Whether a student still in training or a veteran of the job, this blog is dedicated to refreshing the mind with all that relates to the field of Clinical Laboratory Sciences.



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

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.

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.

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

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

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.