Testing in the Clinical Lab
Which Types of Testing are Performed in the Various Areas of the Clinical Laboratory?
Clinical laboratories traditionally classify testing into four major categories: microbiology, chemistry, hematology, and transfusion medicine (also called immunohematology or blood banking). Within each of these areas, many different analytes are assayed using a variety of analytical approaches. A brief description of the scientific focus of each of these areas and examples of some of the methodologies and commonly encountered clinical syndromes in each of the major areas follow.
Regardless of the area of the clinical laboratory, the clinical laboratory scientists who work there not only perform assays and report their results. They also carefully monitor for accuracy, timeliness, and all aspects of each assay—from collection and transport of the sample to the laboratory to completion of the assay and transmission of data back to the physician. In addition, each process is continuously evaluated to determine ways in which the assay or process might be improved to give better patient care. These processes are called quality control, quality assurance, and total quality improvement. Clinical laboratory scientists are devoted to ensuring that these monitors of quality are continuously applied in all aspects of their work.
Microbiology is the area that examines patients’ samples for agents of infectious diseases. The specimen material includes samples from wounds, noses/throats, blood and body fluids, and many other body sites. The agents that are detected may be bacteria (aerobic, anaerobic, acid fast), fungi (molds and yeasts), parasites, or viruses.
Bacteriology and Mycology (fungi): In the microbiology laboratory, clinical laboratory scientists use methods to isolate bacteria and fungi on agar media contained in petri dishes. Depending on the source of the sample and the macro and microscopic appearances of the organisms, the clinical laboratory scientist makes the decision as to whether these organisms might be significant in causing disease. If so, analyses (biochemical, enzymatic, molecular, etc.) are performed to determine the actual identity of the infecting organism. Antimicrobial susceptibility testing is also done to determine which antibiotic should be used for treatment of the infection. Common types of bacterial infections include streptococcal pharyngitis (i.e. “strep throat”), urinary tract infections, pneumococcal pneumonia, meningococcal meningitis, tuberculosis, and gonorrhea. Common fungal infections include histoplasmosis and ringworm. Fungal infections are especially troublesome in patients who are immunosuppressed due to HIV/AIDS infection, cancer chemotherapy treatments, organ transplantation protocols, or other condition that interferes with the function of their immune system.
Parasitology: Often the diagnosis of a parasitic disease is based upon the microscopic appearances of the parasite in the patient specimen. Some parasitic infections seen in the microbiology laboratory include malaria, giardiasis and hookworm infestation. Immunosuppressed patients and individuals traveling to developing countries are at increased risk of parasite infestation.
Virology: The virology area is very active during “cold and flu” season when influenza and other respiratory viruses are circulating in the community. Viruses will not grow on agar plates; they can grow only in living cells. Clinical laboratory scientists in the virology area use tubes containing living cells in order to isolate viruses. Viruses manifest their presence in infected cells by causing a change in the appearance of the infected cells. This may be swelling, shrinking, clustering, or other types of changes. These changes are recognized by the virologist who then conducts further tests to confirm the identity of the virus that is present. Viruses often detected in the virology area include herpes simplex virus, influenza A and B viruses, and many others.
Serology (Antibody Detection): Some infectious agents do not grow well in the laboratory. The best way to detect their presence is to examine the patient’s blood for antibodies produced against the agent. Some infectious diseases detected primarily by this route are infectious mononucleosis, hepatitis A, B, and C, and HIV/AIDS. Antibodies produced in autoimmune syndromes such as systemic lupus erythematosus and rheumatoid arthritis are also detected in the Serology Laboratory.
Chemistry is the area where patients’ samples are checked for various chemical components. When humans are in a state of good health, the levels of various body chemicals fall within highly predictable ranges. In disease, the levels of these chemicals change, thus signaling the disease process. In addition, the chemistry laboratory monitors levels of therapeutic drugs to ensure that the patient is receiving the correct dose. The chemistry laboratory also tests samples to detect the presence of poisons and drugs that should not be present (i.e. “drugs of abuse” such as cocaine and heroin).
In the chemistry area, many of the assays are performed with sophisticated instruments that provide accurate analyses very quickly. These instruments are essential for handling the large number of chemical assays that must be performed each day and for returning results promptly to physicians, often in as few as 20 minutes!
Routine testing: A chemical panel called the “basic metabolic panel” that includes testing for sodium, potassium, chloride, carbon dioxide, blood urea nitrogen, calcium, creatinine, and glucose is the most frequently ordered panel. It does not test for a specific disease; rather, this is a screening panel that detects chemical imbalances seen in many disease states. If results of this panel are abnormal, additional testing is done to help in diagnosing a specific disease. Because of the huge number of basic metabolic panels and other routine assays such as cholesterol or liver enzyme assays performed, the clinical laboratory scientists rely on state-of-the-art instrumentation for performing these assays.
Assays related to acute episodes: In the chemistry laboratory, testing is conducted to determine if patients who are in acute distress are having a heart attack, a stroke, kidney failure, liver dysfunction, or any number of other organ malfunctions. These assays must be done quickly and accurately to provide the information physicians use in determining therapeutic interventions for the acutely ill patient.
Therapeutic drug monitoring: Patients who have chronic illnesses such as diabetes, severe asthma, or seizure disorders that are controlled by medication are monitored to ensure that the dose of medication they are using is appropriate. If the dose of medication is too high, it may cause negative side effects; if the dose is too low, it may fail to prevent damage related to the disease. As described above for routine testing, the number of assays performed each year related to therapeutic drug monitoring is very high. Some of these assays are performed on sophisticated instruments. However, some of these assays require the clinical laboratory scientist to perform manual testing.
Drugs of abuse: Individuals who abuse drugs may be brought to the hospital in a state of disorientation or unconsciousness; thus, they are unable to tell the healthcare team which drug they have used. It is up to the clinical chemistry laboratory to test this patient’s samples and quickly determine which drug is involved so the proper therapy can be applied to save the patient. Assays for various categories of drugs of abuse such as opiates, amphetamines, cocaine, PCP, barbiturates, and others are conducted rapidly with automated methods, and the results are quickly communicated back to the physician so that treatment can be initiated. Additional testing to identify the specific drug may be needed.
In the hematology laboratory, the focus is primarily on the cellular components of blood. When a human is in a state of good health, each cellular component in the blood is present in predictable numbers. This includes erythrocytes (i.e. red blood cells), leukocytes (i.e. white blood cells), and platelets. The appearance of each of the cells is another highly predictable feature. By counting the blood cells and examining their appearance, the clinical laboratory scientist helps detect various diseases. Body fluids such as urine and cerebrospinal fluid are routinely studied in the hematology laboratory area. The many factors that are required for effective blood clotting (hemostasis) are also evaluated in the hematology area of the laboratory.
Clinical laboratory scientists in the hematology area perform analyses by both automated and manual methods. Because the “complete blood count” (CBC) is one of the most commonly-requested assays in the clinical laboratory, there are large numbers of samples to test. Automating of routine cell counting allows the clinical laboratory scientist to focus on the more demanding processes of dealing with samples that are abnormal and need close scrutiny through the microscope.
Routine Hematology: Cellular components of the blood include the erythrocytes (red blood cells), leukocytes (white blood cells) and platelets (involved in clotting). Disease-induced changes in erythrocytes may manifest themselves as altered numbers of cells or as distinct changes in cellular appearance. Diseases associated with changes in erythrocytes are termed “anemias.” There are many kinds of anemia and many causes for the erythrocyte changes that are seen. Some commonly encountered types of anemia include sickle-cell anemia and iron deficiency anemia.
As with diseases affecting erythrocytes, disorders that affect leukocytes may cause changes in the number or appearance of the cells. When a human is healthy, there are five kinds of leukocytes found in the blood: segmented neutrophils, lymphocytes, monocytes, basophils, and eosinophils. These are found in predictable numbers and proportions. Leukemia is one disease that can affect leukocytes. In most leukemias, the number of leukocytes is dramatically increased. Some commonly encountered types of leukemia include acute lymphocytic leukemia and chronic myelogenous leukemia.
Platelets are also counted and their appearance evaluated to help identify problems in blood clotting. The function of the platelets can also be assessed in the coagulation section of the hematology laboratory.
Coagulation: Blood clotting (hemostasis) involves a cellular component of blood called platelets as well as numerous liquid components called clotting factors. In the hemostasis area, there are assays to measure the levels of the various clotting factors and to determine whether the clotting factors that are present are able to function as they should in helping blood clot. The name “hemophilia” is given to certain syndromes that prevent blood from clotting as it should. Individuals with hemophilia or other clotting disorders can bleed to death if they have even a very minor injury unless their clotting disorder is correctly identified, monitored, and treated. Also, the blood of some patients clots too fast or inappropriately, causing painful and potentially life-threatening blood clots. These patients must be given drugs to decrease blood clotting (i.e. “blood thinners”). This therapy requires constant monitoring by the hemostasis laboratory.
Body Fluid Analysis: Body fluids other than blood are often examined to determine chemical content as well as cellular components. One fluid that is routinely examined is urine, and the study of urine is called urinalysis. Chemical and cellular components that appear in urine often are the key to diagnosis of many diseases. Both gross and microscopic techniques are used in analysis of urine. Some diseases that give abnormal findings in urine are diabetes, bladder infections (cystitis), and renal failure and infectious agents. Cerebral spinal fluid, synovial (joint) fluid and bone marrow aspirates are also evaluated for abnormal findings such as evidence of meningitis (spinal fluid), gout (synovial fluid) or leukemia (bone marrow).
In the clinical laboratory area called transfusion medicine (also called immunohematology or blood bank), the clinical laboratory scientist has two main functions: one of these is called compatibility testing, which is matching donated blood and blood products from a donor to a patient, and the is called component therapy, which involves separating whole blood into its various individual components for administration to patients. The transfusion medicine area is the only area of the clinical laboratory that prepares products that will be administered to patients.
Clinical laboratory scientists who work in the transfusion medicine laboratory use a variety of skills including microscopic exams, manual assays, and automated assays. Transfusion medicine is the area of the laboratory most intimately involved in emergency care of patients who are bleeding.
Compatibility testing: All donated blood must be tested first to determine the donor’s blood type and to ensure that the donor is free of certain infectious diseases such has hepatitis. Portions of the donated blood are then mixed with portions of the patient’s blood in an assay called “cross matching.” Mixing the two blood samples allows the clinical laboratory scientist to evaluate whether the two samples are compatible—which means that they can be safely mixed. Donor blood that has been identified as compatible can then be transfused into the patient.
Component preparation: The clinical laboratory scientist manipulates donated whole blood to separate off components such as platelets, plasma, and erythrocytes (red blood cells). The actual separation, preparation, and maintenance of these separated components is delicate work. These components are then matched as needed for patient administration.