Curriculum
The Dutch Curriculum for Clinical Chemistry and Laboratory Medicine is based on the European standard developed within EC4, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine.
This syllabus affords an overview of the fields within the discipline in which the clinical chemist should be able to demonstrate knowledge and experience with regard to scientific, clinical, management and quality assurance aspects of the subject.
Chapters
I Basic knowledge
II Assessment of clinical chemistry procedures
III Indications for clinical chemistry procedures
IV Influences from the collection and storage of specimens
V Clinical chemical analysis
VI Methodological evaluation of analytical findings
VII Haematology and immunohaematology
VIII Case related medical evaluation of laboratory test
methods
IX Clinical training
X Research and development
XI Laboratory management and quality assurance
Appendix A
Knowledge and experience in accordance with sections I-VIII of the Syllabus
in applications in the different fields
Appendix B
Extended haematology
Appendix C
Medical microbiology
Appendix D
Examples of scientific and medical literature
I Basic knowledge
1. Basic knowledge in chemistry:
Homogeneous and heterogeneous systems, distribution and absorption with
regard to analytical separation methods. Study of atoms and molecules,
especially with regard to stoichiometry and isotopes.
Knowledge of thermodynamic laws and their application in analysis and
biological systems. Reaction kinetics with regard to catalysed reactions
and radioactive decay.
2. Basic knowledge in biochemistry:
Molecular structures of the body; metabolism, enzymes, metabolites, molecular
biology of genetics, biological macromolecules.
3. Basic knowledge in medicine:
3.1 Structure and function of the human body, laws on the distribution
of substances in the body.
3.2 Human physiology
3.3. Pathobiochemistry, pathophysiology and pathology.
II Assessment of clinical chemistry
methods of analysis
1. Reference intervals and biological variability
Genetic influences, environmental influences, age, sex, nutrition, season
and time of day, influence of xenobiotics
2. Predictive value of analytical methods, diagnostic sensitivity and
specificity
3. Diagnostic strategies and analytical goals in the use of clinical chemistry
techniques, also with regard to consultation
4. Statistics including common parametric and non-parametric techniques.
Biometry. Medical informatics, data processing and telecommunication.
III Indications for clinical
chemistry procedures
1. In the early detection of disease, and in epidemiology
2. In disease related diagnosis
3. In organ related diagnosis
4. In monitoring vital functions
5. In monitoring response to therapy
6. In therapeutic drug monitoring, suspected poisoning and substance abuse
7. I indications for subsequent special examinations
8. Indications for functional tests.
IV Influences from the collection
and storage of specimens
1. Place and time of sample collection, preservation, influence of nutrition,
drugs, posture, etc.
2. Initial evaluation of examination request
3. Care of the specimens, identification, transport, storage.
V Clinical chemical analysis
1. Separation techniques including chromatography and electrophoresis
2. Standard analytical techniques such as gravimetry, volumetry, titrimetry
and osmometry
3. Photometric methods such as various kinds of spectrometry, spectrophotometry,
reflectometry, turbidimetry, etc.
4. Physical techniques such as mass spectrometry, nuclear magnetic resonance,
etc.
5. Electrochemical techniques such as potentiometry, polarography, etc.
6. Techniques for protein and DNA analysis such as blotting techniques,
PCR, etc.
7. Immunochemical techniques such as immuno-electrophoresis, several types
of binding analysis using different markers (homogeneous and inhomogeneous
systems)
8. Techniques using radioactive isotopes
9. Enzyme activity and substrate determination methods
10. Microscopical analysis of formed elements
11. Cell and particle counting methods
12. Knowledge of analytical instrumentation and evaluation of equipment.
VI Methodological evaluation
of analytical methods
1. Precision and accuracy
2. Reference methods and statistical comparison of methods
3. lnternal quality assurance and external quality assessment
4. Specificity and sensitivity of analytical methods
5. Evaluation of influence parameters and interfering factors.
VII Haematology and immunohaematology
1. General morphology and cell counting methods, blood smear and bone
marrow preparation and staining techniques, labelled immunochemical techniques
2. General haemostasis and fibrinolysis clotting methods, chromogenic
techniques, immunochemical techniques, control of anticoagulation
3. Bloodgroup typing methods, detection methods for irregular antibodies,
cross matching techniques, bloodbanking
4. Electroforetic techniques for haemoglobinopathies, cell enzyme activity
determination methods, knowledge of bloodcell kinetics.
VIII Case-related medical evaluation
of laboratory test methods
The clinical chemist in a consultative role requires a working knowledge
of the subject on which to base the choice of tests and interpretation
of results.
1. Plausibility evaluation (recognition of possible fluctuations in comparison
to previous values, plausibility of patterns of evidence, extreme values,
etc.)
2. Use of reference values (transverse evaluation, decision limits, influences
of age, sex, way of life, etc.)
3. Longitudinal evaluation of disease course and therapy monitoring (critical
differences, trend analysis)
4. Recognition of combinations of findings typical of diseases (medical
decision-making)
5. Application in the formulation of clinical questions
6. The laboratory report with evaluation of data (information enhancement,
multi variate interpretation
7. Independent performance or suggestions for necessary further tests.
IX Clinical training
Training in clinical chemistry requires participation in ward rounds as
a member of the clinical team and other contact with these users of the
laboratory service, for example seminars and case
discussions. Study in the following areas will provide a general basic
knowledge of clinical chemistry from which consultative skill can develop:
1. Organ function, anatomy and physiology
2. Metabolism
3. Biochemical exploration and testing
4. Variations in the physiology leading to pathological conditions and
disease
A more detailed description of the paragraphs mentioned above is given
in appendix A.
X Research and development
As laboratory medicine is continually and rapidly evolving, research and
development of both the laboratory aspects as such and in relation to
clinical liaison are indispensable. Special attention must be paid to
the following:
I. The development of improvements in methods and techniques
2. Procedures to test and evaluate the components of a method or instrument
3. Evaluation of both laboratory based and clinical research projects
4. Analysis and documentation of results obtained through research and
development, with simplification and scientific presentation of data
5. Collaborative planning of clinical research based on the liaison function
of the clinical chemist as an indispensable specialist for interpretation
of laboratory data
6. Publication of papers reporting new or improved laboratory methods
and of clinical research papers.
XI Laboratory Management and
quality assurance
1 Laboratory organisation and management
Work procedures, work load measurements, emergency laboratory, laboratory
planning, laboratory
information systems, selection of equipment and methods, cost-benefit
analysis, costing.
2. Education and training of laboratory personnel, planning and selection
3. Quality management and quality assessment
Quality manual, accreditation and auditing systems, internal quality assessment
procedures and materials, external quality assessment procedures and materials.
4. Basic knowledge of clinical epidemiology
5. Laboratory safety
Handling of potentially infectious samples (HIV, hepatitis-B), handling
of noxious chemicals and isotopes, mechanical and electrical safety, fire
precautions, dealing with an accident.
6. Legal regulations
Laws, guidelines and recommendations on work in clinical laboratories:
in particular accident prevention and hygiene regulations, handling of
isotopes, calibration law, quality control, education regulations, labour
laws and occupational diseases.
Appendix A
Knowledge and experience in accordance with sections i-viii of the syllabus
in applications in the following fields:
1. Carbohydrates
1.1 Glucose metabolism
1.2 Metabolism of other carbohydrates (e.g. galactose, lactose, glycogen)
1.3 Diabetes mellitus.
1.4 Other hereditary and acquired metabolic disorders (e.g. lactose intolerance,
galactosaemia, storage diseases)
2. Lipids and lipoproteins
2.1 Metabolism
2.2 Hereditary and acquired hypo- and hyperlipoproteinaemia, hypercholesterolaemia,
storage diseases
3. Proteins and amino acids
3.1 Metabolism
3.2 Important plasma proteins
3.3 Dysproteinaemia
3.4 Tumour associated proteins
3.5 Hereditary and acquired disorders of amino acid metabolism
4. Nucleic acids and purines
4.1 Metabolism
4.2 Gout
4.3 Other hereditary and acquired disorders of purine metabolism
4.4 DNA and DNA-related disorders; oncogenes
5. Vitamins
5.1 Metabolism
5.2 Function, influence of shortage and overdose
5.3 Important related disorders in neurology, haematology, psychiatry
etc.
6. Porphyrins and bile pigments
6.1 Metabolism
6.2 Porphyrias, lead intoxication and hyperbilirubinaemia
7. Biogenic amines
7.1 Metabolism
7.2 Catecholamines, serotonin an their breakdown products
8. Water and electrolytes
8.1 Fluid spaces
8.2 Osmotic pressure and oncotic pressure
8.3 Specific e1ectro1yte effects on organ and cell functions
9. Acids, bases, bloodgases
10. Blood cells and platelets
10.1 Haemog1obin synthesis
10.2 Morphological and cytochemical differentiation of blood cells
10.3 Normal and disturbed functions
10.4 Reactive changes in the blood cell pattern
10.5 Anaemia
10.6 Haemoglobinopathy.
10.7 Leukaemia
10.8 Growth factors
11. Immunohaematology
11.1 Blood group typing
11.2 Detection of irregular erythrocyte antibodies
12. Blood clotting and fibrinolysis
12.1 Clotting reactions and fibrinolysis, thrombocyte function
12.2 Hereditary and acquired disorders, bleeding and thrombosis
12.3 Mode of action of anticoagulants, fibrinolytics, and aggregation
inhibitors
12.4 Characterisation of normal and disturbed c1otting functions with
the aid of global tests, phase tests and determinations of individual
clotting factors
13. Immune system
13.1 Functions of the humoral and cellular immune systems; cytokines;
inflammation; acute phase proteins; complement system
13.2 Surface antigens
13.3 Hereditary and acquired disorders including AIDS and lymphoma 's
13.4 lmmunoglobulin deficiency and overproduction, monoclonal and polyclonal
immunopathies
13.5 Allergy
13.6 Monitoring of the transplant patient
14. Enzymes
14.1 lnduction, synthesis and elimination
14.2 Enzyme patterns in the various compartments
15. Cerebrospinalfluid (CSF)
15.1 CSF synthesis and circulation
15.2 Composition of CSF in comparison to serum
15.3 CSF cell counting and differentiation
15.4 Hereditary and acquired disorders of CSF homeostasis
16. Digestive tract.
16.1 Digestive enzymes in the various sections of the digestive system
including the exocrine functions of the liver and pancreas
16.2 Hydrochloric acid, bicarbonate and bile secretion 16.3 Fluid and
electrolyte secretion 16.4 Absorption
16.5 Gastrointestinal hormones
16.6 Hereditary and acquired disorders of the digestive system
16.7 Malabsorption including vitamin malabsorption
17. Exocrine functions of the pancreas
17.1 Acute pancreatitis
17.3 Chronic pancreatitis
18. Liver
18.1 Normal and disturbed functions of the liver metabolism, of biotransformation
and of excretion
18.2 Enterohepatic circulation
18.3 Hepatitis, cirrhosis, cholestasis
19. Kidneys and urinary tract
19.1 Normal and disturbed renal function
19.2 Excretory substances in the plasma and urine
19.3 Proteinuria
19.4 Formed components of the urine
19.5 Renal insufficiency, nephritis, nephrotic syndrome
19.6 Biomineral salts in the urine
20. Heart and circulatory system
20.1 Normal and disturbed circulation
20.2 Myocardial infarction and shock
20.3 Hypertension
21. Skeletal and locomotor system
21.1 Function and metabolism of muscles, bones, cartilage, synovia and
connective tissues (fasciae, tendons)
21.2 Hereditary and acquired disorders, especially of calcium and phosphate
metabolism, vitamin D, collagen and proteopolysaccharide metabolism
22. Endocrine system
22.1 Biosynthesis and catabolism of hormones
22.2 Hormonal regu1ation, hormone transport, receptor systems
22.3 Functional disorders of the thyroid gland, the parathyroid glands,
the adrenal cortex, the adrenal medulla, the endocrine part of the pancreas,
the gonads, the placenta, the pituitary-hypothalamus system
Pregnancy, perinatal laboratory analysis
24. Therapeutic drug monitoring, basic knowledge
24.1 Pharmacokinetics of drugs and effects of disease here on
24.2 Therapeutic ranges
25. Poisoning
25.1 Mechanisms of toxicity of the most important poisons
25.2 Determination of the most important types of poisoning
25.3 Drugs of abuse
26. Trace elements and metal ions 26.1 Metabolism
26.2 Function, influence of shortage and overdose
26.2 Important related disorders
Appendix B
Extended haematology
1. Morphology and haematopoiesis
1.1 Morphologica1 investigation of bone marrow smears including staining
and immunochemical procedures
1.2 Investigation of cellular characteristics and abnormalities by flow
cytometry
1.3 Haemoglobinopathies. Haemog1obin electrophoresis, knowledge of DNA
characterisation techniques
1.4 Investigation of anaemia’s, bath congenital and acquired
1.5 Detection of abnormal haemoglobin compounds: spectrophotometric analysis
2. Haemostasis
2.1 Investigation of platelet function
2.2 Chromogenic and immunochemical techniques for the determination of
coagu1ation factors.
2.3 Detection of circulating inhibitors
2.4 Coagu1ation inhibiting factors
2.5 Theoretical background and clinical background and know1edge of haemostatic
and fibrinolytic systems and their components
3. Immunohaematology and blood banking
3.1 Typing of irregular (auto-) antibodies; determination of antibody
titre
3.2 Extended blood group typing (beyond ABO and Rhesus D).
3.3 Knowledge of indications and hazards of transfusion of blood components
3.4 Investigation of transfusion reactions
3.5 Selection, preparation and app1ication of blood components
3.6 Organisation of blood banking
3.7 Typing of B and T lymphocytes 3.8 Platelet antibodies
3.9 Typing of leukocytes and tissue antigens
3.10 Quantitative determination of immunoglobu1ins and complement factors
3.11 Recognition of cel1 markers using monoclonal antibodies
3.12 The application of plasmapheresis both in donors and in patients.
Appendix C
Medical microbiology
1. General aspects:
Mutual interfaces in the investigation of biological samples and safety
procedures in the laboratory require general knowledge of infectious diseases
and medical microbiology which is indispensable in the practice of clinical
chemistry and immunochemistry.
1.1 Definition of infection and infectious disease
1.2 Pathogenicity of microbes and viral agents; desinfection
1.3 General epidemiology of infection and infectious diseases
2. Diagnostic procedures
2.1 Specimen selection and collection (blood, urine, sputum, faeces, others)
2.2 Specimen processing
2.3 Detection of parasites
3. Basic knowledge on antibiotics and antimicrobial therapy
3.1 Methods for the assay of antimicrobial agents
Appendix D
Examples of scientific and medical literature
1. Scientific and medical journals
1.1 European Journal of Clinical Chemistry and Clinical Biochemistry
1.2 Annals of Clinica1 Biochemistry
1.3 Clinical Chemistry
1.4 Clinica Chimica Acta
1.5 Scandinavian Journal of Clinical & Laboratory Investigation
1.6 American Journal of Clinical Pathology
1.7 New England Journal of Medicine
1.8 The Lancet
1.9 British Medical Journal
1.10 British Journal of Haematology
1.11 Thrombosis and Homeostasis
1.12 Transfusion
1.13 Journal of Clinical Endocrinology and Metabolism
1.14 Journal of Biological Chemistry
1.15 Advances in Clinical Chemistry
2. Textbooks
Note: As new (editions or) textbooks appear regularly the following list
only serves as an example and is certainly not exhaustive; frequent updating
is necessary.
2.1 C.A. Burtis, E.R. Ashwood: Tietz' Textbook of Clinical Chemistry;
2nd edition; W.B. Saunders Company, USA, 1994
2.2. H. Greiling, A.M. Gressner: Lehrbuch der Klinischen Chemie und Pathobiochemie;
2. Auflage; F.K. Schattauer Verlag, Stuttgart, Germany, 1989
2.3 A. Johnstone, R. Thorpe: Immunochemistry in practice; B1ackwell Scientific
Publications, Oxford, Great Britain, 1987
2.4 B.D. Rose: Clinical physiology of acid-base and electrolyte disorders;
McGraw-Hill Book Company, New York, U.S.A., 1993
2.5 F.S. Greenspan: Basic & Clinical Endocrinology (fourth edition);
Lange Medical Publications, Los Altos, California, U.S.A., 1994
2.6 Ph. Felig, J.D. Baxter, A.E. Broadus, L.A. Frohman: Endocrinology
and Metabolism; McGraw-Hill Book Company, New York, U.S.A., 1994
2.7 D.L. Sackett, R.B. Haynes, P. Tugwell: Clinical Epidemiology, a basic
science for clinical medicine; Little, Brown and Company, Boston, U.S.A.,
1991
2.8 D.P. Stites, A.I. Terr: Basic and Clinical Immunology (seventh edition);
Lange Medical Books, Appleton & Lange/Prentice Hall International,
London 1991 (8th edition expected 1994)
2.9 R.B. Friedman,'D.S. Young: Effects of disease on clinical laboratory
tests; 2nd edition;
AACC Press, Washington, U.S.A., 1989
2.10 Donald S. Young: Effects of drugs on clinical laboratory tests; 3rd
edition; AACC Press,
Washington, U.S.A., 1990
2.11 M.M. Wintrobe: Clinical Haematology; Lea and Febiger, Philadelphia,
U.S.A., 1992
2.12 J.V. Dacie and S.M. Lewis: Practical Haematology; seventh edition;
Churchill Livingstone,
London, Great Britain, 1990
2.13 J.L. Spivak: Fundamentals of clinical haematology; Harper and Row
Publishers, Cambridge,
Great Britain, 1993
2.14 A.L. BIoom and D.D. Thomas: Haemostasis and Thrombosis; third edition;
Churchill
Livingstone, London, Great Britain, 1994
2.15 P.L. Mollison: Blood transfusion in clinical medicine; 9th edition;
Blackwell Scientific
Publications, Oxford, Great Britain, 1993
2.16 B.M. Barbior, F.P. Stossel: Haematology: "A pathophysiological
approach"; Churchill
Livingstone, New York, U.S.A., 1989
2.17 R. Hall, R.G.Malia: Medical Laboratory Haematology; Butterworths,
London, Great
Britain, 1993
2.18 R.W. Colman, J. Hirsh, V.J. Marder, E.W. Salzman: Hemostasis and
Thrombosis; third
edition; J.B.Lippincott Company, Philadelphia, 1994
2.19 Ch.A. Lotspeich-Steininger, E.A. Stiene-Martin, J.A. Koepke: Clinical
Hematology:
principles, procedures, correlations; J.B.Lippincott Company, Philadelphia,
1992
2.20 D.M. Harmening: Clinical Haematology and Fundamentals of Homeostasis;
second edition;
F.A.Davies Company, Philadelphia, 1992
2.21 Technical Manual of the AABB; S. Karger A.G. Basel, Switzerland,
1993
2.22 E. Jawetz, J.L. Melnick, E.A. Adelberg: Review of medical microbiology;
19th edition;
Lange Medical Publications, Los Altos, California, 1993
2.23 E.H. Lennette, A. Balows, W.J. Hausler, H.J. Shadomy: Manual of clinical
microbiology; 5th
edition; Am. Soc. Microbiol, Washington, U.S.A., 1991 5th
3. Primary literature
It must be stressed that reading so called primary literature (articles,
surveys, etc.) is of outmost
importance to keep informed on "the state of the art" in clinical
chemistry. For this reason students
should adopt a system to keep themselves constantly informed on developments
in the field of
laboratory medicine and related subjects.
