David E. Bruns, M.D., Edward R. Ashwood, M.D. and Carl A. Burtis, Ph.D.

Laboratory Medicine

The term laboratory medicine refers to the discipline involved in the selection, provision, and interpretation of diagnostic testing that uses samples from patients. Those active in the field participate in (1) analytical testing, (2) research, (3) administration, (4) teaching activities, and (5) clinical service to varying degrees.

Testing has many uses in laboratory medicine (Box 1-1). In a hospital setting, its use is vital to establish and monitor the severity of a physiologic disturbance. In hospitalized patients, the latter constitutes the largest volume of testing.

Historically, the clinical laboratory as an entity in providing healthcare services began with the manual measurement of a variety of analytes (now termed measurands),¹⁰ including (1) metabolites, (2) proteins, (3) lipids, (4) carbohydrates, (5) enzymes, and (6) drugs. The first laboratory attached to a hospital was established in 1886 in Munich, Germany, by Hugo Wilhelm von Ziemssen.^5,8 In the United States, the first clinical laboratory was The William Pepper Laboratory of Clinical Medicine, established in 1895 at the University of Pennsylvania in Philadelphia (http://hss.sas.upenn.edu/microbio/insts2.html). As the demand for these analytical services increased, analytical processes were mechanized and ultimately automated.⁹ Technical and scientific advances and the growing understanding of disease at the biochemical and genetic levels have expanded the need for the clinical laboratory to provide analytical services in a broad and diverse spectrum of disciplines (Box 1-2), with clinical chemistry and molecular diagnostics being particularly dynamic as they have developed and expanded alongside the growing understanding of disease at the biochemical and genetic levels. Most individuals entering these two disciplines have backgrounds in biochemistry, molecular biology, physiology, or another biochemistry-related field, and some have backgrounds in areas such as analytical chemistry.¹⁴ Principles of measurement science and metrology, often adapted from the field of analytical chemistry by clinical chemists, have never been more important than they are now, as quantitative molecular methods such as viral load assays and measurement of the numbers of DNA triplet repeats are replacing numerous qualitative techniques throughout medicine.

Clinical Chemistry and Laboratory Medicine

The ties between clinical chemistry and other areas of laboratory medicine have deep roots. Individuals working primarily in the area of clinical chemistry/biochemistry have developed tools and methods that have become part of the fabric of laboratory medicine beyond the clinical chemistry laboratory. Examples include the (1) theory and practice of reference intervals (see Chapter 5), (2) use of both (internal) quality control and proficiency testing (see Chapter 8), (3) introduction of automation into the clinical laboratory (see Chapter 19), and (4) concepts of diagnostic testing (see Chapters 3 and 4). From the physician’s and the patient’s perspective, no distinction is evident between these specialties, and invariably the repertoire of more than one specialty will be called upon when a clinical decision is made. Examples of clinical scenarios that require tests from multiple laboratory areas include the diagnosis and management of many diseases and the management of patients in intensive care (see Chapters 46 through 59 [“Pathophysiology” section of this text]).

Boundaries between and among the parts of the clinical laboratory have become more blurred with increasing emphasis on the use of chemical and “molecular” (nucleic acid) testing. Molecular diagnostic testing has evolved beyond human genetic testing, an area in which clinical chemists have long been active. Now, clinical chemists in “molecular” laboratories contribute their expertise in laboratory medicine to infectious disease testing, cancer diagnostics, and identity testing, activities that formerly were associated primarily or solely with, respectively, clinical microbiology, hematology, and blood bank laboratories. Successful contribution by clinical chemists to these areas requires an understanding of the principles of laboratory medicine and close collaboration with clinical microbiologists, hematologists, and others who have specialized expertise in those areas of laboratory medicine.

The relationship between the clinical chemist and laboratory medicine has evolved further with the advent of “core” laboratories. These laboratories provide all of the high-volume and emergency testing in many hospitals. Their efficient and reliable operation depends on automation (see Chapter 19), computers, and high levels of quality control and quality management (see Chapter 8). Clinical chemists, who have long been active in these areas, have assumed increasing responsibility in core laboratories and thus have become more involved in areas such as hematology, coagulation, urinalysis, and even microbiology. Thus a new type of “clinical chemist” has emerged, and again the functions require a broader knowledge of laboratory medicine and greater collaboration with other specialists.

A virtual merger of clinical chemistry and laboratory medicine has been suggested in many ways. For example, journals in the field of clinical chemistry publish papers in all of the areas of laboratory medicine. The current logo of the American Association for Clinical Chemistry reads, “AACC—Improving Healthcare through Laboratory Medicine.” Moreover, the international association of clinical chemistry societies is now called the International Federation of Clinical Chemistry and Laboratory Medicine. To be active in the field of laboratory medicine today requires, more often than not, familiarity with core concepts in several if not all of the subdisciplines of the field.

During the past two decades, the field of clinical chemistry has been profoundly influenced by new activities in the fields of clinical epidemiology and evidence-based medicine (EBM). Clinical epidemiologists have developed study designs to quantify the diagnostic accuracy (as opposed to analytical accuracy) of the tests developed in laboratory medicine (see Chapter 3). Moreover, they have introduced methods to evaluate the effects and value of laboratory testing in healthcare (see Chapter 2). These developments are expected to play an increasing role in the selection and interpretation of tests. Thus the fourth chapter of this book is devoted to evidence-based laboratory medicine.