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Urinary Information and Courses from MediaLab, Inc.

These are the MediaLab courses that cover Urinary and links to relevant pages within the course.

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Case Studies in Clinical Microbiology
Review 1

Podschun R. Ullmann U.: Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors Clinical Microbiology Reviews. 11(4):589-603, 1998 Bacteria belonging to the genus Klebsiella frequently cause human nosocomial infections. In particular, the medically most important Klebsiella species, Klebsiella pneumoniae, accounts for a significant proportion of hospital-acquired urinary tract infections, pneumonia, septicemias, and soft tissue infections. The principal pathogenic reservoirs for transmission of Klebsiella are the gastrointestinal tract and the hands of hospital personnel. Because of their ability to spread rapidly in the hospital environment, these bacteria tend to cause nosocomial outbreaks. Hospital outbreaks of multidrug-resistant Klebsiella species, especially those in neonatal wards, are often caused by new types of strains, the so-called extended-spectrum-beta-lactamase (ESBL) producers The incidence of ESBL-producing strains among clinical Klebsiella isolates has been steadily increasing over the past years. The resulting limitations on the therapeutic options demand new measures for the management of Klebsiella hospital infections. While the different typing methods are useful epidemiological tools for infection control, recent findings about Klebsiella virulence factors have provided new insights into the pathogenic strategies of these bacteria. Klebsiella pathogenicity factors such as capsules or lipopolysaccharides are presently considered to be promising candidates for vaccination efforts that may serve as immunological infection control measures.

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Clinical History

A 72- year old woman had a history of recurrent urinary tract infections over the past several months, for which she had received different regimens of antibiotics including ampicillin, trimethoprim-sulfasoxazole, and ciprofloxacin.Relapses often occurred 10 days to two weeks after cessation of therapy.The current flare up, manifest by dysuria, lower abdominal pain and cloudy urine was accompanied by shaking chills and spiking fever.A sterile mid-stream urine specimen was sent to the laboratory for culture.

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Vancomycin Resistance

Vancomycin and ampicillin resistance among Enterococcus species, particularly E. faecium have been on a steady increase. The disk diffusion screening test is used in many laboratories to detect vancomycin resistant strains. Note in the upper image that no zone of inhibition is seen around either the vancomycin or the ampicillin disk, indicating resistance to both drugs. Vancomycin-resistant Enterococci (VRE) have been divided into three phenotypes--Van A, Van B, and Van C. Vancomycin-resistant strains of E. faecalis and E. faecium are commonly of the Van A phenotype, demonstrating high level resistance (MIC's higher than 64 ug/mL), as illustrated by total resistance of the test strain in the E test and the VA disk, as illustrated in the lower image. The strain shown in the lower image, however, is ampicillin susceptible at the level of 1 ug/mL (see lower set of yellow arrows), indicating that this drug may be effective in treating the urinary tract infection.

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Review 2

Suppola JP. Kuikka A. Vaara M. Valtonen VV. Comparison of risk factors and outcome in patients with Enterococcus faecalis vs Enterococcus faecium bacteremia. Scandinavian Journal of Infectious Diseases. 30(2):153-7, 1998. The purpose of our study was to determine retrospectively the risk factors for the acquisition of Enterococcus faecalis vs E. faecium bacteremia, as well as the clinical outcomes of these patients. 62 patients with Enterococcus faecalis bacteremia were compared to 31 patients with E. faecium bacteremia. Haematologic malignancies, neutropenia, high-risk source and previous use of aminoglycosides, carbapenems, cephalosporins and clindamycin were significantly associated with E. faecium bacteremia. Instead, urinary catheterization was found to be related to Enterococcus faecalis bacteremia. The mortality rates within 7 d and 30 d were 13% and 27%, respectively, in patients with E. faecalis bacteremia and 6% and 29%, respectively, in patients with E. faecium bacteremia. There was no difference in mortality between E. faecalis and E. faecium bacteremia, nor was there a difference in seriousness of disease at the time of bacteremia. In the subgroups of patients with monomicrobial or clinically significant E. faecalis vs E. faecium bacteremia, the mortality rates were similar to the results of all subjects. Our results do not support the theory that E. faecium would be a more virulent organism than E. faecalis.

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Chemical Screening of Urine by Reagent Strip
Chemical Urinalysis Reagent Strips

A chemical urinaylsis reagent strip, also called a dipstick, for screening urine is a narrow band of paper which has been saturated with chemical indicators for specific substances or properties. Depending on the product being used, chemical urinalysis reagent strips may include test indicators for glucose, bilirubin, ketones, specific gravity, blood, pH, protein, urobilinogen, nitrite, and leukocyte esterase. The results obtained from urine screening using chemical urinalysis strips can indicate the patient's carbohydrate metabolism status, kidney and liver function, urinary tract infection, and acid-base balance. Most chemical urinalysis reagent strips can be read visually and do not require instrumentation for automatic reading, though many laboratories utilize instruments for this purpose. When performing chemical urinalysis reagent strip analysis, the directions must be performed exactly. Accurate timing is paramount in order to achieve appropriate and optimal results. In addition, the reagent strips must be stored properly in their containers with the lid tightly closed to maintain reagent reactivity. It is always essential to utilize well-mixed urine which has been collected within 2 hours of analysis.Always read the package insert for your particular brand of chemical urinalysis reagent strip, as each manufacturer may have slightly different instructions and interpretations.

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Basis of the Urine pH Test

Chemical reagent strips for urine measure pH using methyl red and bromthymol blue indicator dyes. The color change that occurs in this test area correlates with the urine's pH. Sensitivity to pH ranges from 5.0 (acid pH) to 9.0 (alkaline pH) on a typical urine reagent strip. Physiological urine pH ranges from 5.0 to 8.0. With an increase in urinary pH, the indicators bromothymol blue and methyl red, changes from orange to green and blue.

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The indicator(s) used in the pH test region of the chemical reagent strips for urine is/are: (Choose ALL correct answers)View Page
Match the following factors with the expected urine pH type:View Page
Clinical Significance of Urine Protein

The presence of an increased amount of protein in a urine specimen is often the first indicator of renal disease. Proteinuria may signal severe kidney damage, be a warning of impending kidney involvement, or be transient and unrelated to the renal system. Further quantitative testing of urine for protein may be needed to determine the significance of the proteinuria. Proteinuria related to kidney impairment may be due to glomerular membrane damage caused by toxic agents, immune complexes found in lupus erythematosus, or streptococcal glomerulonephritis. The amount of protein present in urine samples from patients with glomerular damage usually ranges from 10-40 mg/dL. If the urinary protein is due to a disorder that affects tubular reabsorption, the urine protein quantities will be much greater. In patients with multiple myeloma, proteinuria is due to the excretion of the Bence Jones protein. This low molecular weight protein produced by a malignant clone of plasma cells circulates in the blood and is filtered in the kidneys in quantities exceeding the tubular capacity. This excess protein is excreted in the urine.

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False Positive and Negative Urine Bilirubin Results

False Positive BilirubinFalse positive results may occur when patients are on large doses of chloropromazine, and may occur in the presence of metabolites of phenazopyridine. When these compounds are present, the urine becomes red. Metabolites of Lodine® (etodolac) may cause false positive or atypical results. False Negative BilirubinFalse negative bilirubin dipstick results are often due to testing a specimen that is not fresh. Bilirubin breaks down when exposed to light. Indoxyl sulfate (Indican) can produce a yellow orange-to-red color response which may interfere with the interpretation of a positive or negative reaction. Positive nitrites due to a urinary tract infection may also cause a false negative result.

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False Positive and Negative Results

False Positives:A false positive result for blood on the urine chemical reagent strip can occur when oxidizing contaminants, such as hypochlorite (bleach), remain in collection bottles after cleaning. Contamination of the urine with provodine-iodine, a strong oxidizing agent, used in surgical procedures can also result in a false positive reaction. Microbial peroxide found in association with urinary tract infections may also cause false-positive results. Capoten® (Captopril) can cause decreased reactivity.The muscle tissue form of hemoglobin, myoglobin is a well-known cause of false-positive reactions on the blood portion of the reagent strip. When tissue hemoglobin is present, the urine specimen has a clear red appearance. Patients suffering from muscle-wasting disorders or muscular destruction due to trauma, prolonged coma, or convulsions or individuals engaging in extensive exertion may have myoglobin in their urine. Specific tests for myoglobin, such as immunodiffusion techniques or protein electrophoresis, are needed to confirm the presence of this substance in a urine specimen. Levels of ascorbic acid normally found in urine do not interfere with this test. False Negatives:False negative results may occur in some analysis methods when the concentration of ascorbic acid is greater than 5 mg/dL. The sensitivity of the blood portion of the test strip is decreased in specimens with a high specific gravity and increased protein. High levels of nitrites may delay the reaction, causing a false negative to be reported. If the pH of a urine sample is below 5, hemolysis of red cells as part of the test reaction is inhibited which results in a false negative reaction. An improperly mixed specimen may test negative if the red blood cells are in the sediment.

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Clinical Significance of Blood in Urine

Blood is normally not present in the urine of healthy individuals, apart from blood during menses that may be detected in urine samples from females, Hematuria is associated with renal or genital disorders in which the bleeding is the result of irritation to the involved organs or some type of trauma. Examples include:Renal calculiPyelonephritisGlomerulonephritisTumorsTraumaExposure to toxic chemicals or drugsStrenuous exerciseHemoglobinuria may be due to the lysis of red blood cells within the urinary tract. This can be caused by intravascular hemolysis, as the hemoglobin is filtered through the glomeruli. In a healthy, normal individual, the hemoglobin molecule attaches to haptoglobin and bypasses the kidney filtration system. When the hemoglobin/haptoglobin system is overwhelmed, hemoglobin passes into the urine. Hemoglobinuria may be associated with:Hemolytic anemiaSevere burnsTransfusion reactionInfection Strenuous exercise

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A urine sample is cloudy pink in appearance. The microscopic examination reveals the presence of intact red blood cells. The term used to describe these findings is:View Page
Urine Analysis for Nitrites

The nitrites portion of the chemical reagent strip provides a rapid screening test for the presence of gram-negative bacteria that are often responsible for urinary tract infections. Urine cultures are still needed to confirm the diagnosis and monitor any urinary tract or kidney infection. Diagnosis and treatment of cystitis (bladder infection) is important because, if left untreated, it may result in kidney damage, impairment of renal function, hypertension and/or septicemia.

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Nitrite Test Sensitivity

This test is sensitive to 0.06-0.1 mg/dL nitrite ion in urines with a low specific gravity and with ascorbic acid concentrations of less than 25 mg/dL. Pink spots or pink edges should not be interpreted as a positive result because some medications can color urine red or turn red in an acid environment. Any degree of uniform pink color should be considered positive, suggesting the presence of 105 organisms/mL. Detection of low levels of nitrite ion may be enhanced by comparing the activated test strip to a white background. It is important to note that color development is NOT proportional to the number of bacteria present. The test is specific for nitrites and does not react with any other substances normally present in urine. Negative results do not necessarily rule out a urinary tract infection with yeasts or gram-positive bacteria unable to reduce nitrates.

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Clinical Significance of Nitrites in Urine

Early detection of bacteria is important in order to prevent cystitis from developing into inflammation or infection involving the kidney and renal pelvis. The nitrite portion of the test strip can be used to screen individuals who are at risk for developing urinary tract infections, such as diabetics, persons with recurrent infections, or pregnant women. The test is also useful in evaluating the success of antibiotic therapy that is used to treat a bladder infection.

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Nitrates in urine are reduce to nitrites by:View Page
Introduction to Urobilinogen

Urobilinogen is a byproduct of hemoglobin breakdown. It is produced in the intestinal tract as a result of the action of bacteria on bilirubin. Almost half of the urobilinogen produced recirculates through the liver and then returns to the intestines through the bile duct. Urobilinogen is then excreted in the feces where it is converted to urobilin. As the urobilinogen circulates in the blood to the liver, a portion of it is diverted to the kidneys and appears as urinary urobilinogen. Up to 1 mg/dL or Ehrlich unit of urobilinogen is present in normal urine. A result of 2.0 mg/dL represents the transition from normal to abnormal levels of urobilinogen and the patient should be evaluated further. It is important to note that the chemical reagent strip cannot determine the absence of urobilinogen, so a negative result is impossible.

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Clinical Significance of Urobilinogen in Urine

Urinary urobilinogen may be increased in the presence of a hemolytic process such as hemolytic anemia. It may also be increased with infectious hepatitis, or with cirrhosis. Comparing the urinary bilirubin result with the urobilinogen result may assist in distinguishing between red cell hemolysis, hepatic disease, and biliary obstruction, as shown in the table below:ConditionUrine Bilirubin ResultUrine Urobilinogen ResultHemolytic diseaseNegativeIncreasedHepatitic diseasePositive or negativeIncreasedBiliary obstructionPositiveNormal* *Urine chemical reagent strip methods cannot distinguish normal urobilinogen from absent urobilinogen, as might be seen in complete biliary obstruction.

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Presence of Granulocytes in Urine

Granulocytic white blood cells in a urine sample suggest the presence of a urinary tract infection. Granulocytes, which include neutrophils, basophils and eosinophils, contain esterases. These esterases catalyze the urine chemical reagent strip reaction where indoxylcarbonic acid ester releases indoxyl. Indoxyl reacts with a diazonium salt to produce a purple color. The intensity of the color produced is proportional to the amount of enzyme present.

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False Positive and Negative Urine Leukocyte Esterase

False Positives:A false positive result may occur in the presence of strong oxidizing agents in the collection container. In random urine specimens from women, a positive result for leukocyte esterase may be due to a source external to the urinary tract. Other urine sediment findings such as bacteria, squamous or renal epithelial cells, lymphocytes or red blood cells do not contain esterases, and would not produce a positive leukocyte esterase test. False Negatives:False negative results may occur in the presence of significant levels of protein or glucose and in urines with high specific gravity which can crenate the white blood cells, leaving them unable to release esterases. Some drugs such as Cephalexin (Kelfex®), Cephalothin Keflin®), Tetracycline, or high concentrations of oxalic acid may also cause falsely decrease leukocyte esterase test results.

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Clinical Significance of Leukocyte Esterase in Urine

Using the esterase test in conjunction with pH, protein and nitrite provides a combination of tests which can screen for the presence of bacterial infections in the urinary system.

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To screen for urinary tract infections, leukocyte esterase results should be evaluated along with the results from which of these other reagent strip tests?View Page

Chemical Screening of Urine by Reagent Strip (retired March 2012)
A patient suspected of a urinary tract infection has a negative nitrite test, but bacteria is present upon microscopic examination. What may have caused this discrepant result? (Choose ALL of the correct answers)View Page
Match the following reagent strip tests to the disease or disorder that would most likely cause a positive test result.View Page
A voided urine specimen is delivered from the women's clinic to the laboratory six hours after collection. The following results are reported:Color: yellow Protein: negative Bilirubin: negativeClarity: cloudy Glucose: negative Urobilinogen: 0.2 mg/dLSp. Gravity: 1.020 Ketone: negative Nitrite: positivepH: 9.0 Blood: negative Leukocyte esterase: negativeWhat might these results indicate?View Page
pH Value

Urine pH results must be evaluated in conjunction with a patient's medical condition. Factors to be considered include:respiratory or metabolic acidosis respiratory or metabolic alkalosis renal function crystal or calculi formation urinary tract status diet

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Clinical Significance cont'd

Proteinuria related to kidney impairment may be due to glomerular membrane damage caused by toxic agents, immune complexes found in lupus erythematosus, or streptococcal glomerulonephritis. The amount of protein present in urine samples from patients with glomerular damage usually ranges from 10-40 mg/dl. If the urinary protein is due to a disorder that affects tubular reabsorption, the urine protein quantities will be much greater. In patients with multiple myeloma, proteinuria is due to the excretion of the Bence Jones protein. This low molecular weight protein produced by a malignant clone of plasma cells circulates in the blood and is filtered in the kidneys in quantities exceeding the tubular capacity. This excess protein is excreted in the urine.

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False Negative Results

False negative bilirubin dipstick results are often due to testing a specimen that is not fresh. Bilirubin breaks down when exposed to light. Indoxyl sulfate (Indican) can produce a yellow orange-to-red color response which may interfere with the interpretation of a positive or negative reaction. Positive nitrites due to a urinary tract infection may also cause a false negative result.

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False Positive Results

A false positive result for blood on the reagent strip can occur when oxidizing contaminants, such as hypochlorite (bleach), remain in collection bottles after cleaning. Contamination of the urine with provodine-iodine, a strong oxidizing agent, used in surgical procedures can result in a false positive reaction. Microbial peroxide found in association with urinary tract infections may also cause false-positive results. Capoten® (Captopril) can cause decreased reactivity. The muscle tissue form of hemoglobin, myoglobin is a well-known cause of false-positive reactions on the blood portion of the reagent strip. When tissue hemoglobin is present, the urine specimen has a clear red appearance. Patients suffering from muscle-wasting disorders or muscular destruction due to trauma, prolonged coma, or convulsions or individuals engaging in extensive exertion may have myoglobin in their urine. Specific tests for myoglobin, such as immunodiffusion techniques or protein electrophoresis, are needed to confirm the presence of this substance in a urine specimen. Levels of ascorbic acid normally found in urine do not interfere with this test.

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Clinical Significance

No blood is found in the urine of healthy individuals although samples from menstruating females, frequently, but not always, test positive for blood. Hematuria is associated with renal or genital urinary disorders in which the bleeding is the result of irritation to the involved organs or trauma. Examples include renal calculi, pyelonephritis, glomerulonephritis, tumors, trauma or exposure to toxic chemicals or drugs and/or strenuous exercise. Hemoglobinuria may be due to the lysis of red cells within the urinary tract. If it is caused by intravascular hemolysis, the hemoglobin is then filtered through the glomeruli. In the normal individual, the hemoglobin molecule attaches to haptoglobin and in this way bypasses the kidney filtration system. When the hemoglobin/haptoglobin system is overwhelmed, as in cases of hemolytic anemia, severe burns, transfusion reaction, infection or strenuous exercise, hemoglobin passes into the urine.

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Nitrite Test

The nitrites portion of the reagent strip provides a rapid screening test for the presence of gram-negative bacteria that are often responsible for urinary tract infections. Although urine cultures are still needed to confirm the diagnosis and monitor any urinary tract or kidney infection, the need for a culture may not be obvious because in some cases of early bladder infection, the symptoms may be vague or the patient may be asymptomatic. Diagnosis and treatment of cystitis (bladder infection) is important because if left untreated it may result in kidney damage, impairment of renal function, hypertension and/or septicemia.

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Test Sensitivity

This test is sensitive to 0.06-0.1 mg/dL nitrite ion in urines with a low specific gravity and ascorbic acid concentrations of less than 25 mg/dL. Pink spots or pink edges should not be interpreted as a positive result because some medications can color urine red or turn red in an acid environment. Any degree of uniform pink color should be considered positive, suggesting the presence of 105 organisms/mL. Detection of low levels of nitrite ion may be enhanced by comparing the activated test strip to a white background. It is important to note that color development is NOT proportional to the number of bacteria present. The test is specific for nitrites and does not react with any other substances normally present in urine. Negative results do not necessarily rule out a urinary tract infection because yeasts or gram-positive bacteria unable to reduce nitrites may be the causative agent.

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Clinical Significance

Early detection of bacteria is important in order to prevent cystitis from developing into inflammation or infection involving the kidney and renal pelvis. The nitrite portion of the test strip can be used to screen individuals who are at risk for developing urinary tract infections, such as diabetics, persons with recurrent infections, or pregnant women. The test is also useful in evaluating the success of antibiotic therapy that is used to treat a bladder infection.

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Urobilinogen

Urobilinogen is a byproduct of hemoglobin breakdown. It is produced in the intestinal tract as a result of the action of bacteria on bilirubin. Almost half of the urobilinogen produced recirculates through the liver and then returns to the intestines through the bile duct. Urobilinogen is then excreted in the feces where it is converted to urobilin. As the urobilinogen circulates in the blood to the liver, a portion of it is diverted to the kidneys and appears as urinary urobilinogen. Up to 1 mg/dL or Ehrlich unit of urobilinogen is present in normal urine. A result of 2.0 mg/dL represents the transition from normal to abnormal and the patient should be evaluated further. It is important to note that the reagent strip cannot determine the absence of urobilinogen.

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Clinical Significance

Urinary urobilinogen may be increased in the presence of a hemolytic process such as hemolytic anemia. It may also be increased with infectious hepatitis, or with cirrhosis. Comparing the urinary bilirubin result with the urobilinogen result may assist in distinguishing between red cell hemolysis, hepatic disease, and biliary obstruction. Urobilinogen is increased in hemolytic disease and urine bilirubin is negative. Urobilinogen is increased in hepatic disease, and urine bilirubin may be positive or negative. Urobilinogen is low with biliary obstruction, and urine bilirubin is positive. Reagent strips methods however, cannot distinguish normal urobilinogen from absent urobilinogen, as might be seen in complete biliary obstruction.

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Granulocytic white blood cells

Granulocytic white blood cells in a urine sample suggest the presence of a urinary tract infection. Granulocytes, which include neutrophils, basophils and eosinophils, contain esterases. These esterases catalyze the strip reagent indoxylcarbonic acid ester to release indoxyl. Indoxyl reacts with a diazonium salt to produce a purple color. The intensity of the color produced is proportional to the amount of enzyme present.

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False Positive Leukocyte Esterase Test

A false positive result may occur in the presence of strong oxidizing agents in the collection container. In random urine specimens from women, a positive result for leukocyte esterase may be due to a source external to the urinary tract. Other urine sediment findings such as bacteria, squamous or renal epithelial cells, lymphocytes or red blood cells do not contain esterases, and would not produce a positive leukocyte esterase test.

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To screen for urinary tract infections leukocyte esterase should be coupled with: (Choose ALL of the correct answers)View Page

Chemistry / Urinalysis Question Bank - Review Mode (no CE)
The cells faintly seen between the arrows are consistent with:View Page
Pheochromocytoma is a tumor of the adrenal medulla that results in elevated urinary levels of all but which of the following:View Page

Confirmatory and Secondary Urinalysis Screening Tests
Heat and Acid Test for Urinary Protein

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Correlation of Urine Glucose and Ketones

Screening for ketonuria is useful in following the effects of treatment for diabetes and in judging the severity of acidosis. Large amounts of ketones will appear in the urine before serum ketone levels are elevated.

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Urinary Ketones

Ketone bodies are formed in the liver as intermediates in the catabolism of fatty acids. In healthy individuals, ketone bodies are almost completely metabolized so that only negligible amounts appear in the urine.

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Diabetes and the Current American Diabetes Association Guidelines
Diabetes - A Metabolic Disorder

Diabetes results when insulin concentrations are absent, reduced, or when insulin action is impaired (referred to as insulin resistance). Without cellular uptake of blood glucose for energy, the balance of metabolizing carbohydrates, fats, and proteins for energy is lost. Hyperglycemia and excess use of fats and proteins for energy result. The latter causes excess acetyl-CoA which is converted to ketone bodies or to cholesterol.Polydipsia, polyuria, and unexplained weight loss are symptoms of diabetes. Polydipsia and polyuria occur as the body tries to lower blood glucose concentrations with increased urinary excretion of glucose. Weight loss results from increased utilization of proteins and fats for energy. The image on the right represents impaired metabolism in diabetes. The thicker arrows represent the pathways that are imbalanced. In normal carbohydrate metabolism, the opposing arrows would be of the same size, representing a normal pathway and a balanced metabolism.

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Urine Glucose

Before glucose meters were available, urine glucose was frequently used to approximate diabetic glucose levels. Blood glucose levels can be related to urine glucose concentration because of urinary excretion of glucose. Physician offices, clinics, and patients at home tested urine with reagent strips for a semi-quantitative measurement of urine glucose and adjustments in insulin therapy were made. Monitoring a diabetic carbohydrate management is seldom performed this way today. Portable meter measurement of blood glucose is a much better management method. Urine glucose measurement is neither sensitive nor specific and does not give information about blood glucose below the renal threshold (usually 180 mg/dL).As a semiquantitative measurement, urine glucose is a routine assay on urinalysis test and an abnormal result would be investigated with blood levels. If quantitative measurements are needed, a timed urine specimen is collected and measured for glucose by blood glucose methods.

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Urinary Albumin

Because of the risk of nephropathy, monitoring renal function is critical in diabetes management. Renal failure occurs more often in type 1 diabetes but because of the greater incidence of type 2 diabetics, a larger number of type 2 individuals are among those with diabetic nephropathy. Diabetic urinary albumin levels are monitored with urinary albumin excretion (UAE); these assays are referred to as microalbuminuria testing.

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Urinary Albumin Excretion

Screening for early occurrence and low amounts of albumin in urine detects microvascular disease before impaired renal function and insufficiency occur. Regular screening of urinary albumin excretion (UAE) is recommended for individuals with both type 1 diabetes and type 2 diabetes as an early indicator of renal disease. It is recommended at the time of initial diagnosis and annually thereafter for patients with type 2 diabetes, and commencing annually 5 years after the initial diagnosis of type 1 diabetes. Control of blood pressure and blood glucose concentrations can slow the rate of renal function decline.

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Microalbuminuria

Microalbumin is not a measurement of a small size albumin molecule but measurement of low concentrations of urinary albumin in diabetes to identify early renal impairment. Microalbuminuria tests measure concentrations of albumin that are lower than levels that can be detected with routine urine dipstick tests for protein. Timed, overnight, and first morning specimens can be screened for microalbuminuria. Quantitative measurements are also utilized for screening of renal impairment and for monitoring treatment.

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What is the role of microalbuminuria testing?View Page

Multi-drug Resistant Organisms: MRSA, VRE, and Clostridium difficile
Healthcare (Hospital)-Associated MRSA versus Community-Associated MRSA

As mentioned in the course introduction, MRSA infections fall into two general types:Healthcare-associated MRSA (HA-MRSA) Infections that occur in people who are, or have recently been, hospitalized. Community-acquired MRSA (CA-MRSA) Infections that are apparently acquired in the community There are a number of factors that distinguish HA-MRSA from CA-MRSA isolates. These factors are summarized in the table below.FactorHA-MRSA CA-MRSAOrigin of strainsNosocomial infectionsFive isolates associated with healthcare settings: USA100, -200, -500, -600, -800USA100 is the predominant isolate while USA 200 is the second most common isolate. USA700 has been isolated in both healthcare and community settings.Evolved from endemic methicillin-susceptible S. aureus (MSSA) strains Two clones, USA300 and USA400, are associated with the majority of CA-MRSA infections in the United States. USA300 has emerged as the most prominent clone and is not found among hospital strains.Genetic lineageIsolates usually carry large SCCmec types I, II or III (34-67 kb)The larger size of SCCmecII and III permits the inclusion of other non-beta-lactam resistance genes so that HA-MRSA strains tend to be multi-drug resistantIsolates carry a smaller SCCmec variant, predominantly type IV (24 kb), less often type V or variant VT. SCCmecIV (except for mecA) does not permit the inclusion of other non-beta lactam resistance genes so that CA-MRSA isolates exhibit resistance to only methicillin and erythromycin and are more often susceptible to other non-beta lactam antibiotics (eg., trimethoprim/sulfamethoxazole (SXT) and clindamycin). Affected populationLargely affects older adults and people with weakened immune systems; those who have undergone surgical procedures are at increased risk. Healthy persons in the general population without established risk factors for MRSA acquisitionClinical syndromesFound at multiple sites, most commonly bloodstream infections, urinary tract infections (UTI) and respiratory tract infectionsPredominantly skin and soft tissue infections (SSTIs), such as abscesses, cellulitis, folliculitis and impetigo and a serious form of pneumoniaGenes for Panton-Valentine leukocidin (PVL) are associated with SCCmecIV; the clinical spectrum of infections caused by CA-MRSA is directly related to the presence of PVL genes, coding for the production of a cytotoxin that causes tissue necrosis and leukocyte destruction.

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Enterococci

Enterococci are catalase-negative gram-positive cocci occurring singly, in pairs, or in chains; cells can be ovoid to coccobacillary. There are over twenty species in the genus, categorized within five major groups. Enterococcus faecalis is the most frequently isolated species; Enterococcus faecium, although less frequently encountered, is a significant pathogen.The Enterococci are widespread in nature; in humans they primarily colonize the gastrointestinal tract but are also found in the genitourinary tract. Enterococci are frequently encountered in urinary tract infections; they are also isolated from wound infections and blood cultures. They are also an important cause of endocarditis.

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Mycology: Yeasts and Dimorphic Pathogens (retired 2/12/2013)
Match the name of each species of yeast listed below with the location listed in the drop-down box where that species may be concentrated.View Page
Arrange the yeast species listed in the drop-down box in order of increasing virulence, from the least to the most pathogenic.View Page
Match the complications that are most likely to be associated with each of the two yeast diseases that are listed in the drop-down box:View Page
The colonies illustrated in this photograph were recovered from a blood culture after 48 hour incubation at 30°C. The most likely source for the septicemia is:View Page

Parasitology Question Bank - Review Mode (no CE)
This stool parasite measures 135 µm by 50 µm and is the causative agent of:View Page

Reading and Reporting Gram Stained Direct Smears
Determine the Quality of a Urine Specimen Submitted for Culture

The presence of many squamous epithelial cells (SQEs) also indicates a poorly collected urine specimen. If many SQEs are noted upon microscopic examination, the specimen should be recollected. The patient must be instructed how to collect a midstream, clean catch specimen. A Gram stain of a fresh, midstream urine sample would provide information that could help the physician decide whether to prescribe an antibiotic and the choice of antibiotic based on gram-reaction of the bacteria. Examine a Gram-stained slide made from a drop of uncentrifuged urine under oil immersion (1000X) magnification. If more than one bacterial organism is observed per oil immersion field, it can be determined that the quantity of bacteria is >105 colony forming units (CFU) per mL, and the patient probably has a urinary tract infection (UTI). The Gram stain reaction would also be important. Most bacteria that cause UTIs are gram-negative Enterobacteriaceae. A Gram stain report in this case would be "gram-negative bacilli consistent with quantity >105 CFU/mL."

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The Urine Microscopic: Microscopic Analysis of Urine Sediment
The sediment from a freshly collected urine specimen is examined microscopically. In addition to bacteria, what other finding from the list below would further indicate the presence of a urinary tract infection (UTI)?View Page
Parasites which can be found in urinary sediment include all of the following EXCEPT:View Page
Which of the following macroscopic findings is MOST consistent with the microscopic finding of casts?View Page
Formation and Significance of Casts

Casts are cylindrical bodies formed either in the distal convoluted tubules or the collecting ducts of the kidney. Since the walls of the tubule act as a mold for cast formation, the width of the tubule determines the width of the cast. Thus, narrow casts are formed in the distal tubules while broad casts are formed in the collecting ducts. The matrix of all casts is thought to be Tamm-Horsfall protein, a glycoprotein secreted by the distal loop of Henle and the distal tubule. This protein entraps cells and granular material of tubular origin. Very few casts are seen in the urine of a person without renal disease, except for hyaline casts, which may be transiently present after strenuous exercise, and during fever, diuretic therapy, and congestive heart failure. A significant number of urinary casts usually indicates the presence of renal disease.

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Broad Cast

Broad casts or "renal failure' casts are formed in the collecting ducts as the result of urinary stasis and are two to six times the size of other types of casts. Any type of cast can be a broad cast. Broad casts are typically seen in patients with advanced renal failure.

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All of the following factors favor cast formation EXCEPT:View Page
Factors Promoting Cast Formation

The following factors promote the formation of casts in the kidney:Larger than normal amounts of plasma proteins entering the tubulesDecreased pHDecreased urinary flow rateIncreased urine concentrationAfter formation, casts are loosened from the tubules and discharged into the urine.

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The Urine Microscopic Exam

The urine microscopic exam is performed on a centrifuged urine sediment. The sediment contains all the formed elements or insoluble materials that have accumulated in the urine through its passage from the kidney to the lower urinary tract. These formed elements include cells, casts, crystals, and miscellaneous structures.

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Microscopic Examination

The microscopic examination was traditionally performed on all urine specimens. Today, many laboratories perform a urine microscopic only if preliminary evaluation indicates the need for microscopic examination. Such laboratories must have criteria determining the specimens on which urine microscopic examinations will be performed. The microscopic exam is often important in detecting and evaluating renal and urinary tract disorders as well as other systemic diseases.

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Urine Sediment

Urine sediment may also contain white blood cells (WBCs). Most of the WBCs in urine are segmented neutrophils. Since it is possible that lymphocytes, monocytes, and/or eosinophils may be present, the cells in urine can be stained if it is necessary to differentiate them. The segmented neutrophil indicated by the blue arrow shows a distinct nucleus. When viewing urinary sediment under the microscope, the fine focus adjustment must be used to identify white blood cells. White blood cells swell in dilute alkaline urine and the cytoplasmic granules exhibit brownian movement resulting in "glitter cells." These cells lyse rapidly. "Glitter cells" are most easily seen when viewed under phase-contrast microscopy.

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Bacteria

Bacteria may also be present, especially during a urinary tract infection. This view shows bacteria as solid gray rods or cocci. Since bacteria may also be a contaminant in specimens remaining at room temperature, or due to an unclean catch, caution must be observed in reporting bacteria. If 20 organisms per high power field (HPF) are seen, the bacteria are considered to be clinically significant.

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The different types of epithelial cells include: (Choose all that apply.)View Page
Cell Types Observed in Urine Sediment

Cells which may be present in the urine include epithelial cells, white blood cells (WBCs) and red blood cells (RBCs). The epithelial cells in the urine may originate from any site in the genitourinary tract. It is normal to find a few epithelial cells in the sediment. WBCs may enter the urinary tract anywhere from the glomerulus to the urethra. The WBCs are mostly neutrophils. RBCs may originate in any part of the urinary tract. Normally, RBCs do not appear in the urine, although the presence of a few RBCs is not considered abnormal.

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Identification of Crystals

Identification of crystals found in the urine sediment requires knowledge of the urinary pH. Large crystals are identifiable under low power. High power magnification is required for smaller crystals. Most crystals can be identified by morphology alone. Urine pH and reagent strip results can provide supporting information. If further examination is necessary birefringence and solubility characteristics should be performed.

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Introduction

In this topic, certain miscellaneous structures found in the urinary sediment will be discussed. These structures include:Parasites Sperm Fat bodies Mucus External contaminants

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Parasites

Parasites which may be found in urinary sediments include Trichomonas vaginalis, Enterobius vermicularis and Schistosoma haematobium. It is also important to note that parasites and parasitic ova may be seen in urine sediments as a result of fecal or vaginal contamination. This slide shows examples of Trichomonas vaginalis. In the female, Trichomonas is usually found as a contaminant from vaginal infection and is often accompanied by an increase in the number of white cells. Trichomonas is highly motile, measuring 5 - 15 microns with a characteristic pear shape. It has multiple anterior flagella and the nucleus is often apparent.

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Which of the following are artifacts often confused with urinary elements? (Choose all that apply.)View Page

Transfusion Reactions
Definition/Manifestation/Prevalence

Post-transfusion purpura (PTP) is a very rare complication of blood transfusion. It has been most commonly associated with the transfusion of red blood cells and whole blood, but has also been seen in platelet and plasma transfusions. It is characterized by a rapid onset of thrombocytopenia, or decreased platelet count, which results from the product of a platelet alloantibody. Platelet counts are usually less than 10,000/µL. Reactions occur around 7 to 14 days post-transfusion. Patients present with purpura, bleeding from the mucous membranes, gastrointesinal ,and/or urinary tract bleeding. Melena and vaginal bleeding have also been reported. The thrombocytopenia is usually self-limiting. Platelet counts and coagulation studies aid in the diagnosis. Patients can also be tested for platelet specific antibodies, human leukocyte antigen (HLA) antibodies and lymphocytotoxic antibodies. The differential diagnosis includes other causes of thrombocytopenia.

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Post-transfusion purpura (PTP) is characterized by which of the following?View Page


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