Read 2006 Educational Activities - CM-B text version

Please circulate to your laboratory staff. ALL staff can now earn free CME/CE credit with the Clinical Microscopy Survey (CM-B)!

Complete the specified reading in the 2006 CM-B Participant Summary and the related online activity on the CAP Web site to earn free CME/CE credit. All staff from laboratories participating in the Clinical Mircroscopy Survey (2006 CM-B) can now individually earn CME/CE credit by following the instructions below. Please note that you will need the Kit ID number and CAP number found in the header of your CM-B evaluation or on your result form in order to access the online activity. You may enroll in and complete this activity until March 30, 2007. After this date the activity will no longer be available. Directions: 1. Complete the specified reading in the Participant Summary that was mailed to your institution. You may also obtain an electronic version of this reading by completing the following steps to access the online portion of this education activity. 2. Go to www.cap.org and log in with your individual User ID and Password. a. If you are unsure whether you have an individual Web account with the CAP, or do not remember your User ID and Password, click on the Forgot your user ID or password? link. You may either enter the requested security information and the system will recognize you and log you in, or you may enter your last name and e-mail address so that the system can send you a temporary ID and password. b. If you do not have an individual Web account, click on the Create an Account link. Complete and submit the account request form. You will be notified within one business day that your individual account has been activated. 3. Click on the Education Programs tab. Under "Course Catalog," click on Surveys. 4. Click on the CM-B 2006 link. 5. Click on the Enroll link. This will bring up the validation screen. 6. Enter and submit the Kit ID and CAP numbers associated with the CM-B Survey. These numbers can be found in the header of your CM-B proficiency testing evaluation or on your result form and are required to access the online activity. 7. Click on the Launch link. The first page of the activity will open. 8. Read and follow the instructions provided online to access the electronic version of the reading and answer the learning assessment questions. 9. Once completed, the CAP will issue and mail your CME/CE certificate within four weeks for the credit(s)/hour(s) earned. For more information, call a CAP Customer Contact Center representative at 800-323-4040 (847-8327000) option 1#. Kit ID #: _____________________________ CAP #: _____________________________

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CM-B 2006: Clinical Microscopy

Continuing Education Information Accreditation

The College of American Pathologists (CAP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CME Category 1

The CAP designates this educational activity for a maximum of one category 1 credit toward the AMA Physician's Recognition Award. Each physician should only claim those credits he/she actually spent in the educational activity.

CME (International physicians)

The American Medical Association has determined that physicians not licensed in the US who participate in this CME activity are eligible for AMA PRA category 1 credit.

CE (Continuing Education for non-physicians)

The CAP designates this educational activity for a maximum of 1 credit/hour of continuing education. Each participant should only claim those credits/hours he/she spent in the educational activity. This activity is acceptable to meet the continuing education requirements for the ASCP Board of Registry Certification Maintenance Program. This activity is approved for continuing education credit in the states of California and Florida.

Disclosure Statement

All authors/planners must disclose to the program audience any financial interest or relationship with the manufacturer(s) of any commercial product(s) that may be discussed in the educational activity or with the manufacturer of a product that is directly competitive with a product discussed in the activity. Relevant financial relationships are considered to be any financial relationships in any amount occurring within the past 12 months that create a conflict of interest. The College of American Pathologists does not view the existence of these interests or uses as implying bias or decreasing the value to participants. The CAP, along with the Accreditation Council for Continuing Medical Education (ACCME), feels that this disclosure is important for the participants to form their own judgment about each activity.

The following authors/planners have financial relationships to disclose: None The following authors/planners have no financial relationships to disclose: Patricia A. Devine, MD, FCAP Barb Flamich, MT(ASCP) The following In-Kind Support has been received for this activity: None The following Commercial Support has been received for this activity: None

Learning Objectives

Upon completing the reading and answering the learning assessment questions, you should be able to: 1. 2. 3. Assess chemical urinalysis with urine sediment findings. Discuss pathogenesis of microscopic urine sediment elements. Describe the clinical significance of chemical and microscopic examination of urine.

All material is © 2006 College of American Pathologists, all rights reserved

CM-B 2006: Clinical Microscopy OVERVIEW

One of the most frequently performed tests in health care facilities is urinalysis, which has several clinical uses. It can be used to screen for the presence of disease, particularly in individuals without medical symptoms; monitor a disease condition; or evaluate the effectiveness of medication and treatment. A urinalysis test generally consists of the following: 1. Physical- determining the physical properties of a urine sample 2. Chemical- analyzing urine for the presence of different chemical substances using reagent strips 3. Microscopic- examining a urine sediment for cells, casts, or non-cellular elements A fourth aspect of urine evaluation is a specialized cytology review. In this cytodiagnostic review, urine is examined for the detection and diagnoses particularly of neoplastic cells, viral inclusions, and other organisms. Physicians and cytology technical staff perform the cytology review, and medical technologists do not perform cytodiagnostic review.

Clinical Case Studies Case I

A 7-year-old boy presents to his pediatrician with vomiting, bloody stools, and joint pain. Physical examination showed on his extremities and buttocks a rash described as purpura. The boy's mother mentioned that he had a recent upper respiratory infection. Laboratory workup included a urinalysis, which shows the findings in Image 1 below. Image 1.

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CM-B 2006: Clinical Microscopy

Case II

A 42-year-old male presents to his primary physician for follow-up of hematuria detected on urine dipstick during a routine pre-employment medical examination. The patient is asymptomatic and has been in good health without significant past medical and surgical history. Urine sediment examination is abnormal. An example of the predominant urinary sediment can be seen in Image 2 below. Image 2.

Case III

A 64-year-old male with recurrent leukemia recently underwent chemotherapy. Routine laboratory workup included a urinalysis, which revealed the findings in Image 3 below. Image 3.

The results of a urinalysis may be the first indication of disease or the presence of a serious medical condition. Urinalysis results may reveal kidney disease or a urinary tract abnormality, but these results may also indicate non-renal diseases that could involve liver or the presence of a metabolic condition such as diabetes mellitus. Urinalysis findings may prompt further clinical evaluation or treatment. What pathological conditions can be associated with the above clinical histories and laboratory findings?

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CM-B 2006: Clinical Microscopy INTRODUCTION

Most urinalyses are performed on voided specimens, which are relatively easy to obtain. In the chemical portion of a urinalysis, a urine sample is tested with different reagent strips using either an automated or manual (dipstick) method. These strips can detect in urine abnormal chemical and metabolic findings such as the presence of blood, sugar, protein, and bilirubin. These abnormal findings can indicate disease involving the kidney, upper and lower urinary tracts, or be systemic in nature. Since the chemical urinalysis test is a screening test, additional testing is necessary. Confirmatory testing is needed particularly if the initial strip results are questionable or for detection of interfering substances that can cause false positive or false negative results. Microscopic examination of urine sediment can identify findings, especially cells and non-cells, which cannot be detected by chemical or physical evaluation. The microscopic sediment examination can supplement the findings of chemical urinalysis as exemplified when blood (hematuria) is detected on chemical analysis and red blood cells are concomitantly seen on microscopic sediment. Further clinical work-up can confirm the disease or detect other significant medical and metabolic conditions. Examination of urine sediment, using bright field or phase contrast microscopy, can reveal the presence of cells, crystals, casts, organisms, and non-cells. These cannot be detected with the chemical urinalysis tests. When examining microscopic urine sediment, a laboratorian must be able to identify and in some instances quantitate morphologically cells, casts, and other non-cellular elements. The presence of these findings can be associated with significant renal or non-renal disease. There are various facets to a urinalysis evaluation, including the: Correlation of urinalysis findings with physiological and pathological abnormalities of the urinary tract system Familiarity with interfering substances that may cause spurious chemical urinalysis test results Microscopic recognition, pathogenesis and overall examination of urine sediment Association among urinalysis results and disease detection and treatment It is beyond the scope of this education activity to provide comprehensive details of all aspects of urinalysis and further information can be obtained in the references listed on page 22.

RENAL PATHOPHYSIOLOGY

The kidney has many functions important to the regulation of body metabolism. Major renal functions include: Elimination of the body's metabolic wastes Regulating electrolyte and fluid balances Maintaining acid and base balance Resorption of essential body substances and water Hormone production, i.e., erythropoietin for red blood cell production Regulate calcium and phosphate absorption Maintain blood pressure and enhance vascular tone A urinalysis test can reveal renal dysfunction and disease especially in asymptomatic individuals.

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CM-B 2006: Clinical Microscopy

The basic functional and structural unit of the kidney is the nephron, which is a microscopic entity. Each kidney has approximately 1 million nephrons. A nephron consists of a glomerulus and tubular structures comprised of proximal convoluted tubules, loop of Henle, distal convoluted tubules, and collecting ducts (See Figure 1 below). Blood enters the glomerulus, which is primarily comprised of capillaries, that function as a filter. Red blood cells normally do not pass through the glomeruli, but are retained in the body's circulatory blood stream. The resultant plasma is considered to be an ultrafiltrate after it passes through the glomeruli. This filtrate then enters into the renal tubules and collecting ducts, which reabsorb vital biochemical substances and ions. Renal tubule cells secrete metabolic wastes into the passing filtrate for removal from the body. The filtrate is eventually excreted as urine. Figure 1: Diagram of a Nephron 1 ­ Bowman's capsule 2 ­ glomerulus 3 ­ afferent arteriole 4 ­ efferent arteriole 5 ­ proximal convoluted tubule 6 ­ distal convoluted tubule 7 ­ collecting duct 8 ­ loop of Henle 9 ­ peritubular capillaries

The various constituents of the nephron have important physiological and biochemical functions, which can be destroyed or compromised if certain diseases are present. In addition to the glomerulus, which essentially filters blood, the following provide a summary of the nephron's functions:

Proximal Convoluted Tubules

Reabsorption of ions (sodium, chloride, calcium, and potassium); phosphate; bicarbonate; amino acids; glucose; and water. These are reabsorbed and returned to blood stream.

Loop of Henle

Has major impact on urine concentration. It is permeable to water and actively reabsorbs ions (sodium, chloride, magnesium, calcium) as necessary to maintain adequate hydration for the body.

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CM-B 2006: Clinical Microscopy

Distal Convoluted Tubules

Reabsorbs sodium and water and secretes ions (potassium, and hydrogen) and ammonia. This resorption and secretion affect urine pH and osmolality.

Collecting Ducts

Reabsorbs water and sodium and is influenced by hormonal regulation, namely anti-diuretic hormone (ADH) and aldosterone. Final product is urine. From the kidney's collecting ducts, the urine passes through the ureters to the bladder and then through the urethra prior to being voided. Urine is predominantly comprised of water and urea although other constituents such as creatinine, ions, ammonia, and phosphates can be present in lower quantities. Urine can also contain cells, casts, and crystals. For approximately 120 mL of plasma that is filtered through the glomerulus in a minute, approximately 1 mL is excreted as urine. Water can be removed or retained by the body depending on physiological need. If an individual is dehydrated, the body will retain water and the urine will be concentrated. The tubules can absorb water and salts. This determines the urine concentration and the body's hydration status. The specific gravity value is an indication of urine concentration. Kidney reabsorption of some substances is influenced by their concentration in plasma. For example, glucose is not normally found in urine. However, if the plasma concentration of glucose is high, i.e., 160-180 mg/dL, this increased concentration cannot be reabsorbed and glucose subsequently passes into the urine.

URINE COLLECTION AND PROCESSING

A properly obtained and processed sample is essential for optimal results from a urinalysis. Improper procurement and/ or technical processing can compromise the results. A urinalysis can be performed on voided or clean-catch voided urine specimens or on urine collected by catheterization or by suprapubic aspiration. The latter technique is used for obtaining urine specimens in babies and young children. Although most urine testing is done on voided specimens, a clean catch specimen may be necessary if contamination of blood, semen, fecal material, and vaginal or urethral discharge is suspected. For microscopic review of urine sediment, a first-voided urine specimen is preferred when possible. Prompt assessment of urine is necessary for reliable results. If this is not possible, refrigeration of the sample is advised to prevent bacterial overgrowth, which occurs if urine remains standing at room temperature.

URINE PHYSICAL EXAMINATION

Appearance of urine is evaluated for its clarity and color. Clarity of urine is usually clear. A variety of conditions may impart a cloudy or turbid appearance to a urine sample. These include: vaginal secretions or semen, increased red or white blood cells, protein, glucose, or crystals. Microscopic examination of the urine sediment can be useful in determining the etiology of the urine turbidity. Lipid in urine can be secondary to trauma of a fatty marrow.

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CM-B 2006: Clinical Microscopy

Color changes may be an indicator for the presence of pathological or non-pathological conditions. For the latter, certain food colors, vitamins, or drugs can affect urine color. Vitamins such as riboflavin commonly cause urine to be a deep yellow color. For patients who have obstructive liver disease and jaundice, urine can be brown in color. Enzymatic activities of certain organisms can cause color changes in urine as seen in blue-green urine associated with Pseudomonas and purple urine associated with Klebsiella infections. Artificial colors, present in foods or drugs, can cause urine discoloration including blue-green hues. While odor is not a routine evaluation of urinalysis, a strong pungent odor can be associated with bacterial infections while a sweet odor may indicate diabetic ketoacidosis. Maple syrup urine disease is a rare but serious amino acid disorder. Patients with this disease have in their urine a distinctive sweet smell resembling maple syrup.

CHEMICAL URINALYSIS

Dipstick/ reagent strips are used as screening tests to evaluate in urine the following parameters: pH, blood, glucose, ketones, protein, bilirubin, urobilinogen, nitrite, leukocyte esterase, and specific gravity. These parameters provide information into the physiological functioning of the kidneys, and test results consist of macroscopic qualitative and semi-quantitative values. Since the chemical reagent strips are a screening test and its results can be influenced by test interferences, false negative, or false positive findings, follow-up confirmatory testing is done. Table 1 on the following pages summarizes the major chemical reagent strip parameters tested in urine.

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CM-B 2006: Clinical Microscopy

Table 1. Chemical Reagent Strip Parameter Facts Parameter pH Fact Assesses acid and base equilibrium - Proximal and distal convoluted tubules regulate bicarbonate and ammonium ions which influence pH levels. - - Blood Test results can be affected if prolonged time lapses prior to testing specimen. Confirmatory test is optional, but results can be compared to those tested with a pH meter. Detects presence of red blood cells, hemoglobin, and myoglobin - Small quantity of blood can be detected that is not apparent on visual examination of specimen. - Intact red blood cells or lysed cells containing hemoglobin can be detected. Destruction of muscle fibers causes release of myoglobin which tests positive. Simultaneous presence of hemoglobin and myoglobin can occur secondary to traumatic injuries. - Blood in urine (hematuria) can result from glomerular disease although several etiologies should be considered including: infection, toxins, increased blood pressure, tumor of upper or lower urinary tract, calculi (stones), hematologic disorders including coagulopathy and hemolysis. - False positive results may be due to bacterial peroxidase activity from urinary tract infections, bleach, or contamination from menstrual blood. - False negative results may be due to poorly mixed specimens, increased ascorbic acid (vitamin C) or antihypertensive drugs. - Confirmatory test is the examination of microscopic urine sediment for erythrocyte detection.

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CM-B 2006: Clinical Microscopy

Table 1. Chemical Reagent Strip Parameter Facts, continued Parameter Glucose Fact Glucose oxidase test is specific for glucose - If copper reduction test is used, glucose and other reducing sugars (sucrose, lactose, galactose, fructose, maltose, mannose, and pentose) can be detected. Due to genetic enzyme deficiencies, these other reducing sugars can be present in urine. This is particularly important in pediatric patients for early detection of diseases involving carbohydrate metabolism. - Elevated glucose blood levels, decreased glomerular filtration flow, and decreased tubular reabsorption can cause glucose in urine (glycosuria). - False positive results can be due to bleach, irregular storage of test reagent strips, and low specific gravity. - False negative results can be due to high specific gravity or increased ingestion of vitamin C. Ketones Abnormal carbohydrate metabolism or inadequate dietary carbohydrates result in increased fatty acid metabolism. Metabolic breakdown of fatty acids forms ketone bodies - - Ketone bodies consist of acetoacetic acid, beta-hydroxybutyric acid, and acetone. Increased ketones are most commonly seen in patients with diabetes mellitus but may also be associated with thyrotoxicosis, fever, or increased vomiting. - False positive results can be due to deeply pigmented urine or to urine with a high specific gravity. - False negative results can be due to unstable reagents.

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CM-B 2006: Clinical Microscopy

Table 1. Chemical Reagent Strip Parameter Facts, continued Parameter Protein Fact Proteinuria can have non-pathological or pathological etiologies - Physiological causes include vigorous physical exercise. Diseases, causing glomerular or renal tubular damage, can result in proteinuria. These include: glomerulonephritis, lupus, diabetes, multiple myeloma, and markedly elevated hypertension. - - - - - Markedly pigmented urine can interfere with test results. False positive results can occur with alkaline urine. Reagent strips are more sensitive to albumin than other proteins in urine. False negative results can occur in samples with increased proteins that are not albumin. Confirmatory testing can be done using sulfosalicylic acid, which forms a precipitate in the presence of protein. Bilirubin Is formed from the breakdown of hemoglobin. There is conjugated and unconjugated bilirubin. Conjugated or direct bilirubin is water soluble and can therefore be filtered through the glomerulus. Unconjugated or indirect bilirubin is insoluble in water and cannot be filtered through the glomerulus - Increased bilirubin is associated with liver disease and with obstruction of the bile outflow from the liver. - - False positive results can be due to drugs such as rifampin and chloropromazine. False negative results can be due to exposure of specimen to light, increased ascorbic acid, and drugs including pyridium. - Confirmatory testing can be done with a diazotization reaction in an acidic medium.

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CM-B 2006: Clinical Microscopy

Table 1. Chemical Reagent Strip Parameter Facts, continued Parameter Urobilinogen Fact In the liver, unconjugated bilirubin is converted to the conjugated form. Conjugated bilirubin is then hydrolyzed in the colon to form free bilirubin which is reduced to form urobilinogen. Urobilinogen is partly re-absorbed in the liver, partly excreted in feces, and a small portion excreted in urine - In liver disease, urobilinogen may not be reabsorbed and subsequently more will pass through the kidney and be excreted in the urine. - - - - - - Increased urinary urobilinogen can be associated with hemolysis. Urobilinogen represents a group of tetrapyrrole compounds and therefore is measured in units. Markedly pigmented urine can interfere with test results. False positive results can be due to drugs including methyldopa and sulfonamides. False negative results can be due to light exposure or if there is a delay in testing. Confirmatory testing may be performed using the Watson-Schwartz test that can differentiate particularly urobilinogen and porphobilinogen.

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CM-B 2006: Clinical Microscopy

Table 1. Chemical Reagent Strip Parameter Facts, continued Parameter Nitrite Fact Indirect test used for evaluating urinary tract infections - Some urinary tract bacteria pathogens, when present in significant numbers, can reduce nitrate in urine to nitrite. These pathogens include: Escherichia coli, Enterobacter, Klebsiella, and Proteus. - False positive results can be due to poor collection, improper storage of specimens, urine dyes, or medications such as phenazopyridine. - False negative results can be due to insufficient incubation of urine in bladder to convert nitrate to nitrite, acidic pH, urobilinogen, insufficient dietary nitrate, and ascorbic acid. - Confirmatory testing can be done by microbiology evaluation including culture and by examination of urine microscopic sediment. Leukocyte esterase Indirect test used for evaluating urinary tract infections - Significant numbers of neutrophils in a urine specimen may indicate a urinary tract infection. A neutrophil contains primary granules that have esterolytic properties and this esterase activity can be used to indicate intact or lysed neutrophils. - - False positive results can be due to vaginal contamination and bleach. False negative results can be due to antibiotics, increased specific gravity, ascorbic acid, and increased glucose and protein. - Confirmatory testing can be done by microbiology evaluation including culture and by examination of urine microscopic sediment.

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CM-B 2006: Clinical Microscopy

Table 1. Chemical Reagent Strip Parameter Facts, continued Parameter Specific gravity Fact Evaluates the kidney's ability to reabsorb ions, chemicals, and water and to maintain fluid and electrolyte balance - - Assesses an individual's state of hydration or dehydration. Low specific gravity of urine indicates low concentration and sample may not be satisfactory for evaluation. - - - - Reagent strips measure substances that can ionize. False positive results can be due to increased proteins. False negative results can be due to alkaline urine. Confirmatory testing can be done by a refractometer, which measures dissolved particles in a specimen solution.

MICROSCOPIC EXAMINATION OF URINARY SEDIMENT

Urinary sediments can be examined by manual, semi-automated, or automated methods. Processing a urine sample for microscopic review should be done promptly. For the manual method, an aliquot of 10-15 mL of urine is centrifuged with careful attention to centrifugation speed and time. Following centrifugation and decanting of the supernatant, the sediment is resuspended for microscopic evaluation. The sediment should be examined at low and high power fields with sublimed light or phase contrast illumination. In urinary sediment microscopic review, four essential aspects have to be considered: 1. Differentiate normal and abnormal sediments ­ understanding what constitutes normal urinary sediment both in its contents and on quantitative evaluation 2. Distinguish variations of normal and abnormal sediment findings 3. Determine artifacts and contaminants 4. Correlate sediment findings with chemical urinalysis results and with clinical presentation and history These objectives can be accomplished by the ability to identify cells, casts, crystals, and organisms and to distinguish these from contaminants or artifacts. For some sediment findings, quantitative assessment is important for clinical information. Red blood cells in small numbers can be a normal sediment finding but these cells in large numbers may signify serious disease. There can be variations of a given sediment finding. For example, uric acid crystals can differ greatly in size and shape. Crystal formation can depend

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CM-B 2006: Clinical Microscopy

on pH, temperature, and concentration. Knowing the results of the pH from the chemical urinalysis can be helpful in crystal identification.

Sediment Cells

Hematopoietic and epithelial cells can be found in urinary sediments. Erythrocytes and white blood cells are not an unexpected finding. Epithelial cells include squamous, urothelial (transitional), and renal tubular cells. Squamous cells are most commonly found. A list of some sediment cells and key facts appears in Table 2 below. Table 2. Sediment Cell Key Facts Sediment Cell Red blood cells Fact Small numbers of erythrocytes (0-3/HPF) can be found in urine as a normal finding and are considered to be a physiological and not a pathological finding. Red blood cells can be distinguished from other cellular elements by their biconcave disc shape and size with normal diameter of 7.5 microns. Shape can vary from normal, crenated, or swollen. In hypertonic or concentrated urine, red blood cells shrink and appear crenated. In hypotonic or dilute urine, red blood cells swell up and lyse Positive chemical urinalysis parameter for blood often prompts a sediment review Increased red blood cells in urine can be associated with disease involving the kidney particularly glomerulus or lower urinary tract including bladder or urethra. This includes malignancy of the urinary tract. Systemic diseases such as malaria or medical conditions including coagulopathies and toxic reactions to drugs can result in hematuria. In rare instances, excessive physical exercise can result in hematuria although this is uncommon and the increase in urine erythrocytes are considered to be a physiological etiology Dysmorphic red blood cells have variable sizes and shapes with protrusions. Their presence may indicate glomerular renal disease or vascular damage

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CM-B 2006: Clinical Microscopy

Table 2. Sediment Cell Key Facts, continued Sediment Cell White blood cells Fact Normal urine specimens may contain less than 5 leukocytes/HPF. Increased numbers of leukocytes can be associated with inflammation and infection of the genitourinary system. Bacterial cultures can be performed for follow-up Since white blood cells, particularly neutrophils, disintegrate in urine; identification of these cells can be difficult. While these inflammatory cells are usually seen in infections, other non-infectious etiologies such as calculi/stones or tumors can be associated with white blood cells When performing microscopic urine sediment review, distinction between red and white blood cells is difficult. 2% acetic acid causes red blood cells/erythrocytes to lyse, and can be used to distinguish the two cell types Squamous cells Squamous cells are the most commonly seen cells in urine sediments although their presence may indicate contamination from the urethra or from the vagina in females Urothelial (Transitional) cells Urothelial cells are epithelial cells that line the ureter, bladder, and a portion of urethra Small numbers of urothelial transitional cells in urine are generally a normal finding and due to normal sloughing or aging of cells Large numbers of transitional cells may be related to medical procedural instrumentation or to the presence of a malignancy. Further cytodiagnostic review should be done

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CM-B 2006: Clinical Microscopy

Table 2. Sediment Cell Key Facts, continued Sediment Cell Renal tubular epithelial cells Fact Renal tubular cells originate from proximal and distal convoluted tubules or collecting ducts. These cells vary in size depending on their origin within the nephron Detection of renal tubular cells can indicate tubular damage. These cells in urine can signify serious kidney disease secondary to acute tubular necrosis or toxic effects of drugs or metals For patients who have received kidney transplants, the presence of renal tubule cells may signify organ rejection Renal tubule cells may contain lipid absorbed from damaged nephritic glomeruli. Fat stains can confirm the presence of lipid Renal tubular cells may contain pigment most commonly hemosiderin. Hemosiderin is formed from the breakdown of hemoglobin or myoglobin and stains positive for iron Renal tubular cells may contain bilirubin pigment

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CM-B 2006: Clinical Microscopy

Table 2. Sediment Cell Key Facts, continued Sediment Cell Miscellaneous Fact Microorganisms can be found in the urine sediment and include bacteria, fungi, parasites, and epithelial cells with viral inclusions. The presence of bacteria can be a contaminant or pathogenic. If inflammatory cells are not present, the bacteria may be a contaminant although further studies including urine culture may be necessary in determining pathogenicity. If inflammatory cells are not present, fungi may be either a contaminant or pathogenic. Yeasts, most commonly Candida species, may be a contaminant Spermatozoa can be present in urinary sediments The presence of fecal material on urinary sediment examination is most commonly a contaminant from an incontinent individual. However, this finding can also be seen in patients who have fistulas linking the bladder with the intestines Environmental contamination from pollen or algae can be passed through skin and/or clothing fibers into urine specimens. Other contaminants include hair and pollen

Casts

Casts are usually formed in the kidney's distal convoluted tubule or collecting duct system and are therefore intrinsic to the kidney. Casts are comprised of plasma proteins from the glomerular filtrate and mucoprotein, known as Tamm-Horsfall, secreted by the renal epithelial cells. Immunoglobulins may be present within the casts. The presence of casts may be of non-pathologic (physiological) or pathologic significance. The presence of abnormal casts in urine is associated with diseases involving the kidney. Casts may be cellular or acellular or a mixture of both known as mixed casts. Acellular casts include: hyaline, granular, waxy, fatty, and pigment. Cellular casts include: red blood cells, white blood cells, and epithelial or bacteria, or mixed. Cellular casts are generally associated with kidney and urinary tract disease. Various factors including pH, high solute concentration, and ionic charges can alter the morphology of casts. As a cast moves through the kidney's tubules and collecting ducts and into the ureter and lower urinary tract, i.e., bladder and urethra, the cast cells undergo breakdown and degenerative changes. Physical properties of the urine and urinary stasis can affect cast morphology resulting in various shapes and configurations. Therefore, a first voided specimen is preferred when evaluating a urine sample for casts. A list of some casts and key facts appears in Table 3 on the following page.

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CM-B 2006: Clinical Microscopy

Table 3. Cast Key Facts Casts Hyaline and Granular casts Fact Both hyaline and granular casts can be found in low numbers (0-2 granular casts/LPF) in urine sediments. These casts are generally considered to be physiological although increased numbers can be associated with renal disease. Hyaline casts are the most commonly observed casts on sediment review. These casts lack color, are semitransparent, and have a low refractive index. Hyaline casts can be seen in individuals undergoing increased strenuous exercise although these casts may be seen in patients with congestive heart failure and dehydration Granular casts are comprised of urinary proteins, considered to be products of renal tubular epithelium. The presence of granular casts can be seen following heavy exercise, fever, or dehydration. Granular casts are brown in color and highly refractile. Increased numbers of granular casts on sediment can be associated with glomerular or renal tubular disease Red blood cell casts The presence of red blood cell casts is medically significant and associated with nephron damage often involving glomeruli, capillaries, and renal tubules. Distinguishing features of red blood cell casts are their refractive nature and color, i.e., redbrown or orange-yellow. Although the presence of red blood cell casts is associated with serious glomerular disease such as glomerulonephritis, these casts are associated with infections, namely pyelonephritis and with vascular damage as seen in renal infarction or renal vein thrombosis. Red blood cell casts are seen in vasculitis, sickle cell, and severe hypertension White blood cell casts White blood cell casts are readily identified by their leukocytes with multilobulated nuclei. These casts are associated with kidney infection, especially pyelonephritis

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CM-B 2006: Clinical Microscopy

Table 3. Cast Key Facts, continued Casts Renal tubular epithelial cell casts Fact Renal tubular epithelial casts occur following damage to renal tubular epithelium secondary to acute tubular necrosis, viruses, or chemotherapeutic drugs. These casts can be distinguished by their epithelial cellular and nuclear morphology and have a high refractive index Other casts Bacterial casts occur in pyelonephritis Waxy casts may be colorless or pale yellow with a high refractive index. The ends of the casts have a characteristic appearance referred to as `broken off' which may be a result of cellular degenerative changes. These casts are present in individuals with serious kidney disease and chronic renal failure Fatty casts contain lipid and are associated with the nephrotic syndrome Broad casts are large sized casts resulting from tubular dilatation and stasis, that is associated with destruction of renal tubules and chronic renal failure

Crystals

Crystals form from the precipitation of urine salts. Changes in urine temperature, pH, and concentration are factors that affect the solubility of urine salts. These changes can contribute to the development of crystals or to the formation of amorphous crystalline material. Crystals are not an uncommon finding in urine and most are without medical significance. The crystals described here will be limited. There are abnormal crystals of metabolic origin. Although these crystals are rare, they are clinically significant in a relatively small number of patients and families with a genetic predisposition. These include cystine, tyrosine and leucine crystals. The reader is encouraged to use the cited references for further details. When a crystal is detected on sediment examination, the pH of the urine can provide information to aid in crystal identification. A crystal is distinguished by morphology, color, pH, and its solubility properties in heated acids or alkali. Crystals can occur secondary to disease as described on the following page. A list of some crystals and key facts appears in Table 4 on the following page.

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CM-B 2006: Clinical Microscopy

Cholesterol Crystals

Are associated with renal diseases including the nephrotic syndrome.

Bilirubin Crystals

Can be seen in individuals with liver and hematological diseases.

Hemosiderin Crystals

Can occur following massive hemolysis. Medications and diagnostic interventions have also been invoked in the etiology of urine crystals. Patients, who are receiving sulfonamide drugs, can develop crystals. Urinary crystals can occur in some patients following use of dyes during radiographic evaluation. Table 4. Crystal Key Facts Crystal Uric acid Fact Uric acid crystals are common crystals identified in urine sediments. The crystals are present in acidic urine. Uric acid crystals have diverse morphological shapes and sizes (rhombic, needle shaped, barrel shaped, stars, club, rosettes, spears). The crystals are more commonly colored yellow to red/brown although colorless forms can occur. When polarized, urate crystals show birefringence, demonstrate various colors, and have a layered appearance The presence of uric acid crystals in fresh voided urine is of probable pathologic origin. Uric acid crystals are associated with high nucleoprotein metabolism and may be seen in individuals with gout, leukemia, and renal diseases Acidic urine, that is left to stand at room temperature, will develop uric acid crystals. In this context, the crystals are not considered to be of clinical significance

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CM-B 2006: Clinical Microscopy

Table 4. Crystal Key Facts, continued Calcium oxalate crystals Calcium oxalate crystals are most commonly present in acidic urine, but they can be found in neutral or slightly alkaline urine The crystals appear small and colorless with an appearance similar to an envelope. Dumb-bell shaped crystals can also occur Difficulty in distinguishing calcium oxalate crystals from triple phosphate crystals can occur although the solubility properties of each crystal differ. Calcium oxalate crystals can form kidney stones The presence of abundant oxalate crystals may indicate severe renal disease or toxicity from ethylene glycol Triple phosphate crystals Triple phosphate (ammonium magnesium phosphate) crystals are present in neutral or alkaline urine These crystals are colorless and show birefringence in polarized light with characteristic appearance resembling "coffin lids." They can appear as flakes

Clinical Case Studies, Conclusion Case I

The image of Case I shows red blood cells. This case is a classic presentation of Henoch-Schonlein purpura, a disease considered to be a hypersensitivity immune complex vasculitis. This disease is particularly seen in children who have had a recent history of an upper respiratory infection. An abnormal response of the immune system can result in inflammation involving blood vessels (vasculitis). Circulating immune complexes are deposited within blood vessels and within glomeruli. The disease can affect skin, joints, intestine, and kidneys. Henoch-Schonlein purpura often resolves spontaneously without treatment or longterm complications. However, if symptoms persist or complications develop including glomerular damage, steroid treatment may be initiated. Henoch-Schonlein purpura is an example of a systemic disease for which urinalysis results can be used clinically to diagnose and monitor progression or resolution of the disease.

Case II

The image of Case II shows a red blood cell cast. Although the patient was healthy and asymptomatic, multiple abnormal findings were detected in the urine sediment. Further clinical evaluation included a renal biopsy, which showed glomerular damage (glomerulonephritis).

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CM-B 2006: Clinical Microscopy

Case III

The image of Case III shows a uric acid crystal. Chemotherapeutic drugs kill malignant cells. As these cells degenerate, uric acid is released. In acidic urine, uric acid can precipitate in collecting tubules and be passed in the urine as urate crystals as were seen in this oncology patient.

Summary Laboratory examination of urine can provide significant clinical information. An abnormal urinalysis may be the first clue to the presence of disease and can precede any symptoms or manifestations of a clinical condition. Technical training and expertise are imperative in recognizing and interpreting qualitative and quantitative abnormal urine findings. Good standardized laboratory practices are essential to an accurate diagnosis, which impact clinical decisions and medical treatments.

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CM-B 2006: Clinical Microscopy

References 1. Henry JB. Clinical Diagnosis and Management by Laboratory Methods. 20th ed. Philadelphia, PA: WB Saunders; 2001. 2. Schuman GB, Friedman SK. Wet Urinalysis. Chicago, IL: American Society for Clinical Pathology; 2003. 3. Strasinger SK. Urinalysis and Body Fluids. Philadelphia, PA: FA Davis; 1994. 4. Haber MH. Urinary Sediment: A Textbook Atlas. Chicago, IL: American Society of Clinical Pathologists; 1981. 5. Underwood JCE, ed. General and Systemic Pathology. London: Churchill Livingstone; 2004. 6. Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Philadelphia, PA: Elsevier Saunders; 2005. 7. Graff L. A Handbook of Routine Urinalysis. Philadelphia, PA: J.B. Lippincott Company; 1983. 8. Rubin E. Rubin's Pathology: Clinicopathological Foundations of Medicine. Philadelphia, PA: Lippincott Williams & Wilkins; 2005. 9. Haber MH. A Primer of Microscopic Urinalysis. Fountain Valley. ICL Scientific; 1978. 10. EKU Department of Biological Sciences. Urogenital system. Available at: http://www.biology.eku.edu/RITCHISO/342notes10.html. Accessed August 24, 2006.

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NOTES

NOTES

NOTES

NOTES

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