by Oscar Fay

In this chapter we have tried to make a synthesis of the current possibilities of the biochemical laboratory in order to offer a guide, as up-to-date as possible, that is useful to the difficult task that the doctor faces when he is in front of a patient who should attend.

For this we have made a brief review of the role that the clinical laboratory in medicine currently fulfills, how it has evolved to this day and the role that laboratory personnel play in this context. Likewise, we have highlighted the most important aspects to consider when requesting and interpreting laboratory tests.

Finally, we present in this chapter as a guide, a list of laboratory tests grouped according to the most common medical profiles or specialties that can be presented in medical practice and we provide various links to sites for online consultation of additional, more detailed information on laboratory tests and their interpretation. We have also included a table with newly emerging methodologies that promise to open our way to new paths in research and clinical practice.

Scientific technological advances in the sciences are increasingly vertiginous with a growth curve of unimaginable magnitude towards the future. Health criteria are developing a close interrelation in the biological, environmental, social and psychological aspects, which has led us to think in a comprehensive way about the relationships between living beings on the planet and human beings as individuals, who are also part of that ecosystem, insofar as they are interrelated with it. For example, from the point of view of microorganisms and their relationship with the ecological environment, with animals, plants, and people.

It is extremely difficult to predict what current technology will provide the benefits that can be reflected in solutions to global health problems.

The current approach to knowledge will have an extraordinary impact in the coming times on the subject of Medical Sciences. The horizontality and the relationships between the different disciplines allow us to envision an extraordinary impact in the coming times in Medical Sciences.

Feeling the challenge of participating with significant contributions to a complex problem requires constant updating. Biochemical professional practice also requires that commitment and leadership.

All of us who have been involved in collaborating in the delivery of this chapter, we are sorry and we have worked with the simple purpose of contributing another look, from our perspective, to the benefit and commitment to continue improving what we do.

Our gratitude to all who have collaborated with this contribution.

Bq. Ricardo Giordano (Mat. 929), Bq. Cesar Yene (Mat 1761), Dr. in Bq. Fernando Elias (44323), Coordination: Dr. in Bq. Oscar Hector Fay (0100/68)

What is the role of a clinical laboratory?

Analyze human biological samples that provide useful information to health teams for the study, diagnosis, prevention and treatment of different pathologies.

What is the role of laboratory personnel?

Clinical laboratory professionals are responsible for:

• Use analytically acceptable methods and techniques in laboratories , taking care of all aspects of quality control in all its stages: pre-analytical, analytical and post-analytical, in addition to participating in external quality evaluation programs.
• Prioritize the correct selection of tests and methodology in terms of predictive value, as well as their sensitivity and specificity and that they are clinically relevant in order to guarantee their clinical utility.
• Eliminate unhelpful tests and those outdated that have not shown a benefit in their use and implement new tests if the evidence has proven their effectiveness.

How has the biochemical laboratory evolved in recent times?

Today's biochemical laboratory is one of the areas of diagnosis that has undergone the most changes in recent years. The availability of new technologies (see attached list of emerging technologies) coupled with increasing automation , has led to higher analytical quality, resulting in increased efficiency and safety.

Currently there are continuous flow analytical systems (absorbance photometry, turbidimetry, nephelometry, fluorescence, colorimetry, enzyme and immunoenzymatic kinetics, etc.), which consist of:

• Sample taking and dispensing system
• Reagent dispensing system
• Incubation baths
• Detectors
• Data processor
• Data processing software

What does automation bring?

The automation requires less operator intervention, increases productivity, with decreasing response times and greater throughput. 

These systems provide greater sensitivity, specificity, precision, and truthfulness. They require a smaller volume of samples and reagents, with high analytical performance, significantly reducing operating costs and allowing the processing of a large number of samples simultaneously. 

This requires systems that allow the handling of a large volume of data: patient admission, sampling, sample preparation and distribution, work lists, quality controls, reception and validation of results, issuance of reports, historical files with background, purchasing management and administrative management. To this is added the existence of networks where external requests are entered to the LIS, reports are issued online, with the possibility of consulting the results from any device. 

What role does the clinical biochemist play in this scenario?

The evolution of the laboratory as a consequence of technological development has improved the quality of the processes, but in this scenario, professional judgment continues to be key. In addition to a technical validation , which is the acceptance of results with technical criteria (maintenance, calibrations, quality controls, alarms issued by the autoanalyzers, Delta Check that indicates the variation with respect to the antecedents), a clinical validation is also necessary , which It involves evaluating the consistency of the data from the different tests in a request together with the patient's demographics (sex, age, etc.).

On the other hand, the greater number of tests available has led to a greater need for interaction with the clinician for the suggestion of complementary studies or for the interpretation of the data, which has substantially modified the profile of the required biochemical professional currently.

What are the factors to consider when requesting a lab test?

Evaluate whether obtaining the result would provide useful information for diagnosing or deciding on any therapeutic action that benefits the patient.

Request the laboratory tests taking into account their sensitivity, specificity, positive and negative predictive value according to the context of the patient and the pathology (s) being evaluated.

What factors should be considered when interpreting laboratory data?

- Variables preanalíticas:

It is important to take into account the existence of preanalytical factors related to the patient and others related to the activity of health personnel (doctors, nurses and laboratory personnel) that can affect laboratory results.

Some cannot be modified, so they must be known in order to properly interpret the exams; however, there are other modifiable ones with the correct sampling and preparation of patients, which are essential to obtain valid results.

Main factors not susceptible to modification that must be known in order to make a correct interpretation of the results :

• Age
• Sex
• Race
• Pregnancy
• Phase of the menstrual cycle

Main factors susceptible to modification with the correct sampling and preparation of the patient :

• Fast
• Diet
• Stress.
• Physical activity
• Circadian rhythm
• Ingestion of medications.
• Smoking habit, intake of alcoholic beverages, caffeine or other stimulant substances.
• Surgery and intramuscular injection.

Factors dependent on health personnel:

Interferences related to the activity of health personnel (doctors, nurses, laboratory personnel, etc.) are generally due to poor compliance with operating standards. Among the most frequent are: errors in sample collection, identification and handling, delay in sending samples to the laboratory, incomplete or incorrect preparation of the patient, incomplete collection in the case of serial samples, information to the laboratory inaccurate, incomplete or illegible, etc.

- Reference values

To be able to interpret a measured value of a biological magnitude of a patient for diagnostic purposes, it is essential to know one or more values ​​of that magnitude evaluated in similar individuals and compare them.

A biological reference value is a measured value of a particular magnitude obtained for comparative purposes in an individual, called a reference individual, that meets certain pre-established requirements.

The reference values ​​always depend on the procedure used to measure it.

In clinical practice, the results are compared against fixed references, which can be:

• Population reference values.
• Local protocols by consensus.
• Values ​​proposed by groups of experts.
• Risk-based values.
• Multiples of the reference values.

- Biological variability and analytical variability:

The values ​​obtained in the laboratory of a certain analysis in a patient vary over time due to two factors which are:

1) Biological variability

Variation of the levels of an analyte around its homeostatic point. These variations can occur throughout the day, weeks, etc., and are specific to each analyte. We can speak of “intra-individual variability” (how it varies in said patient) and “variability between individuals” (how it varies between different people).

Some characteristics that result from this are:

• No individual has results that span the entire reference interval.
• The results of each individual occupy a small portion of the reference interval.
• The mean of the results of each patient falls within the reference interval and differs from that of the rest of the individuals.
• Many individuals may have unusual values, and still be within the reference interval.
• Some individuals randomly have values ​​inside and outside the reference interval.
• Stratification of the reference values ​​(by age, sex, cycle time) makes them more useful for monitoring and diagnosis.

2) Analytical variability

Not all the measurement procedures available to measure a quantity are subject to the same metrological variability, so most measurement procedures lead to different results.

Each time a determination is repeated, it will yield results that are normally distributed around a central value. The amplitude of the dispersion of these values ​​is measured through random error. Laboratories know the magnitude of said dispersion through the evaluation of quality controls, this being another contribution to the variability of a patient's results.

What tests to request for each pathology?

In the current state of clinical biochemistry, the universe of available tests is very wide and complex. An approach strategy for the selection of laboratory tests in different clinical situations, consists of approaching through profiles according to the following table:

Note: this list is intended to serve as a guide to the main laboratory tests that can be requested grouped according to the main profiles or clinical situations that the doctor wishes to investigate.

Links to consult laboratory test catalogs on the Mayo Clinic Reference Laboratory website:

To download Laboratory Test Catalog or Laboratory Test Interpretation Manual:
https://www.mayocliniclabs.com/test-catalog/print-catalog.html/index.html

For online search of laboratory tests:
https://www.mayocliniclabs.com/testcatalog/index.html

Laboratory tests by medical specialties:
https://www.mayocliniclabs.com/test-info/index.html

LabTests Online: Web in Spanish version fruit of the collaboration between Lab Tests Online in the USA (AACC), the European Association of Manufacturers of Diagnostic Material (EDMA), the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) and FENIN (Federation Spanish of Health Technology Companies).
https://labtestsonline.es/

List of new (emerging) technologies applied to clinical diagnosis.

Bibliography:

• Fundamentals of Clinical Interpretation of Laboratory Tests, Guillermo Ruiz Reyes / Alejandro Ruiz Argüelles, 3rd edition, 2017. Editorial Médica Panamericana.
• Laboratory Medicine: Fundamentals and applications in clinical diagnosis. Italo Antonozzi, Elio Gulletta, 2015. Editorial Médica Panamericana.
• Errors in the clinical laboratory, Ruth Cano Corres, Clinical Laboratory, Bellvitge University Hospital, L'Hospitalet de Llobregat, Xavier Fuentes Arderiu, Clinical Laboratory Science Consultant, Barcelona
• Interpreting laboratory results: change reference value and delta-check. Dr. Gabriela D´Isa1, Marta Rubinstein Medicina Infantil 2012; XIX: 8 - 13
• Importance of biological variability and medical relevance, Mexican Journal of Clinical Pathology, Volume 50, Number 3, July - September 2003. Biological variation. Review from a practical perspective, Carmen Ricós, Carmen Perich, Marivı´ Doménech, Pilar Fernández, Carmen Biosca, Joana Minchinela, Margarita Simón, Fernando Cava, Virtudes Álvarez, Carlos Victor Jiménez and José Vicente García Lario, Magazine of the C línico laboratory. 2010 ; 3 (4): 192-200.
• Managing and Validating Laboratory information Systems; Approved Guidelines, Vol 26, Nro. 36. Clinical and laboratory Standards Institute, December 2006.