The medical laboratory, also called the clinical laboratory or the pathology laboratory, provides diagnostic testing services for physicians to help identify the cause of disease and changes produced in the body by disease conditions. Medical laboratories are classified as either clinical pathology laboratories, which analyze blood, urine, culture products, and other body fluids; or anatomical (or surgical) pathology laboratories, which analyze tissue or organ samples obtained during surgery or autopsy and cervical and body fluid samples obtained by biopsy or lavage. A typical hospital medical laboratory will be called the Department of Pathology (investigation of diseaserelated processes) and will offer both types of testing. Medical laboratories of various sizes, offering a variety of testing services, can be found in acute-care hospitals, medical centers, doctor's offices and group practices, skilled nursing facilities, and long-term care facilities. Commercial medical laboratories operate as independent businesses and serve as testing facilities for physicians and for companies engaged in medical or pharmaceutical research. Additional commercial laboratories that specialize in a specific type of testing such as genetic, drug, and fertility testing also serve the medical community. Reference laboratories are often established by universities, state governments, organizations, and companies to provide more comprehensive testing or to perform more difficult tests not needed routinely.
Medical laboratory science, or medical technology, is an important part of diagnostic medicine. It uses sophisticated instruments and methods to evaluate hundreds of body processes that occur constantly as body organs do their work. Combinations of laboratory tests are needed to help diagnose a patient's condition. Clinical pathology evaluates disease by identifying (qualitative testing) and measuring (quantitative testing) chemical substances found in blood, urine, spinal fluid, sputum, feces, and other body fluids. Bacteria and sometimes viruses are grown and identified in culture products (samples of blood, urine, sputum, wounds, etc.) that are transferred onto culture media and incubated until they grow enough to be identified. Biochemical substances such as hormones, enzymes, minerals, and other chemicals produced in the body can be measured, as well as chemicals ingested (eaten with food or consumed as medications or poisons) or produced as waste products.
Normal levels or reference levels of these substances are determined by performing the tests on large numbers of people and establishing a typical range of results expected in the absence of disease. These reference ranges are often gender and age specific and will vary from laboratory to laboratory depending upon the methods used. A level that is higher or lower than normal gives physicians information about a patient's condition at the time of testing and may help physicians diagnose a disorder or disease in that patient. Measuring changes in the levels of chemicals may also help to monitor changes in the patient's condition during and after treatment. For example, a substance produced by the prostate gland called prostate specific antigen is used to screen for prostate cancer. Following treatment, the physician will request that this test be performed because complete removal of the tumor will cause the blood level to return to normal. Following demonstration of successful treatment, the test will be performed at regular intervals to detect any recurrence of the tumor.
Anatomical pathology identifies either the cause of disease or, through autopsy, the consequences of disease (cause of death). Samples of cells, tissues, or organs obtained during surgery or autopsy are examined macroscopically (by the naked eye) and microscopically (by powerful microscopes). Advances in the relatively new sciences of genomics (study of DNA and RNA) and proteomics (study of molecular proteins ), cell genetics, and molecular analysis may also be performed to better understand the origins of disease in individuals. Anatomical pathology gives doctors the most definitive information on the disease process causing a patient's symptoms, illness, or death. Results of anatomical pathology depend upon the qualified opinion of a pathologist, a physician trained and experienced in identifying the causes of disease and changes in body chemistry or tissues in the presence of disease. The anatomical pathology report is written in appropriate detail for the testing physician, and will be used along with clinical data to determine the stage (extent) and prognosis (outlook) of the disease.
Doctors order laboratory tests to make, confirm, or rule out a diagnosis, to select or monitor therapy (drugs, physical therapy, surgery, etc.), to monitor a patient's progress during therapy and help determine a prognosis for the patient. A single test is usually not enough to confirm a diagnosis. Combinations of laboratory tests are used along with the patient's history, physical examination, and diagnostic imaging exams (such as x ray, MRI, CAT scans, and ultrasound) to make a definitive diagnosis. Laboratory screening tests are often performed on apparently healthy patients to make sure they have no underlying disease. Test profiles are also designed that combine a series of related tests (such as a hematology profile or chemistry profile) or organ-related tests (such as a cardiac profile, liver profile, or thyroid profile) to get a broad view of a patient's condition. More specific testing is usually required to make a definitive diagnosis.
Testing laboratories rely on well defined technical procedures, complex precise instruments, and a variety of automated and electronic equipment to do diagnostic testing. Tests are performed by medical technologists, technicians, and laboratory assistants. The technical staff works under the direction of a pathologist, who interprets the results of the laboratory tests. Laboratories, laboratory equipment, and testing personnel are evaluated and accredited by national scientific organizations and government agencies, including the American Society of Clinical Pathologists (ASCP) and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). This accreditation process helps to standardize lab procedures, establish quality control standards, and ensure that labs provide physicians with accurate and timely test results.
The medical laboratory is typically divided into sections that perform related groups of tests. The standard laboratory sections include, but are not limited to:
- Clinical chemistry: the study of body chemistry and the detection and measurement of chemicals such as hormones, enzymes, proteins, fats, vitamins, minerals, metals, and drugs. The chemistry department has subspecialties that include enzymology, toxicology, and immunochemistry.
- Hematology: the study of red and white blood cells, including their concentration and morphology (appearance and stages of growth), and the measurement of hemoglobin (iron-bearing protein in the blood) and other substances in the blood that may help diagnose bleeding and coagulation problems, anemia, infection, and various other illnesses including cancer. In large laboratories it is common practice to combine the automated components of both clinical chemistry and hematology into one section that is staffed by personnel who are skilled in both disciplines.
- Microbiology: the study of microorganisms, and the isolation and identification of disease-causing bacteria, yeasts, fungi, parasites, and viruses. Microbiologists also determine the antibiotic susceptibility of pathogenic bacteria that are grown from clinical specimens.
- Immunology: the study of the body's immune system and immune processes that mediate and regulate the body's defense against bacteria, viruses, and foreign cells or antigens (proteins). Immunology is also the section of the laboratory that tests for organ transplant compatiblity, a specialized area called histocompatibility testing, and autoimmune disease (i.e., an immunological response to one's own tissues). In addition, a branch of immunology called serology measures the concentration of specific antibodies that indicate infectious disease, previous exposure to a pathogen, or immunity resulting from vaccination.
- Urinalysis: the examination of urine and the study of waste products that are eliminated by the kidneys may indicate or help explain metabolic or kidney disease processes and monitor treatment with therapeutic drugs. Urinalysis also includes the analysis of cells, crystals, and other objects that enter the urine or are formed by the kidney or urinary tract.
- Every clinical laboratory will offer testing capabilities within these categories. All hospitals that perform surgery will also have an immunohematology department, which comprises the blood bank and those tests that are used to determine whether blood from a donor will be compatible with the intended recipient. In addition, the blood bank technologists perform tests to detect antibodies on red blood cells, store blood and blood products, and prepare blood products for transfusion. The blood bank also performs therapeutic bleeding or removal of specific blood components for some patients.
Smaller laboratories, such as those in doctors' offices, will perform routine testing and screening tests related to the physician's specialty, usually testing blood and urine samples only, and will still need the hospital or independent testing laboratories for special diagnostic tests. Smaller laboratories generally use state-of-the-art equipment and automated instruments that are designed for less testing volume and that are less complex than those used in larger laboratories.
While some tests are performed manually, medical laboratories depend upon computer-controlled automated equipment for as many tests as possible to keep up with the volume and variety of tests ordered. Multichannel analyzers are commonly used to perform clinical chemistry tests. These large, complicated instruments are computer-controlled to perform many separate chemistry tests simultaneously (often called a chemistry panel or profile) on each patient's sample. The goal of such automation is to reduce the amounts of sample required; reduce the amount of chemicals (reagents) needed per test; reduce the time of analysis; eliminate contamination and error that results from excessive sample handling; and reduce the number of technologists needed to perform the testing. The precise operation of automated systems provides a higher degree of precision avoiding the differences in operator technique that increases the variance of manual testing methods. Computer-calculated results have been shown to be far more reliable than results subject to human manipulation, which is more likely to introduce transcription and random computational errors. Cost savings achieved through automation are important to both the testing facility and the patient. Time savings are important to the testing physicians and unit nurses who are waiting for test results to make critical patient-care decisions.
Laboratory computerization also includes laboratory information systems (LIS) that can access patient information and allow reporting of test results directly to the patient's record. Patient orders and test results can be viewed on a terminal or printed out in a comprehensive record, showing daily or hourly results side by side for comparison. This is especially valuable to physicians and nurses who are monitoring the patient's treatment. Results may be reported more quickly when the LIS interfaces with the healthcare facility's medical information system (MIS), which displays results on computer terminals in point-of-care nursing units, or transfers the information to the testing physician's office.
Hundreds of different types of tests are performed daily in the medical laboratory using different methods on a variety of special instruments. The demand for both rapid and reliable results has led to increased reliance on automation and to new portable testing methods that can be performed at the bedside or other point-of-care. Some of the most common automated testing methods are:
- Automated general chemistry analyzer (automated spectrophotometry). Most automated tests performed on multichannel analyzers use this technique. The instrument consists of components that perform all of the steps of a manual procedure. Robotic arms may be used to convey the samples from the centrifuge to the analyzer and bar code readers are used to input test order and patient information directly to the analyzer's computer. Sample and reagents are added to reaction cells in precise amounts, mixed mechanically, and incubated at constant temperature for a specific period of time. The chemical reaction typically results in production of a colored product. The color intensity (absorbance) is determined by the instrument's optical system or spectrophotometer. The instructions for how to perform each different test (i.e., sample volume, reagent volume, incubation time, wavelengths for analysis) are stored in the computer's memory. The computer also stores calibration information needed to calculate results, and quality control data that is needed to validate instrument performance. Reaction cells may be disposable or cleaned and reused by an automated wash system on the analyzer. In addition to optical analysis, these instruments usually have electrochemical sensors for analysis of electrolytes such as sodium and potassium. The test menu is usually large, for example 40 to 60 different analytes that can be measured in any order or combination. Smaller, single-channel spectophotometers are also used in doctor's offices, clinics, and nursing units to perform a more restrictive number of procedures. Another type of light measuring instrument called a reflectance photometer is often used to read dry reagent strip urine or dry slide chemistry tests.
- Immunoassays. This comprises a wide range of laboratory methods that utilize specific antibodies to facilitate a measurement. Immunoassay platforms are incorporated into several large autoanalyzers (automated chemistry analyzers), and are used to identify minute amounts of analytes (substances analyzed in blood, urine or body fluids), which include hormones, drugs, tumor markers, specific proteins, and cardiac markers. Some systems also support immunological tests to identify bacterial and viral antigens and allergens (responsible for allergies ). The technology is based upon the measurement of antigen-antibody complexes and usually involves the use of a label such as an enzyme, radioactive isotope, or fluorescent molecule to measure the amount of immune complexes formed. New technology allows the selection of individual tests in any order or combination without the need to change reagents or instrument settings manually.
- Electrophoresis. Electrically charged particles of varying size and electrical charge, will move at different rates under the influence of an electric field. These differences can be measured by a technique called electrophoresis. The process permits separation of similar molecules such as proteins with different net charges or of different sizes. Serum protein electrophoresis separates proteins found in blood serum, the clear portion of a blood sample after it clots. It is used as an aid to the diagnosis of diseases such as multiple myeloma, acute and chronic inflammation, kidney disease, liver disease, and nutritional disorders. Immunofixation electrophoresis uses the separation of proteins in conjunction with specific antibodies to help diagnose multiple myeloma (a malignant disease) and immunodeficiency states that occur in disorders such as AIDS. Hemoglobin electrophoresis separates the red pigment in blood cells to diagnose certain anemias and blood disorders.
- Chromatography. Substances can be separated and identified on the basis of their molecular size or chemical properties (how they interact). High performance liquid chromatography (HPLC), thin-layer chromatography, and gas-liquid chromatography each use a different type of medium to separate drugs, certain proteins, amino acids, lipids, organic acids, and hormones in blood or urine. Various detectors can be used to measure the quantity of the analytes following their separation.
- Mass spectrometry. This technology is coupled to gas chromatography in order to conclusively identify a compound based upon its unique chemical structure. The mass spectrometer is most often used to confirm positive drug tests performed by immunoassay. Mass spectrometry equipment is highly specialized and the testing is more likely offered by an independent laboratory specializing in this technique than by a hospital laboratory. Pharmaceutical companies often requires this type of testing on thousands of samples in the research and development of therapeutic drugs.
- Atomic absorption and ion-selective electrodes. These techniques are used to measure trace metals and electrolytes, respectively. Atomic absorption spectrophotometry is an optical method that converts ions to atoms and then measures the absorbance of a wavelength of light by the atoms. Metals most commonly measured are lead, zinc, mercury, selenium, and copper. Ion selective electrodes are sensors that produce a small potential difference (voltage) in response to specific ions. This technique is accurate but not as sensitive as atomic absorption spectrophotometry. Therefore, it is used for measuring ions that are relatively abundant in blood such as sodium, potassium, chloride, hydrogen ions, magnesium, calcium, and lithium.
- Automated blood cell counters. Hematology laboratories count red and white blood cells, measure hemoglobin (the iron-bearing protein in blood), and determine the hematocrit (the volume percentage of blood occupied by the red cells), as well as other tests reported in a complete blood count (CBC). These tests can all be performed on an automated hematology system. Some automated systems can also identify each type of white cell in what is called a differential blood test. This automated system and its results are useful in diagnosing anemias, infections, leukemia and other blood disorders related to various types of cancer, and for general health screening.
- Flow cytometry. A flow cytometer is a more specialized type of cell counter that can differentiate, count, and in some cases sort specific subpopulations of cells. Flow cytometers make use of some of the rapidly expanding tools and molecular diagnostics. Fluorescent labeled antibodies are used to tag the cells of interest and these cells are counted as they flow in single file through an aperature into which a laser is focused. The laser stimulates the fluorochrome to emit light of a specific color. Light filters and detectors respond to the specific colors and the instrument's computer processes the resulting electrical signals to determine the cell count. Two rapidly advancing biosciences, genomics and proteomics, are being applied to flow cytometry to permit measurement of the DNA content of cells to determine if they are benign or cancerous.
Clinical instruments use a variety of measuring technologies to evaluate patient samples, but the principles of operation between analyzers share some fundamental characteristics. All methods on all instruments must undergo a preliminary evaluation of precision and accuracy to demonstrate that they meet the manufacturer's claims for analytical performance. All methods must be calibrated on a regular basis by analyzing samples of known concentration to which the measured signals from patient samples are compared. All methods must be validated using quality control specimens on a daily basis. The quality control sample is made of the same composition as patient samples and has an expected concentration that is specific for the method of assay. When results for quality control samples do not fall within the expected range, the operator must institute correction actions before patient specimens can be analyzed and reported. Automated instruments have intricate computerized monitoring systems and software codes that signal the operator when results are likely to be invalid. The operator must troubleshoot these problems and perform whatever steps are required to facilitate successful measurement of affected patient samples. Every test result is reviewed and evaluated with respect to quality control performance and its reasonableness before it is electronically transferred to the LIS for reporting.
Maintenance and safety
Laboratory personnel often are trained in the operation and maintenance of new equipment by the manufacturers of each type of instrument. Technologists are responsible for calibrating measuring devices such as pipets, equipment such as centrifuges, as well as all instruments. In addition, all incubators, refrigerators, and freezers are monitored for temperature accuracy and electrical lines are checked for current leakage and unstable voltage. All reagents are dated, examined for contamination, and stored in a manner than complies with safety regulations and manufacturer specifications. Instruments, equipment, glassware, and work surfaces are regularly cleaned and disinfected. Gloves, leak-proof gowns, and other forms of barrier protection are utilized to reduce the risk of transmission of bloodborne pathogens and exposure to chemical and physical agents that may be harmful. While large hospitals may rely on staff biomedical engineers to perform some maintenance and instrument repairs, the laboratory personnel are responsible for day-to-day operation, cleaning and maintenance procedures. Each laboratory must maintain records of equipment calibration, cleaning and maintenance, and a manual of all laboratory procedures and policies. Laboratory operations, facilities, and services are inspected by external accrediting agencies that evaluate compliance by the laboratory with the Clinical Laboratory Improvement Act of 1988 (CLIA 88) as well as their own standards.
Health care team roles
Physicians order diagnostic tests from the medical laboratory to help diagnose and treat their patients. When an order is received by the laboratory, either on a manual lab request form or through the hospital MIS, the lab will first obtain the proper type of sample. This may involve drawing blood (venipuncture), which is typically performed by a phlebotomist (person who specializes in venipuncture). Samples such as urine, feces, sputum, or tissue usually are obtained by nurses or physicians in the nursing unit. Surgical samples will be delivered to the lab by surgical technicians. Some samples, such as single or 24-hour urine samples, are brought to the lab by patients themselves (if they are outpatients). Laboratory personnel are responsible for checking all specimens received in order to determine that they are properly labeled and collected in the proper container. Personnel responsible for specimen processing will separate the blood components if required and store the sample at the proper temperature prior to testing. Technologists or technicians perform the analysis, evaluate the test system using quality control procedures, and review each result before reporting it. Inappropriate specimens are rejected, and suspicious results may require repeat testing using a new sample. Critical values and stat requests must be called immediately to the ordering physician. Some physicians have issued a written request for follow-up testing when results are abnormal. Timely communication between the laboratory staff and the primary care provider is essential for effective utilization of laboratory tests and results.
Analyte— A chemical substance in body fluids, cells, or tissues that is the subject of laboratory investigation.
Biochemistry— The study of biochemical origins of humans in health, growth, nutrition, and disease.
Clinical chemistry— A broad field of analytical techniques that detect and measure chemicals in body fluids, cells, or tissues, such as enzymes, hormones, proteins, drugs, or other naturally occurring chemicals or those either ingested or used to treat disease.
Diagnostic medicine— Diagnostic medicine is the scientific study of body fluids, tissues, and organs to diagnose disease, monitor the course of disease, and monitor the response to treatment, particularly drug therapy.
Enzymes— Important naturally occurring biological catalysts present in the body. They enhance all body processes, including growth, maturation, and reproduction, and can be detected and measured in body fluids to diagnose and monitor disease. Synthetic enzyme reagents (not manufactured in the body) can be used as markers or labels in tests for other analytes.
Fluorescence— A phenomenon exhibited by molecules that absorb light energy and then give off the energy as light of a longer wave length. Fluorescent technology is a measurement technique used in clinical laboratory procedures and equipment.
Immunoassay— This type of assay is a measurement technique that uses binding reactions between different types of proteins, one protein being an antigen, the other an antibody that attaches to it. Known amounts of either antigen or antibody are combined with a blood sample or other body fluid to attract the analyte of interest and allow it to be detected and measured. Antigen-antibody reactions can be measured using enzyme technology, fluorescence, or radioisotopes.
Immunology— The scientific study of the immune system, which the body's defense system against bacteria, viruses, foreign cells (as in transfusion or transplantation). Immune reactions in the body involve antigen-antibody reactions that can be detected and evaluated using similar antigen-antibody technology.
Markers— Also called labels or tags. They attach to analytes in patient samples and allow them to be detected and measured by various measurement techniques using light, heat, or radioactivity. The term also refers to analytes that signal the presence of a specific diseaase. For example, troponin I is a marker for a heart attack because it is liberated from myocardial cells following infarction.
Pathology— The scientific study of the causes and consequences of disease.
Reagents— Reagents are chemical preparations (compounds) used to perform laboratory tests or used in the operation of laboratory equipment.
Laboratory medicine is a well developed field based upon natural and physical sciences that requires education in medical science, techniques and research methods. Pathologists are physicians (MDs) who have completed four years of medical school, followed by a residency in a pathology laboratory. Medical laboratory technologists, technicians, and assistants who work in all fields of medical laboratory science are educated and trained at various levels. Those with more education will have greater technical and administrative decision-making responsibilities in the laboratory. Some may have advanced degrees (Ph.D. or M.S.) in sciences such as biochemistry or immunology. Certified technologists are required to have a Bachelor of Science degree and to have successfully completed an accredited laboratory training program. Their course of study typically includes anatomy, physiology, molecular biology, organic and biochemistry, immunology, microbiology, mathematics and statistics. Professional laboratory training includes courses in hematology, diagnostic and pathogenic microbiology, clinical immunology, immunohematology, and clinical biochemistry and urinalysis. A clinical practicum (internship) is typically required either as part of the baccalaureate degree or afterwards. After this training, graduates will be eligible for certification by examination by the American Society of Clinical Pathologists (ASCP) or National Certification Agency for Clinical Laboratory Personnel (NCA). Certified clinical laboratory technicians earn an associate degree from an accredited medical laboratory technician program. The program will include a clinical practicum as part of the training. Following this graduates are eligible for certification by examination by the American Society of Clinical Pathologists (ASCP) or National Certification Agency for Clinical Laboratory Personnel (NCA). Some vocational schools offer basic education and training for medical laboratory assistants, allowing graduates to perform some laboratory procedures and assist more skilled laboratory personnel.
Henry, J.B. Clinical Diagnosis and Management by Laboratory Methods. 20th edition. St. Louis W.B. Saunders, 2001.
American Society for Clinical Laboratory Science (ASCLS), 7910 Woodmont Avenue, Ste. 530, Bethesda, MD 20814. (301) 657-2768. 〈http://www.ascls.org〉.
American Society of Clinical Pathologists (ASCP), 40 West Harrison Street, Chicago, IL 60612. (312) 738-1336. 〈http://www.ascp.org〉.
Medical Laboratory Observer (MLO). 〈http://www.mlo-online.com/article-ind/articles.html〉.