classifying a fluid as a transudate or an exudate can help clinicians determine what disease process is causing fluid to accumulate and enables them to proceed with subsequent treatment. All organs in the body have their own linings that help to protect the organ and are filtered by the lymphatic system. In order for these linings to work properly they must be permeable and allow for the transfer of fluids, proteins, and other metabolites between them. A transudate is a fluid that accumulates in cavities due to a malfunction of the filtering membranes of cavity linings. A malfunction in a membrane can be caused by organ disease or by the back up of the lymphatic system. These systemic disease processes cause the fluid balance between the linings to become disrupted which in turn leads to the buildup of fluid on one side of the membrane. Transudates are usually found in conditions such as liver disease, pancreatic disease, and congestive heart failure. An exudate is a fluid that accumulates inside a cavity due to the presence of foreign materials such as bacteria, viruses, parasites, fungi, and tumor cells. The presence of infection or cancerous cells causes a response by the body that sends large numbers of leukocytes to respond to the site. An exudate forms as a result of all these cells (both leukocytes and foreign material) and their metabolites filling the cavity.
Several tests can be performed in the laboratory to determine if a fluid is either a transudate or an exudate. The results of these tests, specifically the chemistries, should be compared with baseline peripheral blood testing in order to determine the whether the results obtained from the fluid sample are normal or abnormal. This is done at the discretion of the clinician as most laboratories do not provide reference ranges for fluids. The major test used to differentiate between a transudate or an exudate is the concentration of total protein in a fluid. Transudates generally have total protein concentration less than 3.0 g/dL while exudates generally have a total protein greater than 3.0 g/dL. Another way of looking at this value is to compare it to the level of total protein found in the patient’s serum. A transudate will still have a low concentration of total protein while an exudate will generally have a concentration of total protein that is greater than half the concentration of total protein found in the serum. Other chemistry testing that can help to differentiate transudates from exudates includes lactate dehydrogenase (LDH), glucose, and amylase. Lactate dehydrogenase is an enzyme that is used by cells in metabolism and production of energy. When there is a large presence of cells and cell death such as in infection and inflammation the concentration of LDH in the area increases. Transudates will have LDH levels lower than 200 units/L while exudates will have LDH levels higher than 200 units/L. Another way of assessing the levels of LDH in fluid is to compare it to the concentration of LDH in serum. Transudates will have a fluid to serum ratio of LDH lower than 0.6 while exudates will have a ratio of fluid to serum LDH that is higher than 0.6. While the concentration of glucose in a fluid does not necessarily help to determine if a fluid is a transudate or an exudate, it can help determine what might be causing an exudate. Decreased values in the concentration of glucose in an exudate can occur in bacterial infections, malignancies, rheumatoid arthritis, and tuberculosis. The glucose levels in an exudate will be considerably lower in comparison with the serum glucose in these conditions. Like glucose, the purpose for measuring the concentration of amylase in a fluid is to help determine what might be causing an exudate. Concentrations of amylase can accumulate in an exudate in response to esophageal rupture, pancreatitis, and pancreatic cancer. No matter what chemistry testing is ordered on a fluid it is best to compare it in relation to serum levels to help assess whether a fluid is a transudate or an exudate.
Other testing that can help to differentiate between a transudate and an exudate includes noting the appearance of the fluid and performing a differentiated cell count. Transudates are generally clear and pale yellow in appearance as they are basically filtrates of plasma. These fluids contain very little cellular material. The leukocyte count is usually less than 1.0 X 109/L and the erythrocyte count is less than 100.0 X 109/L. The leukocytes that are present consist of monocytes and lymphocytes. On the other hand exudates have an opposite appearance. Exudates will generally appear cloudy or turbid. They can have a variety of colors; yellow, brown, greenish, and even bloody. In some instances they may even be clotted due to the presence of fibrinogen. Exudates will show an abundance of cellular material. The leukocyte count will usually be greater than 1.0 X 109/L and include neutrophils, lymphocytes, monocytes, eosinophils, and even basophils. The erythrocyte count will generally be greater than 100.0 X 109/L, however the count can be falsely increased in the event of a traumatic tap. In instances that an exudate is caused by infection it might be possible to visualize bacteria with a Wright’s stain; however it is more useful to perform a Gram Stain. Finally a cell count and differential can reveal the presence of cancer. Tumor cells can be seen in a peripheral smear and be sent for pathology review in order to determine what type of cancer is present in the patient. The results from both the hematology and chemistry testing of a fluid can help a clinician to determine what type of fluid is being produced by the body and why it is being produced.
Effusions that form within the body are classified as either transudates or exudates. Buildup of fluid most often occurs in the pleural, pericardial, and peritoneal cavities of the body. While it is natural to have a balance of fluid between these linings for the purpose of protection and lymphatic drainage, disease processes can upset this balance. Laboratory testing is performed in order to determine the cause for this buildup of fluid. Classifying a fluid as a transudate or and exudate allows clinicians to determine what disease processes might be occurring and how to subsequently treat them.
References
• Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p. 580.
• Ringsrud, K.M., Linne, J.J., Urinalysis & Body Fluids: A Colortext and Atlas. St. Louis, Missouri: Mosby-Year Book, Inc (1995). p. 202-203.
• Kjeldsberg, C.R., Knight, J.A., Body Fluids. Chicago: American Society of Clinical Pathologists (1986). p. 77-79, 92-93.
Sunday, June 20, 2010
Microfluidics Education
Using Inexpensive Jell-O Chips for Hands-On Microfluidics Education
This article presented in the latest edition of Analytical Chemistry teaches students and budding minds the principles of microfluidics. Microfluidics is the technology used to create new "lab-on-a-chip" testing that will one day be used in the health industry. The full article can be viewed here at http://pubs.acs.org/doi/full/10.1021/ac902926x
This article presented in the latest edition of Analytical Chemistry teaches students and budding minds the principles of microfluidics. Microfluidics is the technology used to create new "lab-on-a-chip" testing that will one day be used in the health industry. The full article can be viewed here at http://pubs.acs.org/doi/full/10.1021/ac902926x
Saturday, June 12, 2010
Urine Coloration
Within the clinical setting a routine urinalysis is performed to determine the health of a patient. This particular test can tell a physician how well a patient’s kidneys are functioning. The test can show not only if infection is present, but it can also show if other organ systems such as the rest of the digestive tract are performing properly. A urinalysis consists of two parts, a urine dipstick test and a urine microscopic test. The urine dipstick tests for the presence of leukocytes, nitrite, urobilinogen, protein, pH, blood, specific gravity, ketones, bilirubin, and glucose. During the microscopic scan a technologist looks for cellular material including white blood cells, red blood cells, bacteria, crystals, casts, epithelial cells, and other foreign materials that would not normally be found in urine. It is also necessary to report out urine color and clarity. These two mostly overlooked results help to complete the picture presented to the physician by a urinalysis report.
Urine can come in many different colors that amaze and excite the medical technologist (and not the patient), however in a normal healthy individual it should be a straw yellow color. The straw yellow color is attributed to urochrome, a pigment excreted into the urine as a result of hemoglobin degradation. Clear urine with little to no yellow color is an indicator of very dilute urine. This can be due to drinking too much water, taking diruetics, or diabetes insipidus. On the other hand dark yellow urine could be a sign that urine is over concentrated. This could be due to dehydration or due to an overproduction of the waste materials that give pigmentation to urine. Red cell destruction in the body (i.e. hemolytic anemia) would cause an increase in the concentration of urochrome pigment in the urine. Hepatitis can cause bilirubin to spill over into the urine in various amounts causing different shades of urine from yellow to brown. The next color in line is orange colored urine. While this could be a result of severe dehydration, it is most likely due to some other factor. The orange coloration of urine can be caused by bilirubin and urobilinogen being spilled over into the urine due to liver or other gastrointestinal diseases. Other less alarming causes of orange urine include food and drug sources. Rifampicin (antibiotic), coumadin, pyridium, and some chemotherapy drugs can all produce various shades of orange urine. Foods that can stain urine orange include vitamin C tablets, large amounts of carrots, and winter squash. The carotene in these vegetables is what discolors the urine and can discolor the palms of hands and soles of feet when eaten in large amounts. Pink colored urine is not very common. Usually it is indicative of a light amount of hematuria. Infrequent sightings of pink urine can be caused by anything from trauma received to the urinary tract when catheterized to intense exercising. Problems with the kidneys, bladder, and prostate are looked at more closely when the passing of pink urine becomes more frequent. Propofol (diprivan), a popular anesthetic, will also cause pink urine. In this case the chemical is a uricosuric agent and favors uric acid crystal formation. Urine from these patients is full of uric acid crystals, which gives it a reddish-pink hue. Red urine which is much more common than pink urine is usually a sure sign of gross hematuria. Common causes of hematuria include kidney stones, infection, and cancer. Keep in mind that the presence of blood in urine can also be due to menstruation or other contaminant bleeds from outside the body. Red urine can also be caused by benign factors such as food and drugs. Foods such as beetroot, rhubarb, and even blackberries can turn urine red. About 10-14% of the population will pass red urine after eating beetroot. Medications that will turn urine red include anisindione (anticoagulant), cerubidine (chemo), phenolphthalein (laxative), prochlorperazine (antipsychotic), senna (laxative), and thorazine (antipsychotic). Chronic lead or mercury poisoning can also turn urine red. In this case the red color of the urine is due to the porphyrins being excreted into the urine from the toxic effects of the metals. Brown or tea-colored urine can have a variety of causes. First and foremost the color can be caused by oxidized hemoglobin and myoglobin. Patients with major bleeds or trauma can produce this color urine due to build up of excess myoglobin and urochrome in the urine. Severe hepatitis or cirrhosis can cause urine to turn brown due to large amounts of biliruin. Other lesser known causes for brown urine include eating large amounts of foods such as fava beans, rhubarb, and aloe. There are several medications that will also turn urine brown. These medications include primaquine (antimalarial), metronidazole (antibiotic), nitrofurantoin (antibiotic), and methocarbamol (muscle relaxant). Blue to green colored urine, while pretty, is fairly rare. There are several medical and non medical causes that can be attributed to this color of urine. Medically speaking urinary tract infections can produce greenish colored urine due to pus buildup. Bile leakage from diarrhea can also tint urine a greenish color. Urinary tract infections caused by Pseudomonas aeruginosa will sometimes cause green colored urine if the pigment pyocyanin is produced. In very rare cases a baby might have what is known as blue diaper syndrome, where blue urine is found in the diaper. This is caused by a rare inherited disorder called familial hypercalcemia that causes the patient to have higher than normal levels of calcium. One of the traits of this disease is urine that turns blue upon contact with air. These strange colors can also be caused by foods and drugs. Eating large amounts of asparagus can lead to greenish colored urine. Drugs that can lead to blue or green urine include rinsapin (antibiotic), indomethacin, amitriptyline, triamterene (diuretic), listerine, tagamet, and phenergan (anti-nausea). Another strange and unusual color is purple. Purple urine has a select few known causes and all are medical. The classic cause is Hartnup disease which is a rare defect of tryptophan transport that results in purplish-blue urine. The other cause is urinary tract infections, most often in nursing home patients, caused by Klebsiella pneumoniae, E. coli, Proteus species, Morganella species, Enterobacter species, Pseudomonas species, and Providencia species. Most patients with these types of multiple organism urinary tract infections will also have intestinal stasis. Stasis of the intestines causes tryptophan to be oxidized to the pigment indican by bacterial flora. Once the indican is passed into the urine the bacteria in the urine ferment it using sulfatase and phosphatase. The pigments that give purple urine its color are indigo and indirubin. Once the urinary infection is treated the color of the urine returns to normal. The final abnormal color that can be found in urine is black. This is extremely rare. The first cause is a condition called alkaptonuria. This is caused by a genetic disorder where a patient is deficient in the enzyme homogentisic oxidase causing homogentisic acid to build up all over the body in the tissues. Homogentisic acid is expelled in the urine and once the urine becomes alkaline this acid oxidizes producing a black color. Patients with disseminated melanoma and rarely Addison’s disease can produce melanogens (melanin) which can be excreted in urine and cause black discoloration once urine becomes alkaline. The antihypertensive drug α-methyldopa also produces melanogens which can cause black colored urine. Whatever a person’s urine color may be, if it is frequently abnormal it is worth getting checked out by a physician.
The other half of the picture is urine clarity. While different labs have different gradients for determining the turbidity of urine there are really only two states of clarity; clear and cloudy. Normal urine is clear, meaning there is no particulate matter floating in it. It can have some bubbles to it but it should not be overly foamy. Foamy urine is a sign that the urine is heavy with protein materials and can occur in either clear or cloudy urine. Cloudy or “milky” urine can be a sign of several issues. The most obvious cause of cloudy urine is an infection. Bacteria and white blood cells will cause urine to become cloudy. Turbidity can also be due to light amounts of red cells. Other cellular material such as casts and crystals when excreted in high amounts can cause urine to cloud. Urine with high lipid content will look cloudy. On rare occasions vaginal contamination or semen discharge will be the culprit. Whatever the case may be a microscopic examination will clear up any questions concerning the cause of cloudy urine.
Just looking at a urine sample and determining its color and clarity can give a person a very good general idea of their state of health. It is a simple act that anyone can do. It only takes a minute but it can impact our health habits greatly. Urine gives us information about our dietary habits and tells us how well our bodies have processed what we have put into it. If the kidneys are the filters of the body, then urine should be the first place to look for indicators of disease in the event something goes awry in any of the other systems. Checking the color and clarity is just the first easy step towards creating the big diagnostic picture of a patient’s state of health.
References
• Urine Colors (2010). XebWeb Network. Retrieved on January 9, 2010 from http://www.urinecolors.com/
• Foot, C., Fraser, J. (2006). Uroscopic rainbow:modern matula medicine. Postgraduate Medical Journal, 82(964), 126-129. Retrieved on January 9, 2010 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596703/
• Health Topics (2009).Ohio Health. Retrieved on January 9, 2010 from http://www.ohiohealth.com/bodymayo.cfm?xyzpdqabc=0&id=6&action=detail&ref=4046
• Hanrun, N., Nainar, S., Chong, V. (2007). Purple Urine Bag Syndrome: A Rare and Interesting Phenomenon. Southern Medical Journal, 100(10), 1048-1050. Retrieved on January 9, 2010 from http://medscape.com/viewarticle/565078
Urine can come in many different colors that amaze and excite the medical technologist (and not the patient), however in a normal healthy individual it should be a straw yellow color. The straw yellow color is attributed to urochrome, a pigment excreted into the urine as a result of hemoglobin degradation. Clear urine with little to no yellow color is an indicator of very dilute urine. This can be due to drinking too much water, taking diruetics, or diabetes insipidus. On the other hand dark yellow urine could be a sign that urine is over concentrated. This could be due to dehydration or due to an overproduction of the waste materials that give pigmentation to urine. Red cell destruction in the body (i.e. hemolytic anemia) would cause an increase in the concentration of urochrome pigment in the urine. Hepatitis can cause bilirubin to spill over into the urine in various amounts causing different shades of urine from yellow to brown. The next color in line is orange colored urine. While this could be a result of severe dehydration, it is most likely due to some other factor. The orange coloration of urine can be caused by bilirubin and urobilinogen being spilled over into the urine due to liver or other gastrointestinal diseases. Other less alarming causes of orange urine include food and drug sources. Rifampicin (antibiotic), coumadin, pyridium, and some chemotherapy drugs can all produce various shades of orange urine. Foods that can stain urine orange include vitamin C tablets, large amounts of carrots, and winter squash. The carotene in these vegetables is what discolors the urine and can discolor the palms of hands and soles of feet when eaten in large amounts. Pink colored urine is not very common. Usually it is indicative of a light amount of hematuria. Infrequent sightings of pink urine can be caused by anything from trauma received to the urinary tract when catheterized to intense exercising. Problems with the kidneys, bladder, and prostate are looked at more closely when the passing of pink urine becomes more frequent. Propofol (diprivan), a popular anesthetic, will also cause pink urine. In this case the chemical is a uricosuric agent and favors uric acid crystal formation. Urine from these patients is full of uric acid crystals, which gives it a reddish-pink hue. Red urine which is much more common than pink urine is usually a sure sign of gross hematuria. Common causes of hematuria include kidney stones, infection, and cancer. Keep in mind that the presence of blood in urine can also be due to menstruation or other contaminant bleeds from outside the body. Red urine can also be caused by benign factors such as food and drugs. Foods such as beetroot, rhubarb, and even blackberries can turn urine red. About 10-14% of the population will pass red urine after eating beetroot. Medications that will turn urine red include anisindione (anticoagulant), cerubidine (chemo), phenolphthalein (laxative), prochlorperazine (antipsychotic), senna (laxative), and thorazine (antipsychotic). Chronic lead or mercury poisoning can also turn urine red. In this case the red color of the urine is due to the porphyrins being excreted into the urine from the toxic effects of the metals. Brown or tea-colored urine can have a variety of causes. First and foremost the color can be caused by oxidized hemoglobin and myoglobin. Patients with major bleeds or trauma can produce this color urine due to build up of excess myoglobin and urochrome in the urine. Severe hepatitis or cirrhosis can cause urine to turn brown due to large amounts of biliruin. Other lesser known causes for brown urine include eating large amounts of foods such as fava beans, rhubarb, and aloe. There are several medications that will also turn urine brown. These medications include primaquine (antimalarial), metronidazole (antibiotic), nitrofurantoin (antibiotic), and methocarbamol (muscle relaxant). Blue to green colored urine, while pretty, is fairly rare. There are several medical and non medical causes that can be attributed to this color of urine. Medically speaking urinary tract infections can produce greenish colored urine due to pus buildup. Bile leakage from diarrhea can also tint urine a greenish color. Urinary tract infections caused by Pseudomonas aeruginosa will sometimes cause green colored urine if the pigment pyocyanin is produced. In very rare cases a baby might have what is known as blue diaper syndrome, where blue urine is found in the diaper. This is caused by a rare inherited disorder called familial hypercalcemia that causes the patient to have higher than normal levels of calcium. One of the traits of this disease is urine that turns blue upon contact with air. These strange colors can also be caused by foods and drugs. Eating large amounts of asparagus can lead to greenish colored urine. Drugs that can lead to blue or green urine include rinsapin (antibiotic), indomethacin, amitriptyline, triamterene (diuretic), listerine, tagamet, and phenergan (anti-nausea). Another strange and unusual color is purple. Purple urine has a select few known causes and all are medical. The classic cause is Hartnup disease which is a rare defect of tryptophan transport that results in purplish-blue urine. The other cause is urinary tract infections, most often in nursing home patients, caused by Klebsiella pneumoniae, E. coli, Proteus species, Morganella species, Enterobacter species, Pseudomonas species, and Providencia species. Most patients with these types of multiple organism urinary tract infections will also have intestinal stasis. Stasis of the intestines causes tryptophan to be oxidized to the pigment indican by bacterial flora. Once the indican is passed into the urine the bacteria in the urine ferment it using sulfatase and phosphatase. The pigments that give purple urine its color are indigo and indirubin. Once the urinary infection is treated the color of the urine returns to normal. The final abnormal color that can be found in urine is black. This is extremely rare. The first cause is a condition called alkaptonuria. This is caused by a genetic disorder where a patient is deficient in the enzyme homogentisic oxidase causing homogentisic acid to build up all over the body in the tissues. Homogentisic acid is expelled in the urine and once the urine becomes alkaline this acid oxidizes producing a black color. Patients with disseminated melanoma and rarely Addison’s disease can produce melanogens (melanin) which can be excreted in urine and cause black discoloration once urine becomes alkaline. The antihypertensive drug α-methyldopa also produces melanogens which can cause black colored urine. Whatever a person’s urine color may be, if it is frequently abnormal it is worth getting checked out by a physician.
The other half of the picture is urine clarity. While different labs have different gradients for determining the turbidity of urine there are really only two states of clarity; clear and cloudy. Normal urine is clear, meaning there is no particulate matter floating in it. It can have some bubbles to it but it should not be overly foamy. Foamy urine is a sign that the urine is heavy with protein materials and can occur in either clear or cloudy urine. Cloudy or “milky” urine can be a sign of several issues. The most obvious cause of cloudy urine is an infection. Bacteria and white blood cells will cause urine to become cloudy. Turbidity can also be due to light amounts of red cells. Other cellular material such as casts and crystals when excreted in high amounts can cause urine to cloud. Urine with high lipid content will look cloudy. On rare occasions vaginal contamination or semen discharge will be the culprit. Whatever the case may be a microscopic examination will clear up any questions concerning the cause of cloudy urine.
Just looking at a urine sample and determining its color and clarity can give a person a very good general idea of their state of health. It is a simple act that anyone can do. It only takes a minute but it can impact our health habits greatly. Urine gives us information about our dietary habits and tells us how well our bodies have processed what we have put into it. If the kidneys are the filters of the body, then urine should be the first place to look for indicators of disease in the event something goes awry in any of the other systems. Checking the color and clarity is just the first easy step towards creating the big diagnostic picture of a patient’s state of health.
References
• Urine Colors (2010). XebWeb Network. Retrieved on January 9, 2010 from http://www.urinecolors.com/
• Foot, C., Fraser, J. (2006). Uroscopic rainbow:modern matula medicine. Postgraduate Medical Journal, 82(964), 126-129. Retrieved on January 9, 2010 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2596703/
• Health Topics (2009).Ohio Health. Retrieved on January 9, 2010 from http://www.ohiohealth.com/bodymayo.cfm?xyzpdqabc=0&id=6&action=detail&ref=4046
• Hanrun, N., Nainar, S., Chong, V. (2007). Purple Urine Bag Syndrome: A Rare and Interesting Phenomenon. Southern Medical Journal, 100(10), 1048-1050. Retrieved on January 9, 2010 from http://medscape.com/viewarticle/565078
Tuesday, June 1, 2010
Kidney Disease
The kidneys are the main organs in the body responsible for filtering waste products out of the bloodstream. They are responsible for filtering out the waste that is not needed and reabsorbing the chemicals and water that can still be utilized by the body. On a daily basis the kidneys process approximately two hundred quarts of blood and filter out two quarts of waste material which becomes urine. If we did not have the kidneys to remove these waste products from the blood they would quickly build up and begin to severely damage the body.
The actual point where filtration occurs in the kidney is in units called nephrons. Inside the millions of nephrons in each kidney rest a glomerulus, which is a tiny cluster of blood vessels surrounding a urine collection tubule. The capillaries of the glomerulus are very permeable allowing wastes and water to pass into the urine tubules while keeping proteins and blood in the bloodstream. Most diseases of the kidneys attack this portion of the kidney. A healthy person has 100% kidney function and most people could live with 30-40% kidney function without noticing any ill health effects. Serious effects on health occur when kidney function falls below 25% and end stage renal disease is classified as renal function below 15%.
Kidney disease is caused by damage to either the vasculature inside the nephron or to the structure inside the organ. The two most common causes of chronic kidney disease are Diabetes and Hypertension. Diabetes causes glucose to build up in the blood and poison the kidney. Unused glucose gets filtered out by the kidney causing damage to the vessels in the glomeruli over time. Hypertension causes damage to the vessels in the glomeruli just as it causes damage to all the blood vessels in the body. In both cases, as the vessels are damaged the walls thicken and the nephrons can no longer filter wastes at full capacity. Other diseases attack the glomeruli such as infections, sclerotic diseases, and autoimmune diseases. Once again, the vessels harden up with damage and cannot filter blood properly. Polycystic kidney disease is a genetic disorder where cysts grow inside the kidney causing structural damage. The cysts grow and eventually replace the mass of the kidney causing kidney failure. Drugs and poisons can cause kidney damage by damaging the glomeruli. Physical trauma can cause structural damage as can obstructions like kidney stones and tumors. Even something like an enlarged prostate gland in men can cause kidney damage. Whether kidney failure is acute (AKF) or chronic (CKF) doctors rely on laboratory tests to help determine on how to diagnose and treat the patient.
There is no one test that can assess kidney function. The clinician uses a variety of tests on both serum and urine to assess a patient’s level of kidney function. The most commonly known test is serum creatinine. Creatinine is a waste product of various bodily processes, especially muscle activity. It is carried by the bloodstream to the kidneys where it is freely filtered by the glomerulus. Some creatinine gets reabsorbed by the tubules and reused by the body. Normal levels are age dependent and can range anywhere between 0.2-1.3 mg/dL. An elevation in serum creatinine is usually a sign that the kidneys are not functioning properly. However estimating kidney function based on old creatinine kidney function formulas is not entirely accurate. The Glomerular Filtration Rate (GFR) calculation was developed to increase the accuracy of accessing kidney function. The calculation is based on values for serum creatinine, age, gender, and race. A true Gomerular Filtration Rate test measures glomerular filtration by injecting the patient with a tracable form of insulin, collecting a twenty-four hour urine, and then testing the urine for the analyte to see how much is recovered. Based on this original test the estimated GFR calculation was developed. The calculation is a cost effective solution to collecting twenty-four hour urines and still measures the functioning renal mass and filtering capacity of the kidneys. GFR’s are said to be “normalized” for body surface area. Normalizing allows for the calculated GFR to be run on people of various body sizes by setting the body surface area (BSA) value in the equation at 1.73m2. Normal ranges can vary from lab to lab. In general a normal range for the GFR is >60 ml/min/1.73m2 for both African Americans (GRFAA) and non- African Americans (GFRNA). In general when assessing chronic kidney disease GFR values between 30 and 59 are indicative a moderate decrease in kidney function. GFR values between 15 and 29 are indicative of a severe reduction of kidney function, and a GFR less than 15 is labeled as kidney failure.
Another test to measure functioning renal mass and filtering capacity of the kidneys is the Creatinine Clearance. This test is also performed on at twenty-four hour urine collection and it approximates the rate that creatinine is filtered out by the glomeruli of the kidneys. However because creatinine is reabsorbed by the tubules this test is not as accurate as the GFR at assessing renal function. A generalized normal range for creatinine clearance is 88-128 ml/min. For a random urine creatinine the range is around 30-125 mg/dL and for a twenty-four hour urine creatine the range is around 600-2500mg/24hr. Checking for urine creatinine becomes more valuable when it can be compared with a urine protein.
Kidney disease is usually first detected by the presence of persistent proteinuria. Random spot checks for protein are done with every urinalysis. When a urinalysis comes back positive for protein a clinician will usually order a urine creatinine, a urine protein, and possibly a microalbumin. These three tests can help determine what level of kidney disease, if any, a patient is experiencing. Healthy kidneys do not release protein into the urine. When a glomerulus becomes damaged proteins can leak through causing even more damage. In early stages of kidney disease when damage is small only small proteins will leak through such as albumin. Once this occurs the patient is said to have microalbuminuria. This is usually seen in patients such as diabetics. The clinician will order a urine microalbumin level. Most labs are actually running an albumin to creatinine ratio when they run a microalbumin level. This ratio compares the two values to determine the level of kidney function of the patient. A generalized normal range for a random microalbumin is <30 mg Mcalb/g Creat. Microalbumin testing is also used to continuously monitor patients, such as diabetics, who are already known to have kidney disease. Because microalbumin testing is looking for such small amounts of protein one should take note that certain conditions can give false positives. Uncontrolled diabetes, uncontrolled hypertension, menstrual contamination, infection, and even strenuous exercise can elevate microalbumin results. These conditions should be taken into consideration before testing the patient. Once the glomeruli become moderately to severely damaged, larger proteins begin to pass through into the urine. The patient is said to have proteinuria. At this point there is no need to test just for small amounts of albumin. A urine total protein will test for all types of protein that are leaking into the urine. A generalized normal range for a random total urine protein is <11.9 mg/dL and the range for a twenty-four hour total urine protein is <149.1 mg/24hr. There is merit to running twenty-four hour urines in that they offer more accuracy in measurement than random urine testing. If the clinician wants to know what types of protein are in the urine, samples can be sent out for chromatographic and electrophoretic testing. The benefit of knowing what types of proteins are in the urine can help out in instances of autoimmune and hereditary kidney diseases. Once testing has confirmed the presence of kidney damage the clinician can take the best course of action to ensure that remaining kidney function is stabilized.
Even though a person can live a normal life with a significant reduction in kidney function, kidney damage is irreversible. Persons with known chronic diseases such as diabetes and hypertension should take care to have their clinician monitor their kidney function. The easiest way to detect kidney problems is with a spot urine protein test, a serum creatinine, and a calculated GFR. Diabetics should have their microalbumin/creatinine ratios checked yearly to monitor for the onset of kidney disease. For everyone the best way to ensure that the kidneys stay healthy is to control glucose levels, blood pressure, cholesterol levels, and not smoke. Having healthy blood vessels will ensure that you have a healthy heart and healthy kidneys.
References
* Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p.797-815.
* The Kidneys and How They Work. (2009).National Kidney and Urologic Diseases Information Clearinghouse: The Kidneys and How They Work. Retrieved on November 28, 2009 from http://kidney.niddk.nih.gov/Kudiseases/pubs/yourkidneys/
* FAQs About the Glomerular Filtration Rate. (2003). The IHS Provider: FAQs About the Glomerular Filtration Rate. Retrieved on November 28, 2009 from http://www.ihs.gov/medicalprograms/kidney/pro_clinicaltools/FAQsaboutGFR.pdf.
* Chronic Kidney Disease. (2009). National Kidney Foundation: Chronic Kidney Disease. Retrieved on November 28, 2009 from http://www.kidney.org/kidneydisease/ckd/index/cfm.
The actual point where filtration occurs in the kidney is in units called nephrons. Inside the millions of nephrons in each kidney rest a glomerulus, which is a tiny cluster of blood vessels surrounding a urine collection tubule. The capillaries of the glomerulus are very permeable allowing wastes and water to pass into the urine tubules while keeping proteins and blood in the bloodstream. Most diseases of the kidneys attack this portion of the kidney. A healthy person has 100% kidney function and most people could live with 30-40% kidney function without noticing any ill health effects. Serious effects on health occur when kidney function falls below 25% and end stage renal disease is classified as renal function below 15%.
Kidney disease is caused by damage to either the vasculature inside the nephron or to the structure inside the organ. The two most common causes of chronic kidney disease are Diabetes and Hypertension. Diabetes causes glucose to build up in the blood and poison the kidney. Unused glucose gets filtered out by the kidney causing damage to the vessels in the glomeruli over time. Hypertension causes damage to the vessels in the glomeruli just as it causes damage to all the blood vessels in the body. In both cases, as the vessels are damaged the walls thicken and the nephrons can no longer filter wastes at full capacity. Other diseases attack the glomeruli such as infections, sclerotic diseases, and autoimmune diseases. Once again, the vessels harden up with damage and cannot filter blood properly. Polycystic kidney disease is a genetic disorder where cysts grow inside the kidney causing structural damage. The cysts grow and eventually replace the mass of the kidney causing kidney failure. Drugs and poisons can cause kidney damage by damaging the glomeruli. Physical trauma can cause structural damage as can obstructions like kidney stones and tumors. Even something like an enlarged prostate gland in men can cause kidney damage. Whether kidney failure is acute (AKF) or chronic (CKF) doctors rely on laboratory tests to help determine on how to diagnose and treat the patient.
There is no one test that can assess kidney function. The clinician uses a variety of tests on both serum and urine to assess a patient’s level of kidney function. The most commonly known test is serum creatinine. Creatinine is a waste product of various bodily processes, especially muscle activity. It is carried by the bloodstream to the kidneys where it is freely filtered by the glomerulus. Some creatinine gets reabsorbed by the tubules and reused by the body. Normal levels are age dependent and can range anywhere between 0.2-1.3 mg/dL. An elevation in serum creatinine is usually a sign that the kidneys are not functioning properly. However estimating kidney function based on old creatinine kidney function formulas is not entirely accurate. The Glomerular Filtration Rate (GFR) calculation was developed to increase the accuracy of accessing kidney function. The calculation is based on values for serum creatinine, age, gender, and race. A true Gomerular Filtration Rate test measures glomerular filtration by injecting the patient with a tracable form of insulin, collecting a twenty-four hour urine, and then testing the urine for the analyte to see how much is recovered. Based on this original test the estimated GFR calculation was developed. The calculation is a cost effective solution to collecting twenty-four hour urines and still measures the functioning renal mass and filtering capacity of the kidneys. GFR’s are said to be “normalized” for body surface area. Normalizing allows for the calculated GFR to be run on people of various body sizes by setting the body surface area (BSA) value in the equation at 1.73m2. Normal ranges can vary from lab to lab. In general a normal range for the GFR is >60 ml/min/1.73m2 for both African Americans (GRFAA) and non- African Americans (GFRNA). In general when assessing chronic kidney disease GFR values between 30 and 59 are indicative a moderate decrease in kidney function. GFR values between 15 and 29 are indicative of a severe reduction of kidney function, and a GFR less than 15 is labeled as kidney failure.
Another test to measure functioning renal mass and filtering capacity of the kidneys is the Creatinine Clearance. This test is also performed on at twenty-four hour urine collection and it approximates the rate that creatinine is filtered out by the glomeruli of the kidneys. However because creatinine is reabsorbed by the tubules this test is not as accurate as the GFR at assessing renal function. A generalized normal range for creatinine clearance is 88-128 ml/min. For a random urine creatinine the range is around 30-125 mg/dL and for a twenty-four hour urine creatine the range is around 600-2500mg/24hr. Checking for urine creatinine becomes more valuable when it can be compared with a urine protein.
Kidney disease is usually first detected by the presence of persistent proteinuria. Random spot checks for protein are done with every urinalysis. When a urinalysis comes back positive for protein a clinician will usually order a urine creatinine, a urine protein, and possibly a microalbumin. These three tests can help determine what level of kidney disease, if any, a patient is experiencing. Healthy kidneys do not release protein into the urine. When a glomerulus becomes damaged proteins can leak through causing even more damage. In early stages of kidney disease when damage is small only small proteins will leak through such as albumin. Once this occurs the patient is said to have microalbuminuria. This is usually seen in patients such as diabetics. The clinician will order a urine microalbumin level. Most labs are actually running an albumin to creatinine ratio when they run a microalbumin level. This ratio compares the two values to determine the level of kidney function of the patient. A generalized normal range for a random microalbumin is <30 mg Mcalb/g Creat. Microalbumin testing is also used to continuously monitor patients, such as diabetics, who are already known to have kidney disease. Because microalbumin testing is looking for such small amounts of protein one should take note that certain conditions can give false positives. Uncontrolled diabetes, uncontrolled hypertension, menstrual contamination, infection, and even strenuous exercise can elevate microalbumin results. These conditions should be taken into consideration before testing the patient. Once the glomeruli become moderately to severely damaged, larger proteins begin to pass through into the urine. The patient is said to have proteinuria. At this point there is no need to test just for small amounts of albumin. A urine total protein will test for all types of protein that are leaking into the urine. A generalized normal range for a random total urine protein is <11.9 mg/dL and the range for a twenty-four hour total urine protein is <149.1 mg/24hr. There is merit to running twenty-four hour urines in that they offer more accuracy in measurement than random urine testing. If the clinician wants to know what types of protein are in the urine, samples can be sent out for chromatographic and electrophoretic testing. The benefit of knowing what types of proteins are in the urine can help out in instances of autoimmune and hereditary kidney diseases. Once testing has confirmed the presence of kidney damage the clinician can take the best course of action to ensure that remaining kidney function is stabilized.
Even though a person can live a normal life with a significant reduction in kidney function, kidney damage is irreversible. Persons with known chronic diseases such as diabetes and hypertension should take care to have their clinician monitor their kidney function. The easiest way to detect kidney problems is with a spot urine protein test, a serum creatinine, and a calculated GFR. Diabetics should have their microalbumin/creatinine ratios checked yearly to monitor for the onset of kidney disease. For everyone the best way to ensure that the kidneys stay healthy is to control glucose levels, blood pressure, cholesterol levels, and not smoke. Having healthy blood vessels will ensure that you have a healthy heart and healthy kidneys.
References
* Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p.797-815.
* The Kidneys and How They Work. (2009).National Kidney and Urologic Diseases Information Clearinghouse: The Kidneys and How They Work. Retrieved on November 28, 2009 from http://kidney.niddk.nih.gov/Kudiseases/pubs/yourkidneys/
* FAQs About the Glomerular Filtration Rate. (2003). The IHS Provider: FAQs About the Glomerular Filtration Rate. Retrieved on November 28, 2009 from http://www.ihs.gov/medicalprograms/kidney/pro_clinicaltools/FAQsaboutGFR.pdf.
* Chronic Kidney Disease. (2009). National Kidney Foundation: Chronic Kidney Disease. Retrieved on November 28, 2009 from http://www.kidney.org/kidneydisease/ckd/index/cfm.
Sunday, May 30, 2010
Disseminated Intravascular Coagulation
Disseminated Intravascular Coagulation (DIC) is a disorder of coagulation that always occurs in the presence of one or more underlying conditions in patients. It is not a disease process that occurs on its own; rather it is the product of an underlying illness that can overwhelm the body. In this disorder the coagulation cascade is thrown so out of balance that thrombosis and hemorrhage can occur at the same time. DIC is defined as the systemic activation of the coagulation system within the blood vessels that leads to depletion of clotting factors, multiple organ damage, and eventually death.
Although the actual mechanism is extremely complex, in general there are four processes that are responsible for the coagulation imbalance that is DIC. To begin to understand these processes it is necessary to remember the coagulation cascade. The instrinisc pathway is activated by procoagulants such as lipids and high molecular weight kininogen within the blood vessels causing clotting factors to activate all the way down the cascade until factor X activates the cleavage of prothrombin to thrombin. In the extrinsic pathway tissue factor activates the pathway and clotting factors are activated until factor X activates thrombin as well. The big picture here is that thrombin is made and thrombin converts fibrinogen into a fibrin clot. In DIC the first process that goes wrong is that thrombin is generated out of control in vast amounts. This constant generation of thrombin depletes the body of clotting factors and platelets. This excess of thrombin in the body also promotes the generation of fibrin clots throughout the vasculature. The second process that goes wrong is that the regulatory proteins that keep thrombin in check are themselves overwhelmed. Antithrombin III, Protein C, and Protein S all normally would work together to limit the action of thrombin. However in DIC these proteins are incapacitated for various reasons. Most notably antithrombin III is constantly consumed during the process of coagulation. It is degraded by the enzyme elastase which is produced by neutrophils that are activated by inflammatory response. Protein C and Protein S are also degraded by cytokines given off in the inflammatory response. Finally production of all three of these proteins is affected once microvascular damage occurs to the liver. The third process that becomes impaired is fibrinolysis. Fibrinolysis is the breakdown of clot formation. This occurs when plasminogen is converted to plasmin which acts upon fibrinogen, fibrin, and fibrin clots. The endothelial cells of blood vessels release chemicals that activate and inhibit plasminogen. In DIC the destruction of vessel walls and the constant consumption of coagulants overwhelm this system causing levels of plasmin to increase out of control (just like thrombin). The result is that plasmin inhibitors are overwhelmed and fibrin/fibrinogen degradation products are produced in great amounts. The fourth process that occurs is inflammatory activation. This is really a circular process as both DIC and the inflammatory state feed off of each other. It is believed that the underlying medical condition sets in motion an inflammatory state which introduces procoagulants (tissue factor, bacteria, lipids, etc.) into the system causing the coagulation cascade to set itself in motion. Many clotting factors, once activated, actually stimulate the release of cytokines from the vascular endothelium to promote inflammation which causes normal events like platelet and neutrophil aggregation. In DIC this adds fuel to the fire. Clots begin to settle into vascular walls and into organs causing more tissue damage and the release of more procoagulants thus propagating the cycle further. At this point the body has no way to bring the system back into balance and without treatment of the underlying condition death will occur.
There are many illnesses that can cause DIC and depending on what type of illness a patient has can determine whether or not DIC is acute or chronic. In acute DIC large amounts of procoagulants are released into the bloodstream within a very short period of time. In this short time the consumption of clotting factors and platelets occurs far more rapidly than the body can replenish them causing mass bleeding. Acute DIC is usually caused by systemic infections due to bacteria but can be caused by viruses, parasites, and even fungi. The idea with acute DIC is that the underlying medical condition is something that damages the body quickly. Other events that can trigger acute DIC include any type of severe trauma, burns, transfusions, obstetric complications, and even snake bites. Some disease states can also provide the right conditions to allow for the development of acute DIC. Acute hepatic failure can trigger a state of acute DIC as can acute myelocytic leukemia. It is important to monitor and treat the underlying condition in order to prevent the possibility of the development of DIC. Chronic DIC is different in that the body is able to compensate for the consumption of coagulation factors and platelets. The body is able to compensate because smaller amounts of procoagulant are being released into the body over a longer period of time. Partners of chronic DIC include diseases such as rheumatoid arthritis, sarcoidosis, ulcerative colitis, and crohn disease. Cancers such as solid tumors, leukemias, and myeloproliferative disorders can also lead to DIC. Even retained products of conception from either miscarriage or an abortion can cause chronic DIC. The key to chronic DIC is that the procoagulant in question leaks into the system slowly over a period of time. In chronic DIC there is little chance for the massive bleeding that is seen with acute DIC, however the chance for tissue and organ damage is just as great.
In order to determine if DIC is present the doctor must use both clinical and laboratory findings. Laboratory testing includes both hematology and coagulation testing. The most important finding early on in patients suspected of having DIC is thrombocytopenia. This can be found by simply running a CBC with differential. When seen under a microscope a peripheral smear will usually include schistocytes, the presence of a left shift in leukocytes, and possibly large young platelets. This would all reflect the presence of clotting in vessels, inflammation, and the high turnover of platelets. The normal values for platelets is age dependent, however the critical value cutoff is around <50,000 platelets/uL and any value under this would certainly be considered thrombocytopenic. The remaining testing is all coagulation. The prothrombin time and activated thromboplastin time will be prolonged since clotting factors are being constantly consumed. Although normal value will differ from lab to lab generally normal ranges for PT are around 9.0-11.0 seconds and for APTT are around 24.0-33.0 seconds. Fibrinogen levels are expected to be decreased since thrombin is busy using it up to make fibrin. However fibrinogen is an acute phase reactant, which will increase in levels in cases of inflammation, so sometimes the levels will remain within normal ranges. A general normal range is 200-475 mg/dL for fibrinogen. The final test that can be run is d-dimer. D-dimer is a degradation product of the cross-linked fibrin polymers that are broken apart during fibrinolysis. D-dimer levels are usually elevated in cases of DIC due to constant formation of fibrin and fibrinolysis. However d-dimer levels are also high after surgery, in cases of trauma, in infections and in cases of inflammation so theses results have to be used in conjunction with other findings. A general normal range for d-dimer is 0.0-3.0 mg/L.
Currently there is no definitive treatment for DIC. The best course of treatment for the patient is to treat the underlying illness in order to rid the body of the procoagulants causing DIC. Through the course of treatment replacement of platelets and clotting factors can be given if needed, however this is only done to stop active bleeding. Although it seems to be common practice there has been no definitive data that giving heparin to reverse the coagulation process is of any benefit to the patient. Heparin will inactivate thrombin but it can only be given to DIC patients in small controlled amounts in order to prevent bleeding. Currently research is being done on giving patients antithrombin III and activated protein C. This research looks promising but the trials are still in their early stages. In the end the best that can be done for the patient is diligent laboratory work and treatment by the clinicans.
References
* Kusuma, B., Schulz, T. (2009). Acute Disseminated Intravascular Coagulation. Hospital Physician, 35-40. Retrieved December 5, 2009 from http://www.turner-white.com/memberfile.php?PubCode=hp_mar09_coagulation.pdf
* Riley, R. (2005). Disseminated Intravascular Coagulation. Retrieved December 5, 2009 from http://www.pathology.vcu.edu/clinical/coag/DIC.pdf
* Becker, J., Wira, C. (2009). Disseminated Intravascular Coagulation. Emedicine from WebMD. Retrieved December 5, 2009 from http://emedicine.medscape.com/article/779097-overview
Although the actual mechanism is extremely complex, in general there are four processes that are responsible for the coagulation imbalance that is DIC. To begin to understand these processes it is necessary to remember the coagulation cascade. The instrinisc pathway is activated by procoagulants such as lipids and high molecular weight kininogen within the blood vessels causing clotting factors to activate all the way down the cascade until factor X activates the cleavage of prothrombin to thrombin. In the extrinsic pathway tissue factor activates the pathway and clotting factors are activated until factor X activates thrombin as well. The big picture here is that thrombin is made and thrombin converts fibrinogen into a fibrin clot. In DIC the first process that goes wrong is that thrombin is generated out of control in vast amounts. This constant generation of thrombin depletes the body of clotting factors and platelets. This excess of thrombin in the body also promotes the generation of fibrin clots throughout the vasculature. The second process that goes wrong is that the regulatory proteins that keep thrombin in check are themselves overwhelmed. Antithrombin III, Protein C, and Protein S all normally would work together to limit the action of thrombin. However in DIC these proteins are incapacitated for various reasons. Most notably antithrombin III is constantly consumed during the process of coagulation. It is degraded by the enzyme elastase which is produced by neutrophils that are activated by inflammatory response. Protein C and Protein S are also degraded by cytokines given off in the inflammatory response. Finally production of all three of these proteins is affected once microvascular damage occurs to the liver. The third process that becomes impaired is fibrinolysis. Fibrinolysis is the breakdown of clot formation. This occurs when plasminogen is converted to plasmin which acts upon fibrinogen, fibrin, and fibrin clots. The endothelial cells of blood vessels release chemicals that activate and inhibit plasminogen. In DIC the destruction of vessel walls and the constant consumption of coagulants overwhelm this system causing levels of plasmin to increase out of control (just like thrombin). The result is that plasmin inhibitors are overwhelmed and fibrin/fibrinogen degradation products are produced in great amounts. The fourth process that occurs is inflammatory activation. This is really a circular process as both DIC and the inflammatory state feed off of each other. It is believed that the underlying medical condition sets in motion an inflammatory state which introduces procoagulants (tissue factor, bacteria, lipids, etc.) into the system causing the coagulation cascade to set itself in motion. Many clotting factors, once activated, actually stimulate the release of cytokines from the vascular endothelium to promote inflammation which causes normal events like platelet and neutrophil aggregation. In DIC this adds fuel to the fire. Clots begin to settle into vascular walls and into organs causing more tissue damage and the release of more procoagulants thus propagating the cycle further. At this point the body has no way to bring the system back into balance and without treatment of the underlying condition death will occur.
There are many illnesses that can cause DIC and depending on what type of illness a patient has can determine whether or not DIC is acute or chronic. In acute DIC large amounts of procoagulants are released into the bloodstream within a very short period of time. In this short time the consumption of clotting factors and platelets occurs far more rapidly than the body can replenish them causing mass bleeding. Acute DIC is usually caused by systemic infections due to bacteria but can be caused by viruses, parasites, and even fungi. The idea with acute DIC is that the underlying medical condition is something that damages the body quickly. Other events that can trigger acute DIC include any type of severe trauma, burns, transfusions, obstetric complications, and even snake bites. Some disease states can also provide the right conditions to allow for the development of acute DIC. Acute hepatic failure can trigger a state of acute DIC as can acute myelocytic leukemia. It is important to monitor and treat the underlying condition in order to prevent the possibility of the development of DIC. Chronic DIC is different in that the body is able to compensate for the consumption of coagulation factors and platelets. The body is able to compensate because smaller amounts of procoagulant are being released into the body over a longer period of time. Partners of chronic DIC include diseases such as rheumatoid arthritis, sarcoidosis, ulcerative colitis, and crohn disease. Cancers such as solid tumors, leukemias, and myeloproliferative disorders can also lead to DIC. Even retained products of conception from either miscarriage or an abortion can cause chronic DIC. The key to chronic DIC is that the procoagulant in question leaks into the system slowly over a period of time. In chronic DIC there is little chance for the massive bleeding that is seen with acute DIC, however the chance for tissue and organ damage is just as great.
In order to determine if DIC is present the doctor must use both clinical and laboratory findings. Laboratory testing includes both hematology and coagulation testing. The most important finding early on in patients suspected of having DIC is thrombocytopenia. This can be found by simply running a CBC with differential. When seen under a microscope a peripheral smear will usually include schistocytes, the presence of a left shift in leukocytes, and possibly large young platelets. This would all reflect the presence of clotting in vessels, inflammation, and the high turnover of platelets. The normal values for platelets is age dependent, however the critical value cutoff is around <50,000 platelets/uL and any value under this would certainly be considered thrombocytopenic. The remaining testing is all coagulation. The prothrombin time and activated thromboplastin time will be prolonged since clotting factors are being constantly consumed. Although normal value will differ from lab to lab generally normal ranges for PT are around 9.0-11.0 seconds and for APTT are around 24.0-33.0 seconds. Fibrinogen levels are expected to be decreased since thrombin is busy using it up to make fibrin. However fibrinogen is an acute phase reactant, which will increase in levels in cases of inflammation, so sometimes the levels will remain within normal ranges. A general normal range is 200-475 mg/dL for fibrinogen. The final test that can be run is d-dimer. D-dimer is a degradation product of the cross-linked fibrin polymers that are broken apart during fibrinolysis. D-dimer levels are usually elevated in cases of DIC due to constant formation of fibrin and fibrinolysis. However d-dimer levels are also high after surgery, in cases of trauma, in infections and in cases of inflammation so theses results have to be used in conjunction with other findings. A general normal range for d-dimer is 0.0-3.0 mg/L.
Currently there is no definitive treatment for DIC. The best course of treatment for the patient is to treat the underlying illness in order to rid the body of the procoagulants causing DIC. Through the course of treatment replacement of platelets and clotting factors can be given if needed, however this is only done to stop active bleeding. Although it seems to be common practice there has been no definitive data that giving heparin to reverse the coagulation process is of any benefit to the patient. Heparin will inactivate thrombin but it can only be given to DIC patients in small controlled amounts in order to prevent bleeding. Currently research is being done on giving patients antithrombin III and activated protein C. This research looks promising but the trials are still in their early stages. In the end the best that can be done for the patient is diligent laboratory work and treatment by the clinicans.
References
* Kusuma, B., Schulz, T. (2009). Acute Disseminated Intravascular Coagulation. Hospital Physician, 35-40. Retrieved December 5, 2009 from http://www.turner-white.com/memberfile.php?PubCode=hp_mar09_coagulation.pdf
* Riley, R. (2005). Disseminated Intravascular Coagulation. Retrieved December 5, 2009 from http://www.pathology.vcu.edu/clinical/coag/DIC.pdf
* Becker, J., Wira, C. (2009). Disseminated Intravascular Coagulation. Emedicine from WebMD. Retrieved December 5, 2009 from http://emedicine.medscape.com/article/779097-overview
Saturday, May 29, 2010
Lactic Acid
Lactic acid is produced and used in the body as a part of carbohydrate metabolism. Under normal circumstances this molecule is very useful to the body and plays an integral role in supplying the body with the energy it needs. However when metabolism is upset due to illness or injury lactic acid can build up in the tissues and the blood. Clinicians can monitor the levels of lactic acid in the body to monitor some disease states and their respective treatments.
Lactic acid is produced and used by the body. All cells can break glucose down into pyruvate via glycolysis; the first step of carbohydrate metabolism. This occurs in the cytoplasm of all cells. Pyruvate is broken down further to produced ATP. This is done in two ways. It can either diffuse into the mitochondria of a cell in order to enter into the Citric Acid cycle (Krebs cycle) or it can be broken down into lactate by lactate dehydrogenase. The Citric Acid cycle produces more ATP and less waste in comparison to the amount of ATP produced when lactate is made. However not all cells have mitochondria (i.e. erythrocytes) nor is there always enough oxygen present in cells to run the Citric Acid cycle. The main producers of lactate are skeletal muscle, erythrocytes, the brain, and the gut. The lactate produced by these cells will diffuse out into the blood stream and be picked up by another group of cells who will convert lactate back to glucose. Lactate metabolizers include the cells of the liver, the heart, and the kidneys.
When the body does not have an adequate supply of oxygen for glucose metabolism pyruvate is converted to lactate in the cells. The ATP created is then hydrolyzed to release the energy needed from its phosphate bond. The byproducts of this reaction are hydrogen ions, ADP, and a Pi ion. Under the normal conditions of the Citric Acid cycle these products would be recycled in the presence of oxygen, however in a hypoxic environment the constant hydrolysis of ATP leads to the accumulation of hydrogen ions causing a state of acidosis. It is important to note that it is the accumulation of these hydrogen ions and not the accumulation of lactate that causes acidosis. As lactate molecules leave a cell they give up a hydroxyl anion (OH-) and pick up a hydrogen ion to form lactic acid. The spare hydroxyl anion picks up another hydrogen ion to form water. This is one way that the excess hydrogen ions are buffered out. Lactate also acts as a buffer in that it can absorb extra hydrogen ions in the reverse reaction back into pyruvate via the enzyme lactate dehydrogenase. This occurs naturally as needed. In a healthy person these buffering capabilities are enough to keep the body balanced and avert a possible acidosis state; however under the conditions of illness and tissue hypoxia lactate production can spiral out of control and add to the problem.
Lactate levels are drawn by clinicians in order to evaluate and monitor conditions where there is a chance that tissue hypoxia or acidosis is occurring. Such conditions include sepsis, shock, heart attack, coma, seizures, uncontrolled diabetes, liver failure, and renal failure. Because lactate is normally being made in the body the normal range in plasma is around 0.4-2.0 mmol/L. A patient is generally considered to have hyperlactatemia once lactate levels rise between 4-5 mmol/L. Hyperlactatemia is a state of increased lactate levels with adequate tissue oxygenation and adequate acid-base balance. This can occur in liver failure and sepsis patients before tissue hypoperfusion sets in. The National Surviving Sepsis Campaign recommends that all patients at risk for sepsis have a baseline lactate level drawn upon admission and all patients with a lactate level >4 mmol/L are entered into special early goal-directed therapy. Hyperlactatemia is different from lactic acidosis. Lactic acidosis is the term given when lactate levels are increased and there is a disruption in the acid-base balance creating a state of acidosis. There are two levels of lactic acidosis. Type A is lactic acidosis with poor tissue perfusion and Type B is lactic acidosis with normal tissue perfusion. Type A cases are usually due to events that cut off oxygen supply such as shock, heart attacks, and strokes. Type B cases are usually due to illnesses such as diabetes, liver failure, drugs, toxins, and inborn errors of metabolism. Lactate can also be measured in cerebrospinal fluid. Lactate levels in CSF will be increased in the event of strokes, intracranial hemorrhage, epilepsy, and most importantly bacterial meningitis. Lactate levels in CSF are usually ordered in order to distinguish between bacterial and viral meningitis. Normal levels for lactate CSF are around 0.6-2.2 mmol/L.
Lactate levels are not a diagnostic marker of disease; rather they are another tool provided by the laboratory that clinicians can use to monitor disease states. When used in conjunction with other testing, lactate levels can tell a clinician whether or not a patient is metabolizing glucose correctly. It can also show that the body is metabolizing lactate correctly. A lactate level in conjunction with other testing can show whether or not the body is getting enough oxygen. More importantly this test can be used as a marker for monitoring patient treatment. It is currently the gold standard test to start and monitor treatment for sepsis patients. It is both an interesting metabolite and an insightful test.
References
· Gunnerson, K., Sat, S. (2009). Lactic Acidosis. Emedicine from WebMD. Retrieved on December 20, 2009 from http://emedicine.medscape.com/article/167027-overview
· Lactate. (2009). Lactate: The Test. Lab Tests Online. Retrieved on December 20, 2009 from http://www.labtestsonline.org/understanding/analytes/lactate/test.html
· Serum Lactate Measured. (2009). Implement the Sepsis Resuscitation Bundle: Serum Lactate Measured. Institute for Healthcare Improvement. Retrieved on December 20, 2009 from http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis/Changes/IndividualChanges/SerumLactateMeasured.htm
· Kraviz, L. (2004). Lactate: Not Guilty as Charged. Retrieved on December 20, 2009 from http://www.unm.edu/~lkravitz/Article%20folder/lactate.html
· Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p. 877-878.
Lactic acid is produced and used by the body. All cells can break glucose down into pyruvate via glycolysis; the first step of carbohydrate metabolism. This occurs in the cytoplasm of all cells. Pyruvate is broken down further to produced ATP. This is done in two ways. It can either diffuse into the mitochondria of a cell in order to enter into the Citric Acid cycle (Krebs cycle) or it can be broken down into lactate by lactate dehydrogenase. The Citric Acid cycle produces more ATP and less waste in comparison to the amount of ATP produced when lactate is made. However not all cells have mitochondria (i.e. erythrocytes) nor is there always enough oxygen present in cells to run the Citric Acid cycle. The main producers of lactate are skeletal muscle, erythrocytes, the brain, and the gut. The lactate produced by these cells will diffuse out into the blood stream and be picked up by another group of cells who will convert lactate back to glucose. Lactate metabolizers include the cells of the liver, the heart, and the kidneys.
When the body does not have an adequate supply of oxygen for glucose metabolism pyruvate is converted to lactate in the cells. The ATP created is then hydrolyzed to release the energy needed from its phosphate bond. The byproducts of this reaction are hydrogen ions, ADP, and a Pi ion. Under the normal conditions of the Citric Acid cycle these products would be recycled in the presence of oxygen, however in a hypoxic environment the constant hydrolysis of ATP leads to the accumulation of hydrogen ions causing a state of acidosis. It is important to note that it is the accumulation of these hydrogen ions and not the accumulation of lactate that causes acidosis. As lactate molecules leave a cell they give up a hydroxyl anion (OH-) and pick up a hydrogen ion to form lactic acid. The spare hydroxyl anion picks up another hydrogen ion to form water. This is one way that the excess hydrogen ions are buffered out. Lactate also acts as a buffer in that it can absorb extra hydrogen ions in the reverse reaction back into pyruvate via the enzyme lactate dehydrogenase. This occurs naturally as needed. In a healthy person these buffering capabilities are enough to keep the body balanced and avert a possible acidosis state; however under the conditions of illness and tissue hypoxia lactate production can spiral out of control and add to the problem.
Lactate levels are drawn by clinicians in order to evaluate and monitor conditions where there is a chance that tissue hypoxia or acidosis is occurring. Such conditions include sepsis, shock, heart attack, coma, seizures, uncontrolled diabetes, liver failure, and renal failure. Because lactate is normally being made in the body the normal range in plasma is around 0.4-2.0 mmol/L. A patient is generally considered to have hyperlactatemia once lactate levels rise between 4-5 mmol/L. Hyperlactatemia is a state of increased lactate levels with adequate tissue oxygenation and adequate acid-base balance. This can occur in liver failure and sepsis patients before tissue hypoperfusion sets in. The National Surviving Sepsis Campaign recommends that all patients at risk for sepsis have a baseline lactate level drawn upon admission and all patients with a lactate level >4 mmol/L are entered into special early goal-directed therapy. Hyperlactatemia is different from lactic acidosis. Lactic acidosis is the term given when lactate levels are increased and there is a disruption in the acid-base balance creating a state of acidosis. There are two levels of lactic acidosis. Type A is lactic acidosis with poor tissue perfusion and Type B is lactic acidosis with normal tissue perfusion. Type A cases are usually due to events that cut off oxygen supply such as shock, heart attacks, and strokes. Type B cases are usually due to illnesses such as diabetes, liver failure, drugs, toxins, and inborn errors of metabolism. Lactate can also be measured in cerebrospinal fluid. Lactate levels in CSF will be increased in the event of strokes, intracranial hemorrhage, epilepsy, and most importantly bacterial meningitis. Lactate levels in CSF are usually ordered in order to distinguish between bacterial and viral meningitis. Normal levels for lactate CSF are around 0.6-2.2 mmol/L.
Lactate levels are not a diagnostic marker of disease; rather they are another tool provided by the laboratory that clinicians can use to monitor disease states. When used in conjunction with other testing, lactate levels can tell a clinician whether or not a patient is metabolizing glucose correctly. It can also show that the body is metabolizing lactate correctly. A lactate level in conjunction with other testing can show whether or not the body is getting enough oxygen. More importantly this test can be used as a marker for monitoring patient treatment. It is currently the gold standard test to start and monitor treatment for sepsis patients. It is both an interesting metabolite and an insightful test.
References
· Gunnerson, K., Sat, S. (2009). Lactic Acidosis. Emedicine from WebMD. Retrieved on December 20, 2009 from http://emedicine.medscape.com/article/167027-overview
· Lactate. (2009). Lactate: The Test. Lab Tests Online. Retrieved on December 20, 2009 from http://www.labtestsonline.org/understanding/analytes/lactate/test.html
· Serum Lactate Measured. (2009). Implement the Sepsis Resuscitation Bundle: Serum Lactate Measured. Institute for Healthcare Improvement. Retrieved on December 20, 2009 from http://www.ihi.org/IHI/Topics/CriticalCare/Sepsis/Changes/IndividualChanges/SerumLactateMeasured.htm
· Kraviz, L. (2004). Lactate: Not Guilty as Charged. Retrieved on December 20, 2009 from http://www.unm.edu/~lkravitz/Article%20folder/lactate.html
· Burtis, C. A., Ashwood, E. R., Bruns, D. E., Tietz Textbook of Clinical Chemistry & Molecular Diagnostics. St. Louis, Missouri: Elsevier (2006). p. 877-878.
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